CA1167726A - Collagenous dressing - Google Patents
Collagenous dressingInfo
- Publication number
- CA1167726A CA1167726A CA000386640A CA386640A CA1167726A CA 1167726 A CA1167726 A CA 1167726A CA 000386640 A CA000386640 A CA 000386640A CA 386640 A CA386640 A CA 386640A CA 1167726 A CA1167726 A CA 1167726A
- Authority
- CA
- Canada
- Prior art keywords
- collagen
- collagenous
- dressing
- groups
- tissue
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
- A61L15/325—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/225—Mixtures of macromolecular compounds
Abstract
ABSTRACT
A collagenous dressing which is characterized in that it contains collagen in combination with a resorbable biopolymer from the group comprising fibrinogen, gelatin modified by SH groups, collagen modified by SH groups, or regenerated oxycellulose modified by SH groups. Said col-lagenous dressing is tissue-agglutinable and does not have the disadvantages of conventional fibrin bonding in com-bination with resorbable collagen.
A collagenous dressing which is characterized in that it contains collagen in combination with a resorbable biopolymer from the group comprising fibrinogen, gelatin modified by SH groups, collagen modified by SH groups, or regenerated oxycellulose modified by SH groups. Said col-lagenous dressing is tissue-agglutinable and does not have the disadvantages of conventional fibrin bonding in com-bination with resorbable collagen.
Description
i'7~
Collaqen has been u~sed in surgery for some time. It can be used in the form of sponges or fibers to control bleeding and, properly modified, is suited also to promote the healing of wounds. However, in the case of patients with defective clot-ting mechanism, or in the case of bleeding over a large area, the usual collagenous dressings are inadequate.
Attempts have therefore been made to bond collagenous ma- , terial as collagen or gelatin to tissue by the use' of ad-hesives bas~ on resorcinol-formaldehyde. While such adhe-sives are hemostatic, they are not suited for practical use because of their tissue irritation. This is true also of acrylate adhesives and their combination with collagenous dressings.
It is known that collagen in the body i5 crosslinked with con-stituents of connective tissue. In the process, collagen is crosslinked through Schiff bases and aldol condensation. It is further known that in basal membranes tissue stxength is enhanced through disulfide bridges of the basalmembrane collagen. It is also known to crosslink proteins such as albumin with intermolecular disulfide bonds through disul-fide bridges after mild reduction followed by oxidation.
In injuries, blood clotting forrns a primary closure of the wound. This is due to aggregated thrombocytes and a fibrin network during the end phase of the plasmatic coagulation. It is also known that individual fibrin molecules are cross-linked through transglutaminase. In the process, new peptide bonds are ~ormed between glutamic acid and lysinbetween ad-jzcent chains. Through the technique of fibrin bonding, in other words, the use of fibrinogen and thromhin, the end phas0 of plasmatic blood clotting is imitated.
Fibrin bonding alone cannot control bleeding over a large area. This becomes possible only through a combination '' ' ~
~ :,a~
of Eibrin boncl:ing and R resorbable collagenous dressing.
~lowever, three components must be kept in readiness: The collagenous dressing, thrombin solution with antifibrino-lytic agents , ancl a deep-frozen highly concentrated fibri-nogen solution ready for use only after thawing. Since bleeding frequently occurs suddenly~and unexpectedly, the fibrinogen component of the three components is often not . s available at the critical moment in a form ready for use since at least the deep-frozen fibrinogerl solution must first be thawed. Moreover;, mixing prior to application is relatively complica-ted.
The objec-t of the invention is to providc a collagenous dressing which will conglutinate with the tissue and which does not have the known drawbacks of fibrin bonding in com bination with resorbable collagen. Coupled with this object is an improvement to collagenous dressings for local hemo-stasis.
This object is accomplished through a tissue-agglutinable collagenous dressing which is characterized in that it con tains collagen in combination with a resorbable biopolymer from the group comprising fibrinogen, gelatin modified by SH groups, collagen modified by SH groups, or oxycellulose modified by SH groups.
Collagen and fibrinogen or the gelatin modified by SH groups, similarly modified collagen or similarly modified oxycellulose may advantageously be combined with each other through freeze dr~ing. However, in the case of a combination of collagen and collagen modified by SH groups it is also possible to intro-; duce SH groups into the collagen.
The invention will now be described with reference to a combi nation of collagen and fibrinogen; however, fibrinogen here takes the place of said resorbable biopolymers, namely, gelatin modiEied by SH groups, collagen modi~ied by SH groups, or o~ycellulose modified by SH groups.
- The occasional occurrence of hepatitis poses a problem in the application of fibrinogen, Of course, this problem can be avoided altogether by introducing, not fibrin-ogen but other biopolymers containing reactive SH groups.
Such biopolymers containing SH groups are gelatin modi~ied by SH groups, regenerated oxycellulose modiEied by SH groups, or collagen modified by SH groups-The introduction o~ SI[ groups into collagen may be effected in a mflnner which per se is known, For example, the procedure set forth by Benesch & Benesch in "Proceedings of the National Academy of the United States, Washington, D, C.", vol. 44 (1958), pp. 848-853, may be followed.
However, SH groups can also be introduced into col-lagen by depositing a gelatin modified by SR groups, or a similarly ~odified regenerated oxycellulose, on collagen or mixing it therewith by means of a gradient mixer. Gelatin ` is Eormed from collagen through chemical or enzymatic decom-position and thus has the same chemical composition. Con-sequently, collagenol~s dressings provided with gelatin modi-^:
fied by SH groups essentially also have the properties of collagen along with the advantage that because of the SH
groups in these materials oxidative crosslinking is able to occur.
The- collagenous dressings in accordance T.~i th the in~
vention may incorporate active substances, in a manner which is known per se.
The collagen used as a dressing has the usual for~
of dressings, i. e " gauze, cloth, sponge, etc.
The purity of the collagen used, expressed by the nitrogen-to-hydroxyproline factor, is less than 4, and prefer~
ably les~s ~han 3. Since hydroxypro].ine occurs only in col lagen, this is a measure for the purity of the collagen.
The resorbable biopolymer is present in the tissue-agglutinable collagenous dressing in an amount ranging from 0.5 to lO mg/cm2, and preferably from 4 to 6 mg/cm2. The number of SH groups per molecule of resorbable biopol~ymer may vary over a wide range. For gelatin of an a~erage molecular weight of about 40tO00 it is about 2 to 7 and on the average about 5, and for the other resorbable blopolymers it is of the same order of magnitude.
It is known that collagen is suitable for use as a vehicle for antibiotlcs such as gentamycin. Tetracycline or other antibiotics or chemotherapeutic agents may also be worked into the collagen modified by SH groups. This is an additional effect that can be obtained with the dressings in accordance with the invention.
Preparat _n of colla~ens Fresh bovine tendons which had been freed of all pigment layers and muscular residues were homogenized, and an 2mount corresponding to lOO g dry weight was extracted for 24 hours in 3 liters of 0.05 M citrate buffer (pH 3.7) and then dialyzed for 12 hours against 1% acetic acid.
The tissue, suspended in 3 liters 1% acetic acid, was incubated for 48 hours at 15 C, with constant stirring, with pepsin in a collagen-to-pepsin ratio of 50:1.
The batch was diluted with 1% acetic acid to 5 liters and freed of undissolved tendon fragments by centri-fugation.
, '7~7~
The viscous collagen solution was dlalyzed against alkaliniz~d tap water (pH 8.0) and then vigorously centri-fuged~ The residue was again dissolved in 5 liters 1% acetlc acid and dialyzed. This procedure was repeated until the nitrogen-to-hydroxyproline factor was less than 3. After the last dialysis, a 1,5% collagen solution was prepared by means of 0.05% acetic acid, which was then used in the tests described below.
Preparation of an SH-modified gelatin, an SH colla~en, or an . . . _ . _ , . . _ _ . ~ . _ SH regenerated oxycellulose 10~0 ml of a 2% gelatin solution (a corresponding recipe applies to a 1.5% collagen solution or Lo a suspension of 50 g collagen or regenerated oxycellulose) was ~ixed at pll 7.0 with 318 mg N-acetylhomocysteinethiolactone, following which 340 mg AgN03 was added, the solution being maintained at pH 7.0 by the addition of NaOH.
. . .
After 2 hours, the pH was adjusted to 2.5 with 1N
HCl, and thiourea was added in excess. Ihe silver ions were removed by means of a cation exchanger and the solution was dialyzed under nitrogen. 1% solutions of the SH-modified gelatin and of the SH-modified collagen were then prepared for the tests described below.
The regenerated oxycellulose was dehydrated by lyo-philization.
Commercially available sterile fibrinogen in bulk was dlssolved in sterile distilled water to give a solution of 50 mg fibrinogen~ml of solution, which was used in the tests described below, . .
~ pLr~ l :
Preparation of a _ol]ag,en/fibrin~en-cont~ r~ _of about 2.5 x 5.0 cm Of a 1.5% collagen solution sterilized by irradia tion, 10 ml was introduced under aseptic conditlons into a sterile bottle having a septum and deep-froæen in a cold ~ i bath (dry ice/ethanol) ~ith mild agitation, After about two-thirds of the solution had frozen, 5 ml of a collagen/fibrin-ogen solution (collagen-to-fibrinogen ratlo, 1:1) was added and also deep-frozen until two-thirds of the solution was frazen, Following this, 5 ml of the fibrinogen solution was added, deep-frozen, and lyophilized.
EXAMPI.E 2 Preparation of a dressing_containin~col-l-a~-e-n -and SH-mo-difi-ed ~elatin Of a 1~5% collagen solution, 10 ml was introduced into a bottle ha~ing a septum and deep-frozen in a cold bath (dry ice/ethanol) with mild agitation~ After about two-thirds of the solution had frozen, 10 ml of the SH-modified gelatin solution was added, deep-frozen, and lyophilized. This sponge was then sterilized by irradiation~
Preparation of gentam ~
For the preparation of gentamycin-containing dressings, 100 mg gentamycin was added to 100 ml of a 1% col-lagen solution, and this sollltion was used as described above to prepare a collagen/fibrinogen-containing dressing and a collagen/SH-gelatin-containing dressing.
~ ~ 4 ~ t~
X~PLE 4 Preparation_of dre~ s containin~ col]a~en and fibrino~en First 100 ml of an 0.5 to 1% collagen solution was poured into a metallic mold and conventionally freeze-dried, and the sponge so produced was sterilized. This sterilized collagen sponge was then spray-coated under asepti.c condi-tions with a fibrinogen solution, from 0.5 to 10 mg ~ibrin-ogen per square centimeter of collagen surface being so de-posited. Freeze drying was then repeatcd and packaging ef-fected under sterile conditions, In the practical use of the modified tissue-agglutinable collagenous dressings in accordance with the in-vention, resorption occurs within clinically appropriate periods of time. In accordance with the invention, they can be used to dress even large-area wounds, especially in the abdominal region.
Collaqen has been u~sed in surgery for some time. It can be used in the form of sponges or fibers to control bleeding and, properly modified, is suited also to promote the healing of wounds. However, in the case of patients with defective clot-ting mechanism, or in the case of bleeding over a large area, the usual collagenous dressings are inadequate.
Attempts have therefore been made to bond collagenous ma- , terial as collagen or gelatin to tissue by the use' of ad-hesives bas~ on resorcinol-formaldehyde. While such adhe-sives are hemostatic, they are not suited for practical use because of their tissue irritation. This is true also of acrylate adhesives and their combination with collagenous dressings.
It is known that collagen in the body i5 crosslinked with con-stituents of connective tissue. In the process, collagen is crosslinked through Schiff bases and aldol condensation. It is further known that in basal membranes tissue stxength is enhanced through disulfide bridges of the basalmembrane collagen. It is also known to crosslink proteins such as albumin with intermolecular disulfide bonds through disul-fide bridges after mild reduction followed by oxidation.
In injuries, blood clotting forrns a primary closure of the wound. This is due to aggregated thrombocytes and a fibrin network during the end phase of the plasmatic coagulation. It is also known that individual fibrin molecules are cross-linked through transglutaminase. In the process, new peptide bonds are ~ormed between glutamic acid and lysinbetween ad-jzcent chains. Through the technique of fibrin bonding, in other words, the use of fibrinogen and thromhin, the end phas0 of plasmatic blood clotting is imitated.
Fibrin bonding alone cannot control bleeding over a large area. This becomes possible only through a combination '' ' ~
~ :,a~
of Eibrin boncl:ing and R resorbable collagenous dressing.
~lowever, three components must be kept in readiness: The collagenous dressing, thrombin solution with antifibrino-lytic agents , ancl a deep-frozen highly concentrated fibri-nogen solution ready for use only after thawing. Since bleeding frequently occurs suddenly~and unexpectedly, the fibrinogen component of the three components is often not . s available at the critical moment in a form ready for use since at least the deep-frozen fibrinogerl solution must first be thawed. Moreover;, mixing prior to application is relatively complica-ted.
The objec-t of the invention is to providc a collagenous dressing which will conglutinate with the tissue and which does not have the known drawbacks of fibrin bonding in com bination with resorbable collagen. Coupled with this object is an improvement to collagenous dressings for local hemo-stasis.
This object is accomplished through a tissue-agglutinable collagenous dressing which is characterized in that it con tains collagen in combination with a resorbable biopolymer from the group comprising fibrinogen, gelatin modified by SH groups, collagen modified by SH groups, or oxycellulose modified by SH groups.
Collagen and fibrinogen or the gelatin modified by SH groups, similarly modified collagen or similarly modified oxycellulose may advantageously be combined with each other through freeze dr~ing. However, in the case of a combination of collagen and collagen modified by SH groups it is also possible to intro-; duce SH groups into the collagen.
The invention will now be described with reference to a combi nation of collagen and fibrinogen; however, fibrinogen here takes the place of said resorbable biopolymers, namely, gelatin modiEied by SH groups, collagen modi~ied by SH groups, or o~ycellulose modified by SH groups.
- The occasional occurrence of hepatitis poses a problem in the application of fibrinogen, Of course, this problem can be avoided altogether by introducing, not fibrin-ogen but other biopolymers containing reactive SH groups.
Such biopolymers containing SH groups are gelatin modi~ied by SH groups, regenerated oxycellulose modiEied by SH groups, or collagen modified by SH groups-The introduction o~ SI[ groups into collagen may be effected in a mflnner which per se is known, For example, the procedure set forth by Benesch & Benesch in "Proceedings of the National Academy of the United States, Washington, D, C.", vol. 44 (1958), pp. 848-853, may be followed.
However, SH groups can also be introduced into col-lagen by depositing a gelatin modified by SR groups, or a similarly ~odified regenerated oxycellulose, on collagen or mixing it therewith by means of a gradient mixer. Gelatin ` is Eormed from collagen through chemical or enzymatic decom-position and thus has the same chemical composition. Con-sequently, collagenol~s dressings provided with gelatin modi-^:
fied by SH groups essentially also have the properties of collagen along with the advantage that because of the SH
groups in these materials oxidative crosslinking is able to occur.
The- collagenous dressings in accordance T.~i th the in~
vention may incorporate active substances, in a manner which is known per se.
The collagen used as a dressing has the usual for~
of dressings, i. e " gauze, cloth, sponge, etc.
The purity of the collagen used, expressed by the nitrogen-to-hydroxyproline factor, is less than 4, and prefer~
ably les~s ~han 3. Since hydroxypro].ine occurs only in col lagen, this is a measure for the purity of the collagen.
The resorbable biopolymer is present in the tissue-agglutinable collagenous dressing in an amount ranging from 0.5 to lO mg/cm2, and preferably from 4 to 6 mg/cm2. The number of SH groups per molecule of resorbable biopol~ymer may vary over a wide range. For gelatin of an a~erage molecular weight of about 40tO00 it is about 2 to 7 and on the average about 5, and for the other resorbable blopolymers it is of the same order of magnitude.
It is known that collagen is suitable for use as a vehicle for antibiotlcs such as gentamycin. Tetracycline or other antibiotics or chemotherapeutic agents may also be worked into the collagen modified by SH groups. This is an additional effect that can be obtained with the dressings in accordance with the invention.
Preparat _n of colla~ens Fresh bovine tendons which had been freed of all pigment layers and muscular residues were homogenized, and an 2mount corresponding to lOO g dry weight was extracted for 24 hours in 3 liters of 0.05 M citrate buffer (pH 3.7) and then dialyzed for 12 hours against 1% acetic acid.
The tissue, suspended in 3 liters 1% acetic acid, was incubated for 48 hours at 15 C, with constant stirring, with pepsin in a collagen-to-pepsin ratio of 50:1.
The batch was diluted with 1% acetic acid to 5 liters and freed of undissolved tendon fragments by centri-fugation.
, '7~7~
The viscous collagen solution was dlalyzed against alkaliniz~d tap water (pH 8.0) and then vigorously centri-fuged~ The residue was again dissolved in 5 liters 1% acetlc acid and dialyzed. This procedure was repeated until the nitrogen-to-hydroxyproline factor was less than 3. After the last dialysis, a 1,5% collagen solution was prepared by means of 0.05% acetic acid, which was then used in the tests described below.
Preparation of an SH-modified gelatin, an SH colla~en, or an . . . _ . _ , . . _ _ . ~ . _ SH regenerated oxycellulose 10~0 ml of a 2% gelatin solution (a corresponding recipe applies to a 1.5% collagen solution or Lo a suspension of 50 g collagen or regenerated oxycellulose) was ~ixed at pll 7.0 with 318 mg N-acetylhomocysteinethiolactone, following which 340 mg AgN03 was added, the solution being maintained at pH 7.0 by the addition of NaOH.
. . .
After 2 hours, the pH was adjusted to 2.5 with 1N
HCl, and thiourea was added in excess. Ihe silver ions were removed by means of a cation exchanger and the solution was dialyzed under nitrogen. 1% solutions of the SH-modified gelatin and of the SH-modified collagen were then prepared for the tests described below.
The regenerated oxycellulose was dehydrated by lyo-philization.
Commercially available sterile fibrinogen in bulk was dlssolved in sterile distilled water to give a solution of 50 mg fibrinogen~ml of solution, which was used in the tests described below, . .
~ pLr~ l :
Preparation of a _ol]ag,en/fibrin~en-cont~ r~ _of about 2.5 x 5.0 cm Of a 1.5% collagen solution sterilized by irradia tion, 10 ml was introduced under aseptic conditlons into a sterile bottle having a septum and deep-froæen in a cold ~ i bath (dry ice/ethanol) ~ith mild agitation, After about two-thirds of the solution had frozen, 5 ml of a collagen/fibrin-ogen solution (collagen-to-fibrinogen ratlo, 1:1) was added and also deep-frozen until two-thirds of the solution was frazen, Following this, 5 ml of the fibrinogen solution was added, deep-frozen, and lyophilized.
EXAMPI.E 2 Preparation of a dressing_containin~col-l-a~-e-n -and SH-mo-difi-ed ~elatin Of a 1~5% collagen solution, 10 ml was introduced into a bottle ha~ing a septum and deep-frozen in a cold bath (dry ice/ethanol) with mild agitation~ After about two-thirds of the solution had frozen, 10 ml of the SH-modified gelatin solution was added, deep-frozen, and lyophilized. This sponge was then sterilized by irradiation~
Preparation of gentam ~
For the preparation of gentamycin-containing dressings, 100 mg gentamycin was added to 100 ml of a 1% col-lagen solution, and this sollltion was used as described above to prepare a collagen/fibrinogen-containing dressing and a collagen/SH-gelatin-containing dressing.
~ ~ 4 ~ t~
X~PLE 4 Preparation_of dre~ s containin~ col]a~en and fibrino~en First 100 ml of an 0.5 to 1% collagen solution was poured into a metallic mold and conventionally freeze-dried, and the sponge so produced was sterilized. This sterilized collagen sponge was then spray-coated under asepti.c condi-tions with a fibrinogen solution, from 0.5 to 10 mg ~ibrin-ogen per square centimeter of collagen surface being so de-posited. Freeze drying was then repeatcd and packaging ef-fected under sterile conditions, In the practical use of the modified tissue-agglutinable collagenous dressings in accordance with the in-vention, resorption occurs within clinically appropriate periods of time. In accordance with the invention, they can be used to dress even large-area wounds, especially in the abdominal region.
Claims (7)
1. A tissue-agglutinable collagenous dressing, comprising collagen present in combination with a re-sorbable biopolymer from the group consisting of fibrinogen, gelatin modified by SH groups, collagen modified by SH groups, and regenerated oxycellulose modified by SH groups; and wherein the purity of the collagen, expressed by the nitrogen-to-hydroxyproline factor, is less than 4.
2. A tissue-agglutinable collagenous dressing according to claim 1, further comprising a medicinally active agent.
3. A tissue-agglutinable collagenous dressing according to claim 2, wherein the medicinally active agent is an antibiotic.
4. A tissue-agglutinable collagenous dressing, according to claim 3, wherein the antibiotic is gentamycin.
5. A tissue-agglutinable collagenous dressing, according to claims 1, 2 or 3, wherein the collagen is present in the form of a cloth.
6. A tissue-agglutinable collagenous dressing, according to claims 1, 2 or 3, wherein the collagen is present in the form of a sponge.
7. A tissue-agglutinable collagenous dressing according to claim 1, wherein the purity of the collagen, expressed by the nitrogen-to-hydroxyproline factor, is less than 3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3037513A DE3037513C2 (en) | 1980-10-03 | 1980-10-03 | Collagen wound dressing |
| DEP3037513.4 | 1980-10-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1167726A true CA1167726A (en) | 1984-05-22 |
Family
ID=6113582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000386640A Expired CA1167726A (en) | 1980-10-03 | 1981-09-25 | Collagenous dressing |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US4407787A (en) |
| EP (1) | EP0049469B2 (en) |
| JP (1) | JPS5841559A (en) |
| AT (1) | ATE5373T1 (en) |
| CA (1) | CA1167726A (en) |
| DE (2) | DE3037513C2 (en) |
| HK (1) | HK53486A (en) |
Families Citing this family (86)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3212412C2 (en) * | 1982-04-02 | 1986-01-02 | Dr. Ruhland Nachf. GmbH, 8425 Neustadt | Tissue-bondable collagen wound dressing |
| DE3214337C2 (en) * | 1982-04-19 | 1984-04-26 | Serapharm - Michael Stroetmann, 4400 Münster | Resorbable flat material for sealing and healing wounds and processes for their manufacture |
| DE3409372A1 (en) * | 1984-03-14 | 1985-09-19 | Dr. Ruhland Nachf. GmbH, 8425 Neustadt | Material for the vitalisation of implant surfaces |
| USRE35748E (en) * | 1984-05-29 | 1998-03-17 | Matrix Pharmaceutical, Inc. | Treatments employing drug containing matrices for introduction into cellular lesion areas |
| US4619913A (en) * | 1984-05-29 | 1986-10-28 | Matrix Pharmaceuticals, Inc. | Treatments employing drug-containing matrices for introduction into cellular lesion areas |
| US4738849A (en) * | 1984-06-28 | 1988-04-19 | Interface Biomedical Laboratories Corp. | Composite medical articles for application to wounds and method for producing same |
| US4606910A (en) * | 1984-06-28 | 1986-08-19 | Interface Biomedical Laboratories | Composite hemostatic article including a hemostatic agent onlay and methods for preparing the same |
| US4563350A (en) * | 1984-10-24 | 1986-01-07 | Collagen Corporation | Inductive collagen based bone repair preparations |
| JPS61253065A (en) * | 1985-05-02 | 1986-11-10 | 片倉チツカリン株式会社 | Medical composite material of chitosan derivative and collagen and its production |
| JPS63502354A (en) * | 1986-01-06 | 1988-09-08 | ザ ユニヴァーシティ オブ メルボルン | collagen products |
| CA1294546C (en) * | 1986-04-23 | 1992-01-21 | John S. Sundsmo | Wound healing composition containing collagen |
| WO1987007153A1 (en) * | 1986-05-29 | 1987-12-03 | Interface Biomedical Laboratories Corporation | Composite hemostatic article including a hemostatic agent onlay and methods for preparing the same |
| WO1988006043A1 (en) * | 1987-02-12 | 1988-08-25 | The University Of Melbourne | Precipitation of collagen in tactoid form |
| US4961707A (en) * | 1987-12-22 | 1990-10-09 | University Of Florida | Guided periodontal tissue regeneration |
| US5284756A (en) * | 1988-10-11 | 1994-02-08 | Lynn Grinna | Heterodimeric osteogenic factor |
| US5700479A (en) * | 1988-12-23 | 1997-12-23 | Guidor Ab | Surgical element and method for selective tissue regeneration |
| JP2805086B2 (en) * | 1989-06-20 | 1998-09-30 | グンゼ株式会社 | Filler for living tissue |
| US4994277A (en) * | 1989-10-31 | 1991-02-19 | Pfizer Hospital Products Group, Inc. | Use of xanthan gum for preventing adhesions |
| US6197325B1 (en) | 1990-11-27 | 2001-03-06 | The American National Red Cross | Supplemented and unsupplemented tissue sealants, methods of their production and use |
| US6117425A (en) | 1990-11-27 | 2000-09-12 | The American National Red Cross | Supplemented and unsupplemented tissue sealants, method of their production and use |
| US6559119B1 (en) | 1990-11-27 | 2003-05-06 | Loyola University Of Chicago | Method of preparing a tissue sealant-treated biomedical material |
| US7196054B1 (en) | 1990-11-27 | 2007-03-27 | The American National Red Cross | Methods for treating wound tissue and forming a supplemented fibrin matrix |
| US6054122A (en) | 1990-11-27 | 2000-04-25 | The American National Red Cross | Supplemented and unsupplemented tissue sealants, methods of their production and use |
| US5219895A (en) * | 1991-01-29 | 1993-06-15 | Autogenesis Technologies, Inc. | Collagen-based adhesives and sealants and methods of preparation and use thereof |
| US5192312A (en) * | 1991-03-05 | 1993-03-09 | Colorado State University Research Foundation | Treated tissue for implantation and methods of treatment and use |
| FR2692582B1 (en) * | 1992-06-18 | 1998-09-18 | Flamel Tech Sa | NEW CROSSLINKABLE DERIVATIVES OF COLLAGEN, THEIR PROCESS FOR OBTAINING IT AND THEIR APPLICATION TO THE PREPARATION OF BIOMATERIALS. |
| FR2699184B1 (en) * | 1992-12-16 | 1995-03-10 | Flamel Tech Sa | New collagen derivatives, their process for obtaining and their application to the preparation of biomaterials. |
| US5330974A (en) * | 1993-03-01 | 1994-07-19 | Fibratek, Inc. | Therapeutic fibrinogen compositions |
| US5383896A (en) * | 1993-05-25 | 1995-01-24 | Gershony; Gary | Vascular sealing device |
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-
1980
- 1980-10-03 DE DE3037513A patent/DE3037513C2/en not_active Expired
-
1981
- 1981-09-21 US US06/303,851 patent/US4407787A/en not_active Expired - Lifetime
- 1981-09-25 CA CA000386640A patent/CA1167726A/en not_active Expired
- 1981-09-30 EP EP81107775A patent/EP0049469B2/en not_active Expired
- 1981-09-30 DE DE8181107775T patent/DE3161508D1/en not_active Expired
- 1981-09-30 AT AT81107775T patent/ATE5373T1/en not_active IP Right Cessation
- 1981-10-02 JP JP56156320A patent/JPS5841559A/en active Granted
-
1986
- 1986-07-17 HK HK534/86A patent/HK53486A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE3037513C2 (en) | 1983-05-05 |
| ATE5373T1 (en) | 1983-12-15 |
| DE3161508D1 (en) | 1983-12-29 |
| US4407787A (en) | 1983-10-04 |
| EP0049469B2 (en) | 1988-10-26 |
| JPS5841559A (en) | 1983-03-10 |
| EP0049469A1 (en) | 1982-04-14 |
| DE3037513A1 (en) | 1982-04-15 |
| JPH0135664B2 (en) | 1989-07-26 |
| HK53486A (en) | 1986-07-25 |
| EP0049469B1 (en) | 1983-11-23 |
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