USRE31268E - Method of recovering immunoglobulin using a polyol and an alkanoic acid - Google Patents
Method of recovering immunoglobulin using a polyol and an alkanoic acid Download PDFInfo
- Publication number
- USRE31268E USRE31268E US06/292,386 US29238681A USRE31268E US RE31268 E USRE31268 E US RE31268E US 29238681 A US29238681 A US 29238681A US RE31268 E USRE31268 E US RE31268E
- Authority
- US
- United States
- Prior art keywords
- acid
- polyol
- alkanoic acid
- precipitation
- carbon atoms
- 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.)
- Expired - Lifetime
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
Definitions
- the present invention relates to a method of recovering immunoglobulin suitable for intravenous administration, by fractionated precipitation of blood plasma, serum or a fraction thereof with a polycondensed di or polyol.
- Immunoglobulins comprising gammaglobulins have therapeutic merit as they are suitable for preparing immunizing preparations.
- Immunoglobulin is found in blood plasma of animal origin, from which it may be recovered by various precipitation and purification processes. Hence, gammaglobulin can be recovered as concentrated solutions by a method developed by Cohn et al, cf. J. Clin. Invest. Chem. Soc., 68, 479-75 (1946). According to Cohn, it is possible to obtain a fraction II being a 16.5% concentrate and which may be injected intramuscularly.
- Cohn's method comprises precipitation with alcohol which has a water-expelling effect and may lead to irreversible denaturation, whereby the globulin is rendered anti-complementary. It has been attempted to avoid this by means of special separation processes and/or by chemical modification of the gammaglobulin.
- the prior art teaches an improved fractionating process in which the gammaglobulin is precipitated from blood plasma by means of polyethylene glycol (PEG) as precipitant, cf. U.S. Pat. No. 3,415,804. This eliminates the undesired denaturation, but the purity of the precipated product is unsatisfactory.
- PEG polyethylene glycol
- this precipitation process may be improved by replacing polyethylene glycol by a block copolymer of ethylene oxide and polyoxypropylene polymer of a further specified nature and observing some specific precipitation conditions.
- the present invention is based on the observation that the fractionated precipitation of immunoglobulins, also known as gammaglobulins, by means of polyethylene glycol or other polycondensed di or polyol may be rendered appreciably more specific if the precipitation is carried out in the presence of a mono or polyalkanoic acid having from .[.4 to 12.]. .Iadd.6 to 9 .Iaddend.carbon atoms, whereby i.a. fibrinogen and lipoproteins are removed.
- the claimed method may be used in connection with any polycondensed di or polyglycol such as polyethylene glycol of varying molecular weights, e.g. 2000 to 12000, preferably 4000 to 6000, or polypropylene glycol. Also copolymers of ethylene oxide with propylene oxide or polyethers are suitable. .[.Suitable as mono or polyalkanoic acid is any alkanoic acid having from 4 to 12 carbon atoms..]. Preferred according to the invention is an alkanoic acid having from 6 to 9 carbon atoms, preferably caprylic acid. Examples of other suitable alkanoic acids are caproic acid and nonanic acid. Also branched alkanoic acids may be used.
- any polycondensed di or polyglycol such as polyethylene glycol of varying molecular weights, e.g. 2000 to 12000, preferably 4000 to 6000, or polypropylene glycol.
- copolymers of ethylene oxide with propylene oxide or polyethers are suitable.
- alkanoic acids When using higher alkanoic acids, .[.such as having from 9 to 12 carbon atoms,.]. it may be advantageous to incorporate additionally one or more carboxyl groups with a view to improving water-solubility. The same effect is achieved by using alkanoic acids having substituents containing, for example, one or more hydroxyl groups or amino groups.
- the immunoglobulin-containing solution is advantageously mixed with from 1 to 8 percent by weight of polyethylene glycol or other polycondensed diol or polyol together with from 0.1 to 5 percent by weight of caprylic acid or other alkanoic acid having from .[.4 to 12.]. .Iadd.6 to 9 .Iaddend.carbon atoms, the precipitation with alkanoic acid according to the invention being advantageously effected at a pH of from 3 to 7, preferably from 4.5 to 5.5.
- the solution is filtered until clear using a Seitz EK-filter.
- the solution formed is admixed with 5 g of caprylic acid and 30 g of PEG 3000 per liter solution, and adjusted to a pH of 4.9. After leaving to stand for 2 hours at 20° C. the mixture is centrifugated, and the liquid phase is filtered to obtain a clear solution.
- the yield of product is 60 percent.
- the degree of purity as determined by DISC PAGE discloses substantially only two bands corresponding to IgG and IgM, respectively. The analysis is performed by application of 500 ⁇ g of product.
- the purified product may, if desired, be converted to an intravenously injectable preparation by dissolution in 0.9 percent sodium chloride solution until a protein concentration of about 5 percent.
- the preparation is distinguished by an extremely low anticomplementary activity, for which reason it is particularly suitable for intravenous administration.
- Example 2 The procedure according to Example 1 is repeated, except that the human blood plasma is replaced by swine plasma.
- Example 1 The procedure according to Example 1 is repeated, except that human blood plasma is replaced by blood serum.
- 100 l of plasma or serum are mixed with 100 l of 600 g/l PEG 3000 solution.
- the pH is adjusted to 6.5.
- the precipitate is separated by centrifugation and redissolved in 100 l of distilled water admixed with 0.015 M of NaCl.
- the pH is adjusted to 5.0.
- the precipitate is separated by centrifugation.
- the centrifugate is admixed with additional 40 g of PEG 3000 per liter.
- the pH is adjusted to 7.5.
- the precipitate is separated by centrifugation and redissolved in distilled water with 0.002 M of NaCl.
- the solution is filtered to clarity (e.g. SEITZ ® EK-Filter).
- the protein concentration should be 50-100 g/l.
- 20 g of DEAE-Sephadex-A25 ® are added per 100 g of protein.
- the DEAE-Sephadex is separated by filtration.
- the DEAE-Sephadex treatment is repeated. After sterile filtration there is obtained an immunoglobulin G preparation free from anticomplementariness and suitable for intravenous administration.
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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)
- Immunology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
Immunoglobulins or gammaglobulins are recovered in a pure and anticomplementary condition by fractionated precipitation of blood plasma with a polycondensed di or polyol, such as PEG, in the presence of a mono or polyalkanoic acid having 4 to 12 carbon atoms, such as caprylic acid.
Description
This is a continuation of application Ser. No. 782,255 filed Mar. 28, 1977 and now abandoned.
The present invention relates to a method of recovering immunoglobulin suitable for intravenous administration, by fractionated precipitation of blood plasma, serum or a fraction thereof with a polycondensed di or polyol.
Immunoglobulins comprising gammaglobulins have therapeutic merit as they are suitable for preparing immunizing preparations.
Immunoglobulin is found in blood plasma of animal origin, from which it may be recovered by various precipitation and purification processes. Hence, gammaglobulin can be recovered as concentrated solutions by a method developed by Cohn et al, cf. J. Clin. Invest. Chem. Soc., 68, 479-75 (1946). According to Cohn, it is possible to obtain a fraction II being a 16.5% concentrate and which may be injected intramuscularly.
In the said prior-art method there are formed molecule aggregates of gammaglobulin rendering the products unsuitable for intravenous administration. Hence, Cohn's method comprises precipitation with alcohol which has a water-expelling effect and may lead to irreversible denaturation, whereby the globulin is rendered anti-complementary. It has been attempted to avoid this by means of special separation processes and/or by chemical modification of the gammaglobulin.
Hence, the prior art teaches an improved fractionating process in which the gammaglobulin is precipitated from blood plasma by means of polyethylene glycol (PEG) as precipitant, cf. U.S. Pat. No. 3,415,804. This eliminates the undesired denaturation, but the purity of the precipated product is unsatisfactory.
According to Danish Patent Application No. 6355/73, this precipitation process may be improved by replacing polyethylene glycol by a block copolymer of ethylene oxide and polyoxypropylene polymer of a further specified nature and observing some specific precipitation conditions.
In this manner it is possible to improve the yield by recovery of gammaglobulin. The precipitated products, however, are not always of satisfactory purity with sufficiently low anticomplementary activity.
The present invention is based on the observation that the fractionated precipitation of immunoglobulins, also known as gammaglobulins, by means of polyethylene glycol or other polycondensed di or polyol may be rendered appreciably more specific if the precipitation is carried out in the presence of a mono or polyalkanoic acid having from .[.4 to 12.]. .Iadd.6 to 9 .Iaddend.carbon atoms, whereby i.a. fibrinogen and lipoproteins are removed.
In the method according to the invention there is obtained in a simple manner purified immunoglobulin of a surprisingly high degree of purity coupled with a high yield. The yield equals that which it is possible to obtain by the best of the aforesaid methods.
The claimed method may be used in connection with any polycondensed di or polyglycol such as polyethylene glycol of varying molecular weights, e.g. 2000 to 12000, preferably 4000 to 6000, or polypropylene glycol. Also copolymers of ethylene oxide with propylene oxide or polyethers are suitable. .[.Suitable as mono or polyalkanoic acid is any alkanoic acid having from 4 to 12 carbon atoms..]. Preferred according to the invention is an alkanoic acid having from 6 to 9 carbon atoms, preferably caprylic acid. Examples of other suitable alkanoic acids are caproic acid and nonanic acid. Also branched alkanoic acids may be used. When using higher alkanoic acids, .[.such as having from 9 to 12 carbon atoms,.]. it may be advantageous to incorporate additionally one or more carboxyl groups with a view to improving water-solubility. The same effect is achieved by using alkanoic acids having substituents containing, for example, one or more hydroxyl groups or amino groups.
The immunoglobulin-containing solution is advantageously mixed with from 1 to 8 percent by weight of polyethylene glycol or other polycondensed diol or polyol together with from 0.1 to 5 percent by weight of caprylic acid or other alkanoic acid having from .[.4 to 12.]. .Iadd.6 to 9 .Iaddend.carbon atoms, the precipitation with alkanoic acid according to the invention being advantageously effected at a pH of from 3 to 7, preferably from 4.5 to 5.5.
The method according to the invention will now be further illustrated below by means of some examples.
415 ml of human blood plasma containing 10 g of immunoglobulin per liter plasma are adjusted to a pH of 5.0 PEG 3000 is added until a concentration of 6 percent, and the solution is left to stand for 45 minutes. The precipitate, being mainly fibrinogen, is separated by centrifugation, and the liquid phase is adjusted to a pH of 7.0. After adding additional PEG 3000 to obtain a concentration of 12 percent, the mixture is left to stand for 45 minutes. The mixture is now centrifugated and the liquid phase containing albumin and alpha and betaglobulin is removed. The precipitate consisting of impure immunoglobulin is redissolved in an 0.9 percent sodium chloride solution to obtain a protein concentration of about 4 percent. The solution is filtered until clear using a Seitz EK-filter. The solution formed is admixed with 5 g of caprylic acid and 30 g of PEG 3000 per liter solution, and adjusted to a pH of 4.9. After leaving to stand for 2 hours at 20° C. the mixture is centrifugated, and the liquid phase is filtered to obtain a clear solution. This solution is adjusted to pH=7.0, and PEG 3000 is added until a concentration of 12 percent PEG. This results in precipitation of pure immunoglobulin which is recovered by centrifugation and drying. The yield of product is 60 percent. The degree of purity as determined by DISC PAGE (with 5 percent polyacrylamide) discloses substantially only two bands corresponding to IgG and IgM, respectively. The analysis is performed by application of 500 μg of product.
In Grabar and William's immunoelectrophoresis, using rabbit antibody against total human serum protein, there is found substantially only three arches, corresponding to IgG, IgM and IgA, respectively.
The purified product may, if desired, be converted to an intravenously injectable preparation by dissolution in 0.9 percent sodium chloride solution until a protein concentration of about 5 percent. The preparation is distinguished by an extremely low anticomplementary activity, for which reason it is particularly suitable for intravenous administration.
The procedure according to Example 1 is repeated, except that the human blood plasma is replaced by swine plasma.
The procedure according to Example 1 is repeated, except that human blood plasma is replaced by blood serum.
100 l of plasma or serum are mixed with 100 l of 600 g/l PEG 3000 solution. The pH is adjusted to 6.5. The precipitate is separated by centrifugation and redissolved in 100 l of distilled water admixed with 0.015 M of NaCl. There is added 40 g of PEG 3000 per liter and 5 g of caprylic acid per liter. The pH is adjusted to 5.0. Standing time 45 minutes. The precipitate is separated by centrifugation. The centrifugate is admixed with additional 40 g of PEG 3000 per liter. The pH is adjusted to 7.5. The precipitate is separated by centrifugation and redissolved in distilled water with 0.002 M of NaCl. The solution is filtered to clarity (e.g. SEITZ ® EK-Filter). The protein concentration should be 50-100 g/l. 20 g of DEAE-Sephadex-A25 ® are added per 100 g of protein. After leaving to stand for 60 minutes while stirring the DEAE-Sephadex is separated by filtration. The DEAE-Sephadex treatment is repeated. After sterile filtration there is obtained an immunoglobulin G preparation free from anticomplementariness and suitable for intravenous administration.
Claims (5)
1. A method of recovering purified immunoglobulin suitable for intravenous administration wherein blood plasma, serum or a fraction thereof is subjected to a fractionated precipitation using a combination of polycondensed polyol and a mono or polyalkanoic acid having from .[.4 to 12.]. .Iadd.6 to 9 .Iaddend.carbon atoms as a precipitant, the fractionating process being performed at approximately room temperature. .[.2. A method according to claim 1, characterized in that the mono or polyalkanoic acid is an alkanoic acid having from 6 to 9 carbon atoms..].
. A method according to claim 1 .[.or claim 2,.]. characterized by
effecting the precipitation with alkanoic acid at a pH of from 3 to 7.
4. A process according to claim 1 wherein the polyol is a diol. 5. A
method according to claim 3 wherein the pH is from 4.5 to 5.5. 6. A method according to claim .[.2.]. .Iadd.1 .Iaddend.wherein the alkanoic acid is caprylic acid.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK1628/76 | 1976-04-06 | ||
DK162876AA DK139056B (en) | 1976-04-06 | 1976-04-06 | Method for recovering immunoglobulin suitable for intravenous administration. |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US78225577A Continuation | 1976-04-06 | 1977-03-28 | |
US05/914,456 Reissue US4164495A (en) | 1976-04-06 | 1978-06-12 | Method of recovering immunoglobulin using a polyol and an alkanoic acid |
Publications (1)
Publication Number | Publication Date |
---|---|
USRE31268E true USRE31268E (en) | 1983-06-07 |
Family
ID=8106680
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US06/292,386 Expired - Lifetime USRE31268E (en) | 1976-04-06 | 1981-08-13 | Method of recovering immunoglobulin using a polyol and an alkanoic acid |
Country Status (20)
Country | Link |
---|---|
US (1) | USRE31268E (en) |
JP (1) | JPS52122620A (en) |
AR (1) | AR211890A1 (en) |
AU (1) | AU511474B2 (en) |
BE (1) | BE852995A (en) |
CA (1) | CA1072444A (en) |
CH (1) | CH628813A5 (en) |
DD (1) | DD129451A5 (en) |
DE (1) | DE2713817A1 (en) |
DK (1) | DK139056B (en) |
ES (1) | ES457482A1 (en) |
FI (1) | FI61191C (en) |
FR (1) | FR2347379A1 (en) |
GB (1) | GB1551865A (en) |
HU (1) | HU175511B (en) |
IL (1) | IL51782A (en) |
IT (1) | IT1075148B (en) |
NL (1) | NL7703572A (en) |
NO (1) | NO146763C (en) |
SE (1) | SE7703843L (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5043427A (en) * | 1988-06-07 | 1991-08-27 | Foundation Nationale De Transfusion Sanguine | Process and installation for continuously fractionating plant, animal or human proteins |
US5367054A (en) * | 1993-04-12 | 1994-11-22 | Stolle Research & Development Corp. | Large-scale purification of egg immunoglobulin |
US5525519A (en) * | 1992-01-07 | 1996-06-11 | Middlesex Sciences, Inc. | Method for isolating biomolecules from a biological sample with linear polymers |
US20050272917A1 (en) * | 2004-05-14 | 2005-12-08 | Hematech, Llc | Methods for immunoglobulin purification |
US20060226086A1 (en) * | 2005-04-08 | 2006-10-12 | Robinson Thomas C | Centrifuge for blood processing systems |
US20090292109A1 (en) * | 2008-04-16 | 2009-11-26 | Biogen Idec Ma Inc. | Method of Isolating Biomacromolecules Using Polyalkylene Glycol and Transition Metals |
US20100145022A1 (en) * | 2006-11-01 | 2010-06-10 | Biogen Idic Ma Inc. | Method of Isolating Biomacromolecules Using Low pH and Divalent Cations |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5625114A (en) * | 1979-08-07 | 1981-03-10 | Green Cross Corp:The | Preparation of human gamma globulin |
US4590002A (en) * | 1984-12-10 | 1986-05-20 | Ortho Diagnostic Systems, Inc. | Methods for preparation of highly purified, gamma globulins free of hepatitis-B-virus infectivity |
FR2578425B1 (en) * | 1985-03-07 | 1988-06-10 | Nal Transfusion Sanguine Centr | IMMUNOGLOBULIN PREPARATIONS HAVING HIGH TITLES OF ANTI-ALLERGENIC BLOCKING ANTIBODIES, THEIR PREPARATION AND THEIR APPLICATIONS FOR THE TREATMENT OF ALLERGIES |
CA1308023C (en) * | 1988-07-29 | 1992-09-29 | William Austin James Mcauley | Immunoglobulin extraction utilizing properties of colloidal solutions |
Citations (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3100737A (en) * | 1958-02-05 | 1963-08-13 | Auerswald Wilhelm | Method of preparing a plasma protein solution free of active hepatitis virus and product produced thereby |
US3415804A (en) * | 1962-01-03 | 1968-12-10 | South African Inventions | Fractionation of mixtures of proteinaceous substances using polyethylene glycol |
US3686395A (en) * | 1966-04-06 | 1972-08-22 | Biotest Serum Institut Gmbh | Process for preparation of storage stable hepatitis-free serum |
US3770631A (en) * | 1971-06-29 | 1973-11-06 | Baxter Laboratories Inc | Clarification of blood serum and plasma |
US3808189A (en) * | 1973-03-15 | 1974-04-30 | American Cyanamid Co | Isolation of gamma globulin preparations enriched in iga and igm using polyethylene glycol |
US3869436A (en) * | 1971-06-01 | 1975-03-04 | Statens Bakteriologiska Lab | Method for fractionating plasma proteins using peg and ion-exchangers |
US3876775A (en) * | 1972-06-19 | 1975-04-08 | Cutter Lab | Stable intravenously injectable plasma protein free from hypotensive effects and process for its production |
US3880989A (en) * | 1973-01-30 | 1975-04-29 | Baxter Laboratories Inc | Production of antisera comprising fractionating plasma or serum with an ethylene oxide-polyoxypropylene block copolymer |
US3916026A (en) * | 1968-09-19 | 1975-10-28 | Biotest Serum Institut Gmbh | Method for the preparation of gamma-globulin suitable for intravenous use |
US4017470A (en) * | 1974-02-18 | 1977-04-12 | The Green Cross Corporation | Method for preparing a heat-stable plasma protein solution from paste IV-1 |
US4021540A (en) * | 1975-07-28 | 1977-05-03 | Ortho Diagnostics Inc. | Preparation of a hepatitis B immune globulin and use thereof as a prophylactic material |
US4075193A (en) * | 1976-11-26 | 1978-02-21 | Parke, Davis & Company | Process for producing intravenous immune globulin |
US4082734A (en) * | 1975-06-18 | 1978-04-04 | Biotest-Serum-Institut Gmbh | Production of intravenously applicable native human immune globulin having a normal half-life |
US4093606A (en) * | 1975-02-18 | 1978-06-06 | Coval M L | Method of producing intravenously injectable gamma globulin and a gamma globulin suitable for carrying out the method |
US4124576A (en) * | 1976-12-03 | 1978-11-07 | Coval M L | Method of producing intravenously injectable gamma globulin |
US4154819A (en) * | 1975-09-06 | 1979-05-15 | Biotest-Serum-Institut Gmbh | Preparation of a gamma-globulin solution suitable for intravenous administration using diketene |
-
1976
- 1976-04-06 DK DK162876AA patent/DK139056B/en not_active IP Right Cessation
-
1977
- 1977-03-29 DE DE19772713817 patent/DE2713817A1/en not_active Withdrawn
- 1977-03-29 BE BE176213A patent/BE852995A/en not_active IP Right Cessation
- 1977-03-30 IL IL51782A patent/IL51782A/en unknown
- 1977-03-31 GB GB13575/77A patent/GB1551865A/en not_active Expired
- 1977-03-31 AR AR267073A patent/AR211890A1/en active
- 1977-03-31 IT IT21982/77A patent/IT1075148B/en active
- 1977-04-01 HU HU77NO212A patent/HU175511B/en unknown
- 1977-04-01 SE SE7703843A patent/SE7703843L/en not_active Application Discontinuation
- 1977-04-01 NL NL7703572A patent/NL7703572A/en not_active Application Discontinuation
- 1977-04-02 ES ES457482A patent/ES457482A1/en not_active Expired
- 1977-04-04 AU AU23910/77A patent/AU511474B2/en not_active Expired
- 1977-04-04 DD DD7700198240A patent/DD129451A5/en unknown
- 1977-04-05 FI FI771071A patent/FI61191C/en not_active IP Right Cessation
- 1977-04-05 FR FR7710326A patent/FR2347379A1/en active Granted
- 1977-04-05 CH CH428777A patent/CH628813A5/en not_active IP Right Cessation
- 1977-04-05 NO NO771225A patent/NO146763C/en unknown
- 1977-04-05 CA CA275,585A patent/CA1072444A/en not_active Expired
- 1977-04-06 JP JP3858877A patent/JPS52122620A/en active Pending
-
1981
- 1981-08-13 US US06/292,386 patent/USRE31268E/en not_active Expired - Lifetime
Patent Citations (16)
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US3100737A (en) * | 1958-02-05 | 1963-08-13 | Auerswald Wilhelm | Method of preparing a plasma protein solution free of active hepatitis virus and product produced thereby |
US3415804A (en) * | 1962-01-03 | 1968-12-10 | South African Inventions | Fractionation of mixtures of proteinaceous substances using polyethylene glycol |
US3686395A (en) * | 1966-04-06 | 1972-08-22 | Biotest Serum Institut Gmbh | Process for preparation of storage stable hepatitis-free serum |
US3916026A (en) * | 1968-09-19 | 1975-10-28 | Biotest Serum Institut Gmbh | Method for the preparation of gamma-globulin suitable for intravenous use |
US3869436A (en) * | 1971-06-01 | 1975-03-04 | Statens Bakteriologiska Lab | Method for fractionating plasma proteins using peg and ion-exchangers |
US3770631A (en) * | 1971-06-29 | 1973-11-06 | Baxter Laboratories Inc | Clarification of blood serum and plasma |
US3876775A (en) * | 1972-06-19 | 1975-04-08 | Cutter Lab | Stable intravenously injectable plasma protein free from hypotensive effects and process for its production |
US3880989A (en) * | 1973-01-30 | 1975-04-29 | Baxter Laboratories Inc | Production of antisera comprising fractionating plasma or serum with an ethylene oxide-polyoxypropylene block copolymer |
US3808189A (en) * | 1973-03-15 | 1974-04-30 | American Cyanamid Co | Isolation of gamma globulin preparations enriched in iga and igm using polyethylene glycol |
US4017470A (en) * | 1974-02-18 | 1977-04-12 | The Green Cross Corporation | Method for preparing a heat-stable plasma protein solution from paste IV-1 |
US4093606A (en) * | 1975-02-18 | 1978-06-06 | Coval M L | Method of producing intravenously injectable gamma globulin and a gamma globulin suitable for carrying out the method |
US4082734A (en) * | 1975-06-18 | 1978-04-04 | Biotest-Serum-Institut Gmbh | Production of intravenously applicable native human immune globulin having a normal half-life |
US4021540A (en) * | 1975-07-28 | 1977-05-03 | Ortho Diagnostics Inc. | Preparation of a hepatitis B immune globulin and use thereof as a prophylactic material |
US4154819A (en) * | 1975-09-06 | 1979-05-15 | Biotest-Serum-Institut Gmbh | Preparation of a gamma-globulin solution suitable for intravenous administration using diketene |
US4075193A (en) * | 1976-11-26 | 1978-02-21 | Parke, Davis & Company | Process for producing intravenous immune globulin |
US4124576A (en) * | 1976-12-03 | 1978-11-07 | Coval M L | Method of producing intravenously injectable gamma globulin |
Non-Patent Citations (4)
Title |
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Encycl. of Chemistry, 3rd Ed. (1973), pp. 466-477, Hampel et al. * |
J. of Immunology, 1962, Frommhagen et al., pp. 336-343 (1962). * |
Rev. Franc. Etudes Clin. et Biol. 1969, XIV, pp. 1054-1058, Steinbuch et al. * |
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Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5043427A (en) * | 1988-06-07 | 1991-08-27 | Foundation Nationale De Transfusion Sanguine | Process and installation for continuously fractionating plant, animal or human proteins |
US5525519A (en) * | 1992-01-07 | 1996-06-11 | Middlesex Sciences, Inc. | Method for isolating biomolecules from a biological sample with linear polymers |
US5599719A (en) * | 1992-01-07 | 1997-02-04 | Middlesex Sciences, Inc. | Method for isolating biomolecules from a biological sample with linear polymers |
US5367054A (en) * | 1993-04-12 | 1994-11-22 | Stolle Research & Development Corp. | Large-scale purification of egg immunoglobulin |
US20050272917A1 (en) * | 2004-05-14 | 2005-12-08 | Hematech, Llc | Methods for immunoglobulin purification |
US20060226086A1 (en) * | 2005-04-08 | 2006-10-12 | Robinson Thomas C | Centrifuge for blood processing systems |
US20100145022A1 (en) * | 2006-11-01 | 2010-06-10 | Biogen Idic Ma Inc. | Method of Isolating Biomacromolecules Using Low pH and Divalent Cations |
US9109015B2 (en) | 2006-11-01 | 2015-08-18 | Biogen Ma Inc | Method of isolating biomacromolecules using low pH and divalent cations |
US20090292109A1 (en) * | 2008-04-16 | 2009-11-26 | Biogen Idec Ma Inc. | Method of Isolating Biomacromolecules Using Polyalkylene Glycol and Transition Metals |
Also Published As
Publication number | Publication date |
---|---|
FR2347379B1 (en) | 1981-11-20 |
NO146763C (en) | 1982-12-08 |
IL51782A0 (en) | 1977-05-31 |
CH628813A5 (en) | 1982-03-31 |
NO146763B (en) | 1982-08-30 |
JPS52122620A (en) | 1977-10-15 |
HU175511B (en) | 1980-08-28 |
FI61191B (en) | 1982-02-26 |
DK162876A (en) | 1977-10-07 |
NO771225L (en) | 1977-10-07 |
GB1551865A (en) | 1979-09-05 |
BE852995A (en) | 1977-07-18 |
FI771071A (en) | 1977-10-07 |
DE2713817A1 (en) | 1977-10-27 |
DK139056B (en) | 1978-12-11 |
AU511474B2 (en) | 1980-08-21 |
NL7703572A (en) | 1977-10-10 |
AU2391077A (en) | 1978-10-12 |
IT1075148B (en) | 1985-04-22 |
DK139056C (en) | 1979-05-21 |
ES457482A1 (en) | 1978-03-16 |
DD129451A5 (en) | 1978-01-18 |
IL51782A (en) | 1980-12-31 |
FI61191C (en) | 1982-06-10 |
AR211890A1 (en) | 1978-03-31 |
SE7703843L (en) | 1977-10-07 |
CA1072444A (en) | 1980-02-26 |
FR2347379A1 (en) | 1977-11-04 |
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