WO1994002182A1 - Composition de colle fibrine a deux composants servant a ameliorer la fertilisation in vitro - Google Patents

Composition de colle fibrine a deux composants servant a ameliorer la fertilisation in vitro Download PDF

Info

Publication number
WO1994002182A1
WO1994002182A1 PCT/EP1993/001797 EP9301797W WO9402182A1 WO 1994002182 A1 WO1994002182 A1 WO 1994002182A1 EP 9301797 W EP9301797 W EP 9301797W WO 9402182 A1 WO9402182 A1 WO 9402182A1
Authority
WO
WIPO (PCT)
Prior art keywords
component
composition
fibrin
fibrinogen
glue
Prior art date
Application number
PCT/EP1993/001797
Other languages
English (en)
Inventor
Efrach Barnea
Original Assignee
Opperbas Holding B.V.
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 Opperbas Holding B.V. filed Critical Opperbas Holding B.V.
Priority to EP93915861A priority Critical patent/EP0651659B1/fr
Priority to JP6503912A priority patent/JPH08502035A/ja
Priority to DE69309685T priority patent/DE69309685T2/de
Priority to AU45668/93A priority patent/AU4566893A/en
Priority to KR1019950700191A priority patent/KR950702434A/ko
Priority to SK50-95A priority patent/SK5095A3/sk
Publication of WO1994002182A1 publication Critical patent/WO1994002182A1/fr
Priority to FI950194A priority patent/FI950194A0/fi
Priority to NO950171A priority patent/NO950171L/no

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/225—Fibrin; Fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives

Definitions

  • This invention relates to a two component fibrin-glue com ⁇ position comprising the components A and B for improving in vitro fertilization.
  • component A comprises fibrinogen and a protease in ⁇ hibitor
  • component B comprises a proteolytic enzyme being capable of cleaving specifically fibrinogen and causing formation of the fibrin polymer and
  • ingredients for culturing embryonic cells of mamals in one or both of the components A and B.
  • cryoprecipitate of whole blood or plasma is used as fibrinogen containing fraction of component A.
  • commercially available cryoprecipitate can be used. It can be advantageous to concentrate the cryoprecipitate between a factor 2 and 5.
  • the cryoprecipitate is virus inactivated.
  • a procedure for virus inactivation is, for example, described in PCT/EP 91/00503.
  • the basic principle of this method is the treatment of the cryoprecipitate with special detergents and removing the detergent later on from the cryoprecipitate.
  • the protease inhibitor present in component A is aprotinin and present in concentrations up to 10,000 U/ml based on total volume of component A.
  • Aprotinin is com- shoutally available under the trademark Trasylol or Antagosan .
  • tranexamic acid [4- (aminomethyl)cyclohexane carboxylic acid] or its acceptable salts is a suitable agent which can be used instead of aprotinin or in combination with.
  • the second component B of the two component fibrin-glue composition of the invention is prepared by solution of proteolytic enzyme being capable of cleaving specifically fibrinogen.
  • proteolytic enzyme being capable of cleaving specifically fibrinogen.
  • thrombin has been used which was isolated from plasma of human beings or mamals such as bovine.
  • the thrombin can be delivered in a lyophilized form.
  • the reconstitution of thrombin occurs with a solution containing calcium chloride.
  • concentration of the prote ⁇ ase specifically for the cleavage of fibrinogen depends on the method of transferring the embryo into the uterus.
  • the concentration of thrombin should be lower whereas if a fast working fibrin glue is desirable the concentration of thrombin should be higher (fast fibrin- glue) .
  • concentration range of thrombin is 0.4 to 4 units/ml in a slow working fibrin-glue.
  • fibrin-glue of the present invention comprises as component B a proteolytic enzyme which is isolated from snake venom.
  • the snake venom enzyme batroxobin which can be isolated from the south american pit viper Bothrpos moujini can be used. Chemically this venom is a single chain glyco peptide with a molecular weight of approximately 36,000. It is known under the name Defibrase which causes cleavage of the ala-16-arg/l7 glue bond in fibrinogen which causes the release of fibrino peptide A and the formation of monomeric fibrin I.
  • the use of any venom converting fibrinogen to fibrin such as Defibrase or Reptilase is preferred when the cryo ⁇ precipitate is made from autologous source and the use of the venom will avoid the use of human blood product.
  • ingredients for culturing embryonic cells of mamals in the fibrin-glue of the invention there must be present ingredients for culturing embryonic cells of mamals in the fibrin-glue of the invention. This can be achieved either by admixing the ingredients into one or both of the components A and B of the invention or dissolve these ingredients in a liquid and mixing this liquid to one or both of components A and B.
  • Preferred ingredients for culturing embryonic cells of mamals are those comprising calcium chloride, potassium chloride, magnesium sulfate, sodium chloride, sodium bi ⁇ carbonate, sodium dihydrogenphosphate, D-glucose as well as phenol.
  • the solution has a pH of about 7.2. It can be advantageous to add additionally pyruvic acid and antibiotics, e. g. gentamycin.
  • EBSS is the abbreviation for Earle's Balanced Salt Solutions. It can be purchased in liquid or powder form. The liquid contains anhydrous calcium chloride in amounts of 0.2 g/1, potassium chloride 0.4 g/1, MgSO. x 7 H 2 0 0.2 g/1, sodium chloride 6.8 g/1, sodium bicarbonate 2.2 g/1, NaH PO.
  • the respective powder form contains after being dissolved in one liter 0.20 g/L calcium chloride anhydrous, 0.4 g/1 sodium chloride, 0.0977 g/1 magnesium sulfate anhydrous, sodium chloride 6.80 g/1, NaH 2 P0. x H 2 0 and the same D-glucose and phenol red content as in the liquid form. It can be advantageous to add pyruvic acid preferably in amounts of 0.015 g/1 and gentamycin in amounts of 50 mg/1.
  • the medium can be modified in order to meet the special requirements which may be differ, for example, with respect with agricultural applications such as breeding.
  • the above mentioned culture medium can be used also in human in vitro fertilization.
  • the advantage of the present fibrin-glue over the known fibrin-glue products having failed to improve the outcome of in vitro fertilization may be due to its increased anti- fibrinolytic activity preventing or postponing the embryo from one hand in the uterus on the other hand to degredate the clot.
  • the two component fibrin-glue composition of the present invention enables the embryo to survive in the environment of the uterus before it is lodged and permenently fixed to the uterus wall. The surviving is supported by the medium containing ingredients for embryo cell culturing. Sur ⁇ prisingly, the high amounts of protease inhibitor like aprotinin do not interfere with the embryo but prevent the digest of the glue.
  • the two component fibrin-glue com ⁇ position is iso-osmolar. Therefore, the disadvantage of the glues of the prior art being hyper-osmolar is prevented. Hyper-osmolarity causes the death of the embryo by drying out phenomena.
  • the advantageous features of the fibrin-glue of the invention are the presence of salts and nutrients which are important for in vitro growing of the embryo, it contains anti- fibrinolytic activity to postpone the early degradation of the glue either by embryo or by the uterus. Moreover, the antifibrinolytic potency of the embryo has to be balanced to the extent that it will enable the fetus to lyse a certain area around itself creating a halo like shape of fluid surrounded by the fibrin-glue.
  • cryoprecipitate as a source of fibrinogen rather than a fibrinogen concentrate is advantageous since the former one contains ingredients like fibronectin, von Wille- brand factor etc. which may be important for adhesion. Moreover, a cryoprecipitate may also contain other agents such as proteins or low molecular substances which support the development and lodging of the embryo. Also compounds having wound healing properties such as hyaluronic acid can be used.
  • cryoprecipitate is dissolved in culture medium as described above. Then aprotinin or tranexamic acid is added to the cryoprecipitate.
  • concentration of aprotinin in the cryoprecipitate containing component A is preferably in the range of 6,000 to 10,000 u/ml.
  • the con ⁇ centration of tranexamic acid is preferably 10 - 200 ⁇ g/ml (final concentration) . This is equivalent to an aprotinin activity of about 3,000 to 10,000 KlU/ml.
  • the final concen ⁇ tration of aprotinin in the mixture of component A and B is lower because of the dilution when component B is added.
  • the dilution factor depends on the amount of component B which is added.
  • the concentration of fibrinogen in the cryo ⁇ precipitate solution is relatively low compared with other fibrin-glues since there is no need for strong tensile strength. Preferred are concentrations of fibrinogen in the range of 5 to 20 g/1.
  • the embryo is injected for example via the following method. The embryo is placed in the reconstituted cryoprecipitate solution in a culture dish. Then thrombin is added in con ⁇ centrations of 0.4 to 4 units. The thrombin concentration determines the clotting time of the glue, the embryo is sucked in the culture fluid and injected into the uterus.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

On décrit une composition de colle fibrine renfermant les composants A et B dans laquelle le composant A comprend du fibrinogène et un inhibiteur de protéase; le composant B comprend une enzyme protéolytique capable d'effectuer le clivage spécifique du fibrinogène et de provoquer la formation du polymère de fibrine; et des ingrédients pour la culture des cellules embryonnaires de mammifères dans le composant A et/ou B.
PCT/EP1993/001797 1992-07-18 1993-07-09 Composition de colle fibrine a deux composants servant a ameliorer la fertilisation in vitro WO1994002182A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP93915861A EP0651659B1 (fr) 1992-07-18 1993-07-09 Composition de colle fibrine a deux composants servant a ameliorer la fertilisation in vitro
JP6503912A JPH08502035A (ja) 1992-07-18 1993-07-09 試験管内受精を改良するための二成分フィブリングルー組成物
DE69309685T DE69309685T2 (de) 1992-07-18 1993-07-09 Zweikomponenten-Fibrinkleber zur Verbesserung von in-Vitro Befruchtung
AU45668/93A AU4566893A (en) 1992-07-18 1993-07-09 A two component fibrin-glue composition for improving in vitro fertilization
KR1019950700191A KR950702434A (ko) 1992-07-18 1993-07-09 시험관내 수정을 향상시켜주는 2성분 피브린-글루 조성물(a two component fibrin-glue composition for improving in vitro fertilization)
SK50-95A SK5095A3 (en) 1992-07-18 1993-07-09 Two component fibrin-glue composition for improving in vitro fertilization
FI950194A FI950194A0 (fi) 1992-07-18 1995-01-17 Kaksikomponenttinen fibriiniliimakoostumus koeputkihedelmöityksen edistämiseksi
NO950171A NO950171L (no) 1992-07-18 1995-01-17 To-komponent fibrin-limblanding for å forbedre in vitro fruktbarhet

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP92112295.8 1992-07-18
EP92112295 1992-07-18
EP93105298.9 1993-03-30
EP93105298 1993-03-30

Publications (1)

Publication Number Publication Date
WO1994002182A1 true WO1994002182A1 (fr) 1994-02-03

Family

ID=26131003

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1993/001797 WO1994002182A1 (fr) 1992-07-18 1993-07-09 Composition de colle fibrine a deux composants servant a ameliorer la fertilisation in vitro

Country Status (12)

Country Link
JP (1) JPH08502035A (fr)
KR (1) KR950702434A (fr)
AT (1) ATE151295T1 (fr)
AU (1) AU4566893A (fr)
CA (1) CA2140427A1 (fr)
CZ (1) CZ5495A3 (fr)
DE (1) DE69309685T2 (fr)
FI (1) FI950194A0 (fr)
HU (1) HUT71873A (fr)
IL (1) IL106293A0 (fr)
SK (1) SK5095A3 (fr)
WO (1) WO1994002182A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994022503A1 (fr) * 1993-03-30 1994-10-13 Opperbas Holding B.V. Colle fibrine a deux constituants
WO1996003160A1 (fr) * 1994-07-26 1996-02-08 Children's Medical Center Corporation Suspension de cellules de fibrine pour la creation de nouveaux tissus
EP0732931A1 (fr) * 1993-12-17 1996-09-25 New York Blood Center, Inc. Procedes pour l'incorporation et la mise en culture de tissus
US5989215A (en) * 1995-01-16 1999-11-23 Baxter International Inc. Fibrin delivery device and method for forming fibrin on a surface
EP1032367A2 (fr) * 1997-11-17 2000-09-06 Haemacure Corporation Agents de scellement ou adhesifs comprenant un materiau derive d'acide hyaluronique

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2102811A (en) * 1981-07-28 1983-02-09 Immuno Ag A tissue adhesive and a method of producing the same
EP0339607A2 (fr) * 1988-04-29 1989-11-02 Samuel Dr. Itay Composition pour la réparation de cartilage et d'os et procédé pour sa préparation comme implant de tissu du squelette
WO1992015341A1 (fr) * 1991-02-28 1992-09-17 Pentapharm Ag Colle pour le collage de tissus biologiques
WO1992022312A1 (fr) * 1991-06-17 1992-12-23 Wadstroem Jonas Composition pour le traitement de tissus corporels, contenant de la fibrine ou du fibrogene et un polymere biodegradable et biocompatible

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2102811A (en) * 1981-07-28 1983-02-09 Immuno Ag A tissue adhesive and a method of producing the same
EP0339607A2 (fr) * 1988-04-29 1989-11-02 Samuel Dr. Itay Composition pour la réparation de cartilage et d'os et procédé pour sa préparation comme implant de tissu du squelette
WO1992015341A1 (fr) * 1991-02-28 1992-09-17 Pentapharm Ag Colle pour le collage de tissus biologiques
WO1992022312A1 (fr) * 1991-06-17 1992-12-23 Wadstroem Jonas Composition pour le traitement de tissus corporels, contenant de la fibrine ou du fibrogene et un polymere biodegradable et biocompatible

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994022503A1 (fr) * 1993-03-30 1994-10-13 Opperbas Holding B.V. Colle fibrine a deux constituants
EP0732931A1 (fr) * 1993-12-17 1996-09-25 New York Blood Center, Inc. Procedes pour l'incorporation et la mise en culture de tissus
EP0732931A4 (fr) * 1993-12-17 1998-08-05 New York Blood Center Inc Procedes pour l'incorporation et la mise en culture de tissus
WO1996003160A1 (fr) * 1994-07-26 1996-02-08 Children's Medical Center Corporation Suspension de cellules de fibrine pour la creation de nouveaux tissus
US5989215A (en) * 1995-01-16 1999-11-23 Baxter International Inc. Fibrin delivery device and method for forming fibrin on a surface
US6074663A (en) * 1995-01-16 2000-06-13 Baxter International Inc. Method of using cross-linked fibrin material
EP1032367A2 (fr) * 1997-11-17 2000-09-06 Haemacure Corporation Agents de scellement ou adhesifs comprenant un materiau derive d'acide hyaluronique
EP1032367A4 (fr) * 1997-11-17 2005-02-02 Haemacure Corp Agents de scellement ou adhesifs comprenant un materiau derive d'acide hyaluronique

Also Published As

Publication number Publication date
JPH08502035A (ja) 1996-03-05
DE69309685D1 (de) 1997-05-15
KR950702434A (ko) 1995-07-29
HU9500141D0 (en) 1995-03-28
IL106293A0 (en) 1993-11-15
ATE151295T1 (de) 1997-04-15
FI950194A (fi) 1995-01-17
SK5095A3 (en) 1995-07-11
CZ5495A3 (en) 1995-06-14
AU4566893A (en) 1994-02-14
HUT71873A (en) 1996-02-28
FI950194A0 (fi) 1995-01-17
CA2140427A1 (fr) 1994-02-03
DE69309685T2 (de) 1997-10-16

Similar Documents

Publication Publication Date Title
EP0528701B1 (fr) Procédé de préparation d'un concentré de thrombine humaine destiné à un usage thérapeutique
EP0534178B1 (fr) Colle améliorée pour tissus préparée à partir de cryoprécipité
US4055635A (en) Fibrinolytic compositions
US5830741A (en) Composition for tissue dissociation containing collagenase I and II from clostridium histolyticum and a neutral protease
FI90826B (fi) Menetelmä kudosliiman valmistamiseksi
EP0856317A1 (fr) Mélange stabilisé contenant du fibrinogène
CA2090410A1 (fr) Agents anti-thrombogeniques
RU96119971A (ru) Способ получения биологического клея, изготовленного из концентрированных коагулирующих факторов посредством "высаливания"
Kornalik Toxins affecting blood coagulation and fibrinolysis
WO1984001786A1 (fr) Derives d'enzymes et leur utilisation dans le traitement de la thrombose
CA2079077C (fr) Colle physiologique preparee au moyen d'un cryoprecipite
DK167738B1 (da) Fremgangsmaade til fremstilling af en oploesning med hoej specifik rumfangsaktivitet af et protein med vaevs-plasminogenaktivator(t-pa)-aktivitet, oploesning der indeholder protein med t-pa-aktivitet, og anvendelsen af oploesningen inden for human- og veterinaermedicinen
IE63528B1 (en) Composition of anticoagulants
US4190708A (en) Production of urokinase
US20120156284A1 (en) Enhanced biological autologous tissue adhesive composition and methods of preparation and use
NO329232B1 (no) Medikament for lokal paforing og framgangsmate for framstilling av en fibrinogenholdig losning
WO1994002182A1 (fr) Composition de colle fibrine a deux composants servant a ameliorer la fertilisation in vitro
US11229688B2 (en) Stabilized thrombin
Mitrakul Effects of green pit viper (Trimeresurus erythrurus and Trimeresurus popeorum) venoms on blood coagulation, platelets and the fibrinolytic enzyme systems: studies in vivo and in vitro
EP0823476B1 (fr) Procédé d'activation de la prothrombine en thrombine
CA1283047C (fr) Precurseur de l'activateur du plasminogene stabilise et methode de production
EP0651659B1 (fr) Composition de colle fibrine a deux composants servant a ameliorer la fertilisation in vitro
Jeljaszewicz et al. Intravascular Coagulation and Fibrinolysis by Stapliylocoagiilase. Comparison with Thrombin
Aronson Factor IX concentrates

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BB BG BR CA CZ FI HU JP KP KR LK MG MN MW NO NZ PL RO RU SD SK UA VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1993915861

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: PV1995-54

Country of ref document: CZ

WWE Wipo information: entry into national phase

Ref document number: 254121

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 5095

Country of ref document: SK

WWE Wipo information: entry into national phase

Ref document number: 2140427

Country of ref document: CA

Ref document number: 950194

Country of ref document: FI

WWP Wipo information: published in national office

Ref document number: 1993915861

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: PV1995-54

Country of ref document: CZ

WWR Wipo information: refused in national office

Ref document number: PV1995-54

Country of ref document: CZ

WWG Wipo information: grant in national office

Ref document number: 1993915861

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1993915861

Country of ref document: EP