Claims for Patent: 9,333,280

Summary for Patent: 9,333,280

Title:	Stabilized enzyme compositions
Abstract:	A medical device includes a base material having an immobilized enzyme and dextran sulfate. The dextran sulfate has a molecular weight that is less than 40 kilo dalton (kDa). The medical device is formed from at least a base material. An enzyme is immobilized on the base material. The enzyme is stabilized with a dextran sulfate having a molecular weight of less than 40 (kDa).
Inventor(s):	Gupta; Nisha (Audubon, PA)
Assignee:	Teleflex Medical Incorporated (Durham, NC)
Application Number:	14/041,947
Patent Claims:	1. A medical device, comprising: a base material; and an immobilized enzyme covalently bound to the base material in the presence of dextran sulfate, wherein the medical device is configured to be implanted in the vascular system of a patient, and wherein the dextran sulfate has a molecular weight of about 8 kilodaltons (kDa) to stabilize the immobilized enzyme when in contact with blood of the patient. 2. The medical device according to claim 1, wherein the immobilized enzyme includes at least one of: a blood clot digestive enzyme including one or more of: a urokinase-type plasminogen activator (uPA); a tissue plasminogen activator (tPA); and a streptokinase; and an extracellular matrix digestive enzyme including one or more of: a protease; an aminopeptidase; a collagenase; a matrix metalloproteinase; a metalloendopeptidase; a serine endopeptidase; a hydrolase; a glucuronidase; a hyaluronoglucosaminidase; a heparanase; a cathepsin; a hyaluronidase; and a matriptase. 3. The medical device according to claim 1, further comprising: a combination of two or more antimicrobial agents impregnating the base material. 4. The medical device according to claim 3, wherein the combination of two or more antimicrobial agents includes: a pharmaceutically acceptable salt of a bis-biguanide including at least one of: a chlorhexidine base; and an alexidine; and a guanide including polyhexamethylene biguanide (PHMB). 5. The medical device according to claim 1, further comprising: an antimicrobial agent impregnating the base material. 6. The medical device according to claim 5, wherein the antimicrobial agent includes: a chlorhexidine base; a pharmaceutically acceptable salt of a chlorhexidine base; chlorhexidine diacetate; alexidine; or polyhexamethylene biguanide (PHMB). 7. The medical device according to claim 1, wherein at least a part of the medical device has a tubular structure including the base material. 8. The medical device according to claim 1, wherein the base material is a polymer. 9. The medical device according to claim 8, wherein the polymer is a polyurethane. 10. A medical device, comprising: a polyurethane base material configured to be implanted in the vascular system of a patient; an amount of a blood clot digestive enzyme sufficient to reduce the formation of device related blood clots and an amount of an extracellular matrix digestive enzyme sufficient to reduce neo-initimal hyperplasia, the enzymes being immobilized on the medical device by covalently binding the enzymes to the polyurethane base material; a low molecular weight dextran sulfate configured to stabilize the enzymes when in contact with blood of the patient, the low molecular weight dextran sulfate having a molecular weight of about 8 kilodaltons; and an antimicrobial agent disposed in the polyurethane base material in an amount sufficient to reduce microbial growth. 11. A medical device comprising: a polyurethane base material configured to be implanted in the vascular system of a patient; an amount of an enzyme sufficient to reduce the formation of blood clots in a patient or sufficient to reduce neo-initimal hyperplasia, the enzyme being covalently immobilized in the base material; a low molecular weight dextran sulfate configured to stabilize the enzyme when in contact with blood of the patient, the low molecular weight dextran sulfate having a molecular weight of about 8 kilodaltons; and a chlorhexidine base or a pharmaceutically acceptable salt thereof disposed in the polyurethane base material in an amount sufficient to reduce microbial growth. 12. A medical device, comprising: a base material; an immobilized enzyme covalently bound to the base material in the presence of dextran sulfate; and a cationic selective antimicrobial impregnating the base material, wherein the medical device is configured to be implanted in the vascular system of a patient, and wherein the dextran sulfate has a molecular weight of about 8 kilodaltons (kDa) to stabilize the immobilized enzyme when in contact with blood of the patient. 13. The medical device according to claim 12, wherein the immobilized enzyme includes at least one of: a blood clot digestive enzyme including one or more of: a urokinase-type plasminogen activator (uPA); a tissue plasminogen activator (tPA); and a streptokinase; and an extracellular matrix digestive enzyme including one or more of: a protease; an aminopeptidase; a collagenase; a matrix metalloproteinase; a metalloendopeptidase; a serine endopeptidase; a hydrolase; a glucuronidase; a hyaluronoglucosaminidase; a heparanase; a cathepsin; a hyaluronidase; and a matriptase. 14. The medical device according to claim 12, wherein at least a part of the medical device has a tubular structure including the base material. 15. The medical device according to claim 12, wherein the base material is a polymer. 16. The medical device according to claim 15, wherein the polymer is a polyurethane. 17. The medical device according to claim 12, wherein the cationic selective antimicrobial is a ceragenin. 18. The medical device according to claim 12, wherein the cationic selective antimicrobial is in an amount sufficient to reduce microbial growth.

Details for Patent 9,333,280

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2029-02-25
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2029-02-25
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2029-02-25
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	10/25/2005		2029-02-25
Microbix Biosystems Inc.	KINLYTIC	urokinase	For Injection	021846	01/16/1978		2029-02-25
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2029-02-25