WO2001003774A2 - Composition pharmaceutique de traitement de la calcification - Google Patents

Composition pharmaceutique de traitement de la calcification Download PDF

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Publication number
WO2001003774A2
WO2001003774A2 PCT/HU2000/000053 HU0000053W WO0103774A2 WO 2001003774 A2 WO2001003774 A2 WO 2001003774A2 HU 0000053 W HU0000053 W HU 0000053W WO 0103774 A2 WO0103774 A2 WO 0103774A2
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WIPO (PCT)
Prior art keywords
composition
weight
active agent
agents
agent
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Application number
PCT/HU2000/000053
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English (en)
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WO2001003774A3 (fr
Inventor
Zoltán Dárdai
Original Assignee
Dardai Zoltan
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 Dardai Zoltan filed Critical Dardai Zoltan
Priority to AU54165/00A priority Critical patent/AU5416500A/en
Publication of WO2001003774A2 publication Critical patent/WO2001003774A2/fr
Publication of WO2001003774A3 publication Critical patent/WO2001003774A3/fr

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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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A61K31/125—Camphor; Nuclear substituted derivatives thereof
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/618—Salicylic acid; Derivatives thereof having the carboxyl group in position 1 esterified, e.g. salsalate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the invention relates to pharmaceutical compositions (including veterinary compositions, too) which can be used in the therapy of calcification.
  • Calcification of cartilages, joints and interior organs is a disorder impending over everyone with the progress in lifetime; said disorder plays a causative role in the development of numerous diseases or medical conditions (such as joint inflammations, rheuma, locomotor diseases, deformations, etc.).
  • Numerous therapeutical methods have been known for the treatment of calcification and its consequences. These methods include non-drug treatments (such as diet, curative gymnastics, massage, mud pack, balneotherapy, etc.) and various drug therapies (such as administration of antiphlogistic, analgesic, muscle-relaxant etc. agents), which are frequently used in combination.
  • none of the therapies used at present can cease the once-established calcification; only the progress of the disease can be slowed down and the secondary symptoms can be alleviated.
  • Pharmaceutical compositions used for internal therapy have the disadvantage that the administered active agent cannot reach the site of calcification in a targeted manner but it exerts a loading on the entire organism, which frequently leads to undesired side-effects.
  • the ulcerative effects of certain orally administered non-steroidal anti-inflammatory drugs, applied to alleviate rheumatic inflammations can be mentioned as an example.
  • the invention aims at providing pharmaceutical compositions (including veterinary compositions, too) which can be used either to cease already established calcification or to considerably reduce its extent, and which, when administered in a preferred form, can be directed in a targeted manner (i.e. without exerting an un- necessary loading on the whole organism or on the organs requiring no treatment) to the organ or region where calcification should be ceased or its extent should be reduced.
  • pharmaceutical compositions including veterinary compositions, too
  • the invention relates to a pharmaceutical (including veterinary) composition for the treatment of calcification.
  • the composition according to the invention is
  • an injectable composition or an infusion comprises as active agent acetylsalicylic acid either as a free acid or as its pharmaceutically acceptable water-soluble salt or as its pharmaceutically acceptable water-soluble biologically labile ester, together with a carrier, a diluent and/or an other auxiliary agent conventionally used in such compositions.
  • salts and esters refer to salts and esters, respectively, which undergo hydrolysis or double decomposition under physiological conditions in the presence of a carbonate.
  • Such derivatives of acetylsalicylic acid are e.g. its alkali metal and ammonium salts (including quaternary ammonium salts, too), and its esters formed with lower alkanols and aminoalkanols comp ⁇ sing pre-ferably 1-3 carbon atoms.
  • Acetylsalicylic acid and its derivatives discussed above react with the calcive deposit, and remove the calcive deposit in the form of calcium acetylsalicylate, which latter is a well-known, tested pharmaceutical substance.
  • Acetylsalicylic acid has been known since more than 100 years, and it has been widely used in the therapy, either as such or in the form of its salts, as an antiphlogistic, antipyretic and pain-relieving agent.
  • no data can be found in the literature on a possible anti-calcificative effect of acetylsalicylic acid, and neither acetylsalicylic acid itself nor its salts and esters discussed above have been utilized in a form suitable for targeted therapy (i.e. as a topically applicable composition or as an injection or infusion to be administered into the organ requiring therapy).
  • compositions according to the invention consists of topically applicable compositions, which may be e.g. solutions, emulsions, suspensions, ointments, creams, gels, lotions, shake-up mixtures, plasters and similar formulations routinely used in topical treatments.
  • compositions comprise, beside the active agent, carriers, diluents and/or other auxiliary agents conventionally applied in such compositions, examples of which are as follows: ointment bases, such as vaseline and lanonile; solvents and liquid diluents, such as water; alcohols and glycerol; thickeners and gellifying agents, such as poly- vinyl alcohol, polyvinyl acetate and polymeric cellulose derivatives; ionic and non- ionic tenzides; odourants; substances for adjusting osmotic pressure; colourants and dyestuffs.
  • ointment bases such as vaseline and lanonile
  • solvents and liquid diluents such as water
  • alcohols and glycerol thickeners and gellifying agents, such as poly- vinyl alcohol, polyvinyl acetate and polymeric cellulose derivatives
  • ionic and non- ionic tenzides such as poly- vinyl alcohol, polyvinyl acetate and poly
  • topical compositions are those comprising a thickener, optionally along with a stabilizer, since they enable one to apply a relatively high local dose onto the area to be treated.
  • the topical compositions may optionally also comprise other biologically active substances as activity-complementing agents, examples of which are as follows: antiphlogistic agents, analgesic agents, antirheumatic agents, muscle relaxants, local anaesthetics, pore dilatators and/or agents alleviating skin irritations.
  • the activity-complementing agents also comprise active agents utilized in conventional formulations for the topical treatment of joint and rheumatic pains, such as camphor, menthol, lidocain, methyl salicylate, snake venom extract, and the like.
  • the topical compositions also comprise agents for dilatating skin pores and/or vasopermeability-increasing agents as activity-complementing substances; such compositions can also reduce vascular sclerosis by transdermal way.
  • the active agent content of topically applicable compositions may vary with the type of the formulation concerned.
  • the active agent content of such compositions may be generally 0.1-20 % by weight, preferably 0.5-15 % by weight, more preferably 1-10 % by weight.
  • the amounts of pore dilatators and/or vasopermeability-increasing agents (such as capsaicine and/or histamine), if present, may be generally 0.01-2 % by weight, preferably 0.05-0.5 % by weight.
  • the amounts of other activity-complementing agents, which can be optionally admixed into the topical compositions may vary within wide limits; the actual values depend mainly on the type and effect of the agents concerned and on their compatibility with the other components of the composition.
  • injectable compositions and infusions may contain, beside the active agent, a wide variety of auxiliary agents well known from pharmacotechnology, examples of which are liquid diluents, buffers and salts for adjusting osmotic pressure.
  • injectable compositions and infusions may also contain activity-complementing agents, such as antithrombotic, antiphlogistic, analgesic or antipyretic agents.
  • activity-complementing agents such as antithrombotic, antiphlogistic, analgesic or antipyretic agents.
  • an analgesic agent assists in the early mobilisation of the patient.
  • the active agent Upon moving, the active agent reaches more quickly the targeted organ, where (due to commonly known crystalphysical reasons) the dissolution process starts at the calcic peaks, which are the main causatives of rheumatic pains.
  • Injectable compositions and infusions may also contain the active agent in sustained-release form.
  • the active agent may be entrapped into a cyclic starch or may be microencapsulated into a biodegradable material.
  • topical formulations may contain the active agent in sustained-release form. This has the additional advantage that when appropriately selected enveloping materials are used, the initially hydrophylic active agent can be converted into a form which can easily be combined with hydrophobic carriers.
  • Injectable compositions and infusions may contain generally 0.01-2 % by weight, preferably 0.005-0.5 % by weight of active agent, taken in non-enveloped form.
  • compositions according to the invention may be prepared by conventional pharmacotechological operations well known to one skilled in the art.
  • the composition according to the invention is applied onto the body part or into the organ to be treated.
  • cartilage-, joint- and parosteal calcifications are to be treated, it is preferred to use a topical formulation which is applied onto the region to be treated.
  • an injectable formulation can also be introduced into the body part at the location of calcification.
  • calcifications of interior organs such as of liver or kidney
  • intravascular formulations or infusions which, when introduced into the blood vessels concerned, cause only a minimum gas evolution if at all.
  • These compositions may comprise CO 2 -absorbing components or may comprise acetylsalicylic acid as its ammonium salt, quaternary ammonium salt or ester formed with an amino alcohol.
  • Diclofenac an antiphlogistic agent
  • camphor an agent alleviating skin irritations
  • capsaicine a pore dilatating agent
  • a concentrated aqueous solution of 3 g of acetylsalicylic acid and of 2 g of lidocain (a loc,al anaesthetic) and a concentrated alcoholic solution of 0.2 g of histamine were admixed with 90 g of a hydrophilic pharmaceutical ointment base (Ph.Hg.V). An ointment for topical administration was obtained.
  • lidocain 0.1 % by weight of lidocain, 0.5 % by weight of acetylsalicylic acid and 0.01 % by weight of a nonionic surfactant were dissolved in Ringer solution. An infusion was obtained.
  • acetylsalicylic acid 4 g were entrapped into cyclodextrin by a known technology, and the resulting product was added to 1000 ml of sterile water containing 0.1 % by weight of lidocain and 0.1 % of a nonionic surfactant.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une composition pharmaceutique (y compris vétérinaire) destinée au traitement de la calcification. La composition de l'invention est (a) soit une composition applicable localement (b) soit une composition injectable ou une perfusion, elle comprend en tant que principe actif de l'acide acétyle salicylique soit sous la forme d'un acide libre soit sous la forme de son sel hydrosoluble acceptable sur le plan pharmaceutique, ou de son ester labile biologiquement hydrosoluble et acceptable sur le plan pharmaceutique, avec un excipient, un diluant et/ou un autre agent auxiliaire utilisé de façon classique dans de telles compositions.
PCT/HU2000/000053 1999-07-07 2000-06-02 Composition pharmaceutique de traitement de la calcification WO2001003774A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU54165/00A AU5416500A (en) 1999-07-07 2000-06-02 Pharmaceutical composition for the treatment of calcification

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HUP9902296 1999-07-07
HU9902296A HU9902296D0 (en) 1999-07-07 1999-07-07 Pharmaceutical composition for treating caltification

Publications (2)

Publication Number Publication Date
WO2001003774A2 true WO2001003774A2 (fr) 2001-01-18
WO2001003774A3 WO2001003774A3 (fr) 2002-03-21

Family

ID=89998669

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU2000/000053 WO2001003774A2 (fr) 1999-07-07 2000-06-02 Composition pharmaceutique de traitement de la calcification

Country Status (3)

Country Link
AU (1) AU5416500A (fr)
HU (1) HU9902296D0 (fr)
WO (1) WO2001003774A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003041743A1 (fr) * 2001-11-16 2003-05-22 Dardai Zoltan Composition pharmaceutique transdermique contenant de l'aspirine destinee au traitement de la calcification
WO2010045415A2 (fr) * 2008-10-16 2010-04-22 Novartis Ag Compositions topiques d'ains comprenant un composant apportant des sensations
WO2011076401A1 (fr) 2009-12-23 2011-06-30 Holger Schankin Compositions pharmaceutiques sensiblement exemptes d'eau, contenant de l'acide acétylsalicylique

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE596326A (fr) * 1959-11-02 1961-02-15 Guy Leopold Van Moorleghem Soluté injectable d'aspirine et sou procédé de préparation
GB1036314A (en) * 1962-10-10 1966-07-20 Ile De Rech S Phamaceutiques E Injectable solution of acetylsalicylic acid
FR2295753A1 (fr) * 1974-12-23 1976-07-23 Despin Jean Composition a base d'acide acetyl-salicylique a usage topique
FR2297612A1 (fr) * 1975-01-20 1976-08-13 Moorleghem Guy Van Procede de fabrication d'un produit analgesique a usage externe
US4275059A (en) * 1977-03-28 1981-06-23 The Procter & Gamble Company Salicylate anti-inflammatory composition
FR2556218A1 (fr) * 1983-12-12 1985-06-14 Gerard Alain Produit pharmaceutique pour application locale constitue par l'association d'un principe actif medicamenteux-agent enzymatique
US4533551A (en) * 1984-02-17 1985-08-06 American Home Products Corporation Method of treating arthritis with etodolac
FR2648711A1 (fr) * 1989-05-17 1990-12-28 Jean Blum Complexe soluble dans l'eau et stabilise de l'acide acetyl-salicylique et son procede de fabrication
WO1996028168A1 (fr) * 1993-04-22 1996-09-19 The Hope Heart Institute Methodes de traitement de la thrombose
US5763425A (en) * 1991-04-03 1998-06-09 Gundersen Clinic, Ltd. Suppression of thromboxane levels by percutaneous administration of aspirin
WO2000002565A1 (fr) * 1998-07-09 2000-01-20 Alexander Galat Composition d'acetylsalicylate de sodium injectable et procede afferent

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JPS53124607A (en) * 1977-04-06 1978-10-31 Fujimoto Seiyaku Kk Novel preparation of aspirin included in dextrine analogue
JPS6416726A (en) * 1987-07-08 1989-01-20 Teisan Seiyaku Kk Production of aspirin dl-lysine injection

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE596326A (fr) * 1959-11-02 1961-02-15 Guy Leopold Van Moorleghem Soluté injectable d'aspirine et sou procédé de préparation
GB1036314A (en) * 1962-10-10 1966-07-20 Ile De Rech S Phamaceutiques E Injectable solution of acetylsalicylic acid
FR2295753A1 (fr) * 1974-12-23 1976-07-23 Despin Jean Composition a base d'acide acetyl-salicylique a usage topique
FR2297612A1 (fr) * 1975-01-20 1976-08-13 Moorleghem Guy Van Procede de fabrication d'un produit analgesique a usage externe
US4275059A (en) * 1977-03-28 1981-06-23 The Procter & Gamble Company Salicylate anti-inflammatory composition
FR2556218A1 (fr) * 1983-12-12 1985-06-14 Gerard Alain Produit pharmaceutique pour application locale constitue par l'association d'un principe actif medicamenteux-agent enzymatique
US4533551A (en) * 1984-02-17 1985-08-06 American Home Products Corporation Method of treating arthritis with etodolac
FR2648711A1 (fr) * 1989-05-17 1990-12-28 Jean Blum Complexe soluble dans l'eau et stabilise de l'acide acetyl-salicylique et son procede de fabrication
US5763425A (en) * 1991-04-03 1998-06-09 Gundersen Clinic, Ltd. Suppression of thromboxane levels by percutaneous administration of aspirin
WO1996028168A1 (fr) * 1993-04-22 1996-09-19 The Hope Heart Institute Methodes de traitement de la thrombose
WO2000002565A1 (fr) * 1998-07-09 2000-01-20 Alexander Galat Composition d'acetylsalicylate de sodium injectable et procede afferent

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Title
BEKEMEIER H ET AL: "ON STEROID-SAVING DRUG COMBINATIONS IN CARRAGEENIN PAW EDEMA AND ADJUVANT ARTHRITIS" ARZNEIMITTEL FORSCHUNG. DRUG RESEARCH, EDITIO CANTOR. AULENDORF, DE, vol. 36, no. 10, 1986, pages 1521-1524, XP001015554 ISSN: 0004-4172 *
DATABASE WPI Section Ch, Week 197849 Derwent Publications Ltd., London, GB; Class B05, AN 1978-88532A XP002176996 & JP 53 124607 A (FUJIMOTO SEIYAKU), 31 October 1978 (1978-10-31) *
DATABASE WPI Section Ch, Week 198909 Derwent Publications Ltd., London, GB; Class B05, AN 1989-064967 XP002176997 & JP 01 016726 A (TEISAN SEIYAKU KK), 20 January 1989 (1989-01-20) *
EULERT J ET AL: "HETROTOPE OSSIFIKATIONEN" UNFALLCHIRURGIE, URBAN UND VOGEL, MUNCHEN,, DE, vol. 100, no. 8, August 1997 (1997-08), pages 667-674, XP001014549 ISSN: 0340-2649 *
KEITEL W: "KOMPLEXTHERAPIE IN DER RHEUMATOLOGIE" ZEITSCHRIFT FUER AERZTLICHE FORTBILDUNG, JENA, DD, vol. 85, no. 9, 1991, pages 410-415, XP001015395 ISSN: 0044-2178 *
SAWAR A ET AL: "DRUG THERAPY OF RHEUMATOID ARTHRITIS" DRUGS OF TODAY / MEDICAMENTOS DE ACTUALIDAD, J.R. PROUS SS.A. INTERNATIONAL PUBLISHERS, ES, vol. 33, no. 5, June 1997 (1997-06), pages 299-306, XP001014547 ISSN: 0025-7656 *
SOMOGYI A ET AL: "INHIBITION BY SALICYLATES OF VARIOUS CALCIFYING CONNECTIVE TISSUE REACTIONS" ARCHIVES INTERNATIONALES PHARMACODYNAMIE ET DE THERAPIE, NEW YORK, NY, US, vol. 177, no. 1, 1969, pages 211-223, XP001015523 ISSN: 0003-9780 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003041743A1 (fr) * 2001-11-16 2003-05-22 Dardai Zoltan Composition pharmaceutique transdermique contenant de l'aspirine destinee au traitement de la calcification
CN100342913C (zh) * 2001-11-16 2007-10-17 佐尔坦·达戴 用于治疗钙化的含阿司匹林的透皮吸收药物组合物
WO2010045415A2 (fr) * 2008-10-16 2010-04-22 Novartis Ag Compositions topiques d'ains comprenant un composant apportant des sensations
WO2010045415A3 (fr) * 2008-10-16 2010-06-10 Novartis Ag Compositions topiques d'ains comprenant un composant apportant des sensations
JP2012505909A (ja) * 2008-10-16 2012-03-08 ノバルティス アーゲー 感覚成分を有する局所ｎｓａｉｄ組成物
WO2011076401A1 (fr) 2009-12-23 2011-06-30 Holger Schankin Compositions pharmaceutiques sensiblement exemptes d'eau, contenant de l'acide acétylsalicylique

Also Published As

Publication number Publication date
WO2001003774A3 (fr) 2002-03-21
HU9902296D0 (en) 1999-10-28
AU5416500A (en) 2001-01-30

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