CA1249490A - Vascular graft - Google Patents
Vascular graftInfo
- Publication number
- CA1249490A CA1249490A CA000493462A CA493462A CA1249490A CA 1249490 A CA1249490 A CA 1249490A CA 000493462 A CA000493462 A CA 000493462A CA 493462 A CA493462 A CA 493462A CA 1249490 A CA1249490 A CA 1249490A
- Authority
- CA
- Canada
- Prior art keywords
- gelatin
- amino groups
- treated
- cause
- vascular graft
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S623/00—Prosthesis, i.e. artificial body members, parts thereof, or aids and accessories therefor
- Y10S623/92—Method or apparatus for preparing or treating prosthetic
- Y10S623/921—Blood vessel
Abstract
ABSTRACT
A method of producing a vascular graft comprises impregnating a tube of flexible porous material with gelatinous material which contains a gelatin with has been treated to cause it to con-tain a predetermined number of amino groups less than that normally present in untreated gelatin then treating the impregnated tube to cause the amino groups to form cross links with one another.
The gelatin may be treated by reacting it with the anhydride or the chloride of a polycarboxylic acid.
A method of producing a vascular graft comprises impregnating a tube of flexible porous material with gelatinous material which contains a gelatin with has been treated to cause it to con-tain a predetermined number of amino groups less than that normally present in untreated gelatin then treating the impregnated tube to cause the amino groups to form cross links with one another.
The gelatin may be treated by reacting it with the anhydride or the chloride of a polycarboxylic acid.
Description
~9~9~
yAs~uLAB-GR9FT
Th;s invention relates to artificial vascular grafts used to take the place of at least sections of blood vessels in human and animal bodies. It is an object of the present invention to provide a vascular graft which has important advantages over known artificial grafts.
Artificial grafts must have or acquire some degree of permeability after implantation so that tissue ingrowth can take place. The commercially 10 acceptable manufacturing processes usually employed at present produce grafts which while meeting satis-factorily the other necessary characteristics have such a high degree of porosity that the seepage of blood through the grafts initially at least ;s 15 unacceptably high.
To reduce this initial high rate of seepage of blood it has been the custom to impregnate grafts prior to implantation with blood usually obtained from the prospective recipient. This operation 20 has the ef-fect of causiny enough pre-clotting of blood on the graft to reduce -the initial escape of blood through the wall of the graft to an acceptable level while leaving the permeability sufficient to allow the commencement and continuation of tissue 25 growth into the grafts.
With the described method of pre--impreg-nation there is still present the difficulty that pre-impregnat;on is time-consuming, ;t requ;res the use of some of the blood of the prospective recipient 3û 3nd there is little or no control over the rate of the necessary break down of the -fibrin in the ;mpregnating blood. There is also an added 9~
-- i2~ 0 diff;cuLty where the prospective recipient suffers from a blood coaguLation defect.
Attempts have been made to produce grafts wh;ch can be implanted in a substantially ;mpermeable dry state and wh;ch immed;ately after ;mplantation beg;n to become permeable. Such proposals have taken the form of impregnating porous tubular structures with such mat,erials as gelatin, collagen or albumin.
A gelatin impregnated graft is not porous but when 10 exposed to water the gelatin degrades by hydrolysis the rate at which hydrolysis proceeds being higher at the body temperature of 37C than it is at normal temperature. As such grafts normally become progress-;vely more porous at a rate too fast to keep pace 15 with clott;ng and t;ssue growth ;t has been proposed to treat the gelat;n ;n such a way as to cause cross l;nks to form between the amino groups present in the gelat;n molecules~ Such cross linking renders the gelatin more resistant to hydrolysis and thus 20 reduces considerably the rate at which the permeability of the graft increases. One method of init;ating cross link;ng compr;ses expos;ng the gelat;n to formaldehyde~ The difficulty here ;s ;n controlling the number of cross links formed and thus the rate 25 of increase of poros;ty and heretofore there has been no sure method of prov;d;ng a graft wh;ch would become progress;vely more porous at a predetermined rate. All that could be done was to expose the gelatin to the cross l;nking agent for a time bel;eved 30 to prov;de the desired amount of cross linking and then to remove the cross l;nking agent. The known method ;s actually an art rather than a science and the behaviour of the grafts produced is unpredict-able and ;nconsistent.
The present invention relates to a graft which requires no pre-impregnation with blood and which after implantation starts to degrade and become permeable at an accurately known rate. It is ts be understood that ac~ording to the medical circumstances of different implan-tations the porosity of -the implanted grafts should increase at a rate only sufficient to avoid haemorrhage occurring. The process of the invention permits such a degree of control of the rate of porosity increase.
The invention pro~ldes a m2thod of producing a vascular graft by impregnating a tube of flexible porous material with gelatinous material then treating the impregnated tube to cause only the amino groups always present in the molecules of gelatinous material to form cross lin}~s in which there is included in the gelatinous material a gelatin which has been treated to cause it to contain a predetermined number of amino groups less than that normally present in untreated gelatin.
In another aspect, the invention provides a method of producing a vascular graft which after implantation becomes per-meable at a predictable rate comprising ascertaining the propor-tion of amino groups present in a particular sample of untreated gelatin, treating a first quantity of gelatin taken from said sample to cause a predetermined proportion of the amino groups in said first quantity of gelatin to be converted to other groups whereby to cause the proportion of amino groups present in said first quantity of gelatin to be reduced to a predetermined pro-portion, mixing a further quantity of untreated gelatin taken from ~ ~
~, '3~90 - 3a - 25455-12 sald sample and a quantity of said treated gelatin in a predeter-mined proportion to produce a gelatinous mixture having a predetermined proportion of amino groups, impregnating a tube of flexible porous material with said gelatinous mixture, and treating the impregnated tube to cause the amino groups present in the gelatinous mixture to form cross links with one another.
It is an easy matter to ascertain the number o~ amino groups present in any particular sam~le of gelatin the other main ionic groups being hydroxyl, carboxyl and arginine groups. ~ow-ever it may be said here that the number o~ amino groups present in untreated gelatin normally constitutes around 3.5% of all groups present, see The Science and Technology of Gelatin published by Academic Press, 1977, particularly page 94.
For manu~acturing reasons it is sometimes convenientto have all the treated gelatin intended to be used for grafts with different porosity characteristics treated to the same extent, for example 75%, ~' ~2~
i.e. 75% of all the amino groups originally present are converted to other groups, the rate of porosity change being then controlled by mixing the treated gelatin containing the known proportion of converted amino groups with a gelatin not so treated in a predetermined proportion.
The treatment to reduce the number of amino groups only in a gelatin may comprise reacting the gelatin with the anhydride or the chlor`ide of a 10 polycarboxylic acid. A suitable polycarboxylic acid ;s succ;nic ac;d COOHCH2CH2COOH. The treatment is accurately controllable so that it is possible to produce a treated gelatin in which a predetermined proportion of the amino groups originally occurr;ng 15 in the gelatin has been converted to groups of other types. An example of a gelatin mixture found to be satisfactory in particular c;rcumstances conta;ns a gelatin treated to convert 75% of the amino groups to carboxyl groups.
A plasticizing agent may be included ;r-the mixture of treated and untreated gelatin.
Materials capable of causing the formation of cross links between the amino groups only in a gelatin are aldehydes such as formaldehyde or 25 gluteraldehyde or a mixture of formaldehyde and gluteraldehyde in predetermined proportions; Ihe cross l;nk;ng treatment may be a two part treatment in which the impregnated graft is treated first with formaldehyde and then with gluteraldehyde.
As a final step the graft may be ster;lized purely as an additional precaution. Such a sterilizing step is not strictly speaking necessary since the formaldehyde treatment is a steril;zing treatment in itself.
The treatment causes at least some of the amino groups on each gelatin molecule to be converted to other groups on the gelatin molecule, particularly hydroxyl and carboxyl groups. Since the treatment can be performed to prov;de accurately known proportions of amino and other groups on each molecule of gelatin and -the proport;on of other groups to amino groups is known within close limits in ordinary untreated 10 gelatin, by treating the impregnating gelatin to a predetermined percentage of amino group conversion or choosing particular proportions for a mixture containing gelatin treated to a known percentage amino group conversion and untreated gelatin it 15 is possible to know exactly how many amino groups are present in relation to the other groups. Since it is only the amino groups which become cross linked the degree of cross linking can be accurately determined since when the gelatin mixture is exposed to the 20 cross linking medium, irrespective of how long such exposure takes place cross linking can only take place up to the extent of the number of amino groups present since the other groups will not cross link.
It is the number of cross links which determines 25 the rate at which degradation of the gelatin takes place because it is through the breaking of the cross links that the gelatin becomes permeable.
In the cross linking operation the amino groups which cross link form cross links with other amino 30 groups on the same molecule and on other molecules ~hether of treated or untreated gelatin.
When the graft is implanted the aqueous constituent of the recipient's blood causes hydrolysis of the gelatin mixture to start~ causing the gelatin to swell giving increased access o-f the water to the cross links which start to rupture under the hydroL;zing action. A low degree oF cross linking resulting from a high percentage of amino group conversion provides a high degree of swelling and quicker rupture under the hydrolizing action whereas a high degree of cross linking causes less swelling and a smaller rate of rupture of the cross links.
Thus the time taken for the cross links to be destroyed 10 is readily predetermined according to the percentage of amino group conversion whether using only a treated gelatin alone or a mixture of a treated gelatin and an untreated gelatin.
Further control of the rate of degradation 15 can be effected by the proportion of formaldehyde or gluteraldehyde used in the cross linking treatment.
Cross links Formed by the action of formaldehyde are more readily broken than those Formed by gluter-aldehyde. A high proportion of gluteraldehyde to 20 formaldehyde used in the treatment process provides a graft ;n which degradation starts to take place a comparatively long time after implantation of the graft.
The control of the rate of degradation 25 also provides an improved effect in gelatin coatings intended to promote other biological actions. It is known that gelatin contains binding sites for fibronectins. Fibronectin is a protein associated with the adhesion of cells to substrates and collagen-30based materials have been used for example as burndressings to encourage the adhesion and growth of epithelial cells.
3(;~
A tube formed as a knitted structure of textile material was impregnated under vacuum with a mixture of a gelatin which had been treated with the chloride of succinic acid to cause 75% of the amino groups present to be converted to other groups and a normal gelatin not so treated in the proportion 50% treated to 50% untreated gelatin, the temperature at which impregnation took place was 65 C. The 10 gelatin mixture was allowed to gel and the tube was then subjected to a treatment with a 20% solution of formaldehyde at pH4 and 4C -for a period of 16 hours.
The formed vascular graft was then washed 15 in five changes of pyrogen-free water at room temp-erature.
A graft produced according to the example described became fully porous in 25 - 30 hours under laboratory test conditions.
EX9MPLE_2 A graft was prepared as described in Example 1 except that 75% treated gelatin, i.e. gela-tin which had 75% of its amino groups converted to other groups, was used without admixture with untreated 25 gelatin. This graft became fully porous in 5 -8 hours under laboratory test conditions.
For purposes of comparison grafts were prepared using untreated gela~in only and these were found to ~ecome fully porous in a time exceeding 30 45 hours under the same laboratory test conditions.
yAs~uLAB-GR9FT
Th;s invention relates to artificial vascular grafts used to take the place of at least sections of blood vessels in human and animal bodies. It is an object of the present invention to provide a vascular graft which has important advantages over known artificial grafts.
Artificial grafts must have or acquire some degree of permeability after implantation so that tissue ingrowth can take place. The commercially 10 acceptable manufacturing processes usually employed at present produce grafts which while meeting satis-factorily the other necessary characteristics have such a high degree of porosity that the seepage of blood through the grafts initially at least ;s 15 unacceptably high.
To reduce this initial high rate of seepage of blood it has been the custom to impregnate grafts prior to implantation with blood usually obtained from the prospective recipient. This operation 20 has the ef-fect of causiny enough pre-clotting of blood on the graft to reduce -the initial escape of blood through the wall of the graft to an acceptable level while leaving the permeability sufficient to allow the commencement and continuation of tissue 25 growth into the grafts.
With the described method of pre--impreg-nation there is still present the difficulty that pre-impregnat;on is time-consuming, ;t requ;res the use of some of the blood of the prospective recipient 3û 3nd there is little or no control over the rate of the necessary break down of the -fibrin in the ;mpregnating blood. There is also an added 9~
-- i2~ 0 diff;cuLty where the prospective recipient suffers from a blood coaguLation defect.
Attempts have been made to produce grafts wh;ch can be implanted in a substantially ;mpermeable dry state and wh;ch immed;ately after ;mplantation beg;n to become permeable. Such proposals have taken the form of impregnating porous tubular structures with such mat,erials as gelatin, collagen or albumin.
A gelatin impregnated graft is not porous but when 10 exposed to water the gelatin degrades by hydrolysis the rate at which hydrolysis proceeds being higher at the body temperature of 37C than it is at normal temperature. As such grafts normally become progress-;vely more porous at a rate too fast to keep pace 15 with clott;ng and t;ssue growth ;t has been proposed to treat the gelat;n ;n such a way as to cause cross l;nks to form between the amino groups present in the gelat;n molecules~ Such cross linking renders the gelatin more resistant to hydrolysis and thus 20 reduces considerably the rate at which the permeability of the graft increases. One method of init;ating cross link;ng compr;ses expos;ng the gelat;n to formaldehyde~ The difficulty here ;s ;n controlling the number of cross links formed and thus the rate 25 of increase of poros;ty and heretofore there has been no sure method of prov;d;ng a graft wh;ch would become progress;vely more porous at a predetermined rate. All that could be done was to expose the gelatin to the cross l;nking agent for a time bel;eved 30 to prov;de the desired amount of cross linking and then to remove the cross l;nking agent. The known method ;s actually an art rather than a science and the behaviour of the grafts produced is unpredict-able and ;nconsistent.
The present invention relates to a graft which requires no pre-impregnation with blood and which after implantation starts to degrade and become permeable at an accurately known rate. It is ts be understood that ac~ording to the medical circumstances of different implan-tations the porosity of -the implanted grafts should increase at a rate only sufficient to avoid haemorrhage occurring. The process of the invention permits such a degree of control of the rate of porosity increase.
The invention pro~ldes a m2thod of producing a vascular graft by impregnating a tube of flexible porous material with gelatinous material then treating the impregnated tube to cause only the amino groups always present in the molecules of gelatinous material to form cross lin}~s in which there is included in the gelatinous material a gelatin which has been treated to cause it to contain a predetermined number of amino groups less than that normally present in untreated gelatin.
In another aspect, the invention provides a method of producing a vascular graft which after implantation becomes per-meable at a predictable rate comprising ascertaining the propor-tion of amino groups present in a particular sample of untreated gelatin, treating a first quantity of gelatin taken from said sample to cause a predetermined proportion of the amino groups in said first quantity of gelatin to be converted to other groups whereby to cause the proportion of amino groups present in said first quantity of gelatin to be reduced to a predetermined pro-portion, mixing a further quantity of untreated gelatin taken from ~ ~
~, '3~90 - 3a - 25455-12 sald sample and a quantity of said treated gelatin in a predeter-mined proportion to produce a gelatinous mixture having a predetermined proportion of amino groups, impregnating a tube of flexible porous material with said gelatinous mixture, and treating the impregnated tube to cause the amino groups present in the gelatinous mixture to form cross links with one another.
It is an easy matter to ascertain the number o~ amino groups present in any particular sam~le of gelatin the other main ionic groups being hydroxyl, carboxyl and arginine groups. ~ow-ever it may be said here that the number o~ amino groups present in untreated gelatin normally constitutes around 3.5% of all groups present, see The Science and Technology of Gelatin published by Academic Press, 1977, particularly page 94.
For manu~acturing reasons it is sometimes convenientto have all the treated gelatin intended to be used for grafts with different porosity characteristics treated to the same extent, for example 75%, ~' ~2~
i.e. 75% of all the amino groups originally present are converted to other groups, the rate of porosity change being then controlled by mixing the treated gelatin containing the known proportion of converted amino groups with a gelatin not so treated in a predetermined proportion.
The treatment to reduce the number of amino groups only in a gelatin may comprise reacting the gelatin with the anhydride or the chlor`ide of a 10 polycarboxylic acid. A suitable polycarboxylic acid ;s succ;nic ac;d COOHCH2CH2COOH. The treatment is accurately controllable so that it is possible to produce a treated gelatin in which a predetermined proportion of the amino groups originally occurr;ng 15 in the gelatin has been converted to groups of other types. An example of a gelatin mixture found to be satisfactory in particular c;rcumstances conta;ns a gelatin treated to convert 75% of the amino groups to carboxyl groups.
A plasticizing agent may be included ;r-the mixture of treated and untreated gelatin.
Materials capable of causing the formation of cross links between the amino groups only in a gelatin are aldehydes such as formaldehyde or 25 gluteraldehyde or a mixture of formaldehyde and gluteraldehyde in predetermined proportions; Ihe cross l;nk;ng treatment may be a two part treatment in which the impregnated graft is treated first with formaldehyde and then with gluteraldehyde.
As a final step the graft may be ster;lized purely as an additional precaution. Such a sterilizing step is not strictly speaking necessary since the formaldehyde treatment is a steril;zing treatment in itself.
The treatment causes at least some of the amino groups on each gelatin molecule to be converted to other groups on the gelatin molecule, particularly hydroxyl and carboxyl groups. Since the treatment can be performed to prov;de accurately known proportions of amino and other groups on each molecule of gelatin and -the proport;on of other groups to amino groups is known within close limits in ordinary untreated 10 gelatin, by treating the impregnating gelatin to a predetermined percentage of amino group conversion or choosing particular proportions for a mixture containing gelatin treated to a known percentage amino group conversion and untreated gelatin it 15 is possible to know exactly how many amino groups are present in relation to the other groups. Since it is only the amino groups which become cross linked the degree of cross linking can be accurately determined since when the gelatin mixture is exposed to the 20 cross linking medium, irrespective of how long such exposure takes place cross linking can only take place up to the extent of the number of amino groups present since the other groups will not cross link.
It is the number of cross links which determines 25 the rate at which degradation of the gelatin takes place because it is through the breaking of the cross links that the gelatin becomes permeable.
In the cross linking operation the amino groups which cross link form cross links with other amino 30 groups on the same molecule and on other molecules ~hether of treated or untreated gelatin.
When the graft is implanted the aqueous constituent of the recipient's blood causes hydrolysis of the gelatin mixture to start~ causing the gelatin to swell giving increased access o-f the water to the cross links which start to rupture under the hydroL;zing action. A low degree oF cross linking resulting from a high percentage of amino group conversion provides a high degree of swelling and quicker rupture under the hydrolizing action whereas a high degree of cross linking causes less swelling and a smaller rate of rupture of the cross links.
Thus the time taken for the cross links to be destroyed 10 is readily predetermined according to the percentage of amino group conversion whether using only a treated gelatin alone or a mixture of a treated gelatin and an untreated gelatin.
Further control of the rate of degradation 15 can be effected by the proportion of formaldehyde or gluteraldehyde used in the cross linking treatment.
Cross links Formed by the action of formaldehyde are more readily broken than those Formed by gluter-aldehyde. A high proportion of gluteraldehyde to 20 formaldehyde used in the treatment process provides a graft ;n which degradation starts to take place a comparatively long time after implantation of the graft.
The control of the rate of degradation 25 also provides an improved effect in gelatin coatings intended to promote other biological actions. It is known that gelatin contains binding sites for fibronectins. Fibronectin is a protein associated with the adhesion of cells to substrates and collagen-30based materials have been used for example as burndressings to encourage the adhesion and growth of epithelial cells.
3(;~
A tube formed as a knitted structure of textile material was impregnated under vacuum with a mixture of a gelatin which had been treated with the chloride of succinic acid to cause 75% of the amino groups present to be converted to other groups and a normal gelatin not so treated in the proportion 50% treated to 50% untreated gelatin, the temperature at which impregnation took place was 65 C. The 10 gelatin mixture was allowed to gel and the tube was then subjected to a treatment with a 20% solution of formaldehyde at pH4 and 4C -for a period of 16 hours.
The formed vascular graft was then washed 15 in five changes of pyrogen-free water at room temp-erature.
A graft produced according to the example described became fully porous in 25 - 30 hours under laboratory test conditions.
EX9MPLE_2 A graft was prepared as described in Example 1 except that 75% treated gelatin, i.e. gela-tin which had 75% of its amino groups converted to other groups, was used without admixture with untreated 25 gelatin. This graft became fully porous in 5 -8 hours under laboratory test conditions.
For purposes of comparison grafts were prepared using untreated gela~in only and these were found to ~ecome fully porous in a time exceeding 30 45 hours under the same laboratory test conditions.
Claims (10)
1. A method of producing a vascular graft by impregnating a tube of flexible porous material with gelatinous material then treating the impregnated tube to cause only the amino groups always present in the molecules of gelatinous material to form cross links in which there is included in the gelatinous material a gelatin which has been treated to cause it to contain a predetermined number of amino groups less than that normally present in untreated gelatin.
2. A method of producing a vascular graft as claimed in claim 1 in which the gelatinous material comprises a mixture of gelatin treated to contain the predetermined number of amino groups and untreated gelatin, the two gelatins being present in the mixture in a predetermined proportion one to the other.
3. A method of producing a vascular graft as claimed in claim 1 in which the treated gelatin is treated by reacting it with the anhydride or the chloride of a polycarboxylic acid.
4. A method of producing a vascular graft as claimed in claim 3 in which the polycarboxylic acid is succinic acid COOHCH2CH2COOH.
5. A method of producing a vascular graft as claimed in claim 1 in which the gelatinous material contains a gelatin which has been previously treated to cause 75% of the amino groups originally in the gelatin before treatment to be converted to carboxyl groups.
6. A method of producing a vascular graft as claimed in claim 1 in which the gelatinous material is treated with at least one aldehyde to cause the formation of cross links in the amino groups.
7. A method of producing a vascular graft as claimed in claim 6 in which the cross linking treatment is a two part treatment comprising treating the impregnated tube first with formaldehyde and then with gluteraldehyde.
8. A vascular graft produced by impregnating a tube of flexible porous material with gelatinous material then treating the impregnated tube to cause only the amino groups always present in the molecules of gelatinous material to form cross links in which the gelatinous material includes a gelatin which has been previously treated to cause it to contain a predetermined number of amino groups less than that normally present in untreated gelatin.
9. A method of producing a vascular graft which after implantation becomes permeable at a predictable rate comprising ascertaining the proportion of amino groups present in a particular sample of untreated gelatin, treating a first quantity of gelatin taken from said sample to cause a predetermined proportion of the amino groups in said first quantity of gelatin to be converted to other groups whereby to cause the proportion of amino groups present in said first quantity of gelatin to be reduced to a predetermined proportion, mixing a further quantity of untreated gelatin taken from said sample and a quantity of said treated gelatin in a predetermined proportion to produce a gelatinous mixture having a predetermined proportion of amino groups, impregnating a tube of flexible porous material with said gelatinous mixture, and treating the impregnated tube to cause the amino groups present in the gelatinous mixture to form cross links with one another.
10. A method of producing a vascular graft as claimed in claim 9 in which said first quantity of gelatin is treated to cause 75% of the amino groups originally in the gelatin before treatment to be converted to carboxyl groups.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848430265A GB8430265D0 (en) | 1984-11-30 | 1984-11-30 | Vascular graft |
| GB8430265 | 1984-11-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1249490A true CA1249490A (en) | 1989-01-31 |
Family
ID=10570504
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000493462A Expired CA1249490A (en) | 1984-11-30 | 1985-10-21 | Vascular graft |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4747848A (en) |
| EP (1) | EP0183365B1 (en) |
| JP (1) | JPS61135651A (en) |
| AT (1) | ATE83911T1 (en) |
| AU (1) | AU569645B2 (en) |
| CA (1) | CA1249490A (en) |
| DE (1) | DE3586941T2 (en) |
| DK (1) | DK172304B1 (en) |
| ES (1) | ES8801577A1 (en) |
| GB (1) | GB8430265D0 (en) |
| GR (1) | GR852872B (en) |
| IE (1) | IE59421B1 (en) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3608158A1 (en) * | 1986-03-12 | 1987-09-17 | Braun Melsungen Ag | VESSELED PROSTHESIS IMPREGNATED WITH CROSSLINED GELATINE AND METHOD FOR THE PRODUCTION THEREOF |
| CH670759A5 (en) * | 1986-06-02 | 1989-07-14 | Sulzer Ag | |
| CH670760A5 (en) * | 1986-06-02 | 1989-07-14 | Sulzer Ag | |
| US5447966A (en) * | 1988-07-19 | 1995-09-05 | United States Surgical Corporation | Treating bioabsorbable surgical articles by coating with glycerine, polalkyleneoxide block copolymer and gelatin |
| RU2007969C1 (en) * | 1990-03-26 | 1994-02-28 | Виктор Владимирович Кешелава | Prosthesis for substitution of tubular organs |
| US5413601A (en) * | 1990-03-26 | 1995-05-09 | Keshelava; Viktor V. | Tubular organ prosthesis |
| US5120833A (en) * | 1991-03-15 | 1992-06-09 | Alexander Kaplan | Method of producing grafts |
| DE69229312T2 (en) * | 1991-03-29 | 1999-11-04 | Vascular Graft Research Center | ARTIFICIAL BLOOD VESSEL FROM COMPOSITE MATERIAL |
| US5605938A (en) * | 1991-05-31 | 1997-02-25 | Gliatech, Inc. | Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate |
| US5705178A (en) * | 1991-05-31 | 1998-01-06 | Gliatech, Inc. | Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers |
| US5584875A (en) * | 1991-12-20 | 1996-12-17 | C. R. Bard, Inc. | Method for making vascular grafts |
| DE69434422T2 (en) * | 1993-11-30 | 2006-04-20 | Canon K.K. | Method and apparatus for encryption / decryption based on the Montgomery method using efficient modular multiplication |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US3106483A (en) * | 1961-07-27 | 1963-10-08 | Us Catheter & Instr Corp | Synthetic blood vessel grafts |
| CH472219A (en) * | 1963-06-15 | 1969-05-15 | Spofa Vereinigte Pharma Werke | Highly porous collagen tissue blood vessel prosthesis and method for producing the same |
| US4167045A (en) * | 1977-08-26 | 1979-09-11 | Interface Biomedical Laboratories Corp. | Cardiac and vascular prostheses |
| AU529411B2 (en) * | 1980-07-01 | 1983-06-02 | Wilkracht Pty. Ltd. | Vascular prosthesis |
| EP0124659A1 (en) * | 1983-04-13 | 1984-11-14 | Koken Co. Ltd. | Medical material |
| EP0141004B1 (en) * | 1983-10-20 | 1988-01-07 | Oscobal Ag | Bone substitute material based on natural bone |
-
1984
- 1984-11-30 GB GB848430265A patent/GB8430265D0/en active Pending
-
1985
- 1985-10-10 IE IE250185A patent/IE59421B1/en not_active IP Right Cessation
- 1985-10-10 AT AT85307255T patent/ATE83911T1/en not_active IP Right Cessation
- 1985-10-10 EP EP85307255A patent/EP0183365B1/en not_active Expired - Lifetime
- 1985-10-10 DE DE8585307255T patent/DE3586941T2/en not_active Expired - Fee Related
- 1985-10-17 US US06/788,718 patent/US4747848A/en not_active Expired - Lifetime
- 1985-10-21 CA CA000493462A patent/CA1249490A/en not_active Expired
- 1985-10-23 ES ES548138A patent/ES8801577A1/en not_active Expired
- 1985-11-28 DK DK551185A patent/DK172304B1/en not_active IP Right Cessation
- 1985-11-29 JP JP60267619A patent/JPS61135651A/en active Granted
- 1985-11-29 GR GR852872A patent/GR852872B/el unknown
- 1985-11-29 AU AU50593/85A patent/AU569645B2/en not_active Ceased
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|---|---|
| ATE83911T1 (en) | 1993-01-15 |
| GB8430265D0 (en) | 1985-01-09 |
| US4747848A (en) | 1988-05-31 |
| DE3586941D1 (en) | 1993-02-11 |
| EP0183365A2 (en) | 1986-06-04 |
| DK551185A (en) | 1986-05-31 |
| AU569645B2 (en) | 1988-02-11 |
| EP0183365B1 (en) | 1992-12-30 |
| IE852501L (en) | 1986-05-30 |
| JPS61135651A (en) | 1986-06-23 |
| DE3586941T2 (en) | 1993-04-29 |
| DK172304B1 (en) | 1998-03-09 |
| GR852872B (en) | 1986-04-03 |
| ES8801577A1 (en) | 1988-02-16 |
| EP0183365A3 (en) | 1988-04-06 |
| ES548138A0 (en) | 1988-02-16 |
| JPH0211258B2 (en) | 1990-03-13 |
| IE59421B1 (en) | 1994-02-23 |
| AU5059385A (en) | 1986-06-05 |
| DK551185D0 (en) | 1985-11-28 |
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