WO1988007078A1 - Immobilization substance - Google Patents

Immobilization substance Download PDF

Info

Publication number
WO1988007078A1
WO1988007078A1 PCT/DE1988/000165 DE8800165W WO8807078A1 WO 1988007078 A1 WO1988007078 A1 WO 1988007078A1 DE 8800165 W DE8800165 W DE 8800165W WO 8807078 A1 WO8807078 A1 WO 8807078A1
Authority
WO
WIPO (PCT)
Prior art keywords
substance according
adhesives
adhesins
immobilization
immobilizing
Prior art date
Application number
PCT/DE1988/000165
Other languages
German (de)
French (fr)
Inventor
Wolfgang Georg Konrad MÜLLER-LIERHEIM
Original Assignee
Dr. Müller-Lierheim Ag
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Dr. Müller-Lierheim Ag filed Critical Dr. Müller-Lierheim Ag
Publication of WO1988007078A1 publication Critical patent/WO1988007078A1/en

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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10—Polypeptides; Proteins
    • A61L24/106—Fibrin; Fibrinogen
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier

Definitions

  • the object of the invention is to provide an immobilizing substance for binding biological material to carriers.
  • This immobilization substance is characterized in that adhesive proteins which are isolated from extracellular structures, in particular fimbriae, pili, outer membranes or capsules of Gram-negative bacteria, in particular coli bacteria, are used.
  • adhesive proteins typically have a molecular weight of the order of 12,000 to 30,000 daltons and can recognize carbohydrate components of glycolipoids and glycoproteins of higher cells. These adhesive proteins mediate the adherence of the bacteria to higher cells (e.g. erythrocytes, ymphocytes) and to tissues (e.g. epithelium). These adhesive proteins are generally not cleaved by mammalian proteoses.
  • the isolated adhesive proteins (glycoproteins) or the corresponding binding sites of these proteins or the protein fragments or the z.
  • B. polypeptides obtained by hydrolysis are according to the invention for the immobilization of cells, in particular mammalian cells, tissue, pharmaceutical active ingredients, antibodies or
  • these adhesive proteins can be used as attachment factors for mammalian cells or tissues.
  • the cells or tissues can be found on the surface of an implant using the adhesive proteins. tie the basic body of the body irreversibly. Blood serum or parts thereof as well as fibronectin come into consideration as growth factors.
  • a combination of metabolic products of cells and biochemically modified natural products are also suitable as growth factors.
  • Further growth factors can be proteins which lead to cell differentiation and proteins which induce bone substance.
  • the implants can be extra-corporal or implantable artificial organs, vessels, prostheses, skin replacements, dentures, artificial eye lenses, contact lenses and the like.
  • the adhesins can be bound to the implant surfaces by covalent binding.
  • the adhesive proteins can also be used in the formulation of pharmaceuticals to bind the pharmaceutical active substances, in particular blood coagulants, to the carrier bodies, in particular powdered carrier bodies.
  • Carbohydrate components of glycolipoids and higher cell containing glycoproteins are also suitable as carrier bodies, since these are specifically recognized by the adhesive proteins.
  • the adhesive proteins can be used as immobilizing substance for antibody-producing cells, in particular mammalian cells, of tissue and the like.
  • the adhesives in the formation of endothelium in vascular grafts.
  • the adhesives are used in surgery as tissue adhesives. Since the adhesins are water-soluble, they can be used as a single component can be used. The areas of application are in particular trauma surgery, soft tissue surgery and also liver surgery, since in these cases sutures often do not lead to the desired success. Compared to the Fimbrienklebern hitherto used, which are ⁇ ich is a Z "weikomponentenkleber, which must be mixed tion during the Opera and quickly processed, and to use therefore difficult and not without risk for d clotting, contact tissue adhesive adhesins wherein di se disadvantages do not occur. Because adhesions are water soluble, you can take it nen g ln the form of a single-component used was ⁇ to.
  • Non-Fi brien-associated adhesives are preferably used, since they can be isolated from the cell surface of the bacteria with greater yield. These non-fimbria-associated adhesins, which are preferably obtained from Escherichia coli bacteria, bind selectively to human cell membranes. The molecular weight is on the order of 12,000 to 30,000 daltons, preferably in the range of 20,000 daltons. The non-fimbria-associated adhesins can form aggregates. This then apparent
  • the following procedure can be carried out for obtaining the adhesins.
  • the corresponding E. coli bacteria can be cultivated on agar in, for example, petri dishes. Separation of the adhesins from the cell membranes of the bacteria are first sonicated and then separated by ultracentrifugation and then purified by subsequent chromatographic purification. In the cultivation in 10 petri dishes with a diameter of 14 cm, about 40 to 50 mg of coarsely purified adhesins or about 30 mg of highly purified adhesions are obtained.
  • the non-fimbria-associated adhesins obtained can have the following specificities depending on the E. coli strain:
  • NFA non-fimbria associated adhesins
  • NFA-1 the receptor is glycophorin A (occurs mainly on erythrocytes, but also binds to kidney cells)
  • NFA-2 The receptor is glycophorin A.
  • NFA-3 receptor is the blood group antigen N
  • NFA-4 receptor is the blood group antigen M
  • NFA-5 The receptor is the blood group antigen M.

Abstract

An immobilization substance, characterized by adhesive proteins (adhesins), isolated from extracellular structures, in particular fimbria, pili, external membranes or capsules of Gram-negative bacteria, in particular coli bacteria, for binding cells, in particular mammal cells, tissues, pharmaceutical active principles, antibodies and growth factors to carriers.

Description

Beschreibung description
ImmobilisierungssubstanzImmobilizing substance
Die Aufgabe der Erfindung besteht darin, eine Immobilisie¬ rungssubstanz zur Bindung von biologischem Material an Trägern zu schaffen.The object of the invention is to provide an immobilizing substance for binding biological material to carriers.
Diese Immobilisierungεsubstanz ist' dadurch gekennzeichnet, daß adhäεive Proteine, die aus extrazellulären Strukturen, inεbesonTlere Fimbrien, Pili, äußeren Membranen oder Kapsel von Gram-negativen Bakterien, insbesondere Colibakterien, isoliert sind, verwendet werden.This immobilization substance is characterized in that adhesive proteins which are isolated from extracellular structures, in particular fimbriae, pili, outer membranes or capsules of Gram-negative bacteria, in particular coli bacteria, are used.
Diese adhäsiven Proteine (Adhäεine) besitzen typiεcherweis ein Molekulargewicht in der Größenordnung von 12 000 bis 30 000 Dalton und können Kohlehydratkomponenten von Glyco- lipoiden und Glycoproteinen höherer Zellen erkennen. Diese adhäsiven Proteine vermitteln die Adhärenε der Bakterien an höhere Zellen (z. B. Erythrozyten, ymphozyten) und an Gewebe (z. B. Epithel). Diese adhäεiven Proteine werden im allgemeinen von Säugetier-Proteoεen nicht geεpalten.These adhesive proteins (adhesins) typically have a molecular weight of the order of 12,000 to 30,000 daltons and can recognize carbohydrate components of glycolipoids and glycoproteins of higher cells. These adhesive proteins mediate the adherence of the bacteria to higher cells (e.g. erythrocytes, ymphocytes) and to tissues (e.g. epithelium). These adhesive proteins are generally not cleaved by mammalian proteoses.
Dieεe iεolierten adhäεiven Proteine (Glycoproteine) bzw. di entsprechenden Bindungsstellen dieser Proteine oder der Proteinfragmente oder der gegebenenfalls daraus z. B. durch Hydrolyse gewonnenen Polypeptide werden erfindungsgemäß zur Immobilisierung von Zellen, insbeεondere Säugerzellen, Gewe ben, von pharmazeutischen Wirkstoffen, Antikörpern oderThe isolated adhesive proteins (glycoproteins) or the corresponding binding sites of these proteins or the protein fragments or the z. B. polypeptides obtained by hydrolysis are according to the invention for the immobilization of cells, in particular mammalian cells, tissue, pharmaceutical active ingredients, antibodies or
Wachstumεkörpern an Trägern verwendet. Inεbesondere für die Oberflächenaufbereitung von Implantaten lassen sich diese adhäsiven Proteine als Anheftfaktoren für Säugetierzellen bzw. Gewebe verwenden. Die Zellen bzw. Gewebe lassen sich über die adhäεiven Proteine an der Oberfläche eines Implan- tatgrundkörperε quaεi irreversibel binden. Als Wachεtumε- faktoren kommen Blutserum oder Beεtandteile davon εowie Fibronektin in Frage. Auch eine Kombination auε Stoff- Wechselprodukten von Zellen und auf biochemischem Weg modi- fizierten Naturprodukten sind als Wachstumεfaktoren geeig¬ net. Weitere Wachεtumsfaktoren können zur Zelldifferenzie¬ rung führende Proteine und Knochenεubstanz induzierende Pro teine sein. Bei den Implantaten kann es sich um extra- korporale oder implantierbare künstliche Organe, Gefäße, Prothesen, Hautersatz, Zahnersatz, künstliche Augenlinsen, Kontaktlinsen und dgl. handeln. Durch kovalente Bindung können die Adhäsine an den Implantatoberflächen gebunden sein.Growth bodies used on carriers. In particular for the surface preparation of implants, these adhesive proteins can be used as attachment factors for mammalian cells or tissues. The cells or tissues can be found on the surface of an implant using the adhesive proteins. tie the basic body of the body irreversibly. Blood serum or parts thereof as well as fibronectin come into consideration as growth factors. A combination of metabolic products of cells and biochemically modified natural products are also suitable as growth factors. Further growth factors can be proteins which lead to cell differentiation and proteins which induce bone substance. The implants can be extra-corporal or implantable artificial organs, vessels, prostheses, skin replacements, dentures, artificial eye lenses, contact lenses and the like. The adhesins can be bound to the implant surfaces by covalent binding.
Auch bei der Formulierung von Arzneimitteln lasεen εich die adhäsiven Proteine zur Bindung der pharmazeutischen Wirk¬ sto fe, insbesondere von Blutgerinnungsmitteln, an den Trä¬ gerkörpern, inεbeεondere pulverförmigen Trägerkörpern, ver¬ wenden.The adhesive proteins can also be used in the formulation of pharmaceuticals to bind the pharmaceutical active substances, in particular blood coagulants, to the carrier bodies, in particular powdered carrier bodies.
Alε Trägerkörper kommen auch Kohlehydratkomponenten von Glycolipoiden und Glycoproteinen enthaltenden höheren Zelle in Frage, da dieεe von den adhäεiven Proteinen spezifisch erkannt werden.Carbohydrate components of glycolipoids and higher cell containing glycoproteins are also suitable as carrier bodies, since these are specifically recognized by the adhesive proteins.
Ferner können die adhäsiven Proteine als Immobilisierungε- substanz für Antikörper produzierende Zellen, inεbeεondere Säugerzellen, von Gewebe und dgl. verwendet werden. Ferner besteht eine Anwendungsmöglichkeit der Adhäεine in der Endo theliumbildung bei Gefäßverpflanzungen.Furthermore, the adhesive proteins can be used as immobilizing substance for antibody-producing cells, in particular mammalian cells, of tissue and the like. There is also an application of the adhesives in the formation of endothelium in vascular grafts.
Eine weitere wichtige Anwendung besteht darin, daß die Ad¬ häεine in der Chirurgie als Gewebekleber zum Einsatz kommen Da die Adhäsine wasεerlöεlich sind, können sie als Einkompo nentenkleber zur Anwendung kommen. Die Anwendungεgebiete sind insbesondere die Unfallchirurgie, die Weichteilchirur gie und auch die Leberchirurgie, da in diesen Fällen Nähte häufig nicht zum gewünschten Erfolg führen. Gegenüber den bislang verwendeten Fimbrienklebern, bei denen es εich um einen Z"weikomponentenkleber handelt, der während der Opera tion angemischt und schnell verarbeitet werden muß, und in der Handhabung daher schwierig und nicht ohne Risiko für d Blutgerinnung ist, treten bei dem Adhäsine-Gewebekleber di se Nachteile nicht auf. Da Adhäsine wasserlöslich sind, kö nen siegln Form eines Einkomponentenklebers verwendet wer¬ den.Another important application is that the adhesives are used in surgery as tissue adhesives. Since the adhesins are water-soluble, they can be used as a single component can be used. The areas of application are in particular trauma surgery, soft tissue surgery and also liver surgery, since in these cases sutures often do not lead to the desired success. Compared to the Fimbrienklebern hitherto used, which are εich is a Z "weikomponentenkleber, which must be mixed tion during the Opera and quickly processed, and to use therefore difficult and not without risk for d clotting, contact tissue adhesive adhesins wherein di se disadvantages do not occur. Because adhesions are water soluble, you can take it nen g ln the form of a single-component used wer¬ to.
Bevorzugt kommen Nicht-Fi brien-assoziierte Adhäεine zum Einsatz, da diese εich mit größerer Ausbeute von der Zell¬ oberfläche der Bakterien isolieren laεsen. Diese Nicht- Fimbrien-assoziierten Adhäsine, welche bevorzugt aus Escherichia Coli-Bakterien gewonnen werden, binden selekti an Humanzellmembranen. Das Molekulargewicht liegt in der Größenordnung von 12 000 bis 30 000 Dalton, bevorzugt im Bereich von 20 000 Dalton. Die Nicht-Fimbrien-aεsoziierten Adhäεine können Aggregate bilden. Dieses dann apparenteNon-Fi brien-associated adhesives are preferably used, since they can be isolated from the cell surface of the bacteria with greater yield. These non-fimbria-associated adhesins, which are preferably obtained from Escherichia coli bacteria, bind selectively to human cell membranes. The molecular weight is on the order of 12,000 to 30,000 daltons, preferably in the range of 20,000 daltons. The non-fimbria-associated adhesins can form aggregates. This then apparent
Molekulargewicht nach der Aggregatbildung beträgt etwaMolecular weight after aggregate formation is approximately
6 7 10 bis 10 Dalton. Ferner sind dieεe Adhäsine wasserlösli6 7 10 to 10 daltons. Furthermore, these adhesins are water-soluble
Für die Gewinnung der Adhäsine läßt εich folgendes Verfahr durchführen. Auf Agar lassen sich in beispielsweise Petri- schalen die entsprechenden E. Coli-Bakterien kultivieren. Trennung der Adhäsine von den Zellmembranen der Bakterien werden dieεe zunächst ultrabeschallt und dann durch Ultraz trifugieren getrennt urid nachfolgende chromatographische A reinigung gereinigt. Man erhält bei der Kultivierung in 10 Petrischalten mit 14 cm Durchmeεεer etwa 40 bis 50 mg grob gereinigte Adhäsine bzw. etwa 30 mg hoch gereinigte Adhäεi Die gewonnenen Nicht-Fimbrien-assoziierten Adhäsine können je nach E. Coli-Stamm folgende Spezifizitäten aufweisen:The following procedure can be carried out for obtaining the adhesins. The corresponding E. coli bacteria can be cultivated on agar in, for example, petri dishes. Separation of the adhesins from the cell membranes of the bacteria are first sonicated and then separated by ultracentrifugation and then purified by subsequent chromatographic purification. In the cultivation in 10 petri dishes with a diameter of 14 cm, about 40 to 50 mg of coarsely purified adhesins or about 30 mg of highly purified adhesions are obtained The non-fimbria-associated adhesins obtained can have the following specificities depending on the E. coli strain:
Spezifitäten bei den Nicht-Fimbrien-assoziierten Adhäsinen (NFA)Specificities in non-fimbria associated adhesins (NFA)
NFA-1: Rezeptor ist das Glycophorin A (Vorkommen ist vor allem auf Erythrozyten, Bindung aber auch an Nierenzellen)NFA-1: the receptor is glycophorin A (occurs mainly on erythrocytes, but also binds to kidney cells)
NFA-2: Rezeptor ist daε Glycophorin ANFA-2: The receptor is glycophorin A.
NFA-3: Rezeptor iεt daε Blutgruppenantigen NNFA-3: receptor is the blood group antigen N
NFA-4: Rezeptor iεt daε Blutgruppenantigen MNFA-4: receptor is the blood group antigen M
NFA-5: Rezeptor ist das Blutgruppenantigen M. NFA-5: The receptor is the blood group antigen M.

Claims

Λ101520Patentansprüche: Λ101520Patent claims:
1. Immobilisierungεsubstanz, gekennzeichnet durch adhäsive 25 Proteine (Adhäsine), die aus extrazellulären Strukturen, insbesondere Fimbrien, Pili, äußeren Membranen oder Kapsel von Gram-negativen Bakterien, insbeεondere Colibakterien, iεoliert sind, zur Bindung von Zellen, insbesondere Säuger zellen,, Geweben, pharmazeutischen Wirkstoffen, Antikörpern 30 Wachεtumsfaktoren an Trägern.1. Immobilisierungεsubstanz, characterized by adhesive 25 proteins (adhesins), which are iεoliert from extracellular structures, in particular fimbriae, pili, outer membranes or capsule of Gram-negative bacteria, insbeεondere coli bacteria, cells for binding of cells, in particular mammalian, tissues , active pharmaceutical ingredients, antibodies 30 growth factors on carriers.
2. Immobilisierungssubstanz nach Anspruch 1, dadurch ge¬ kennzeichnet, daß durch die Adhäεine εpezifiεch Kohle¬ hydratkomponenten von Glycolipoiden oder Glycoproteinen er2. immobilizing substance according to claim 1, characterized ge indicates that by the Adhäεine εpecific Kohl¬ hydrate components of glycolipoids or glycoproteins he
35 kannt bzw. adsorptiv gebunden werden.35 can be bound or adsorptively bound.
Λ Λ
3. Immobiliεierungssubstanz nach Anεpruch 1 oder 2, dadurch gekennzeichnet, daß die von den Adhäεinen erkannten bzw. ge bundenen Kohlehydratkomponenten Glycolipoide oder Glyco- proteine sind, die in der äußeren Membran von Säugetier- zellen vorkommen.3. immobilizing substance according to claim 1 or 2, characterized in that the carbohydrate components recognized or bound by the adhesives are glycolipoids or glycoproteins which occur in the outer membrane of mammalian cells.
4. Immobilisierungsεubstanz nach den Ansprüchen 1 bis 3, dadurch gekennzeichnet", daß die Bindung der Adhäεine an Säugetier-zellmembranbeεtändige Glycolipoide oder Glyco- proteine artεpezifisch erfolgt.4. Immobilizing substance according to claims 1 to 3, characterized in "that the binding of the adhesives to mammalian cell membrane-resistant glycolipoids or glycoproteins takes place in a species-specific manner.
5. Immobilisierungεεubεtanz nach einem der Anεprüche 1 bis5. Immobilization substance according to one of claims 1 to
4, dadurch gekennzeichnet, daß die Adhäεine auε extrazellu¬ lären Strukturen von Eεcherichia Coli-Bakterien iεoliert sind.4, characterized in that the adhesives are isolated from extracellular structures of Echerichia coli bacteria.
6. Immobiliεierungεεubεtanz nach einem der Anεprüche 1 bis6. Immobilization substance according to one of claims 1 to
5, gekennzeichnet durch Nicht-Fimbrien-asεoziierte Adhäεine aus E.coli.5, characterized by non-fimbria-associated adhesives from E. coli.
7. Immobilisierungssubεtanz nach einem der Anεprüche 1 bis7. Immobilization substance according to one of claims 1 to
6, dadurch gekennzeichnet, daß die Adhäεine waεserlöslich εind.6, characterized in that the adhesives are water-soluble.
8. Immobiliεierungεsubεtanz nach einem der Anεprüche 1 bis8. Immobilization substance according to one of claims 1 to
7, dadurch gekennzeichnet, daß die Nicht-Fimbrien-asεoziier ten Adhäsine ein Molekulargewicht in der Größenordnung von 12000 bis 30 000 Dalton aufweisen.7, characterized in that the non-fimbria-associated adhesins have a molecular weight of the order of 12,000 to 30,000 daltons.
9. Immobilisierungssubstanz nach einem der Ansprüche 1 bis9. immobilization substance according to one of claims 1 to
8, dadurch gekennzeichnet, daß die Nicht-Fimbrien-assoziier ten Adhäsine im Aggregationszustand ein apparenteε Moleku-8, characterized in that the non-fimbria-associated adhesins in the state of aggregation are an apparenteε molecule
6 7 largewicht von etwa 10 biε 10 Dalton aufweisen. 6 7 lar weight of about 10 to 10 daltons.
10. Immobilisierungssubstanz nach den Ansprüchen 1 biε 6, dadurch gekennzeichnet, daß die Adhäεine zur Immobiliεieru von Säugetierzellen und -geweben, inεbesondere menschliche Zellen und Gewebe, an Implantate oder künstliche Organe ve wendet werden.10. Immobilizing substance according to claims 1 to 6, characterized in that the adhesives for immobilizing mammalian cells and tissues, in particular human cells and tissues, are used on implants or artificial organs.
11. Immobilisierungssubstanz nach den Ansprüchen 1 bis 10, dadurch gekennzeichnet, daß die Adhäsine zur Formulierung oder als Wirkstoff von Arzneimitteln oder zur Herstellung von Diagnostika Verwendung finden.11. Immobilizing substance according to claims 1 to 10, characterized in that the adhesins are used for the formulation or as an active ingredient of medicaments or for the production of diagnostics.
12. Immobilisierungεsubεtanz nach den Ansprüchen 1 biε 11, dadurch gekennzeichnet, daß die Adhäεine zur Zellkultur oder Zelltrennung in vitro Verwendung finden.12. Immobilization substance according to claims 1 to 11, characterized in that the adhesives are used for cell culture or cell separation in vitro.
13. Immobiliεierungssubεtanz nach einem der Anεprüche 1 bi13. Immobilization substance according to one of claims 1 to 2
12, dadurch gekennzeichnet, daß die Adhäεine alε Gewebe¬ kleber für menschliches oder tierisches Gewebe ausgebildet sind.12, characterized in that the adhesives are designed as tissue adhesives for human or animal tissue.
14. Immobiliεierungssubεtanz nach einem der Ansprüche 1 bi14. Immobiliεierungssubεtanz according to any one of claims 1 bi
13, dadurch gekennzeichnet, daß die Adhäsine in einer Lösu (insbesondere wäßrigen Lösung) vorliegen.13, characterized in that the adhesins are present in a solution (in particular an aqueous solution).
15. Verwendung einer Immobilisierungεεubεtanz nach einem der Ansprüche 1 bis 14 für die Endotheliumbildung an ver¬ pflanzten Gefäßen. 15. Use of an immobilization substance according to one of claims 1 to 14 for the formation of endothelium on transplanted vessels.
PCT/DE1988/000165 1987-03-20 1988-03-17 Immobilization substance WO1988007078A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19873709101 DE3709101A1 (en) 1987-03-20 1987-03-20 IMMOBILIZATION SUBSTANCE
DEP3709101.8 1987-03-20

Publications (1)

Publication Number Publication Date
WO1988007078A1 true WO1988007078A1 (en) 1988-09-22

Family

ID=6323543

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1988/000165 WO1988007078A1 (en) 1987-03-20 1988-03-17 Immobilization substance

Country Status (3)

Country Link
EP (1) EP0349558A1 (en)
DE (1) DE3709101A1 (en)
WO (1) WO1988007078A1 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990004963A1 (en) * 1988-11-08 1990-05-17 Danbiosyst Uk Limited Adhesive drug delivery composition
WO1990005522A1 (en) * 1988-11-17 1990-05-31 Per Prisell Pharmaceutical preparation
WO1991006324A1 (en) * 1989-11-03 1991-05-16 Karlheinz Schmidt Active substance complex for the production of biological parts, especially organs for living organisms; process for its production and its use
EP0572364A2 (en) * 1992-05-29 1993-12-01 Istituto Nazionale Per La Ricerca Sul Cancro Differentiated ocular surface epithelial cell cultures, process for the preparation and carrier for uses thereof
US5916553A (en) * 1992-09-17 1999-06-29 Schmidt; Karlheinz Complex for inducing bone growth in the mastoid cavity
US5928635A (en) * 1994-12-07 1999-07-27 Schmidt; Karlheinz Process for producing active agent complexes
US7214654B1 (en) 1994-12-07 2007-05-08 Karlheinz Schmidt Agent for the manufacture of biological parts including an active ingredient complex and carrying materials suitable for the active ingredient complex

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5605938A (en) * 1991-05-31 1997-02-25 Gliatech, Inc. Methods and compositions for inhibition of cell invasion and fibrosis using dextran sulfate

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Affinity Chromatography, Principles & Methods", Juni 1979, Pharmacia Fine Chemicals AB, (Uppsala, SE), siehe Seiten 48-51 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2243778A (en) * 1988-11-08 1991-11-13 Danbiosyst Uk Adhesive drug delivery composition
GB2243778B (en) * 1988-11-08 1992-06-24 Danbiosyst Uk Adhesive drug delivery composition
WO1990004963A1 (en) * 1988-11-08 1990-05-17 Danbiosyst Uk Limited Adhesive drug delivery composition
US6387408B1 (en) 1988-11-08 2002-05-14 West Pharmaceutical Services Drug Delivery And Clinical Research Limited Adhesive drug delivery composition
US6355276B1 (en) * 1988-11-08 2002-03-12 West Pharmacuetical Services Drug Delivery & Clinical Adhesive drug delivery composition
WO1990005522A1 (en) * 1988-11-17 1990-05-31 Per Prisell Pharmaceutical preparation
AU632074B2 (en) * 1988-11-17 1992-12-17 Gunnar Norstedt Pharmaceutical preparation
US5932207A (en) * 1989-11-03 1999-08-03 Schmidt; Karlheinz Complex active ingredient for the production of biological parts, especially organs for living organisms: method for the production of the same and its use
WO1991006324A1 (en) * 1989-11-03 1991-05-16 Karlheinz Schmidt Active substance complex for the production of biological parts, especially organs for living organisms; process for its production and its use
EP0572364A2 (en) * 1992-05-29 1993-12-01 Istituto Nazionale Per La Ricerca Sul Cancro Differentiated ocular surface epithelial cell cultures, process for the preparation and carrier for uses thereof
EP0572364A3 (en) * 1992-05-29 1995-02-15 Ist Naz Ric Sul Cancro Differentiated ocular surface epithelial cell cultures, process for the preparation and carrier for uses thereof.
US5916553A (en) * 1992-09-17 1999-06-29 Schmidt; Karlheinz Complex for inducing bone growth in the mastoid cavity
US5928635A (en) * 1994-12-07 1999-07-27 Schmidt; Karlheinz Process for producing active agent complexes
US7214654B1 (en) 1994-12-07 2007-05-08 Karlheinz Schmidt Agent for the manufacture of biological parts including an active ingredient complex and carrying materials suitable for the active ingredient complex

Also Published As

Publication number Publication date
DE3709101A1 (en) 1988-09-29
EP0349558A1 (en) 1990-01-10

Similar Documents

Publication Publication Date Title
US6949625B2 (en) Injectable implant of insoluble globin
CA1328237C (en) Bioadhesives for cell and tissue adhesion
RU2667964C1 (en) Method, test tube and device for making of compositions for wound healing
EP0285370B1 (en) Injectable soft tissue augmentation materials from the placenta and their method of manufacture
DE69918159T2 (en) METHOD AND DEVICE FOR CONTROLLING TISSUE IMPLANT INTERACTIONS
EP1077072B1 (en) In vitro process for the preparation of heart valve or vessel prothese
CA2786400C (en) Biomaterials made from human hair
JP2741378B2 (en) Improved biocompatibility of solid surfaces
KR20190112868A (en) Native(telopeptide) Placental Collagen Compositions
EP0244688B1 (en) Adhesives derived from bioadhesive polyphenolic proteins
DE69531712T2 (en) Hybrid gel that secretes a biologically active substance
JPH05501208A (en) Active substance complexes for producing biological parts, in particular organs of living organisms; methods for preparing these active substance complexes and their applications.
WO1988007078A1 (en) Immobilization substance
EP2493453B1 (en) Therapeutic use of biocompatible compositions and materials polymerized therefrom for inhibiting angiogenesis
JPH03503167A (en) Site-directed angioplasty device and its usage
CN109771694A (en) The preparation method and application of self assembly polypeptide nano fiber water gel scaffold material
DE69938130T2 (en) NEW PEPTIDE
AU2004237992B2 (en) Insoluble globin injectable implant
CN110711264B (en) Composite material, medical adhesive, and preparation method and application thereof
US20160129045A1 (en) Composition for wound-healing comprising adult stem cells and elastin-like polypeptides
EP0049341B1 (en) Process for conditioning alloplastic implantations and transplantations
US10813954B2 (en) Pharmaceutical composition for treating diabetes, comprising pancreatic islet cells and elastin-like artificial extracellular matrix
CN110225920A (en) Difunctional novel peptide and application thereof with cell permeability and bone tissue regeneration ability
CN103301153A (en) Application of umbilical cord mesenchymal stem cell culture solution or product prepared from umbilical cord mesenchymal stem cell culture solution in preparation of medicament for treating skin wound
RU2736480C2 (en) Method for production of collagen-laminin matrix for healing of ulcers, burns and wounds of human skin

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP SU US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE

WWE Wipo information: entry into national phase

Ref document number: 1988902404

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1988902404

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1988902404

Country of ref document: EP