WO2002022139A1 - Agent intra-articulaire destine au traitement de l'arthrose - Google Patents

Agent intra-articulaire destine au traitement de l'arthrose Download PDF

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Publication number
WO2002022139A1
WO2002022139A1 PCT/IB2000/001300 IB0001300W WO0222139A1 WO 2002022139 A1 WO2002022139 A1 WO 2002022139A1 IB 0001300 W IB0001300 W IB 0001300W WO 0222139 A1 WO0222139 A1 WO 0222139A1
Authority
WO
WIPO (PCT)
Prior art keywords
agent
gelling
cross
osteoarthritis
composition
Prior art date
Application number
PCT/IB2000/001300
Other languages
English (en)
Inventor
Robert Theiler
Original Assignee
Robert Theiler
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 Robert Theiler filed Critical Robert Theiler
Priority to PCT/IB2000/001300 priority Critical patent/WO2002022139A1/fr
Priority to AU2000268609A priority patent/AU2000268609A1/en
Publication of WO2002022139A1 publication Critical patent/WO2002022139A1/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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/717—Celluloses
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
    • 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
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis

Definitions

  • Intraarticular agent for the treatment of osteoarthritis is an Intraarticular agent for the treatment of osteoarthritis
  • the present invention concerns an agent for the intraarticular treatment of osteoarthritis, in particular an agent comprising a gel forming agent or a solidifying agent such as e.g. a gel forming agent with cross-linking ability.
  • HA hyaluronic acid
  • fractions of hyaluronic acid, or rather salts of HA have been used for treating osteoarthritis, i.e. damaged bone joints.
  • Such fractions differ e.g. in the viscosity of the respective solutions.
  • gelling agents or solidifying agents also referred to as prepolymer, or reactive polymer resin
  • hyaluronic acid in particular celluloses including cellulose derivatives and "mixed" celluloses such as hydroxypropyl methyl cellulose.
  • hyaluronic acid While hyaluronic acid is soluble in water leading to more or less viscous solutions dependent on the fraction and concentration used, it can only be transferred into a gel by cross-linking (see EP 0 939 086) .
  • cross-linking and in particular the use of cross-linking agents, can be avoided by using readily gelling agents such as celluloses.
  • gelling agents with slightly acidic groups such as OH-groups are preferred.
  • a preferred cellulose is e.g. hydroxypropyl methylcellulose .
  • Another gelling agent with very good gelling properties, that for said good gelling properties can be used in very small amounts, are vinyl polymers such as e.g. polyacrylates .
  • Polyacrylates have the great advantage that they lead to very viscous gels in small amounts, their disadvantage, however, is that they need a neutralizing agent in order to achieve the desired gelling.
  • Preferred neutralizing agents are of course such that are physiologically acceptable and much preferred, such neutralizing agents are effective substances, e.g. anti-inflammatory agents such as steroids, non-steroidal anti-inflam- matory agents, cytokine-binding antibodies, anti-infec- tuous agents such as antibiotics.
  • Such effective substances can of course also be incorporated in a cellulose preparation.
  • solidifying agent encompasses all physiologically acceptable cross-linkable resins or pre- polymers, respectively.
  • reactive polymer resins e.g.' are gelling agents comprising reactive groups such as suitably substituted celluloses.
  • Celluloses as well as polyacrylates, have the advantage that - due to the inability of the bodies of several mammals including man to degrade (digest) them - they have good long lasting properties.
  • the cross-linked polymers not only the prepolymer but also the cross-linking agent, or the groups produced upon cross-linking should be undegradable to improve the long time effect.
  • Modes for Carrying Out the Invention Although a broad variety of celluloses is usable, due to the presence of OH groups, hydroxy substi- tuted celluloses, such as hydroxypropyl methylcellulose, are preferred.
  • Hydroxy substituted celluloses as well as other "acidic" substituted compounds, more readily migrate to an inflamed place than "not acidic” substituted compounds, however very acidic groups or too many acidic groups might lead to undesired solubility.
  • concentrations can be applied whereby the injectability must be conserved. This may be achieved by suitably low concentration or - in the case of gelling agents needing neutralization - by mixing with the neutralization agent just prior to injection so that gelling does not yet occur within the syringe.
  • the same procedure is also suitable for solidifying agents, whereby the solidifying agent, prior to application, is present in one component and the cross-linking agent in a second component, and whereby both components are mixed just prior to application.
  • one of the components can furthermore comprise a catalyst or other reaction/reactivity improv- ing agent .
  • one of the components comprises a resin component and the second component a cross-linking agent.
  • one of the components may comprise a catalyst and/or other reaction/reactivity improving agent .
  • the gelling or solidifying agent comprising solution may be supplemented with physiologically acceptable or even necessary substances, such as isotonicity providing agents, but also with other effective substances to e.g. reduce the inflammation and/or pain.
  • physiologically acceptable or even necessary substances such as isotonicity providing agents, but also with other effective substances to e.g. reduce the inflammation and/or pain.
  • mixtures of such compounds e.g. mixtures of gelling agents, mix- tures of solidifying agents etc. can be used provided that they are compatible with each other.
  • Such possible mixtures are e.g. mixtures of different cellulose derivatives .
  • the gelling or solidifying agent comprising injectable medical agent is preferably stored in sterile syringes of e.g. 2 ml, 3 ml and 4 ml volume, whereby for the production of a cross-linked product, in particular in the case of damaged bones, larger amounts and therefore larger syringes, or infusion bags with volumes up to 200 ml may be suitable.
  • An example for a suitable cellulose solution comprises
  • the balanced salt solution e.g. comprises
  • the hydroxypropyl methyl cellulose is e.g. added to about 1/3 of the needed balanced salt solution that previously was heated to about 60 °C. As soon as the product is homogeneous, the remaining balanced salt solu- tion (cool) is added. The obtained gel is then dosed into syringes or vials or other sterilizable containers and sterilized according to known methods.
  • a respectively prepared product can be di- rectly injected into a joint to be treated with the same methods known for the treatment with hyaluronic acid.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne l'utilisation d'agents gélifiants et d'agents qui se solidifient par suite d'une réticulation, en tant qu'agents de traitement de l'arthrose.
PCT/IB2000/001300 2000-09-14 2000-09-14 Agent intra-articulaire destine au traitement de l'arthrose WO2002022139A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/IB2000/001300 WO2002022139A1 (fr) 2000-09-14 2000-09-14 Agent intra-articulaire destine au traitement de l'arthrose
AU2000268609A AU2000268609A1 (en) 2000-09-14 2000-09-14 Intraarticular agent for the treatment of osteoarthritis

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2000/001300 WO2002022139A1 (fr) 2000-09-14 2000-09-14 Agent intra-articulaire destine au traitement de l'arthrose

Publications (1)

Publication Number Publication Date
WO2002022139A1 true WO2002022139A1 (fr) 2002-03-21

Family

ID=11003973

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2000/001300 WO2002022139A1 (fr) 2000-09-14 2000-09-14 Agent intra-articulaire destine au traitement de l'arthrose

Country Status (2)

Country Link
AU (1) AU2000268609A1 (fr)
WO (1) WO2002022139A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1455552A (en) * 1974-04-11 1976-11-17 Warner Lambert Co Pharmaceutical composition for topical administration
JPH01207055A (ja) * 1987-07-28 1989-08-21 F Treiger Seymour 変性関節疾患処置方法及び薬剤
WO1990004971A1 (fr) * 1988-11-03 1990-05-17 M.D.R. Group, Inc. Fluide viscoelastique ameliore utilise en chirurgie ainsi que dans d'autres therapies, et son procede d'utilisation
EP0499164A1 (fr) * 1991-02-12 1992-08-19 C.R. Bard, Inc. Compositions injectables pour remplacer les fluides lubrifiants corporels
WO1994025004A1 (fr) * 1993-04-30 1994-11-10 Webb Bradford C Matiere viscoelastique synthetique destinee a des applications ophtalmiques
US5442053A (en) * 1982-09-28 1995-08-15 Fidia, S.P.A. Salts and mixtures of hyaluronic acid with pharmaceutically active substances, pharmaceutical compositions containing the same and methods for administration of such compositions
EP0939086A1 (fr) * 1998-02-27 1999-09-01 Stichting Hippomedics Procédé pour préparer un acide hyaluronique réticulé

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1455552A (en) * 1974-04-11 1976-11-17 Warner Lambert Co Pharmaceutical composition for topical administration
US5442053A (en) * 1982-09-28 1995-08-15 Fidia, S.P.A. Salts and mixtures of hyaluronic acid with pharmaceutically active substances, pharmaceutical compositions containing the same and methods for administration of such compositions
JPH01207055A (ja) * 1987-07-28 1989-08-21 F Treiger Seymour 変性関節疾患処置方法及び薬剤
WO1990004971A1 (fr) * 1988-11-03 1990-05-17 M.D.R. Group, Inc. Fluide viscoelastique ameliore utilise en chirurgie ainsi que dans d'autres therapies, et son procede d'utilisation
EP0499164A1 (fr) * 1991-02-12 1992-08-19 C.R. Bard, Inc. Compositions injectables pour remplacer les fluides lubrifiants corporels
WO1994025004A1 (fr) * 1993-04-30 1994-11-10 Webb Bradford C Matiere viscoelastique synthetique destinee a des applications ophtalmiques
EP0939086A1 (fr) * 1998-02-27 1999-09-01 Stichting Hippomedics Procédé pour préparer un acide hyaluronique réticulé

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ADAMS M E ET AL: "THE ROLE OF VISCOSUPPLEMENTATION WITH HYLAN G-F 20 (SYNVISC) IN THETREATMENT OF OSTEOARTHRITIS OF THE KNEE: A CANADIAN MULTICENTER TRIAL COMPARING HYLAN G-F 20 ALONE, HYLAN G-F 20 WITH NON-STERIODALANTI-INFLAMMATORY DRUGS (NSAIDS) AND NSAIDS ALONE", OSTEOARTHRITIS AND CARTILAGE,GB,BAILLIERE TINDALL, LONDON, vol. 3, no. 4, 1995, pages 213 - 225, XP002045971, ISSN: 1063-4584 *
M. H. BEERS: "The Merk Manual", 1999, MERK RESEARCH LABORATORIES, USA, XP002166390 *
PATENT ABSTRACTS OF JAPAN vol. 1999, no. 06 31 March 1999 (1999-03-31) *

Also Published As

Publication number Publication date
AU2000268609A1 (en) 2002-03-26

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