WO2017216677A1 - Single use pharmaceutical composition for rectal administration - Google Patents

Single use pharmaceutical composition for rectal administration Download PDF

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Publication number
WO2017216677A1
WO2017216677A1 PCT/IB2017/053318 IB2017053318W WO2017216677A1 WO 2017216677 A1 WO2017216677 A1 WO 2017216677A1 IB 2017053318 W IB2017053318 W IB 2017053318W WO 2017216677 A1 WO2017216677 A1 WO 2017216677A1
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WO
WIPO (PCT)
Prior art keywords
ginger
nausea
form according
vomiting
grams
Prior art date
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PCT/IB2017/053318
Other languages
French (fr)
Inventor
Celestino RICCIARDI
Giovanna ADELIZZI
Original Assignee
Space International S.A.S.
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Publication date
Application filed by Space International S.A.S. filed Critical Space International S.A.S.
Priority to EP17733895.1A priority Critical patent/EP3471700A1/en
Publication of WO2017216677A1 publication Critical patent/WO2017216677A1/en

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Classifications

    • 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
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • 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)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • 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

Definitions

  • the present invention relates to a single use (disposable) pharmaceutical composition form for rectal administration.
  • the object of this invention is to be conveniently and effectively used in the field of medical devices, in particular as for the treatment of symptoms related to irritative states of the ano-rectal mucosa, such as irritation, itching and burning caused by the high number of daily diarrheal discharges due to viral gastroenteritis or intestinal infections characterized by aqueous diarrhoea, abdominal cramps, nausea, vomiting.
  • Another object of the present invention is to develop a pharmaceutical form, e.g.
  • a suppository or a gel, a ointment, a cream or the like, in its version for adults or, alternatively, for use in the paediatric field, which might be able to effectively help restore the integrity and the physiological functionality of the ano-rectal mucosa and reduce the symptoms related to the irritative processes of the ano-rectal mucosa itself.
  • this single use disposable pharmaceutical composition form is a suppository for rectal use having the following composition:
  • Triticum vulgare (or Triticum aestivum) is soft wheat, or wheat, the know plant belonging to the Gramineae family, being cultivated for over 10,000 years. This is clearly a very widespread plant species, which is also equally studied, mainly for its food applications (its flour is the most suitable one for bread-making and it is used instead of all other flours that were used for this purpose in many countries of the world). What is also clear is that the grown varieties stem from a long artificial selection, which still continues, aimed at improving its resistance, yield, cultivation ease, ripening speed and all those features that may be useful for its cultivation and use. In particular, this pharmaceutical form is the aqueous extract obtained from the so called "wheat germ", which is incorporated as the active ingredient.
  • the term "Wheat germ” refers to a special portion of the caryopsis (the grain) of wheat, which amounts to just a narrow percentage by weight of the entire grain and which represents its sprouting part (from which the plant grows).
  • the wheat germ can be mechanically separated from its grain and it has been marketed for direct food consumption for a long time.
  • the wheat germ contains many different substances (fat, vitamins, minerals), which make it an interesting ingredient thanks to its nutritional properties. D Thanks to its special composition, characterized by the presence of starches, phospholipids and glycolipids, the wheat germ extract plays its role within this DM.
  • the wheat germ extract is also used in moisturising dermatological products and as a skin protective and conditioning ingredient.
  • This ingredient is, in fact, included in the European database of cosmetic ingredients (COSING) and can be used without limitations for those products intended for cosmetic use.
  • Tocopherols are a class of organic compounds having, in general, the same activities as vitamin E; this is the reason why the definition of vitamin E does not refer to just one chemical entity.
  • the product dl-a-Tocopheryl Acetate which is commercially one of the most widely used products due to various reasons related to its stability, has been added.
  • tocopherols are fat-soluble alcohols having a strong antioxidant activity, even if they also perform many other physiological functions in the body. DTheir antioxidant activity counteracts radical oxidation phenomena, and has an inhibitory action against free radicals. Vitamin E is able to stop the radical cascade reaction by giving a hydrogen atom to the reactive radicals, and turning into an inert radical.
  • Vitamin E plays an important role, as an antioxidant factor, in the prevention of the oxidation of polyunsaturated fatty acids, which is the key event in the development of the lipid peroxidation process.
  • the industrial sector (in addition to its obvious use as a food supplement) uses vitamin E as a low cost food preservative, characterized by a high safety level.
  • Vitamin E also plays an important role as an ingredient for cosmetic preparations, in which (in addition to acting as a preservative) it also protects the skin and mucosa against any damage caused by free radicals and oxidative stress factors (exposure to UV, pollution, etc.).
  • this ingredient is used as a preservative, thus preserving this form from oxidative stress, both inside its final container and after the product has been used.
  • Ginger is a herbaceous plant belonging to the Zingiberaceae family (the same family as cardamom) stemming from the far east. Ginger is cultivated in the entire tropical and subtropical belts. It is characterized by a fleshy and densely branched rhizome, out of which both long hollow and sterile trunks - formed by lanceolate sheathing leaves - and short fertile flower stalks grow, and bear yellow- greenish flowers with crimson stains. Its fruit is a capsule subdivided into three locules by septa.
  • the rhizome is the used part of the plant and which contains the active ingredients: essential oil (mainly composed by zingiberene), gingerols and shogaols (which cause its sharp taste), resins and mucilage, and is characterized by the typical taste and aroma thanks to which ginger is widely used as a spice, in its dried or pulverized form, or fresh as thin slices. It is also used to prepare alcoholic drinks and beverages. Although mainly intended for food use, it is also well known as a medicinal plant, mainly as an antiemetic, but also as an anti-inflammatory agent. However, these functions are not relevant to this medical preparation (since it is not intended for oral administration).
  • ginger helps develop the film- forming and protective effect of the wheat germ extract, therefore supporting its action. In addition to this, and also thanks to this film-forming effect, it has a soothing effect on the irritated mucosa, thus alleviating the pain.
  • the European legislation regulates its use in cosmetic products (without safety restrictions) as a skin conditioning agent. Ginger is very effective against nausea, and according to some clinical studies, this may be due to its activity of antiserotoninergic type, stopping the transmission of the 5-HT3 emetic signal.
  • 5-HT3 gastric receptors are important for the onset of vomiting. Experimental evidence suggests that some ginger components are able to stop this receptor, thus reducing the emetic signal reaching the central system (through the vagal connections) and increasing the gastric motility (the block of 5-HT3 gastro-intestinal receptors implies an increase of acetylcholine release, a neurotransmitter that stimulates the gastro-intestinal motility).
  • gingerols 33%
  • shogaols zingerone
  • Gingerols especially the 6-gingerol, and shogaols, are the active ingredients responsible for its biological activity, since these elements are capable of inhibiting vomiting induced by copper sulphate in frogs.
  • a study involving healthy volunteers showed that nausea induced by circular movement was inhibited by therapeutic doses of ginger.
  • ginger The effectiveness of ginger for treating nausea depends on the condition causing it; as a matter of fact, it has been observed that ginger can counteract nausea and vomiting arising during pregnancy.
  • ginger is safe if used during pregnancy, since there are no significant differences with respect to placebos, as for side effects or adverse reactions during pregnancy and it does not entail any significant risk of causing possible side effects, such as heartburn or drowsiness.
  • ginger could be considered as an effective and harmless alternative for women suffering from nausea and vomiting during pregnancy (Estelle Viljoen, Janicke Visser, Nelene Koen and Alfred Musekiwa; Viljoen et al.; A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy- associated nausea and vomiting; Nutrition Journal 2014, 13:20).
  • Ginger has proved to be effective even when nausea and vomiting are caused by chemotherapy (Inaki Lete and Jose Allue; The Effectiveness of Ginger in the Prevention of Nausea and Vomiting during Pregnancy and Chemotherapy; Libertas academica; Integrative Medicine Insights 2016:1 1 ).
  • Ginger is effective in diminishing post-surgery nausea and vomiting symptoms both in individuals that underwent open nephrectomy, and in individuals that underwent laparoscopic nephrectomy. Ginger may thus be recommended as a complementary remedy to prevent and treat post-op nausea and vomiting in patients that underwent nephrectomy.
  • ginger may also be a reasonable and safe alternative for the treatment of nausea and vomiting in pregnant women and that it may be useful for the treatment of nausea and vomiting symptoms induced by chemotherapy.
  • the prokinetic effects affecting gastric motility may suggest a potential role of ginger extracts in treating various digestive diseases and in particular functional dyspepsia, as well as those patients who suffer from neurological or endocrinological side effects due to the use of prokinetic drugs, such as domperidone, levosulpiride or metoclopramide.
  • the treatment based on ginger extracts might avoid the risk of sudden cardiac death, observed in elderly patients treated with domperidone doses higher than 30 mg for 31 -34 days. Further studies are needed to be able to confirm such hypothesis and other interesting properties that are worth studying. (A. GIACOSA, P. MORAZZONI, et.al; Can nausea and vomiting be treated with ginger extract?; European Review for Medical and Pharmacological Sciences; 2015; 19: 1291 -1296). Suppocire BS2X, or other triglyceride equivalent excipient.
  • This pharmaceutical form is mono-, bi- and triglycerides of saturated fatty acids (the preferred, but not limiting, mixture is sold with the following trade name: SUPPOCIRE BS2X).
  • SUPPOCIRE BS2X the preferred, but not limiting, mixture is sold with the following trade name: SUPPOCIRE BS2X.
  • This product is specifically manufactured to be the vehicle for suppositories and vaginal suppositories: it is solid at room temperature and melts after being inserted because of the body temperature. This is a standard ingredient, prepared according to the rules of good manufacturing of pharmaceutical excipients.
  • the pharmaceutical suppository form melts at body temperature after being inserted and the semi-synthetic triglycerides, constituting the vehicle of the formulation, release the substances contained in the form upon contact with the rectal mucosa: ⁇ -
  • the Triticum aqueous extract characterized by film-forming properties, lays on the rectal mucosa and has a moisturising and protective effect against irritating stimuli, especially where the mucosa is already irritated, thus helping diminishing the symptoms affecting the irritated mucosa, such as itching and burning.
  • the protective film allows to keep the needed humidity conditions in the treated area for a proper healing of the mucosa itself;
  • the fat-soluble ginger extract exerts a lenitive action and is effective against nausea and vomiting;
  • Vitamin E essentially preserves the formulation thanks to the anti-oxidizing action, which is needed to maintain the features of the semi-synthetic triglycerides.
  • the above described pharmaceutical form is, preferably but not limited to, marketed as adult suppositories, 2.0 grams each packed in a blister containing 20
  • suppositories and, as children suppositories, 1 .0 grams each packed in a blister containing 10 suppositories.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
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Abstract

Single use pharmaceutical composition form suitable for rectal administration, containing the following components: aqueous extract of Triticum Vulgare, and fat-soluble ginger extract, vitamin E, and triglyceride excipient or equivalent.

Description

SINGLE USE PHARMACEUTICAL COMPOSITION FOR RECTAL ADMINISTRATION.
Applicant: SPACE INTERNATIONAL S.A.S., Via Martiri di Via Fani, 2 - 71122 Foggia (FG).
Designated inventors: Celestino Ricciardi and Giovanna Adelizzi
The present invention relates to a single use (disposable) pharmaceutical composition form for rectal administration.
The object of this invention is to be conveniently and effectively used in the field of medical devices, in particular as for the treatment of symptoms related to irritative states of the ano-rectal mucosa, such as irritation, itching and burning caused by the high number of daily diarrheal discharges due to viral gastroenteritis or intestinal infections characterized by aqueous diarrhoea, abdominal cramps, nausea, vomiting. Another object of the present invention is to develop a pharmaceutical form, e.g. a suppository, or a gel, a ointment, a cream or the like, in its version for adults or, alternatively, for use in the paediatric field, which might be able to effectively help restore the integrity and the physiological functionality of the ano-rectal mucosa and reduce the symptoms related to the irritative processes of the ano-rectal mucosa itself. The structural and functional characteristics of the present invention and its advantages with respect to pharmaceutical forms of the known art that are now available on the market, will be clearer and more evident from the claims below and, in particular, from an examination of the following detailed description.
According to a preferred, but not limiting, structural embodiment, this single use disposable pharmaceutical composition form is a suppository for rectal use having the following composition:
Figure imgf000003_0001
Component details.
Triticum Vulgare (Soft wheat)
Triticum vulgare (or Triticum aestivum) is soft wheat, or wheat, the know plant belonging to the Gramineae family, being cultivated for over 10,000 years. This is clearly a very widespread plant species, which is also equally studied, mainly for its food applications (its flour is the most suitable one for bread-making and it is used instead of all other flours that were used for this purpose in many countries of the world). What is also clear is that the grown varieties stem from a long artificial selection, which still continues, aimed at improving its resistance, yield, cultivation ease, ripening speed and all those features that may be useful for its cultivation and use. In particular, this pharmaceutical form is the aqueous extract obtained from the so called "wheat germ", which is incorporated as the active ingredient. The term "Wheat germ" refers to a special portion of the caryopsis (the grain) of wheat, which amounts to just a narrow percentage by weight of the entire grain and which represents its sprouting part (from which the plant grows). The wheat germ can be mechanically separated from its grain and it has been marketed for direct food consumption for a long time. Unlike the endosperm (the main element of the grain, which is mainly made of starch and proteins), the wheat germ contains many different substances (fat, vitamins, minerals), which make it an interesting ingredient thanks to its nutritional properties. DThanks to its special composition, characterized by the presence of starches, phospholipids and glycolipids, the wheat germ extract plays its role within this DM. As a matter of fact, it is able to create a film on the surface of the skin or mucosa, which is useful to prevent the loss of liquids, thereby facilitating the return of fibroplastic cells intended for synthesizing the collagen fibres and responsible for the healing process. Since the proteins contained in the wheat germ extract are able to create a moisturising, soothing and skin-protecting colloidal type protective film, the wheat germ extract is also used in moisturising dermatological products and as a skin protective and conditioning ingredient. This ingredient is, in fact, included in the European database of cosmetic ingredients (COSING) and can be used without limitations for those products intended for cosmetic use.
Vitamin E.
Tocopherols are a class of organic compounds having, in general, the same activities as vitamin E; this is the reason why the definition of vitamin E does not refer to just one chemical entity. In this DM, the product dl-a-Tocopheryl Acetate, which is commercially one of the most widely used products due to various reasons related to its stability, has been added. In terms of reactivity, tocopherols are fat-soluble alcohols having a strong antioxidant activity, even if they also perform many other physiological functions in the body. DTheir antioxidant activity counteracts radical oxidation phenomena, and has an inhibitory action against free radicals. Vitamin E is able to stop the radical cascade reaction by giving a hydrogen atom to the reactive radicals, and turning into an inert radical. Vitamin E plays an important role, as an antioxidant factor, in the prevention of the oxidation of polyunsaturated fatty acids, which is the key event in the development of the lipid peroxidation process. The industrial sector (in addition to its obvious use as a food supplement) uses vitamin E as a low cost food preservative, characterized by a high safety level.□ Vitamin E also plays an important role as an ingredient for cosmetic preparations, in which (in addition to acting as a preservative) it also protects the skin and mucosa against any damage caused by free radicals and oxidative stress factors (exposure to UV, pollution, etc.). This is the reason why it is widely used in many topical products, such as creams, sera, anti-age gels, antioxidants and brightening products, as well as preparations for vaginal or anorectal use. In this form, this ingredient is used as a preservative, thus preserving this form from oxidative stress, both inside its final container and after the product has been used.
Ginger extract.
Ginger (Zingiber officinalis) is a herbaceous plant belonging to the Zingiberaceae family (the same family as cardamom) stemming from the far east. Ginger is cultivated in the entire tropical and subtropical belts. It is characterized by a fleshy and densely branched rhizome, out of which both long hollow and sterile trunks - formed by lanceolate sheathing leaves - and short fertile flower stalks grow, and bear yellow- greenish flowers with crimson stains. Its fruit is a capsule subdivided into three locules by septa. The rhizome is the used part of the plant and which contains the active ingredients: essential oil (mainly composed by zingiberene), gingerols and shogaols (which cause its sharp taste), resins and mucilage, and is characterized by the typical taste and aroma thanks to which ginger is widely used as a spice, in its dried or pulverized form, or fresh as thin slices. It is also used to prepare alcoholic drinks and beverages. Although mainly intended for food use, it is also well known as a medicinal plant, mainly as an antiemetic, but also as an anti-inflammatory agent. However, these functions are not relevant to this medical preparation (since it is not intended for oral administration). Thanks to the presence of mucilage, ginger helps develop the film- forming and protective effect of the wheat germ extract, therefore supporting its action. In addition to this, and also thanks to this film-forming effect, it has a soothing effect on the irritated mucosa, thus alleviating the pain. The European legislation regulates its use in cosmetic products (without safety restrictions) as a skin conditioning agent. Ginger is very effective against nausea, and according to some clinical studies, this may be due to its activity of antiserotoninergic type, stopping the transmission of the 5-HT3 emetic signal.
5-HT3 gastric receptors are important for the onset of vomiting. Experimental evidence suggests that some ginger components are able to stop this receptor, thus reducing the emetic signal reaching the central system (through the vagal connections) and increasing the gastric motility (the block of 5-HT3 gastro-intestinal receptors implies an increase of acetylcholine release, a neurotransmitter that stimulates the gastro-intestinal motility).
The main elements constituting ginger are: gingerols (33%), shogaols, zingerone. Gingerols, especially the 6-gingerol, and shogaols, are the active ingredients responsible for its biological activity, since these elements are capable of inhibiting vomiting induced by copper sulphate in frogs. A study involving healthy volunteers showed that nausea induced by circular movement was inhibited by therapeutic doses of ginger. These beneficial effects were associated with a normalization of the gastric motility and inhibition of the vasopressin release (Lien and coll. 2003).
The effectiveness of ginger for treating nausea depends on the condition causing it; as a matter of fact, it has been observed that ginger can counteract nausea and vomiting arising during pregnancy. A study carried out on 187 pregnant women showed that ginger does not increase the risk of malformations (Portnoi and coll. -
2003).
More studies on ginger have further highlighted its ability to reduce the symptoms of nausea and vomiting in pregnant women, thus becoming an alternative choice to conventional medical products that may have possible harmful side effects. Orally administered ginger significantly improved those symptoms related to nausea if compared to the placebo administered to the control group (MD 1 .20, 95% CI 0.56- 1 .84, p = 0.0002, I2 = 0%) and, even if it did not reduce significantly the number of episodes of vomiting compared to placebo, it showed a trend towards improvement. Research also shows that ginger is safe if used during pregnancy, since there are no significant differences with respect to placebos, as for side effects or adverse reactions during pregnancy and it does not entail any significant risk of causing possible side effects, such as heartburn or drowsiness. On the basis of the evidence of this study, ginger could be considered as an effective and harmless alternative for women suffering from nausea and vomiting during pregnancy (Estelle Viljoen, Janicke Visser, Nelene Koen and Alfred Musekiwa; Viljoen et al.; A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy- associated nausea and vomiting; Nutrition Journal 2014, 13:20).
Ginger has proved to be effective even when nausea and vomiting are caused by chemotherapy (Inaki Lete and Jose Allue; The Effectiveness of Ginger in the Prevention of Nausea and Vomiting during Pregnancy and Chemotherapy; Libertas academica; Integrative Medicine Insights 2016:1 1 ).
Another study proposed the assessment of the effectiveness of ginger on the intensity of nausea and vomiting as post-operative side effects after surgery. 160 patients were divided into two groups: one was treated with control placebo and the other one was treated with ginger; the two groups were given 4 capsules of product one hour before surgery and the effects of this administration on nausea and vomiting were assessed 2, 4 and 6 hours after surgery. The intensity of vomiting and nausea was significantly lower in those groups treated with ginger at all times considered by the study. Ginger could then be safely used as an antiemetic drug after surgery. (Akram Sadat Montazeri, Azam Hamidzadeh e coll.; Evaluation of Oral Ginger Efficacy against Postoperative Nausea and Vomiting A Randomized Double - Blinded Clinical Trial; Iran Red Crescent Med J. 2013 December; 15(12): e12268.)
Ginger is effective in diminishing post-surgery nausea and vomiting symptoms both in individuals that underwent open nephrectomy, and in individuals that underwent laparoscopic nephrectomy. Ginger may thus be recommended as a complementary remedy to prevent and treat post-op nausea and vomiting in patients that underwent nephrectomy. (Fatemeh Sadat Hosseini; Mohsen Adib-Hajbaghery; Ginger Essence Effect on Nausea and Vomiting After Open and Laparoscopic Nephrectomies; Nurs Midwifery Stud. 2015 June; 4(2): e28625);
Studies were also performed to assess ginger effectiveness on arthritis; however, for these studies to be significant, they should be further developed (BRETT WHITE; Ginger: An Overview; American Family Physician; Volume 75, Number 1 1 ; June 1 , 2007)
Other studies show that ginger may also be a reasonable and safe alternative for the treatment of nausea and vomiting in pregnant women and that it may be useful for the treatment of nausea and vomiting symptoms induced by chemotherapy. The prokinetic effects affecting gastric motility may suggest a potential role of ginger extracts in treating various digestive diseases and in particular functional dyspepsia, as well as those patients who suffer from neurological or endocrinological side effects due to the use of prokinetic drugs, such as domperidone, levosulpiride or metoclopramide.
In particular, the treatment based on ginger extracts might avoid the risk of sudden cardiac death, observed in elderly patients treated with domperidone doses higher than 30 mg for 31 -34 days. Further studies are needed to be able to confirm such hypothesis and other interesting properties that are worth studying. (A. GIACOSA, P. MORAZZONI, et.al; Can nausea and vomiting be treated with ginger extract?; European Review for Medical and Pharmacological Sciences; 2015; 19: 1291 -1296). Suppocire BS2X, or other triglyceride equivalent excipient.
Other components of this pharmaceutical form are mono-, bi- and triglycerides of saturated fatty acids (the preferred, but not limiting, mixture is sold with the following trade name: SUPPOCIRE BS2X). This product is specifically manufactured to be the vehicle for suppositories and vaginal suppositories: it is solid at room temperature and melts after being inserted because of the body temperature. This is a standard ingredient, prepared according to the rules of good manufacturing of pharmaceutical excipients.
Mechanism of action.
The pharmaceutical suppository form melts at body temperature after being inserted and the semi-synthetic triglycerides, constituting the vehicle of the formulation, release the substances contained in the form upon contact with the rectal mucosa:□ - The Triticum aqueous extract, characterized by film-forming properties, lays on the rectal mucosa and has a moisturising and protective effect against irritating stimuli, especially where the mucosa is already irritated, thus helping diminishing the symptoms affecting the irritated mucosa, such as itching and burning. The protective film allows to keep the needed humidity conditions in the treated area for a proper healing of the mucosa itself;
- The fat-soluble ginger extract exerts a lenitive action and is effective against nausea and vomiting;
Vitamin E essentially preserves the formulation thanks to the anti-oxidizing action, which is needed to maintain the features of the semi-synthetic triglycerides.□
Therefore, functional substances - through the above described mechanisms of action - help restore the integrity and the physiological functions of the ano-rectal mucosa and reduce the symptoms related to the inflammatory process of the mucosa itself. DThe remaining components are common excipients that are used in forms for rectal use in the pharmaceutical field.□
The above described pharmaceutical form is, preferably but not limited to, marketed as adult suppositories, 2.0 grams each packed in a blister containing 20
suppositories and, as children suppositories, 1 .0 grams each packed in a blister containing 10 suppositories.

Claims

1. Single use pharmaceutical form suitable for rectal administration, containing the following components: aqueous extract of Triticum Vulgare, fat-soluble ginger extract, Vitamin E, and an excipient triglyceride or equivalent.
2. Form according to claim 1 , containing a percentage up to 10 grams of said aqueous extract of Triticum Vulgare.
3. Form according to claim 2, wherein said aqueous extract of Triticum Vulgare is equal to 0.005 grams.
4. Form according to one or more of claims 1 to 3, containing a percentage up to 10 grams of said soluble ginger extract.
5. Form according to claim 4, wherein said soluble ginger extract is equal to 0,300 grams.
6. Form according to one or more of claims 1 to 5, containing a percentage up to 10 grams of said vitamin E.
7. Form according to claim 6, wherein said Vitamin E is equal to 0.005 grams.
8. Suppository comprising the pharmaceutical form according to one or more of the preceding claims 1 to 7.
9. Use of the pharmaceutical form according to one or more of the preceding claims 1 to 7 or 8, in the treatment of symptoms of irritation of the anorectal mucosa.
PCT/IB2017/053318 2016-06-17 2017-06-06 Single use pharmaceutical composition for rectal administration WO2017216677A1 (en)

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ITUA2016A004447A ITUA20164447A1 (en) 2016-06-17 2016-06-17 PHARMACEUTICAL FORM DISPOSABLE FOR RECTAL USE.

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101339706B1 (en) * 2013-06-20 2013-12-10 재단법인 금산국제인삼약초연구소 A compound for immune strengthen inclusion reducing the bitterness of red ginseng, the extract of immune, and the probiotics

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101339706B1 (en) * 2013-06-20 2013-12-10 재단법인 금산국제인삼약초연구소 A compound for immune strengthen inclusion reducing the bitterness of red ginseng, the extract of immune, and the probiotics

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