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WO1991002535A1 - Composition et procede de prevention du cancer - Google Patents

Composition et procede de prevention du cancer Download PDF

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Publication number
WO1991002535A1
WO1991002535A1 PCT/US1990/004508 US9004508W WO9102535A1 WO 1991002535 A1 WO1991002535 A1 WO 1991002535A1 US 9004508 W US9004508 W US 9004508W WO 9102535 A1 WO9102535 A1 WO 9102535A1
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WO
WIPO (PCT)
Prior art keywords
vitamin
animal
carotene
quantities
body mass
Prior art date
Application number
PCT/US1990/004508
Other languages
English (en)
Inventor
Gerald Shklar
Original Assignee
Basil, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Basil, Inc. filed Critical Basil, Inc.
Publication of WO1991002535A1 publication Critical patent/WO1991002535A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A23K20/147—Polymeric derivatives, e.g. peptides or proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/174—Vitamins
    • 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
    • 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
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof

Definitions

  • This invention generally relates to various compositions and methods for preventing and treating tumors in animals. It specifically relates to the administration of nutritional compositions for the prevention of cancer in animals.
  • U.S. Patent No. 4,564,686 to Ogata discloses a phosphoric acid diester having a ascorbic acid moiety and tocopherol moiety.
  • the agent of Ogata is used as a proplylactic and therapeutic agent for cataracts.
  • U.S. Patent No. 4,323,581 to Gander discloses the use of a retinoid to prevent and treat certain forms of epithelial cancer.
  • U.S. Patent No. 4,665,098 to Gibbs, et al. discloses the use of the same retinoid as Gander in the treatment of bladder cancer, psoriasis, and acne.
  • U.S. Patent No. 4,320,141 to Komatsu, et al. discloses the use of a ef--tocopherol vitamin A acid ester to treat tumors.
  • the invention includes a method of preventing cancer in an animal involving mixing the animal's food with an exogenous source of vitamin E in admixture with a carotene.
  • the vitamin E and carotene should be in sufficient quantities to prevent tumor growth in the animal when administered on a periodic (e.g. daily or twice daily) basis.
  • the vitamin E will be dl-alpha tocopherol and will be present in quantities containing about 5 to about 32 international units (I.U.) of vitamin E per kilogram of animal body mass when administered on a daily basis.
  • the carotene will generally be beta-carotene and will be present in quantities containing about 140 to about 3400 I. U. of beta carotene per kilogram of animal body mass when administered on a daily basis.
  • the admixture of vitamin E and carotene is contained within an airtight pouch impermeable to the admixture so that the vitamin E or other anti-oxidant do not oxidize too rapidly.
  • the pouch or unit dose packet will typically contain a single dosage of the admixture for mixing with the animal's food.
  • the invention also includes improvements in animal food.
  • Typical animal foods e.g. dog food
  • the food is supplemented with a vitamin mixture comprising a sufficient quantity of vitamin E and carotene to prevent tumor occurrence or growth in an animal.
  • vitamin E as used herein is intended to include vitamin E from natural sources as well as pure alpha tocopherol, alpha tocopherol alkanoates in which the alkanoate has from one to five carbon atoms, and alpha- tocopherol acid malonate, succinate and glutamate.
  • the dextrorotary compound is preferred.
  • Vitamin E in its various forms, is available from various sources.
  • dry dosage forms e.g. tablets, powders, hard gelatin capsules
  • a 50 percent dry powder of dl-alpha tocopherol acetate 3,000 I.U. per 6 grams powder
  • Liquid forms of vitamin E are available from Nature Made Nutritional Products of Los Angeles, California.
  • carotenes useful in the present invention are beta carotene, alpha carotene, ca thaxanthin, and mixtures thereof.
  • Beta carotene (pro vitamin A) and alpha carotene are readily commercially available from Hoffman-LaRoche and other sources.
  • Canthaxanthin is available under the trademark Orobronze from William H. Rorer (Canada) Ltd. of Bramalea, Ontario.
  • Vitamin C as used herein, includes ascorbic acid, sodium ascorbate, and the lipid soluble ascorbyl palmitate. Vitamin C is available from Bronson Pharmaceuticals of LaCanada, California.
  • Glutathione contains the amino acid cysteine, and is believed to be an anti-oxidant. Glutathione is available from Sigma Chemical Company of St. Louis, Missouri. "Animal food” as used herein is generally intended to refer to commercially prepared animal foods and feeds such as those available from Purina; Kal Kan Foods, Inc. of Vernon, California; and Carnation Company of Los Angeles, California. However, it is to be understood that other sources of animal nutrition are also included, such as table scraps. Absorption of vitamin E and beta carotene is enhanced by admixture with fat containing foods.
  • the animal food will generally be mixed to contain dl-alpha tocopherol which will be present in quantities containing from about 5 to about 7 I.U. (3 to 20 mg of dl-alpha tocopherol of vitamin E per kilogram of animal body mass when administered on a daily basis.
  • the animal food will also be mixed to contain beta-carotene which will be present in quantities of about 3 to about 4 mg of beta-carotene per kilogram of animal body mass when administered on a daily basis.
  • the animal food will further contain vitamin C and glutathione. The vitamin C will then be present in quantities of about 14 to about 28 milligrams per kilogram of animal body mass and the glutathione will be present in quantities of about 4 to about 8 milligrams per kilogram of animal body mass, both on a daily basis.
  • the previously described animal food will be mixed with a vitamin source containing a sufficient quantity of vitamin E and carotene to prevent tumor growth in the animal.
  • the animal food will contain dl-alpha tocopherol present in quantities containing from about 5 to about 32 I.U. of vitamin E per kilogram of animal body mass when administered on a daily basis.
  • the carotene will preferably be beta carotene and will preferably be present in quantities containing about 275 to about 3400 I.U. of beta-carotene per kilogram of animal body mass when administered on a daily basis.
  • the prophylactic animal food may also contain vitamin C and glutathione, with the vitamin C present in quantities of about 14 to about 28 milligrams per kilogram of animal body mass and the glutathione present in quantities of about 4 to about 8 milligrams per kilogram of animal body weight on a daily basis.
  • compositions of the present invention are preferably presented for administration to animals in unit dosage forms, such as tablets, capsules, pills, powders, granules, suppositories, sterile parenteral solutions or suspensions, sterile non-parenteral solutions or suspensions, and oral solutions or suspensions and the like, containing suitable quantities of an active ingredient.
  • solid or fluid unit dosage forms can be prepared.
  • Powders are prepared quite simply by comminuting the active ingredient (e.g. powdered vitamin E) to a suitably fine size and mixing with a similarly comminuted diluent.
  • the diluent can be an edible carbohydrate material such as lactose or starch.
  • a sweetening agent or sugar is present as well as a flavoring oil
  • Capsules are produced by preparing a powder mixture as hereinbefore described and filling onto formed gelatin sheaths.
  • a lubricant such as talc, magnesium stearate, calcium stearate and the like is added to the powder mixture before the filling operation.
  • Soft gelatin capsules are prepared by machine encapsulation of a slurry of active ingredients with an acceptable vegetable oil, light liquid petrolatum or other inert oil or triglyceride.
  • Tablets are made by preparing a powder mixture, granulating or slugging, adding a lubricant and pressing into tablets.
  • the powder mixture is prepared by mixing an active ingredient, suitably comminuted, with a diluent or base such as starch, lactose, kaolin, dicalcium phosphate and the like.
  • the powder mixture can be granulated by wetting with a binder such as corn syrup, gelatin solution, methylcellulose solution or acacia mucilage and forcing through a screen.
  • a binder such as corn syrup, gelatin solution, methylcellulose solution or acacia mucilage
  • the powder mixture can be slugged, i.e., run through the tablet machine and the resulting imperfectly formed tablets broken into pieces (slugs) .
  • the slugs can be lubricated to prevent sticking to the tablet-forming dies by means of the addition of stearic acid, a stearic salt, talc or mineral oil
  • the tablet can be provided with a protective coating consisting of a sealing coat or enteric coat of shellac, a coating of sugar and methylcellulose and polish coating of carnauba wax.
  • Fluid unit dosage forms for oral administration such as syrups, elixirs and suspensions can be prepared wherein each teaspoonful of composition contains predetermined amounts of active ingredients for administration.
  • the water- soluble forms can be dissolved in an aqueous vehicle together with sugar, flavoring agents and preservatives to form a syrup.
  • An elixir is prepared by using a hydroalcoholic vehicle with suitable sweeteners together with a flavoring agent.
  • Suspensions can be prepared of the insoluble forms with a suitable vehicle with the aid of a suspending agent such as acacia, tragacanth, methylcellulose and the like.
  • a suspending agent such as acacia, tragacanth, methylcellulose and the like.
  • fluid unit dosage forms are prepared utilizing active ingredients and a sterile vehicle, ethyl oleate being preferred especially for* intramuscular injection.
  • the active ingredients depending on the form and concentration used, can be either suspended or dissolved in the vehicle.
  • water- soluble active ingredients can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampule and sealing.
  • adjuvants such as local anesthetic, preservative and buffering agents can be dissolved in the vehicle.
  • Parenteral suspensions are prepared in substantially the same manner except that active ingredient is suspended in the vehicle instead of being dissolved and sterilization cannot be accomplished by filtration. Active ingredients can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the active ingredients.
  • rectal and vaginal routes can be utilized.
  • An active ingredient can be administered by means of a suppository.
  • a vehicle which has a melting point at about body temperature or one that is readily soluble can be utilized.
  • cocoa butter and various polyethylene glycols (Carbowaxes) can serve as the vehicle.
  • the active ingredients can also be admixed in animal feed.
  • the active ingredients can conveniently be prepared in the form of a food premix.
  • the food premix can comprise active ingredients in admixture with an edible pharmaceutical diluent such as starch, oatmeal, flour, calcium carbonate, talc, dried fish meal and the like nontoxic, orally acceptable pharmaceutical diluents.
  • the prepared premix is then conveniently added to the regular feed.
  • unit dosage form refers to physically discrete units suitable as unitary dosages for animal subjects, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical diluent, carrier or vehicle.
  • the specifications for the novel unit dosage forms of this invention are dictated by and are directly dependent on (a) the unique characteristics of the active material and the particular therapeutic effect to be achieved, and (b) the limitation inherent in the art of compounding such an active material for therapeutic use in humans, as disclosed in this specification, these being features of the present invention.
  • suitable unit dosage forms in accord with this invention are tablets, capsules, troches, suppositories, powder packets, wafers, cachets, teaspoonfuls, tablespoonfuls, dropperfuls, ampules, vials, segregated multiples of any of the foregoing, and other forms as herein described.
  • the active ingredients to be employed as anti-tumor agents can be easily prepared in unit dosage form with the employment of pharmaceutical materials which themselves are available in the art and can be prepared by established procedures.
  • the following formulations are illustrative of the formulation of the unit dosage forms of the present invention, but are not intended to be limiting.
  • dl-alpha tocopherol Sigma chemical of St. Louis, Missouri
  • beta carotene Hoffman-LaRoche
  • the resulting admixture is then divided into 100 separate dosage units each containing 21 I.U. of dl-alpha tocopherol and 1837.5 I.U. of beta carotene.
  • the dosage units are separately packaged into individual vacuum sealed packets for use as unit dosage forms.
  • unit dosage forms can be opened and the ingredients mixed with the food of an animal to be treated immediately before service of the food to the animal.
  • one unit dosage form per 5 kilograms of animal body mass on a daily basis is preferably used.
  • Formulation 2 The unit dosage forms of Formulation 1 may be further admixed with vitamin C especially ascorbyl palmitate, in amounts of 21 milligrams (mg) per unit dosage form. These unit dosage forms too may be admixed with the animal's food prior to service.
  • unit dosage forms of Formulation 1 and Formulation 2 respectively are further admixed with the compound glutathione in amounts of 6 mg per unit dosage form. These unit dosage forms too may be admixed with the animal's food prior to service.
  • One hundred young male adult Syrian hamsters (Mesocricetus auratus) are randomly divided in to five equal groups of 20 animals.
  • the hamsters would be randomly bred (e.g. Lakeview Strain LVG available from Charles River Breeding Laboratories) .
  • the animals are housed five to a cage and maintained in a controlled environment under standardized conditions of temperature and humidity with an alternative twelve hour light-dark cycle.
  • the animals would be 60-90 days of age and would weigh 95-125 grams (g) at the beginning of the test.
  • the animals are fed standard Purina Laboratory - ⁇ -
  • Group 1 no treatment
  • Group 2 beta carotene 200 ug and dl-alpha tocopherol 200 ug in 0.2 ml vegetable oil daily by mouth.
  • Group 3 beta carotene 400 ug in 0.2 ml vegetable oil daily by mouth.
  • Group 4 - dl-alpha tocopherol 400 ug in 0.2 ml vegetable oil daily by mouth.
  • Group 5 - 0.2 ml vegetable oil vehicle only.
  • DMBA application After 14 weeks of DMBA application (week 28) , moderate size tumors are present in Groups 1 and 5. Smaller tumors are present in Groups 3 and 4. No tumor or only very small tumors are present in Groups 2 animals. Prophylactic treatment continues. DMBA application is stopped after Week 28.
  • Groups 1 and 5 animals Eight weeks after the DMBA application is stopped. Groups 1 and 5 animals have large and extensive tumor growth. Some of the animals in these groups will have died. The animals in Groups 3 and 4 should appear more healthy, and the tumors are smaller than those in Groups 1 and 5. The Group 2 animals have even smaller, or no, tumors. The animals may be subsequently sacrificed for analysis of the tumors. Such sacrifice may be accomplished through the use of carbon dioxide chamber. Pouches may be excised and sections fixed in 10 percent formalin, sectioned in paraffin and stained with hematoxylin and eosin. Cervical lymph nodes may also be dissected with adjacent tissue and also prepared for histologic study.
  • the tumors should be epidermoid carcinomas, consistent with the application of DMBA.
  • Groups 1 and 3-5 have animals displaying metastatic spread to cervical lymph nodes, while no such tumor activity is present in the Group 2 animals.
  • Example A The test of Example A may be duplicated except that 500 I.U. of alpha carotene on a kilogram basis may be substituted for the beta-carotene. Similar results are obtained.
  • Examples C and D The tests of Examples A and B may be repeated except that the prophylactic treatment admixture is administered in a suitable vehicle (e.g. ethyl oleate) by intramuscular injection. Similar results are obtained.
  • a suitable vehicle e.g. ethyl oleate
  • One hundred tumor inflicted dogs are randomly divided into five equal groups of 20 animals.
  • the animals would be of various breeds.
  • the animals are housed in a kennel, and maintained in a controlled environment under standardized conditions of temperature and humidity with an alternative twelve hour light-dark cycle.
  • Each of the animals would be weighed.
  • the size of each animal's tumor would be determined along with a preliminary classification as to tumor type.
  • the dogs are fed standard Purina Dog Chow and water - li ⁇
  • the five groups are treated as follows: Group 1 - no treatment Group 2 - One packet per 5 kg of animal body mass of
  • Formulation 1 is mixed with the animal's food daily immediately prior to service.
  • Group 3 - Formulation 2 is mixed with the animal's food daily immediately prior to service.
  • Group 4 - One packet of Formulation 3 per 5 kg of animal body mass is mixed with the animal's food daily immediately prior to service.
  • Group 5 One packet of Formulation 4 per 5 kg of animal body mass is mixed with the animal's food daily immediately prior to service. The animals are monitored on a daily basis, and tumor size, body mass, and survival times are recorded. Group 1 animals die quickly. The animals in Groups 2-5 retain body mass longer, exhibit a decreased tumor size and growth, and the animals survive longer.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Food Science & Technology (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Animal Husbandry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nanotechnology (AREA)
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  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

On a mis au point un procédé de prévention du cancer chez l'animal consistant à mélanger les aliments de ce dernier avec une source exogène de vitamine E à quoi l'on ajoute un carotène. La vitamine E et le carotène doivent avoir des quantités suffisantes afin de prévenir la croissance ou l'apparition de tumeurs chez l'animal lorsqu'on les administre de manière périodique. Typiquement, la vitamine E est le tocophérole dl-alpha et est présente en des quantités contenant 5 à 32 U.I. (unités internationales) de vitamine E par kilogramme de masse corporelle de l'animal, lorsqu'on l'administre quotidiennement. Le carotène est typiquement un carotène bêta et est présent un des quantités contenant environ 140 à 3400 U.I. de carotène par kilogramme de masse corporelle de l'animal, lorsqu'on l'administre quotidiennement. Selon un mode de réalisation, le mélange de vitamine E et de carotène est contenu dans une poche étanche à l'air et imperméable au mélange, se présentant sous la forme d'un paquet à dose unitaire. L'invention comprend également des améliorations relatives aux aliments d'animaux. Selon un mode de réalisation, les aliments d'animaux contiennent des sources exogènes de vitamines E et C, du glutathione ainsi qu'un carotène.
PCT/US1990/004508 1989-08-11 1990-08-09 Composition et procede de prevention du cancer WO1991002535A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US39285789A 1989-08-11 1989-08-11
US392,857 1989-08-11

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WO1991002535A1 true WO1991002535A1 (fr) 1991-03-07

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0604433A1 (fr) * 1991-06-06 1994-07-06 Life Sciences' Technologies, Inc. Composition et procede de traitement de maladies
WO1994027624A1 (fr) * 1993-05-22 1994-12-08 Junyao Li Formulations de prevention du cancer contenant des vitamines et des mineraux
EP0746202A1 (fr) * 1992-01-06 1996-12-11 Health Maintenance Programs, Inc. Composition contenant un anti-oxydant pharmaceutiquement actif et son procede d'utilisation dans la prevention et le traitement d'une restenose apres angioplastie
EP1470817A1 (fr) * 2002-01-31 2004-10-27 Kansai Technology Licensing Organization Co., Ltd. Composition et procede pour la prevention du cancer chez des sujets humains
MD611Z (ro) * 2012-02-14 2013-10-31 Раиса МЕРЕУЦА Metodă de tratament al gastritei cronice atrofice
US8728532B2 (en) 2007-04-12 2014-05-20 Regents Of The University Of Minnesota Ischemia/reperfusion protection compositions and methods of using
MD783Z (ro) * 2013-10-08 2015-01-31 Адриан КИШКА Metodă de tratament al gastritei cronice atrofice
MD4341C1 (ro) * 2013-11-21 2015-11-30 Ион МЕРЕУЦЭ Sirop pentru tratamentul stărilor precanceroase gastrice
US10307398B2 (en) 2016-09-20 2019-06-04 Regents Of The University Of Minnesota Resuscitation composition and methods of making and using

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1110392A (en) * 1964-09-28 1968-04-18 Yamanouchi Pharma Co Ltd Composition containing glutathione and an amino acid or amino acids, and salts thereof
US4710489A (en) * 1985-04-22 1987-12-01 Cornell Research Foundation, Inc. Glutathione delivery system

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1110392A (en) * 1964-09-28 1968-04-18 Yamanouchi Pharma Co Ltd Composition containing glutathione and an amino acid or amino acids, and salts thereof
US4710489A (en) * 1985-04-22 1987-12-01 Cornell Research Foundation, Inc. Glutathione delivery system

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
FREE RADICAL BIOLOGY AND MEDICINE, Vol. 3, 1987, DRAPER, "Micronutrients and Cancer Prevention: Are the RDAs Adequate?", pages 203-207. *
J.S. ROTH, "ALL ABOUT CANCER", Published 1985, by GEORGE F. STICKLEY COMPANY, (Philadelphia), see pages 123-128. *
JAMA, Vol. 255, No. 14, 11 April 1986, SIMMONS, "Evaluating Vitamin Prophylaxis of Cancer", pages 1832 and 1835. *
PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE, Vol. 183, 1986, BIRT, "Updated on the Effects of Vitamin A, C, and E and Selenium on Carcinogenesis", pages 311-320. *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0604433A1 (fr) * 1991-06-06 1994-07-06 Life Sciences' Technologies, Inc. Composition et procede de traitement de maladies
EP0604433A4 (fr) * 1991-06-06 1994-10-12 Life Sciences Tech Inc Composition et procede de traitement de maladies.
EP0746202A1 (fr) * 1992-01-06 1996-12-11 Health Maintenance Programs, Inc. Composition contenant un anti-oxydant pharmaceutiquement actif et son procede d'utilisation dans la prevention et le traitement d'une restenose apres angioplastie
EP0746202A4 (fr) * 1992-01-06 1997-06-25 Health Maintenance Programs Composition contenant un anti-oxydant pharmaceutiquement actif et son procede d'utilisation dans la prevention et le traitement d'une restenose apres angioplastie
WO1994027624A1 (fr) * 1993-05-22 1994-12-08 Junyao Li Formulations de prevention du cancer contenant des vitamines et des mineraux
EP1470817A4 (fr) * 2002-01-31 2006-03-22 Kansai Tech Licensing Org Co Composition et procede pour la prevention du cancer chez des sujets humains
EP1470817A1 (fr) * 2002-01-31 2004-10-27 Kansai Technology Licensing Organization Co., Ltd. Composition et procede pour la prevention du cancer chez des sujets humains
US8728532B2 (en) 2007-04-12 2014-05-20 Regents Of The University Of Minnesota Ischemia/reperfusion protection compositions and methods of using
US9149450B2 (en) 2007-04-12 2015-10-06 Regents Of The University Of Minnesota Ischemia/reperfusion protection compositions and methods of using
US9186340B2 (en) 2007-04-12 2015-11-17 Regents Of The University Of Minnesota Ischemia/reperfusion protection compositions and methods of using
MD611Z (ro) * 2012-02-14 2013-10-31 Раиса МЕРЕУЦА Metodă de tratament al gastritei cronice atrofice
MD783Z (ro) * 2013-10-08 2015-01-31 Адриан КИШКА Metodă de tratament al gastritei cronice atrofice
MD4341C1 (ro) * 2013-11-21 2015-11-30 Ион МЕРЕУЦЭ Sirop pentru tratamentul stărilor precanceroase gastrice
US10307398B2 (en) 2016-09-20 2019-06-04 Regents Of The University Of Minnesota Resuscitation composition and methods of making and using

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