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WO2001060337A1 - Compositions a oxydation reduite utilisees pour l'administration locale d'un agent actif sur le plan pharmaceutique - Google Patents

Compositions a oxydation reduite utilisees pour l'administration locale d'un agent actif sur le plan pharmaceutique Download PDF

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Publication number
WO2001060337A1
WO2001060337A1 PCT/US2001/004697 US0104697W WO0160337A1 WO 2001060337 A1 WO2001060337 A1 WO 2001060337A1 US 0104697 W US0104697 W US 0104697W WO 0160337 A1 WO0160337 A1 WO 0160337A1
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WIPO (PCT)
Prior art keywords
weight
compositions
composition
composition according
acid
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2001/004697
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English (en)
Inventor
Jeffrey Warren Clymer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Procter and Gamble Co
Original Assignee
Procter and Gamble Co
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 Procter and Gamble Co filed Critical Procter and Gamble Co
Priority to AU2001236997A priority Critical patent/AU2001236997A1/en
Publication of WO2001060337A1 publication Critical patent/WO2001060337A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/51—Chelating agents

Definitions

  • the present invention relates to compositions comprising a high level of at least one phospholipid, at least one pharmaceutically active agent, and at least one chelating agent.
  • the present invention further relates to a method of preventing or reducing the oxidation of compositions containing high levels of at least one phospholipid and at least one pharmaceutically active agent.
  • the method comprises adding a safe and effective amount of a chelating agent to compositions containing high levels of phospholipids and at least one pharmaceutically active agent.
  • phospholipids offer the potential of improved transdermal drug delivery. It is known, for example, that liposomes made from phospholipids are able to facilitate the uptake of certain compounds across the skin barrier. Phospholipids are used in a wide variety of pharmaceutical compositions, as well as cosmetics and food products. Phospholipids are used in pharmaceutical compositions as dispersing, emulsifying, and stabilizing agents and are included in intramuscular, intravenous, parenteral, and topical compositions. Examples of topical compositions comprising phospholipids include U.S.
  • Patent 5,064,655 (Uster, et al.), which discloses a topical liposome gel composition having a high viscosity for application and delivery of a drug active at a wound site or mucosal tissue site;
  • U.S. Patent 5,945,409 (Crandall), which discloses topical compositions comprising phospholipids for moisturizing keratinous tissue of a human or animal;
  • U.S. Patent 5,814,343 Japaneseones, et al), which discloses a cosmetic composition comprising phospholipids for delivering a cosmetically-effective benefit agent to a target site on the skin and/or hair;
  • Patent 5,654,337 (Roentsch, et al.), which discloses a topical composition comprising phospholipids useful in delivering pharmaceutically active agents through the skin; and U.S. Patent 5,869,090 (Rosenbaum), which discloses a topical composition comprising phospholipids as vehicles for the transdermal delivery of dehydroepiandrosterone (DHEA).
  • DHEA dehydroepiandrosterone
  • Liposomes are typically comprised of phospholipids from natural sources, e.g., soy phosphatidylcholine. Natural lipid sources are unsaturated, and so may be susceptible to oxidation. Medicaments added to liposomes, in particular non-steroidal anti-inflammatory drugs (NSAID), e.g., ketoprofen, ibuprofen, and the like, are also susceptible to oxidation under certain conditions.
  • NSAID non-steroidal anti-inflammatory drugs
  • US Patent 5,185,373 discloses a method for stabilizing ibuprofen subjected to thermal degradation. It has been determined that the combination of a phospholipid and an NSAID are more susceptible to oxidation than either component alone, and that this oxidation may proceed readily even at ambient temperatures.
  • compositions for the topical delivery of at least one pharmaceutically active agent comprising from about 1% to about 50% by weight of at least one phospholipid, from about 0.01% to about 10% of at least one pharmaceutically active agent, from about 0.01% to about 0.5% by weight of at least one chelating agent, and at least one suitable carrier material selected from components used in compositions for topical application.
  • the present invention further relates to a method of preventing or reducing the oxidation of compositions containing greater than about 1% by weight, of at least one phospholipid and at least one pharmaceutically active agent.
  • the method of the present invention comprises adding a safe and effective amount, preferably from about 0.01% to about 0.5%) by weight, of a chelating agent to compositions containing greater than about 1% by weight, of at least one phospholipid and at least one pharmaceutically active agent.
  • compositions of the present invention may be in the form of emulsions, creams, lotions, ointments, gels, pastes, solutions, or any other suitable topical skin formulation.
  • compositions having greater than about 1% by weight of a phospholipid compound, especially unsaturated or partially saturated phospholipids, and at least one pharmaceutically active agent can be reduced or prevented by the addition of a safe and effective amount of at least one chelating agent to these compositions
  • Such compositions are typically used for dermal or transdermal delivery of pharmaceutically active agent or agents.
  • compositions which contain from about 1% to about 50%) by weight of at least one phospholipid, from about 0.01% to about 10% of at least one pharmaceutically active agent, from about 0.01% to about 0.5%) by weight of at least one chelating agent, and at least one suitable carrier material selected from components used in compositions for topical application.
  • the present invention further relates to a method of preventing or reducing the oxidation of compositions having greater than about 1% by weight of at least one phospholipid and at least one pharmaceutically active agent.
  • the method comprises adding a safe and effective amount, preferably from about 0.01% to about 0.5% by weight, of at least one chelating agent, preferably selected from the group consisting of edetic acid (EDTA) and its salts including, edetate sodium, edetate disodium, and edetate trisodium, and the like, and mixtures thereof, to compositions containing greater than about 1% by weight, of at least one phospholipid and at least one pharmaceutically active agent.
  • EDTA edetic acid
  • compositions of the present invention may be in the form of emulsions, creams, lotions, ointments, gels, pastes, solutions, or any other suitable topical skin formulation. Depending upon the intended use of the skin preparation, other components may be incorporated into the compositions. Such formulations may comprise topically acceptable carrier materials as are helpful.
  • Topical application means directly spreading, spraying or laying of a compound or composition onto epidermal tissue. Topical application can be achieved by rubbing, applicator pads, containers with applicator filaments, sprays, or any other convenient means.
  • safe and effective amount means an amount of a substance, compound, or composition high enough to provide a significant positive modification of the condition to be treated, e. g., drying, irritation, and/or itching of the skin of an animal or human, but low enough to avoid serious side effects (at a reasonable benefit/risk ratio), within the scope of sound medical judgment.
  • a "safe and effective amount” of the substance, compound, or composition may vary with the kind and amount(s) of other ingredients used in combination with the particular substance, compound, or composition, the condition being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, and like factors.
  • compositions of the present invention can contain other ingredients which are compatible with the compositions and which preferably do not substantially modify the compositions of the present invention.
  • the term encompasses the terms “consisting of and “consisting essentially of.
  • pastes are liquids for topical application, preferably to the skin of an animal or human, whose viscosity is enhanced to the point that flow is largely inhibited by the presence of undissolved, as well as dissolved, solids.
  • gels are semisolid systems of suspended inorganic particles or organic macromolecules interpenetrated by a liquid for topical application, preferably to the skin of an animal or human.
  • emulsions are multiphase liquids for topical application, preferably to the skin of an animal or human, containing special components such as surfactants and/or thickeners that inhibit or delay the separation of the phases.
  • solutions are single phase liquids substantially free of solids, but small amounts of haze or cloudiness may be tolerated, for topical application, preferably to the skin of an animal or human.
  • suitable carrier materials may include components typically used in compositions for topical application, preferably to the skin of an animal or human, but are not limited to, solvents, emollients, emulsif ⁇ ers, humectants, thickeners, antioxidants, chelating agents, dispersing agents, preservatives, buffers, fragrances, colorants, substances which are used for the microbial and chemical stabilization of the composition, and the like.
  • solvents emollients
  • emulsif ⁇ ers emulsif ⁇ ers
  • humectants thickeners
  • compositions of the present invention The following provides a detailed description of the essential and non-essential components of the compositions of the present invention. All percentages and ratios used herein are by weight, and all measurements made at 25°C, unless otherwise specified.
  • compositions of the present invention comprise at least one phospholipid.
  • Phospholipids useful in the compositions of the present invention may be selected by the skilled artisan according to the kind and amount(s) of other ingredients used in the compositions of the present invention, the condition being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, and like factors.
  • the preferred phospholipids useful in the compositions of the present invention include all lipoidal constituents, natural and/or synthetic, saturated, partially saturated, or unsaturated, that contain phosphorus in their molecules.
  • the more preferred phospholipids for use in the compositions of the present invention include, but are not limited to, lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelins, and mixtures thereof. While there are no particular limitations to the quality, purity, and/or saturation level of the phospholipids used, the phospholipids are preferably unsaturated or partially saturated, of high quality, pharmaceutical grade. A most preferred phospholipid for use in the compositions of the present invention is phosphatidylcholine.
  • Phosphatidylcholine may be obtained as commercially available soya or egg phosphatidylcholine. More preferably the phosphatidylcholine for use in the compositions of the present invention is soya phosphatidylcholine.
  • the amount of phospholipid used in the compositions of the present invention is typically from about 1% to about 50%, preferably from about 1.5% to about 40%), more preferably from about 2%> to about 30%, most preferably from about 2.5% to about 20%) by weight of the compositions of the present invention.
  • compositions of the present invention comprise at least one pharmaceutically active agent.
  • Pharmaceutically active agents to be delivered topically and found useful in the compositions of the present invention include, but are not limited to, analgesic/anti- inflammatory agents such as aspirin, ibuprofen, ketoprofen, diclofenac, naproxen, indomethacin, piroxicam, flurbiprofen, meclofenamate, ketorolac, tenidap, tebufelone, and their derivatives, isomers, and salts; anti-infective agents such as penicillin, erythromycin, tetracycline, clotrimazole and their derivatives, isomers, and salts; anti- diabetics such as chlorpropamide, glymidine, insulin, and their derivatives, isomers, and salts; anti-arrhythmics such as moricizine, propanolol, amiodarone, and their derivatives, isomers, and salts
  • the particular pharmaceutically active agent(s) and amount of pharmaceutically active agent(s) used in the compositions of the present invention are selected to be safe and effective and may vary with the kind and amount(s) of other ingredients used in combination with the particular pharmaceutically active agent(s), the condition being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, and like factors.
  • the amount of pharmaceutically active agent(s) used in the compositions of the present invention is from about 0.01% to about 10%), preferably from about 0.025%) to about 8%>, more preferably from about 0.05%> to about 6%, most preferably from about 0.1 %> to about 4%> by weight of the compositions of the present invention.
  • the preferred pharmaceutically active agent(s) used in the compositions of the present invention comprises analgesic/anti-inflammatory agents selected from the group consisting of aspirin, ibuprofen, naproxen, indomethacin, piroxicam, flurbiprofen, meclofenamate, ketoprofen, ketorolac, diclofenac, tenidap, tebufelone, their derivatives, isomers, and salts, and mixtures thereof.
  • analgesic/anti-inflammatory agents selected from the group consisting of aspirin, ibuprofen, naproxen, indomethacin, piroxicam, flurbiprofen, meclofenamate, ketoprofen, ketorolac, diclofenac, tenidap, tebufelone, their derivatives, isomers, and salts, and mixtures thereof.
  • the more preferred pharmaceutically active agent(s) used in the compositions of the present invention analgesic/anti-inflammatory agents selected from the group consisting of ibuprofen, naproxen, indomethacin, piroxicam, flurbiprofen, ketoprofen, ketorolac, diclofenac, their derivatives, isomers, and salts, and mixtures thereof.
  • the most preferred pharmaceutically active agent(s) used in the compositions of the present invention analgesic/anti-inflammatory agents selected from the group consisting of ketoprofen, ibuprofen, diclofenac, naproxen, their derivatives, isomers, and salts, and mixtures thereof.
  • compositions of the present invention comprise at least one chelating agent.
  • Chelating agents useful in the compositions of the present invention may be selected according to the kind and amount(s) of the phospholipids and pharmaceutically active agent used in the compositions of the present invention.
  • Chelating agents of particular usefulness in the compositions of the present invention include, but are not limited to, edetic acid (EDTA) and its salts including edetate sodium, edetate disodium, and edetate trisodium, sodium hexametaphosphate, gentisic acid ethanolamide, oxyquinoline sulfate, citric acid, sodium citrate, thioglycolic acid, thiolactic acid, thioglycerol, and the like.
  • EDTA edetic acid
  • EDTA edetic acid
  • its salts including edetate sodium, edetate disodium, and edetate trisodium, sodium hexametaphosphate, gentis
  • the amount of chelating agents used in the compositions of the present invention is from about 0.01% to about 0.5%, preferably from about 0.02% to about 0.2%, more preferably from about 0.05% to about 0.15%> by weight of the compositions of the present invention.
  • the preferred chelating agent includes edetic acid (EDTA), edetate sodium, edetate disodium, and edetate trisodium. The more preferred chelating agent is edetate disodium.
  • Water employed in the compositions of the present invention should preferably be of low ion content and free of organic impurities. Typically, water comprises from about 2% to about 99%o, preferably from about 20%o to about 95%>, more preferably from about 40%) to about 90%), most preferably from about 60%> to about 85%> by weight of the compositions of the present invention.
  • Carrier materials may or may not be used in the compositions of the present invention. If used, they may be selected from components typically used in compositions for topical application, preferably to the skin of an animal or human, i. e., emulsions, creams, lotions, ointments, gels, pastes, solutions, and the like.
  • the carrier materials may be selected from polar and/or non-polar solvents such as glycerin, polyglycerin, glycerin esters, propylene glycol, polypropylene glycol, ethylene glycol, triethylene glycol, polyethylene glycol, diethylene glycol monoethyl ether, 1,3-butylene glycol, maltitol, benzyl alcohol, ethanol, ethyl acetate, heptane, canola oil, olive oil, mineral oil, water, and the like; skin conditioning agents such as petrolatum, liquid paraffin, paraffin wax, beeswax, spermaceti, microcrystalline wax, cetyl alcohol, hexadecyl alcohol, stearyl alcohol, oleyl alcohol, isopropyl myristate, isopropyl palmitate, vegetable oil, squalene, squalane, palmitic acid, stearic acid, cetyl palmitate, lanolin, tocop
  • thickeners such as agar, carrageenan, food starch, modified starch, gelatin, gum arabic, guar gum, cellulose gel, carbomer (Carbopol ® ), hydroxyethylcellulose, hydroxypropyl methylcellulose, pectin, sodium carboxymethylcellulose, polyacrylic acid, polyvinyl alcohol, polyethylene glycol, and the like; antioxidants such as benzenesulfonic acid, 4-[(3-(3,5-bis(l,l-dimethylethyl)-4- hydroxyphenyl)-l-oxopropyl) amino] monosodium salt (Tinogard TM AO-6, Ciba Specialty Chemical Co., High Point, NC), ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate, sodium formaldehyde sulf
  • these carrier materials may be present in the compositions of the present invention in amounts which provide their intended purpose.
  • solvents typically comprise from about 2%> to about 99%>, preferably from about 20%> to about 95%, more preferably from about 40%> to about 90% by weight of the compositions of the present invention
  • skin conditioning agents typically comprise from about 0.1% to about 50%, preferably from about 1% to about 40%, more preferably from about 2% to about 30%, most preferably from about 3% to about 20% by weight of the compositions of the present invention
  • emulsifiers typically comprise from about 0.05% to about 20%>, preferably from about 0.1%> to about 15%), more preferably from about 0.3%> to about 10%) by weight of the compositions of the present invention
  • thickeners typically comprise from about 0.05%> to about 10%>, preferably from about 0.1% to about 7.5%, more preferably from about 0.2%> to about 5%> by weight of the compositions of the present invention
  • antioxidants typically comprise from about 0.01% to about 0.5%>, preferably from about 0.0
  • the pharmaceutically active agent is added to most of the water and enough sodium hydroxide is added to the mixture to raise the pH to allow complete dissolution of the pharmaceutically active agent.
  • the sodium phosphate salts, EDTA disodium, and benzyl alcohol are added to the solution containing the pharmaceutically active agent and the mixture is stirred until all the components are dissolved.
  • the phosphatidylcholine is added to the solution which is then stirred for at least 4 hours to insure liposomes are formed.
  • the liposome solution is then filtered to achieve a selected size distribution of the liposomes.
  • the petrolatum, lanolin, fragrance, and acrylates/C 10-30 acrylate crosspolymer are added to the remaining amount of the water in a separate container which is agitated vigorously to form an emulsion. This emulsion is then added to the liposomes and blended. Carbomer is added slowly to the mix along with the glycerin and the remainder of the sodium hydroxide. The liposome preparation is then agitated for at least 30 minutes until a smooth mixture of the proper viscosity is obtained.

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  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract

La présente invention concerne des compositions utilisées pour l'administration topique d'au moins un agent actif sur le plan pharmaceutique contenant au moins entre environ 1 % et environ 50 % en poids d'au moins un phospholipide, entre environ 0,01 % et environ 10 % d'au moins un agent actif sur le plan pharmaceutique, entre environ 0,01 % et environ 0,5 % en poids d'au moins un agent chélatant, et au moins un excipient approprié sélectionné à partir de composants utilisés dans les compositions destinées à l'application locale. L'agent chélatant empêche ou réduit l'oxydation des compositions topiques de cette invention.
PCT/US2001/004697 2000-02-14 2001-02-13 Compositions a oxydation reduite utilisees pour l'administration locale d'un agent actif sur le plan pharmaceutique Ceased WO2001060337A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001236997A AU2001236997A1 (en) 2000-02-14 2001-02-13 Compositions for topical delivery of a pharmaceutically active agent having reduced oxidation

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US50379300A 2000-02-14 2000-02-14
US50434200A 2000-02-14 2000-02-14
US09/503,793 2000-02-14
US09/504,342 2000-02-14

Publications (1)

Publication Number Publication Date
WO2001060337A1 true WO2001060337A1 (fr) 2001-08-23

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PCT/US2001/004697 Ceased WO2001060337A1 (fr) 2000-02-14 2001-02-13 Compositions a oxydation reduite utilisees pour l'administration locale d'un agent actif sur le plan pharmaceutique

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AU (1) AU2001236997A1 (fr)
CO (1) CO5261580A1 (fr)
PE (1) PE20011099A1 (fr)
WO (1) WO2001060337A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008524304A (ja) * 2004-12-22 2008-07-10 チバ ホールディング インコーポレーテッド 抗ラジカル剤
US8119103B2 (en) 2006-02-24 2012-02-21 Mallinckrodt Llc Bifunctional resorcinol, thioresorcinol, and dithioresorcinol derivative metal chelating conjugates

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0256821A2 (fr) * 1986-08-11 1988-02-24 Advanced Oral Healthcorp Limited Liquide de lubrification et de nettoyage du corps
EP0274174A1 (fr) * 1985-12-06 1988-07-13 Yissum Research Development Company Of The Hebrew University Of Jerusalem Composition de dérivé anthraquinone-liposome et sa préparation
WO1993013765A1 (fr) * 1992-01-21 1993-07-22 Rosenberg, Joerg Solutions contenant des lecithines avec du levemopamil

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0274174A1 (fr) * 1985-12-06 1988-07-13 Yissum Research Development Company Of The Hebrew University Of Jerusalem Composition de dérivé anthraquinone-liposome et sa préparation
EP0256821A2 (fr) * 1986-08-11 1988-02-24 Advanced Oral Healthcorp Limited Liquide de lubrification et de nettoyage du corps
WO1993013765A1 (fr) * 1992-01-21 1993-07-22 Rosenberg, Joerg Solutions contenant des lecithines avec du levemopamil

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GUTTERIDGE J M C: "LIPID PEROXIDATION INITIATED BY SUPEROXIDE-DEPENDENT HYDROXYL RADICALS USING COMPLEXED IRON AND HYDROGEN PEROXIDE", FEBS LETTERS,XX,XX, vol. 172, no. 2, July 1984 (1984-07-01), pages 245 - 249, XP001005505, ISSN: 0014-5793 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008524304A (ja) * 2004-12-22 2008-07-10 チバ ホールディング インコーポレーテッド 抗ラジカル剤
US8119103B2 (en) 2006-02-24 2012-02-21 Mallinckrodt Llc Bifunctional resorcinol, thioresorcinol, and dithioresorcinol derivative metal chelating conjugates

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CO5261580A1 (es) 2003-03-31
AU2001236997A1 (en) 2001-08-27
PE20011099A1 (es) 2001-11-23

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