EP1023078A1 - Precipitation of growth-factor-enriched fibrinogen concentrate from platelet rich plasma - Google Patents

Precipitation of growth-factor-enriched fibrinogen concentrate from platelet rich plasma

Info

Publication number
EP1023078A1
EP1023078A1 EP98953467A EP98953467A EP1023078A1 EP 1023078 A1 EP1023078 A1 EP 1023078A1 EP 98953467 A EP98953467 A EP 98953467A EP 98953467 A EP98953467 A EP 98953467A EP 1023078 A1 EP1023078 A1 EP 1023078A1
Authority
EP
European Patent Office
Prior art keywords
platelet rich
rich plasma
fibrinogen
plasma
precipitating agent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP98953467A
Other languages
German (de)
French (fr)
Other versions
EP1023078A4 (en
Inventor
Lou Blasetti
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Harvest Technologies Corp
Original Assignee
Harvest Technologies Corp
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 Harvest Technologies Corp filed Critical Harvest Technologies Corp
Publication of EP1023078A1 publication Critical patent/EP1023078A1/en
Publication of EP1023078A4 publication Critical patent/EP1023078A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5094—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for blood cell populations
    • 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
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A61K38/363—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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0028—Polypeptides; Proteins; Degradation products thereof
    • A61L26/0042—Fibrin; Fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D17/00—Separation of liquids, not provided for elsewhere, e.g. by thermal diffusion
    • B01D17/02—Separation of non-miscible liquids
    • B01D17/0217—Separation of non-miscible liquids by centrifugal force
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D17/00—Separation of liquids, not provided for elsewhere, e.g. by thermal diffusion
    • B01D17/02—Separation of non-miscible liquids
    • B01D17/04—Breaking emulsions
    • B01D17/047—Breaking emulsions with separation aids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D21/00—Separation of suspended solid particles from liquids by sedimentation
    • B01D21/01—Separation of suspended solid particles from liquids by sedimentation using flocculating agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D21/00—Separation of suspended solid particles from liquids by sedimentation
    • B01D21/26—Separation of sediment aided by centrifugal force or centripetal force
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D21/00—Separation of suspended solid particles from liquids by sedimentation
    • B01D21/26—Separation of sediment aided by centrifugal force or centripetal force
    • B01D21/262—Separation of sediment aided by centrifugal force or centripetal force by using a centrifuge
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D21/00—Separation of suspended solid particles from liquids by sedimentation
    • B01D21/30—Control equipment
    • B01D21/34—Controlling the feed distribution; Controlling the liquid level ; Control of process parameters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2221/00—Applications of separation devices
    • B01D2221/10—Separation devices for use in medical, pharmaceutical or laboratory applications, e.g. separating amalgam from dental treatment residues

Definitions

  • This application relates to improved processes for recovery and concentration
  • the invention relates to the production of growth-
  • factor-enriched fibrinogen concentrate from platelet-rich plasma.
  • thrombin a surgical patient intraoperatively and is combined with thrombin, usually in a seven-
  • the gel achieves faster haemostasis than do other conventional
  • the gel also seals air and fluid leakage due to its viscous
  • PDGF derived growth factors
  • the adhesive, tensile and shear strength of the clot formed by this gel is generally less than is desirable. Further, failure of haemostasis
  • volume e.g., 50ml
  • a fibrinogen-precipitating agent is placed in the second
  • the container is then placed in a centrifuge, and the whole blood is
  • the plasma e.g., PEG or ammonium sulfate.
  • the precipitating agent e.g., PEG or ammonium sulfate.
  • plasma from which fibrinogen is precipitated contains increased levels of platelets.
  • the fibrinogen yield obtained with prior art methods is generally about 50%
  • invention is about 72%, which represents a 44% increase in recovered fibrinogen.
  • the disclosed invention produces FVIII and concentrated (up to 10+ fold
  • proteins preferably fibrinogen, FXIII, and recovered platelets (and
  • a clinically effective dose is produced from a smaller volume
  • the preferred method utilizes the dedicated centrifuge and disposable
  • ammonium sulfate is placed in the second chamber.
  • the ammonium sulfate can be
  • ammonium sulfate 25% to 100% ammonium sulfate, and is preferably about 95% ammonium sulfate.
  • the disposable is loaded into the dedicated centrifuge as described in United States
  • Red cells are separated from whole blood in the centrifuge at a spin rate that
  • the spin rate is known as a "soft spin"
  • a precipitating agent such as PEG or ammonium sulfate
  • PRP has been found to provide greater protein (preferably fibrinogen)
  • PPP platelet poor plasma
  • a suitable diluent volume preferably a citrate buffer, is added to re-dissolve
  • a platelet gel is formed within seconds of application. The gel achieves
  • the gel's properties include FVIII and increased levels of
  • fibrinogen fibrinogen, FXIII, and greater than native levels of human growth factors.
  • TGF-B-1 TGF-B-1 and a thirty-fold increase in PDGF-AB.
  • the container was subjected to a hard spin to obtain a fibrinogen
  • pellet was about 72% a four-to-ten fold increase in TGF-B-1 and a thirty-fold

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Cell Biology (AREA)
  • Thermal Sciences (AREA)
  • Ecology (AREA)
  • Pathology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Materials Engineering (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Food Science & Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Zoology (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Increased fibrinogen yields are obtained by adding a precipitating agent to plasma having a high platelet concentration, such as platelet rich plasma. The precipitating agent may be any of several known agents, including polyethylene glycol and ammonium sulfate. The platelet rich plasma is obtained in the preferred embodiment by subjecting plasma to 'soft spin' centrifugation of about 580G. An automatic, multiple decanting and multiple-speed centrifuge is preferably used to separate anti-coagulated whole blood into the platelet rich plasma component and red blood cells. The proteins, preferably fibrinogen, FXIII, and FVIII, in the platelet rich component are precipitated, and the proteins and platelets are then concentrated by further centrifugation.

Description

PRECIPITATION OF GROWTH-FACTOR-ENRICHED FIBRINOGEN
CONCENTRATE FROM PLATELET RICH PLASMA
TECHNICAL FIELD
This application relates to improved processes for recovery and concentration
of blood components. In particular, the invention relates to the production of growth-
factor-enriched fibrinogen concentrate from platelet-rich plasma.
BACKGROUND
The need exists for means quickly to concentrate and recover certain blood
proteins from whole blood, which also contains platelets and certain growth factors,
in a closed-process system for use by physicians to assist in closing wounds, to
achieve faster haemostasis, to seal air and fluid leakage, and to aid in faster healing
and for drug and biologic delivery.
Those skilled in the art know that when platelet-rich plasma is harvested from
a surgical patient intraoperatively and is combined with thrombin, usually in a seven-
to-one ratio, and deposited on a wound site, a platelet gel is formed within seconds
of application. The gel achieves faster haemostasis than do other conventional
haemostatic agents. The gel also seals air and fluid leakage due to its viscous
properties, and results in faster healing resulting from the presence of platelet
derived growth factors (PDGF). Such a gel contains only native levels of fibrinogen,
FXIII, FVIII, and PDGF. Thus, the adhesive, tensile and shear strength of the clot formed by this gel is generally less than is desirable. Further, failure of haemostasis
or sealing can occur because of these low levels of desirable proteins, resulting in a
failure to achieve the desired outcome.
Harvesting platelet rich plasma from a patient in the intra-operative setting
requires a "blood processor," one of which is sold under the trademark "Cell Saver,"
but other devices manufactured by various companies are known. The Cell Saver
device requires a highly-skilled, sometimes certified, operator to set-up and operate
the device. Operation (which can take 30 to 60 minutes) requires large-bore venous
or arterial access and processing of up to several liters of biood to obtain and
sequester sufficient platelets and plasma volume. The patient's haemodynamic and
cardiac status must be stable to allow processing of such large volumes.
An automated system for obtaining autologous fibrinogen has been described
in United States Patent 5,707,331 (Wells et al.), the disclosure of which is
incorporated herein by reference. According to that system, a relatively small
volume (e.g., 50ml) of whole blood is placed in a first chamber of a two-chamber
disposable container. A fibrinogen-precipitating agent is placed in the second
chamber. The container is then placed in a centrifuge, and the whole blood is
centrifuged to separate the plasma to produce platelet-poor plasma. The platelet-
poor plasma, thus obtained is then decanted into the second chamber where it is
mixed with the precipitating agent (e.g., PEG or ammonium sulfate). The plasma
and precipitating agent are then centrifuged to obtain a pellet of fibrinogen for
combination with thrombin to make a fibrin sealant. DESCRIPTION OF THE PREFERRED EMBODIMENT
An important factor for processes that recover fibrinogen, such as the one
described in the mentioned United States Patent 5,707,331 , is the percentage of the
fibrinogen in the whole blood that is recovered in the pellet. Applicant has
discovered that this factor, the "fibrinogen yield," is unexpectedly greater when the
plasma from which fibrinogen is precipitated contains increased levels of platelets.
Thus, according to the process of the invention, a known fibrinogen precipitating
agent is added to platelet-rich plasma to obtain increased yields of fibrinogen.
The fibrinogen yield obtained with prior art methods is generally about 50%,
whereas the fibrinogen yield obtained in accordance with the methods of the
invention is about 72%, which represents a 44% increase in recovered fibrinogen.
In the preferred embodiments, the platelet-rich plasma from which fibrinogen
is precipitated contains at least 50K platelets per mm3 and preferably about
200K/mm3.
The disclosed invention produces FVIII and concentrated (up to 10+ fold
increase) proteins, preferably fibrinogen, FXIII, and recovered platelets (and
resultant increase in human growth factors) from relatively small aliquots (20cc-
150cc) of anti-coagulated whole blood in a short time (approx. 20 minutes). The
increased coagulation protein concentration of the disclosed invention over the
current Cell Saver methods results in a clinically more effective (greater tensile and
shear strength) clot. A clinically effective dose is produced from a smaller volume
(20cc-150 cc) of the patient's blood obtained by simple phlebotomy known in the art
versus the Cell Saver method (several liters). The preferred method utilizes the dedicated centrifuge and disposable
container described in United States Patent 5,707,331 to process anti-coagulated
whole blood drawn from a patient (or directed blood donor). In accordance with the
invention, the process described there is modified to provide platelet-rich plasma by
appropriate control of the centrifuge speed and the length of time the blood is
subjected to centrifugation.
Anticoagulated blood retrieved from a mammal by simple phlebotomy
techniques is dispensed into a first chamber of a 2-chamber disposable, and an
appropriate volume of a precipitating agent, for example PEG or saturated
ammonium sulfate, is placed in the second chamber. The ammonium sulfate can be
25% to 100% ammonium sulfate, and is preferably about 95% ammonium sulfate.
The disposable is loaded into the dedicated centrifuge as described in United States
Patent 5,707,331 , and the process in that patent initiated. The centrifuge is
programmed to effect the following steps automatically:
1. Red cells are separated from whole blood in the centrifuge at a spin rate that
produces platelet-rich plasma (PRP). The spin rate is known as a "soft spin"
and preferably one that produces about 580G. The centrifuge is then
stopped, and the PRP is decanted from the first chamber to the second,
where it is mixed with the precipitating agent. This soft spin has been found
to produce plasma having a platelet concentration of from about 50K/mm3 to
about 450K/mm3.
2. After mixing is complete, the centrifuge re-starts and the precipitated proteins,
along with the platelets, are concentrated by a "hard spin," preferably one that
produces about 3500G. 3. Following step 2 above, the platelet-poor and fibrinogen-poor plasma and
residual precipitating agent are decanted from the second chamber back to
the first, leaving a relatively-dry, growth-factor-enriched protein/platelet pellet.
The use of a precipitating agent, such as PEG or ammonium sulfate, with
PRP has been found to provide greater protein (preferably fibrinogen)
recovery than obtained with techniques using a precipitating agent with
platelet poor plasma (PPP).
4. A suitable diluent volume, preferably a citrate buffer, is added to re-dissolve
and recover the protein/platelet pellet to allow transport by, for example,
syringe.
5. When the recovered, concentrated protein, containing increased levels of
human growth factors, is combined with thrombin and deposited on a wound
site, a platelet gel is formed within seconds of application. The gel achieves
faster haemostasis than when other conventional haemostatic agents are
used. It can also seal air and fluid leakage due to its viscous properties, and
results in faster healing from the presence of enriched platelet derived growth
factors (PDGF). The gel's properties include FVIII and increased levels of
fibrinogen, FXIII, and greater than native levels of human growth factors.
These increased levels result in a clot with more desirable adhesive, tensile
and shear strength. Because of these' higher levels of desirable proteins, the
risk of premature failure of the clot is reduced and the likelihood of achieving
the desired outcome is increased. Example 1.
Fifty milliliters of whole blood were placed in the first chamber of a container
for use in an automated centrifuge, and 15 milliliters of 30% polyethylene glycol
(MW1000) were placed in the second chamber. The container was then subjected
to a soft spin of about 580G for three minutes. The platelet-rich plasma thus
obtained (23-25ml) was then decanted to the second chamber and mixed with the
PEG. The container was then subjected to hard centrifugation and the supernatant
was decanting back to the first chamber. The result was a fibrinogen pellet
representing a fibrinogen yield of approximately 70%, a four-to-ten fold increase in
TGF-B-1 and a thirty-fold increase in PDGF-AB.
Example 2.
Fifty milliliters of whole blood were placed in the first chamber of a container
for use in an automated centrifuge, and 7ml of saturated ammonium sulfate was
placed in the second chamber. The container was then subjected to a soft spin of
about 580G for three minutes and 23-25 milliliters of platelet-rich plasma were
decanted to the second chamber. After mixing with the platelet-rich plasma with the
ammonium sulfate, the container was subjected to a hard spin to obtain a fibrinogen
pellet, and the supernatant decanted to the first chamber. The fibrinogen yield of the
pellet was about 72% a four-to-ten fold increase in TGF-B-1 and a thirty-fold
increase in PDGF-AB.
Modifications within the scope of the appended claims will be apparent to
those of skill in the art.

Claims

I Claim:
1. A process for isolating growth factor enriched fibrinogen concentrate
comprising the steps of:
obtaining platelet rich plasma,
adding a fibrinogen-precipitating agent to said platelet rich plasma; and
recovering growth factor enriched fibrinogen concentrate from said platelet
rich plasma.
2. A process according to claim 1 wherein said precipitating agent is
polyethylene glycol.
3. A process according to claim 1 wherein said precipitating agent is ammonium
sulfate.
4. A process according to claim 1 wherein said step of obtaining platelet rich
plasma comprises the step of subjecting plasma to centrifugation.
5. A process according to claim 4 wherein said step of centrifugation comprises
the step of subjecting said plasma to a force of about 580G for about three minutes.
6. A process according to claim 1 wherein said platelet rich plasma comprises
plasma having 50K to 450K platelets/mm3.
7. A process according to claim 1 wherein said step of recovering fibrinogen
comprises the step of subjecting said platelet rich plasma and said precipitating
agent to centrifugation.
8. A process according to claim 1 wherein the step of obtaining platelet rich
plasma comprises the step of subjecting about 50ml of anticoagulated whole blood to centrifugation and decanting 23-25ml of said platelet rich plasma, and said step of
adding a precipitating agent comprises adding about 15ml of 30% polyethylene
glycol (MW1000) to said platelet rich plasma.
9. A process according to claim 1 wherein the step of obtaining platelet rich
plasma comprises the step of subjecting about 50ml of anticoagulated whole blood
to centrifugation and decanting 23-25ml of said platelet rich plasma, and said step of
adding a precipitating agent comprises adding about 7ml of saturated ammonium
sulfate.
10. A process according to claim 1 wherein said step of recovering fibrinogen
further comprises the step of adding a buffer to said fibrinogen.
11. A product made by the process of any one of claims 1 -10.
EP98953467A 1997-10-17 1998-10-16 Precipitation of growth-factor-enriched fibrinogen concentrate from platelet rich plasma Withdrawn EP1023078A4 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US6226497P 1997-10-17 1997-10-17
US62264P 1997-10-17
PCT/US1998/021626 WO1999020288A1 (en) 1997-10-17 1998-10-16 Precipitation of growth-factor-enriched fibrinogen concentrate from platelet rich plasma

Publications (2)

Publication Number Publication Date
EP1023078A1 true EP1023078A1 (en) 2000-08-02
EP1023078A4 EP1023078A4 (en) 2004-09-29

Family

ID=22041325

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98953467A Withdrawn EP1023078A4 (en) 1997-10-17 1998-10-16 Precipitation of growth-factor-enriched fibrinogen concentrate from platelet rich plasma

Country Status (5)

Country Link
EP (1) EP1023078A4 (en)
JP (1) JP2001520198A (en)
CN (1) CN1113656C (en)
CA (1) CA2306629A1 (en)
WO (1) WO1999020288A1 (en)

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Publication number Priority date Publication date Assignee Title
DE60018607T2 (en) * 1999-12-22 2006-05-04 Henogen S.A. BONE-MAKING MATERIAL
CN1303413C (en) * 2003-06-17 2007-03-07 余伟明 Protein and virus quick-speed concentration method
PL1824988T3 (en) * 2004-11-12 2018-01-31 Bayer Healthcare Llc Site-directed modification of fviii
CN1908005B (en) * 2006-08-11 2010-05-12 哈尔滨医科大学 Composite protein precipitator
EP2077118A1 (en) * 2008-01-07 2009-07-08 Gwo Rei Biomedical Technology Corp. Clottable concentrate of platelet growth factors and preparation method thereof
CN105708858A (en) * 2014-12-05 2016-06-29 国玺干细胞应用技术股份有限公司 Preparation method of growth-factor-platelet-rich fibrin and releasate
CN104711221B (en) * 2015-02-15 2017-09-15 第五空间健康管理江苏有限公司 Isolating immune cells and the method for extracting PRP are automated from adult peripheral blood
CN107198893A (en) * 2017-07-01 2017-09-26 张方亮 Leucocyte-removing PRP preparation method
CN107412878B (en) * 2017-08-07 2018-04-24 上海交通大学医学院附属第九人民医院 Composite fibrous scaffold and preparation method thereof
EP4206324A1 (en) * 2022-01-04 2023-07-05 Phynexus, Inc. Purification of macromolecules

Citations (1)

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Publication number Priority date Publication date Assignee Title
WO1996023039A1 (en) * 1995-01-23 1996-08-01 The Regents Of The University Of California Plasma and polymer containing surgical hemostatic adhesives

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Publication number Priority date Publication date Assignee Title
US5226877A (en) * 1989-06-23 1993-07-13 Epstein Gordon H Method and apparatus for preparing fibrinogen adhesive from whole blood
US5030215A (en) * 1990-01-03 1991-07-09 Cryolife, Inc. Preparation of fibrinogen/factor XIII precipitate
US5585007A (en) * 1994-12-07 1996-12-17 Plasmaseal Corporation Plasma concentrate and tissue sealant methods and apparatuses for making concentrated plasma and/or tissue sealant
US5707331A (en) * 1995-05-05 1998-01-13 John R. Wells Automatic multiple-decanting centrifuge

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996023039A1 (en) * 1995-01-23 1996-08-01 The Regents Of The University Of California Plasma and polymer containing surgical hemostatic adhesives

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No further relevant documents disclosed *
See also references of WO9920288A1 *

Also Published As

Publication number Publication date
CA2306629A1 (en) 1999-04-29
CN1276725A (en) 2000-12-13
CN1113656C (en) 2003-07-09
EP1023078A4 (en) 2004-09-29
JP2001520198A (en) 2001-10-30
WO1999020288A1 (en) 1999-04-29

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