CA2286357A1 - Antacid and papain combination - Google Patents

Antacid and papain combination Download PDF

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Publication number
CA2286357A1
CA2286357A1 CA002286357A CA2286357A CA2286357A1 CA 2286357 A1 CA2286357 A1 CA 2286357A1 CA 002286357 A CA002286357 A CA 002286357A CA 2286357 A CA2286357 A CA 2286357A CA 2286357 A1 CA2286357 A1 CA 2286357A1
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French (fr)
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Constantine Georgiades
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Warner Lambert Co LLC
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/22Cysteine endopeptidases (3.4.22)
    • C12Y304/22002Papain (3.4.22.2)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)

Abstract

A composition for relieving stomach distress is disclosed. The composition comprises a combination of one or more compositions that reduce gastric acidity and a composition extracted from papaya, preferably comprising one or more proteolytic enzymes. Also disclosed are methods of making and methods of using such compositions.

Description

s 1 TITLE
zo ANTACID AND PAPAIN COMBINATION
Field of the Invention i5 This invention relates to a composition for treating the symptoms of excess gastric acid secretion, such as heartburn, sour stomach, acid indigestion and upset stomach.
The composition of this invention is a combination of: 1 ) one or more compositions that reduce gastric acidity; and, 2) papaya extract.
a o Background Of The Invention It is well known that excess production of stomach acid can cause symptoms of gastric distress, heartburn, dyspepsia, and the like. For the vast majority of people, symptoms of gastric hyperacidity occur after certain foods have been consumed.
Spicy foods, pickled foods, peppers, tomatoes and citrus fruits are among those 2s foods that frequently cause hyperacidity. There are a number of compositions that provide relief from gastric hyperacidity. These compositions include, but are not WO 99/03486 PCTNS98/i4233 limited to, compositions that reduce intragastric hydrogen ion concentration by chemical neutralization such as calcium carbonate (e.g. Tums~), magnesium hydroxide (e.g. Mylanta~), a combination of calcium carbonate and magnesium hydroxide (e.g. Rolaids~) and the like; H2 receptor antagonists such as ranitidine (e.g. Zantac~), cimetidine (e.g. Tagemet~), and the like; proton-pump inhibitors such as omeprazole; bismuth compounds; prostaglandins; sucralfate; and, dopamine antagonists such as cisapride. Each of these classes of compositions have different mechanisms of action, yet all have been shown to be effective in reducing or eliminating symptoms of gastric hyperacidity.
While the foregoing compositions are effective, some are not long lasting, while others have a delayed onset of action. More specifically, compositions such as Tums~, Mylanta~, and Rolaids~ are not long lasting. whereas HZ receptor antagonists, proton-pump inhibitors, and others do not have a rapid onset of action (i.e. less than one minute). A composition capable of overcoming these disadvantages is therefore desired.
The digestive action of papaya, a fruit of the melon tree Carica papaya Linn has been known for centuries. Studies have shown the juice from the fruit, also referred to as latex, contains proteolytic enzymes, which have been identified as papain, chymopapain and papaya proteinase III. Papain is the most characterized among the three. Its approximate molecular weight is 21,000, and it contains 18 different amino acids in a sequence of 211 amino acids.
While it is not certain exactly what compounds in papaya reduce gastric acidity, studies in rats have shown that feeding the latex of unripe papaya fruit significantly reduced acid secretion induced by methocholine. Feeding of crystalline papain in doses of 3.2 mg/kg reduced reduced gastric acid secretion. Reduction of gastric acid ,..
secretion was observed as early as 2 hours after administration and lasted as long as 48 hours in the rat. Cho, et al., Proc. Natl. Sci. Counc. ROC(B), 8(2), 177-( 1984).
s Combinations of pure digestive enzymes, such as proteases, in a stable aqueous colloidal suspension with aluminum hydroxide are disclosed in U.S. Pat. No.
3,329,564. The proteases or other digestive enzymes are added to the aluminum hydroxide antacid in small quantities to provide the digestive benefits of enzymatic action to an antacid preparation. However, these compositions are inconvenient to io use because they are suspensions.
It is therefore an object of this invention to provide a composition that is capable of providing improved relief from the effects of excess gastric acid secretion.
It is also desired to provide such a composition in a form that is convenient to carry or is transport.
SUMMARY OF THE INVENTION
The present invention is directed to a composition comprising: 1 ) one or more compositions that reduce stomach acidity; and, 2) a composition extracted from 2o papaya, preferably comprising one or more proteolytic enzymes, including but not limited to, papain, chymopapain and papaya proteinase III. This composition can be used to provide improved, convenient relief from gastric distress resulting from excess gastric acid secretion.
The present invention is further directed to a method of preparing a composition comprising: 1) one or more compositions that reduce stomach acidity; and, 2) a composition extracted from papaya, preferably comprising one or more proteolytic enzymes, including but not limited to, papain, chymopapain and papaya proteinase s III.
The present invention is further directed to a method of using a composition comprising: 1 ) one or more compositions that reduce stomach acidity; and, 2) a composition extracted from papaya, preferably comprising one or more proteolytic to enzymes, including but not limited to, papain, chymopapain and papaya proteinase III.
DETAILED DESCRIPTION OF THE INVENTION
15 The present invention is directed to a composition for relieving stomach distress comprising: 1 ) one or more compositions that reduce gastric acidity; and, 2) a composition extracted from papaya, preferably comprising one or more proteolytic enzymes, including but not limited to, papain, chymopapain and papaya proteinase III. This composition can be used to provide improved, convenient relief from 2o gastric distress resulting from excess gastric acid secretion. This invention is further directed to a method of preparing and a method of using such a composition for providing improved relief of gastric distress.

The amounts of the ingredients that can be used in this composition are generally the ordinary dosages required to obtain the desired result. In one embodiment the amount of the first component that reduces gastric acidity is present in an amount of from about 10 mg/dose to about 1500 mg/dose and the amount of the papaya extract is present in an amount of from about SO mg/dose to about 3000 mg/dose.
In accordance with this invention compositions that reduce gastric acidity may be any of the following: compositions that reduce intragastric hydrogen ion io concentration by chemical neturalization; HZ receptor antagonists; proton-pump inhibitors: bismuth compounds; prostaglandins; sucralfate; and dopamine antagonists. These compositions are herewith defined as "antacids." The composition of this invention may comprise one or more than one of these antacids.
is In accordance with this invention improved relief from gastric distress can be either relief that has a longer duration of action and/or a faster onset of action than would occur from ingesting the antacid component alone of this inventive composition alone.
ao Nonlimiting examples of compositions that reduce gastric acidity by chemical neutralization are: aluminum-containing active ingredients; bicarbonate-containing active ingredients; bismuth-containing active ingredients; calcium-containing active ingredients; citrate-containing active ingredients; glycine; magnesium-containing active ingredients; dried milk solids; phosphate-containing active ingredients;
2s potassium-containing active ingredients; sodium-containing active ingredients;
silicates and tartrate-containing active ingredients; and other compositions recognized by the U.S. Food and Drug Administration (FDA) as useful for the relief of heartburn, sour stomach, or acid indigestion and upset stomach. These compositions are listed in 21 C.F.R. ~ 331, which is hereby incorporated by reference in its entirety.
In this invention calcium carbonate and magnesium hydroxide are the preferred chemical neutralizing compositions. Calcium carbonate is the most preferred.
Receptor antagonists reduce gastric acid secretion by blocking histamine receptors in the stomach lining. Histamine stimulates gastric secretion via H~ receptors.
Nonlimiting examples of HZ receptor antagonists are: ranitidine, cimetidine, famotidine, mifentidine, roxatidine, and mizatidine. The amount of H, receptor antagonist that can be used in this invention is from about 10 mg/dose to about 800 mg/dose. In this invention ranitidine is the preferred H, receptor antagonist.
The amount of ranitidine that can be used in this invention is from about 75 mg/dose to about 300 mg/dose.
Proton pump inhibitors block the membrane pump on the parietal cells in the stomach that are responsible for exchanging potassium from the gastric lumen with hydrogen ions. Blocking this membrane pump inhibits gastric acid secretion. A
nonlimiting example of a proton pump inhibitor is omeprazole.
Bismuth compounds act in a number of ways to reduce gastrointestinal distress.
A
nonlimiting example of a bismuth compound is bismuth subcitrate, also known as tripotassium dicitrato bismuthate.
Prostaglandins are Iipid hormones found in virtually all tissues. It is believed that one effect of prostaglandins in the stomach is reduction of acid secretion.
They may also enhance mucosal resistance to stomach irntation. Nonlimiting examples of prostaglandins are PGE1, of which misoprostol is an analogue: PGE2, of which arabaprostil and enprostil are analogues; PGII, and methyl analogs of prostaglandins of the E series.
Sucralfate is a complex salt of polyaluminium hydroxide with a sulphated saccharide skeleton which has been proven clinically to be effective in the treatment of gastric and duodenal ulceration. It is a weak buffer with a pK of approximately 4.5.
Dopamine antagonists are believed to relieve gastric distress by increasing gastrointestinal motility and decreasing transit time. Nonlimiting examples of to dopamine antagonists are metoclopramide, domperidone. and cisapride.
The amount of the foregoing compositions that reduce gastric acidity that are used in this invention may vary depending upon the therapeutic dosage recommended or permitted for the particular agent. In general, the amount of these compositions is 15 the ordinary dosage required to obtain the desired result. In one embodiment of this invention the amount of compositions that reduce gastric acidity by chemical neutralization are present in an amount of from about 250 mg to about 1450 mg/dose. The dosage form may be a tablet, caplet, capsule, powder, troche, lozenge, elixir, and the like. Such dosages are known to the skilled practitioner in the 2 o medical arts. Preferred dosage forms are tablets and caplets.
In a preferred embodiment magnesium hydroxide is in an amount of from about 50 to about 800 mg/dose; preferably in an amount of from about 80 mg to about 600 mg/dose; and most preferably from about 100 mg to about 400 mg/dose.
In another preferred embodiment calcium carbonate is in an amount of about 200 to about 1250 mg/dose; preferably from about 400 mg to about I 000 mg/dose; and most preferably from about 500 mg to about 800 mg/dose.

Another preferred embodiment of this invention contains both magnesium hydroxide and calcium carbonate in an amount of magnesium hydroxide of from about 50 mg s to about 400 mg/dose and calcium carbonate in an amount of from about 200 mg to about 1250 mg/dose; preferably an amount of magnesium hydroxide of from about 80 mg to about 300 mg/dose and calcium carbonate in an amount of from about mg to about 1000 mg/dose; and most preferably an amount of magnesium hydroxide of from about 100 mg to about 260 mg/dose and calcium carbonate in an amount of to from about about 500 mg to about 800 mg/dose.
The present invention further includes a composition extracted from the juice, pulp, or other parts of papaya. In this invention the composition extracted from papaya is defined as papaya extract. One embodiment of this invention comprises one or more is proteolytic enzymes from papaya extract. Nonlimiting examples of proteolytic enzymes are papain, chymopapain, and papaya proteinase III. The preferred enzyme is papain. The papaya extract of this invention may be in a variety of forms.
Nonlimiting examples of these forms are: the dried powdered latex of papaya;
freeze dried papaya powder; papaya juice powder; crystalline papain; and crystalline ao chymopapain. The preferred forms are freeze dried papaya powder and papaya juice powder.
In one embodiment of this invention the amount of papaya extract in each dose of the composition of this invention is from about 50 mg to about 3000 mg. The zs preferred amount is from about 100 mg to about 1000 mg. The most preferred amount is from about 200 mg to about 800 mg.

Another embodiment of this inventive composition contains one or more proteolytic enzymes found in papaya extract, including but not limited to papain, chymopapain, and papaya protease III. These enzymes may be relatively pure (i.e. of pharmaceutical grade), but preparations of less pure enzymes are also acceptable.
The amount of the one or more proteolytic enzymes per dose in this embodiment is from about 0.5 to about 600 mg; preferably from about 1.5 mg to about 300 mg;
and most preferably from about 2.5 mg to about 200 mg.
io The composition of this invention may also contain other ingredients and excipients known to one skilled in the art. Nonlimiting examples of these additional ingredients include excipients, binders, coloring, flavoring, sugars, starches and the like. The composition of this invention may be used in many distinct physical forms well known in the pharmaceutical art to provide an initial dosage of the inventive 15 composition and/or a further time-release form of the inventive composition.
Without being limited thereto, such physical forms include tablets, caplets, capsules, powders, troches, lozenges, elixirs, and the like.
This invention extends to methods of making the inventive composition. In general a o the composition of this invention is made by admixing one or more antacids of this invention with dried papaya extract as well as other dry ingredients such as excipients, binders, starches, sugars and the like. These ingredients are then blended thoroughly and prepared as powders, tablets, caplets, capsules, and the like according to skills known in the art. Another method of preparing the composition 2s of this invention comprises thoroughly blending the dry ingredients then further combining them with liquid papaya extract and blending, then further combining with water, corn syrup, and the like in order to prepare a liquid form of the invention. By using additional methods known to one skilled in the art, this liquid form of the invention can then be prepared to form a lozenge, troche, and the like.
This invention extends to methods for using the inventive composition. In general s these methods employ ingesting the inventive composition in an amount and frequency sufficient to provide improved treatment of symptoms caused by excess gastric acid secretion.
Examples of compositions according to this invention are provided to illustrate, but to not limit, the claimed invention.
Example I
Sugar, Confectioners 6X (with starch)3.54 grams Calcium Carbonate Heavy USP 18.54 grams Calcium Carbonate 9.13 grams Magnesium Hydroxide 5.53 grams Starch, Pregelatinized, NF .77 grams Polyethylene Glycol 800 (Powdered) .70 grams Papaya Juice Powder 25.00 grams Flavor 0.60 gram Starch 1500 3.376 grams Silica, Amorphous Fumed 0.30 grams Magnesium Stearate 0.50 grams The papaya juice powder was obtained from Island Organics, Inc., located at ' Metuchen Rd., South Plainfield, New Jersey 07080.
s The above ingredients were formed into fifty tablets following the procedure below:
The sugar, calcium carbonates, magnesium hydroxide, pregelatinized starch and polyethylene glycol were previously combined with water, and blended to from a uniform, dry, powdered composition. These ingredients were then blended with the to papaya juice powder, flavor, starch 1500, and silica for twenty minutes using a half quart P-K blender. The magnesium stearate is then added to this mixture and blended for five minutes.
The blended composition is then compressed into hard, pleasant tasting tablets using Zs conventional technology.
Example 2 Sugar, Confectioners 6X (with starch)21.32 gram Calcium Carbonate Heavy USP 11.12 gram Calcium Carbonate 5.48 grams Magnesium Hydroxide 3.32 grams Starch, Pregelatinized, NF .46 grams Polyethylene Glycol 800 (Powdered) .42 grams Freeze dried papaya powder 30.00 grams Flavor 0.45 grams Starch 1500 1.816 grams Silica, Amorphous Fumed 0.225 grams Magnesium Stearate 0.375 grams The freeze-dried papaya powder is available from Freeze Dry Product, USA
located at 68 Leveioni Court, Suite 100, Navato, California. Thirty tablets were made using the same method described in Example 1. The tablet tastes good, but the blended ingredients showed less than ideal flowability.
The amount of papaya extract contained in each dose (or tablet) can range from about 50 mg to 3000 mg with about 100 mg to about 1000 mg preferred. The particular form of papaya extract used is not believed to be critical in the present invention, however, the purer the form used the less the amount of extract needed for each dose.

Claims (22)

WE CLAIM:
1. A composition for relieving stomach distress comprising: 1) one or more compositions that reduce gastric acidity; and, 2) papaya extract.
2. The composition according to claim 1 wherein said compositions that reduce gastric acidity are selected from the group consisting of: compositions that reduce intragastric hydrogen ion concentration by chemical neutralization; H2 receptor antagonists; proton-pump inhibitors; bismuth compounds; prostaglandins;
sucralfate;
and dopamine antagonists.
3. The composition according to claim 2 wherein said composition that reduces gastric acidity is a composition that reduces intragastric hydrogen ion concentration by chemical neutralization.
4. The composition according to claim 3 wherein said composition that reduces intragastric hydrogen ion concentration by chemical neutralization is selected from the group consisting of calcium carbonate, magnesium hydroxide, and combinations therein.
5. The composition according to claim 4 wherein said composition that reduces intragastric hydrogen ion concentration by chemical neutralization is calcium carbonate and magnesium hydroxide.
6. The composition according to claim 5 wherein said magnesium hydroxide is in an amount of from about 50 mg/dose to about 400 mg/dose and said calcium carbonate is in an amount of from about 200 mg/dose to about 1250 mg/dose.
7. The composition according to claim 6 wherein said magnesium hydroxide is an amount of from about 80 mg/dose to about 300 mg/dose and said calcium carbonate is in an amount of from about 400 mg/dose to about 1000 mg/dose.
8. The composition according to claim 7 wherein said magnesium hydroxide is an amount of from about 100 mg/dose to about 260 mg/dose and said calcium carbonate is in an amount of from about 500 mg/dose to about 800 mg/dose.
9. The composition according to claim 2 wherein said composition that reduces gastric acidity is an H2 receptor antagonist and wherein said H2 receptor antagonist is in an amount of from about 10 mg/dose to about 800 mg/dose.
10. The composition according to claim 9 wherein said H2 receptor antagonist is ranitidine and wherein said ranitidine is in an amount of from about 75 mg/dose to about 300 mg/dose.
11. The composition according to claim 1 wherein said papaya extract is present in an amount of from about 50 mg to about 3000 mg/dose.
12. The composition according to claim 1 wherein said papaya extract consists of one or more proteolytic enzymes.
13. The composition according to claim 12 wherein said proteolytic enzymes are selected from the group consisting of papain, chymopapain, and papaya proteinase III.
14. The composition according to claim 13 wherein said proteolytic enzyme is papain.
15. The composition of claim 14 wherein said one or more proteolytic enzymes are present in an amount of from about 0.5 mg/dose to about 600 mg/dose.
16. The composition of claim 15 wherein said one or more proteolytic enzymes are present in an amount of from about 1.5 mg/dose to about 300 mg/dose.
17. The composition of claim 16 wherein said one more proteolytic enzymes are present in an amount of from about 2.5 mg/dose to about 200 mg/dose.
18. The composition according to claim 1 wherein said one or more compositions that reduce gastric acidity are present in an amount of from about 250 mg to about 1450 mg per tablet; and said papaya extract is present in an amount of from about 50 mg/dose to about 3000 mg/dose.
19. A method for preparing a composition for relieving stomach distress comprising one or more compositions that reduce gastric acidity; and, a composition extracted from papaya comprising the steps of: 1) admixing one or more compositions that reduce gastric acidity that are in dry form, dried papaya extract, and other dry ingredients selected from the group consisting of excipients, binders, starches, and sugars; and, 2) thoroughly blending the ingredients of step 1;
and, 3) preparing the ingredients of step 2 as a powder.
20. The method of claim 19 further comprising the step of compressing said powder to form a tablet or caplet.
21. A method for preparing a composition for relieving stomach distress comprising one or more compositions that reduce gastric acidity; and, a composition extracted from papaya comprising the steps of: 1) admixing one or more compositions that reduce gastric acidity that are in dry form with other dry ingredients selected from the group consisting of excipients, binders, starches, and sugars; 2) further combining the ingredients of step 1) with liquid papaya extract and blending; and, 3) then further combining the ingredients of step 2 with water and corn syrup.
22. A method of using a composition for relieving stomach distress comprising:
1) one or more compositions that reduce gastric acidity; and, 2) a composition extracted from papaya comprising the step of ingesting said composition in an amount and frequency sufficient to provide relief of said stomach distress.
CA002286357A 1997-07-15 1998-07-08 Antacid and papain combination Abandoned CA2286357A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5254397P 1997-07-15 1997-07-15
US60/052,543 1997-07-15
PCT/US1998/014233 WO1999003486A1 (en) 1997-07-15 1998-07-08 Antacid and papain combination

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CA2286357A1 true CA2286357A1 (en) 1999-01-28

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EP (1) EP1001796A1 (en)
JP (1) JP2002509539A (en)
AR (1) AR016514A1 (en)
AU (1) AU8296898A (en)
BR (1) BR9809419A (en)
CA (1) CA2286357A1 (en)
PE (1) PE102699A1 (en)
WO (1) WO1999003486A1 (en)
ZA (1) ZA986247B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000083619A (en) * 1998-07-15 2000-03-28 Oju Seiyaku:Kk Health food and its preparation
BRPI0006503B1 (en) * 2000-02-04 2017-05-09 Biolab Sanus Farmacêutica Ltda gel, cream, aerosol, spray, liquid and lyophilized composition of papain-based carrier
WO2007010547A1 (en) * 2004-11-04 2007-01-25 Abhoy Sankar Arora A phyto-medicine and a process for the preparation thereof
GB0820846D0 (en) * 2008-11-14 2008-12-24 Carson John W Improved proteinaceous digestates
IT201700090582A1 (en) * 2017-08-04 2019-02-04 Neilos S R L Composition for use in the prevention and / or treatment of gastric or gastroesophageal disorders.

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AU8296898A (en) 1999-02-10
WO1999003486A1 (en) 1999-01-28
PE102699A1 (en) 1999-11-05
EP1001796A1 (en) 2000-05-24
JP2002509539A (en) 2002-03-26
BR9809419A (en) 2000-06-13
ZA986247B (en) 1999-02-05
AR016514A1 (en) 2001-07-25

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