ZA200106738B - Hemocompatible surfaces and method for producing same. - Google Patents
Hemocompatible surfaces and method for producing same. Download PDFInfo
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- ZA200106738B ZA200106738B ZA200106738A ZA200106738A ZA200106738B ZA 200106738 B ZA200106738 B ZA 200106738B ZA 200106738 A ZA200106738 A ZA 200106738A ZA 200106738 A ZA200106738 A ZA 200106738A ZA 200106738 B ZA200106738 B ZA 200106738B
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- South Africa
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- materials
- hemocompatible
- blood
- cells
- constituents
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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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/12—Polypeptides, proteins or derivatives thereof, e.g. degradation products thereof
- A61L33/128—Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
-
- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/08—Polysaccharides
-
- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/18—Use of ingredients of undetermined constitution or reaction products thereof
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Materials For Medical Uses (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
- Saccharide Compounds (AREA)
- Dental Preparations (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention relates to hemocompatible surfaces, characterized in that they contain materials and that components of the outer layer of blood cells and/or mesothelial cells are deposited on and/or introduced into the surface of said materials. The invention also relates to a method for preparing hemocompatible surfaces and to their use in numerous areas of the health sector, such as medicine, dentistry, surgery, cosmetics or in fields relating to blood, tissue and/or other body fluids.
Description
The present invention concerns hemocompatible surfaces which are characterized in that constituents of the outer layers of blood cells and/or mesothelial cells are applied and/or incorporated onto and/or into the surfaces of materials.
The present invention further concerns a process for manufacturing hemocompatible surfaces and their use in extensive fields of health, in medicine, dentistry, surgery, cosmetics and/or fields having direct contact with blood, tissue and/or other body fluids.
Ir the case of vertebrates, blood coagulation is a complex process which temporarily protects against critical losses of blood in the case of injury. The blood coagulation system is activated, among other things, by contact with unphysiologic, i. e., ‘exogenous’ substances in this case. Substances which actively suppress the blood coagulation system are also referred to as anti-thrombogenic. Substances which do not even activate the blood coagulation system are defined as non- thrombogenic.
Especially in the case of invasive operations, the activation of the blood coagulation system is a serious problem for the patient. This is, in particular, the case for people dependent on implants, such as intra-coronary stents, cardiac valves, prosthetic devices, artificial vascular systems, dialysers, or oxygenators, catheters, biosensors etc.. Contact with surgical suture materials can also cause problems.
Until now, in order to prevent the formation of critical occlusions of vessels (thrombi), the blood coagulation system has been deactivated or actively suppressed. This is normally } done by the administration of anti-thrombogenic medicine, so- called anticoagulants, which however, have many serious side : effects for the patient, such as thrombocytopenia, nausea, vomiting, hair loss, haemorrhagic skin gangrenes, higher tendency to bleed etc.. Moreover, if intra-coronary stents or cardiac valves are used, even the complete medicamentous suppression of blood coagulation often does not sufficiently prevent the formation of thrombosis, which can cause death.
Tn extensive fields of health, in medicine, dentistry, surgery, cosmetics or, in general, fields having contact with blood and/or other body fluids in invasive operations, it is therefore very important to avoid the above-mentioned serious side effects caused by anticoagulants. .
From prior art, various processes are known which are intended to make unphysiologic ‘foreign surfaces’ more blood compatible (hemocompatible) or histocompatible by coating with different substances.
DE 28 31 360, for example, describes a process for coating a surface of a medical article with a substance (heparin) which actively suppresses the coagulation system, i. e., is anti- thrombogenic. Said substance, however, has the disadvantage of serious side effects for the patient, as already mentioned before by way of example. oC
In DE 44 35 652, materials are coated with a thin coat of lacquer of polymers into which medicinal agents can be additionally incorporated, wherein said coat of lacquer permanently degrades in the body and is thus released. The disadvantages of this method are, first of all, that because of the permanent degradation of the coating only a temporally limited effect can be achieved. Secondly, cue to the permanent
AMENDED SHEET 9902 -gs- 19 separation of particles of lacquer, there is a high danger of the formation of thrombosis, which can cause embolisms.
DE 196 30 879 exclusively uses chemically modified derivatives of polysaccharides for coating substrates. There are various disadvantages regarding this process, ranging from excessive preparative expenses to synthesis steps including many stages, a wide range of undesirable side reactions and poor exploitation up to worse properties of the derivatives in every respect when compared to commercially available anti- thrombogenic substances such as heparin.
Verhagen et al. (British Journal of Heamatology, 1996, 95: 542-549) describes the use of entire living cells of the endothelium or the mesothelium for the colonisation of implants. The disadvantage of using entire cells is the fact that, due to specific cell surface proteins, immune reactions are caused, which cause rejection reactions against the coated implants for the patients. Substances inducing such an immune reaction are also called immunogenic. To prevent a rejection by immune reactions, it is necessary that exclusively cell material of the patients themselves is used in this process.
This is a further disadvantage because considerable time and costs are involved in culturing these cells. A further problem regarding the use of entire cells are the high shearing forces to which these cells are subjected in the blood stream. This leads to an increased degradation of the cells at the surfaces, which has a negative effect on the durability of the coated implants.
Also WO 93/01843, WO 95/29712 and DE 195 05 070 describe the - use of entire living endothelial cells for coating unphysiologic materials or the use of substances contributing to the growing of living endothelial cells on artificial materials. But also in these cases, all processes are based on the cultivation of living endothelial cells, which involves the disadvantages mentioned above with respect to the time ) required and the cost involved or the considerable limitation that the coated material cannot be used universally, but has to be produced separately for every patient.
From patent specification DE 36 39 561, the production of substrates coated with the specific endothelial cell surface proteopolysaccharide HS-l is known. The disadvantage of the process is the fact that also in this case considerable amounts of endothelial cells of the patients themselves are required for isolating these components. This requires for every patient a time-consuming and cost-intensive cultivation of his endogenous endothelial cells, which, in addition, is followed by a costly preparation of the proteopolysaccharide
HS-l. Therefore, the mass production of HS-l and thus an economic use of this process for coating implants cannot be realized.
Accordingly, the object of the present invention is to provide blood compatible (hemocompatible) or histocompatible surfaces which do not show the disadvantages mentioned above and are, at the same time, suitable for mass production.
According to the invention, the object is solved by means of hemocompatible surfaces characterized in that they contain as the materials artificial and/or natural organic and/or inorganic compounds and/or mixtures thereof and/or materials having contact with blood and/or other body fluids in invasive operations and/or animal organs and/or organ parts, and constituents of the outer layer of blood cells and/or : mesothelial cells are applied and/or incorporated onto and/or into the surface of said materials.
The hemocompatible surfaces of the invention thus substantially imitate the outer surface of blood and/or mesothelial cells, synonymous with the imitation of the natural surface of non-thrombogenic cells and/or tissue.
The blood coagulation system is therefore neither activated nor actively suppressed by the hemocompatible surfaces.
Accordingly, a blood coagulation which is, for example, caused by secondary injuries (cuts or the like) can take place in a completely natural and undisturbed way.
A further advantage of the present invention is the fact that an adhesion of cells such as thrombocytes on the hemocompatible surfaces according to the invention does not occur. This is desired by the invention because the risk of the formation of thrombi, i. e., the danger of a thrombosis (embolism) for the patient treated is minimized thereby. The hemocompatible surfaces according to the invention do no cause any side effects.
According to the invention, the hemocompatible surfaces are further characterized by the fact that they are non- thrombogenic in the long term. This means that their advantageous properties are not used up in the course of time, which is, for example, the case for pharmaceutically active systems (for example release system). For this reason, the surfaces according to the invention are also suitable for permanent use, so that additional burdening and risks for the patients by repeated invasive operations for renewing the implants are minimized.
According to the invention, the hemocompatible surfaces contain as the materials artificial and/or natural organic and/or inorganic compounds and/or mixtures thereof and/or materials having contact with blood and/or other body fluids in invasive operations and/or animal organs and/or organ parts, and constituents of the outer layers of blood cells and/or mesothelial cells are applied and/or incorporated onto and/or into the surfaces thereof.
In the sense of the invention, materials refer to any materials which, according to the invention, are suitable for being loaded with cell constituents. Also comprised are any materials which can come into contact with blood and/or body fluids during invasive operations or in connection with respective postoperative care.
Organic compounds refer, for example, to synthetically produced or naturally occurring high-molecular substances and their derivatives. Examples for these are, among others, any kinds of plastics, elastomers, silicones or fibrous substances. They include, for example, polyethylenes (PE), polyvinyl chlorides (PVC), polyurethanes (PUR), polyamides (pa), phenoplasts (PF), aminoplasts, polystyrene, polyester, resins, silicones, rubbers, man-made fibers, cellulose fibers, cellulose membranes, protein fibers, collagens, as well as derivatives thereof or combinations thereof. Further comprised according to the invention are mixtures of these polymers, so- called polymer blends.
In a special embodiment of the present invention, as materials, the hemocompatible surfaces according to the invention can include animal organs, organ parts or vascular systems. They can, for example, be cardiac valves and/or vascular systems, wherein pigs or cattle are especially suitable as sources.
Examples for inorganic compounds included by the hemocompatible surfaces according to the invention are metals, metal oxides, alloys or ceramics, glasses and/or minerals as well as derivatives thereof or any possible combinations and/or mixtures thereof. According to the invention, any
Claims (14)
1. Hemocompatible surfaces, characterized in that they contain as materials artificial and/or natural organic and/or inorganic compounds and/or mixtures thereof and/or materials having contact with blood and/or other body fluids in invasive operations and/or animal organs and/or organ parts, and constituents of the outer layers of blood cells and/or mesothelial cells are applied and/or incorporated onto and/or into the surfaces of said materials.
2. The hemocompatible surfaces according to claim 1, characterized in that they are non-thrombogenic and/or non- immunogenic. .
3. The hemocompatible surfaces according to one of claims 1 or 2, containing glycophorins on and/or in the surfaces of the materials.
4. The hemocompatible surfaces according to one of claims 1 - 3, containing on and/or in the surfaces of the materials oligosaccharide, polysaccharide and/or lipid portions of the glycoproteins, glycolipids and/or proteoglycans from the outer layer of blood cells and/or mesothelial cells.
5. The hemocompatible surfaces according to one of claims 1 - 4, containing glycosphingolipids on and/or in the surfaces of the materials.
6. The hemocompatible surfaces according to one of claims 1 - 5, containing on and/or in the surfaces of the materials as the oligosaccharide and/or polysaccharide portions of the proteoglycans hyaluronic acids, chondroitin sulfates, dermatan sulfates, heparan sulfates, keratan sulfates or mixtures thereof.
7. The hemocompatible surfaces according to one of claims 1 - 6, containing on and/or in the surfaces of the materials heparan sulfate of the erythrocyte plasma membrane of animal and/or human origin.
8. The hemocompatible surfaces according to one of claims 1 - 7, containing as the materials high-molecular organic compounds and/or metals, metal oxides, alloys, ceramics, glasses, minerals and/or mixtures of the materials mentioned before.
9. A process for making hemocompatible surfaces, characterized in that : a) glycophorins and/or oligosaccharide, polysaccharide and/or lipid portions of the glycoproteins, glycolipids and/or proteoglycans are isolated from the outer layer of blood cells and/or mesothelial cells, and b) said cell constituents are applied and/or incorporated onto and/or into the surfaces of materials of artificial and/or natural organic and/or inorganic compounds and/or mixtures thereof and/or materials having contact with blood and/or other body fluids in invasive operations and/or animal organs and/or organ parts by physical or chemical bonding.
10. The process according to claim 9, characterized in that the constituents of the outer layer of blood cells are isolated from whole blood and/or from cell fractions obtained therefrom of human or animal origin.
11. The process according to one of claims 9 or 10, characterized in that cell constituents are isolated from erythrocytes, leucocytes and/or thrombocytes and/or mixtures thereof.
12. The process according to one of claims 9 - 11, characterized in that constituents of the outer layer of mesothelial cells are isolated from omentum, peritoneum and/or inner organs.
13. The process according to one of claims 9 - 12, characterized in that a chemical immobilization, photoimmobilization, adhesion, drying process or a combination thereof is carried out for applying and/or incorporating the cell constituents onto and/or into the surfaces of the materials.
14. Use of hemocompatible surfaces according to one of claims 1-8 in extensive fields of health, in medicine, dentistry, surgery, cosmetics and/or in fields having contact with blood, tissue and/or other body fluids during invasive operations.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19908318A DE19908318A1 (en) | 1999-02-26 | 1999-02-26 | Hemocompatible surfaces and methods of making them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200106738B true ZA200106738B (en) | 2002-08-15 |
Family
ID=7898933
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200106738A ZA200106738B (en) | 1999-02-26 | 2001-08-15 | Hemocompatible surfaces and method for producing same. |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1152778B1 (en) |
| JP (1) | JP3597474B2 (en) |
| KR (1) | KR100503913B1 (en) |
| CN (1) | CN1198660C (en) |
| AT (1) | ATE250437T1 (en) |
| AU (1) | AU758873B2 (en) |
| BR (1) | BR0008968A (en) |
| CA (1) | CA2363119C (en) |
| DE (2) | DE19908318A1 (en) |
| IL (1) | IL144912A (en) |
| WO (1) | WO2000050106A2 (en) |
| ZA (1) | ZA200106738B (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1435877T3 (en) * | 2001-10-15 | 2009-08-03 | Hemoteq Ag | Coating of stents to prevent restenosis |
| ATE404232T1 (en) * | 2002-05-09 | 2008-08-15 | Hemoteq Ag | HEMOCOMPATIBLE COATED MEDICAL DEVICES, THEIR PRODUCTION AND USE |
| DE10329296B4 (en) * | 2003-06-24 | 2007-07-12 | Leibniz-Institut Für Polymerforschung Dresden E.V. | Coating system for biomaterials |
| DE102005040211B4 (en) | 2005-08-16 | 2010-02-11 | Maquet Cardiopulmonary Ag | Use of nonionic esters in a coating for blood contacting surfaces and medical device |
| CA2656635C (en) | 2006-07-03 | 2013-05-28 | Hemoteq Ag | Stent with polymeric coating comprising rapamycin as an active agent |
| RU2447901C2 (en) | 2007-01-21 | 2012-04-20 | Хемотек Аг | Medical device for treating lumen obturations and preventing threatening recurrent obturations |
| US9192697B2 (en) | 2007-07-03 | 2015-11-24 | Hemoteq Ag | Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis |
| EP3064230B1 (en) | 2009-07-10 | 2019-04-10 | Boston Scientific Scimed, Inc. | Use of nanocrystals for a drug delivery balloon |
| WO2011008393A2 (en) | 2009-07-17 | 2011-01-20 | Boston Scientific Scimed, Inc. | Nucleation of drug delivery balloons to provide improved crystal size and density |
| US8889211B2 (en) | 2010-09-02 | 2014-11-18 | Boston Scientific Scimed, Inc. | Coating process for drug delivery balloons using heat-induced rewrap memory |
| US8669360B2 (en) | 2011-08-05 | 2014-03-11 | Boston Scientific Scimed, Inc. | Methods of converting amorphous drug substance into crystalline form |
| US9056152B2 (en) | 2011-08-25 | 2015-06-16 | Boston Scientific Scimed, Inc. | Medical device with crystalline drug coating |
| CN102501344B (en) * | 2011-09-29 | 2014-07-16 | 华东交通大学 | Method for constructing hemocompatible material surface with bionic periodic structure |
| KR101874819B1 (en) | 2013-02-08 | 2018-07-05 | 아셀, 인크. | Methods of manufacturing bioactive gels from extracellular matrix material |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4350629A (en) * | 1981-07-29 | 1982-09-21 | Massachusetts Institute Of Technology | Procedures for preparing composite materials from collagen and glycosaminoglycan |
| DE3639561A1 (en) * | 1986-11-20 | 1988-06-01 | Baumann Hanno | METHOD FOR PRODUCING NON-THROMBOGEN SUBSTRATES |
| US5236835A (en) * | 1988-10-05 | 1993-08-17 | Hapgood, C.V. | Electro insertion of proteins into red cell membranes |
| US5043164A (en) * | 1989-01-17 | 1991-08-27 | The University Of Tennessee Research Corporation | Blood-stable, cholesterol-free liposomes |
| GB9116036D0 (en) * | 1991-07-25 | 1991-09-11 | Univ Leicester | Preparing grafts for implantation |
| DE4402064A1 (en) * | 1994-01-25 | 1995-07-27 | Kohlensaeurewerk Deutschland | Process for controlling pests in bulk material |
| US5643712A (en) * | 1994-05-20 | 1997-07-01 | Brasile; Lauren | Method for treating and rendering grafts nonthrombogenic and substantially nonimmunogenic using an extracellular matrix coating |
| DE19505070C2 (en) * | 1995-02-15 | 1997-03-27 | Axel Prof Dr Med Haverich | Artificial vascular systems and processes for their manufacture |
| DE19648876C2 (en) * | 1996-11-16 | 1999-10-07 | Will Minuth | Method of making a natural implant |
| DE19700078A1 (en) * | 1997-01-03 | 1998-07-09 | Huels Chemische Werke Ag | Production of polymeric materials with cell proliferation-promoting properties |
| DE19706667A1 (en) * | 1997-02-20 | 1998-08-27 | Merck Patent Gmbh | Bone replacement material with a surface covering with peptides with RGD amino acid sequence |
| DE19724869C2 (en) * | 1997-06-12 | 1999-05-12 | Henkel Kgaa | Use of citosan derivatives for surface coating |
-
1999
- 1999-02-26 DE DE19908318A patent/DE19908318A1/en not_active Withdrawn
-
2000
- 2000-02-24 JP JP2000600716A patent/JP3597474B2/en not_active Expired - Fee Related
- 2000-02-24 DE DE50003828T patent/DE50003828D1/en not_active Expired - Fee Related
- 2000-02-24 CN CNB008042330A patent/CN1198660C/en not_active Expired - Fee Related
- 2000-02-24 EP EP00922483A patent/EP1152778B1/en not_active Expired - Lifetime
- 2000-02-24 BR BR0008968-0A patent/BR0008968A/en not_active Application Discontinuation
- 2000-02-24 CA CA002363119A patent/CA2363119C/en not_active Expired - Fee Related
- 2000-02-24 AU AU42871/00A patent/AU758873B2/en not_active Ceased
- 2000-02-24 AT AT00922483T patent/ATE250437T1/en not_active IP Right Cessation
- 2000-02-24 KR KR10-2001-7010550A patent/KR100503913B1/en not_active IP Right Cessation
- 2000-02-24 WO PCT/EP2000/001497 patent/WO2000050106A2/en active IP Right Grant
-
2001
- 2001-08-15 IL IL144912A patent/IL144912A/en not_active IP Right Cessation
- 2001-08-15 ZA ZA200106738A patent/ZA200106738B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR0008968A (en) | 2001-11-27 |
| JP2002537075A (en) | 2002-11-05 |
| IL144912A (en) | 2009-09-22 |
| CA2363119C (en) | 2007-04-10 |
| EP1152778B1 (en) | 2003-09-24 |
| JP3597474B2 (en) | 2004-12-08 |
| WO2000050106A2 (en) | 2000-08-31 |
| AU4287100A (en) | 2000-09-14 |
| CA2363119A1 (en) | 2000-08-31 |
| ATE250437T1 (en) | 2003-10-15 |
| EP1152778A1 (en) | 2001-11-14 |
| DE50003828D1 (en) | 2003-10-30 |
| IL144912A0 (en) | 2002-06-30 |
| KR100503913B1 (en) | 2005-07-26 |
| AU758873B2 (en) | 2003-04-03 |
| CN1198660C (en) | 2005-04-27 |
| DE19908318A1 (en) | 2000-08-31 |
| WO2000050106A3 (en) | 2001-04-26 |
| CN1341033A (en) | 2002-03-20 |
| KR20010104343A (en) | 2001-11-24 |
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