CA1283505C - Vessel prosthesis impregnated with crosslinked gelatin and processfor the production thereof - Google Patents
Vessel prosthesis impregnated with crosslinked gelatin and processfor the production thereofInfo
- Publication number
- CA1283505C CA1283505C CA000531723A CA531723A CA1283505C CA 1283505 C CA1283505 C CA 1283505C CA 000531723 A CA000531723 A CA 000531723A CA 531723 A CA531723 A CA 531723A CA 1283505 C CA1283505 C CA 1283505C
- Authority
- CA
- Canada
- Prior art keywords
- gelatin
- vessel prosthesis
- weight
- impregnating
- solution
- 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 - Lifetime
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
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- 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
-
- 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
- Y10S128/00—Surgery
- Y10S128/08—Collagen
-
- 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
- Y10S623/901—Method of manufacturing prosthetic device
-
- 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
-
- 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
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31551—Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
- Y10T428/31565—Next to polyester [polyethylene terephthalate, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
- Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
- Manufacturing Of Magnetic Record Carriers (AREA)
- Manufacture Of Macromolecular Shaped Articles (AREA)
- Polymerisation Methods In General (AREA)
- Facsimile Transmission Control (AREA)
Abstract
The invention relates to vessel prostheses formed from a porous basic body and an impregnating coating of crosslinked gelatin for sealing the pores. Crosslinking takes place accompanied by the use of a diisocyanate. The impregnating coating has good mechanical and physiological properties.
Description
~L2 ~33~3~
VESSEL PROSTHESIS IMPREGNATED WITH CROSSLINKED G_LATIN AND
PROCESS FOR THE PRODUCTION THEREOF
The present invention relates to a vessel prosthesis which is in itself porous, but is sealed by impregnating with crosslinked gelatin and to a process for the production thereof.
Yessel prosthesis for replacing hollow organs in humans and animals and in particular blood vessels have long been known. They are generally made from textile material and in particular a knitted fabric (DE-A2-26 13 575, DE-A2-20 09 349 and DE-Al-24 61 370). However, they can also be made from non-textile materials (EP-Al-O 106 49~ and GB Al-15 06 432). In general, the vessel prostheses are porous, so as to permit a growing in of the tissue for obtaining conditions which are as natural as possible. However, since after the implantation of tlle prosthesis, these pores frequently lead to undesirably high body fluid losses, it is desirable to seal said pores with a material resorbable by the body and which is successively replaced by the growing in tissue.
It is known from DE-A2-14 94 939 to use procollagen as the impregnating agent, which is applied to the porous prosthesis in acid solution and then rendered insoluble by increasing the pH-value.
The use of collagen for sealing is known from DE-A2-14 91 218, US-Al-41 67 045, DE-Al-35 03 127 and DE-AI-35 03 126. The crosslinking of collagen normally takes place with aldehydes, particularly formaldehyde.
It is also known to impregnate porous vessel prostheses with soluble gelatin and to crosslink the same (DE-A2-14 94 939), crosslinking taking place with the aid of thiol group-containing compounds with - ,~
' , ~ ' .
', , . " ':
..
~LZ~335~i subsequent oxidative crosslinking, accompanied by the formation of disulphide bridges.
High demands are made on the characteristics of the impregnating coating, which must adhere well to the prosthesis body, provide a good sealing thereof, be elastic and in particularlt release any harmful products during resorption. The known impregnated prostheses only partly fulfil these requirements. In addition, they are far from easy to produce, or expensive starting materials are required, which is prejudicial to industrial manufacture.
The problem of the present invention is therefore to provide an impregnated vessel prosthesis, which is easier to manufacture, has good mechanical characteristics and is completely tight, is not harmful for the receiver organism and can be easily handled particularly during implantation.
This problem is solved by a vessel prosthesis which is porous as such, but sealed by impregnating with crosslinked gelatin and which is characterized in that the gelatin is crosslinked with a diisocyanate.
Isocyanates react with the reactive nucleophilic groups of gelatin, particularly the amino groups and also the hydroxyl groups, accompanied by the formation of stable bonds and crosslinking products.
Crosslinking with diisocyanates is irreversible contrary to crosslinking with aldehydes, in which there is a state of equilibrium, so that aldehydes re-form and are released again. At the end of the reaction there are no longer any isocyanate residues and ~hey are also not re-fonmed from the crosslinking product. A gelatin crosslinked with diisocyanate forms a tight impregnation with good mechanical character-istics, so that in relation to the porosity of the vessel prosthesis ', , ' ', ' ~2~3~
little gelatin and crosslinking agent is required, but nevertheless a complete seal is obtained.
The crosslinking of biological material with diisocyanates is known per se. Thus, DE-A2-27 34 503 describes a process for producing a coliagen sponge, in which a paste or slurry of partly decomposed collagen is mixed with diisocyanate, shock-frozen to temperatures of -10 to -30C, left at temperatures below 0C, washed, subsequently treated and then dried. This gives a soft, porous foam or sponge.
In a process kno~n from DE-A2-30 20 611 Achilles' tendons are macerated and reduced to fibres, after which the fibres are crosslinked using hexamethylene diisocyanate emulsified in an aqueous saline solution and then inter alia knittable yarns are produced from the crosslinked fibres. However, thçse processes are in no way linked with the proble~ o~ the invention.
The vessel prosthesis which is porous as such can have a porosity of approximately 2000 cm3/min/cm2. As a result of the inventive impregnating coating of gelatin mlxed with diisocyanate, it is possible to completely eliminate this porosity. The decomposition of the thus crosslinked gelatin in the body is slowed down to coincide with the rate at which the new tissue grows into the porous body of the vessel prosthesis and ensures natural sealing.
The porous body of the vessel prosthesis can have the conventional structure of a textile vessel prosthesis, e.g. a smooth warp knitted ~abric according to German patent 20 09 349, the structure of a one-sided velour prosthesis according to US patent 38 78 565 or that of a double velour prosthesis according to &erman patent 26 13 575. However, the prosthesis can also be a porous, non-textile prosthesis, e.g. of - , ~ . .
. . , . , ' ' . ' , ~ ' " ' ':
, . . . .
~33~
stretched polytetrafluoroethylene, as described in British patent 15 06 432. The prosthesis structures bounding the pores are coated with a thin crosslinked gelatin film for sealing purposes, the pores being closed by thin gelatin membranes. As a result of the film-like coating of the individual structural elements of the vessel prosthesis and the joining thereof by membranes, a seal is obtained which differs from a coating completely filling or covering the porosity. For example, in the case of textile prostheses individual fibres or fibre bundles or strands are coated with a film of cross-linked gelatin and through the membranes are interconnected over and beyond the cavities between the fibres or strands and namely in different planes within the vessel prosthesis wall. As a result of this fine structure the vessel prosthesis handling is improved rather than impaired by the impregnation.
The good sealing of the vessel prosthesis when using only a little impregnating material is also made possible in that gelatin is a material present in the form of a homogeneous solution, as opposed to collagen which is a heterogeneous fibrous material and is not therefore completely tight in thin layer form. The weight ratio of porous prosthesis body to impregnating coating can be in the range 1:0.2 to 1:3, particularly approximately 1:1, including the further additives optionally present in the impregnating coating such as plasticizers. Hydrophilic plasticizers, particularly glycerol and other known polyols are used with advantage, to prevent a complete drying out of the impregnating coating and to improve the elasticity thereof.
The moisture content of the impregnating coating in the dried state is preferably in the range 15 to 25, especially 17 to 22% by weight?
. . '. . ' ;.
. ' . ' ' . ~, ` :
' ' ~ ' ':
,- ' ' "'', ' ' ', .
~8351D~i based on the weight of the crosslinked impregnating coating.
The preFerred crosslinking agent is hexamethylene diisocyanate.
However, it is also possible to use other diisocyanates, particularly aliphatic diisocyanates with 4 to 12 and preferably 6 to 10 C-atoms.
As opposed to formaldehyde, it has been found that a greater chain length crosslinking agent is more favourable for the elasticity of the product due to the so-called spacer function of the bridges between the pro-tein chains~
The impregnating coating of the vessel prosthesis according to the invention can in per se known manner contain therapeutically active materials or other active substances. In a particularly preferred embodiment said materials or active substances are not merely mixed into the impregnating coating and are instead bonded or enclosed in the support or carrier, so that they are only released in retarded form. To this end, the impregnating coating and in particular the gelatin can contain constituents which absorb or adsorb the active substances and only gradually release the same.
Particularly suitable constituents of this type are exchangers, particularly ion exchangers. In a particularly preferred embodiment of the invention at least part of the gelatin comprises succinylated gelatin, which has such properties. As a resuit of their basic functions aminoglycosides, such as gentamycin, can be well held by such modified gelatinsO As modified gelatin gelatinizes or gels less ~ell than normal gelatin, the modified gel~tin proportion is normally dependent on the gelability of the mixture and can be in the range 10 to 50X by weight with respect to the total gelatin quantity.
Readily gelable gelatins, such as edible gelatin is preferred (8100m -. , ' ~ ' " . .
~35(~i value 110 to 3no, preferably 240 to 280). When crosslinking withdiisocyanate the modified gelatin having the exchanger functions is also crosslinked in, so that the therapeutically active material or the active substance adheres to the ac-tual gelatin structure.
The inventive process for producing the impregnated vessel prosthesis is characterized in that a porous vessel prosthesis is impregnated with an aqueous gelatin solution, the gelatin is allowed to gel and then carefully dehydrated, particularly dried in air and then the preimpregnate obtained is crosslinked with diisocyanate.
Diisocyanates react not only with gelatin, but also with compounds having other polar groups, such as e.g. with water and alcohols, accompanied by the formation of undesired by-products, such as insoluble urethane and urea derivatives. Although, as a result of its tightness, the impregnating coating does not allow a washlng out of any by-products formed in the coating, as is the case with the known porous fibrous products crosslinked wlth diisocyanate, it has been found that the tendency of diisocyanates to form by-products does not have a harmful effect.
For impregnating the porous vessel prosthesis with the gelatin solution, the vessel prosthesis is preferably immersed in the solution.
As a result of the application of a vacuum, the pores can be completely filled with the gelatin solution. The gelatin concentration in the solution can vary within wide limits and is preferably between 3 and 20, particularly between 5 and 15% by weight of the impregnating solution. However, it is important that there is a homogeneous solution. Impregnation takes place at elevated temperature, i.e. over 40C, in order to bring about gelling by cooling. As in aqueous .
.
, ,~ ~
~Z~35~
solution at temperatures over 60C, gelatin decomposes when left standing for a long time, the temperatures should not be significantly above this. Therefore temperature ranges between 45 and 70, especially 55 and 60C are preferred. The impregnating solution can also contain the plasticizer in quantities up to 60% by weight, particularly 10 to 40X by weight. The water content is normally 30 to 97% by weight, preferably 50 to 80% by weight. As a function of the gelability of the gelatin or gelatin mixture, the quantity ratios are so matched with one another that the gelatin is dissolved at the impregnating temperature and the impregnating solution is able to flow, but whilst ensuring that the gelatin gels on cooling to approximately 20 to 30C.
During cooling the prostheses impregnated with the gelatin solution are preferably moved in order to,obtain a uniform coating thickness of the gelled gelatin. For this purpose, the prostheses can be rotated about their longitudinal axis or subject to a tumbling movement after removal from the impregnating bath and after briefly being left to drip.
It is important that the dehydration or dewatering of the gelled gelatin coating or the drying thereof is performed in a careful manner, in order to obtain a good and uniformly structured impregnating coating. Air drying at 25 to 35, particularly approximately 30C is suitable. The relative humidity of the drying air is preferably between 30 and 50%9 particularly approximately 40X. Particularly if the prostheses are immersed in the gelatin solution accompanied by the application of a vacuum, a single impregnation or treatment is sufficient for obtaining a complete tightness, accompanied by the advantage of the resulting low material quantity and favourable mechanical characteristics.
' ~ ' . .
.
~L~33 5CI~
Working takes place with a diisocyanate excess for crosslinking the gelatin, firs-tly to obtain a complete gelatin crosslinking and to make it insoluble and secondly in view of the expected secondary reactions. Working preferably takes place without influencing the pH-value. lhe gelatin can be left at a normal pH-value, which is usually approximately 5.5. The crosslinking reaction can be performed in a pH range of 3.5 to 7.5. Acceptable reaction times of approximately 5 to 10 hours are attainable during crosslinking at ambient temperature, without secondary reactions having a disadvantageous effect and without special measures having to be taken.
It is particularly advantageous for performing the crosslinking reaction to use solutions of diisocyanate in polar organic solvents, which readily wet the predried gelatin impregnating coating.
Preference is given to solvents which are miscible with water and plasticizer; isopropanol being particularly suitable. The diisocyanate diffuses from the crosslinking solution into the gelatin coating and reacts, accompanied by crosslinking, with the gelatin. The diffusion of diisocyanate into the gelatin coating preferably takes place both from the outside and from the inside. For this purpose, the prostheses can advantageously be immersed in the crosslinking solution. Although working takes place with a considerable di-isocyanate excess, which is preferably more than 10 times the stoichiometric quantity needed for crosslinking, the diisocyanate concentration in the crosslinking solution is preferably under 3% by weight, in order to suppress secondary reactions to the greatest possible extent, because diisocyanate is also able to react with co~ponents of the crosslinking solution. The diisocyanate concentration `
`
~L~Z~3~
can be between 0.03 and 3% by weight, preferably between 0.05 and 0.5X by weight, preference being given to roughly 0.1% by weight.
The crosslinking solution preferably also contains plastici~ers and/or water in order to introduce the plasticizer and water into the gelatin coating or prevent a washing out of water and/or plasticizer from the gelatin coating during the crosslinking reaction. The concentration of plasticizer, particularly glycerol can be 0 to 60 and in particular 10 to 20~ by weight. In extreme cases the water content can be ~p to 70X by weight, but is normally much lower, namely between 3 and 30 and particularly between 5 and 10~ by weight. It is important for the preferred embodiment that the water content is so low that the di-isocyanate is present in the dissolved state in the crosslinking solution. Through a relative mov,ement between the crosslinking solution and vessel prosthesis it is possible to ensure that the diisocyanate concentration on the prosthesis surface is kept as high as possible. 3n a preferred embodiment the crosslinking solution is constantly circulated or pumped round and is simultaneously filtered.
Insoluble by-products are continuously removed, so that deposits on the vessel prosthesis and therefore contamination are avoided. The low diisocyanate concentration permits a safe handling of the cross-linking solution. The diisocyanate concentration constantly decreases during the crosslinking reaction, so that safe disposal is possible at the end of the reaction. However, process variants are possible in which working e.g. takes place with ~ substantially constant diisocyanate concentration.
In a particularly preferred embodiment o~ the invention the moisture content and preferably also the plasticizer content of the : ` .: , ~33~
dehydrated, still uncrosslinked, but predried gela-tin impregnating coating, together with the water content and preferably also the plasticizer content of the crosslinking solution are adjusted in such a way tha-t they are substantially in equilibrium with one another on immersing the predried impregnated vessel prosthesis in the cross-linking solution. This makes it possible to avoid undesired concentration changes, which could e.g. Iead to the leaching or swelling of the not yet crosslinked gelatin impregnating coating.
At the end of crosslinking the gelatin impregnating coating is waterproof, so that it can be washed with water, to which optionally a plasticizer is added and then carefully dried. Sterilization takes place preferably by per se known radiation.
Further features and details of the invention can be gathered from the following description of preferred embodiments in conjunction with the subclaims. The individual features can be realized alone or in tne form of combinations.
EXAMPLE I
Knitted double microvelour vessel prostheses of polyethylene terephthalate fibres provided with a pleat are fixed in a frame and immersed in an aqueous gelatin impregnating solution containing 7.5%
by weight of gelatin and 15% by weight of glycerol as the plasticizer in demineralized water and at a temperature of 60C.
A vacuum is now applied to the gelatin solution to completely remove the air enclosed in the textile prostheses. Following the rising of the air bubbles, the prostheses are left for approximately 15 minutes in the solution under reduced pressure and the latter is , ~Z~33~
then raised to normal pressure again. The prostheses are then removed ~rom the impregnating solution and are briefly allowed to drip. They are then cooled to normal temperature, accompanied by a slight tumbling movement~ Following the gelling of the coating material, the coated prostheses are placed in a clima-tic chamber and dried in air therein having a relative atmospheric humidity of 40%
at 30~C until the residual moisture content in the impregnating so'ution is approximately 20%.
The predried prostheses are them immersed in a crosslinking solution containing 0.1% by weight of hexamethylene diisocyanate, 15% by weight of glycerol, 8.5~ by weight of water and 76.4% by weight of isopropanol. The coated prostheses are left for 8 hours at ambient temperature in this s,olution, whilst the latter is simultaneously constantly pumped round and ~iltered. At the end of crosslinking the prostheses are removed from the crosslinking solution and washed in water with a 15% glycerol solution, followed by careful drying again at 30C and 40g relative atmospheric humidity until there is a residual moisture content of 15 to 20g, based on the impregnating coating. The prostheses are then cut to the nominal length, individually packed and sterilized by radiation.
The prostheses impregnated in this way are completely tight.
The impregnating coating is located in the textile fibrous structure and can hardly be seen with the naked eye. The prosthesis has a bright white appearance, is flexible and can be compressed and stretched in the axial direction. Following implantation of the prosthesis, the crosslinked coating material is resorbed in the degree in which the natural tissue subsequently grows, without the ~ r -" ~ ' .
~L~33 decomposition products revealing any harmful effects. The impregnating coating is also bo-th immunologically and toxicologically unobjectionable.
The procedure of example I is repeated, but the edible gelatin is replaced by a mixture of 70% by weight of edible gelatin and 30~ by weight of succinylated gelatin. The crosslinked impregnating coating obtained in this way contains additional acid radicals making the impregnating coating suitable for storage, e.g. by diffusion and binding of therapeutic active substances with basic characteristics.
These therapeutic active substances are only very slowly released following the implantation of the prosthesis, so that e.g. infection protection is provided over a long period.
Knitted vessel prostheses of the double velour type formed from polyethyleneterephthalate fibres and having a pleat, are secured in a frame as in example 1 and then impregnated with gelatin in an immersion process. The aqueous impregnating solution contains 10% by weight of gelatin and 20% by weight of glycerol, whilst having a temperature of 60C. As in example 1, the textile prostheses are thoroughly vented under reduced pressure. Following removal, they are briefly allowed to drip and the frame is tumbled slightly during the gelling phase of the Impregnating solwtion. Following the separating of the coating mass9 the impregnated prostheses are transferred into a climatic chamber and, as in example 1, subject to , ~l2 ~33 careful in-termediate drying until the residual mois-ture content of the impregnating coating is approximately 25%. The predried prostheses are then introduced in the clamped state into a cross-linking bath containing 0.2% by weight of hexamethylene diisocyanate, 50X by weight of glycerol, 43.3% by weight of isopropanol and 6.5%
by weight of water. As in example 1, the coated prostheses are left in the crosslinking solution for 8 hours at ambient temperature.
The subsequent rinsing stage takes place in such a way that the clamped prostheses are exposed for approximately 5 minutes to a 30%
aqueous glycerol solution at ambient temperature and in the circulating process. After drying the impregnating coating of the thus produced prostheses has a residual moisture content of approximately 22~. , The coated prosthesis according to example 1 contains 9.5% by weight of water 22% by weight of glycerol 18% by weight of crosslinked gelatin .
i.e. 49.5% by weight impregnating coating and 50.5~ by weight porous basic body.
The prosthesis according to example 3 contains 13% by weight of water 32~ by weight of glycerol 16~ by weight of crosslinked gelatin i.e. 61X by weight impregnating coating and 39X by weight knitted porous prosthesis.
.
: : -~LZ ~33 Based on the total weight of the impregnating coating, the latter generally contains 10 to ~OX by weight water 10 to 60% by weight plasticizer and 20 to 60% by weight crosslinked gelatin.
, .
''~" ~ ~ ' '" ," ' '' .
` ~ ' ' ' ' ' .
VESSEL PROSTHESIS IMPREGNATED WITH CROSSLINKED G_LATIN AND
PROCESS FOR THE PRODUCTION THEREOF
The present invention relates to a vessel prosthesis which is in itself porous, but is sealed by impregnating with crosslinked gelatin and to a process for the production thereof.
Yessel prosthesis for replacing hollow organs in humans and animals and in particular blood vessels have long been known. They are generally made from textile material and in particular a knitted fabric (DE-A2-26 13 575, DE-A2-20 09 349 and DE-Al-24 61 370). However, they can also be made from non-textile materials (EP-Al-O 106 49~ and GB Al-15 06 432). In general, the vessel prostheses are porous, so as to permit a growing in of the tissue for obtaining conditions which are as natural as possible. However, since after the implantation of tlle prosthesis, these pores frequently lead to undesirably high body fluid losses, it is desirable to seal said pores with a material resorbable by the body and which is successively replaced by the growing in tissue.
It is known from DE-A2-14 94 939 to use procollagen as the impregnating agent, which is applied to the porous prosthesis in acid solution and then rendered insoluble by increasing the pH-value.
The use of collagen for sealing is known from DE-A2-14 91 218, US-Al-41 67 045, DE-Al-35 03 127 and DE-AI-35 03 126. The crosslinking of collagen normally takes place with aldehydes, particularly formaldehyde.
It is also known to impregnate porous vessel prostheses with soluble gelatin and to crosslink the same (DE-A2-14 94 939), crosslinking taking place with the aid of thiol group-containing compounds with - ,~
' , ~ ' .
', , . " ':
..
~LZ~335~i subsequent oxidative crosslinking, accompanied by the formation of disulphide bridges.
High demands are made on the characteristics of the impregnating coating, which must adhere well to the prosthesis body, provide a good sealing thereof, be elastic and in particularlt release any harmful products during resorption. The known impregnated prostheses only partly fulfil these requirements. In addition, they are far from easy to produce, or expensive starting materials are required, which is prejudicial to industrial manufacture.
The problem of the present invention is therefore to provide an impregnated vessel prosthesis, which is easier to manufacture, has good mechanical characteristics and is completely tight, is not harmful for the receiver organism and can be easily handled particularly during implantation.
This problem is solved by a vessel prosthesis which is porous as such, but sealed by impregnating with crosslinked gelatin and which is characterized in that the gelatin is crosslinked with a diisocyanate.
Isocyanates react with the reactive nucleophilic groups of gelatin, particularly the amino groups and also the hydroxyl groups, accompanied by the formation of stable bonds and crosslinking products.
Crosslinking with diisocyanates is irreversible contrary to crosslinking with aldehydes, in which there is a state of equilibrium, so that aldehydes re-form and are released again. At the end of the reaction there are no longer any isocyanate residues and ~hey are also not re-fonmed from the crosslinking product. A gelatin crosslinked with diisocyanate forms a tight impregnation with good mechanical character-istics, so that in relation to the porosity of the vessel prosthesis ', , ' ', ' ~2~3~
little gelatin and crosslinking agent is required, but nevertheless a complete seal is obtained.
The crosslinking of biological material with diisocyanates is known per se. Thus, DE-A2-27 34 503 describes a process for producing a coliagen sponge, in which a paste or slurry of partly decomposed collagen is mixed with diisocyanate, shock-frozen to temperatures of -10 to -30C, left at temperatures below 0C, washed, subsequently treated and then dried. This gives a soft, porous foam or sponge.
In a process kno~n from DE-A2-30 20 611 Achilles' tendons are macerated and reduced to fibres, after which the fibres are crosslinked using hexamethylene diisocyanate emulsified in an aqueous saline solution and then inter alia knittable yarns are produced from the crosslinked fibres. However, thçse processes are in no way linked with the proble~ o~ the invention.
The vessel prosthesis which is porous as such can have a porosity of approximately 2000 cm3/min/cm2. As a result of the inventive impregnating coating of gelatin mlxed with diisocyanate, it is possible to completely eliminate this porosity. The decomposition of the thus crosslinked gelatin in the body is slowed down to coincide with the rate at which the new tissue grows into the porous body of the vessel prosthesis and ensures natural sealing.
The porous body of the vessel prosthesis can have the conventional structure of a textile vessel prosthesis, e.g. a smooth warp knitted ~abric according to German patent 20 09 349, the structure of a one-sided velour prosthesis according to US patent 38 78 565 or that of a double velour prosthesis according to &erman patent 26 13 575. However, the prosthesis can also be a porous, non-textile prosthesis, e.g. of - , ~ . .
. . , . , ' ' . ' , ~ ' " ' ':
, . . . .
~33~
stretched polytetrafluoroethylene, as described in British patent 15 06 432. The prosthesis structures bounding the pores are coated with a thin crosslinked gelatin film for sealing purposes, the pores being closed by thin gelatin membranes. As a result of the film-like coating of the individual structural elements of the vessel prosthesis and the joining thereof by membranes, a seal is obtained which differs from a coating completely filling or covering the porosity. For example, in the case of textile prostheses individual fibres or fibre bundles or strands are coated with a film of cross-linked gelatin and through the membranes are interconnected over and beyond the cavities between the fibres or strands and namely in different planes within the vessel prosthesis wall. As a result of this fine structure the vessel prosthesis handling is improved rather than impaired by the impregnation.
The good sealing of the vessel prosthesis when using only a little impregnating material is also made possible in that gelatin is a material present in the form of a homogeneous solution, as opposed to collagen which is a heterogeneous fibrous material and is not therefore completely tight in thin layer form. The weight ratio of porous prosthesis body to impregnating coating can be in the range 1:0.2 to 1:3, particularly approximately 1:1, including the further additives optionally present in the impregnating coating such as plasticizers. Hydrophilic plasticizers, particularly glycerol and other known polyols are used with advantage, to prevent a complete drying out of the impregnating coating and to improve the elasticity thereof.
The moisture content of the impregnating coating in the dried state is preferably in the range 15 to 25, especially 17 to 22% by weight?
. . '. . ' ;.
. ' . ' ' . ~, ` :
' ' ~ ' ':
,- ' ' "'', ' ' ', .
~8351D~i based on the weight of the crosslinked impregnating coating.
The preFerred crosslinking agent is hexamethylene diisocyanate.
However, it is also possible to use other diisocyanates, particularly aliphatic diisocyanates with 4 to 12 and preferably 6 to 10 C-atoms.
As opposed to formaldehyde, it has been found that a greater chain length crosslinking agent is more favourable for the elasticity of the product due to the so-called spacer function of the bridges between the pro-tein chains~
The impregnating coating of the vessel prosthesis according to the invention can in per se known manner contain therapeutically active materials or other active substances. In a particularly preferred embodiment said materials or active substances are not merely mixed into the impregnating coating and are instead bonded or enclosed in the support or carrier, so that they are only released in retarded form. To this end, the impregnating coating and in particular the gelatin can contain constituents which absorb or adsorb the active substances and only gradually release the same.
Particularly suitable constituents of this type are exchangers, particularly ion exchangers. In a particularly preferred embodiment of the invention at least part of the gelatin comprises succinylated gelatin, which has such properties. As a resuit of their basic functions aminoglycosides, such as gentamycin, can be well held by such modified gelatinsO As modified gelatin gelatinizes or gels less ~ell than normal gelatin, the modified gel~tin proportion is normally dependent on the gelability of the mixture and can be in the range 10 to 50X by weight with respect to the total gelatin quantity.
Readily gelable gelatins, such as edible gelatin is preferred (8100m -. , ' ~ ' " . .
~35(~i value 110 to 3no, preferably 240 to 280). When crosslinking withdiisocyanate the modified gelatin having the exchanger functions is also crosslinked in, so that the therapeutically active material or the active substance adheres to the ac-tual gelatin structure.
The inventive process for producing the impregnated vessel prosthesis is characterized in that a porous vessel prosthesis is impregnated with an aqueous gelatin solution, the gelatin is allowed to gel and then carefully dehydrated, particularly dried in air and then the preimpregnate obtained is crosslinked with diisocyanate.
Diisocyanates react not only with gelatin, but also with compounds having other polar groups, such as e.g. with water and alcohols, accompanied by the formation of undesired by-products, such as insoluble urethane and urea derivatives. Although, as a result of its tightness, the impregnating coating does not allow a washlng out of any by-products formed in the coating, as is the case with the known porous fibrous products crosslinked wlth diisocyanate, it has been found that the tendency of diisocyanates to form by-products does not have a harmful effect.
For impregnating the porous vessel prosthesis with the gelatin solution, the vessel prosthesis is preferably immersed in the solution.
As a result of the application of a vacuum, the pores can be completely filled with the gelatin solution. The gelatin concentration in the solution can vary within wide limits and is preferably between 3 and 20, particularly between 5 and 15% by weight of the impregnating solution. However, it is important that there is a homogeneous solution. Impregnation takes place at elevated temperature, i.e. over 40C, in order to bring about gelling by cooling. As in aqueous .
.
, ,~ ~
~Z~35~
solution at temperatures over 60C, gelatin decomposes when left standing for a long time, the temperatures should not be significantly above this. Therefore temperature ranges between 45 and 70, especially 55 and 60C are preferred. The impregnating solution can also contain the plasticizer in quantities up to 60% by weight, particularly 10 to 40X by weight. The water content is normally 30 to 97% by weight, preferably 50 to 80% by weight. As a function of the gelability of the gelatin or gelatin mixture, the quantity ratios are so matched with one another that the gelatin is dissolved at the impregnating temperature and the impregnating solution is able to flow, but whilst ensuring that the gelatin gels on cooling to approximately 20 to 30C.
During cooling the prostheses impregnated with the gelatin solution are preferably moved in order to,obtain a uniform coating thickness of the gelled gelatin. For this purpose, the prostheses can be rotated about their longitudinal axis or subject to a tumbling movement after removal from the impregnating bath and after briefly being left to drip.
It is important that the dehydration or dewatering of the gelled gelatin coating or the drying thereof is performed in a careful manner, in order to obtain a good and uniformly structured impregnating coating. Air drying at 25 to 35, particularly approximately 30C is suitable. The relative humidity of the drying air is preferably between 30 and 50%9 particularly approximately 40X. Particularly if the prostheses are immersed in the gelatin solution accompanied by the application of a vacuum, a single impregnation or treatment is sufficient for obtaining a complete tightness, accompanied by the advantage of the resulting low material quantity and favourable mechanical characteristics.
' ~ ' . .
.
~L~33 5CI~
Working takes place with a diisocyanate excess for crosslinking the gelatin, firs-tly to obtain a complete gelatin crosslinking and to make it insoluble and secondly in view of the expected secondary reactions. Working preferably takes place without influencing the pH-value. lhe gelatin can be left at a normal pH-value, which is usually approximately 5.5. The crosslinking reaction can be performed in a pH range of 3.5 to 7.5. Acceptable reaction times of approximately 5 to 10 hours are attainable during crosslinking at ambient temperature, without secondary reactions having a disadvantageous effect and without special measures having to be taken.
It is particularly advantageous for performing the crosslinking reaction to use solutions of diisocyanate in polar organic solvents, which readily wet the predried gelatin impregnating coating.
Preference is given to solvents which are miscible with water and plasticizer; isopropanol being particularly suitable. The diisocyanate diffuses from the crosslinking solution into the gelatin coating and reacts, accompanied by crosslinking, with the gelatin. The diffusion of diisocyanate into the gelatin coating preferably takes place both from the outside and from the inside. For this purpose, the prostheses can advantageously be immersed in the crosslinking solution. Although working takes place with a considerable di-isocyanate excess, which is preferably more than 10 times the stoichiometric quantity needed for crosslinking, the diisocyanate concentration in the crosslinking solution is preferably under 3% by weight, in order to suppress secondary reactions to the greatest possible extent, because diisocyanate is also able to react with co~ponents of the crosslinking solution. The diisocyanate concentration `
`
~L~Z~3~
can be between 0.03 and 3% by weight, preferably between 0.05 and 0.5X by weight, preference being given to roughly 0.1% by weight.
The crosslinking solution preferably also contains plastici~ers and/or water in order to introduce the plasticizer and water into the gelatin coating or prevent a washing out of water and/or plasticizer from the gelatin coating during the crosslinking reaction. The concentration of plasticizer, particularly glycerol can be 0 to 60 and in particular 10 to 20~ by weight. In extreme cases the water content can be ~p to 70X by weight, but is normally much lower, namely between 3 and 30 and particularly between 5 and 10~ by weight. It is important for the preferred embodiment that the water content is so low that the di-isocyanate is present in the dissolved state in the crosslinking solution. Through a relative mov,ement between the crosslinking solution and vessel prosthesis it is possible to ensure that the diisocyanate concentration on the prosthesis surface is kept as high as possible. 3n a preferred embodiment the crosslinking solution is constantly circulated or pumped round and is simultaneously filtered.
Insoluble by-products are continuously removed, so that deposits on the vessel prosthesis and therefore contamination are avoided. The low diisocyanate concentration permits a safe handling of the cross-linking solution. The diisocyanate concentration constantly decreases during the crosslinking reaction, so that safe disposal is possible at the end of the reaction. However, process variants are possible in which working e.g. takes place with ~ substantially constant diisocyanate concentration.
In a particularly preferred embodiment o~ the invention the moisture content and preferably also the plasticizer content of the : ` .: , ~33~
dehydrated, still uncrosslinked, but predried gela-tin impregnating coating, together with the water content and preferably also the plasticizer content of the crosslinking solution are adjusted in such a way tha-t they are substantially in equilibrium with one another on immersing the predried impregnated vessel prosthesis in the cross-linking solution. This makes it possible to avoid undesired concentration changes, which could e.g. Iead to the leaching or swelling of the not yet crosslinked gelatin impregnating coating.
At the end of crosslinking the gelatin impregnating coating is waterproof, so that it can be washed with water, to which optionally a plasticizer is added and then carefully dried. Sterilization takes place preferably by per se known radiation.
Further features and details of the invention can be gathered from the following description of preferred embodiments in conjunction with the subclaims. The individual features can be realized alone or in tne form of combinations.
EXAMPLE I
Knitted double microvelour vessel prostheses of polyethylene terephthalate fibres provided with a pleat are fixed in a frame and immersed in an aqueous gelatin impregnating solution containing 7.5%
by weight of gelatin and 15% by weight of glycerol as the plasticizer in demineralized water and at a temperature of 60C.
A vacuum is now applied to the gelatin solution to completely remove the air enclosed in the textile prostheses. Following the rising of the air bubbles, the prostheses are left for approximately 15 minutes in the solution under reduced pressure and the latter is , ~Z~33~
then raised to normal pressure again. The prostheses are then removed ~rom the impregnating solution and are briefly allowed to drip. They are then cooled to normal temperature, accompanied by a slight tumbling movement~ Following the gelling of the coating material, the coated prostheses are placed in a clima-tic chamber and dried in air therein having a relative atmospheric humidity of 40%
at 30~C until the residual moisture content in the impregnating so'ution is approximately 20%.
The predried prostheses are them immersed in a crosslinking solution containing 0.1% by weight of hexamethylene diisocyanate, 15% by weight of glycerol, 8.5~ by weight of water and 76.4% by weight of isopropanol. The coated prostheses are left for 8 hours at ambient temperature in this s,olution, whilst the latter is simultaneously constantly pumped round and ~iltered. At the end of crosslinking the prostheses are removed from the crosslinking solution and washed in water with a 15% glycerol solution, followed by careful drying again at 30C and 40g relative atmospheric humidity until there is a residual moisture content of 15 to 20g, based on the impregnating coating. The prostheses are then cut to the nominal length, individually packed and sterilized by radiation.
The prostheses impregnated in this way are completely tight.
The impregnating coating is located in the textile fibrous structure and can hardly be seen with the naked eye. The prosthesis has a bright white appearance, is flexible and can be compressed and stretched in the axial direction. Following implantation of the prosthesis, the crosslinked coating material is resorbed in the degree in which the natural tissue subsequently grows, without the ~ r -" ~ ' .
~L~33 decomposition products revealing any harmful effects. The impregnating coating is also bo-th immunologically and toxicologically unobjectionable.
The procedure of example I is repeated, but the edible gelatin is replaced by a mixture of 70% by weight of edible gelatin and 30~ by weight of succinylated gelatin. The crosslinked impregnating coating obtained in this way contains additional acid radicals making the impregnating coating suitable for storage, e.g. by diffusion and binding of therapeutic active substances with basic characteristics.
These therapeutic active substances are only very slowly released following the implantation of the prosthesis, so that e.g. infection protection is provided over a long period.
Knitted vessel prostheses of the double velour type formed from polyethyleneterephthalate fibres and having a pleat, are secured in a frame as in example 1 and then impregnated with gelatin in an immersion process. The aqueous impregnating solution contains 10% by weight of gelatin and 20% by weight of glycerol, whilst having a temperature of 60C. As in example 1, the textile prostheses are thoroughly vented under reduced pressure. Following removal, they are briefly allowed to drip and the frame is tumbled slightly during the gelling phase of the Impregnating solwtion. Following the separating of the coating mass9 the impregnated prostheses are transferred into a climatic chamber and, as in example 1, subject to , ~l2 ~33 careful in-termediate drying until the residual mois-ture content of the impregnating coating is approximately 25%. The predried prostheses are then introduced in the clamped state into a cross-linking bath containing 0.2% by weight of hexamethylene diisocyanate, 50X by weight of glycerol, 43.3% by weight of isopropanol and 6.5%
by weight of water. As in example 1, the coated prostheses are left in the crosslinking solution for 8 hours at ambient temperature.
The subsequent rinsing stage takes place in such a way that the clamped prostheses are exposed for approximately 5 minutes to a 30%
aqueous glycerol solution at ambient temperature and in the circulating process. After drying the impregnating coating of the thus produced prostheses has a residual moisture content of approximately 22~. , The coated prosthesis according to example 1 contains 9.5% by weight of water 22% by weight of glycerol 18% by weight of crosslinked gelatin .
i.e. 49.5% by weight impregnating coating and 50.5~ by weight porous basic body.
The prosthesis according to example 3 contains 13% by weight of water 32~ by weight of glycerol 16~ by weight of crosslinked gelatin i.e. 61X by weight impregnating coating and 39X by weight knitted porous prosthesis.
.
: : -~LZ ~33 Based on the total weight of the impregnating coating, the latter generally contains 10 to ~OX by weight water 10 to 60% by weight plasticizer and 20 to 60% by weight crosslinked gelatin.
, .
''~" ~ ~ ' '" ," ' '' .
` ~ ' ' ' ' ' .
Claims (19)
1. A vessel prosthesis which is porous as such and which is sealed by impregnation with gelatin wherein the gelatin is crosslinked with a diisocyanate.
2. A vessel prosthesis according to claim 1 wherein the vessel prosthesis which is porous as such is a textile vessel prosthesis.
3. A vessel prosthesis according to claim 1 or 2, wherein the structures of the vessel prosthesis bounding the pores are coated with a thin film of crosslinked gelatin and the pores are closed by gelatin membranes.
4. A vessel prosthesis according to claim 1, wherein the weight ratio of the porous vessel prosthesis to the impregnating material is 1:0.2 to 1:3.
5. A vessel prosthesis according to claim 1, wherein the impregnating material contains a hydrophilic plasti-cizer.
6. A vessel pros-thesis according to claim 1, wherein the impregnating material contains 10 to 30 % by weight of water based on the weight of the impregnating ma-terial.
7. A vessel prosthesis according to claim 1, wherein the diisocyanate is an aliphatic diisocyanate.
8. A vessel prosthesis according to claim 1, wherein in the impregnating material is incorporated at least one therapeutically active material.
9. A vessel prosthesis according to claim 8, wherein the impregnating material contains constituents with exchanger characteristics.
10. A process for producing impregnated vessel prostheses, wherein a porous vessel prosthesis is impregnated with an aqueous gelatin solution, the gelatin is allowed to gel, the gelatin is then carefully partially dehydrated and then the impregnating coating obtained is crosslinked with the diisocyanate.
11. A process according to claim 10, wherein the im-pregnation of porous vessel prosthesis with the gelatin solution takes place by immersion.
12. A process according to claims 10 or 11, wherein porous vessel prosthesis is only treated once with the gelatin solution.
13. A process according to claim 10, wherein for cross-linking the gelatin impregnating coating use is made of a solution of diisocyanate in an organic solvent.
14. A process according to claim 10, wherein for crosslinking the gelatin impregnating coating use is made of a solution of 0.03 to 3 % by weight of diiso-cyanate, 0 to 60 % by weight of plasticizer, 30 to 95 %
by weight of solvent, and 5 to 70 % by weight of water, the quantity ratios being so matched to one another that the diisocyanate is present in the dissolved state.
by weight of solvent, and 5 to 70 % by weight of water, the quantity ratios being so matched to one another that the diisocyanate is present in the dissolved state.
15. A process according to one of the claims 10, wherein the gelatin-impregnated vessel prosthesis is immersed in the cross-linking solution and moved relative thereto.
16. A process according to claim 15, wherein the cross-linking solution is constantly circulated during the cross-linking reaction and insoluble by-products are removed by filtration.
17. A process according to one of the claims 10 to 16, wherein the moisture content and optionally also in the plasticizer content of the partly dehydrated, not yet crosslinked gelatin impregnating coating is adjusted in such a way that it is substantially in equilibrium with the water content and optionally the plasticizer content of the crosslinking solution.
18. A process according to claim 11, wherein the im-pregnation takes place by immersion under a vacuum.
19. A vessel prosthesis according to claim 8, wherein the therapeutical active material is incorporated in de-pot-like manner for producing a retard effect.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19863608158 DE3608158A1 (en) | 1986-03-12 | 1986-03-12 | VESSELED PROSTHESIS IMPREGNATED WITH CROSSLINED GELATINE AND METHOD FOR THE PRODUCTION THEREOF |
DEP3608158.2 | 1986-03-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1283505C true CA1283505C (en) | 1991-04-30 |
Family
ID=6296120
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000531723A Expired - Lifetime CA1283505C (en) | 1986-03-12 | 1987-03-11 | Vessel prosthesis impregnated with crosslinked gelatin and processfor the production thereof |
Country Status (14)
Country | Link |
---|---|
US (2) | US4784659A (en) |
EP (1) | EP0237037B1 (en) |
JP (1) | JPS62258666A (en) |
AT (1) | ATE66126T1 (en) |
BR (1) | BR8701135A (en) |
CA (1) | CA1283505C (en) |
DE (2) | DE3608158A1 (en) |
DK (1) | DK127987A (en) |
ES (1) | ES2025078B3 (en) |
FI (1) | FI87143C (en) |
GR (1) | GR3002895T3 (en) |
MX (1) | MX165145B (en) |
MY (2) | MY104291A (en) |
NO (1) | NO168083C (en) |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7713297B2 (en) | 1998-04-11 | 2010-05-11 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
US7942926B2 (en) | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
US8002823B2 (en) | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US8071156B2 (en) | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8221822B2 (en) | 2007-07-31 | 2012-07-17 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
US8353949B2 (en) | 2006-09-14 | 2013-01-15 | Boston Scientific Scimed, Inc. | Medical devices with drug-eluting coating |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
US8449603B2 (en) | 2008-06-18 | 2013-05-28 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8574615B2 (en) | 2006-03-24 | 2013-11-05 | Boston Scientific Scimed, Inc. | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8771343B2 (en) | 2006-06-29 | 2014-07-08 | Boston Scientific Scimed, Inc. | Medical devices with selective titanium oxide coatings |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
US8900292B2 (en) | 2007-08-03 | 2014-12-02 | Boston Scientific Scimed, Inc. | Coating for medical device having increased surface area |
US8920491B2 (en) | 2008-04-22 | 2014-12-30 | Boston Scientific Scimed, Inc. | Medical devices having a coating of inorganic material |
US8932346B2 (en) | 2008-04-24 | 2015-01-13 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
US9284409B2 (en) | 2007-07-19 | 2016-03-15 | Boston Scientific Scimed, Inc. | Endoprosthesis having a non-fouling surface |
Families Citing this family (117)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5181903A (en) * | 1988-03-25 | 1993-01-26 | Duke University | Method for improving a biomaterial's resistance to thrombosis and infection and for improving tissue ingrowth |
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 |
DE68922497T2 (en) * | 1988-08-24 | 1995-09-14 | Marvin J Slepian | ENDOLUMINAL SEAL WITH BISDEGRADABLE POLYMERS. |
JP2678945B2 (en) * | 1989-04-17 | 1997-11-19 | 有限会社ナイセム | Artificial blood vessel, method for producing the same, and substrate for artificial blood vessel |
US5104400A (en) * | 1989-05-26 | 1992-04-14 | Impra, Inc. | Blood vessel patch |
US5152782A (en) * | 1989-05-26 | 1992-10-06 | Impra, Inc. | Non-porous coated ptfe graft |
JP2799596B2 (en) * | 1989-08-10 | 1998-09-17 | 株式会社ジェイ・エム・エス | Bioimplant device and method for producing the same |
US5092841A (en) * | 1990-05-17 | 1992-03-03 | Wayne State University | Method for treating an arterial wall injured during angioplasty |
EP0495127B1 (en) * | 1990-07-31 | 1996-11-27 | Ube Industries, Ltd. | Artificial blood vessel and production thereof |
US5549664A (en) * | 1990-07-31 | 1996-08-27 | Ube Industries, Ltd. | Artificial blood vessel |
US5298276A (en) * | 1990-08-24 | 1994-03-29 | Swaminathan Jayaraman | Process for producing artificial blood vessels of controlled permeability and product produced thereby |
CA2038596A1 (en) * | 1990-10-17 | 1992-04-18 | Leonard Pinchuk | Antithrombogenic composition and methods of making same |
US5632776A (en) * | 1990-11-22 | 1997-05-27 | Toray Industries, Inc. | Implantation materials |
GB9026687D0 (en) * | 1990-12-07 | 1991-01-23 | Vascutek Ltd | Process for providing a low-energy surface on a polymer |
CS277367B6 (en) * | 1990-12-29 | 1993-01-13 | Krajicek Milan | Three-layered vascular 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 |
US5811447A (en) | 1993-01-28 | 1998-09-22 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6515009B1 (en) | 1991-09-27 | 2003-02-04 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5584875A (en) * | 1991-12-20 | 1996-12-17 | C. R. Bard, Inc. | Method for making vascular grafts |
US5342387A (en) * | 1992-06-18 | 1994-08-30 | American Biomed, Inc. | Artificial support for a blood vessel |
DE4222380A1 (en) * | 1992-07-08 | 1994-01-13 | Ernst Peter Prof Dr M Strecker | Endoprosthesis implantable percutaneously in a patient's body |
GB9306812D0 (en) * | 1993-04-01 | 1993-05-26 | Vascutek Ltd | Textile prostheses |
DE69412474T2 (en) * | 1993-04-28 | 1998-12-17 | Focal Inc | DEVICE, PRODUCT AND USE REGARDING INTRALUMINAL PHOTOTHERMO MOLDING |
DE69432023T2 (en) * | 1993-09-10 | 2003-10-23 | Univ Queensland Santa Lucia | STEREOLITHOGRAPHIC ANATOMIC MODELING PROCESS |
EP0652017B2 (en) † | 1993-10-07 | 2004-01-07 | Axel Dr. Stemberger | Coating for biomaterial |
US5487392A (en) * | 1993-11-15 | 1996-01-30 | Haaga; John R. | Biopxy system with hemostatic insert |
US6334872B1 (en) | 1994-02-18 | 2002-01-01 | Organogenesis Inc. | Method for treating diseased or damaged organs |
JPH07250887A (en) * | 1994-03-15 | 1995-10-03 | Seikagaku Kogyo Co Ltd | Artificial blood vessel and its production |
DE69534640T2 (en) * | 1994-04-29 | 2006-08-10 | Scimed Life Systems, Inc., Maple Grove | Stent with collagen |
EP0698396B1 (en) * | 1994-08-12 | 2001-12-12 | Meadox Medicals, Inc. | Vascular graft impregnated with a heparin-containing collagen sealant |
US5665114A (en) * | 1994-08-12 | 1997-09-09 | Meadox Medicals, Inc. | Tubular expanded polytetrafluoroethylene implantable prostheses |
US5649977A (en) * | 1994-09-22 | 1997-07-22 | Advanced Cardiovascular Systems, Inc. | Metal reinforced polymer stent |
WO1996028115A1 (en) * | 1995-03-10 | 1996-09-19 | Impra, Inc. | Endoluminal encapsulated stent and methods of manufacture and endoluminal delivery |
US5605696A (en) * | 1995-03-30 | 1997-02-25 | Advanced Cardiovascular Systems, Inc. | Drug loaded polymeric material and method of manufacture |
US20020095218A1 (en) | 1996-03-12 | 2002-07-18 | Carr Robert M. | Tissue repair fabric |
US5628786A (en) * | 1995-05-12 | 1997-05-13 | Impra, Inc. | Radially expandable vascular graft with resistance to longitudinal compression and method of making same |
US5591199A (en) * | 1995-06-07 | 1997-01-07 | Porter; Christopher H. | Curable fiber composite stent and delivery system |
DE69533289T2 (en) | 1995-08-24 | 2005-08-18 | Bard Peripheral Vascular, Inc., Tempe | ARRANGEMENT PROCESS OF A COVERED, ENDOLUMINARY STENT |
US7241309B2 (en) | 1999-04-15 | 2007-07-10 | Scimed Life Systems, Inc. | Self-aggregating protein compositions and use as sealants |
US6177609B1 (en) | 1997-03-10 | 2001-01-23 | Meadox Medicals, Inc. | Self-aggregating protein compositions and use as sealants |
US6056993A (en) * | 1997-05-30 | 2000-05-02 | Schneider (Usa) Inc. | Porous protheses and methods for making the same wherein the protheses are formed by spraying water soluble and water insoluble fibers onto a rotating mandrel |
DE19811900C2 (en) * | 1998-03-18 | 2003-12-11 | Kallies Feinchemie Ag | Biocompatible composite material, process for its production and its use |
US6129757A (en) | 1998-05-18 | 2000-10-10 | Scimed Life Systems | Implantable members for receiving therapeutically useful compositions |
JP4341050B2 (en) * | 1998-06-05 | 2009-10-07 | オルガノジェネシス インク. | Vascular graft prosthesis made by bioengineering |
JP4341049B2 (en) * | 1998-06-05 | 2009-10-07 | オルガノジェネシス インク. | Tubular graft prosthesis made by biotechnology |
CA2334228C (en) | 1998-06-05 | 2010-09-28 | Organogenesis Inc. | Bioengineered vascular graft support prostheses |
JP4606583B2 (en) * | 1998-06-05 | 2011-01-05 | オルガノジェネシス インク. | Planar sheet transplant prosthesis using biotechnological techniques |
US6630457B1 (en) | 1998-09-18 | 2003-10-07 | Orthogene Llc | Functionalized derivatives of hyaluronic acid, formation of hydrogels in situ using same, and methods for making and using same |
US6540780B1 (en) | 1998-11-23 | 2003-04-01 | Medtronic, Inc. | Porous synthetic vascular grafts with oriented ingrowth channels |
US6554857B1 (en) | 1999-07-20 | 2003-04-29 | Medtronic, Inc | Transmural concentric multilayer ingrowth matrix within well-defined porosity |
US6702848B1 (en) * | 1999-07-20 | 2004-03-09 | Peter Paul Zilla | Foam-type vascular prosthesis with well-defined anclio-permissive open porosity |
GB9920732D0 (en) * | 1999-09-03 | 1999-11-03 | Sulzer Vascutek Ltd | Sealant |
US6521284B1 (en) | 1999-11-03 | 2003-02-18 | Scimed Life Systems, Inc. | Process for impregnating a porous material with a cross-linkable composition |
US6475235B1 (en) | 1999-11-16 | 2002-11-05 | Iowa-India Investments Company, Limited | Encapsulated stent preform |
US6251136B1 (en) | 1999-12-08 | 2001-06-26 | Advanced Cardiovascular Systems, Inc. | Method of layering a three-coated stent using pharmacological and polymeric agents |
US6702849B1 (en) | 1999-12-13 | 2004-03-09 | Advanced Cardiovascular Systems, Inc. | Method of processing open-celled microcellular polymeric foams with controlled porosity for use as vascular grafts and stent covers |
US6863696B2 (en) * | 2000-02-16 | 2005-03-08 | Viktoria Kantsevitcha | Vascular prosthesis |
LV12702B (en) | 2000-02-16 | 2001-10-20 | Viktorija Kancevica | Artery Prosthesis |
US20040260392A1 (en) * | 2000-02-16 | 2004-12-23 | Viktoria Kantsevitcha | Arterial prosthesis |
ES2257436T3 (en) * | 2000-08-23 | 2006-08-01 | Thoratec Corporation | VASCULATOR IMPLANTS COVERED AND USE PROCEDURES. |
EP1320390A2 (en) * | 2000-09-18 | 2003-06-25 | Organogenesis Inc. | Bioengineered flat sheet graft prosthesis and its use |
US6652574B1 (en) | 2000-09-28 | 2003-11-25 | Vascular Concepts Holdings Limited | Product and process for manufacturing a wire stent coated with a biocompatible fluoropolymer |
WO2003002243A2 (en) | 2001-06-27 | 2003-01-09 | Remon Medical Technologies Ltd. | Method and device for electrochemical formation of therapeutic species in vivo |
EP1414369A2 (en) * | 2001-07-27 | 2004-05-06 | Medtronic, Inc. | Adventitial fabric reinforced porous prosthetic graft |
US7022135B2 (en) * | 2001-08-17 | 2006-04-04 | Medtronic, Inc. | Film with highly porous vascular graft prostheses |
US20040137066A1 (en) * | 2001-11-26 | 2004-07-15 | Swaminathan Jayaraman | Rationally designed therapeutic intravascular implant coating |
DE10149392A1 (en) * | 2001-09-27 | 2003-04-24 | Aesculap Ag & Co Kg | Sealed (especially vascular) implants have their pores and outside walls coated with a hydrophilic material which seals a sewing thread running through it |
US7789908B2 (en) * | 2002-06-25 | 2010-09-07 | Boston Scientific Scimed, Inc. | Elastomerically impregnated ePTFE to enhance stretch and recovery properties for vascular grafts and coverings |
US7255891B1 (en) * | 2003-02-26 | 2007-08-14 | Advanced Cardiovascular Systems, Inc. | Method for coating implantable medical devices |
US7658975B2 (en) * | 2003-12-12 | 2010-02-09 | Intel Corporation | Sealing porous dielectric materials |
DE102004024635A1 (en) * | 2004-05-12 | 2005-12-08 | Deutsche Gelatine-Fabriken Stoess Ag | Process for the preparation of moldings based on crosslinked gelatin |
US7794490B2 (en) * | 2004-06-22 | 2010-09-14 | Boston Scientific Scimed, Inc. | Implantable medical devices with antimicrobial and biodegradable matrices |
US20060009839A1 (en) * | 2004-07-12 | 2006-01-12 | Scimed Life Systems, Inc. | Composite vascular graft including bioactive agent coating and biodegradable sheath |
US20060127443A1 (en) * | 2004-12-09 | 2006-06-15 | Helmus Michael N | Medical devices having vapor deposited nanoporous coatings for controlled therapeutic agent delivery |
US20070038176A1 (en) * | 2005-07-05 | 2007-02-15 | Jan Weber | Medical devices with machined layers for controlled communications with underlying regions |
DE102005054940A1 (en) * | 2005-11-17 | 2007-05-24 | Gelita Ag | Composite material, in particular for medical use, and method for its production |
DE102005054943A1 (en) * | 2005-11-17 | 2007-05-24 | Gelita Ag | Process for producing a hollow profile based on a crosslinked, gelatin-containing material and implants in the form of hollow profiles |
US8840660B2 (en) | 2006-01-05 | 2014-09-23 | Boston Scientific Scimed, Inc. | Bioerodible endoprostheses and methods of making the same |
US8089029B2 (en) | 2006-02-01 | 2012-01-03 | Boston Scientific Scimed, Inc. | Bioabsorbable metal medical device and method of manufacture |
US8048150B2 (en) | 2006-04-12 | 2011-11-01 | Boston Scientific Scimed, Inc. | Endoprosthesis having a fiber meshwork disposed thereon |
US20070264303A1 (en) * | 2006-05-12 | 2007-11-15 | Liliana Atanasoska | Coating for medical devices comprising an inorganic or ceramic oxide and a therapeutic agent |
WO2008017028A2 (en) | 2006-08-02 | 2008-02-07 | Boston Scientific Scimed, Inc. | Endoprosthesis with three-dimensional disintegration control |
US8057534B2 (en) | 2006-09-15 | 2011-11-15 | Boston Scientific Scimed, Inc. | Bioerodible endoprostheses and methods of making the same |
JP2010503489A (en) | 2006-09-15 | 2010-02-04 | ボストン サイエンティフィック リミテッド | Biodegradable endoprosthesis and method for producing the same |
ES2368125T3 (en) | 2006-09-15 | 2011-11-14 | Boston Scientific Scimed, Inc. | BIOEROSIONABLE ENDOPROOTHESIS WITH BIOESTABLE INORGANIC LAYERS. |
JP2010503485A (en) | 2006-09-15 | 2010-02-04 | ボストン サイエンティフィック リミテッド | Medical device and method for manufacturing the same |
CA2663762A1 (en) | 2006-09-18 | 2008-03-27 | Boston Scientific Limited | Endoprostheses |
EP2084310A1 (en) * | 2006-10-05 | 2009-08-05 | Boston Scientific Limited | Polymer-free coatings for medical devices formed by plasma electrolytic deposition |
US9474833B2 (en) | 2006-12-18 | 2016-10-25 | Cook Medical Technologies Llc | Stent graft with releasable therapeutic agent and soluble coating |
EP2277563B1 (en) | 2006-12-28 | 2014-06-25 | Boston Scientific Limited | Bioerodible endoprostheses and method of making the same |
DE102007024256A1 (en) * | 2007-05-16 | 2008-11-20 | Gelita Ag | vascular stent |
US8052745B2 (en) | 2007-09-13 | 2011-11-08 | Boston Scientific Scimed, Inc. | Endoprosthesis |
US20090076591A1 (en) * | 2007-09-19 | 2009-03-19 | Boston Scientific Scimed, Inc. | Stent Design Allowing Extended Release of Drug and/or Enhanced Adhesion of Polymer to OD Surface |
US20090112315A1 (en) * | 2007-10-29 | 2009-04-30 | Zimmer, Inc. | Medical implants and methods for delivering biologically active agents |
US20090118809A1 (en) * | 2007-11-02 | 2009-05-07 | Torsten Scheuermann | Endoprosthesis with porous reservoir and non-polymer diffusion layer |
US20090118813A1 (en) * | 2007-11-02 | 2009-05-07 | Torsten Scheuermann | Nano-patterned implant surfaces |
US7833266B2 (en) | 2007-11-28 | 2010-11-16 | Boston Scientific Scimed, Inc. | Bifurcated stent with drug wells for specific ostial, carina, and side branch treatment |
DE102007063214B4 (en) | 2007-12-20 | 2019-06-27 | Aesculap Ag | Flat implant, especially for hernia care |
US20090163936A1 (en) * | 2007-12-21 | 2009-06-25 | Chunlin Yang | Coated Tissue Engineering Scaffold |
WO2009099935A2 (en) * | 2008-02-01 | 2009-08-13 | Boston Scientific Scimed, Inc. | Drug-coated medical devices for differential drug release |
US7998192B2 (en) | 2008-05-09 | 2011-08-16 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8236046B2 (en) | 2008-06-10 | 2012-08-07 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
US20110106243A1 (en) * | 2008-07-04 | 2011-05-05 | Elisabeth Marianna Wilhelmina Maria Van Dongen | Coating Method for Medical Devices |
US7951193B2 (en) | 2008-07-23 | 2011-05-31 | Boston Scientific Scimed, Inc. | Drug-eluting stent |
US7985252B2 (en) | 2008-07-30 | 2011-07-26 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
JP2012504445A (en) * | 2008-10-02 | 2012-02-23 | フジフィルム・マニュファクチュアリング・ヨーロッパ・ベスローテン・フエンノートシャップ | Antimicrobial coating |
US8382824B2 (en) | 2008-10-03 | 2013-02-26 | Boston Scientific Scimed, Inc. | Medical implant having NANO-crystal grains with barrier layers of metal nitrides or fluorides |
US8267992B2 (en) | 2009-03-02 | 2012-09-18 | Boston Scientific Scimed, Inc. | Self-buffering medical implants |
JP2010213984A (en) * | 2009-03-18 | 2010-09-30 | Naisemu:Kk | In-vivo implanting medical material containing softener and/or moisturizer, method of adjusting content of softener and/or moisturizer in in-vivo implanting medical material, and method for producing in-vivo implanting medical material |
US20100274352A1 (en) * | 2009-04-24 | 2010-10-28 | Boston Scientific Scrimed, Inc. | Endoprosthesis with Selective Drug Coatings |
DE102009037134A1 (en) | 2009-07-31 | 2011-02-03 | Aesculap Ag | Tubular implant for replacement of natural blood vessels |
US8486013B2 (en) * | 2010-03-18 | 2013-07-16 | Biotronik Ag | Balloon catheter having coating |
WO2011119573A1 (en) | 2010-03-23 | 2011-09-29 | Boston Scientific Scimed, Inc. | Surface treated bioerodible metal endoprostheses |
DE102012008656A1 (en) | 2011-12-29 | 2013-07-04 | Nonwotecc Medical Gmbh | Structure with fibers glued together in places |
BR112019006967A2 (en) | 2016-10-07 | 2019-07-02 | Toray Industries | tubular woven cloth |
WO2023091998A1 (en) * | 2021-11-18 | 2023-05-25 | Board Of Regents, The University Of Texas System | Antimicrobial wraps for medical implants |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3057782A (en) * | 1958-01-22 | 1962-10-09 | Hoechst Ag | Cross-linked gelatin plasma substitute and production thereof |
US3106483A (en) * | 1961-07-27 | 1963-10-08 | Us Catheter & Instr Corp | Synthetic blood vessel grafts |
DE1494939B2 (en) * | 1963-06-11 | 1972-03-02 | Buddecke, Eckhart, Prof Dr , 4400 Munster | Implantation material for prostheses for the replacement of arteries and other pathways and hollow organs containing body juices and processes for the production thereof |
DE1491218C3 (en) * | 1963-06-15 | 1973-01-04 | Spofa Sdruzheni Podniku Pro Zdravotnickou Vyrobu, Prag | Blood vessel prosthesis and method for making the same |
US4464468A (en) * | 1968-03-29 | 1984-08-07 | Agence Nationale De Valorisation De La Recherche (Anvar) | Immobilization of active protein by cross-linking to inactive protein |
CA972501A (en) * | 1969-10-10 | 1975-08-12 | William J. Liebig | Synthetic vascular graft and method for manufacturing the same |
US3878565A (en) * | 1971-07-14 | 1975-04-22 | Providence Hospital | Vascular prosthesis with external pile surface |
DE2461370A1 (en) * | 1974-01-02 | 1975-07-03 | Sauvage Lester R | POROESE VASCULAR PROSTHESIS |
AR205110A1 (en) * | 1974-04-02 | 1976-04-05 | Gore & Ass | ARTIFICIAL VASCULAR PROSTHESIS |
US4060081A (en) * | 1975-07-15 | 1977-11-29 | Massachusetts Institute Of Technology | Multilayer membrane useful as synthetic skin |
US4047252A (en) * | 1976-01-29 | 1977-09-13 | Meadox Medicals, Inc. | Double-velour synthetic vascular graft |
DE2734503C2 (en) * | 1977-07-30 | 1984-04-05 | Fa. Carl Freudenberg, 6940 Weinheim | Process for the production of collagen sponge |
US4167045A (en) * | 1977-08-26 | 1979-09-11 | Interface Biomedical Laboratories Corp. | Cardiac and vascular prostheses |
JPS565535A (en) * | 1979-06-27 | 1981-01-21 | Fuji Photo Film Co Ltd | Heat developing photosensitive material |
DE3020611C2 (en) * | 1980-05-30 | 1983-01-05 | Chemokol Gesellschaft zur Entwicklung von Kollagenprodukten, 5190 Stolberg | Process for the production of collagen material for surgical purposes |
FI77880C (en) * | 1982-09-10 | 1989-05-10 | Gore & Ass | POROEST MATERIAL BESTAOENDE VAESENTLIGEN AV EN PTFE-POLYMER. |
IL74179A (en) * | 1984-01-30 | 1992-05-25 | Meadox Medicals Inc | Collagen synthetic vascular graft |
IL74180A (en) * | 1984-01-30 | 1992-06-21 | Meadox Medicals Inc | Drug delivery collagen-impregnated synthetic vascular graft |
JPS61122222A (en) * | 1984-11-19 | 1986-06-10 | Koken:Kk | Hemostatic agent composed of collagen or gelatin and protamine |
GB8430265D0 (en) * | 1984-11-30 | 1985-01-09 | Vascutek Ltd | Vascular graft |
-
1986
- 1986-03-12 DE DE19863608158 patent/DE3608158A1/en active Granted
-
1987
- 1987-02-26 NO NO870809A patent/NO168083C/en unknown
- 1987-03-03 US US07/021,129 patent/US4784659A/en not_active Expired - Lifetime
- 1987-03-04 MY MYPI90000991A patent/MY104291A/en unknown
- 1987-03-04 MY MYPI87000221A patent/MY100495A/en unknown
- 1987-03-10 JP JP62053221A patent/JPS62258666A/en active Granted
- 1987-03-10 DE DE8787103451T patent/DE3772070D1/en not_active Expired - Lifetime
- 1987-03-10 AT AT87103451T patent/ATE66126T1/en not_active IP Right Cessation
- 1987-03-10 ES ES87103451T patent/ES2025078B3/en not_active Expired - Lifetime
- 1987-03-10 EP EP87103451A patent/EP0237037B1/en not_active Expired - Lifetime
- 1987-03-11 CA CA000531723A patent/CA1283505C/en not_active Expired - Lifetime
- 1987-03-11 FI FI871065A patent/FI87143C/en not_active IP Right Cessation
- 1987-03-11 MX MX5550A patent/MX165145B/en unknown
- 1987-03-12 BR BR8701135A patent/BR8701135A/en not_active IP Right Cessation
- 1987-03-12 DK DK127987A patent/DK127987A/en not_active Application Discontinuation
-
1988
- 1988-07-29 US US07/226,434 patent/US4902290A/en not_active Expired - Lifetime
-
1991
- 1991-10-15 GR GR91401540T patent/GR3002895T3/en unknown
Cited By (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7713297B2 (en) | 1998-04-11 | 2010-05-11 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US8066763B2 (en) | 1998-04-11 | 2011-11-29 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US8574615B2 (en) | 2006-03-24 | 2013-11-05 | Boston Scientific Scimed, Inc. | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
US8771343B2 (en) | 2006-06-29 | 2014-07-08 | Boston Scientific Scimed, Inc. | Medical devices with selective titanium oxide coatings |
US8353949B2 (en) | 2006-09-14 | 2013-01-15 | Boston Scientific Scimed, Inc. | Medical devices with drug-eluting coating |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
US8002823B2 (en) | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7942926B2 (en) | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US9284409B2 (en) | 2007-07-19 | 2016-03-15 | Boston Scientific Scimed, Inc. | Endoprosthesis having a non-fouling surface |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
US8221822B2 (en) | 2007-07-31 | 2012-07-17 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
US8900292B2 (en) | 2007-08-03 | 2014-12-02 | Boston Scientific Scimed, Inc. | Coating for medical device having increased surface area |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
US8920491B2 (en) | 2008-04-22 | 2014-12-30 | Boston Scientific Scimed, Inc. | Medical devices having a coating of inorganic material |
US8932346B2 (en) | 2008-04-24 | 2015-01-13 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
US8449603B2 (en) | 2008-06-18 | 2013-05-28 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
US8071156B2 (en) | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
Also Published As
Publication number | Publication date |
---|---|
MY100495A (en) | 1990-10-30 |
EP0237037B1 (en) | 1991-08-14 |
US4784659A (en) | 1988-11-15 |
ATE66126T1 (en) | 1991-08-15 |
FI87143C (en) | 1992-12-10 |
NO870809D0 (en) | 1987-02-26 |
DK127987D0 (en) | 1987-03-12 |
FI871065A0 (en) | 1987-03-11 |
DE3608158C2 (en) | 1988-03-31 |
GR3002895T3 (en) | 1993-01-25 |
JPS62258666A (en) | 1987-11-11 |
NO168083C (en) | 1992-01-15 |
MY104291A (en) | 1994-02-28 |
JPH0151263B2 (en) | 1989-11-02 |
MX165145B (en) | 1992-10-29 |
DE3772070D1 (en) | 1991-09-19 |
FI87143B (en) | 1992-08-31 |
EP0237037A2 (en) | 1987-09-16 |
US4902290A (en) | 1990-02-20 |
NO870809L (en) | 1987-09-14 |
FI871065A (en) | 1987-09-13 |
EP0237037A3 (en) | 1988-04-06 |
ES2025078B3 (en) | 1992-03-16 |
BR8701135A (en) | 1988-01-05 |
NO168083B (en) | 1991-10-07 |
DE3608158A1 (en) | 1987-09-17 |
DK127987A (en) | 1987-09-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA1283505C (en) | Vessel prosthesis impregnated with crosslinked gelatin and processfor the production thereof | |
US4842575A (en) | Method for forming impregnated synthetic vascular grafts | |
US5108424A (en) | Collagen-impregnated dacron graft | |
US4747848A (en) | Vascular grafts | |
US5415619A (en) | Method of manufacturing a vascular graft impregnated with polysaccharide derivatives | |
US5676698A (en) | Soft tissue implant | |
US5028695A (en) | Process for the manufacture of collagen membranes used for hemostasis, the dressing of wounds and for implants | |
US5350583A (en) | Cell-penetrable medical material and artificial skin | |
KR100721752B1 (en) | Water-swellable polymer gel and process for preparing the same | |
CA1264207A (en) | Collagen synthetic vascular graft composite | |
EP0212881B1 (en) | Antithrombogenic medical material | |
EP0212209B1 (en) | A production process of an antithrombogenic and antiadhesive material for medical use | |
CA2547559A1 (en) | Blood-tight implantable textile material and method of making | |
KR20000057130A (en) | Artificial esophagus | |
EP0411124B1 (en) | Medical material permitting cells to enter thereinto and artificial skin | |
JPH06285150A (en) | Artificial blood vessel | |
Machy et al. | A new vascular polyester prosthesis impregnated with cross-linked dextran | |
RU2135214C1 (en) | Method of pre-implantation treatment of textile articles for cardiovascular surgery | |
RU2794740C2 (en) | Method for pre-implantation processing of textile products for cardiovascular surgery | |
JPH06125975A (en) | Base material for curing wound | |
CN100342924C (en) | Skin substitute and its preparation method | |
JPH07246234A (en) | Sheet material | |
JPH07136242A (en) | Artificial blood vessel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MKEX | Expiry |