WO1994014460A1 - Method for crosslinking of haemoglobin and use of such crosslinked haemoglobin - Google Patents

Method for crosslinking of haemoglobin and use of such crosslinked haemoglobin Download PDF

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Publication number
WO1994014460A1
WO1994014460A1 PCT/DK1993/000397 DK9300397W WO9414460A1 WO 1994014460 A1 WO1994014460 A1 WO 1994014460A1 DK 9300397 W DK9300397 W DK 9300397W WO 9414460 A1 WO9414460 A1 WO 9414460A1
Authority
WO
WIPO (PCT)
Prior art keywords
haemoglobin
crosslinked
crosslinking
transglutaminase
fact
Prior art date
Application number
PCT/DK1993/000397
Other languages
English (en)
French (fr)
Inventor
Bent Riber Petersen
Original Assignee
Novo Nordisk A/S
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 Novo Nordisk A/S filed Critical Novo Nordisk A/S
Priority to EP94919454A priority Critical patent/EP0671921A1/en
Priority to US08/432,172 priority patent/US5563047A/en
Publication of WO1994014460A1 publication Critical patent/WO1994014460A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/795—Porphyrin- or corrin-ring-containing peptides
    • C07K14/805—Haemoglobins; Myoglobins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the invention comprises a method for crosslinking of haemoglobin and a use of such crosslinked haemoglobin. From Biotechnology of Blood, edited by Jack Goldstein, 1991 , page
  • the prior art methods for polymerisation of haemoglobin are associated with several drawbacks, especially the heterogenous distribution of polymers due to the unspecificity of the hitherto used crosslinking agents and the fact that the degree of polymerisation is difficult to control.
  • the method according to the invention for crosslinking of haemoglobin is characterized by the fact that haemoglobin present in an aqueous solution thereof with a pH between 5 and 9 is crosslinked by means of transglutaminase (EC
  • transglutaminase is a very specific crosslinking agent, and that it is possible to obtain a very good controllable degree of polymerisation by means of the method according to the invention.
  • a preferred embodiment of the method according to the invention is characterized by the fact that the pH value of the aqueous solution is between 6.5 and 8.
  • the crosslinking reaction proceeds with a most satisfactory velocity in this pH interval.
  • a preferred embodiment of the method according to the invention is characterized by the fact that the maximum amount of transglutaminase is 2% of pure transglutaminase protein, calculated in regard to the haemoglobin protein.
  • a preferred embodiment of the method according to the invention is characterized by the fact that the crosslinking is stopped by heat inactivation of the transglutaminase, preferably by heating to up to 65°C for 5 minutes. This is the most simple and effective way of inactivation.
  • the invention comprises a use of the crosslinked haemoglobin producible by means of the method according to the invention, due to any of the inherent properties of the crosslinked haemoglobin.
  • a preferred embodiment of the use of the crosslinked haemoglobin producible by means of the method according to the invention is as a molecular agent for oxygen transportation, i.e. as a blood substitute.
  • the desirability of new blood substitutes are well known, vide Biotechnology of Blood, edited by Jack Goldstein, 1991, page 101. It has been found that it is easy to produce the crosslinked haemoglobin according to the invention with a molecular weight well above 64,000 Dalton, which is above the cut-off value of the kidneys, 60,000 Dalton. This is one of the conditions for a satisfactory blood substitute.
  • a preferred embodiment of the use of the crosslinked haemoglobin producible by means of the method according to the invention is as an oxygen scavenger. It has been found that this haemoglobin functions effectively as an oxygen scavenger, e.g. in food items, and that addition of antioxidants hereby can be eliminated or reduced.
  • a preferred embodiment of the use of the crosslinked haemoglobin producible by means of the method according to the invention is as a constituent of a food composition.
  • BRD BRD
  • concentration of Ca ++ of 5 mM transglutaminase was added in an amount of 0.4% (w/w) in relation to the amount of haemoglobin, i.e. 112 mg.
  • the transglutaminase was produced as indicated in -Example 1 of PCT/DK92/00022. The reaction was carried out for 200 minutes, and subsequently the activity of the transglutaminase was inactivated by heating to 65°C for 5 minutes. Reference is made to Fig. 1 , which shows the progression of the polymerization expressed as viscosity.
  • the crosslinked haemoglobin was isolated by lyophilization.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Specific Sealing Or Ventilating Devices For Doors And Windows (AREA)
  • Peptides Or Proteins (AREA)
PCT/DK1993/000397 1992-12-03 1993-12-01 Method for crosslinking of haemoglobin and use of such crosslinked haemoglobin WO1994014460A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP94919454A EP0671921A1 (en) 1992-12-03 1993-12-01 Method for crosslinking of haemoglobin and use of such crosslinked haemoglobin
US08/432,172 US5563047A (en) 1992-12-03 1993-12-01 Method for crosslinking of haemoglobin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK921450A DK145092D0 (US20100012521A1-20100121-C00001.png) 1992-12-03 1992-12-03
DK1450/92 1992-12-03

Publications (1)

Publication Number Publication Date
WO1994014460A1 true WO1994014460A1 (en) 1994-07-07

Family

ID=8104955

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK1993/000397 WO1994014460A1 (en) 1992-12-03 1993-12-01 Method for crosslinking of haemoglobin and use of such crosslinked haemoglobin

Country Status (5)

Country Link
US (1) US5563047A (US20100012521A1-20100121-C00001.png)
EP (1) EP0671921A1 (US20100012521A1-20100121-C00001.png)
DK (1) DK145092D0 (US20100012521A1-20100121-C00001.png)
HU (1) HU214814B (US20100012521A1-20100121-C00001.png)
WO (1) WO1994014460A1 (US20100012521A1-20100121-C00001.png)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6894150B1 (en) * 1999-10-01 2005-05-17 Ross Walden Tye Non-pyrogenic, endotoxin-free, stroma-free tetrameric hemoglobin
US7858679B2 (en) * 2001-07-20 2010-12-28 Northwestern University Polymeric compositions and related methods of use
US8815793B2 (en) * 2001-07-20 2014-08-26 Northwestern University Polymeric compositions and related methods of use
US7618937B2 (en) * 2001-07-20 2009-11-17 Northwestern University Peptidomimetic polymers for antifouling surfaces
US8911831B2 (en) * 2002-07-19 2014-12-16 Northwestern University Surface independent, surface-modifying, multifunctional coatings and applications thereof
WO2004042068A2 (en) * 2002-10-31 2004-05-21 Northwestern University Injectable and bioadhesive polymeric hydrogels as well as related methods of enzymatic preparation
US7732539B2 (en) * 2006-02-16 2010-06-08 National Science Foundation Modified acrylic block copolymers for hydrogels and pressure sensitive wet adhesives
WO2008091386A2 (en) * 2006-08-04 2008-07-31 Northwestern University Biomimetic modular adhesive complex: material, methods and applications therefore
CA2656681C (en) 2006-08-04 2014-04-22 Nerites Corporation Biomimetic compounds and synthetic methods therefor
US7504377B2 (en) * 2006-10-23 2009-03-17 Ikor, Inc. Nitric oxide-blocked cross-linked tetrameric hemoglobin
US7494974B2 (en) * 2006-10-24 2009-02-24 Ikor, Inc. Carboxymethylated cross-linked tetrameric hemoglobin
WO2008089032A1 (en) * 2007-01-11 2008-07-24 Northwestern University Fouling resistant coatings and methods of making same
US8383092B2 (en) * 2007-02-16 2013-02-26 Knc Ner Acquisition Sub, Inc. Bioadhesive constructs
US8673286B2 (en) 2007-04-09 2014-03-18 Northwestern University DOPA-functionalized, branched, poly(aklylene oxide) adhesives
US20110130465A1 (en) * 2009-12-01 2011-06-02 Nerites Corporation Coatings for prevention of biofilms
US9320826B2 (en) 2010-11-09 2016-04-26 Kensey Nash Corporation Adhesive compounds and methods use for hernia repair
JP7387597B2 (ja) 2017-07-18 2023-11-28 ヴァーテック・バイオ・インコーポレイテッド ヘモグロビンを含む代用血液及び作製方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992003153A1 (en) * 1990-08-17 1992-03-05 Baxter International Inc. Hemoglobin-oligomer based composition and method to make same

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4001200A (en) * 1975-02-27 1977-01-04 Alza Corporation Novel polymerized, cross-linked, stromal-free hemoglobin
DE3144705C2 (de) * 1981-11-11 1983-12-08 Biotest-Serum-Institut Gmbh, 6000 Frankfurt Verfahren zur Herstellung eines lagerstabilen, vernetzten Hämoglobinpräparates mit hoher Sauerstoff-Transportkapazität, sowie das nach diesem Verfahren hergestellte Hämoglobinpräparat
US4529719A (en) * 1983-05-04 1985-07-16 Tye Ross W Modified crosslinked stroma-free tetrameric hemoglobin
JPH0665280B2 (ja) * 1987-03-04 1994-08-24 味の素株式会社 タンパクゲル化剤及びそれを用いるタンパクのゲル化方法
US5330778A (en) * 1988-09-19 1994-07-19 Opta Food Ingredients, Inc. Hydrophobic protein microparticles
US5270030A (en) * 1988-12-29 1993-12-14 Bio-Technology General Corp. Fibrin binding domain polypeptide and method of producing
US5128452A (en) * 1989-04-19 1992-07-07 Baxter International Inc. Process for the production of crosslinked hemoglobin in the presence of sodium tripolyphosphate
JP2958801B2 (ja) * 1990-09-14 1999-10-06 味の素株式会社 脱苦味された機能性ペプチドの製造法
DE4041533A1 (de) * 1990-12-22 1992-06-25 Roehm Gmbh Backmittel oder backmehl, sowie verfahren zur herstellung von backteigen und backwaren
US5409731A (en) * 1992-10-08 1995-04-25 Tomei Sangyo Kabushiki Kaisha Method for imparting a hydrophilic nature to a contact lens
US5399671A (en) * 1992-11-18 1995-03-21 Kluger; Ronald Specifically crosslinked hemoglobin with free functionality

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992003153A1 (en) * 1990-08-17 1992-03-05 Baxter International Inc. Hemoglobin-oligomer based composition and method to make same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Dialog Information Services, File 351, WPI, Dialog Accession No. 009068823, WPI Accession No. 92-196222/24, AJINOMOTO KK: "Functional Peptide - Obtd. by Partially Hydrolysing Food-Stuff Protein with Protease and/or Acid to Give Hydrolysed Peptide, which is Treated with Transglutaminase"; & JP,A,04 126 039, *

Also Published As

Publication number Publication date
HUT71940A (en) 1996-02-28
HU214814B (hu) 1998-05-28
HU9501526D0 (en) 1995-07-28
US5563047A (en) 1996-10-08
EP0671921A1 (en) 1995-09-20
DK145092D0 (US20100012521A1-20100121-C00001.png) 1992-12-03

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