WO1990011759A1 - Composition a deux constituants contenant de la coumarine ou du calcium dobesilate pour le traitement de l'osteoarthrose - Google Patents

Composition a deux constituants contenant de la coumarine ou du calcium dobesilate pour le traitement de l'osteoarthrose Download PDF

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Publication number
WO1990011759A1
WO1990011759A1 PCT/CH1990/000072 CH9000072W WO9011759A1 WO 1990011759 A1 WO1990011759 A1 WO 1990011759A1 CH 9000072 W CH9000072 W CH 9000072W WO 9011759 A1 WO9011759 A1 WO 9011759A1
Authority
WO
WIPO (PCT)
Prior art keywords
benzopyrone
stage
portions
preparation
coumarin
Prior art date
Application number
PCT/CH1990/000072
Other languages
German (de)
English (en)
Inventor
Christian Fricker
Original Assignee
Stuker, Gerhard
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 Stuker, Gerhard filed Critical Stuker, Gerhard
Publication of WO1990011759A1 publication Critical patent/WO1990011759A1/fr

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Classifications

    • 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
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • 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

Definitions

  • This invention relates to human or veterinary pharmacological
  • 1,2-benzopyrone (or 5,6-benzocoumarin) is a well-known and extensively described, naturally occurring organic compound:
  • 1,2-benzopyrone is used as a flavoring agent in the essence industry and perfumery, among other things to flavor tobacco, to mask unpleasant odors and as a fluorescence indicator.
  • Coumarin derivatives serve as rodenticides.
  • 1,2-benzopyrone entry 2543 to: Pharmaceutical auxiliary agent (flavor, smell).
  • auxiliary agent flavor, smell
  • Dobesilate calcium is listed in THE MERCK INDEX, 10th edition, 1983 (entry 3406); above all, the compound is said to have a vasotropic effect.
  • Paracetamol (acetaminophen) is also known as an analgesic; see THE MERCK INDEX, 10th edition, entry 39. Phenylbutazone is described in THE MERCK INDEX, 7th edition, pages 800/801; it shows analgesic properties.
  • Bones, ligaments and joint capsules form a limiting shell for the structures embedded in them.
  • the "edema” cannot expand, resulting in an interstitial pressure increase.
  • Lymphatic vessels are closed. Hemodynamically and lymph dynamically disused areas arise in which the circulatory disorder is maintained in the sense of a vicious circle. The delayed microcirculation reduces the oxygen supply. The oxygen deficit leads to anaerobic glucolysis and
  • the vascular permeability is increased, i.e. there is an increased influx of fluid into the interstitium.
  • 1,2-benzoparone causes histological liver damage in the rat and in the dog with high-dose long-term administration, it does not cause harm to the baboon (67.5 mg / kg daily for two years).
  • the diagnosis of "biliary tract carcinoma" after feeding 5000 and 6000 ppm diets for two years must be questioned from today's perspective, given the lack of metastases and the negative results of other experiments with rats.
  • 1,2-benzopyrone has no mutagenic properties and does not act as a carcinogen on the mouse skin. Repeated subcutaneous administration in rats showed no evidence of carcinogenic activity. In view of the different metabolism processes of primates and rats, rat experiments as a basis for liver toxicity tests must be assessed with caution. A sensitization study on 25 volunteers showed no occurrence of hypersensitivity reactions. Teratogenicity studies in rats with 1,2-benzopyrone and a 1,2-benzopyrone-rutin combination showed negative results with regard to absorption rate, fetal mortality and occurrence of fetal malformations, both after oral and intravenous administration. As already mentioned, it is known to influence the vessel walls in the Meaning of a pre-capillary angiospasmolytic effect
  • 1,2-benzopyrone and its effect on tissue change 1,2-benzopyrone is rapidly absorbed after oral administration and bound to serum albumin. Together with these proteins, coumarin is produced by the monocytes e.g. of damaged tissue and the macrophages present there. This results in proteolysis of the proteins present in the edema area. The proteins are broken down into small fragments and transported away. This and the spasmolytic effect on the vessel wall leads to effective lymphatic drainage.
  • the inventive human or veterinary pharmacological 2-step preparation for the prophylactic and therapeutic treatment of osteoarthritis contains, as active ingredient, 1,2-benzopyrone (coumarin) or 2,5-dihydroxybenzenesulfonic acid
  • the active ingredient being present in the portions of the first stage in concentrations ⁇ 4% by weight and in the portions of the second stage in a concentration of> 1% by weight in addition to excipients.
  • the preferred, new 2-stage preparation has, as active ingredients, in the first stage 1, 2-benzopyrone or 2,5-dihydroxybenzenesulfonic acid Ca as a causal component, in addition to one of the following pain-relieving active ingredients: acetylsalicylic acid plus salts, Paracetamol and phenylbutazone, and in the second stage 1,2-benzopyrone (coumarin) or 2,5-dihydroxybenzenesulfonic acid Ca (dobesilate calcium), the active compounds in the form of solutions to be administered parenterally in packs containing those separated according to the two stages and labeled individual preparation portions or in the form of solid preparations in packs with the individual preparation portions separated and written according to the two stages.
  • active ingredients in the first stage 1, 2-benzopyrone or 2,5-dihydroxybenzenesulfonic acid Ca as a causal component, in addition to one of the following pain-relieving active ingredients: acetylsalicylic acid plus salts, Paracetamol and
  • Special forms of the new 2-stage preparations are characterized by the fact that the individual active ingredients - besides Excipients - contain the active ingredient to 0.1 to 100 wt .-%, and that the weight ratio between the active ingredients, ie 1,2-benzo ⁇ yron or 2,5-dihydroxybenzenesulfonic acid Ca and the pain reliever, in the combine portions between Can vary 20: 1 and 0.05: 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Les douleurs arthritiques sont dues en premier lieu à une pression intérieure accrue dans les os qui résulte d'une accumulation de lymphe. Cette accumulation de lymphe peut être éliminée par administration de compositions à deux constituants qui contiennent de la coumarine ou du calcium dobésilate éventuellement associés à des sels de l'acide acétylsalicylique, de paracétamol ou de phénylbutazone. Ce traitement permet d'obtenir une amélioration clinique rapide et durable de l'état de patients souffrant d'arthrose.
PCT/CH1990/000072 1989-04-07 1990-03-15 Composition a deux constituants contenant de la coumarine ou du calcium dobesilate pour le traitement de l'osteoarthrose WO1990011759A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH1312/89-4 1989-04-07
CH131289A CH679372A5 (fr) 1989-04-07 1989-04-07

Publications (1)

Publication Number Publication Date
WO1990011759A1 true WO1990011759A1 (fr) 1990-10-18

Family

ID=4207501

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CH1990/000072 WO1990011759A1 (fr) 1989-04-07 1990-03-15 Composition a deux constituants contenant de la coumarine ou du calcium dobesilate pour le traitement de l'osteoarthrose

Country Status (3)

Country Link
EP (1) EP0419604A1 (fr)
CH (1) CH679372A5 (fr)
WO (1) WO1990011759A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0620720A4 (fr) * 1991-11-14 1995-02-15 Univ Wake Forest Procede et appareil servant a traiter des lesions tissulaires.
WO2008020033A1 (fr) * 2006-08-16 2008-02-21 Action Medicines, S.L. Utilisation de dérivés de 2,5-dihydrobenzène pour le traitement de l'arthrite et de la douleur
EP1970059A1 (fr) * 2007-03-12 2008-09-17 DOBAVET GmbH Médicament avec Dobesilate de Calcium destiné au traitement et à la prophylaxie des maladies des tendons

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1985003864A1 (fr) * 1984-03-01 1985-09-12 Casley Smith John Royle Traitement des oedemes a forte teneur en proteines par application directe de benzo-pyrones
WO1985003865A1 (fr) * 1984-03-01 1985-09-12 Casley Smith John Royle Traitement des oedemes a forte teneur en proteines chez les animaux

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1985003864A1 (fr) * 1984-03-01 1985-09-12 Casley Smith John Royle Traitement des oedemes a forte teneur en proteines par application directe de benzo-pyrones
WO1985003865A1 (fr) * 1984-03-01 1985-09-12 Casley Smith John Royle Traitement des oedemes a forte teneur en proteines chez les animaux

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
Agents Actions, Band 8, Nr. 1-2, Januar 1978, D.A. WILLOUGHBY et al.: "New Types of Therapy for the Arthropathies and Inflammatory Disease", seiten 166-168, siehe seite 167 *
Angiologica, Band 9, Nr. 2, 1972, E. FOLDI-BORCSOK et al.: "Effect of External Lymph Drainage and of Coumarin Treatment on Dextran Edema", seiten 99-105, siehe den ganze artikel *
Arzneim.-Forsch.(Drug Res.), Band 21, Nr. 12, 1971, E. FOLDI-BORCSOK et al.: "Die Antiphlogistische und Odemhemmende Wirkung von Cumarin aus Melilotus Officinalis", seiten 2025-2030, siehe den ganzen artikel *
Arzneim.-Forsch.(Drug Res.), Band 33(I), Nr. 3, 1983, P. DAYRENS et al.: "Antiinflammatory and Immunostimulant Activities of Six Sulphur Compounds - four Benzenesulphonates, Levamisole, and Pyritinol Hydrochloride - Assayed in Mouse Cell Activation Studies", seiten 372-377, siehe den ganzen artikel *
Arzneim.-Forsch.(Drug Res.), Band 33(II), Nr. 12, 1983, T.J. HARDT et al.: "Investigation of the Dose-Response Relationship upon Intraperitoneal Administration of Coumarin and 7-Hydroxycoumarin on the Carrageenan Induced Edema of the Rats Hind Paw", seiten 1662-1666, siehe den ganzen artikel *
Beitr. Orthop. u. traumatol., Band 23, Nr. 12, Dezember 1976, F. HUTH et al.: "Experimentelle Lymphostatische Arthropathie", seiten 689-695 *
Br. J. Exp. Pathol., Band 57, Nr. 6, 1976, N.B. Piller: "The Action of the Benzopyrones on an Experimental Model of Lymphoedema: A Contribution to their Mode of Action", seiten 713-721 *
Res. Exp. Med., Band 186, Nr. 2, 1986, Springer-Verlag, (DE), N.B. PILLER et al.: "The Effect of Coumarin (5,6 Benzo-alpha-Pyrone) on Elicited Members of the Mononuclear System in Dogs with Chronic Secondary Lymphedema", seiten 109-115, siehe den ganzen artikel *
Rote Liste, 1974, Editio Cantor, (Aulendorf/Wurtt, DE), Nr. 91049 "Venalot", siehe den ganzen artikel *
Z. Rheumatol., Band 36, 1977, Dr. Dietrich Steinkopff Verlag, (Darmstadt, DE), N. BEUSCHER: "Beeinflussung einer Rheumatoiden Modellkrankheit Durch ein Benzopyron-Praparat", seiten 285-293, siehe den ganzen aktikel *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0620720A4 (fr) * 1991-11-14 1995-02-15 Univ Wake Forest Procede et appareil servant a traiter des lesions tissulaires.
WO2008020033A1 (fr) * 2006-08-16 2008-02-21 Action Medicines, S.L. Utilisation de dérivés de 2,5-dihydrobenzène pour le traitement de l'arthrite et de la douleur
US20110152222A1 (en) * 2006-08-16 2011-06-23 Sanchez Pedro Cuevas Use of 2,5-dihydroxybenzene derivatives for the treatment of arthritis and pain
US9060966B2 (en) * 2006-08-16 2015-06-23 Pedro Cuevas Sánchez Use of 2,5-dihydroxybenzene derivatives for the treatment of arthritis and pain
EP1970059A1 (fr) * 2007-03-12 2008-09-17 DOBAVET GmbH Médicament avec Dobesilate de Calcium destiné au traitement et à la prophylaxie des maladies des tendons

Also Published As

Publication number Publication date
CH679372A5 (fr) 1992-02-14
EP0419604A1 (fr) 1991-04-03

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