US4378803A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for producing antithrombogenic vinyl acetate polymer or hydrolyzate thereof
Assignee: Unitika Ltd
•
Filing: 1980-11-24
•
Granted: 1983-04-05
•
Expires: 2000-11-24
Abstract
Abstract A process for producing an antithrombogenic vinyl acetate polymer or a hydrolyzate thereof which comprises treating the vinyl acetate polymer or hydrolyzate with a solution of a fibrinolytic enzyme so as to fix the fibrinolytic enzyme to the polymer. The resulting antithrombogenic vinyl acetate polymer or hydrolyzate is advantageously used in a material which comes into contact with the blood in use and is especially useful in a surgical tube.
Inventors
- 👤 Kunihiko Takagi
- 👤 Yasunori Yabushita
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 19:31
CPC Classifications
A; A61; A61L; A61L33/00; A61L33/0005; A61L33/0047
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
311 words
A process for producing an antithrombogenic hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene which comprises treating a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene in the form of a shaped article with a solution of a fibrinolytic enzyme so as to fix the enzyme to the copolymer wherein the hydrolyzed vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with the fibrinolytic enzyme and the enzyme is fixed to the copolymer through covalent bonding, said reactive functional group being selected from the group consisting of (A) an isocyanate group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyisocyanate, (B) an epoxy group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyepoxide, (C) a formyl group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyaldehyde, (D) an acid chloride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an acid chloride, (E) a carboxylic acid anhydride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polycarboxylic acid anhydride, (F) an amino group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal, and (G) an amino group which has been introduced thereinto by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with both a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 2
Dependent Claim
311 words
A process for producing an antithrombogenic hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene which comprises treating a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene in the form of a shaped article with a solution of a fibrinolytic enzyme so as to fix the enzyme to the copolymer wherein the hydrolyzed vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with the fibrinolytic enzyme and the enzyme is fixed to the copolymer through covalent bonding, said reactive functional group being selected from the group consisting of (A) an isocyanate group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyisocyanate, (B) an epoxy group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyepoxide, (C) a formyl group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyaldehyde, (D) an acid chloride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an acid chloride, (E) a carboxylic acid anhydride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polycarboxylic acid anhydride, (F) an amino group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal, and (G) an amino group which has been introduced thereinto by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with both a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 3
Dependent Claim
11 words
The process of claim 1, wherein the fibrinolytic enzyme is urokinase.
Claim 4
Dependent Claim
11 words
The process of claim 1, wherein said fibrinolytic enzyme is streptokinase.
Claim 5
Dependent Claim
11 words
The process of claim 1, wherein said fibrinolytic enzyme is plasmin.
Claim 6
Dependent Claim
11 words
The process of claim 1, wherein said fibrinolytic enzyme is brinolase.
Claim 7
Dependent Claim
28 words
The process of claim 1, wherein a functional group having an affinity for substances in the blood which inhibit fibrinolytic enzymes is present in the polymer or hydrolyzate.
Claim 8
Dependent Claim
12 words
The process of claim 6, wherein said group is a nitrophthaloyl group.
Claim 9
Dependent Claim
290 words
A process for producing an antithrombogenic hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene which comprises treating a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene in the form of a shaped article with a solution of a fibrinolytic enzyme so as to fix the enzyme to the copolymer wherein the hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with the fibronolytic enzyme and the enzyme is fixed to the polymer through covalent bonding, said reactive functional group being selected from the group consisting of an isocyanate group, an epoxy group, a formyl group, an acid chloride group, a carboxylic acid anhydride group and the reactive functional group having been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer having an amino group with a polyfunctional reagent, selected from the group consisting of a polyisocyanate, a polyepoxide, a polyaldehyde, a polyacid chloride and a polycarboxylic acid anhydride, having at least two of the reactive functional groups capable of reacting with an amino group, and the fibrinolytic enzyme is fixed to the polymer through covalent bonding, wherein said amino group has been introduced: (A) by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal; or (B) by first treating the hydrolyzed ethylenevinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 10
Dependent Claim
290 words
A process for producing an antithrombogenic hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene which comprises treating a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene in the form of a shaped article with a solution of a fibrinolytic enzyme so as to fix the enzyme to the copolymer wherein the hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with the fibronolytic enzyme and the enzyme is fixed to the polymer through covalent bonding, said reactive functional group being selected from the group consisting of an isocyanate group, an epoxy group, a formyl group, an acid chloride group, a carboxylic acid anhydride group and the reactive functional group having been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer having an amino group with a polyfunctional reagent, selected from the group consisting of a polyisocyanate, a polyepoxide, a polyaldehyde, a polyacid chloride and a polycarboxylic acid anhydride, having at least two of the reactive functional groups capable of reacting with an amino group, and the fibrinolytic enzyme is fixed to the polymer through covalent bonding, wherein said amino group has been introduced: (A) by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal; or (B) by first treating the hydrolyzed ethylenevinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 11
Dependent Claim
21 words
The process of claim 8, wherein the reactive functional group is an isocyanate group and the polyfunctional reagent is a polyisocyanate.
Claim 12
Dependent Claim
21 words
The process of claim 8, wherein the reactive functional group is an epoxy group and the polyfunctional reagent is a polyepoxide.
Claim 13
Dependent Claim
25 words
The process of claim 8, wherein the reactive functional group is a carboxylic acid anhydride group and the polyfunctional reagent is a polycarboxylic acid anhydride.
Claim 14
Dependent Claim
21 words
The process of claim 8, wherein the reactive functional group is a formyl group and the polyfunctional reagent is a polyaldehyde.
Claim 15
Dependent Claim
23 words
The process of claim 8, wherein the reactive functional group is an acid chloride group and the polyfunctional reagent is a polyacid chloride.
Claim 16
Dependent Claim
280 words
An antithrombogenic hydrolyzed ethylenevinyl acetate copolymer article, comprising: a shaped article of a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene, to the surface of which is fixed a fibrinolytic enzyme, wherein the hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with said fibrinolytic enzyme and said enzyme is fixed to the polymer through covalent bonding, said reactive functional group being selected from the group consisting of: (A) an isocyanate group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyisocyanate, (B) an epoxy group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyepoxide, (C) a formyl group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyaldehyde, (D) an acid chloride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an acid chloride, (E) a carboxylic acid anhydride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polycarboxylic acid anhydride, (F) an amino group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal, and (G) an amino group which has been introduced thereinto by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with both a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 17
Dependent Claim
280 words
An antithrombogenic hydrolyzed ethylenevinyl acetate copolymer article, comprising: a shaped article of a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene, to the surface of which is fixed a fibrinolytic enzyme, wherein the hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with said fibrinolytic enzyme and said enzyme is fixed to the polymer through covalent bonding, said reactive functional group being selected from the group consisting of: (A) an isocyanate group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyisocyanate, (B) an epoxy group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyepoxide, (C) a formyl group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyaldehyde, (D) an acid chloride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an acid chloride, (E) a carboxylic acid anhydride group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with a polycarboxylic acid anhydride, (F) an amino group which has been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal, and (G) an amino group which has been introduced thereinto by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with both a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 18
Dependent Claim
11 words
The article of claim 14, wherein said article is a tube.
Claim 19
Dependent Claim
12 words
The article of claim 15, wherein said tube is a surgical drain.
Claim 20
Dependent Claim
12 words
The article of claim 15, wherein said tube is an intravenous catheter.
Claim 21
Dependent Claim
14 words
The article of claim 14 wherein said shaped article is formed by extrusion molding.
Claim 22
Dependent Claim
13 words
The article of claim 14 wherein said article is suitable for surgical use.
Claim 23
Dependent Claim
17 words
The article of claims 14, 15, 16, 17, 18 or 19, wherein said fibrinolytic enzyme is urokinase.
Claim 24
Dependent Claim
28 words
The article of claim 14 wherein a functional group having an affinity for substances in the blood which inhibit fibrinolytic enzymes is present in the polymer or hydrolyzate.
Claim 25
Dependent Claim
12 words
The article of claim 21 wherein said group is a nitrophthaloyl group.
Claim 26
Dependent Claim
273 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene having an antithrombogenic property, comprising: a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene having fixed thereto a fibrinolytic enzyme, wherein the water-insoluble hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with said fibrinolytic enzyme and said enzyme is fixed to said copolymer through covalent bonding, and said reactive functional group being selected from the group consisting of an isocyanate group, an epoxy group, a formyl group, an acid chloride group, a carboxylic acid anhydride group and the reactive functional group having been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer having an amino group with a polyfunctional reagent selected from the group consisting of a polyisocyanate, a polyepoxide, a polyaldehyde, a polyacid chloride and a polycarboxylic acid anhydride, having at least two of the reactive functional groups capable of reacting with an amino group, and the fibrinolytic enzyme is fixed to the polymer through covalent bonding, wherein said amino group has been introduced: (A) by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal; or (B) by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 27
Dependent Claim
273 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene having an antithrombogenic property, comprising: a water-insoluble hydrolyzed ethylene-vinyl acetate copolymer containing about 3 to 45 weight % vinyl acetate and about 97 to 55 weight % ethylene having fixed thereto a fibrinolytic enzyme, wherein the water-insoluble hydrolyzed ethylene-vinyl acetate copolymer contains a reactive functional group capable of forming a covalent bond with said fibrinolytic enzyme and said enzyme is fixed to said copolymer through covalent bonding, and said reactive functional group being selected from the group consisting of an isocyanate group, an epoxy group, a formyl group, an acid chloride group, a carboxylic acid anhydride group and the reactive functional group having been introduced thereinto by treating the hydrolyzed ethylene-vinyl acetate copolymer having an amino group with a polyfunctional reagent selected from the group consisting of a polyisocyanate, a polyepoxide, a polyaldehyde, a polyacid chloride and a polycarboxylic acid anhydride, having at least two of the reactive functional groups capable of reacting with an amino group, and the fibrinolytic enzyme is fixed to the polymer through covalent bonding, wherein said amino group has been introduced: (A) by treating the hydrolyzed ethylene-vinyl acetate copolymer with an amino acetal; or (B) by first treating the hydrolyzed ethylene-vinyl acetate copolymer with a polyfunctional reagent having at least two functional groups capable of reacting with a hydroxy group and amino group and then treating the copolymer with a polyamine, said polyfunctional reagent being selected from the group consisting of a polyisocyanate, a polyepoxide, a polycarboxylic acid anhydride, a polyaldehyde and a polyacid chloride.
Claim 28
Dependent Claim
14 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer of claim 23, wherein said enzyme is urokinase.
Claim 29
Dependent Claim
14 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer of claim 23, wherein said enzyme is streptokinase.
Claim 30
Dependent Claim
14 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer of claim 23, wherein said enzyme is plasmin.
Claim 31
Dependent Claim
14 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer of claim 23, wherein said enzyme is brinolase.
Claim 32
Dependent Claim
30 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer of claim 23 wherein a functional group having an affinity for substances in the blood which inhibit fibrinolytic enzymes is present in the hydrolyzate.
Claim 33
Dependent Claim
16 words
A water-insoluble hydrolyzed ethylene-vinyl acetate copolymer of claim 28 wherein said group is a nitrophthaloyl group.
References Cited (Backward Citations)
US3616229A
Cited
US3625827A
Cited
US3625745A
Cited
US3673612A
Cited
US4055635A
Cited
US4273873A
Cited
US4307151A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-04-04 | 1986-10-04 | 1987-04-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-04-04 | 1990-10-04 | 1991-04-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-04-04 | 1994-10-04 | 1995-04-05 | $7700.00 | Window Closed / Lapsed |