COMPOSITIONS AND METHODS FOR INDUCING OR ENHANCING CONNECTIVE TISSUE REPAIR

• US 20160045534A1
• Filed: 10/28/2015
• Published: 02/18/2016
• Est. Priority Date: 09/23/2009
• Status: Active Grant

• Current Assignee: Glenpharma AB
• Original Assignee: Glenpharma AB
• Inventors: Buckley, Peter Byron, Messmer, Konrad, Phillips, Mark William
• Granted Patent: US 9,795,630 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 31/721 Dextrans
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A method of synergistically attenuating platelet hyperactivation and enhancing connective tissue regeneration including administering an aqueous parenteral solution to a subject, the aqueous parenteral solution containing a glycosaminoglycan having a weight average molecular weight from about 1.5 to about 6000 kD, and a concentration of about 0.1% to about 7.0%, a neutral colloidal polysaccharide having a weight average molecular weight of about 20 to about 75 kD, and a concentration of about 1.0% to about 25%, and an isomaltose oligomer having a weight average molecular weight of about 0.4 to about 8 kD, and a concentration of about 0.3% to about 25%.

Claims

1. A method of treating platelet hyperactivation or an associated disease, a condition or pathophysiological sequelae thereof by administering to a subject an effective synergistic amount of an aqueous parenteral solution containing a glycosaminoglycan, an isomaltose oligomer and a neutral colloidal polysaccharide.

2. The method of claim 1, wherein the associated disease, condition or pathophysiological sequelae includes a disorder selected from the group consisting of:

thrombosis, a thrombotic complication of an atherosclerotic disease, a thrombotic complication of an intervention of an atherosclerotic disease, a thrombotic complication associated with surgical or mechanical damage, a mechanically-induced platelet activation, a shunt occlusion, thrombosis secondary to vascular damage and inflammation, an indication with a diffuse thrombotic or platelet consumption component, venous thrombosis, coronary arterial thrombosis, a pathological effect of atherosclerosis and arteriosclerosis, a platelet aggregation and clot formation in blood and blood products during storage, a chronic or acute state of hyper-aggregability, a reocclusion of an artery or vein following fibrinolytic therapy, platelet adhesion associated with extracorporeal circulation, a thrombotic complication associated with thrombolytic therapy, a thrombotic complication associated with coronary and other angioplasty, a thrombotic complication associated with coronary artery bypass procedures, and a disorder, a procedure or a sequelae characterized by inflammatory cascades triggered by platelet degranulation, including a disorder selected from the group consisting of;

an intimal hyperplasia, artheroma and restenosis of arteries or veins, platelet-leukocyte-fibrin micro- and macro-embolism, stroke, myocardial infarction, raised leukocyte activation, aggregation, adhesion and free-radical injury in association with ischemia-reperfusion injury following clot thrombolysis, declamping, angioplasty, organ and tissue transplantation, tissue salvaging reconstructive surgery or restoration of blood volume in hypovolemia, an inflammatory joint disorder and a sequela of excessive fibrin clot retraction including fibrosis and scarring in connective tissue.

3. The method of claim 1, wherein the glycosaminoglycan is selected from at least one of hyaluronan, chondroitin, dermatin, keratin, heparan, heparin, and glycosaminoglycan analogues dextran sulphate and pentosan sulphate and is present in an amount of from about 0.1% to about 7.0% by weight of the aqueous parenteral solution and, wherein the neutral colloidal polysaccharide is selected from at least one of a dextran, a hydroxyethyl starch and a fucoidan and is present in an amount of from about 1.0% to about 25% by weight of the aqueous parenteral solution.

4. The method of claim 1, wherein the glycosaminoglycan is hyaluronan having a weight average molecular weight from about 1.5 kD to about 6,000 kD, the neutral colloidal polysaccharide is dextran having a weight average molecular weight from about 20 kD to about 100 kD and the isomaltose oligomer has a weight average molecular weight from about 0.3 kD to about 10 kD.

5. The method of claim 1, wherein the neutral colloidal polysaccharide is hydroxyethyl starch having a weight average molecular weight of from about 10 kD to about 500 kD and wherein the isomaltose oligomer has a weight average molecular weight of from about 0.3 kD to about 10 kD.

6. The method of claim 1, wherein the glycosaminoglycan is a partially cross-linked hyaluronan having a degree of cross-linking that is less than about 25%.

7. The method of claim 1, wherein the step of administering to the subject an effective synergistic amount of the aqueous parenteral solution comprises at least one of topically applying the aqueous parenteral solution to the subject or injecting the aqueous parenteral solution into the subject.

8. The method of claim 1, wherein the aqueous parenteral solution further comprises at least one of an antioxidant, a scavenger, a cytokine, a growth factor, an interleukin, a gene therapy agent, a viscoelastic agent and a stem cell.

9. A method for synergistically accelerating repair, regeneration, treatment or inducing the repair of an injury, a defect or a condition of a connective tissue by administering to a subject an aqueous parenteral solution containing from about 0.1% to about 7.0% by weight of a glycosaminoglycan, from about 1.0% to about 25% by weight of a neutral colloidal polysaccharide and from about 0.3% to about 35% by weight of an isomaltose oligomer, wherein the glycosaminoglycan has a weight average molecular weight from about 2 kD to about 5,000 kD, the neutral colloidal polysaccharide has a weight average molecular weight of from about 20 kD to about 100 kD and the isomaltose oligomer has a weight average molecular weight of from about 0.4 kD to about 4 kD.

10. The method of claim 9, wherein the glycosaminoglycan is selected from at least one of hyaluronan, chondroitin, dermatin, keratin, heparan, heparin, and glycosaminoglycan analogues dextran sulphate, pentosan sulphate and the neutral colloidal polysaccharide is selected from at least one of dextran, a hydroxyethyl starch, and fucoidan.

11. The method of claim 9, wherein the glycosaminoglycan is a partially cross-linked hyaluronan having a degree of cross-linking that is less than about 25%.

12. The method of claim 9, wherein the connective tissue is selected from at least one of a tendon, a ligament, cartilage, bone, skin and a cornea.

13. The method of claim 9, wherein the administration step comprises implanting into the subject the aqueous parenteral solution to augment direct repair of the connective tissue.

14. The method of claim 9, wherein the aqueous parenteral solution further comprises at least one of an antioxidant, a scavenger, a cytokine, a growth factor, an interleukin, a gene therapy agent, a viscoelastic agent and a stem cell.

15. A method of synergistically attenuating platelet hyperactivation and enhancing connective tissue regeneration, the method comprising:

administering an aqueous parenteral solution to a subject, the aqueous parenteral solution containing;

a glycosaminoglycan having a weight average molecular weight from about 1.5 to about 6000 kD, and a concentration of about 0.1% to about 7.0%;

a neutral colloidal polysaccharide having a weight average molecular weight of about 20 to about 75 kD, and a concentration of about 1.0% to about 25%; and

an isomaltose oligomer having a weight average molecular weight of about 0.4 to about 8 kD, and a concentration of about 0.3% to about 25%.

16. The composition of claim 15, wherein the glycosaminoglycan is selected from at least one of hyaluronan, chondroitin, dermatin, keratin, heparan, heparin, and glycosaminoglycan analogues dextran sulphate, pentosan sulphate, and wherein the neutral colloidal polysaccharide is selected from at least one of dextran, a hydroxyethyl starch and fucoidan.

17. The method of claim 15, wherein the glycosaminoglycan is hyaluronan, and the neutral colloidal polysaccharide is dextran.

18. The method of claim 15, wherein the glycosaminoglycan is a partially cross-linked hyaluronan having a degree of cross-linking that is less than about 25%.

19. The method of claim 15, wherein the aqueous parenteral solution further comprises at least one of an antioxidant, a scavenger, a cytokine, a growth factor, an interleukin, a gene therapy agent, a viscoelastic agent and a stem cell.