Stabilized enzyme compositions
View Patent ↗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).
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.