CA2514158A1 - Enhanced production of clotting factors by cryoprecipitation - Google Patents

Enhanced production of clotting factors by cryoprecipitation Download PDF

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Publication number
CA2514158A1
CA2514158A1 CA002514158A CA2514158A CA2514158A1 CA 2514158 A1 CA2514158 A1 CA 2514158A1 CA 002514158 A CA002514158 A CA 002514158A CA 2514158 A CA2514158 A CA 2514158A CA 2514158 A1 CA2514158 A1 CA 2514158A1
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CA
Canada
Prior art keywords
cryoprecipitate
plasma
extraction solution
trisodium citrate
separating
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.)
Granted
Application number
CA002514158A
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French (fr)
Other versions
CA2514158C (en
Inventor
Edward Shanbrom
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.)
Shanbrom Technologies LLC
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Shanbrom Technologies Llc
Edward Shanbrom
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Filing date
Publication date
Priority claimed from US10/280,501 external-priority patent/US7297716B2/en
Application filed by Shanbrom Technologies Llc, Edward Shanbrom filed Critical Shanbrom Technologies Llc
Publication of CA2514158A1 publication Critical patent/CA2514158A1/en
Application granted granted Critical
Publication of CA2514158C publication Critical patent/CA2514158C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14Extraction; Separation; Purification
    • C07K1/30Extraction; Separation; Purification by precipitation
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02Preservation of living parts
    • A01N1/0205Chemical aspects
    • A01N1/021Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/74Synthetic polymeric materials
    • A61K31/785Polymers containing nitrogen
    • A61K31/787Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
    • A61K31/79Polymers of vinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14Blood; Artificial blood
    • A61K35/16Blood plasma; Blood serum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0023Heat
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/10Polypeptides; Proteins
    • A61L24/106Fibrin; Fibrinogen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745Blood coagulation or fibrinolysis factors

Abstract

The blood collection, processing and transfer by separation of discrete components containing additional citrate (at least about trisodium citrate 9%
w/v) in one or other of collection or processing bag provides for enhanced yield and purity of cryoprecipitate. Inhibiting the activation or denaturation of blood components including blood cells and plasma proteins and with the removal of the activated and denatured components thereby improving safety and efficacy of end products. The inventive process is particularly suited to an improved extraction process to yield concentrated clotting factors from single donors or limited pools without use of chromatography. Following extraction the remaining cryoprecipitate can advantageously be formed into a fibrin fabric used in surgeries and in the treatment of wounds.

Claims (10)

1. A method for producing a clotting factor concentrate without using chromatography comprising the steps of:
adding trisodium citrate to plasma to yield a concentration of trisodium citrate of at least about 9% weight by volume;
allowing cryoprecipitate to form in the plasma;
separating the cryoprecipitate from the plasma;
extracting the cryoprecipitate at a low temperature with a cold extraction solution containing calcium chloride; and separating the cryoprecipitate from the extraction solution wherein the separated extraction solution is the clotting factor concentrate.
2. The method according to Claim 1, wherein forming cryoprecipitate does not involve freezing the plasma.
3. The method according to Claim 1, wherein the concentration of the trisodium citrate is between about 10% and about 15% weight by volume.
4. The method according to Claim 1, wherein the step of separating the cryoprecipitate from the plasma employs centrifugation.
5. The method according Claim 1, wherein the step of extracting takes place at a temperature below about 10°C.
6. The method according Claim 1 further comprising the step of removing citrate from the clotting factor concentrate.
7. The method according Claim 1 further comprising the step of removing calcium from the clotting factor concentrate.
8. The method according to Claim 1, wherein the step of separating the cryoprecipitate from the extraction solution employs centrifugation.
9. The method according to Claim 1, wherein the extraction solution contains about 0.9% sodium chloride, weight by volume and about 0.3M
calcium chloride.
10. The method according to Claim 1, wherein the extraction solution has a pH between about 5.0 and about 7Ø
1 1. The method according to Claim 1, wherein the step of adding trisodium citrate is accomplished by collecting the plasma directly into a container holding the trisodium citrate.
12. The method of Claim 11, wherein the plasma is collected by plasmapheresis.

13. ~A method for producing a clotting factor concentrate without using chromatography comprising the steps of:
adding trisodium citrate to plasma to yield a concentration of trisodium citrate of about 12% weight by volume;
allowing cryoprecipitate to form in the plasma;
separating the cryoprecipitate from the plasma by centrifugation;
extracting the cryoprecipitate at a low temperature with a cold extraction solution containing sodium chloride and calcium chloride; and separating the cryoprecipitate from the extraction solution by centrifugation wherein the separated extraction solution is the clotting factor concentrate.

14. ~The method according to Claim 13, wherein forming cryoprecipitate does not involve freezing the plasma.

15. ~The method according Claim 13, wherein the step of extracting takes place at a temperature below about 10 °C.

16. ~The method according Claim 13 further comprising the step of removing citrate from the clotting factor concentrate.

17. ~The method according Claim 13 further comprising the step of removing calcium from the clotting factor concentrate.

18. The method according to Claim 13, wherein the extraction solution contains about 0.9% sodium chloride, weight by volume and about 0.3M
calcium chloride.

19. The method according to Claim 13, wherein the extraction solution has a pH between about 5.0 and about 7Ø

20. The method according to Claim 13, wherein the extraction solution has a pH of about 5.5.

21. The method according to Claim 13, wherein the step of adding trisodium citrate is accomplished by collecting the plasma directly into a container holding the trisodium citrate.

22. The method of Claim 21, wherein the plasma is collected by plasmapheresis.

23. A method for producing a fibrin membrane without using chromatography comprising the steps of:
adding trisodium citrate to plasma to yield a concentration of trisodium citrate of at least about 9% weight by volume;
allowing cryoprecipitate to form in the plasma;
separating the cryoprecipitate from the plasma;
extracting the cryoprecipitate at a low temperature with a cold extraction solution containing calcium chloride;
separating the extraction solution from the cryoprecipitate;
molding the cryoprecipitate into a sheet; and treating the molded cryoprecipitate to form a fibrin membrane.

24. The method according to Claim 23, wherein treating the molded cryoprecipitate involves heating the molded cryoprecipitate.

25. The method according to Claim 23 further comprising a step of embedding a mess within the cryoprecipitate prior to the step of treating the molded cryoprecipitate.

26. The method according to Claim 23, wherein forming cryoprecipitate does not involve freezing the plasma.

27. The method according to Claim 23, wherein the concentration of the trisodium citrate is between about 10% and about 15% weight by volume.

28. The method according to Claim 23, wherein the step of separating the cryoprecipitate from the plasma employs centrifugation.

29. The method according Claim 23, wherein the step of extracting takes place at a temperature below about 10°C.

30. The method according. to Claim 23, wherein the step of separating the cryoprecipitate from the extraction solution employs centrifugation.

31. The method according to Claim 23, wherein the extraction solution contains about 0.9% sodium chloride, weight by volume and about 0.3M
calcium chloride.

32. The method according to Claim 23, wherein the extraction solution has a pH between about 5.0 and about 7Ø

33. The method according to Claim 23, wherein the step of adding trisodium citrate is accomplished by collecting the plasma directly into a container holding the trisodium citrate.

34. The method of Claim 33, wherein the plasma is collected by plasmapheresis.
CA2514158A 2002-10-25 2003-10-23 Enhanced production of clotting factors by cryoprecipitation Expired - Fee Related CA2514158C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US10/280,501 US7297716B2 (en) 2000-10-23 2002-10-25 Enhanced production of blood components, blood cells and plasma without freezing
US10/280,501 2002-10-25
US10/459,804 US7411006B2 (en) 2000-10-23 2003-06-12 Enhanced production of blood clotting factors and fibrin fabric
US10/459,804 2003-06-12
PCT/US2003/033646 WO2004039382A1 (en) 2002-10-25 2003-10-23 Enhanced production of clotting factors by cryoprecipitation

Publications (2)

Publication Number Publication Date
CA2514158A1 true CA2514158A1 (en) 2004-05-13
CA2514158C CA2514158C (en) 2010-05-04

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA2514158A Expired - Fee Related CA2514158C (en) 2002-10-25 2003-10-23 Enhanced production of clotting factors by cryoprecipitation

Country Status (4)

Country Link
US (2) US7411006B2 (en)
AU (1) AU2003295354B2 (en)
CA (1) CA2514158C (en)
WO (1) WO2004039382A1 (en)

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Also Published As

Publication number Publication date
AU2003295354A1 (en) 2004-05-25
CA2514158C (en) 2010-05-04
WO2004039382A1 (en) 2004-05-13
AU2003295354B2 (en) 2008-04-03
US7411006B2 (en) 2008-08-12
US20090018313A1 (en) 2009-01-15
US20050196393A1 (en) 2005-09-08
US8003706B2 (en) 2011-08-23

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