Compositions for treating joint or connective tissue disease comprising dextran or poloxamer
Inventors
Assignees
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Publication Number
US-11278565-B2
Publication Date
2022-03-22
Expiration Date
Abstract
Disclosed is a composition for treating a joint disease or a connective tissue disease, a composition for cartilage regeneration, or a composition for treating an inflammatory disease, each of the compositions containing dextran, poloxamer or a mixture thereof. The composition stays in the joint or connective tissue for a long time due to the shock-absorbing effect, coating effect or anti-inflammation effect, relieves the shock, covers a damaged portion in a specific manner thereto, or reduces inflammation of an adhered portion. Thus, the composition may be useful for the treatment of the joint disease, the connective tissue disease, or for the cartilage regeneration.
Core Innovation
The patent discloses pharmaceutical compositions comprising dextran having an average molecular weight in a range of 4,000 Da to 6,000 Da and/or poloxamer for treating joint and connective tissue diseases, including cartilage regeneration. It addresses degenerative diseases of joints and degenerative connective tissue diseases of intervertebral discs, ligaments, skin, or tendons by administering a subject in need thereof a composition containing defined dextran molecular-weight fractions and specified dextran and poloxamer concentration ranges.
The compositions are described in terms of dextran average molecular weight selections and concentrations, including mixtures of dextran fractions with different average molecular weights, and mixtures of dextran with poloxamer. The document also describes considerations for toxicity/allergy in connection with higher molecular-weight dextran and higher concentrations of poloxamer 188, and includes exclusion constraints such as excluding dextran having molecular weight 8,000 Da or greater.
In vitro osteoarthritis model testing is described using rat chondrocytes induced with rhIL-1α, demonstrating cytocompatibility and anti-inflammatory and cartilage-protective effects associated with specific dextran and poloxamer 188 combinations. The patent reports increased IL-10/IL-6 gene-expression ratio, inhibition of MMP-3 and MMP-13 gene expression, and enhanced cartilage matrix markers such as increased type II collagen production and aggrecan content under selected formulation concentrations.
The document further describes that stem cells may be included with the dextran-containing composition, and it discusses formulation and administration modalities including intra-articular/topical and oral, and injection/infusion, together with pharmaceutically acceptable excipients and possible anti-inflammatory co-agents.
Claims Coverage
The partial content provides four independent method claims. Across them, the inventive features center on treating degenerative diseases of joints or degenerative connective tissue diseases of specified anatomical targets using dextran-defined molecular-weight compositions and optionally poloxamer mixtures, with specific concentration ranges and (in some claims) dextran molecular-weight exclusion constraints or fraction mixtures.
Dextran molecular weight band for joint and connective tissue degenerative disease treatment
A method of treating a degenerative disease of joints or degenerative connective tissue diseases of intervertebral discs, ligaments, skin, or tendons by administering a composition comprising dextran having an average molecular weight in a range of 4,000 Da to 6,000 Da, wherein a concentration of dextran in the composition is in a range of 2 to 30 (w/v) %.
Mixed dextran fractions at specified molecular weights and concentrations
A method of treating a degenerative disease of joints or degenerative connective tissue diseases of intervertebral discs, ligaments, skin, or tendons by administering a composition comprising a mixture of dextran having an average molecular weight in a range of 4,000 Da to 6,000 Da and dextran having an average molecular weight in a range of 800 Da to 1,200 Da, wherein a concentration of the dextran of the 4,000 Da to 6,000 Da fraction is in a range of 2 to 40 (w/v) % and a concentration of the dextran of the 800 Da to 1,200 Da fraction is in a range of 2.5 to 40 (w/v) %.
Dextran and poloxamer mixture at specified concentration ranges
A method of treating a degenerative disease of joints or degenerative connective tissue diseases of intervertebral discs, ligaments, skin, or tendons by administering a composition comprising a mixture of dextran having an average molecular weight in a range of 4,000 Da to 6,000 Da and poloxamer, wherein a concentration of the dextran in the composition is in a range of 2 to 40 (w/v) % and a concentration of the poloxamer is in a range of 1 to 20 (w/v) %.
Dextran component with defined molecular weight band and concentration
A method of treating a degenerative disease of joints or degenerative connective tissue diseases of intervertebral discs, ligaments, skin, or tendons by administering a composition comprising a dextran component consisting of dextran having an average molecular weight in a range of 4,000 Da to 6,000 Da, wherein a concentration of the dextran component in the composition is in a range of 2 to 30 (w/v) %.
Across the independent claims in the partial content, treatment is implemented by administering dextran-defined molecular-weight compositions to subjects with degenerative joint/connective tissue diseases, with additional claim coverage for mixtures of two dextran molecular-weight fractions, mixtures of dextran with poloxamer, and a dextran component consisting of a defined molecular-weight band, each with specified dextran and poloxamer concentration ranges.
Stated Advantages
Anti-inflammation effect via increased IL-10/IL-6 gene-expression ratio.
Cartilage-protective effects by inhibiting MMP-3 and MMP-13 gene expression.
Enhanced cartilage matrix markers via increased type II collagen production and aggrecan content in specific dextran/poloxamer concentration combinations.
Documented Applications
Treating degenerative diseases of joints and degenerative connective tissue diseases of intervertebral discs, ligaments, skin, or tendons, including osteoarthritis and cartilage regeneration, using dextran-containing and optionally poloxamer-containing pharmaceutical compositions.
In vitro osteoarthritis model testing using rat chondrocytes induced with rhIL-1α to evaluate cytocompatibility, anti-inflammation effects, and cartilage-related gene expression and matrix markers.
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