US5141747A — Denatured collagen membrane

Claim 1

Independent Claim 64 words

An artificial membrane comprising a product made by cross-linking molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or combination thereof on the coupler wherein non-coupled lysine epsilon amino groups are bonded to a modifier wherein the modifier is selective from the group consisting of a carbonyl, sulfonyl, carbamoyl, or β-malic acid group.

Claim 2

Dependent Claim 64 words

An artificial membrane comprising a product made by cross-linking molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or combination thereof on the coupler wherein non-coupled lysine epsilon amino groups are bonded to a modifier wherein the modifier is selective from the group consisting of a carbonyl, sulfonyl, carbamoyl, or β-malic acid group.

Claim 3

Dependent Claim 36 words

The membrane of claim 1 wherein cross-linking is effected by reacting the molecules with a polyfunctional amine reactive agent selected from the group consisting of a carboxylic acid halide, sulfonyl halide, anhydride, reactive ester, and aldehyde.

Claim 4

Dependent Claim 16 words

The membrane of claim 1 wherein cross-linking is effected by exposing the molecules to actinic radiation.

Claim 5

Dependent Claim 16 words

The membrane of claim 1 wherein cross-linking is effected by dehydrating a gel containing the molecules.

Claim 6

Dependent Claim 24 words

The membrane of claim 1 wherein cross-linking is effected by dehydrating a gel containing the molecules and exposing the dehydrated molecules to actinic radiation.

Claim 7

Dependent Claim 65 words

The membrane of claim 1 wherein the coupler comprises the carbonyl groups, sulfonyl groups, or combination thereof bonded together through an organic radical wherein the organic radical is a C 2-20 saturated or unsaturated aliphatic, aromatic, or aliphatic-aromatic group that is substituted or unsubstituted with halogen or C 1-4 alkyl, alkoxy, or carboxy and has 0-5 heteroatoms wherein the heteroatom is oxygen, sulfur, or nitrogen.

Claim 8

Dependent Claim 24 words

The membrane of claim i wherein the coupler has the formula --CO--CH 2 --CH 2 --CO-- or --CO--CH 2 --CH 2 --CH 2 --CO--.

Claim 9

Dependent Claim 66 words

The membrane of claim 1 wherein the modifier has the formula RCO--, RNHCO--, RSO 2 --, or COOR'CHOHCH(COOR')-- wherein R is a C 2-20 saturated or unsaturated aliphatic, aromatic, or aliphatic-aromatic group that is substituted or unsubstituted with halogen or C 1-4 alkyl, alkoxy, or carboxy and has 0-5 heteroatoms wherein the heteroatom is oxygen, sulfur, or nitrogen and R' is H, Na, K, or Li.

Claim 10

Dependent Claim 12 words

The membrane of claim 8 wherein the modifier has the formula R--NH--CO--.

Claim 11

Dependent Claim 18 words

The membrane of claim 1 wherein the modifier has the formula CH 3 (CH 2 ) 3 --NH--CO--.

Claim 12

Dependent Claim 30 words

The membrane of claim 1 wherein the modifier has the formula CH 3 (CH 2 ) 3 --NH--CO-- and the coupler has the formula --CO-- CH 2 --CH 2 --CO--.

Claim 13

Dependent Claim 27 words

The membrane of claim 1 wherein the molecules were denatured by heating in aqueous media to a temperature between about 40° and 120° C. and thereafter cooling.

Claim 14

Dependent Claim 35 words

An artificial membrane comprising a product made by cross-linking molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or combination thereof on the coupler.

Claim 15

Dependent Claim 35 words

An artificial membrane comprising a product made by cross-linking molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or combination thereof on the coupler.

Claim 16

Dependent Claim 36 words

The membrane of claim 13 wherein cross-linking is effected by reacting the molecules with a polyfunctional amine reactive agent selected from the group consisting of a carboxylic acid halide, sulfonyl halide, anhydride, aldehyde, and reactive ester.

Claim 17

Dependent Claim 16 words

The membrane of claim 13 wherein cross-linking is effected by exposing the molecules to actinic radiation.

Claim 18

Dependent Claim 13 words

The membrane of claim 13 wherein cross-linking is effected by dehydrating the molecules.

Claim 19

Dependent Claim 20 words

The membrane of claim 13 wherein cross-linking is effected by dehydrating the molecules and exposing the molecules to actinic radiation.

Claim 20

Dependent Claim 22 words

The membrane of claim 13 wherein the coupler is --CO--CH 2 --CH 2 --CO-- or --CO--CH 2 --CH 2 --CH 2 --CO--.

Claim 21

Dependent Claim 27 words

The membrane of claim 13 wherein the molecules were denatured by heating in aqueous media to a temperature between about 40° and 120° C. and thereafter cooling.

Claim 22

Independent Claim 101 words

A method for making an artificial membrane comprising the steps of: a) reacting native collagen molecules with a polyfunctional amine-reactive agent selected from the group consisting of a carboxylic acid halide, sulfonyl halide, anhydride, and reactive ester in aqueous media at a pH greater than about 8 and at a temperature between 0° and 35° C. to form coupled collagen molecules; b) heating the coupled collagen molecules at a temperature between about 40° and 120° C. to denature the collagen; c) purifying the coupled collagen molecules; and d) cooling and forming the denatured and coupled collagen molecules into a membranous gel.

Claim 23

Independent Claim 101 words

A method for making an artificial membrane comprising the steps of: a) reacting native collagen molecules with a polyfunctional amine-reactive agent selected from the group consisting of a carboxylic acid halide, sulfonyl halide, anhydride, and reactive ester in aqueous media at a pH greater than about 8 and at a temperature between 0° and 35° C. to form coupled collagen molecules; b) heating the coupled collagen molecules at a temperature between about 40° and 120° C. to denature the collagen; c) purifying the coupled collagen molecules; and d) cooling and forming the denatured and coupled collagen molecules into a membranous gel.

Claim 24

Dependent Claim 19 words

The method of claim 20 further comprising the step of sufficiently dehydrating the gel to cross-link the collagen molecules.

Claim 25

Dependent Claim 42 words

The method of claim 20 further comprising the step of reacting the collagen molecules with a polyfunctional amine-reactive agent selected from the group consisting of a carboxylic acid halide, sulfonyl halide, anhydride, and reactive ester after dehydration and subsequently purifying the product.

Claim 26

Dependent Claim 22 words

The method of claim 20 further comprising the step of exposing the gel to sufficient actinic radiation to cross-link the collagen molecules.

Claim 27

Dependent Claim 29 words

The method of claim 20 further comprising the steps of dehydrating the gel followed by exposing the collagen molecules to sufficient actinic radiation to further cross-link the collagen molecules.

Claim 28

Dependent Claim 23 words

The method of claim 20 wherein the weight ratio of poly-functional amine-reactive agent to native collagen molecules is between about 1:100 and 6:1.

Claim 29

Dependent Claim 19 words

The method of claim 20 wherein the poly-functional amine reactive agent is succinic acid dichloride or glutaric acid dichloride.

Claim 30

Dependent Claim 60 words

The method of claim 20 further comprising the step of reacting the native collagen molecules with a mono-functional amine reactive agent selected from the group consisting of an anhydride, acid halide, sulfonyl halide, active ester, isocyanate, and epoxy succinic acid in aqueous media at a pH greater than about 8 and at a temperature between about 0° and 35° C.

Claim 31

Dependent Claim 19 words

The method of claim 27 further comprising the step of sufficiently dehydrating the gel to cross-link the collagen molecules.

Claim 32

Dependent Claim 43 words

The method of claim 28 further comprising the step of reacting the collagen molecules with a polyfunctional amine-reactive agent selected from the group consisting of a carboxylic acid halide, sulfonyl halide, anhydride, and reactive active ester after dehydration and subsequently purifying the product.

Claim 33

Dependent Claim 22 words

The method of claim 27 further comprising the step of exposing the gel to sufficient actinic radiation to cross-link the collagen molecules

Claim 34

Dependent Claim 29 words

The method of claim 27 further comprising the steps of dehydrating the gel followed by exposing the collagen molecules to sufficient actinic radiation to further cross-link the collagen molecules.

Claim 35

Dependent Claim 13 words

The method of claim 27 wherein the mono-functional amine reactive agent is n-butylisocyanate.

Claim 36

Dependent Claim 14 words

The method of claim 27 wherein the mono-functional amine reactive agent is epoxysuccinic acid.

Claim 37

Dependent Claim 23 words

The method of claim 27 wherein the weight ratio of mono-functional amine-reactive agent to native collagen molecules is between about 1:100 and 10:1.

Claim 38

Dependent Claim 58 words

A composition comprising molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or combination thereof on the coupler wherein non-cross-linked lysine epsilon amino groups are bonded to a modifier wherein the modifier is selective from the group consisting of a carbonyl, sulfonyl, carbamoyl, or β-malic acid group.

Claim 39

Dependent Claim 58 words

A composition comprising molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or combination thereof on the coupler wherein non-cross-linked lysine epsilon amino groups are bonded to a modifier wherein the modifier is selective from the group consisting of a carbonyl, sulfonyl, carbamoyl, or β-malic acid group.

Claim 40

Dependent Claim 29 words

A composition comprising molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or mixture thereof on the coupler.

Claim 41

Dependent Claim 29 words

A composition comprising molecules of interpenetrating denatured collagen coupled at their lysine epsilon amino groups with a coupler through carbonyl groups, sulfonyl groups, or mixture thereof on the coupler.

Claim 42

Dependent Claim 34 words

In a method for repairing the tympanic membrane of a mammal comprising surgically applying an artificial membrane over the tympanic membrane the improvement wherein the artificial membrane comprises the artificial membrane of claim 1.

Claim 43

Dependent Claim 34 words

In a method for repairing the tympanic membrane of a mammal comprising surgically applying an artificial membrane over the tympanic membrane the improvement wherein the artificial membrane comprises the artificial membrane of claim 13.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1995-08-25	1996-02-24	1996-08-25	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1999-08-25	2000-02-24	2000-08-25	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2003-08-25	2004-02-24	2004-08-25	$7700.00	Window Closed / Lapsed

Denatured collagen membrane

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