WO2022123605A1 - Herbal composition for covid 19 treatment - Google Patents
Herbal composition for covid 19 treatment Download PDFInfo
- Publication number
- WO2022123605A1 WO2022123605A1 PCT/IN2021/051158 IN2021051158W WO2022123605A1 WO 2022123605 A1 WO2022123605 A1 WO 2022123605A1 IN 2021051158 W IN2021051158 W IN 2021051158W WO 2022123605 A1 WO2022123605 A1 WO 2022123605A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- mucor
- rhizopus
- infection
- cunninghamella
- covid
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 61
- 238000011282 treatment Methods 0.000 title claims abstract description 51
- 208000025721 COVID-19 Diseases 0.000 title claims abstract description 49
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 claims abstract description 33
- 244000273928 Zingiber officinale Species 0.000 claims abstract description 29
- 235000006886 Zingiber officinale Nutrition 0.000 claims abstract description 28
- 235000008397 ginger Nutrition 0.000 claims abstract description 28
- 208000015181 infectious disease Diseases 0.000 claims abstract description 27
- 235000019510 Long pepper Nutrition 0.000 claims abstract description 22
- 240000003455 Piper longum Species 0.000 claims abstract description 22
- 241001678559 COVID-19 virus Species 0.000 claims abstract description 21
- 235000002639 sodium chloride Nutrition 0.000 claims abstract description 17
- 239000001841 zingiber officinale Substances 0.000 claims abstract description 16
- 208000031888 Mycoses Diseases 0.000 claims abstract description 15
- 244000203593 Piper nigrum Species 0.000 claims abstract description 15
- 235000008184 Piper nigrum Nutrition 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 11
- 239000003112 inhibitor Substances 0.000 claims abstract description 11
- 239000008601 oleoresin Substances 0.000 claims abstract description 11
- 239000011780 sodium chloride Substances 0.000 claims abstract description 11
- 238000011321 prophylaxis Methods 0.000 claims abstract description 10
- 230000000977 initiatory effect Effects 0.000 claims abstract description 9
- 244000000010 microbial pathogen Species 0.000 claims abstract description 9
- 206010017533 Fungal infection Diseases 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 7
- 239000000341 volatile oil Substances 0.000 claims abstract description 7
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 claims abstract description 6
- 208000036142 Viral infection Diseases 0.000 claims abstract description 6
- 230000002519 immonomodulatory effect Effects 0.000 claims abstract description 5
- 230000009385 viral infection Effects 0.000 claims abstract description 5
- 102000053723 Angiotensin-converting enzyme 2 Human genes 0.000 claims abstract 9
- 239000003921 oil Substances 0.000 claims description 18
- 241000235395 Mucor Species 0.000 claims description 15
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 claims description 12
- 244000053214 Ipomoea obscura Species 0.000 claims description 10
- KKOXKGNSUHTUBV-UHFFFAOYSA-N racemic zingiberene Natural products CC(C)=CCCC(C)C1CC=C(C)C=C1 KKOXKGNSUHTUBV-UHFFFAOYSA-N 0.000 claims description 10
- KKOXKGNSUHTUBV-LSDHHAIUSA-N zingiberene Chemical compound CC(C)=CCC[C@H](C)[C@H]1CC=C(C)C=C1 KKOXKGNSUHTUBV-LSDHHAIUSA-N 0.000 claims description 10
- 229930001895 zingiberene Natural products 0.000 claims description 10
- 241000220317 Rosa Species 0.000 claims description 9
- 235000008216 herbs Nutrition 0.000 claims description 9
- 241000711573 Coronaviridae Species 0.000 claims description 8
- 244000061408 Eugenia caryophyllata Species 0.000 claims description 8
- 241000235527 Rhizopus Species 0.000 claims description 8
- 235000016639 Syzygium aromaticum Nutrition 0.000 claims description 8
- -1 Umonene Chemical compound 0.000 claims description 8
- NLDDIKRKFXEWBK-AWEZNQCLSA-N gingerol Chemical compound CCCCC[C@H](O)CC(=O)CCC1=CC=C(O)C(OC)=C1 NLDDIKRKFXEWBK-AWEZNQCLSA-N 0.000 claims description 8
- JZLXEKNVCWMYHI-UHFFFAOYSA-N gingerol Natural products CCCCC(O)CC(=O)CCC1=CC=C(O)C(OC)=C1 JZLXEKNVCWMYHI-UHFFFAOYSA-N 0.000 claims description 8
- 235000002780 gingerol Nutrition 0.000 claims description 8
- 244000302413 Carum copticum Species 0.000 claims description 7
- 235000007034 Carum copticum Nutrition 0.000 claims description 7
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 7
- 244000303040 Glycyrrhiza glabra Species 0.000 claims description 7
- 235000001978 Withania somnifera Nutrition 0.000 claims description 7
- 240000004482 Withania somnifera Species 0.000 claims description 7
- LDWAIHWGMRVEFR-UHFFFAOYSA-N (6,6-dimethyl-4-bicyclo[3.1.1]heptanyl)methanol Chemical compound C1C2C(C)(C)C1CCC2CO LDWAIHWGMRVEFR-UHFFFAOYSA-N 0.000 claims description 6
- WRYLYDPHFGVWKC-UHFFFAOYSA-N 4-terpineol Chemical compound CC(C)C1(O)CCC(C)=CC1 WRYLYDPHFGVWKC-UHFFFAOYSA-N 0.000 claims description 6
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 claims description 6
- 241000235555 Cunninghamella Species 0.000 claims description 6
- ZFMSMUAANRJZFM-UHFFFAOYSA-N Estragole Chemical compound COC1=CC=C(CC=C)C=C1 ZFMSMUAANRJZFM-UHFFFAOYSA-N 0.000 claims description 6
- 239000005770 Eugenol Substances 0.000 claims description 6
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 claims description 6
- 241000235526 Mucor racemosus Species 0.000 claims description 6
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 claims description 6
- 240000005384 Rhizopus oryzae Species 0.000 claims description 6
- 235000013752 Rhizopus oryzae Nutrition 0.000 claims description 6
- 241000235546 Rhizopus stolonifer Species 0.000 claims description 6
- 235000017089 Scutellaria baicalensis Nutrition 0.000 claims description 6
- 240000004534 Scutellaria baicalensis Species 0.000 claims description 6
- KQAZVFVOEIRWHN-UHFFFAOYSA-N alpha-thujene Natural products CC1=CCC2(C(C)C)C1C2 KQAZVFVOEIRWHN-UHFFFAOYSA-N 0.000 claims description 6
- CRPUJAZIXJMDBK-UHFFFAOYSA-N camphene Chemical compound C1CC2C(=C)C(C)(C)C1C2 CRPUJAZIXJMDBK-UHFFFAOYSA-N 0.000 claims description 6
- QMVPMAAFGQKVCJ-UHFFFAOYSA-N citronellol Chemical compound OCCC(C)CCC=C(C)C QMVPMAAFGQKVCJ-UHFFFAOYSA-N 0.000 claims description 6
- 229960002217 eugenol Drugs 0.000 claims description 6
- CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 claims description 6
- NDVASEGYNIMXJL-UHFFFAOYSA-N sabinene Chemical compound C=C1CCC2(C(C)C)C1C2 NDVASEGYNIMXJL-UHFFFAOYSA-N 0.000 claims description 6
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 claims description 6
- RUVINXPYWBROJD-ONEGZZNKSA-N trans-anethole Chemical compound COC1=CC=C(\C=C\C)C=C1 RUVINXPYWBROJD-ONEGZZNKSA-N 0.000 claims description 6
- SASUFNRGCZMRFD-JCUIILOWSA-N withanolide D Chemical compound C1C(C)=C(C)C(=O)O[C@H]1[C@](C)(O)[C@@H]1[C@@]2(C)CC[C@@H]3[C@@]4(C)C(=O)C=C[C@H](O)[C@@]54O[C@@H]5C[C@H]3[C@@H]2CC1 SASUFNRGCZMRFD-JCUIILOWSA-N 0.000 claims description 6
- NPNUFJAVOOONJE-ZIAGYGMSSA-N β-(E)-Caryophyllene Chemical compound C1CC(C)=CCCC(=C)[C@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-ZIAGYGMSSA-N 0.000 claims description 6
- 235000015752 Aframomum melegueta Nutrition 0.000 claims description 5
- 244000227206 Aframomum melegueta Species 0.000 claims description 5
- 240000002234 Allium sativum Species 0.000 claims description 5
- 235000003097 Artemisia absinthium Nutrition 0.000 claims description 5
- 240000002877 Artemisia absinthium Species 0.000 claims description 5
- 241000472349 Asparagus adscendens Species 0.000 claims description 5
- 241000202726 Bupleurum Species 0.000 claims description 5
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 5
- 241000207199 Citrus Species 0.000 claims description 5
- 241001349574 Diplocyclos palmatus Species 0.000 claims description 5
- 241001013934 Erigeron breviscapus Species 0.000 claims description 5
- 235000000554 Glycyrrhiza uralensis Nutrition 0.000 claims description 5
- 240000008917 Glycyrrhiza uralensis Species 0.000 claims description 5
- 241000124020 Heteromorpha Species 0.000 claims description 5
- 235000002598 Inula helenium Nutrition 0.000 claims description 5
- 244000116484 Inula helenium Species 0.000 claims description 5
- 235000001167 Melaleuca cajuputi Nutrition 0.000 claims description 5
- 244000304222 Melaleuca cajuputi Species 0.000 claims description 5
- 240000001740 Momordica dioica Species 0.000 claims description 5
- 235000018365 Momordica dioica Nutrition 0.000 claims description 5
- 241000207746 Nicotiana benthamiana Species 0.000 claims description 5
- 235000012920 Oroxylum indicum Nutrition 0.000 claims description 5
- 240000005790 Oroxylum indicum Species 0.000 claims description 5
- 235000017927 Pelargonium graveolens Nutrition 0.000 claims description 5
- 244000270673 Pelargonium graveolens Species 0.000 claims description 5
- 235000010627 Phaseolus vulgaris Nutrition 0.000 claims description 5
- 244000046052 Phaseolus vulgaris Species 0.000 claims description 5
- 241000003841 Scrophularia scorodonia Species 0.000 claims description 5
- 241000606265 Valeriana jatamansi Species 0.000 claims description 5
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 5
- 240000006365 Vitis vinifera Species 0.000 claims description 5
- 239000001138 artemisia absinthium Substances 0.000 claims description 5
- 235000020971 citrus fruits Nutrition 0.000 claims description 5
- 235000004611 garlic Nutrition 0.000 claims description 5
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 3
- NZGWDASTMWDZIW-MRVPVSSYSA-N (+)-pulegone Chemical compound C[C@@H]1CCC(=C(C)C)C(=O)C1 NZGWDASTMWDZIW-MRVPVSSYSA-N 0.000 claims description 3
- NDVASEGYNIMXJL-NXEZZACHSA-N (+)-sabinene Natural products C=C1CC[C@@]2(C(C)C)[C@@H]1C2 NDVASEGYNIMXJL-NXEZZACHSA-N 0.000 claims description 3
- SDOFMBGMRVAJNF-KVTDHHQDSA-N (2r,3r,4r,5r)-6-aminohexane-1,2,3,4,5-pentol Chemical compound NC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO SDOFMBGMRVAJNF-KVTDHHQDSA-N 0.000 claims description 3
- 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 claims description 3
- JWQKMEKSFPNAIB-SNVBAGLBSA-N (5r)-1-methyl-5-prop-1-en-2-ylcyclohexene Chemical compound CC(=C)[C@@H]1CCC=C(C)C1 JWQKMEKSFPNAIB-SNVBAGLBSA-N 0.000 claims description 3
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 claims description 3
- QMVPMAAFGQKVCJ-SNVBAGLBSA-N (R)-(+)-citronellol Natural products OCC[C@H](C)CCC=C(C)C QMVPMAAFGQKVCJ-SNVBAGLBSA-N 0.000 claims description 3
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 claims description 3
- WEEGYLXZBRQIMU-UHFFFAOYSA-N 1,8-cineole Natural products C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 claims description 3
- WRYLYDPHFGVWKC-SNVBAGLBSA-N 4-Terpineol Natural products CC(C)[C@]1(O)CCC(C)=CC1 WRYLYDPHFGVWKC-SNVBAGLBSA-N 0.000 claims description 3
- NVEQFIOZRFFVFW-UHFFFAOYSA-N 9-epi-beta-caryophyllene oxide Natural products C=C1CCC2OC2(C)CCC2C(C)(C)CC21 NVEQFIOZRFFVFW-UHFFFAOYSA-N 0.000 claims description 3
- 244000205574 Acorus calamus Species 0.000 claims description 3
- 241001013906 Apophysomyces ossiformis Species 0.000 claims description 3
- 241001013909 Apophysomyces trapeziformis Species 0.000 claims description 3
- 241000239998 Apophysomyces variabilis Species 0.000 claims description 3
- 241000228197 Aspergillus flavus Species 0.000 claims description 3
- 241001225321 Aspergillus fumigatus Species 0.000 claims description 3
- 241000222122 Candida albicans Species 0.000 claims description 3
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 claims description 3
- 241000010216 Cunninghamella blakesleeana Species 0.000 claims description 3
- 241000010217 Cunninghamella clavata Species 0.000 claims description 3
- 241001290628 Cunninghamella echinulata Species 0.000 claims description 3
- 241000235556 Cunninghamella elegans Species 0.000 claims description 3
- 241000010218 Cunninghamella homothallica Species 0.000 claims description 3
- 241000010224 Cunninghamella intermedia Species 0.000 claims description 3
- 241000010226 Cunninghamella multiverticillata Species 0.000 claims description 3
- 241000010228 Cunninghamella phaeospora Species 0.000 claims description 3
- 241000293023 Cunninghamella polymorpha Species 0.000 claims description 3
- 241000430426 Cunninghamella septata Species 0.000 claims description 3
- 241000010230 Cunninghamella vesiculosa Species 0.000 claims description 3
- 235000018791 Cymbopogon nardus Nutrition 0.000 claims description 3
- 244000166675 Cymbopogon nardus Species 0.000 claims description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 3
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 claims description 3
- 240000006927 Foeniculum vulgare Species 0.000 claims description 3
- 239000005792 Geraniol Substances 0.000 claims description 3
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 claims description 3
- 241000144128 Lichtheimia corymbifera Species 0.000 claims description 3
- 241001351976 Lichtheimia ramosa Species 0.000 claims description 3
- 241000306281 Mucor ambiguus Species 0.000 claims description 3
- 241000293033 Mucor amphibiorum Species 0.000 claims description 3
- 241001456797 Mucor ellipsoideus Species 0.000 claims description 3
- 241000907547 Mucor fragilis Species 0.000 claims description 3
- 241000907556 Mucor hiemalis Species 0.000 claims description 3
- 241000010214 Mucor hiemalis f. silvaticus Species 0.000 claims description 3
- 241001149951 Mucor mucedo Species 0.000 claims description 3
- 244000309698 Mucor paronychius Species 0.000 claims description 3
- 241001506781 Mucor piriformis Species 0.000 claims description 3
- 241000293032 Mucor ramosissimus Species 0.000 claims description 3
- PXRCIOIWVGAZEP-UHFFFAOYSA-N Primaeres Camphenhydrat Natural products C1CC2C(O)(C)C(C)(C)C1C2 PXRCIOIWVGAZEP-UHFFFAOYSA-N 0.000 claims description 3
- NZGWDASTMWDZIW-UHFFFAOYSA-N Pulegone Natural products CC1CCC(=C(C)C)C(=O)C1 NZGWDASTMWDZIW-UHFFFAOYSA-N 0.000 claims description 3
- 241000648446 Rhizopus americanus Species 0.000 claims description 3
- 241000006328 Rhizopus azygosporus Species 0.000 claims description 3
- 241000006329 Rhizopus caespitosus Species 0.000 claims description 3
- 241000378861 Rhizopus circinans Species 0.000 claims description 3
- 241000006330 Rhizopus homothallicus Species 0.000 claims description 3
- 241001228751 Rhizopus lyococcus Species 0.000 claims description 3
- 241000593344 Rhizopus microsporus Species 0.000 claims description 3
- 241000235545 Rhizopus niveus Species 0.000 claims description 3
- 244000205939 Rhizopus oligosporus Species 0.000 claims description 3
- 235000000471 Rhizopus oligosporus Nutrition 0.000 claims description 3
- 241000006333 Rhizopus schipperae Species 0.000 claims description 3
- 241001640341 Rhizopus stolonifer var. reflexus Species 0.000 claims description 3
- UXZIDIYMFIBDKT-UHFFFAOYSA-N Sylvestrene Natural products CC(=C)C1CCCC(C)=C1 UXZIDIYMFIBDKT-UHFFFAOYSA-N 0.000 claims description 3
- 239000005844 Thymol Substances 0.000 claims description 3
- 241000222126 [Candida] glabrata Species 0.000 claims description 3
- FAMPSKZZVDUYOS-UHFFFAOYSA-N alpha-Caryophyllene Natural products CC1=CCC(C)(C)C=CCC(C)=CCC1 FAMPSKZZVDUYOS-UHFFFAOYSA-N 0.000 claims description 3
- XCPQUQHBVVXMRQ-UHFFFAOYSA-N alpha-Fenchene Natural products C1CC2C(=C)CC1C2(C)C XCPQUQHBVVXMRQ-UHFFFAOYSA-N 0.000 claims description 3
- USMNOWBWPHYOEA-UHFFFAOYSA-N alpha-thujone Natural products CC1C(=O)CC2(C(C)C)C1C2 USMNOWBWPHYOEA-UHFFFAOYSA-N 0.000 claims description 3
- 229940011037 anethole Drugs 0.000 claims description 3
- 229940091771 aspergillus fumigatus Drugs 0.000 claims description 3
- NPNUFJAVOOONJE-UHFFFAOYSA-N beta-cariophyllene Natural products C1CC(C)=CCCC(=C)C2CC(C)(C)C21 NPNUFJAVOOONJE-UHFFFAOYSA-N 0.000 claims description 3
- JGQFVRIQXUFPAH-UHFFFAOYSA-N beta-citronellol Natural products OCCC(C)CCCC(C)=C JGQFVRIQXUFPAH-UHFFFAOYSA-N 0.000 claims description 3
- 229930006739 camphene Natural products 0.000 claims description 3
- ZYPYEBYNXWUCEA-UHFFFAOYSA-N camphenilone Natural products C1CC2C(=O)C(C)(C)C1C2 ZYPYEBYNXWUCEA-UHFFFAOYSA-N 0.000 claims description 3
- 229940095731 candida albicans Drugs 0.000 claims description 3
- 208000032343 candida glabrata infection Diseases 0.000 claims description 3
- HHTWOMMSBMNRKP-UHFFFAOYSA-N carvacrol Natural products CC(=C)C1=CC=C(C)C(O)=C1 HHTWOMMSBMNRKP-UHFFFAOYSA-N 0.000 claims description 3
- RECUKUPTGUEGMW-UHFFFAOYSA-N carvacrol Chemical compound CC(C)C1=CC=C(C)C(O)=C1 RECUKUPTGUEGMW-UHFFFAOYSA-N 0.000 claims description 3
- 235000007746 carvacrol Nutrition 0.000 claims description 3
- 229940117948 caryophyllene Drugs 0.000 claims description 3
- NPNUFJAVOOONJE-UONOGXRCSA-N caryophyllene Natural products C1CC(C)=CCCC(=C)[C@@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-UONOGXRCSA-N 0.000 claims description 3
- 229960005233 cineole Drugs 0.000 claims description 3
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 claims description 3
- 229940117916 cinnamic aldehyde Drugs 0.000 claims description 3
- WJSDHUCWMSHDCR-VMPITWQZSA-N cinnamyl acetate Natural products CC(=O)OC\C=C\C1=CC=CC=C1 WJSDHUCWMSHDCR-VMPITWQZSA-N 0.000 claims description 3
- 229940043350 citral Drugs 0.000 claims description 3
- 235000000484 citronellol Nutrition 0.000 claims description 3
- 239000010642 eucalyptus oil Substances 0.000 claims description 3
- 229940044949 eucalyptus oil Drugs 0.000 claims description 3
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 claims description 3
- 229940113087 geraniol Drugs 0.000 claims description 3
- WYXXLXHHWYNKJF-UHFFFAOYSA-N isocarvacrol Natural products CC(C)C1=CC=C(O)C(C)=C1 WYXXLXHHWYNKJF-UHFFFAOYSA-N 0.000 claims description 3
- 229930007744 linalool Natural products 0.000 claims description 3
- 229940041616 menthol Drugs 0.000 claims description 3
- 150000007823 ocimene derivatives Chemical class 0.000 claims description 3
- 229930007459 p-menth-8-en-3-one Natural products 0.000 claims description 3
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 claims description 3
- LCYXQUJDODZYIJ-UHFFFAOYSA-N pinocarveol Chemical compound C1C2C(C)(C)C1CC(O)C2=C LCYXQUJDODZYIJ-UHFFFAOYSA-N 0.000 claims description 3
- 229930006721 pinocarveol Natural products 0.000 claims description 3
- 229930006696 sabinene Natural products 0.000 claims description 3
- 229930006978 terpinene Natural products 0.000 claims description 3
- 150000003507 terpinene derivatives Chemical class 0.000 claims description 3
- 150000007873 thujene derivatives Chemical class 0.000 claims description 3
- 229960000790 thymol Drugs 0.000 claims description 3
- XJPBRODHZKDRCB-UHFFFAOYSA-N trans-alpha-ocimene Natural products CC(=C)CCC=C(C)C=C XJPBRODHZKDRCB-UHFFFAOYSA-N 0.000 claims description 3
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 claims description 2
- 241000228257 Aspergillus sp. Species 0.000 claims description 2
- 235000011996 Calamus deerratus Nutrition 0.000 claims description 2
- 241000723346 Cinnamomum camphora Species 0.000 claims description 2
- 241001558145 Mucor sp. Species 0.000 claims description 2
- 241001248037 Rhizopus sexualis Species 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 229930008380 camphor Natural products 0.000 claims description 2
- 229960000846 camphor Drugs 0.000 claims description 2
- WTWBUQJHJGUZCY-UHFFFAOYSA-N cuminaldehyde Chemical compound CC(C)C1=CC=C(C=O)C=C1 WTWBUQJHJGUZCY-UHFFFAOYSA-N 0.000 claims description 2
- 239000001941 cymbopogon citratus dc and cymbopogon flexuosus oil Substances 0.000 claims description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 claims description 2
- 150000003505 terpenes Chemical class 0.000 claims description 2
- 235000007586 terpenes Nutrition 0.000 claims description 2
- 239000009637 wintergreen oil Substances 0.000 claims description 2
- 241000378863 Mucor plumbeus Species 0.000 claims 1
- 241001456258 Mucor velutinosus Species 0.000 claims 1
- 241000700605 Viruses Species 0.000 abstract description 51
- 230000001717 pathogenic effect Effects 0.000 abstract description 2
- 239000007916 tablet composition Substances 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 63
- 238000009472 formulation Methods 0.000 description 30
- 230000003612 virological effect Effects 0.000 description 29
- 239000003826 tablet Substances 0.000 description 26
- 239000004615 ingredient Substances 0.000 description 25
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 description 24
- 238000000034 method Methods 0.000 description 24
- 230000009467 reduction Effects 0.000 description 22
- 239000003814 drug Substances 0.000 description 21
- 239000000843 powder Substances 0.000 description 19
- 230000000694 effects Effects 0.000 description 17
- 229940079593 drug Drugs 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 208000024891 symptom Diseases 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- 230000000840 anti-viral effect Effects 0.000 description 12
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- 239000006286 aqueous extract Substances 0.000 description 10
- 238000011084 recovery Methods 0.000 description 10
- 206010011224 Cough Diseases 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 241000233866 Fungi Species 0.000 description 8
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 241000712431 Influenza A virus Species 0.000 description 7
- 206010037660 Pyrexia Diseases 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000006386 neutralization reaction Methods 0.000 description 7
- 238000010998 test method Methods 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 206010013975 Dyspnoeas Diseases 0.000 description 6
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 6
- 240000003428 Tinospora crispa Species 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- HTNPEHXGEKVIHG-QCNRFFRDSA-N molnupiravir Chemical compound C(OC(=O)C(C)C)[C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C(=O)N=C(NO)C=C1 HTNPEHXGEKVIHG-QCNRFFRDSA-N 0.000 description 6
- MXXWOMGUGJBKIW-YPCIICBESA-N piperine Chemical compound C=1C=C2OCOC2=CC=1/C=C/C=C/C(=O)N1CCCCC1 MXXWOMGUGJBKIW-YPCIICBESA-N 0.000 description 6
- WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000000069 prophylactic effect Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000010200 validation analysis Methods 0.000 description 6
- 239000009364 Ayush 64 Substances 0.000 description 5
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 5
- 208000000059 Dyspnea Diseases 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 241000711467 Human coronavirus 229E Species 0.000 description 5
- 229930003268 Vitamin C Natural products 0.000 description 5
- 206010061418 Zygomycosis Diseases 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 239000002955 immunomodulating agent Substances 0.000 description 5
- 229940121354 immunomodulator Drugs 0.000 description 5
- 201000007524 mucormycosis Diseases 0.000 description 5
- 235000019100 piperine Nutrition 0.000 description 5
- 229940075559 piperine Drugs 0.000 description 5
- 239000003087 receptor blocking agent Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 235000019154 vitamin C Nutrition 0.000 description 5
- 239000011718 vitamin C Substances 0.000 description 5
- 208000010470 Ageusia Diseases 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 108010074051 C-Reactive Protein Proteins 0.000 description 4
- 102100032752 C-reactive protein Human genes 0.000 description 4
- 206010061818 Disease progression Diseases 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 4
- 235000019666 ageusia Nutrition 0.000 description 4
- 230000000843 anti-fungal effect Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 206010016256 fatigue Diseases 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 230000007954 hypoxia Effects 0.000 description 4
- 230000002584 immunomodulator Effects 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 235000017807 phytochemicals Nutrition 0.000 description 4
- 229930000223 plant secondary metabolite Natural products 0.000 description 4
- 238000003757 reverse transcription PCR Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000005541 ACE inhibitor Substances 0.000 description 3
- 206010002653 Anosmia Diseases 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 235000010469 Glycine max Nutrition 0.000 description 3
- 244000068988 Glycine max Species 0.000 description 3
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 3
- 206010019233 Headaches Diseases 0.000 description 3
- 241001633760 Maurya Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000282339 Mustela Species 0.000 description 3
- 235000004072 Ocimum sanctum Nutrition 0.000 description 3
- 240000002837 Ocimum tenuiflorum Species 0.000 description 3
- 241001483078 Phyto Species 0.000 description 3
- 206010035664 Pneumonia Diseases 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 229910003798 SPO2 Inorganic materials 0.000 description 3
- 101100478210 Schizosaccharomyces pombe (strain 972 / ATCC 24843) spo2 gene Proteins 0.000 description 3
- 238000011053 TCID50 method Methods 0.000 description 3
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 229940121357 antivirals Drugs 0.000 description 3
- 239000002012 ayurvedic medicine Substances 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 201000003984 candidiasis Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000001364 causal effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000005750 disease progression Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 231100000869 headache Toxicity 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 206010022000 influenza Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 235000013599 spices Nutrition 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 230000007502 viral entry Effects 0.000 description 3
- 239000012873 virucide Substances 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 201000002909 Aspergillosis Diseases 0.000 description 2
- 208000036641 Aspergillus infections Diseases 0.000 description 2
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 2
- 108010076119 Caseins Proteins 0.000 description 2
- 235000002787 Coriandrum sativum Nutrition 0.000 description 2
- 244000018436 Coriandrum sativum Species 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- 235000007129 Cuminum cyminum Nutrition 0.000 description 2
- 244000304337 Cuminum cyminum Species 0.000 description 2
- 244000163122 Curcuma domestica Species 0.000 description 2
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
- 235000018142 Hedysarum alpinum var americanum Nutrition 0.000 description 2
- 240000006461 Hedysarum alpinum var. americanum Species 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 238000000585 Mann–Whitney U test Methods 0.000 description 2
- 235000010676 Ocimum basilicum Nutrition 0.000 description 2
- 240000007926 Ocimum gratissimum Species 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 201000007100 Pharyngitis Diseases 0.000 description 2
- 241000722363 Piper Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000315672 SARS coronavirus Species 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 229960004099 azithromycin Drugs 0.000 description 2
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 235000013614 black pepper Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 235000021240 caseins Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 235000003373 curcuma longa Nutrition 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 238000003113 dilution method Methods 0.000 description 2
- 208000017574 dry cough Diseases 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000010442 halite Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000007721 medicinal effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 208000030247 mild fever Diseases 0.000 description 2
- 238000003032 molecular docking Methods 0.000 description 2
- 239000002324 mouth wash Substances 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 244000309711 non-enveloped viruses Species 0.000 description 2
- 239000006191 orally-disintegrating tablet Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 238000002640 oxygen therapy Methods 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 235000010603 pastilles Nutrition 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000021251 pulses Nutrition 0.000 description 2
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 2
- 230000036454 renin-angiotensin system Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- 230000003253 viricidal effect Effects 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- KJLPSBMDOIVXSN-UHFFFAOYSA-N 4-[4-[2-[4-(3,4-dicarboxyphenoxy)phenyl]propan-2-yl]phenoxy]phthalic acid Chemical compound C=1C=C(OC=2C=C(C(C(O)=O)=CC=2)C(O)=O)C=CC=1C(C)(C)C(C=C1)=CC=C1OC1=CC=C(C(O)=O)C(C(O)=O)=C1 KJLPSBMDOIVXSN-UHFFFAOYSA-N 0.000 description 1
- 241000235389 Absidia Species 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 235000006480 Acorus calamus Nutrition 0.000 description 1
- 240000005369 Alstonia scholaris Species 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000293035 Apophysomyces Species 0.000 description 1
- 239000009405 Ashwagandha Substances 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101100421200 Caenorhabditis elegans sep-1 gene Proteins 0.000 description 1
- 244000296749 Caesalpinia crista Species 0.000 description 1
- 235000016513 Caesalpinia crista Nutrition 0.000 description 1
- 235000002566 Capsicum Nutrition 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 235000004310 Cinnamomum zeylanicum Nutrition 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 241000494545 Cordyline virus 2 Species 0.000 description 1
- 241000293018 Cunninghamella bertholletiae Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 206010050685 Cytokine storm Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 240000002943 Elettaria cardamomum Species 0.000 description 1
- 235000015489 Emblica officinalis Nutrition 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000555712 Forsythia Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 101710114810 Glycoprotein Proteins 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 1
- 244000309467 Human Coronavirus Species 0.000 description 1
- 241000482741 Human coronavirus NL63 Species 0.000 description 1
- 241001428935 Human coronavirus OC43 Species 0.000 description 1
- 206010020601 Hyperchlorhydria Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010022004 Influenza like illness Diseases 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- OFFWOVJBSQMVPI-RMLGOCCBSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O.N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 OFFWOVJBSQMVPI-RMLGOCCBSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 241001352082 Lichtheimia Species 0.000 description 1
- 244000024873 Mentha crispa Species 0.000 description 1
- 235000014749 Mentha crispa Nutrition 0.000 description 1
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 239000006002 Pepper Substances 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 240000009120 Phyllanthus emblica Species 0.000 description 1
- 241001470703 Picrorhiza kurrooa Species 0.000 description 1
- 235000016761 Piper aduncum Nutrition 0.000 description 1
- 235000017804 Piper guineense Nutrition 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 241000235402 Rhizomucor Species 0.000 description 1
- 208000037847 SARS-CoV-2-infection Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 241000207929 Scutellaria Species 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- 101000629318 Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein Proteins 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 101710167605 Spike glycoprotein Proteins 0.000 description 1
- 241000977603 Swertia chirayita Species 0.000 description 1
- 241000736854 Syncephalastrum Species 0.000 description 1
- 244000191422 Terminalia bellirica Species 0.000 description 1
- 235000012023 Terminalia bellirica Nutrition 0.000 description 1
- 235000011517 Terminalia chebula Nutrition 0.000 description 1
- 241000001522 Terminalia chebula Species 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 235000004417 Zanthoxylum alatum Nutrition 0.000 description 1
- 244000294617 Zanthoxylum alatum Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 229940086245 acetaminophen 650 mg Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000010616 ajwain oil Substances 0.000 description 1
- 239000012675 alcoholic extract Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229960001040 ammonium chloride Drugs 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 235000019558 anosmia Nutrition 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000010518 anu thailam Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 208000027499 body ache Diseases 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 235000005300 cardamomo Nutrition 0.000 description 1
- 230000002026 carminative effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 208000027744 congestion Diseases 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 238000011359 convalescent plasma therapy Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 206010052015 cytokine release syndrome Diseases 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 229940084971 dexamethasone 6 mg Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000013367 dietary fats Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000011869 dried fruits Nutrition 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- ZCGNOVWYSGBHAU-UHFFFAOYSA-N favipiravir Chemical compound NC(=O)C1=NC(F)=CNC1=O ZCGNOVWYSGBHAU-UHFFFAOYSA-N 0.000 description 1
- 229950008454 favipiravir Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000027950 fever generation Effects 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 239000012909 foetal bovine serum Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000010520 ghee Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229960002146 guaifenesin Drugs 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 208000034737 hemoglobinopathy Diseases 0.000 description 1
- 239000012674 herbal formulation Substances 0.000 description 1
- 235000015092 herbal tea Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 230000001632 homeopathic effect Effects 0.000 description 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940113983 lopinavir / ritonavir Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000001220 mentha spicata Substances 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000003641 microbiacidal effect Effects 0.000 description 1
- 229940124561 microbicide Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 231100001079 no serious adverse effect Toxicity 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 1
- 229960003752 oseltamivir Drugs 0.000 description 1
- 238000012946 outsourcing Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229940006344 pantoprazole 40 mg Drugs 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- RWWYLEGWBNMMLJ-MEUHYHILSA-N remdesivir Drugs C([C@@H]1[C@H]([C@@H](O)[C@@](C#N)(O1)C=1N2N=CN=C(N)C2=CC=1)O)OP(=O)(N[C@@H](C)C(=O)OCC(CC)CC)OC1=CC=CC=C1 RWWYLEGWBNMMLJ-MEUHYHILSA-N 0.000 description 1
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000008786 sensory perception of smell Effects 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 239000010519 shadbindu oil Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 208000016255 tiredness Diseases 0.000 description 1
- 230000003867 tiredness Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000008977 triphala Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 230000007501 viral attachment Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 229940046001 vitamin b complex Drugs 0.000 description 1
- DBRXOUCRJQVYJQ-CKNDUULBSA-N withaferin A Chemical compound C([C@@H]1[C@H]([C@@H]2[C@]3(CC[C@@H]4[C@@]5(C)C(=O)C=C[C@H](O)[C@@]65O[C@@H]6C[C@H]4[C@@H]3CC2)C)C)C(C)=C(CO)C(=O)O1 DBRXOUCRJQVYJQ-CKNDUULBSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
Definitions
- This invention relates to composition for treatment of viral diseases. More particularly, the invention pertains to efficacy of Ardrakadi Nishthivan (Bharat Bhaishajya Ratnakar (BBR) Jvaradhikarl43-145) against COVID-19; and their dosage forms including, without limitation, tablet, capsule, powder, pastilles, inhaler, mouthwash and the like.
- coronavirus disease (COVID-19) is caused by a virus, NOT by bacteria
- the virus that causes COVID-19 is in a family of viruses called Coronaviridae. Antibiotics are not effective against viruses.
- Xionga et al. 2020 reported eighteen randomized controlled trials (RCTs) in which 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquorice Root (Gancao, Radix glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellaria baicalensis), Pineilia Rhizome (Banxia, Rhizoma pinelliae tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae suspensae), and Bitter Apricot Seed (Kuxingren, Semen armeniacae amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction.
- CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein).
- Prophylactic care high risk population, primary contacts: Ashwagandha (Aqueous extract of Withania somnifera Dunal.LinnIP) or its powder: a. 500 mg extract or 1-3 g powder twice daily with warm water for 15 days or one month or as directed by Ayurveda physician. b. Guduchi Ghana vati (Samshamanivati or Giloy Ghana vati having Aqueous extract of Tinospora cordifolia IP) or the powder of Tinospora cordifolia:500 mg extract or 1-3 g powder twice daily with warm water for 15 days or one month or as directed by Ayurveda physician. c. Chyawanaprasha: 10 g with warm water / milk once a day.
- Asymptomatic COVID-19 positive a.
- Guduchi Ghana vati Sudshamanivati or Giloyvati having Aqueous extract of Tinospora cordifolia (Willd.) Miers.) or the powder of Tinospora cordifolia (Willd.) Miers.: 500 mg extract or 1-3 g powder twice daily with warm water for 15 days or one month or as directed by Ayurveda physician ii. Guduchi + Pippali (Aqueous extracts Tinospora cordifolia (Willd.) Miers.
- Mild COVID-19 Positive a. Symptomatic management Fever, Headache, Tiredness Dry Cough, Sore throat Nasal congestion: Without evidence of breathlessness or hypoxia
- AYUSH 64 500 mg twice daily with warm water for 15 days or as directed by Ayurveda physician.
- Clinical management protocol are not for cure, but for the management of asymptomatic and mild cases of COVID 19 and for prophylactic care. One should not get a false feeling of safety from adopting these measures.
- AYUSH-64 along-with standard care in ILI is safe and efficacious and this may use in other viral infections with pyrexia as add-on to standard care for early recovery and better outcome.
- Each capsule of AYUSH 64 consists of Alstoniascholaris R. Br.(Saptaparna) Bark Aqueous Extract 100 mg., Picrorhizakurroa Royle ex. Benth (Katuki) Root Aqueous Extract 100 mg., Swertiachirata Pexbex. Karst (Kiratatikta) Whole-plant Aqueous Extract 100 mg., Caesalpinia crista L.(Kuberaksha) Seed powder 200 mg.
- Wanjarkhedkar et al. reported that ayurvedic formulation was administered as an add-on to
- SoC Standard of Care
- Control group received SoC only.
- Patients receiving Dasamoolkaduthrayam Kashaya (Sahasrayogam) and Guluchyadi kwatham in tablet (Ashtang Hridayam) form in addition to the SoC showed a faster recovery from breathlessness with reduced ageusia .
- Patients on the treatment group could be discharged earlier than those from the control group.
- Table 1 Detailed formulation of Dashamoolakadutrayadi Kashaya Gulika tablet
- Table 2 Detailed formulation of GuluchyadiKwatham tablet
- Median hospital stay for COVID pharyngitis patients in the study group was 5 days as compared to 7 days in the control group.
- the patients with COVID pneumonia had the median hospital stay of 7 days in study group as compared to 8 days in control group.
- Ayurvedic intervention in a COVID-19 patient with severe hypoxia requiring supportive oxygen therapy Patient developed fever, severe cough, loss of smell, loss of taste, nasal block, anorexia, headache, body ache, chills, and fatigue and was hospitalized when she developed severe breathing difficulty. Later, she tested positive for COVID-19 by RT PCR. The patient sought Ayurvedic treatment voluntarily when her SPO2 remained at 80% even after being given oxygen support.
- the patient was administered Ayurvedic medicines while undergoing oxygen therapy at the hospital.
- the patient refused to take Fabiflu recommended by the treating physician and discontinued other allopathic drugs except for Vitamin C.
- the patient showed clinical improvement within a day of administration of Ayurvedic medicines and was able to talk, eat, and sit on the bed without breathing difficulty and her SPO2 became stable between 95 and 98%.
- she was asymptomatic without oxygen support and was discharged from the hospital in the following week. Since obesity and high plasma CRP indicated high risk for progression to severe disease, the favorable outcomes with Ayurvedic treatment in this patient is significant and warrants further studies.
- Ayurveda care may be considered as first -line cost-effective alternative for COVID-19 patients presenting with symptomatic hypoxia in an integrative setup.
- Kanakasavam 1 ml every two hours for first three days and 1 ml four times a day for next 8 days
- Indukantam Kasayam 1 ml every two hours for first three days, 1 ml four times a day for next 8 days.
- This invention discloses a composition
- a composition comprising at least Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose; and Rock Salt for treatment of patients of one or more of the diseases selected from the group consisting of: (a) Covid- 19 for overcoming viral infection, or (b) fungal disease for overcoming fungal infection, or (c) both.
- This invention also discloses a composition
- a composition comprising at least Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose, Rock Salt and ACE2 inhibitor active ingredients of herbs.
- composition as disclosed in above two paragraphs is a mouth dissolving tablet.
- composition is efficacious on the fungal infections including, but not limited to, infection from Mucor sp., Aspergillus sp.and Candida sp.
- the composition the fungal infection comprises infection from one or more fungi including, but not limited to, Rhizopus caespitosus, Rhizopus delemari, Rhizopus homothallicus, Rhizopus microspores, Rhizopus oryzae, Rhizopus reflexus, Rhizopus schipperae, Rhizopus stolonifer (black bread mold), Rhizopus arrhizus, Rhizopus oligosporus, , Rhizopus circinans, Rhizopus lyococcus, Rhizopus americanus, Rhizopus azygosporus, Rhizopus rhizopodiformis, Rhizopus niveus and Rhizopus sexuahs; Mucor amphibiorum, Mucor circinelloides, Mucor ellipsoideus, Mucor fragilis, Mucor hiemali, Mucor hiemalis f.
- fungi including, but not limited to, Rhizopus caespitosus, Rhizopus delemari,
- inventive composition as claimed herein is effective for immunomodulation and prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection, including, but not limited to, infection from SARS-CoV-2 and its mutants.
- the ACE2 inhibitors used as ingredient in the compositions of this invention include one or more, without limitation, extracts from Nicotiana benthamiana, Pelargonium graveolens L’Hér Momordica dioica roxb.ex willd, Valeriana jatamansijones ex roxb., Oroxylum indicum (L.), Artemisia absinthium L, Syzygium aromaticum (L.), Phaseolus vulgaris L Inula helenium L, Allium sativum L, Piper longum L, Ipomoea obscura (L.), Ipomoea obscura (L.), Piper nigrum L, Piper retrofractum vahl, Melaleuca cajuputi maton, Scutellaria baicalensis georgi, Erigeron breviscapus, Glycyrrhiza glabra L, Glycyrrhiza uralensis fisch.
- this invention comprises an inhaler for immunomodulation and prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection.
- the pathogenic viruses include SARS-CoV-2.
- the inhaler uses ACE 2 inhbitors are essential oils and oleoresins.
- the essential oils include, one or more, without limitation, Wintergreen Oil, Nilgiri/Eucalyptus oil, Terpeon Oil/Terpene oil, Camphor, Lemongrass oil, Terpinene, Anethole, Camphene, Carvacrol, Caryophyllene, Cinnamaldehyde, Cinnamyl acetate, Citral, Citronella, Citronellol, Criminal, Estragole, Eucalyptol, Eugenol, Fenchel, Geraniol, Umonene, Linalool, Menthol, Myrtanol, Ocimene, p- Cymene, Pinocarveol, Pulegone, Sabinene, Sylvestrene, Terpinen-4-ol, Thujene, Thymol and Zingiberene.
- the ACE2 inhibitors include, without limitation, one or more of zingiberene, zingiberenece, Gingerol, Eugenol, A co run calamus L, Zingiber officinale Rose, Trachyspermum ammi, Trachyspermum ammi L. and Syzygium aromaticum L & L.M., Nicotiana benthamiana, Pelargonium graveolens L’Hér.
- composition Take equal quantity of Rock salt, Ginger, long pepper and black pepper. Whole formulation processed with fresh juice of ginger.
- Black pepper (Piper nigrum Linn), also called pepper, perennial climbing vine of the family Piperaceae and the hotly pungent spice made from its fruits.
- Black pepper is native to the Malabar Coast of India and is one of the earliest spices known. Widely used as a spice around the world, pepper also has a limited usage in medicine as a carminative (to relieve flatulence) and as a stimulant of gastric secretions.
- Zingiber officinale Rose. commonly known as ginger
- ginger is a spice consumed worldwide for culinary and medicinal purposes.
- the plant has a number of chemicals responsible for its medicinal properties, such as anti-arthritis, anti- inflammatory, antidiabetic, antibacterial, antifungal, anticancer etc.
- the present chapter compiled scientific data retrieved from websites, such as PubMed, Science Direct, Scopus, Web-of-Knowledge, Google Scholar, and others related to the phytochemistry and pharmacology of ginger.
- PubMed Science Direct
- Scopus Web-of-Knowledge
- Google Scholar and others related to the phytochemistry and pharmacology of ginger.
- a synopsis of the world production of the plant as well as some patents related to Z. officinale are also provided.
- Rock salt on the other hand, is already found in solid form and is simply mined. This type of salt is also known as halite and often comes in larger crystals or has a coarser texture.
- Ayurvedic ingredients work in synergism and deliver efficacy as a whole in combination with each other.
- Immunomodulators are medications used to help regulate or normalize the immune system. Examples include one class of immunomodulation which is used as an add-on therapy to treat support in viral, bacterial and fungal infections and even in auto immune disorders.
- the immunomodulator formulation was made in the instant invention comprising the ingredients provided in Table 5; the efficacies of which are also mentioned in the Table 5. Table 5
- an invention is claimed also in an inhaler for prevention and prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection.
- the inhaler is made from oils and oleoresins of herbs having
- ACE2 blocking activity receptor blocker activity (Dear DR. Milind: Please confirm again by making reference work on whether the phrase “having ACE2 blocking activity receptor blocker activity” is applicable to oils as well as the oleoresins of hers. Clarity and accuracy on this is very much essential from the point of view of claims to be made. Is it possible that “Oils” serve as “carriers” for the oleoresins and the oleoreins are only actives which are ACE inhibitors? For oils please check where is their mention made as ACE inhibitors and cite the same here) and not as ACE inhibitors .
- the inhaler made from oleoresins of herbs having ACE2 receptor blocker activity is used as prophylactic/preventive for infection from Coronavirus- 19 infection. It is also an embodiment of this invention wherein inhalers of oleoresins of selected herbs having ACE2 receptor blocker activity are used to keep a person healthy. It is also an embodiment of this invention wherein inhalers the oleoresins include, without limitations, zingiberene, zingiberenece, Gingerol and Eugenol.
- Yadalam et al (2021) have listed following essential oils as anti-virals against SARS-CoV-2 which can be used in inhaler: Terpinene, Anethole, Camphene, Carvacrol, Caryophyllene, Cinnamaldehyde, Cinnamyl acetate, Citral, Citronella, Citronellol, Cuminal, Estragole, Eucalyptol, Eugenol, Fenchel, Geraniol, Umonene, Linalool, Menthol, Myrtanol, Ocimene, p- Cymene, Pinocarveol, Pulegone, Sabinene, Sylvestrene, Terpinen-4-ol, Thujene, Thymol and Zingiberene.
- Muchtaridi et al have enlisted Plant derivatives with potential effect on the SpikeRBD/TMPRSS2/ACE2 axis.
- the list comprises: Nicotiana benthamiana, Pelargonium graveolens L’Hér Momordica dioica roxb.ex willd, Valeriana jatamansijones ex roxb., Oroxylum indicum (L.), Artemisia absinthium L, Syzygium aromaticum (L.), Phaseolus vulgaris L Inula helenium L, Allium sativum L, Piper longum L, Ipomoea obscura (L.), Ipomoea obscura (L.), Piper nigrum L, Piper retrofractum vahl, Melaleuca cajuputi maton, Scutellaria baicalensis georgi, Erigeron breviscapus, Glycyrrhiza glabra L, Glycyrrhiza uralensis fi
- oleoresins form all these plants can be sued in the inhaler according to this invention.
- the fungi that cause Mucormycosis includes Rhizopus caespitosus, Rhizopus delemari, Rhizopus homothallicus, Rhizopus microspores, Rhizopus oryzae, Rhizopus reflexus, Rhizopus schipperae, Rhizopus stolonifer (black bread mold), Rhizopus arrhizus, Rhizopus oligosporus, , Rhizopus circinans, Rhizopus lyococcus, Rhizopus americanus, Rhizopus azygosporus, Rhizopus rhizopodiformis, Rhizopus niveus and Rhizopus sexualis; Mucor amphibiorum, Mucor circinelloides, Mucor ellipsoideus, Mucor fragilis, Mucor hiemali, Mucor hiemalis f.
- Mucor recemosus and the fmgicieds have generic efficacy against all fingi,a person skille din the art can recognise that it shall be equally efficacious against above list fo fingi also which cause Mucormycosis, Aspergillosis and Candidosis.
- Ardrakadi Nishthivan its ingredients and method of preparation Verse 143 describes ingredients and composition of Ardrakadi Nishthivan original reference from BHARAT BHAISHAJYA RATNAKAR. This powder contains following ingredients: Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose; and Rock Salt. Table 6
- the COVID-19 RT-PCR test is a well-known real-time reverse transcription polymerase chain reaction (RT-PCR) test for the qualitative detection of nucleic acid of the causal virus SARS- CoV-2 in upper and lower respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate) collected from individuals suspected of patients suspected of COVID-19 by their healthcare provider (HCP); as well as upper respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, nasal swabs, or mid-turbinate swabs) collected from any individual, including for testing of individuals without symptoms or other reasons to suspect COVID19 infection
- HCP healthcare provider
- upper respiratory specimens such as nasopharyngeal or oropharyngeal swabs, nasal swabs, or mid-tur
- Table 8 Pilot study done on 4 patients . 500 mg 1 mouth dissolving tablets of Ardrakadi Nishthivan 4 hourly for 3 days at regular intervals between 8 am to 8 pm .Nasal+Oral swab taken for quantitative Viral load (RTqPCR) each 24 hrly. Decline in 99% of the viral load is considered as virus free status of the patient. Since there was no treatment between 72 and 96 hours, the patients are considered to have become virus free with maximum 72 hours of treatment.
- Example 5 Example 5
- Immunity Booster Formulation comprise following ingredients
- Aqueous extract of ingredients 1 to 5 that were readily available in market were procured. In the alternative, the extracts can also be made by methods well known to a person of an ordinary skill in the art. 2. Ingredient 6 was also procured from the market and the same is readily available.
- Ingredient 7 is prepared by sohxlet extraction process using solvent ether, hexane using seeds of Zanthoxylum armatum DC.
- This API can be converted in tablet, Orally Dissolving Tablet, syrup, lozenges, capsules, Pills, pastilles as per standard industrial dosage forms by methods well known in the art.
- Scope of Method This test determines if test product can inactivate virus in suspension. One part of the virus suspension with nine Parts of the test substance are held at the desired temperature for the required contact time and then assayed for viable virus in an appropriate host system.
- Test Product 10 mg/ml Cone.
- Contact time 4 hours
- Test Method 24 Well plate, Neutralisation and Dilution method
- Virus strains and host cells Virus strains and hosA12:D17t cells:
- Test Virus Human Coronavirus HCoV-229E (Surrogate of SARS-CoV-2)
- Test Virus Human Coronavirus HCoV-229E (Surrogate of SARS-CoV-2)
- Test Virus Human Coronavirus HCoV-229E (Surrogate of SARS-CoV-2)
- Test Sample Thinqure 20 (Trademark for Ardrakadi Nishthivan) 10 mg/ml Cone.
- HCoV-229E belongs to the family Coronaviridae and subfamily Orthocoronavirinae.
- HCoV-229E is one of seven known coronaviruses that infect humans. The other six are Human HCoV-OC43, HCoV-NL63, HCoV- HKU1, MERS-CoV, SARS-CoV-1, SARS-CoV-2.
- test product determines if test product can inactivate virus in suspension.
- One part of the virus suspension with nine Parts of the test substance are held at the desired temperature for the required contact time and then assayed for viable virus in an appropriate host system.
- Test Method 24 Well plate, Neutralisation and Dilution method
- Eagle Eagle’s minimal essential medium (EMEM), supplemented with inactivated FBS (Fetal Bovine Serum) and antibiotics Virus strains and host cells:
- Test Virus Influenza A virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
- the prepared Virus inoculum is added to the test product and the virus recovery control media at a ratio of 1 part virus + 9 parts test product.
- test and recovery suspensions are neutralized.
- Test Virus Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679 Table 12
- Test Virus Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
- Test Virus Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
- Test Virus Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
- Test Virus Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
- Test Virus Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
- Scope of Method This test determines if test product can inactivate virus in suspension. One part of the virus suspension with nine parts of the test substance are held at the desired temperature for the required contact time and then assayed for viable virus in an appropriate host system.
- Test was inoculated with test fungus individually (approximately10 8 CFU/ml). After the specified exposure time of 1 hour and 4 hours surviving microorganisms were recovered by drawing an aliquot, neutralizing and performing Standard Pour plate Technique. Culture count was ascertained by dilution Blank. Adequate Validation of Neutralizing agent was also carried. Test was carried out in duplicate and average count was taken as CFU/ml.
- the Ardrakadi Nishthivan was standardized by HPLC method to evaluate the piperine and gingerol content in the formulation.
- patient must have had RT-PCR test positive for both oral and nasal swabs.
- the patients who were diagnosed Covid positive and were taking Ardrakadi Nishthivan as prescribed by physician were also included in the study.
- the patients with history of intracranial bleeding, incomplete medical history, or suffering from haemoglobinopathies, active malignancies were excluded from the study.
- the pregnant or lactating women, smokers, alcohol drinkers, and the females not ready to use acceptable contraceptive methods during treatment periods were also excluded from the study. After screening with inclusion and exclusion criteria, total 30patients were included in the study.
- the patients were asked to take tablets in the mouth and slowly to be sucked (licked within mouth by tongue) till entire tablet is dissolved in mouth and not to swallow or chew or crush.
- the first dose was 2 tablets of Ardrakadi Nishthivan and from second dose it was reduced to 1 tablet at a time at 4 hours interval; thus on day 1, five tablets were given. From day 2 to day 5 one tablet was given every 4 hrs. (08:00 AM, 12:00 noon, 04:00 PM, and 08:00 PM). Out of 30 patients, 29 completed the treatment, one patient was excluded from the study due to not completing the treatment.
- the viral load after treatment was statistically compared with viral load before treatment by performing Wilcoxon rank sum test as it is performed when sample size is below 40.
- the data was represented as Mean ⁇ SD (Standard Deviation).
- the p ⁇ 0.05 was considered as significant.
- the analysis was performed using statistical software GraphPad Prism Version 8. EFFICACY RESULTS AND TABULATIONS OF INDIVIDUAL SUBJECT DATA
- the viral load after treatment was statistically compared with viral load before treatment by performing Wilcoxon rank sum test as it is performed when sample size is below 40.
- the data was represented as Mean ⁇ SD (Standard Deviation).
- the p ⁇ 0.05 was considered as significant.
- the analysis was performed using statistical software GraphPad Prism Version 8.
- Covid-19 virus load is poorly characterized in Covid- 19.
- the plasma viral load is directly associated with progression of disease severity (Fajnzylber et al, 2020; Pujadaset al. 2020).
- Increase in plasma viral load leads to worsening of disease severity, marked reduction in lymphocytes count, and significant increase in plasma inflammatory markers such as interleukin 6 (IL-6), and C-reactive protein (CRP) leading to increased mortality (Fajnzylber et al, 2020).
- IL-6 interleukin 6
- CRP C-reactive protein
- Ardrakadi Nishthivan treatment showed significant reduction in the viral load indicating its beneficial role in the inhibition of disease progression and mortality rate.
- the active components of the Ardrakadi Nishthivan (Piperine and Gingerol, Zingeberene) possess potent anti-inflammatory and antiarthritic effects of piperin in human interleukin 1 -stimulated fibroblast-like synoviocytes and in rat arthritis models activities (Bang et al. 2009) and Anti- oxidative and anti-inflammatory effects of ginger in health and physical activity (Mashhadi et al. 2013) may also help in reducing the cytokine storm and further worsening of conditions.
- the angiotensin converting enzyme - 2 (ACE2) receptors play a very pivotal role in viral entry and its expression in the major vital organs such as heart, kidney and lungs (Habas et al. 2019).
- SARS-CoV-2 virus causes balance between ACE and ACE2 and activate the renin angiotensin aldosterone system (RAAS) leading to entry of virus in host cell and its replication (Beyerstedt 2021).
- RAAS renin angiotensin aldosterone system
- Inhibition of ACE2 receptors and RAAS system can limit the viral load and disease progression by inhibiting viral entry and replication in the host cells 1.
- the piperine, zingiberene and gingerol have proven ACE inhibitory activity (Maurya et al, 2020; Bare et al.
- Ardrakadi Nishthivan This action of Ardrakadi Nishthivan may be attributed to ACE2 inhibition and inhibition of viral entry in the host cells. Founded results suggests that phytochemicals from Ardrakadi Nishthivan might be effective as a therapeutic as well as prophylaxis against COVID-19 by preventing viral attachment to the host cells through inhibition of spike glycoprotein. Molecular docking results are indicated with excellent binding affinity of phytochemical piperine, Zingiberene against SARS-CoV-2 spike glycoprotein and its cellular receptor along with MolDock score and other parameters (Maurya et al, 2020; Bare et al. Ardrakadi Nishthivan.
- Mole dock study shows phytochemicals from of Zingiber officinale as entry inhibitor of SARS- COVID 2 VIRUS. Gingerol and Zingiberene had effective binding activity with ACE2 receptors (Maurya et al, 2020; Bare et al. 2020; Chakotiya and Sharma 2020).
- Ardrakadi Nishthivan comprising of Piper longumLinn, Piper nigrumLinn.
- Zingiber officinale Rose and rock salt possess various active agents like piperine, Zingiberene, gingerol which play their role for its effectiveness against SARS-Co2 virus.
- Ardrakadi Nishthivan might be acting on single target or multiple targets for inhibiting SARS-CoV2 viral load.
- Covid-19 can cause significant discomfort, continuous cough, fever/high temperature (37.8°C or greater), Loss of, or change in, sense of smell or taste, respiratory failure, shock, or multi- organ dysfunction, reduce quality of life, and lead to a loss of productivity.
- Ardrakadi Nishthivan have been shown to improve quality of life in Covid-19 patients. Treatment with Ardrakadi Nishthivan was safe and it was well tolerated. Adverse event experienced during clinical trial, all of them were mild in the nature. In addition, there were no serious adverse events reported at any time during the study.
- Ardrakadi Nishthivan has beneficial effects in treatment of Covidl9 which may be linked to decrease in total viral load in patients. It provided better relief for recovery of the COVID-19 disease. Ardrakadi Nishthivan is well-tolerated, safe and is effective in COVID-19 patients, especially with reference to the reduction in viral load.
- Herbal Inhaler having ACE2 receptor blocking activity In the following is an illustrative example of the inhaler made using ACE2 inhibitors.
- Sunthi Oil Oil ofZinziber officinale Rose
- solvent used hexane or petroleum ether.
- iii. Ajwain oil Oil oil of Trachyspermum ammi (L.) Sprague ex Turrill
- was prepared by extracting seeds was extracted by using soxhlet method .
- iv. Clove oil Oil oil of Syzygium aromaticum L & L.M.
- flowder buds was extracted by using soxhlet method, solvent used hexane or petroleum ether
- Base B c Final API (Active Pharma Ingredient) is prepared by mixing Base A with Base B in a mixer accompanied with stirring for 15 minutes. 3. Dosage form a. Standard inhaler - cotton absorbent stick is filled with API as per optimum level.
- Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nature Microbiology 2020 December 3.
- Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets
- COVID-19 Expert Rev. Anti. Infect. Ther. 2020; 18: 1201-11 Beyerstedt S, Casaro EB, Rangel ÉB.
- COVID-19 angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis 2021; 40: 905—19
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Botany (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Zoology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
This invention discloses a mouth dissolving tablet composition comprising at least Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rosc; and Rock Salt (Saindhav in Sanskrit language) as a composition and also for treatment of one or more of the diseases selected from the group consisting of: (a) Covid-19 for overcoming viral infection, or (b) fungal disease for overcoming fungal infection, or (c) both. The claimed composition is effective for immunomodulation and prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection, including, but not limited to, infection from SARS-CoV-2 and its mutants. In one aspect this invention comprises an inhaler for prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection. The pathogenic viruses includes SARS-CoV-2. The inhaler uses ACE 2 inhibitors are essential oils and oleoresins.
Description
HERBAL COMPOSITION FOR COVID 19 TREATMENT
FIELD OF INVENTION
This invention relates to composition for treatment of viral diseases. More particularly, the invention pertains to efficacy of Ardrakadi Nishthivan (Bharat Bhaishajya Ratnakar (BBR) Jvaradhikarl43-145) against COVID-19; and their dosage forms including, without limitation, tablet, capsule, powder, pastilles, inhaler, mouthwash and the like.
BACKGROUND OF THE INVENTION
World is confronting an extraordinary pandemic of COVID 19 caused by Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2), spread globally with more than 35 million confirmed cases and 1 million deaths till October 2020. This contagion is still continuing to spread and there is no confirmed / assured cure seen coming. The world badly needs clinically-proven prophylaxis and therapeutic strategies. Various systems of Medicine are trying to find solution in some or the other way.
It is acknowledged by WHO (World Health Organization) that no currently available Allopathic medicines, including anti-virals, are effective against COVID-19.
The coronavirus disease (COVID-19) is caused by a virus, NOT by bacteria
The virus that causes COVID-19 is in a family of viruses called Coronaviridae. Antibiotics are not effective against viruses.
Some people who become ill with COVID-19 can also develop a bacterial infection as a complication. In this case, antibiotics may be recommended by a health care provider.
There is currently no medication to cure COVID-19. If you have symptoms, call your health care provider or COVID-19 hotline for assistance. Guidance given by World Health Organization is available on the link: https://www.who.int/emergencies/diseases/novel- coronavirus-2019/advice-for public/mythbusters#:~:text=There%20is%20currently%20no%201icensed,19%20hotline%20f or%20assistance
While the work reported here is progressing, current status of knowledge, as on 3 rd December 2020is that there is , on treatment of COVID-19, there is no allopathic antiviral that has proven efficacy against COVID- 19 in human beings. In a latest development it has been shown by Cox et (2020) that a therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. This is at an early stage of development, has not shown efficacy in human beings; and will take a long time to reach human beings for treatment.
Agarwal et al (2020) have reported that in a clinical trial conducted by Indian Council of Medical Research, Convalescent Plasma therapy has also failed to show any significant impact in treating the COVID-19 patients; and antivirals (Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir, Oseltamivir), broad spectrum antibiotics are also considered as not effective.
Hence, exploring herbal medicines becomes relevant.
Remedies based on Chinese traditional herbs have been investigated in clinical trials and reviewed in a publication available on the link https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331568/
Xionga et al. (2020) reported eighteen randomized controlled trials (RCTs) in which 2275 patients were enrolled. Most of CHMs were originated from classical Chinese herbal formulas. Liquorice Root (Gancao, Radix glycyrrhizae), Baical Skullcap Root (Huangqin, Radix Scutellaria baicalensis), Pineilia Rhizome (Banxia, Rhizoma pinelliae tematae), Forsythia Fruit (Lianqiao, Fructus Forsythiae suspensae), and Bitter Apricot Seed (Kuxingren, Semen armeniacae amarum) were most frequently used Chinese herbs. The most commonly used dosage formulation was decoction. Their meta-analyses found that comparing CHM group and conventional western medicine group, CHM group has improvements in several clinical parameters including lung CT, clinical cure rate, ranging from mild to critical cases, length of hospital stay, total score of clinical symptoms, fever reduction time, symptom score of fever, number of cough reduction cases, symptom score of cough, number of fatigue reduction cases, symptom score of fatigue, disappearing time of fatigue, TCM syndrome, viral nucleic acid testing, and inflammatory biomarkers (C-reactive protein).
However, the reviewers regarded that firstly, poor methodological design is a very common problem in most of included trials. Significant drawbacks regarding sequence generation of randomization, concealment of allocation, reporting on blinding, dropouts, and pre-estimation of sample size was not done. Secondly, as viral nucleic acid testing turning positive again is very common in the recovery stage of COVID-19, no trial adopted long-term follow-up.
Ayurveda is the ancient school of medicine in India which has history of medicines derived from medicinal plants validated for thousands of years for several diseases.
National Clinical Management Protocol based on Ayurveda and Yoga for management of Covid-19 published by Ministry of AYUSH (Ayurveda, Yoga, Unanni, Siddha and Homeopathic medicine) published on date 6th October, 2020 on (1) Knowledge from Ayurveda classics and experience from clinical practices (2) Empirical evidences and Biological plausibility (3) Emerging trends of ongoing clinical studies. This consensus document is developed by expert committees from All India Institute of Ayurveda (AIIA), Delhi, Institute of Post Graduate Training and Research in Ayurved (IPGTRA), Jamnagar, and National Institute of Ayurveda (NIA), Jaipur, Central Council for Research in Ayurveda (CCRAS), Central Council for Research in Yoga and Naturopathy (CCRYN), other national research organizations. This protocol is for management of mild COVID-19. Moderate to Severe COVID-19 individuals may have informed choice of treatment options. All severe cases will be referred. This protocol and its annexure are approved by the Chairman, Interdisciplinary Committee for inclusion of Ayurveda and Yoga in the management of mild COVID-19 and approved by the empowered committee of the Interdisciplinary AYUSH Research and Development Taskforce on COVID-19, both constituted by the Ministry of AYUSH. Thus, this consensus document represents all that is considered applicable from Ayurveda by a person skilled in the art as well as by those who are highly knowledgeable and qualified in Ayurveda. A complete document entitled “National Clinical Management Protocol based on Ayurveda and Yoga for management of Covid- 19” is available on the link https://www.ayush.gov.in/docs/ayush-Protocol-covid-19.pdf Important highlights of the same are provided below:
"General and Physical measures:
1. Gargle with warm water added with a pinch of turmeric and salt. Water boiled with Triphala (dried fruits of Emblica officinalis, Terminalia chebula,Terminalia bellerica') or Yashtimadhu (Glycyrrhiza glabra) also can be used for gargling.
2. Nasal instillation/application of medicated oil (Anutaila or ShadbinduTaila) or plain oil (Sesame or Coconut) or nasal application of cow's ghee (Goghrita) once or twice in a day, especially before going out and after coming back to home.
3. Steam inhalation with Ajwain (Trachyspermum ammi) or Pudina (Mentha spicata) or Eucalyptus oil once a day.
Dietary measures:
1. Use warm water or boiled with herbs like ginger (Zingiber officinale) or coriander (Coriandrum sativum) or basil (Ocimum sanctum / Ocimum basilicum), or cumin (Cuminum cyminum) seeds etc., for drinking purpose.
2. Drink Golden Milk (Half tea spoon Haldi (Curcuma longa) powder in 150 ml hot milk) once at night. Avoid in case of indigestion.
3. Drink AyushKadha or Kwath (hot infusion or decoction) once a day. This Kadha, in 100gmcontains Tulsi (Ocimum sanctum) leaves 44.3gm, Dalchini (Cinnamomum zeylanicum) stem bark 22.3gm, Sunthi (Zingiber officinale) 22.3gm, Krishna Marich (Piper nigrum) 11.1 gm. Less than 1 teaspoon (3 gms) is used to make decoction or herbal tea, consumed once or twice a day by adding the powder to water, adding jaggary to taste and/or Fresh lemon Juice and or resins to taste if needed, the liquid is boiled and strained using a tea strainer/filter.
Specific Measures / Symptom Management:
1. Prophylactic care (high risk population, primary contacts): Ashwagandha (Aqueous extract of Withania somnifera Dunal.LinnIP) or its powder: a. 500 mg extract or 1-3 g powder twice daily with warm water for 15 days or one month or as directed by Ayurveda physician. b. Guduchi Ghana vati (Samshamanivati or Giloy Ghana vati having Aqueous extract of Tinospora cordifolia IP) or the powder of Tinospora cordifolia:500 mg extract or 1-3 g powder twice daily with warm water for 15 days or one month or as directed by Ayurveda physician. c. Chyawanaprasha: 10 g with warm water / milk once a day.
2. Asymptomatic COVID-19 positive: a. For prevention of disease progression to symptomatic and severe form and to improve recovery rate: i. Guduchi Ghana vati (Samshamanivati or Giloyvati having Aqueous extract of Tinospora cordifolia (Willd.) Miers.) or the powder of Tinospora cordifolia (Willd.) Miers.: 500 mg extract or 1-3 g powder twice daily with warm water for 15 days or one month or as directed by Ayurveda physician ii. Guduchi + Pippali (Aqueous extracts Tinospora cordifolia (Willd.) Miers. IP and Piper longum L.375 mg twice daily with warm water for 15 days or as directed by Ayurveda physician. iii. AYUSH64: 400 mg twice daily with warm water for 15 days or as directed by Ayurveda physician.
3. Mild COVID-19 Positive: a. Symptomatic management Fever, Headache, Tiredness Dry Cough, Sore throat Nasal congestion: Without evidence of breathlessness or hypoxia
(normal situation): i. Guduchi + Pippali (Aqueous extracts Tinospora cordifolia Wild and Piper longum L.) - 375 mg twice daily with warm water for
15 days or as directed by Ayurveda physician. ii. AYUSH 64: 500 mg twice daily with warm water for 15 days or as directed by Ayurveda physician.
However, it is underlined in this protocol that the interventions and measures proposed in the
Clinical management protocol are not for cure, but for the management of asymptomatic and mild cases of COVID 19 and for prophylactic care. One should not get a false feeling of safety from adopting these measures.
Gudetiet al (2020) have shown that AYUSH-64 along-with standard care in ILI is safe and efficacious and this may use in other viral infections with pyrexia as add-on to standard care for early recovery and better outcome. Each capsule of AYUSH 64 consists of Alstoniascholaris R. Br.(Saptaparna) Bark Aqueous Extract 100 mg., Picrorhizakurroa Royle ex. Benth (Katuki) Root Aqueous Extract 100 mg., Swertiachirata Pexbex. Karst (Kiratatikta) Whole-plant Aqueous Extract 100 mg., Caesalpinia crista L.(Kuberaksha) Seed powder 200 mg.
Wanjarkhedkar et al. reported that ayurvedic formulation was administered as an add-on to
Standard of Care (SoC) in patients with mild to moderate symptoms, in this prospective, open-
label, comparative study. Control group received SoC only. Patients receiving Dasamoolkaduthrayam Kashaya (Sahasrayogam) and Guluchyadi kwatham in tablet (Ashtang Hridayam) form in addition to the SoC showed a faster recovery from breathlessness with reduced ageusia . Patients on the treatment group could be discharged earlier than those from the control group. Addition of Dasamoolkaduthrayam kashaya (Sahasrayogam) and Guluchyadi kwatham (Ashtanghridayam)to SoC appeared to accelerate recovery of patients hospitalized for CO VID 19 infection, in terms of reduction of symptoms and duration of hospital stay.
Above two formulations have following contents:
Table 1: Detailed formulation of Dashamoolakadutrayadi Kashaya Gulika tablet
Table 2 Detailed formulation of GuluchyadiKwatham tablet
Early clinical improvement in breathlessness was observed with the present add-on Ayurveda regimen. Ageusia reduced early with add-on Ayurveda regimen. The median duration of hospital stay was reduced; this factor is of importance in view of shortage of hospital beds in
India. The learning from this study is the potential of Ayurvedic therapy in treating COVID 19.
Median hospital stay for COVID pharyngitis patients in the study group was 5 days as compared to 7 days in the control group. The patients with COVID pneumonia had the median hospital stay of 7 days in study group as compared to 8 days in control group.
Thus, here also the Ayurvedic treatment was “an add-on to Standard of Care (SoC)”, and not a first line treatment.
Joshi and Puthiyedath (2020) reported a case study wherein for the first time, the outcomes of
Ayurvedic intervention in a COVID-19 patient with severe hypoxia requiring supportive oxygen therapy.
Patient developed fever, severe cough, loss of smell, loss of taste, nasal block, anorexia, headache, body ache, chills, and fatigue and was hospitalized when she developed severe breathing difficulty. Later, she tested positive for COVID-19 by RT PCR. The patient sought Ayurvedic treatment voluntarily when her SPO2 remained at 80% even after being given oxygen support.
The patient was administered Ayurvedic medicines while undergoing oxygen therapy at the hospital. The patient refused to take Fabiflu recommended by the treating physician and discontinued other allopathic drugs except for Vitamin C.
The patient showed clinical improvement within a day of administration of Ayurvedic medicines and was able to talk, eat, and sit on the bed without breathing difficulty and her SPO2 became stable between 95 and 98%. In the next two days, she was asymptomatic without oxygen support and was discharged from the hospital in the following week. Since obesity and high plasma CRP indicated high risk for progression to severe disease, the favorable outcomes with Ayurvedic treatment in this patient is significant and warrants further studies.
Ayurveda care may be considered as first -line cost-effective alternative for COVID-19 patients presenting with symptomatic hypoxia in an integrative setup.
She was administered the following Ayurvedic medicines immediately.
1. Sadangapaniyam with Guduci: One sip - every 10 minutes for 3 days, One sip every half hour for next 2 days, One sip every two hours for next 6 days.
2. Saddharanacurna: 1 pinch every hour for 7 days.
3. Suksmatriphala: 250 mg tab at bed time for four days
4. Kanakasavam: 1 ml every two hours for first three days and 1 ml four times a day for next 8 days
4. Indukantam Kasayam: 1 ml every two hours for first three days, 1 ml four times a day for next 8 days.
On first day of hospitalization she was prescribed: Azee (Azithromycin) 625 mg 1-0-0, Cefexime 200 mg 1-0-1, T. Dexamethasone 6 mg 1-0-0, T. Acetaminophen 650 mg SOS, T. Vitamin C 500 mg 1-0-1, T. Pantoprazole 40 mg 1-0-0, C. Becosule (Vitamin B Complex) 1- 0-0, Syp. Grilinctus (Guaifenesin, Chlorpheniramine maleate and Ammonium chloride) 2 tsp 1-1-1. In addition, she was prescribed by the doctors the option of starting Fabiflu, but the patient declined to take this medicine. She stopped taking all the above prescribed medicines after starting the Ayurvedic treatment (22 June 2020 by 7 pm). Only Vitamin C and oxygen support was continued. By 24.6.2020 her cough became mild and breathing difficulty was experienced only on exertion. All other symptoms subsided except for mild headache. The SPO2 levels improved and stabilised at 95-98%. She was maintained on intermittent oxygen, which was completely withdrawn on 26 June 2020 by 7 pm. Futher, Ayurvedic treatment was continued along with Vitamin C supplementation. She was not given any other medications except on the first two days of hospitalization prior to starting Ayurvedic treatment.
This is first report of Ayurvedic treatment being efficacious without Allopathic treatment except for vitamin C.
However, this protocol of Ayrvedic treatment included five formulations and very elaborate frequency of administration of the medicines, which is very difficult for compliance. Hence, there was still a need for lesser number of formulations/ingredients and simple schedule of administration of the medicines.
SUMMARY OF THE INVENTION
This invention discloses a composition comprising at least Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose; and Rock Salt for treatment of patients of one or more of the diseases selected from the group consisting of: (a) Covid- 19 for overcoming viral infection, or (b) fungal disease for overcoming fungal infection, or (c) both.
This invention also discloses a composition comprising at least Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose, Rock Salt and ACE2 inhibitor active ingredients of herbs.
In one embodiment the composition as disclosed in above two paragraphs is a mouth dissolving tablet.
The composition is efficacious on the fungal infections including, but not limited to, infection from Mucor sp., Aspergillus sp.and Candida sp.
The composition the fungal infection comprises infection from one or more fungi including, but not limited to, Rhizopus caespitosus, Rhizopus delemari, Rhizopus homothallicus, Rhizopus microspores, Rhizopus oryzae, Rhizopus reflexus, Rhizopus schipperae, Rhizopus stolonifer (black bread mold), Rhizopus arrhizus, Rhizopus oligosporus, , Rhizopus circinans, Rhizopus lyococcus, Rhizopus americanus, Rhizopus azygosporus, Rhizopus rhizopodiformis,
Rhizopus niveus and Rhizopus sexuahs; Mucor amphibiorum, Mucor circinelloides, Mucor ellipsoideus, Mucor fragilis, Mucor hiemali, Mucor hiemalis f. silvaticus, Mucor. indicus, Mucor mucedo, Mucor paronychius, Mucor piriformis, Mucor phimbeus, Mucor pseudolusitanicus, Mucor racemosus, Mucor ramosissimus, Mucor variicolumellatus, Mucor vehutinosus, Apophysomyces variabilis, Apophysomyces trapeziformis, Apophysomyces ossiformis: Lichtheimia ramosa L. corymbifera, Cunninghamella binarieae R.Y. Zheng 2001, Cunninghamella blakesleeana, Cunninghamella Candida Yosh. Yamam. 1929, Cunninghamella clavata R.Y. Zheng & G.Q.Chen 1998, Cunninghamella echinulata (Thaxt.) Thaxt. ex Blakeslee 1905, Cunninghamella elegans Lendn. 1905, Cunninghamella homothallica Komin. & Tubaki 1952, Cunninghamella intermedia K.B.Deshp. & Mantri 1966, Cunninghamella multiverticillata R.Y. Zheng & G.Q. Chen 2001, Cunninghamella phaeospora Boedijn 1959, Cunninghamella polymorpha Pispek 1929, Cunninghamella septata R.Y.Zheng 2001 and Cunninghamella vesiculosa P.C.Misra 1966, Aspergillus flavus , Aspergillus fumigatus, Candida albicans and Candida glabrata.
The inventive composition as claimed herein is effective for immunomodulation and prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection, including, but not limited to, infection from SARS-CoV-2 and its mutants.
The ACE2 inhibitors used as ingredient in the compositions of this invention include one or more, without limitation, extracts from Nicotiana benthamiana, Pelargonium graveolens L’Hér Momordica dioica roxb.ex willd, Valeriana jatamansijones ex roxb., Oroxylum indicum (L.), Artemisia absinthium L, Syzygium aromaticum (L.), Phaseolus vulgaris L Inula helenium L, Allium sativum L, Piper longum L, Ipomoea obscura (L.), Ipomoea obscura (L.),
Piper nigrum L, Piper retrofractum vahl, Melaleuca cajuputi maton, Scutellaria baicalensis georgi, Erigeron breviscapus, Glycyrrhiza glabra L, Glycyrrhiza uralensis fisch. ex DC. Bupleurum spp. Heteromorpha spp., Scrophularia scorodonia L, Withania somnifera (L.), Asparagus racemosus willd., Diplocyclos palmatus (L.), Citrus spp., Vitis vinifera L. and Aframomum melegueta K.Schum
In one aspect this invention comprises an inhaler for immunomodulation and prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection. The pathogenic viruses include SARS-CoV-2.
The inhaler uses ACE 2 inhbitors are essential oils and oleoresins. The essential oils include, one or more, without limitation, Wintergreen Oil, Nilgiri/Eucalyptus oil, Terpeon Oil/Terpene oil, Camphor, Lemongrass oil, Terpinene, Anethole, Camphene, Carvacrol, Caryophyllene, Cinnamaldehyde, Cinnamyl acetate, Citral, Citronella, Citronellol, Criminal, Estragole, Eucalyptol, Eugenol, Fenchel, Geraniol, Umonene, Linalool, Menthol, Myrtanol, Ocimene, p- Cymene, Pinocarveol, Pulegone, Sabinene, Sylvestrene, Terpinen-4-ol, Thujene, Thymol and Zingiberene. The ACE2 inhibitors include, without limitation, one or more of zingiberene, zingiberenece, Gingerol, Eugenol, A co run calamus L, Zingiber officinale Rose, Trachyspermum ammi, Trachyspermum ammi L. and Syzygium aromaticum L & L.M., Nicotiana benthamiana, Pelargonium graveolens L’Hér. Momordica dioica roxb.ex willd, Valeriana jatamansijones ex roxb., Oroxylum indicum (L.), Artemisia absinthium L, Syzygium aromaticum (L.), Phaseolus vulgaris L Inula helenium L, Allium sativum L, Piper longum L, Ipomoea obscura (L.), Ipomoea obscura (L.), Piper nigrum L, Piper retrofractum vahl, Melaleuca cajuputi maton, Scutellaria baicalensis georgi, Erigeron breviscapus, Glycyrrhiza glabra L, Glycyrrhiza uralensis fisch. ex DC. Bupleurum spp. Heteromorpha spp.,
Scrophularia scorodonia L, Withania somnifera (L.), Asparagus racemosus willd., Diplocyclos palmatus (L.), Citrus spp., Vitis vinifera L. and Aframomum melegueta K. Schum
DETAILED DESCRIPTION OF THE INVENTION
“National Clinical Management Protocol based on Ayurveda and Yoga for management of Covid- 19” published by Ministry of AYUSH, Government of India, is an authentic source of current status of Ayurveda in the context of Covid- 19 treatment. It has very categorically concluded with clear advice that:
“ - the interventions and measures proposed in the Clinical management protocol are not for cure, but for the management of asymptomatic and mild cases of COVID 19 and for prophylactic care. One should not get a false feeling of safety from adopting these measures”
On this background, it was surprising to find one Ayurvedic formulation, known in Ayurveda scriptures as “Ardrakadi Nishthivan” in which worked with very high virucidal efficacy as stand-alone treatment in absence of Standard-care-of-Allopathic Covid- 19 treatment; and has provided a complete control on infection, a complete cure to Covid-19 patients within a matter of 72 hours with administration of a tablet each four times a day.
Subsequently, this formulation has also been added with ingredients that would make it useful as prophylactic too.
The “Ardrakadi Nishthivan" is described in the ancient reference BHARAT BHAISHAJYA RATNAKAR (BBR)(Jvaradhikarl43 to 146rdverse) as a powder. It is one of the embodiments of this invention that we have made the powder into a mouth disintegrating tablet.
Details of Ardrakadi Nishthivan reference in BBR are as follows:
(English translation of above verses-
• Composition -Take equal quantity of Rock salt, Ginger, long pepper and black pepper. Whole formulation processed with fresh juice of ginger.
• Dosage administration - Put that powder in mouth some time and spit it out. Do repeatedly. • Therapeutic effect - This composition will help to cure Fever Fainting Dry or wet cough, Pain in throat Overall drowsiness, heaviness in body , Hyperacidity , Indigestion , Kapha in heart
• Translation of the indication provided in the Verse 143 is as follows
Table 3
• These indications are of Influenza and Pneumonia, which are not Covid-19. It is now well known that treatments that are known to cure Influenza and Pneumonia do not cure Covid-19. The Covid-19 symptoms which are not shared in above Verse 143 are: Anosmia, Rhinitis, Anxiety, Breathlessness, diarrhea, loss of taste or smell a rash on skin, or discoloration of fingers or toes in mild cases, Lung fibrosis, difficulty breathing or shortness of breath, chest pain or pressure, and loss of speech or movement. Hence, the Verse 143 by no means suggests that this formulation shall cure Covid-19.
• This is perhaps the reason that even after about 9 months of Cobid- 19 pandemic in India and about 12 months in China, no practitioner in Ayurveda, including the Ministry of Ayush nor above cited publications using Ayurvedic formulations ever contemplated that a single Ayurvedic tablet formulation in general and Ardrakadi Nishthivan in particular given four times a day shall provide an efficacious and a virucidal medication for Covid-19 providing cure for the patient in three days; where all chemical/Allopathic virucides have failed.
• Thus, it is an embodiment of this invention that the Ayurvedic formulation Ardrakadi Nishthivan which is converted into mouth dissolving tablet, rather than as powder given in original reference, has been seen surprisingly, not just as an immunity booster but as a highly efficacious virucide against SARS-CoV 2 and as a remedy for Covid- 19 that has better efficacy than the State-of-Art virucides. This has not been anticipated by publication in any document in the context of Covid-19 nor used for this purpose in the country, there is no known state-of-art medicine on Covid-19; this is a breakthrough in treatment of the dreaded pandemic of Covid-19. Hence, this is a case of totally unanticipated and totally unobvious new use, a breakthrough for Ardrakadi
Nishthivan, and not just a mere discovery of new use for known substance. This new use has not fallen in public domain nor is part of State of Art treatment anywhere in the world for Covid- 19
The Medicinal properties of its ingredients are given as follows
Pippali (Piper longum Linn)-
• This herb is known from the ancient Sanskrit Ayurvedic texts. It is believed that Pippali was first mentioned in “Charaka Samhita” (IV-II B.C.) - the ancient Indian treatise to a healthy and balanced way of living. Very often it has been described as a remedy for the treatment of respiratory diseases, as well as for the treatment of the problems related to the intestinal flora. In the past it was even used to treat diseases such as cholera, tuberculosis, tetanus and leprosy.
• According to the classification of Ayurveda, it is heavy (to digest), slightly oily and it has moisturizing properties. The long pepper is very powerful and it has a quick and almost immediate effect after consumption.
Black Piper (Piper nigrum Linn)
• Black pepper, (Piper nigrum Linn), also called pepper, perennial climbing vine of the family Piperaceae and the hotly pungent spice made from its fruits. Black pepper is native to the Malabar Coast of India and is one of the earliest spices known. Widely used as a spice around the world, pepper also has a
limited usage in medicine as a carminative (to relieve flatulence) and as a stimulant of gastric secretions.
Sunthi (Zingiber officinale Rose.)
• Zingiber officinale Rose., commonly known as ginger, is a spice consumed worldwide for culinary and medicinal purposes. The plant has a number of chemicals responsible for its medicinal properties, such as anti-arthritis, anti- inflammatory, antidiabetic, antibacterial, antifungal, anticancer etc. The present chapter compiled scientific data retrieved from websites, such as PubMed, Science Direct, Scopus, Web-of-Knowledge, Google Scholar, and others related to the phytochemistry and pharmacology of ginger. A synopsis of the world production of the plant as well as some patents related to Z. officinale are also provided.
Rock salt (Halite; ‘Saindhav’ in Sanskrit language)
• It's a superior salt, according to Ayurveda and is a highly crystalline salt.
• Rock salt, on the other hand, is already found in solid form and is simply mined. This type of salt is also known as halite and often comes in larger crystals or has a coarser texture.
Fresh juice of ginger
Improves digestion. Is helpful in cough, cold; and relieves congestion and pain. It also controls high blood pressure, and has antiviral properties
Pharmacodynamics of Ardrakadi Nishthivan tablets
Following are general principles applicable for Ayurvedic therapy; which are applicable to Ardrakadi Nishthivan tablets also.
1. Ayurvedic ingredients work in synergism and deliver efficacy as a whole in combination with each other.
2. Single herb has hundreds of phyto -ingredients and in poly-herbal formulation there is further heterogeneity in phyto -ingredients. Ayurveda is not a single molecule therapy so BA, BE or Pharmacodynamics of a poly-herbal composition is always a challenge. Answer to this is found in Reverse pharmacology.
3. All Phyto -ingredient molecules work in synergy. If one tries to Isolate single molecule or take aqueous / alcoholic extract, it may fail to deliver expected result and may even have side effects.
4. Use herb as a whole is always safe and has optimum therapeutic effects.
This invention also discloses immunomodulator formulations. Immunomodulators are medications used to help regulate or normalize the immune system. Examples include one class of immunomodulation which is used as an add-on therapy to treat support in viral, bacterial and fungal infections and even in auto immune disorders.
Literature references for ingredients as immunomodulator is provided in Table 4.
Table 4: Immune Boosting structures of herbs and properties of the ingredients of
Immunity Booster formulation
Above all references mentioned in table no. 4 are known for their individual immune booster or therapeutic or both activities
The immunomodulator formulation was made in the instant invention comprising the ingredients provided in Table 5; the efficacies of which are also mentioned in the Table 5. Table 5
An invention is claimed also in an inhaler for prevention and prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection. In one embodiment of the invention, the inhaler is made from oils and oleoresins of herbs having
ACE2 blocking activity receptor blocker activity (Dear DR. Milind: Please confirm again by making reference work on whether the phrase “having ACE2 blocking activity receptor blocker
activity” is applicable to oils as well as the oleoresins of hers. Clarity and accuracy on this is very much essential from the point of view of claims to be made. Is it possible that “Oils” serve as “carriers” for the oleoresins and the oleoreins are only actives which are ACE inhibitors? For oils please check where is their mention made as ACE inhibitors and cite the same here) and not as ACE inhibitors . In another embodiment, the inhaler made from oleoresins of herbs having ACE2 receptor blocker activity is used as prophylactic/preventive for infection from Coronavirus- 19 infection. It is also an embodiment of this invention wherein inhalers of oleoresins of selected herbs having ACE2 receptor blocker activity are used to keep a person healthy. It is also an embodiment of this invention wherein inhalers the oleoresins include, without limitations, zingiberene, zingiberenece, Gingerol and Eugenol.
Yadalam et al (2021) have listed following essential oils as anti-virals against SARS-CoV-2 which can be used in inhaler: Terpinene, Anethole, Camphene, Carvacrol, Caryophyllene, Cinnamaldehyde, Cinnamyl acetate, Citral, Citronella, Citronellol, Cuminal, Estragole, Eucalyptol, Eugenol, Fenchel, Geraniol, Umonene, Linalool, Menthol, Myrtanol, Ocimene, p- Cymene, Pinocarveol, Pulegone, Sabinene, Sylvestrene, Terpinen-4-ol, Thujene, Thymol and Zingiberene.
Muchtaridi et al (2020) have enlisted Plant derivatives with potential effect on the SpikeRBD/TMPRSS2/ACE2 axis. The list comprises: Nicotiana benthamiana, Pelargonium graveolens L’Hér Momordica dioica roxb.ex willd, Valeriana jatamansijones ex roxb., Oroxylum indicum (L.), Artemisia absinthium L, Syzygium aromaticum (L.), Phaseolus vulgaris L Inula helenium L, Allium sativum L, Piper longum L, Ipomoea obscura (L.), Ipomoea obscura (L.), Piper nigrum L, Piper retrofractum vahl, Melaleuca cajuputi maton, Scutellaria baicalensis georgi, Erigeron breviscapus, Glycyrrhiza glabra L, Glycyrrhiza
uralensis fisch. ex DC. Bupleurum spp. Heteromorpha spp., Scrophularia scorodonia L, Withania somnifera (L.), Asparagus racemosus willd., Diplocyclos palmatus (L.), Citrus spp., Vitis vinifera L. and Aframomum melegueta K.Schum. A person skilled in the art immediately understands that oleoresins form all these plants can be sued in the inhaler according to this invention.
Thus. In addition to case studies on Covid- 19 patients, in non -clinical in-vitro studies, Ardrakadi Nishthivan is shown in Example 6 to have antiviral activity against non- enveloped virus, in enveloped virus as well as having anti-fungal activity. These observations explain the observed surprising effect of Ardrakadi Nishthivan in below mentioned case studies on Covid-19 patients and in clinical trial reported below. The anti- fungal properties are also very much relevant for Covid-19 patients since almost an epidemic of fungal diseases have been recorded post-recovery from Covid- 19 that includes Mucormycosis, Candidosis and Aspergillosis. These fungal diseases are killer diseases and are expensive to treat also. A person skilled in the art can certainly make out from the above examples that use of Ardrakadi Nishthivan in main treatment will not allow the fungal diseases also to come up at all; and in other therapies where Ardrakadi Nishthivan was not used and the fungal diseases that have occurred concurrent to or post-Covid- 19 can potentially be treated using Ardrakadi Nishthivan. The link https://www.cdc.gov/fungal/diseases/mucormycosis/definition.html provides information that Mucormycosis is caused by
Rhizopus species, Mucor species, Rhizomucor species, Syncephalastrum species, Cunningha mella bertholletiae, Apophysomyces species, and Lichtheimia (formerly Absidia) species. Example 6 has shown that Ardrakari Nishthivan has excellent efficacy against Mucor
racemosus ATCC 42647. A person skilled in the art would understand that Ardrakari Nishthivan would be efficacious against all fungi that cause Mucromycosis. The fungi that cause Mucormycosis includes Rhizopus caespitosus, Rhizopus delemari, Rhizopus homothallicus, Rhizopus microspores, Rhizopus oryzae, Rhizopus reflexus, Rhizopus schipperae, Rhizopus stolonifer (black bread mold), Rhizopus arrhizus, Rhizopus oligosporus, , Rhizopus circinans, Rhizopus lyococcus, Rhizopus americanus, Rhizopus azygosporus, Rhizopus rhizopodiformis, Rhizopus niveus and Rhizopus sexualis; Mucor amphibiorum, Mucor circinelloides, Mucor ellipsoideus, Mucor fragilis, Mucor hiemali, Mucor hiemalis f. silvaticus, Mucor. indicus, Mucor mucedo, Mucor paronychius, Mucor piriformis, Mucor phimbeus, Mucor pseudohisitanicus, Mucor racemosus, Mucor ramosissimus, Mucor variicolumellatus, Mucor vehitinosus, Apophysomyces variabilis, Apophysomyces trapeziformis, Apophysomyces ossiformis: Lichtheimia ramosa L. corymbifera, Cunninghamella binarieae R.Y. Zheng 2001, Cunninghamella blakesleeana, Cunninghamella Candida Yosh.Yamam. 1929, Cunninghamella clavata R.Y. Zheng & G.Q.Chen 1998, Cunninghamella echinulata (Thaxt.) Thaxt. ex Blakeslee 1905, Cunninghamella elegans Lendn. 1905, Cunninghamella homothallica Komin. & Tubaki 1952, Cunninghamella intermedia K.B.Deshp. & Mantri 1966, Cunninghamella multiverticillata R.Y. Zheng & G.Q. Chen 2001, Cunninghamella phaeospora Boedijn 1959, Cunninghamella polymorpha Pispek 1929, Cunninghamella septata R.Y. Zheng 2001 and Cunninghamella vesiculosa P.C.Misra 1966
Muchtarid et al (2020) have mentioned that Aspergillus flavus, Aspergillus fumigatus cause A spergillom icosis.
Abdullah et al. (2021) have mentioned that Candida albicans and Candida glabrata are causal fungi of Candidosis in Covid-19 patients.
Since Ardrakari Nishthivan has been shown to be effective against the pahtogenic fungus
Mucor recemosus, and the fmgicieds have generic efficacy against all fingi,a person skille din the art can recognise that it shall be equally efficacious against above list fo fingi also which cause Mucormycosis, Aspergillosis and Candidosis.
Results provided in Table 8 clearly indicate following properties of the Investigational
Product (mouth dissolving tablets of Ardrakadi Nishthivan):
1. Antiviral as therapeutic effect 2. Prophylactic as ACE2 receptor blocker effect
3. Inducer of salivation, providing locally viral wash effect
4. Reduction in the risk of further viral infections and secondary bacterial infections colonization.
5. Efficacious dosage: 1 mouth dissolving tablet of Ardrakadi Nishthivan 3 to 4 times at regular intervals.
EXAMPLES
EXAMPLE 1
Ardrakadi Nishthivan its ingredients and method of preparation
Verse 143 describes ingredients and composition of Ardrakadi Nishthivan original reference from BHARAT BHAISHAJYA RATNAKAR. This powder contains following ingredients: Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose; and Rock Salt. Table 6
Method of preparation specified in BBR is as follows:
1. T ake all ingredients numbered from 1 to 4
2. Dry those in shade and then pulverize to powder. 3. Mix the powders well in grinder.
4. Crush fresh ginger after thorough wash with water.
5. Put the paste in a clean cotton cloth.
6. Squeeze the juice out.
7. Add sufficient ginger juice to the powder-mix in mortar and pestle such that the powder-mix should be completely immersed in the ginger juice.
8. Start the grinding till all the powder gets soaked in the juice well
9. Grind for 1 hour
10. Let it dry completely
11. make the tablets.
Example 2
In April 2020, a patient was diagnosed with COVID 19. He was home quarantined. He was treated with the allopathic medicines. After treatment also he was not feeling fresh and mild fever continued. Given standard care of treatment was the one which was recommended at that time for CO VID 19, the same was as follows:
• Azithromycin 500 OD 3 days
• VitaminC500 mg+Zink 10 mg+ Multivitamin especially B12 daily
• Paracetamol 650 TDS SOS
• In first 7 days Tab Favipiravir
After telephonic conversation with him, he was treated with Ayurvedic ODT (Orally disintegrating tablet) of “Ardrakadi Nishthivan
In the instant example, which was carried out while there was a lockdown and access to laboratories and ready-made Ardrakadi Nishthivan was not available, the same was prepared by collecting all ingredients and as per the process described in the treatise BBR. Pills were
prepared at home and the dose advised was 1 pill (by allowing dissolution in mouth) three times a day. Surprisingly, all symptoms of the patient were gone completely in 4 days.
Example 3
Efficacy of Ardrakadi Nishthivan tablets
Case I - A middle aged female patient of 45 years was suffering from Covid-19 symptoms. Dry cough, mild fever always below 990Fahrenheit, occasional sneezing and continuous sore. She was treated immediately after detection of symptoms. She was not receiving any State-of- art treatment. Since she was of close acquaintance to me, and she knew that I am an Ayurvedic medical practitioner, she desired that I should give her an Ayurvedic treatment. Hence, we tried giving her Ardrakadi Nishthivan as sole treatment by making the tablets at home. To our surprise, she got relief within 3 days from date of giving mouth dissolving tablets of Ardrakadi Nishthivan for 4 times in a day.
PCR test for diagnosis of Covid-19
The COVID-19 RT-PCR test is a well-known real-time reverse transcription polymerase chain reaction (RT-PCR) test for the qualitative detection of nucleic acid of the causal virus SARS- CoV-2 in upper and lower respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate) collected from individuals suspected of patients suspected of COVID-19 by their healthcare provider (HCP); as well as upper respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, nasal swabs, or mid-turbinate swabs) collected from
any individual, including for testing of individuals without symptoms or other reasons to suspect COVID19 infection
(https://www.fda.gov/media/136151/download)These tests were used in the examples described here. Example 4
Documented Case Studies
It was decided to check viral load i.e., quantitative PCR through Indian Council of Medical Research (ICMR) recognised laboratory (address: GenePath DX, Above Phadake Hospital, 1206/B Jungli Maharaj Road Shivajinagar Pune 411004 www.genepathdx.com) initially in 2 patients of COVID-19 by treating them with Ardrakadi Nishthivan mouth dissolving tablets.
The observations are as follows:
Surprising decline in virus load in one hour was observed. After these initial observations, we decided to go for the pilot study of 4 patients.
Table 8: Pilot study done on 4 patients . 500 mg 1 mouth dissolving tablets of Ardrakadi Nishthivan 4 hourly for 3 days at regular intervals between 8 am to 8 pm .Nasal+Oral swab taken for quantitative Viral load (RTqPCR) each 24 hrly.
Decline in 99% of the viral load is considered as virus free status of the patient. Since there was no treatment between 72 and 96 hours, the patients are considered to have become virus free with maximum 72 hours of treatment.
Example 5
IMMUNOMODULATOR FORMULATION
Immunity Booster Formulation comprise following ingredients”
Process of making above formulation comprised following steps:
1. Aqueous extract of ingredients 1 to 5 that were readily available in market were procured. In the alternative, the extracts can also be made by methods well known to a person of an ordinary skill in the art. 2. Ingredient 6 was also procured from the market and the same is readily available.
3. Ingredient 7 is prepared by sohxlet extraction process using solvent ether, hexane using seeds of Zanthoxylum armatum DC.
4. Ingredients 1 to 7 were mixed together as per the percentage provided above, and the mixture was prepared.
5. Fresh juice of ginger was prepared and added in mixture.
6. Whole mixture is dried and powdered. This powder is the API (Active Pharmaceutical Ingredient) of the Immunity Booster Formulation.
This API can be converted in tablet, Orally Dissolving Tablet, syrup, lozenges, capsules, Pills, pastilles as per standard industrial dosage forms by methods well known in the art.
Example 6
NON-CLINICAL IN VITRO ANTI-VIRAL EFFICACY STUDIES
1. Ardrakadi Nishthivan
Name of the test - Assess the Activity of Microbicides against Viruses in Suspension
Test Method: - ASTM E 1052: 2020
Scope of Method: This test determines if test product can inactivate virus in suspension. One part of the virus suspension with nine Parts of the test substance are held at the desired temperature for the required contact time and then assayed for viable virus in an appropriate host system.
Experimental Conditions:
Experimental Conditions:
Test Product : 10 mg/ml Cone.
Contact time : 4 hours
Organic Load : 0.5gpl BSA Bovine serum albumin
Test Method : 24 Well plate, Neutralisation and Dilution method
Neutralization : SCDLP medium Soyabean Casein Digest Medium Medium of Cell culture : Eagle’s minimal essential medium (EMEM), supplemented with inactivated FBS Foetal Bovine serum & antibiotics
Virus strains and host cells: Virus strains and hosA12:D17t cells:
Test Virus: Human Coronavirus HCoV-229E (Surrogate of SARS-CoV-2)
Host Cell: MRC-5 cell line (ATCC CCL-171); Passage No.: Cells from PN 16 Infectivity titre test: TCID50 method Results:
Test Virus: Human Coronavirus HCoV-229E (Surrogate of SARS-CoV-2)
Results:
Test Virus: Human Coronavirus HCoV-229E (Surrogate of SARS-CoV-2)
1. Test Sample: Thinqure 20 (Trademark for Ardrakadi Nishthivan) 10 mg/ml Cone.
Note:
HCoV-229E belongs to the family Coronaviridae and subfamily Orthocoronavirinae.
HCoV-229E is one of seven known coronaviruses that infect humans. The other six are Human HCoV-OC43, HCoV-NL63, HCoV- HKU1, MERS-CoV, SARS-CoV-1, SARS-CoV-2.
The standardized preparation of Ardrakadi Nishthivan was provided by the inventors for these studies and analyses were got done by outsourcing analytical services from BIOTECH TESTING SERVICES (7O4|LO5, Malwa, Patanwalalnd. Estate, L.B.S. Marg, Ghatkopar (W), Mumbai - 400086, INDIA)
(A) Activity of Ardrakadi Nishthivan against Viruses in Suspension
Table 11
Test Method:
ASTM E 1052: 2020
Scope of Method:
This test determines if test product can inactivate virus in suspension. One part of the virus suspension with nine Parts of the test substance are held at the desired temperature for the required contact time and then assayed for viable virus in an appropriate host system.
Experimental Conditions: Ardrakadi Nishthivan : 1mg/ml, 10 mg/ml and 50 mg/ml
The above test sample of Ardrakadi Nishthivan was prepared by following procedure:
1. Ardrakari Nishthivan formulation 50 g was added to 500 ml of solvent
2. The sample was refluxed in Soxhlet for 6 hours
3. Two different solvents were used and carried out in two different Soxhlet apparatus i.e. Ethanol and Methanol
4. The extracts were concentrated in rotary evaporator
5. The concentrate was dried in hot air oven
6. Both the extracts were diluted in 1 :2 volume in distilled water in 0.1%
Phosphate Buffer Saline to give combined concentration of 100 mg/ml
7. The samples were further diluted in respective media for specific tests at either
50mg/ml, 10mg/ml and 1mg/ml
8. The extracts were stored at 4°C.
Contact time : 1 hours and 4 hours
Organic Load : 0.5gpl BSA
Test Method : 24 Well plate, Neutralisation and Dilution method
Neutralization : Soybean Casein Lecithin Polysorbate (SCDLP) medium
Medium of Cell culture: Eagle’s minimal essential medium (EMEM), supplemented with inactivated FBS (Fetal Bovine Serum) and antibiotics
Virus strains and host cells:
Test Virus: Influenza A virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
Host Cell: MDCK cell ATCC CCL-34
Infectivity titre test: TCID50 method Test Procedure:
1. The prepared Virus inoculum is added to the test product and the virus recovery control media at a ratio of 1 part virus + 9 parts test product.
2. At the end of contact time, the test and recovery suspensions are neutralized.
3. An aliquot removed from the cytotoxicity control and inoculated with a low- concentration viral suspension was used to generate the neutralization control to confirm the efficacy of neutralization method.
4. The neutralized test, recovery, cytotoxicity control, and neutralization control suspensions were serially diluted in the appropriate media. Each dilution is plated in quadruplicate to host cell monolayers in a 24-well plate. 5. Plates were incubated for 5 - 7 days duration for Visible CPE (cytopathic effect by examined under microscope and Confirmatory TCID 50 method.
Results:
Test Virus: Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
Table 12
Test Virus: Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
Table 13
Results:
Test Virus: Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
12
Table 14
Test Virus: Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
Results:
Test Virus: Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
Table 16
Test Virus: Influenza A Virus (H3N2): A/Hong Kong/8/68: ATCC VR-1679
Table 17
(B) Activity of Ardrakadi Nishthivan against Viruses in Suspension
Table 18
SAMPLE DESCRIPTION : Test sample labeled as:THINQURE20 (Trade Name of Ardrakadi Nishthivan formulation)
Test Method:
ASTM E 1052: 2020
Scope of Method: This test determines if test product can inactivate virus in suspension. One part of the virus suspension with nine parts of the test substance are held at the desired temperature for the required contact time and then assayed for viable virus in an appropriate host system.
Experimental Details: Test product concentration : Ready to use
Virus : MS2Bacteriophage;
Permissive Host Cell : Escherichia coli
ATCC15597
Interfering agent : No soiling agent was used
Contact Period : 1 hour and 4 hours
Neutralizer : DE broth Medium : Trypticase soya agar
Incubation for survivors : 37°C for 3 days
Validation and Records:
Table 19
Where -
A=No. of PFU/ml of Test organism in
Experimental condition validation B=No. of PFU/ml of Test organism in
Neutralizer Toxicity validation
Test Procedure:
Thoroughly mixed virus suspension was added to nine parts of Test substrate. It was
held at Room temperature for 1 minute and 10 minutes following exposure time, aliquots were withdrawn, neutralized and by serial tenfold dilution assayed to determined surviving Viruses in comparison with Control without test product. Virus assay was quantitative as Plaque forming unit (PFU) visible as area of Clearance. Results:
INTERPRETATION:
Test product Ardrakadi Nishthivan formulation — 10 mg/ml has shown 66.66% and 54.76% reduction; Ardrakadi Nishthivan formulation — 50 mg/ml hasShown78.92%and85.00%reduction of MS2 Bacteriophage as surrogate virus in
1 hour and 4 hours when tested as per standard ASTM E 1052: 2020.
(C) Time Kill Test
SAMPLE DESCRIPTION : Test sample labeled as: Ardrakadi Nishthivan
Test Standard:
ASTM E 2315 - 16
Test Inoculum:
Mucor racemosus ATCC 42647
Test Conditions:
Concentration 1mg/ml, 10mg/ml and 50mg/ml
Diluent/Neutraliser Lecithin, Polysorbate80, Sodium thiosulphate, Histidine, Saponinin
Phosphate buffer 0.0025mol/l
Contact time : 1 hours and 4 hours
Contact Temperature : Room temperature
Media and Reagent : Sabourauds Dextrose agar, incubated at 28°C
Procedure:
Product was inoculated with test fungus individually (approximately108CFU/ml). After the specified exposure time of 1 hour and 4 hours surviving microorganisms were recovered by drawing an aliquot, neutralizing and performing Standard Pour plate
Technique. Culture count was ascertained by dilution Blank. Adequate Validation of Neutralizing agent was also carried. Test was carried out in duplicate and average count was taken as CFU/ml.
Results:
Percentage Reduction of Microorganism = 100(Initial — After Exposure) / Initial Log Reduction = Log Initial - Log After Exposure
INTERPRETATION:
Sample labeled as Ardrakadi Nishthivan — 1mg /ml has shown >1 log reduction I 92% reduction; Ardrakadi Nishthivan- lOmg/ml has shown >1 log reduction / 93% reduction; Ardrakadi Nishthivan— 50mg/ml has shown >1 log reduction/94% reduction of test fungus viz. Mucor racemosus in 1 hour and 4 hours when analysed as per ASTME 2315 — 16 Method.
In summary:
• Antiviral activity against Human Coronavirus HC0V-229E - Ardrakadi Nishthivan was tested at 10 mg/ml for anti-Corona virus activity on cell line MRC-5 and has shown 97% kill against Coronavirus (ASTM E 1052: 2020) in 4 hrs.
• Antiviral activity against Non-Enveloped virus -Ardrakadi Nishthivan — 50 mg/ml has shown 85.00% reduction of MS2 Bacteriophage as surrogate virus in 4 hours per standard ASTM E 1052: 2020
• Antiviral activity against Enveloped virus - Ardrakadi Nishthivan — 50 mg/ml has shown 99.00% reduction of INFLUENZA as surrogate virus in 4 hours ASTM E 1052: 2020
• Antifungal activity- Arar akadi Nishthivan 50mg/ml has shown reduction 96% reduction of test fungus ASTM E 2315 - 16 Method.
Example 7
CTRI registered Clinical Trial Report of Ardrakadi Nishthivan
STUDY TITLE
A Non-Interventional, Retrospective, Observational study to analyze Safety, Efficacy and Tolerability of Ardrakadi Nishthivan in COVID-19 patients.
For these studies, standardized A rdrakadi Nishthivan was made available by the inventors and clinical trial services were sourced from Mediclin Clinical research 4th Floor Ambika Industries, Opp Thakur Mall, Mira Road Thane 401107
MATERIALS AND METHODS
Materials
The Thiqure 20 - A standardized and ready to use formulation comprising Ardrakari Nishthivan was obtained from Thinq pharma CRO, Mumbai.
Standardization of Ardrakadi Nishthivan
The Ardrakadi Nishthivan was standardized by HPLC method to evaluate the piperine and gingerol content in the formulation.
Study design and objectives
This was a non-interventional, retrospective, observational study conducted between 12-Aug- 2020 and 12-Nov-2020. The primary objective of the study was to evaluate efficacy of
Ardrakadi Nishthivan in Covid-19 patients. The secondary objectives were to analyze safety, and tolerability of the formulation following fixed dose combination treatment with time in Covid patients. The study was performed in Yashwantrao Chavan Memorial Hospital, Pune, India. The study was performed in compliance with good clinical practice and all applicable laws and regulations. The necessary approvals for study design were approved by Ethicare Ethics Committee and the protocol was registered with Clinical Trial Registry of India (CTRI) with Registration No.: CTRI/2021/03/032471. All procedures followed the tenets of the Declaration of Helsinki, were in accordance with all regulatory standards, were approved by an Institutional Review Board and all subjects signed an informed consent form.
Patients
The study included male (21) and female (09) patients between agel8 to 75 years with diagnosis of Covid positive by RT -qPCR test. For inclusion in the study, patient must have had RT-PCR test positive for both oral and nasal swabs. The patients who were diagnosed Covid positive and were taking Ardrakadi Nishthivan as prescribed by physician were also included in the study. The patients with history of intracranial bleeding, incomplete medical history, or suffering from haemoglobinopathies, active malignancies were excluded from the study. The pregnant or lactating women, smokers, alcohol drinkers, and the females not ready to use acceptable contraceptive methods during treatment periods were also excluded from the study. After screening with inclusion and exclusion criteria, total 30patients were included in the study. At the time of screening, a written informed consent was taken from all the subjects and their demographics, complete medical history, past history and history of any other treatment was recorded. Additionally, vital signs including pulse, BP, temperature, body weight, and physical examination and Viral load by RT-qPCR were also assessed.
Treatment
The patients were asked to take tablets in the mouth and slowly to be sucked (licked within mouth by tongue) till entire tablet is dissolved in mouth and not to swallow or chew or crush. The first dose was 2 tablets of Ardrakadi Nishthivan and from second dose it was reduced to 1 tablet at a time at 4 hours interval; thus on day 1, five tablets were given. From day 2 to day 5 one tablet was given every 4 hrs. (08:00 AM, 12:00 noon, 04:00 PM, and 08:00 PM). Out of 30 patients, 29 completed the treatment, one patient was excluded from the study due to not completing the treatment.
Outcome parameters
The change in viral load from the baseline to end of study was recorded with RT-qPCR test. Evaluation of vital signs including pulse, BP, temperature, body weight, and physical examination, recording of concomitant medication, Dietary and lifestyle counselling were done to evaluate the safety of Ardrakadi Nishthivan formulation (Thinqure20™). The safety and tolerability of the Ardrakadi Nishthivan was determined by recording all serious adverse events (SAE) and adverse events (AE) regardless of treatment group or suspected causal relationship to study drug.
Statistical analysis
The viral load after treatment was statistically compared with viral load before treatment by performing Wilcoxon rank sum test as it is performed when sample size is below 40. The data was represented as Mean ± SD (Standard Deviation). The p< 0.05 was considered as significant. The analysis was performed using statistical software GraphPad Prism Version 8.
EFFICACY RESULTS AND TABULATIONS OF INDIVIDUAL SUBJECT DATA
Analysis of Efficacy
Efficacy of the investigational product was analyzed on the basis of increase in the Viral load from baseline to end of study visit. As per the statistical analysis plan, the efficacy data was analyzed for effect on individual and cumulative efficacy parameter.
• Primary Efficacy Parameter
A) Changes in Viral Load:
p-value calculated using chi-square test. The below table is considered for analysis of viral load after log10 transformation:
Viral load
The treatment with Ardrakadi Nishthivan for 5 days significantly (p<0.001) reduced the viral load in the Covid 19 Patients when compared with viral load before treatment (Figure 1).
Statistical analysis
The viral load after treatment was statistically compared with viral load before treatment by performing Wilcoxon rank sum test as it is performed when sample size is below 40. The data was represented as Mean ± SD (Standard Deviation). The p< 0.05 was considered as significant. The analysis was performed using statistical software GraphPad Prism Version 8.
DISCUSSION
The relationship between Covid-19 virus load and the severity of disease progression is poorly characterized in Covid- 19. The plasma viral load is directly associated with progression of
disease severity (Fajnzylber et al, 2020; Pujadaset al. 2020). Increase in plasma viral load leads to worsening of disease severity, marked reduction in lymphocytes count, and significant increase in plasma inflammatory markers such as interleukin 6 (IL-6), and C-reactive protein (CRP) leading to increased mortality (Fajnzylber et al, 2020).
Ardrakadi Nishthivan treatment showed significant reduction in the viral load indicating its beneficial role in the inhibition of disease progression and mortality rate. In addition, the active components of the Ardrakadi Nishthivan (Piperine and Gingerol, Zingeberene) possess potent anti-inflammatory and antiarthritic effects of piperin in human interleukin 1 -stimulated fibroblast-like synoviocytes and in rat arthritis models activities (Bang et al. 2009) and Anti- oxidative and anti-inflammatory effects of ginger in health and physical activity (Mashhadi et al. 2013) may also help in reducing the cytokine storm and further worsening of conditions.
The angiotensin converting enzyme - 2 (ACE2) receptors play a very pivotal role in viral entry and its expression in the major vital organs such as heart, kidney and lungs (Habas et al. 2019). SARS-CoV-2 virus causes balance between ACE and ACE2 and activate the renin angiotensin aldosterone system (RAAS) leading to entry of virus in host cell and its replication (Beyerstedt 2021). Inhibition of ACE2 receptors and RAAS system can limit the viral load and disease progression by inhibiting viral entry and replication in the host cells 1. The piperine, zingiberene and gingerol have proven ACE inhibitory activity (Maurya et al, 2020; Bare et al. 2020) This action of Ardrakadi Nishthivan may be attributed to ACE2 inhibition and inhibition of viral entry in the host cells. Founded results suggests that phytochemicals from Ardrakadi Nishthivan might be effective as a therapeutic as well as prophylaxis against COVID-19 by preventing viral attachment to the host cells through inhibition of spike glycoprotein.
Molecular docking results are indicated with excellent binding affinity of phytochemical piperine, Zingiberene against SARS-CoV-2 spike glycoprotein and its cellular receptor along with MolDock score and other parameters (Maurya et al, 2020; Bare et al.
Ardrakadi Nishthivan.
Mole dock study shows phytochemicals from of Zingiber officinale as entry inhibitor of SARS- COVID 2 VIRUS. Gingerol and Zingiberene had effective binding activity with ACE2 receptors (Maurya et al, 2020; Bare et al. 2020; Chakotiya and Sharma 2020).
Ardrakadi Nishthivan comprising of Piper longumLinn, Piper nigrumLinn. Zingiber officinale Rose and rock salt, possess various active agents like piperine, Zingiberene, gingerol which play their role for its effectiveness against SARS-Co2 virus. Ardrakadi Nishthivan might be acting on single target or multiple targets for inhibiting SARS-CoV2 viral load.
Covid-19 can cause significant discomfort, continuous cough, fever/high temperature (37.8°C or greater), Loss of, or change in, sense of smell or taste, respiratory failure, shock, or multi- organ dysfunction, reduce quality of life, and lead to a loss of productivity. In this study Ardrakadi Nishthivan have been shown to improve quality of life in Covid-19 patients. Treatment with Ardrakadi Nishthivan was safe and it was well tolerated. Adverse event experienced during clinical trial, all of them were mild in the nature. In addition, there were no serious adverse events reported at any time during the study.
CONCLUSION
Evidence supports that the use of Ardrakadi Nishthivan has beneficial effects in treatment of Covidl9 which may be linked to decrease in total viral load in patients. It provided better relief
for recovery of the COVID-19 disease. Ardrakadi Nishthivan is well-tolerated, safe and is effective in COVID-19 patients, especially with reference to the reduction in viral load.
Example 8
Herbal Inhaler having ACE2 receptor blocking activity In the following is an illustrative example of the inhaler made using ACE2 inhibitors.
Table 25
1. Composition
Method of Preparation a. Preparation of base A: Ingredients from 1 to 6 are bought in market and mixed in quantity indicated in Table 25 to prepare base A b. Preparation of base B: Ingredients 7, 8, 9 and 10 were prepared as Oleoresins by solvent extraction in Soxhlet Apparatus and mixed in quantity indicated in Table 25 to prepare base B. i. Vekhand Oil (oil of Acorus calamus L) was prepared by extracting rhizome was extracted by using soxhlet method .solvent used hexane, pet ether ii. Sunthi Oil (Oil ofZinziber officinale Rose) was prepared by extracting rhizome was extracted by using soxhlet method .solvent used hexane, or petroleum ether. iii. Ajwain oil Oil (oil of Trachyspermum ammi (L.) Sprague ex Turrill) was prepared by extracting seeds was extracted by using soxhlet method .solvent used hexane or pet ether iv. Clove oil Oil (oil of Syzygium aromaticum L & L.M. ) flowder budswas extracted by using soxhlet method, solvent used hexane or petroleum ether
1. These extracts were mixed together in quantity indicated in Table 25 to prepare Base B c. Final API (Active Pharma Ingredient) is prepared by mixing Base A with Base B in a mixer accompanied with stirring for 15 minutes.
3. Dosage form a. Standard inhaler - cotton absorbent stick is filled with API as per optimum level.
Dose b. As a prophylaxis for adults - 2 deep inhalations in each nostril 1 hrly c. 2 year to 12 year - 1 inhalation in each nostril once a day. d. Children under 12 years (with adult supervision) 1 inhalation in each nostril once a day. e. Not to use for children below 2 years f. Or as per directed by physician
References:
Agarwal Anup and other PLACID Trial Collaborators. Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicenter randomized controlled trial (PLACID Trial). https://doi.org/10.1101/2020.09.03.2Q187252; https://www.medrxiv.org/content/10T 101/2020.09.03.20187252vl.full.pdf
Akinyemi Ayodele Jacob, Adedayo Oluwaseun Ademiluyi, Ganiyu Oboh Inhibition of angiotensin-1-converting enzyme activity by two varieties of ginger (Zingiber officinale) in rats fed a high cholesterol diet. J Med Food 2014 Mar;17(3):317-23. doi: 10.1089/jmf.2012.0264. Epub 2014 Jan 16.
BHARAT BHAISHAJYA RATNAKAR (BBR) (Jvaradhikar 143 to 146rdverse (shloka)
Chakraborty, Kaustav. ‘ ACE2 receptor blockers: a novel therapeutic approach for COVID- 19. https://ers.app.box.eom/s/ps5h8i8ulp4vskxpz5gyjl6u22k9fnus
Chaudhary, Sushil Kumar, Mukherjee, Pulok K, Maiti, Niladri. De, Apurba Kumar, Bhadra, Santanu, Saha, Bishnu Pada. Evaluation of Angiotensin converting enzyme inhibition and antioxidant activity of Piper longum L. NISCAIR-CSIR, India. Jul-2013. http ://n opr, niscair, res, in/handle/123456789/19446.
Cinatl J, B Morgenstern, G Bauer, P Chandra, H Rabenau, H W Doerr Glycyrrhizin, an active component of liquorice roots, and replication of SARS -associated coronavirus THE LANCET • Vol 361 • June 14, 2003 • www.thelancet.com.
Cox, Robert M, Josef D Wolf and Richard K Plemper. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nature Microbiology 2020 December 3. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets | Read by QxMD
Fei Zhou*, Ting Yu*, Ronghui Du*, Guohui Fan*, Ying Liu*, Zhibo Liu*, Jie Xiang*, Yeming Wang, Bin Song, XiaoyingGu, Lulu Guan, Yuan Wei, Hui Li, Xudong Wu, JiuyangXu, ShengjinTu, Yi Zhang, Hua Chen, Bin Cao Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, www.thelancet.com Vol 395 March 28, 2020. 1054 — 1062.
Gudeti, Manohar S., Laxman W. Bhrke, Pallavi S. Mumdada, Sanjay Madhukar, AshitaSurve, Ramavtar Sharma, Sunita Mata, RakeshRana, RichaSinghal, Meera Vyas,
ShrutiKhandiri, B.S. Sharma, Shrikanth N., Dhiman KS. AYUSH 64, a polyherbalAyurvedic formulation in Influenza like Illness: results of a pilot study. Journal of Ayurveda and Integrative Medicine. Available online 14 May 2020,
Joshi Jyoti Anand and Rammanohar Puthiyedath. Case Report Outcomes of Ayurvedic care in a COVID- 19 patient with hypoxia - A Case Report. Journal of Ayurveda and Integrative Medicine. Available online 13 October 2020 https://doi.org/10.1016/j.jaim.2020.10.006
Wang Liqiang, Rui Yang, Bochuan Yuan, Ying Liun, Chunsheng Liu The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. ActaPharmaceuticaSinicaBVolume 5, Issue 4, July 2015, Pages 310-315
Maurya, Vimal K., SwatantraKumar, Anil K. Prasad, Madan L. B. Bhatt &Shailendra K. Saxena. Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor VirusDisease volume 31, pagesl79— 193(2020)
National Clinical Management Protocol based on Ayurveda and Yoga for management of Covid-19; MINISTRY OF AYUSH AYUSH BHAWAN, B Block, GPO Complex, INA, NEW DELHI - 110023. Published 6th October 2020
Xionga Xingjiang.PcngqianWangb.c , KeleiSud,e, , William C. Chof , YanweiXinga, Chinese herbal medicine for coronavirus disease 2019: A systematic review and meta- analysis. Pharmacological Research 160 (2020) 105056.
Xu Hao, Liang Zhong, Jiaxin Deng, JiakuanPeng, Hongxia Dan, XinZeng,Taiwen Li, and Qianming Chen. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa Int J Oral Sci. 2020; 12: 8. Published online 2020 Feb 24. doi: 10.1038/s41368-020-0074-xPMCID: PMC7039956 PMID: 32094336
Shiva Kazemi1, Fatemeh Yaghooblou1, Fereydoun Siassi1, Abbas Rahimi Foroushani2, Mahsa Ghavipour3 , Fariba Koohdani4 , Gity Sotoudeh1 Cardamom supplementation improves inflammatory and oxidative stress biomarkers in hyperlipidemic, overweight, and obese pre-diabetic women: a randomized double-blind clinical trial. J Sci Food Agric 2017 Dec; 97(15):5296-5301, doi: 10.1002/jsfa.8414. Epub 2017 Jul 17.PMID: 28480505
Fajnzylber J, Regan J, Coxen K, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun 2020; 11: 5493.
Pujadas E, Chaudhry F, McBride R, et al. SARS-CoV-2 viral load predicts COVID-19 mortality. Lancet Respir Med 2020; 8: e70.
Habas K, Nganwuchu C, Shahzad F, et al. Resolution of coronavirus disease 2019
(COVID-19). Expert Rev. Anti. Infect. Ther. 2020; 18: 1201-11
Beyerstedt S, Casaro EB, Rangel ÉB. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis 2021; 40: 905—19
Bare Y, Helvina M, Krisnamurti GC, S M. The Potential Role of 6-gingerol and 6-shogaol as ACE Inhibitors in Silico Study. Biog J Ilm Biol 2020; 8: 210.
Bang JS, Oh DH, Choi HM, el al. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 10-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res Ther 2009; 11: R49.
Mashhadi NS, Ghiasvand R, Askari G, Hariri M, Darvishi L, Mofid MR. Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: Review of current evidence. Int J Prev Med 2013; 4: S1— 7
Chakotiya, Ankita Singh, Sharma, Rakesh Kumar Phyto-constituents of Zingiber officinale Targeting Host- viral Protein Interaction at Entry Point of SARS-CoV-2: A Molecular Docking Study Defence Life Science Journal. 2020 ;5. 4: 268-277Muchtaridi
Muchtaridi,M. Fauzi, Nur Kusaira Khairul Ikram, Amirah Mohd Gazzali, and Habibah A. Wahab Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2 Molecules. 2020 Sep; 25(17): 3980. Published online 2020 Sep 1. doi: 10.3390/molecules25173980
Abdullah M.S. Al-Hatmi,a,b,c Jalila Mohsin,d Aisha Al-Huraizi,e and Faryal Khamise, COVID-19 associated invasive candidiasis J Infect. 2021 Feb; 82(2): e45-e46. Published online 2020 Aug 7. doi: 10.1016/j .jinf.2020.08.005
Yadalam Pradeep Kumar, Kalaivani Varatharajan, K. Rajapandian, Priyanka Chopra, Deepavalli Arumuganainar, Thilgavathi Nagarathnam, Honglae Sohn and Thirumurthy Madhavan Antiviral Essential Oil Components Against SARS-CoV-2 in Pre-procedural Mouth Rinses for Dental Settings During COVID- 19: A Computational Study Front. Chem., 29 March 2021 | https://doi.org/10.3389/fchem.2021.642026
Claims
1. A composition comprising at least Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose; and Rock Salt (in Sanskrit called as 'Saindhav') for treatment of patients of one or more of the diseases selected from the group consisting of: a. Covid-19 for overcoming viral infection, or b. fungal disease for overcoming fungal infection, or c. both.
2. A composition comprising at least Piper longum Linn, Piper Nigrum Linn, Zingiber officinale Rose, Rock Salt and ACE2 inhibitor active ingredients of herbs.
3. The composition as claimed in claim l is a mouth dissolving tablet.
4. The composition as claimed in claim 1 wherein the fungal infection comprises infection from Mucor sp., Aspergillus sp.and Candida sp.
5. The composition as claimed in claim 4 wherein the fungal infection comprises one or more selected from the group consisting of Rhizopus caespitosus, Rhizopus delemari, Rhizopus homothallicus, Rhizopus microspores, Rhizopus oryzae, Rhizopus reflexus, Rhizopus schipperae, Rhizopus stolonifer (black bread mold), Rhizopus arrhizus, Rhizopus oligosporus, , Rhizopus circinans, Rhizopus lyococcus, Rhizopus americanus, Rhizopus azygosporus, Rhizopus rhizopodiformis, Rhizopus niveus and Rhizopus sexualis; Mucor amphibiorum, Mucor circinelloides, Mucor ellipsoideus, Mucor fragilis, Mucor hiemali, Mucor hiemalis f. silvaticus, Mucor. indicus, Mucor mucedo, Mucor paronychius, Mucor piriformis, Mucor plumbeus, Mucor pseudolusitanicus, Mucor racemosus, Mucor
ramosissimus, Mucor variicolumellatus, Mucor velutinosus, Apophysomyces variabilis,Apophysomyces trapeziformis, Apophysomyces ossiformis.’Lichtheimia ramosa L. corymbifera, Cunningham ella binarieae R.Y. Zheng 2001, Cunninghamella blakesleeana, Cunninghamella Candida Yosh.Yamam. 1929, Cunninghamella clavata R.Y. Zheng & G.Q.Chen 1998, Cunninghamella echinulata (Thaxt.) Thaxt. ex Blakeslee 1905, Cunninghamella elegans Lendn. 1905, Cunninghamella homothallica Komin. & Tubaki 1952, Cunninghamella intermedia K.B.Deshp. & Mantri 1966, Cunninghamella multiverticillata R.Y.Zheng & G.Q. Chen 2001, Cunninghamella phaeospora Boedijn 1959, Cunninghamella polymorpha Pispek 1929, Cunninghamella septata R.Y. Zheng 2001 and Cunninghamella vesiculosa P.C.Misra 1966, Aspergillus flavus , Aspergillus fumigatus, Candida albicans and Candida glabrata. The composition as claimed in claim 2 for immunomodulation and prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection. The composition as claimed in claim 6 wherein the infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection comprises infection from SARS-CoV-2 and its mutants. The composition as claimed in the claim 2 wherein the ACE2 inhibitors are selected one or more from the group consisting of Nicotiana benthamiana, Pelargonium graveolens L’Hér Momordica dioica roxb.ex willd, Valeriana jatamansijones ex roxb., Oroxylum indicum (L.), Artemisia absinthium L, Syzygium aromaticum (L.), Phaseolus vulgaris L Inula helenium L, Allium
sativum L, Piper longum L, Ipomoea obscura (L.), Ipomoea obscura (L.), Piper nigrum L, Piper retrofractum vahl, Melaleuca cajuputi maton, Scutellaria baicalensis georgi, Erigeron breviscapus, Glycyrrhiza glabra L, Glycyrrhiza uralensis fisch. ex DC. Bupleurum spp. Heteromorpha spp., Scrophularia scorodonia L, Withania somnifera (L.), Asparagus racemosus willd., Diplocyclos palmatus (L.), Citrus spp., Vitis vinifera L. Aframomum melegueta K.Schum An inhaler for prevention/prophylaxis from infection of pathogenic microorganisms attaching to ACE2 receptors for initiating an infection. The inhaler as claimed in claim 9 wherein the pathogenic microorganisms attaching to ACE2 receptors for initiating an infection is a Coronavirus. The inhaler as claimed in claim 9 wherein the Coronavirus is SARS-CoV-2. The inhaler as claimed in claim 9 wherein the ACE 2 inhibitors are essential oils and oleoresins. The inhaler as claimed in claim 10 wherein: a. the one or more essential oils are selected from the group consisting of Wintergreen Oil, Nilgiri/Eucalyptus oil, Terpeon Oil/Terpene oil, Camphor, Lemongrass oil, Terpinene, Anethole, Camphene, Carvacrol, Caryophyllene, Cinnamaldehyde, Cinnamyl acetate, Citral, Citronella, Citronellol, Cuminal, Estragole, Eucalyptol, Eugenol, Fenchel, Geraniol, Umonene, Linalool, Menthol, Myrtanol, Ocimene, p-Cymene, Pinocarveol, Pulegone, Sabinene, Sylvestrene, Terpinen-4-ol, Thujene, Thymol and Zingiberene., and.
b. the ACE2 inhibitors are selected, one or more, from the group consisting of zingiberene, zingiberenece, Gingerol, Eugenol, Acorun calamus L, Zingiber officinale Rose, Trachyspermum ammi, Trachyspermum ammi L. and Syzygium aromaticum L & L.M., Nicotiana benthamiana, Pelargonium graveolens L’Hér Momordica dioica roxb.ex willd, Valeriana jatamansijones ex roxb., Oroxylum indicum (L.), Artemisia absinthium L, Syzygium aromaticum (L.), Phaseolus vulgaris L Inula helenium L, Allium sativum L, Piper longum L, Ipomoea obscura (L.), Ipomoea obscura (L.), Piper nigrum L, Piper retrofractum vahl, Melaleuca cajuputi maton, Scutellaria baicalensis georgi, Erigeron breviscapus, Glycyrrhiza glabra L, Glycyrrhiza uralensis fisch. ex DC. Bupleurum spp. Heteromorpha spp., Scrophularia scorodonia L, Withania somnifera (L.), Asparagus racemosus willd., Diplocyclos palmatus (L.), Citrus spp., Vitis vinifera L. and Aframomum melegueta K.Schum,
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN202021053841 | 2020-12-10 | ||
IN202021053841 | 2020-12-10 | ||
IN202121044544 | 2021-10-01 | ||
IN202121044544 | 2021-10-01 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2022123605A1 true WO2022123605A1 (en) | 2022-06-16 |
WO2022123605A4 WO2022123605A4 (en) | 2022-08-04 |
Family
ID=81974278
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2021/051158 WO2022123605A1 (en) | 2020-12-10 | 2021-12-09 | Herbal composition for covid 19 treatment |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2022123605A1 (en) |
-
2021
- 2021-12-09 WO PCT/IN2021/051158 patent/WO2022123605A1/en active Application Filing
Non-Patent Citations (8)
Title |
---|
ARNIMESH SHANKER: "MP govt to give out free ayurvedic powder packets, herbal oil to boost immunity against Covid", THE PRINT, 29 April 2020 (2020-04-29), XP055943849, Retrieved from the Internet <URL:https://theprint.in/health/mp-govt-to-give-out-free-ayurvedic-powder-packets-herbal-oil-to-boost-immunity-against-covid/411369/> [retrieved on 20220719] * |
BEHL TAPAN, KAUR ISHNOOR, BUNGAU SIMONA, KUMAR ARUN, UDDIN MD SAHAB, KUMAR CHANCHAL, PAL GIRIDHARI, SAHIL, SHRIVASTAVA KAMAL, ZENG: "The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions", LIFE SCIENCE, PERGAMON PRESS, OXFORD, GB, vol. 257, 1 September 2020 (2020-09-01), GB , pages 118075, XP055943847, ISSN: 0024-3205, DOI: 10.1016/j.lfs.2020.118075 * |
DATABASE TKDL 15 December 2009 (2009-12-15), "NASYA AND ANJANA", XP055943854, Database accession no. RS2/153B * |
DATABASE TKDL 15 December 2009 (2009-12-15), "TRIKATU GUNA", XP055943850, Database accession no. RG9/198 * |
DATABASE TKDL 15 December 2009 (2009-12-15), "VYOSADI YOGA", XP055943851, Database accession no. AK11/1212B * |
JOSHI T., T. JOSHI, P. SHARMA, S. MATHPAL, H. PUNDIR, V. BHATT, S. CHANDRA: "In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking", EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, vol. 24, no. 8, 1 April 2020 (2020-04-01), pages 4529 - 4536, XP055837791 * |
REDDY SEETHARAM, REDDY B UMA, SEETHARAM Y N: "Antimicrobial and analgesic activities of Trikatu churna and its ingredients", PHARMACOLOGYONLINE, vol. 3, 1 September 2009 (2009-09-01), pages 489 - 495, XP055943848 * |
SENTHIL KUMAR, K. J. ET AL.: "Geranium and lemon essential oils and their active compounds downregulate angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike receptor-binding domain, in epithelial cells", PLANTS, vol. 9, no. 6, 19 June 2020 (2020-06-19), pages 770, XP055814995, DOI: 10.3390/plants9060770 * |
Also Published As
Publication number | Publication date |
---|---|
WO2022123605A4 (en) | 2022-08-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Mirabi et al. | Effect of medicinal herbs on primary dysmenorrhoea-a systematic review | |
Husen | Traditional herbal therapy for the human immune system | |
Saxena et al. | A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold™) in patients with uncomplicated upper respiratory tract infection | |
JP6966998B2 (en) | Formulations for the treatment of oral, throat and airway disorders | |
Ene et al. | Ethnomedicinal survey of plants used by the Kanuris of North-eastern Nigeria | |
Fatima et al. | Herbal approach for the management of C0VID-19: an overview | |
Sieniawska et al. | Plant‐based food products for antimycobacterial therapy | |
Erarslan et al. | A cross-sectional survey of herbal remedy taking to prevent Covid-19 in Turkey | |
Dehyab et al. | A review of medicinal plant of Middle East and North Africa (MENA) region as source in tuberculosis drug discovery | |
Nasir Ahmed et al. | Role of ethno-phytomedicine knowledge in healthcare of COVID-19: advances in traditional phytomedicine perspective | |
Kilgore et al. | Common respiratory diseases | |
Bary et al. | Moroccan traditional medicine for the prevention and relief of corona virus COVID-19 symtomes | |
Widoyo et al. | Herbal therapy in Covid-19: A systematic review of medicinal plants effective against Covid-19 | |
WO2022123605A1 (en) | Herbal composition for covid 19 treatment | |
Iyer et al. | Biomedical applications of phytomedicines: Dental perspective | |
Rao et al. | Role of Indian traditional medicine in mitigating novel corona virus effects | |
Shomali | Zataria multiflora and Gastrointestinal Tract Disorders | |
Singh et al. | Overview of COVID-19 pandemic: Its management and prevention in light of the Indian traditional medicine system | |
Dsouza et al. | A review on the correlation of traditional plants used for antiviral therapy as a possible treatment for Covid-19 | |
Debroy et al. | Covid-19 Outbreak: An Analysis of Risk Factors and Potential Role of Medicinal Plants to Combat the Disease | |
SINGH | Identifying Herbal Drugs and Phytoconstituents in post-Covid 19 Indian Households | |
Lodhi et al. | Herbal Formulation and COVID-19 | |
Mattioli et al. | Long COVID‐19 gastrointestinal related disorders and traditional Chinese medicine: A network target‐based approach | |
Srivastava et al. | Role of Medicinal Plants in the Treatment of COVID-19: A Review | |
Adeniran et al. | Epidemiological status of coronavirus diseases and the remedy potentials of medicinal plants in Africa |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21902905 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21902905 Country of ref document: EP Kind code of ref document: A1 |