WO2002022139A1 - Intraarticular agent for the treatment of osteoarthritis - Google Patents
Intraarticular agent for the treatment of osteoarthritis Download PDFInfo
- 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
Links
- 201000008482 osteoarthritis Diseases 0.000 title claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 38
- 239000003349 gelling agent Substances 0.000 claims abstract description 13
- 229920002678 cellulose Polymers 0.000 claims description 15
- 235000010980 cellulose Nutrition 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 11
- 239000001913 cellulose Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000003431 cross linking reagent Substances 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 5
- 230000003472 neutralizing effect Effects 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 3
- 239000002952 polymeric resin Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229920013730 reactive polymer Polymers 0.000 claims description 3
- 102000004127 Cytokines Human genes 0.000 claims description 2
- 108090000695 Cytokines Proteins 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 2
- 229920002125 Sokalan® Polymers 0.000 claims 1
- 239000004584 polyacrylic acid Substances 0.000 claims 1
- 238000004132 cross linking Methods 0.000 abstract description 7
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 12
- 229920002674 hyaluronan Polymers 0.000 description 11
- 229960003160 hyaluronic acid Drugs 0.000 description 11
- 239000000499 gel Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000003855 balanced salt solution Substances 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 229920000058 polyacrylate Polymers 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 208000006820 Arthralgia Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229920006037 cross link polymer Polymers 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920003102 Methocel™ E4M Polymers 0.000 description 1
- 229920001730 Moisture cure polyurethane Polymers 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000000159 acid neutralizing agent Substances 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
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)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Gelling agents and agents that are solidifying due to cross-linking as agents for the treatment of osteoarthritis are described.
Description
Intraarticular agent for the treatment of osteoarthritis
Technical Field
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.
Background Art
Osteoarthritis, i.e. painful joints, is due to a production deficiency of hyaluronic acid (HA) . HA is a high molecular weight, straight-chain heteropolysaccha- ride consisting of alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine that is present in the synovial fluid of joints where it has a function as a lu- bricant and as a shock absorber.
With water, HA forms a highly viscous solution.
Hitherto, specific 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.
Such application, as well as the isolation of useful fractions of hyaluronic acid for such purposes, is e.g. described in US 5,925,626, US 5,631,241, US 5,442,053 and 5,166,331.
It is also already known to crosslink hyaluronic acid such that it is suitable for visco-supplemen- tation of joints (see EP 0 939 086) .
Although such treatment with hyaluronic acid has proved to be suitable to reduce the pain in joints, it is quite expensive and the treatment has to be repeated regularly.
Therefore, there is still a need for an alternative, cheaper and preferably longer lasting alternative .
Disclosure of the Invention
It is therefore an object of the present invention to provide an improved agent for the intraarticular treatment of osteoarthritis. It is a further object of the present invention to provide such an agent that is a viscosupplementa- tion agent.
It has now surprisingly been found that specific gelling agents or solidifying agents (also referred to as prepolymer, or reactive polymer resin) can be used instead of hyaluronic acid, in particular celluloses including cellulose derivatives and "mixed" celluloses such as hydroxypropyl methyl cellulose.
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) . Such cross-linking, and in particular the use of cross-linking agents, can be avoided by using readily gelling agents such as celluloses.
In view of their greater ability to migrate to inflamed tissue, gelling agents with slightly acidic groups such as OH-groups are preferred. Thus, 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.
Since also gels, similar to viscous solu- tions, due to their features lead to reduced protection with time, the effect can be enhanced if such gelling agents are furthermore cross-linked to "stabilize" the structure. Such viscosupplementation leads to a shock absorbing mass, a buffer, provided that said cross-linked polymer has sufficient elasticity. Methods to enhance elasticity of a formed polymer and to achieve cross- linking are known in the field of polymer chemistry and agents that are physiologically acceptable are also known . Besides of elastic cross-linked products also inelastic products may be used if the bones are already damaged to an extent where a "bone restitution" seems appropriate .
The term solidifying agent encompasses all physiologically acceptable cross-linkable resins or pre- polymers, respectively. Such 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. Also with regard to 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.
Dependent on the viscosity desired, different 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. Possibly, one of the components can furthermore comprise a catalyst or other reaction/reactivity improv- ing agent .
In the case of a solidifying agent, a similar method can be applied, whereby one of the components comprises a resin component and the second component a cross-linking agent. Furthermore, one of the components may comprise a catalyst and/or other reaction/reactivity improving agent .
Besides of the gelling or solidifying 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.
Wherever a gelling or solidifying compound or other possible ingredients are mentioned, it is also within the scope of the present invention that 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
i) hydroxypropyl methylcellulose 23.0 g (e.g. Methocel E 4 M Premium) ii) balanced salt solution ad. 1 liter
the balanced salt solution e.g. comprises
sodium chloride 4.90 g potassium chloride 0.75 g calcium chloride 0.48 g magnesium chloride 0.50 g sodium acetate 3.90 g sodium citrate 1.70 g hydrochloric acid ad pH 7.45 water ad 1 liter
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..
An analogous method can be applied to prepare other sterilized gelling or solidifying components and neutralizing or cross-linking components. While there are shown and described presently preferred embodiments of the invention, it is to be distinctly understood that the invention is not limited thereto but may be otherwise variously embodied and practiced within the scope of the following claims.
Claims
1. Use of at least one gelling or solidifying agent for the preparation of a medicament for the intraarticular treatment of osteoarthritis.
2. The use of claim 1 wherein the gelling agent is a cellulose derivative, in particular an OH substituted cellulose derivative.
3. The use of claim 2 wherein the gelling agent comprises and preferably is hydroxypropyl methyl cellulose .
4. The use of claim 1 wherein the gelling agent is a vinyl polymer, in particular a polyacrylic acid.
5. The use of anyone of claims 1 to 4 , wherein the solidifying agent is a reactive polymer resin, that solidifies if cross-linked.
6. A medical 2 -component-composition, in par- ticular as agent for the intraarticular treatment of osteoarthritis, wherein one component comprises a solidifying agent and a second component comprises a cross- linking agent.
7. The composition of claim 6, wherein one of the components comprises a catalyst that activates the cross-1inking .
8. A method for preparing a gelled or solidified agent comprising mixing a gelling agent with a neutralizing agent, or a solidifying agent with a cross- linking agent, whereby the mixing is performed directly prior to injection.
9. A medical composition comprising in one or more components a gelling or solidifying agent of one of claims 1 to 5 and at least one further effective sub- stance.
10. The composition of claim 6 wherein the further effective substance is selected from the group comprising anti-inflammatory agents such as steroids, non-steroidal anti-inflammatory agents, cytokine-binding antibodies, anti-infectuous agents such as antibiotics, and mixtures thereof .
11. Use of a composition of claim 9 or 10 for the preparation of a medicament for the intraarticular treatment of osteoarthritis.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2000268609A AU2000268609A1 (en) | 2000-09-14 | 2000-09-14 | Intraarticular agent for the treatment of osteoarthritis |
| PCT/IB2000/001300 WO2002022139A1 (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 (en) | 2000-09-14 | 2000-09-14 | Intraarticular agent for the treatment of osteoarthritis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2002022139A1 true WO2002022139A1 (en) | 2002-03-21 |
Family
ID=11003973
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2000/001300 WO2002022139A1 (en) | 2000-09-14 | 2000-09-14 | Intraarticular agent for the treatment of osteoarthritis |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2000268609A1 (en) |
| WO (1) | WO2002022139A1 (en) |
Citations (7)
| 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 (en) * | 1987-07-28 | 1989-08-21 | F Treiger Seymour | Modified joint disease treatment method and drug |
| WO1990004971A1 (en) * | 1988-11-03 | 1990-05-17 | M.D.R. Group, Inc. | Improved viscoelastic fluid for use in surgery and other therapies and method of using same |
| EP0499164A1 (en) * | 1991-02-12 | 1992-08-19 | C.R. Bard, Inc. | Injectable compositions to replace lubricating body fluids |
| WO1994025004A1 (en) * | 1993-04-30 | 1994-11-10 | Webb Bradford C | Synthetic viscoelastic material for ophthalmic applications |
| 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 (en) * | 1998-02-27 | 1999-09-01 | Stichting Hippomedics | Process for producing crosslinked hyaluronic acid |
-
2000
- 2000-09-14 AU AU2000268609A patent/AU2000268609A1/en not_active Abandoned
- 2000-09-14 WO PCT/IB2000/001300 patent/WO2002022139A1/en active Application Filing
Patent Citations (7)
| 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 (en) * | 1987-07-28 | 1989-08-21 | F Treiger Seymour | Modified joint disease treatment method and drug |
| WO1990004971A1 (en) * | 1988-11-03 | 1990-05-17 | M.D.R. Group, Inc. | Improved viscoelastic fluid for use in surgery and other therapies and method of using same |
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|---|---|
| AU2000268609A1 (en) | 2002-03-26 |
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