GB1577031A - Process of increasing the intravenous compatibility of gamma globulins - Google Patents
Process of increasing the intravenous compatibility of gamma globulins Download PDFInfo
- Publication number
- GB1577031A GB1577031A GB5017/77A GB501777A GB1577031A GB 1577031 A GB1577031 A GB 1577031A GB 5017/77 A GB5017/77 A GB 5017/77A GB 501777 A GB501777 A GB 501777A GB 1577031 A GB1577031 A GB 1577031A
- Authority
- GB
- United Kingdom
- Prior art keywords
- gamma globulin
- silicate
- weight
- aqueous solution
- percent
- 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
Links
- 108010074605 gamma-Globulins Proteins 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims description 40
- 230000008569 process Effects 0.000 title claims description 35
- 238000001990 intravenous administration Methods 0.000 title claims description 9
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000002244 precipitate Substances 0.000 claims abstract description 17
- 239000007864 aqueous solution Substances 0.000 claims abstract description 16
- 229910052902 vermiculite Inorganic materials 0.000 claims abstract description 12
- 239000010455 vermiculite Substances 0.000 claims abstract description 12
- 235000019354 vermiculite Nutrition 0.000 claims abstract description 12
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 8
- 239000000725 suspension Substances 0.000 claims abstract description 7
- 239000000440 bentonite Substances 0.000 claims abstract description 6
- 229910000278 bentonite Inorganic materials 0.000 claims abstract description 6
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000010836 blood and blood product Substances 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 15
- 230000003171 anti-complementary effect Effects 0.000 claims description 12
- 229920001612 Hydroxyethyl starch Polymers 0.000 claims description 10
- 229940050526 hydroxyethylstarch Drugs 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims description 8
- 229910052901 montmorillonite Inorganic materials 0.000 claims description 8
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 6
- 239000011707 mineral Substances 0.000 claims description 6
- 239000002002 slurry Substances 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 229940125691 blood product Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- 238000010586 diagram Methods 0.000 claims description 2
- 238000000760 immunoelectrophoresis Methods 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 238000012360 testing method Methods 0.000 claims description 2
- 238000005341 cation exchange Methods 0.000 abstract description 4
- 108010044091 Globulins Proteins 0.000 abstract description 3
- 102000006395 Globulins Human genes 0.000 abstract description 3
- 229910052615 phyllosilicate Inorganic materials 0.000 abstract 3
- 230000001376 precipitating effect Effects 0.000 abstract 2
- 229920002521 macromolecule Polymers 0.000 abstract 1
- 230000035484 reaction time Effects 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 150000001768 cations Chemical class 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000004760 silicates Chemical class 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007614 solvation Methods 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 108010045362 Serum Globulins Proteins 0.000 description 1
- 102000005686 Serum Globulins Human genes 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- HPTYUNKZVDYXLP-UHFFFAOYSA-N aluminum;trihydroxy(trihydroxysilyloxy)silane;hydrate Chemical compound O.[Al].[Al].O[Si](O)(O)O[Si](O)(O)O HPTYUNKZVDYXLP-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 229910052621 halloysite Inorganic materials 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
Abstract
A precipitate, which consists of fractions which are tolerated and those which are not tolerated by the body, of gamma-globulins precipitated from blood and blood products is chemically fractionated. The entire precipitate is for this purpose taken up or dissolved in an aqueous solution which contains macromolecular substances which are capable of uniting with the fractions which are not tolerated. The resulting aqueous solution containing gamma-globulin is then additionally mixed with a suspension of micaceous sheet silicates which have cation-exchange capacity. After a reaction time sufficient for the globulin fractions which are not tolerated to bind, by cation exchange, in the sheets of the sheet silicate has elapsed, a precipitating medium is added in order to remove the gamma-globulin fraction which separates out, together with the sheet silicates. Examples of suitable sheet silicates are bentonite, batavite and vermiculite, and an example of a suitable precipitating medium is polyethylene glycol.
Description
(54) IMPROVED PROCESS OF INCREASING THE
INTRAVENOUS COMPATIBILITY OF GAMMA GLOBULINS
(71) We, PLASMESCO AG., a company organised under the laws of the
Confederation of Switzerland, of Hänibühl 8, Cho300 Zug Switzerland, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed to be particularly described in and by the following statement:- This invention relates to a process for improving the intravenous compatibility of gamma globulins precipitated from blood or from blood products and is an improvement in or modification of the process described and claimed in the
Specification of our Patent No. 1495159. In the aforesaid Specification there is described and claimed a process for improving the intravenous compatibility of gamma globulin precipitated from blood or blood products, wherein a gamma globulin precipitate is dissolved in an aqueous solution containing a concentration of from 1 to 30% of a hydroxyethyl starch having a molecular weight of 1000 to 900,000, for shielding the globulin molecules from each other and displacing them from the solution.
In a preferred embodiment of our earlier process, the portion of undesirable gamma globulins is removed by introducing the gamma globulins into an aqueous solution of hydroxyethyl starch present in a concentration of from 8 to 10%. The mixture is centrifuged after the addition of polyethylene glycol (PEG), and the precipitate which settles contains the undesirable portion of gamma globulin, whereas the desirable portion is recovered in another centrifuging step at a pH of 7.2 and with 20% of PEG.
Even if the gamma globulin obtained by the above-described process meets the usual requirements of medical practice, nevertheless it has been found to be desirable to increase the yield and to provide a still higher quality and purity of the desired gamma globulin. According to the present invention there is provided a process for improving the intravenous compatibility of gamma globulin precipitated from blood or from blood products by reducing the anticomplementary activity of the gamma globulin precipitate, wherein the gamma globulin precipitate is dissolved in an aqueous solution containing a concentration of 1 to 30 of a hydroxyethyl starch having a molecular weight of 1000 to 900,000, a slurry or suspension or a micaceous stratified silicate (as herein defined) is added to said aqueous solution to provide a concentration of said stratified silicate of from 0.2 to 10 percent by weight, and after allowing a sufficient period to elapse to allow the anticomplementary activity present with the gamma globulin to bond to said stratified silicate, adding a precipitant and removing the anticomplementary activity to be separated or disposed of together with said stratified silicate.
The term "micaceous stratified silicate" is employed in this specification to mean a silicate, the composition of which is expressed by one or other of the following average formulae:
Me+ is a cation which may be replaced zeolitically by another, even an organic, cation, y is a liquid, other than a saturated hydrocarbon, which increases the stratum distance by spacing the positive and negative charges of the silicate from each other, and x is the number of monovalent cations per structural unit of (Si, Al)40,U, namely the stratification or stratified charge. The quantity of the liquid y may be varied within broad limits, and in view of the fact that the value of x varies, too, there is an extremely large variety of micaceous stratified silicates which may be employed in the present process.
Extensive research work has been conducted particularly with respect to montmorillonite (compare in this connection the bibliography according to "Organische Derivate der glmmerartigen Schichtsilikate" by WEISS; "Angewandte Chemie" 1963; pages 113 et seq.). Montmorillonite comprises twodimensionally infinite macro anions which are electrostatically reticulated through the intermediate cations. The energy for the swelling action, i.e. for increasing the stratum distance by spacing the positive and negative charges from each other, is provided by the hydration or solvation of the cations and anion strata. Since the solvation energy in general is substantially smaller than the hydration energy, only molecule species having high dielectric constants or having the capability of forming hydrogen links can be incorporated.
Amino acids, peptides and proteins may be incorporated into micaceous stratified silicates. At a low pH, proteins are exchanged almost quantitatively. With increasing pH value, the number of the cationic positions within the proteins decreases, and the exchange tends to be incomplete.
Albumins, globulins and prolamines are likewise bonded. With serum globulins, the reaction appears to proceed from the edge of the silicate crystals into the interior thereof to a depth of only from 20 to 30 (Angstr5m). Albumins are spread between the silicate strata, the stratum spacing of from 14.5 to 15.or showing that a stratum thickness of a maximum of 5.5 to 6 is available to the spread protein.
In view of the fact that the quantity of gamma globulin introduced contains both damaged (injured) and undamaged or intact molecules, it must be attempted so far as possible, to bond the damaged molecules in one way or other so as to render them chemically distinguishable from the physiologically perfect molecules.
The damaged molecules are capable of forming hydrogen link bonds. Therefore, they are deposited and bonded to greater degree within the silicate strata, whereas the intact gamma globulin molecules are left in the solution. In their state as bonded within the strata of the stratified silicate, the damaged gamma globulin molecules can easily be removed subsequently, e.g. by centrifuging.
The cation exchange capacity which is desirable for the present process, is also exhibited, according to HOFMANN [Z. Kristallogr. (A) 98 (1937) 31; Chemie 55 (1942) 283] by kaolin and related substances (for instance halloysite,
Al203.2SiO2.4H2O) and certain micaceous minerals the lattice structure of which is related to that of kaolin.
These substances also include vermiculite and the related material batavite (= iron-free vermiculite). According to WEISS and HOFMANN (Z. Naturf., 6b, 405) the structural formula of batavite is as follows:
It has been found that this material, in the same way as montmorillonite, exhibits an intercrystalline swelling capacity and a high capacity for cation exchange. Investigations (compare the above references) showed that batavite absorbs up to 5 percent by weight of human albumin, with the protein being deposited between the silicate strata. Likewise, vermiculite having the approximate structural formula
exhibits the desired properties regarding the strata formation and swellability.
Vermiculite corresponds to a tri-octahedral montmorillonite, but its crystals are larger and the lattice is more regularly shaped.
Summarizing, it may therefore be concluded that those minerals are suitable for the purification process which have a stratified structure, which have cations between the silicate strata, and which tend to swell. According to experimental experience, minerals of this type act to retain the defective gamma globulin molecules-apparently due to their strong cation activation -- whereas intact molecules are not bonded, it being necessary to maintain specific limits of concentration and, preferably, of pH value.
In carrying out the present process, the minerals montmorillonite, batavite or vermiculite are preferably employed. Depending on the quantity of gamma globulin dissolved during the formation of the solution, from 0.2 to 10, preferably 0.2 to 5 percent by weight of silicate is added. According to experimental experience, the reaction preferably takes place within a temperature range of from 4 to 20"C., and the process is preferably carried out at a pH of from 4.0 to 7.6. A reaction period of at least from 3 to 10 hours is usually desirable and the process thus is preferably carried out overnight, since the reaction proceeds relatively slowly and an extended period of time provides improved results. Discharge or separation of the silicates is performed preferably by a centrifuging step. However, other methods conventional in general process techniques may alternatively be used, such as e.g. alluvial filtration.
The following Examples are intended further to explain the invention.
EXAMPLE 1.
a) Separation of gamma globulin:
The starting material is a collected plasma which has been mixed with 8% of ethanol, and which has been precipitated at a pH of 7.2 and at a temperature of minus 3"C. A first fraction, fraction I is separated, whereafter, the supernatant liquid is mixed with 19% of ethanol at a temperature of minus 5"C. and at a pH of 5.8. In this step, a fraction, fraction Il-Ill, is separated which comprises gamma globulins. The precipitate is again dissolved and again precipitated at a pH of 5 and with 8% of ethanol. The remaining supernatant material is then again precipitated with 25% of ethanol at a pH of 7.2. The resulting precipitate (= fraction II) comprises at least 90% of gamma globulin.
b) Reduction of the anti-complementary activity:
The gamma globulin precipitate is introduced into a buffered aqueous solution having a pH of 7.0, in a concentration of about 6% and about 10% of hydroxyethyl starch is added to the aqueous solution. An aqueous slurry or suspension of bentonite SF (mains components: montmorillonite; grain size less than 80 microns; manufacturer: Feinbiochemika, Heidelberg) is added to the solution, the solution being mixed with 2.5 percent by weight of bentonite, and the mixture is agitated thoroughly. Then, the solution is allowed to stand for 6 hours at a temperature of 15"C + 2". Following this, the bentonite together with the undesirable components is removed by centrifuging after the addition of 10% of polyethylene glycol.
c) Conversion into a physiological normal saline solution:
The supernatant material obtained by the centrifuging step contains the desirable gamma globulin constituents in the form of a solution. The supernatant liquid is adjusted to a pH of 7.2 by means of 0.1 sodium hydroxide and mixed with 20 percent by weight or polyethylene glycol whereby a precipitate of pure gamma globulin settles. The precipitate is recovered by centrifuging, adjusted to a coricentration of 5.2% of protein in a physiological normal saline solution, and thereafter subjected to sterile filtration. This material is then ready for therapeutic use.
EXAMPLE 2.
In this Example steps a) and c) are identical with same steps in Example 1, but step b) is modified as follows:
The gamma globulin precipitate is introduced into a buffered aqueous solution having a pH of 7.4, in a concentration of about 4 percent by weight, and approximately 8% of hydroxyethyl starch is added to the aqueous solution. Furthermore, an aqueous slurry or suspension of finely divided (particle size less than 80 microns) vermiculite is added to the solution until a proportion of 5 percent by weight is reached. The whole composition is agitated vigorously. Thereupon, the solution is allowed to stand foi 8 hours at a temperature of 15" + 2"C. About 10 percent by weight of hydroxyethyl starch is then added to the solution. Finally, the vermiculite is removed by centrifuging together with the undesirable components. This operation is followed by method step c).
Calculations and measurements by immune electrophoresis diagrams demonstrate that the yield of pure gamma globulin is increased by carrying out the present process. The gamma globulin recovered is not modified or chemically varied. It is of absolute compatibility when administered intravenously, and it does not substantially show any anti-complementary properties of characteristics.
Furthermore" the substance possesses a high degree of stability which could be verified by storage tests.
WHAT WE CLAIM IS:
1. A process for improving the intravenous compatibility of gamma globulin precipitated from blood or from blood products by reducing the anticomplementary activity of the gamma globulin precipitate, wherein the gamma globulin precipitate is dissolved in an aqueous solution containing a concentration of 1 to 30% of a hydroxyethyl starch having a molecular weight of 1000 to 900,000, a slurry or suspension of a micaceous stratified silicate (as herein defined) is added to said aqueous solution to provide a concentration of said stratified silicate of from 0.2 to 10 percent by weight, and after allowing a sufficient period to elapse to allow the anticomplementary activity present with the gamma globulin to bond to said stratified silicate anticomplementary activity to be separated or disposed of together with said stratified silicate.
2. A process as claimed in Claim 1, wherein said stratified silicate is bentonite including as its primary component montmorillonite.
3. A process as claimed in Claim 1, wherein said stratified silicate is the mineral batavite or vermiculite.
4. A process as claimed in any one of Claims 1 to 3, wherein from 0.2 to 5 percent by weight of silicate is added.
5. A process as claimed in any one of Claims 1 to 4, wherein the reaction is carried out at a temperature of from 4" to 200 C.
6. A process as claimed in any one of Claims 1 to 5, wherein the reaction with said stratified silicate is carried out at a pH of from 4.0 to 7.6.
7. A process as claimed in any one of Claims 1 to 6, wherein said period is from 3 to 10 hours.
8. A process as claimed in any one of Claims 1 to 7, wherein said precipitant is polyethylene glycol.
10. A process for improving the intravenous compatibility of gamma globulin, substantially as hereinbefore described in either of the foregoing Examples.
Il. Gamma globulin prepared by the process claimed in any preceding Claim.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (1)
- **WARNING** start of CLMS field may overlap end of DESC **.EXAMPLE 2.In this Example steps a) and c) are identical with same steps in Example 1, but step b) is modified as follows: The gamma globulin precipitate is introduced into a buffered aqueous solution having a pH of 7.4, in a concentration of about 4 percent by weight, and approximately 8% of hydroxyethyl starch is added to the aqueous solution. Furthermore, an aqueous slurry or suspension of finely divided (particle size less than 80 microns) vermiculite is added to the solution until a proportion of 5 percent by weight is reached. The whole composition is agitated vigorously. Thereupon, the solution is allowed to stand foi 8 hours at a temperature of 15" + 2"C. About 10 percent by weight of hydroxyethyl starch is then added to the solution. Finally, the vermiculite is removed by centrifuging together with the undesirable components. This operation is followed by method step c).Calculations and measurements by immune electrophoresis diagrams demonstrate that the yield of pure gamma globulin is increased by carrying out the present process. The gamma globulin recovered is not modified or chemically varied. It is of absolute compatibility when administered intravenously, and it does not substantially show any anti-complementary properties of characteristics.Furthermore" the substance possesses a high degree of stability which could be verified by storage tests.WHAT WE CLAIM IS:1. A process for improving the intravenous compatibility of gamma globulin precipitated from blood or from blood products by reducing the anticomplementary activity of the gamma globulin precipitate, wherein the gamma globulin precipitate is dissolved in an aqueous solution containing a concentration of 1 to 30% of a hydroxyethyl starch having a molecular weight of 1000 to 900,000, a slurry or suspension of a micaceous stratified silicate (as herein defined) is added to said aqueous solution to provide a concentration of said stratified silicate of from 0.2 to 10 percent by weight, and after allowing a sufficient period to elapse to allow the anticomplementary activity present with the gamma globulin to bond to said stratified silicate anticomplementary activity to be separated or disposed of together with said stratified silicate.2. A process as claimed in Claim 1, wherein said stratified silicate is bentonite including as its primary component montmorillonite.3. A process as claimed in Claim 1, wherein said stratified silicate is the mineral batavite or vermiculite.4. A process as claimed in any one of Claims 1 to 3, wherein from 0.2 to 5 percent by weight of silicate is added.5. A process as claimed in any one of Claims 1 to 4, wherein the reaction is carried out at a temperature of from 4" to 200 C.6. A process as claimed in any one of Claims 1 to 5, wherein the reaction with said stratified silicate is carried out at a pH of from 4.0 to 7.6.7. A process as claimed in any one of Claims 1 to 6, wherein said period is from 3 to 10 hours.8. A process as claimed in any one of Claims 1 to 7, wherein said precipitant is polyethylene glycol.10. A process for improving the intravenous compatibility of gamma globulin, substantially as hereinbefore described in either of the foregoing Examples.Il. Gamma globulin prepared by the process claimed in any preceding Claim.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2604759A DE2604759C2 (en) | 1976-02-07 | 1976-02-07 | Method of Obtaining IV Compatible Gamma Globulins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1577031A true GB1577031A (en) | 1980-10-15 |
Family
ID=5969262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB5017/77A Expired GB1577031A (en) | 1976-02-07 | 1977-02-07 | Process of increasing the intravenous compatibility of gamma globulins |
Country Status (22)
| Country | Link |
|---|---|
| JP (1) | JPS52117414A (en) |
| AT (1) | AT351672B (en) |
| AU (1) | AU508852B2 (en) |
| BE (1) | BE851151R (en) |
| CA (1) | CA1087524A (en) |
| CH (1) | CH629669A5 (en) |
| DD (1) | DD132758A6 (en) |
| DE (1) | DE2604759C2 (en) |
| DK (1) | DK151609C (en) |
| ES (1) | ES455708A2 (en) |
| FI (1) | FI62624C (en) |
| FR (1) | FR2340738A2 (en) |
| GB (1) | GB1577031A (en) |
| HU (1) | HU177708B (en) |
| IE (1) | IE44591B1 (en) |
| IN (1) | IN144987B (en) |
| MX (1) | MX5356E (en) |
| NL (1) | NL7700975A (en) |
| PL (1) | PL104234B3 (en) |
| SE (1) | SE442707B (en) |
| YU (1) | YU30577A (en) |
| ZA (1) | ZA77684B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2837168A1 (en) * | 1978-08-25 | 1980-03-06 | Blutspendedienst Dt Rote Kreuz | METHOD FOR PRODUCING AN IMMUNAL GLOBULIN SOLUTION SUITABLE FOR INTRAVENOUS APPLICATION |
| JPS60222773A (en) * | 1984-04-19 | 1985-11-07 | Sekisui Chem Co Ltd | Manufacture of latex reagent |
| ATE59144T1 (en) * | 1984-07-07 | 1991-01-15 | Armour Pharma Gmbh | PROCESS FOR THE PREPARATION OF GAMMA GLOBULIN FOR INTRAVENOUS USE. |
| DE3440444A1 (en) * | 1984-11-06 | 1986-05-07 | Dechema Deutsche Gesellschaft für chemisches Apparatewesen e.V., 6000 Frankfurt | METHOD FOR THE PRODUCTION OF COARSE GRAINED LAYERED SILICATES AND THE USE THEREOF AS ADSORBENTS FOR PROTEINS |
| UA64742C2 (en) * | 1997-12-24 | 2004-03-15 | Альфа Терапевтик Корпорейшн | Process for producing intravenously-administrable gamma globulin solution and product manufactured by this process |
| EP3118209B1 (en) | 2014-03-11 | 2020-02-19 | Green Cross Holdings Corporation | Method for purifying immunoglobulin |
| EP3118210B1 (en) | 2014-03-11 | 2019-11-13 | Green Cross Holdings Corporation | Method for purifying immunoglobulin |
| KR101657690B1 (en) | 2015-06-05 | 2016-09-19 | 주식회사 녹십자홀딩스 | Methods for Preparing Hepatitis B immune globulin derived from plasma |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3449316A (en) * | 1967-03-03 | 1969-06-10 | American Cyanamid Co | Process for the purification of gamma globulin employing bentonite |
| DE2500076C3 (en) * | 1975-01-02 | 1982-11-18 | SCHURA Blutderivate GmbH & Co KG, 4150 Krefeld | Process for the production of intravenously tolerated gamma globulins |
-
1976
- 1976-02-07 DE DE2604759A patent/DE2604759C2/en not_active Expired
-
1977
- 1977-01-28 FI FI770290A patent/FI62624C/en not_active IP Right Cessation
- 1977-01-28 IE IE186/77A patent/IE44591B1/en unknown
- 1977-01-31 NL NL7700975A patent/NL7700975A/en not_active Application Discontinuation
- 1977-01-31 SE SE7700960A patent/SE442707B/en not_active IP Right Cessation
- 1977-02-03 AU AU21902/77A patent/AU508852B2/en not_active Expired
- 1977-02-04 DD DD7700197241A patent/DD132758A6/en unknown
- 1977-02-04 PL PL1977195821A patent/PL104234B3/en unknown
- 1977-02-04 DK DK047277A patent/DK151609C/en not_active IP Right Cessation
- 1977-02-04 AT AT74177A patent/AT351672B/en not_active IP Right Cessation
- 1977-02-04 HU HU77PA1277A patent/HU177708B/en unknown
- 1977-02-04 YU YU00305/77A patent/YU30577A/en unknown
- 1977-02-04 FR FR7703139A patent/FR2340738A2/en active Granted
- 1977-02-04 BE BE6045865A patent/BE851151R/en not_active IP Right Cessation
- 1977-02-04 MX MX775414U patent/MX5356E/en unknown
- 1977-02-05 IN IN168/CAL/77A patent/IN144987B/en unknown
- 1977-02-07 GB GB5017/77A patent/GB1577031A/en not_active Expired
- 1977-02-07 CA CA271,204A patent/CA1087524A/en not_active Expired
- 1977-02-07 JP JP1172177A patent/JPS52117414A/en active Granted
- 1977-02-07 ES ES455708A patent/ES455708A2/en not_active Expired
- 1977-02-07 CH CH146277A patent/CH629669A5/en not_active IP Right Cessation
- 1977-02-07 ZA ZA770684A patent/ZA77684B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DD132758A6 (en) | 1978-11-01 |
| FI770290A7 (en) | 1977-08-08 |
| FI62624C (en) | 1983-02-10 |
| AU2190277A (en) | 1978-08-10 |
| DE2604759C2 (en) | 1983-06-01 |
| HU177708B (en) | 1981-12-28 |
| BE851151R (en) | 1977-08-04 |
| JPS6231695B2 (en) | 1987-07-09 |
| FI62624B (en) | 1982-10-29 |
| CA1087524A (en) | 1980-10-14 |
| CH629669A5 (en) | 1982-05-14 |
| FR2340738B2 (en) | 1981-07-31 |
| ATA74177A (en) | 1979-01-15 |
| AU508852B2 (en) | 1980-04-03 |
| IE44591L (en) | 1977-08-07 |
| YU30577A (en) | 1984-04-30 |
| MX5356E (en) | 1983-06-29 |
| ZA77684B (en) | 1977-12-28 |
| DE2604759A1 (en) | 1977-09-29 |
| ES455708A2 (en) | 1978-01-16 |
| AT351672B (en) | 1979-08-10 |
| SE442707B (en) | 1986-01-27 |
| FR2340738A2 (en) | 1977-09-09 |
| PL104234B3 (en) | 1979-08-31 |
| NL7700975A (en) | 1977-08-09 |
| IN144987B (en) | 1978-08-05 |
| DK151609C (en) | 1988-06-20 |
| IE44591B1 (en) | 1982-01-27 |
| DK151609B (en) | 1987-12-21 |
| JPS52117414A (en) | 1977-10-01 |
| SE7700960L (en) | 1977-08-08 |
| DK47277A (en) | 1977-08-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2322552C2 (en) | Process for separating protein A from Staphylococcus aureus from a liquid | |
| US6835379B2 (en) | Method of producing IgG | |
| DE2417619C2 (en) | Intramolecularly cross-linked hemoglobin, process for its production and its use | |
| US4918059A (en) | Low molecular weight alkali metal huminates, method for their preparation and applications thereof | |
| DE2801123C2 (en) | Process for the production of a serum protein preparation which can be administered intravenously | |
| GB1577031A (en) | Process of increasing the intravenous compatibility of gamma globulins | |
| US4126605A (en) | Process of improving the compatibility of gamma globulins | |
| US4322403A (en) | Method for the preparation of an immune globulin solution suitable for intravenous use | |
| DE69002033T2 (en) | Gel filtration of heat-treated factor VIII. | |
| US4476109A (en) | Method of preparing gamma globulin suitable for intravenous administration | |
| DE69004429T2 (en) | METHOD FOR RECOVERY OF RECOMBINANT PROTEINS. | |
| DE2616984C3 (en) | Method for the isolation and purification of a placenta-specific glycoprotein | |
| DE3430320A1 (en) | Process for the preparation of immunoglobulin preparations with reduced complement activity | |
| DE2658334B2 (en) | Process for the production of immunoglobulin preparations with reduced complement binding and a pharmaceutical containing the same | |
| EP0301374A2 (en) | Process for the purification of the placenta tissue protein PP4 | |
| DE1617332C3 (en) | Method for isolating a water-soluble protein-metal chelate with anti-inflammatory activity | |
| US4515776A (en) | Method of preparing gamma globulin suitable for intravenous administration | |
| US1718282A (en) | Medical serum | |
| DE2014957C2 (en) | Process for purifying proteins from blood serum or plasma | |
| US4610815A (en) | Process for producing and obtaining anaphylatoxin- and cocytotaxin-containing leucotaxine preparations and of anaphylatoxin and cocytotaxin proteins in molecularly homogeneous, biologically active form | |
| JP2026501074A (en) | Laminin extraction, purification and polymerization process, uses, polylaminin and kits | |
| DE102010054766A1 (en) | A method of separating, concentrating or purifying a (blood) plasma protein or viral component from a mixture | |
| DE102010054767B4 (en) | Process for the separation, concentration and / or purification of (blood) plasma protein, viruses or viral components | |
| US3634196A (en) | Process for the separation of pyrogens from crude preparations of l-asparaginase | |
| AT367297B (en) | METHOD FOR PRODUCING A SERUM PROTEIN PR [PARATE |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| 732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
| PE20 | Patent expired after termination of 20 years |
Effective date: 19951228 |