US6074663A — Method of using cross-linked fibrin material

Claim 1

Independent Claim 111 words

A method of using a self-supporting film material of cross-linked fibrin for the preparation of a medicament for the prevention of adhesion formation as a post-operative complication, comprising the step of applying the film material of cross-linked fibrin to an injured surface, wherein the film material of cross-linked fibrin is prepared by the steps comprising: (a) converting fibrinogen to fibrin using a thrombin-containing solution having a concentration of at least 20 IU/ml; (b) converting the fibrinogen such that the conversion to fibrin is substantially complete in that there is essentially no unreacted fibrinogen in the fibrin material; and (c) forming a fibrin material having a pore size of below 5 μm.

Claim 2

Independent Claim 111 words

A method of using a self-supporting film material of cross-linked fibrin for the preparation of a medicament for the prevention of adhesion formation as a post-operative complication, comprising the step of applying the film material of cross-linked fibrin to an injured surface, wherein the film material of cross-linked fibrin is prepared by the steps comprising: (a) converting fibrinogen to fibrin using a thrombin-containing solution having a concentration of at least 20 IU/ml; (b) converting the fibrinogen such that the conversion to fibrin is substantially complete in that there is essentially no unreacted fibrinogen in the fibrin material; and (c) forming a fibrin material having a pore size of below 5 μm.

Claim 3

Dependent Claim 12 words

The method of claim 1, wherein the cross-linked fibrin material is non-haemostatic.

Claim 4

Dependent Claim 17 words

The method of claim 1, further comprising the step of separating the injured surface from another surface.

Claim 5

Dependent Claim 17 words

The method of claim 1, wherein the fibrin material is used in combination with a fibrin glue.

Claim 6

Dependent Claim 18 words

The method of claim 4, wherein the fibrin glue is used for the treatment of the injured surface.

Claim 7

Dependent Claim 64 words

The method of claim 5, wherein the fibrin glue applied to the injured surface has been made by mixing a fibrinogen-containing solution having a factor XIII content of 10-40 IU/ml with an equal volume of a thrombin-containing solution comprising 1-300 IU/ml thrombin, and calcium; said fibrinogen-containing solution being a protein solution with a content of 90-140 mg protein/ml comprising up to 90% clottable protein.

Claim 8

Dependent Claim 28 words

The method of claim 5, wherein the fibrin glue is allowed to set undisturbed on the surface applied to until the conversion of fibrinogen to fibrin is complete.

Claim 9

Dependent Claim 14 words

The method of claim 1, wherein said fibrin material has a regular pore size.

Claim 10

Dependent Claim 21 words

The method of claim 1, wherein the fibrin material in the wet state has a thickness of at least 20 μm.

Claim 11

Dependent Claim 28 words

The method of claim 1, wherein the fibrin material further comprises at least one additive selected from the group consisting of antibiotics, fibrinolytic agents and biological response modifiers.

Claim 12

Dependent Claim 92 words

A process of preparing a self-supporting film material of cross-linked fibrin, said process comprising the steps of: a. simultaneously mixing a stream of a first, fibrinogen-containing solution with a stream of a second, thrombin-containing solution having a concentration of at least 20 IU/ml; b. applying the obtained mixture to a solid support; c. incubating the mixture until the conversion of fibrinogen to fibrin is substantially complete such that there is essentially no unreacted fibrinogen in the fibrin material; and d. forming a fibrin material having a pore size of below 5 μm.

Claim 13

Dependent Claim 92 words

A process of preparing a self-supporting film material of cross-linked fibrin, said process comprising the steps of: a. simultaneously mixing a stream of a first, fibrinogen-containing solution with a stream of a second, thrombin-containing solution having a concentration of at least 20 IU/ml; b. applying the obtained mixture to a solid support; c. incubating the mixture until the conversion of fibrinogen to fibrin is substantially complete such that there is essentially no unreacted fibrinogen in the fibrin material; and d. forming a fibrin material having a pore size of below 5 μm.

Claim 14

Dependent Claim 19 words

The process of claim 11, wherein in step (a) equal volumes of the first and second solution are mixed.

Claim 15

Dependent Claim 18 words

The process of claim 11, wherein the mixing in step (a) is performed using a dual syringe device.

Claim 16

Dependent Claim 60 words

The process of claim 11, wherein the first, fibrinogen-containing solution has a factor XIII content of 10-40 IU/ml, and the second, thrombin-containing solution has a thrombin content of 20-300 IU/ml, and a calcium content of up to 45 mM, said first fibrinogen-containing solution being a protein solution with a content of 90-140 mg protein/ml comprising up to 90% clottable protein.

Claim 17

Dependent Claim 30 words

The process of claim 11, wherein at least one additive selected from the group consisting of antibiotics, fibrinolytic agents and biological response modifiers is added to the second, thrombin-containing solution.

Claim 18

Dependent Claim 12 words

The process of claim 11 wherein an autologous first solution is used.

Claim 19

Dependent Claim 16 words

The process of claim 11, wherein step (c) is performed at 37° C. for 1-200 min.

Claim 20

Dependent Claim 125 words

A process of preparing a self-supporting film material of cross-linked fibrin, said process comprising the steps of: a. applying a first, aqueous, fibrinogen-containing solution having a factor XIII content of 10-40 IU/ml and a protein content of 90-140 mg protein/ml comprising up to 90% clottable protein to a solid support; b. removing water until dryness, forming a sheet-like fibrinogen material; c. applying to the sheet-like fibrinogen material a second, thrombin-containing solution having a thrombin content of 20-300 IU/ml and a calcium content of up to 45 ml; and d. incubating until the conversion of fibrinogen to fibrin is substantially complete such that there is essentially no unreacted fibrinogen in the fibrin material to form said fibrin material having a pore size of below 5 μm.

Claim 21

Dependent Claim 125 words

A process of preparing a self-supporting film material of cross-linked fibrin, said process comprising the steps of: a. applying a first, aqueous, fibrinogen-containing solution having a factor XIII content of 10-40 IU/ml and a protein content of 90-140 mg protein/ml comprising up to 90% clottable protein to a solid support; b. removing water until dryness, forming a sheet-like fibrinogen material; c. applying to the sheet-like fibrinogen material a second, thrombin-containing solution having a thrombin content of 20-300 IU/ml and a calcium content of up to 45 ml; and d. incubating until the conversion of fibrinogen to fibrin is substantially complete such that there is essentially no unreacted fibrinogen in the fibrin material to form said fibrin material having a pore size of below 5 μm.

Claim 22

Dependent Claim 22 words

The process of claim 18, wherein in steps (a) and (c) equal volumes of the first and the second solutions are used.

Claim 23

Dependent Claim 32 words

The process of claim 18 wherein in step (b) water removal is performed by a process selected from the group consisting of air-drying, freeze-drying, and drying under increased temperature and reduced pressure.

Claim 24

Dependent Claim 21 words

The process of claim 18, wherein step (d) comprises incubating at 37° C. for about 20 min. to about 200 min.

Claim 25

Dependent Claim 108 words

The process of using a first fibrin glue acting as a haemostatic agent in combination with a second fibrin glue acting as a bio-mechanical barrier for the preparation of a medicament for the prevention of adhesion formation as a post-operative complication, wherein the second fibrin glue is prepared by the steps comprising: (a) converting fibrinogen to fibrin using a thrombin-containing solution having a concentration of at least 20 IU/ml; (b) converting the fibrinogen such that the conversion to fibrin is substantially complete in that there is essentially no unreacted fibrinogen in the fibrin material; and (c) forming a fibrin material having a pore size of below 5 μm.

Claim 26

Dependent Claim 108 words

The process of using a first fibrin glue acting as a haemostatic agent in combination with a second fibrin glue acting as a bio-mechanical barrier for the preparation of a medicament for the prevention of adhesion formation as a post-operative complication, wherein the second fibrin glue is prepared by the steps comprising: (a) converting fibrinogen to fibrin using a thrombin-containing solution having a concentration of at least 20 IU/ml; (b) converting the fibrinogen such that the conversion to fibrin is substantially complete in that there is essentially no unreacted fibrinogen in the fibrin material; and (c) forming a fibrin material having a pore size of below 5 μm.

Claim 27

Dependent Claim 19 words

The process of claim 22, wherein the first and second fibrin glues are applied to a lesion in sequence.

Claim 28

Dependent Claim 31 words

The process of claim 22, further comprising the steps of applying the first fibrin glue to the lesion, allowing the first fibrin glue to set, and applying the second fibrin glue.

Claim 29

Dependent Claim 83 words

The process of claim 22 wherein the first fibrin glue has been made by mixing a fibrinogen-containing solution having a factor XIII content of 10-40 IU/ml and a protein content of 90-140 mg protein/ml comprising up to 90% clottable protein with an equal volume of a thrombin-containing solution comprising less than 1000 IU/ml thrombin and the second fibrin glue has been made by mixing said fibrinogen-containing solution with an equal volume of a thrombin-containing solution comprising at least 50 IU/ml thrombin and calcium.

Claim 30

Dependent Claim 11 words

The process of claim 22 wherein a double coating is obtained.

Claim 31

Dependent Claim 17 words

The method of claim 1, further comprising the step of isolating an injured surface from another surface.

Claim 32

Dependent Claim 22 words

The method of claim 1 comprising the further step of forming a fibrin material having a pore size of below 1 μm.

Claim 33

Dependent Claim 19 words

The method of claim 1 wherein the fibrin material in a wet state has a thickness of 20-2000 μm.

Claim 34

Dependent Claim 19 words

The method of claim 1 wherein the fibrin material in a wet state has a thickness of 5000 μm.

Claim 35

Dependent Claim 13 words

The method of claim 4 wherein the fibrin glue is used for haemostatis.

Claim 36

Dependent Claim 15 words

The method of claim 6 wherein the thrombin-containing solution comprises at least 20 IU/ml thrombin.

Claim 37

Dependent Claim 15 words

The method of claim 6 wherein the thrombin-containing solution comprises at least 100 IU/ml thrombin.

Claim 38

Dependent Claim 22 words

The method of claim 10 wherein the biological response modifier is selected from the group consisting of cytokines and wound repair promoters.

Claim 39

Dependent Claim 16 words

The process of claim 11 wherein the mixing step (a) is performed using a spray device.

Claim 40

Dependent Claim 12 words

The process of claim 11 wherein an autologous second solution is used.

Claim 41

Dependent Claim 14 words

The process of claim 11 wherein an autologous first and second solution are used.

Claim 42

Dependent Claim 17 words

The process of claim 11 wherein the fibrin material has a pore size of below 1 μm.

Claim 43

Dependent Claim 19 words

The process of claim 14 wherein the thrombin-containing solution comprises a thrombin content of more than 300 IU/ml thrombin.

Claim 44

Dependent Claim 22 words

The process of claim 15 wherein the biological response modifier is selected from the group consisting of cytokines and wound repair promoters.

Claim 45

Dependent Claim 17 words

The process of claim 18 wherein the fibrin material has a pore size of below 1 μm.

Claim 46

Dependent Claim 12 words

The process of claim 18 wherein the first fibrogen solution is autologous.

Claim 47

Dependent Claim 28 words

The process of claim 18 wherein the second thrombin-containing solution further comprises disinfectants or drugs selected from the group consisting of antibiotics, fibrinolytic agents and biological response modifiers.

Claim 48

Dependent Claim 22 words

The process of claim 43 wherein the biological response modifiers are selected from the group consisting of cytokines and wound repair promoters.

Claim 49

Dependent Claim 12 words

The process of claim 18 wherein the second thrombin-containing solution is autologous.

Claim 50

Dependent Claim 14 words

The process of claim 18 wherein an autologous first and second solution are used.

Claim 51

Dependent Claim 21 words

The process of claim 18 wherein the second thrombin containing solution has a thrombin content of more than 300 IU/ml thrombin.

Claim 52

Dependent Claim 18 words

The process of claim 21 wherein step (d) further comprises incubation at 37° C. for about 120 minutes.

Claim 53

Dependent Claim 20 words

The process of claim 25 wherein the thrombin-containing solution of the first fibrin glue comprises less that 150 IU/ml thrombin.

Claim 54

Dependent Claim 20 words

The process of claim 25 wherein the second fibrin glue comprises a thrombin-containing solution comprising at least 150 IU/ml thrombin.

Claim 55

Dependent Claim 20 words

The process of claim 25 wherein the second fibrin glue comprises a thrombin-containing solution comprising at least 300 IU/ml thrombin.

Claim 56

Dependent Claim 11 words

The process of claim 25 wherein the fibrinogen-containing solution is autologous.

Claim 57

Dependent Claim 11 words

The process of claim 25 wherein the thrombin-containing solution is autologous.

Claim 58

Dependent Claim 15 words

The process of claim 25 wherein the fibrinogen-containing solution and the thrombin-containing solution are autologous.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2003-06-13	2003-12-13	2004-06-13	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2007-06-13	2007-12-13	2008-06-13	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2011-06-13	2011-12-13	2012-06-13	$7700.00	Window Closed / Lapsed

Method of using cross-linked fibrin material

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