CA1058075A - Process of improving the compatibility of gamma globulins - Google Patents
Process of improving the compatibility of gamma globulinsInfo
- Publication number
- CA1058075A CA1058075A CA242,734A CA242734A CA1058075A CA 1058075 A CA1058075 A CA 1058075A CA 242734 A CA242734 A CA 242734A CA 1058075 A CA1058075 A CA 1058075A
- Authority
- CA
- Canada
- Prior art keywords
- gamma globulin
- solution
- blood
- process according
- precipitated
- 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
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Abstract
Abstract A process of improving the intravenous compatibility of gamma globulin precipitated from blood or blood products, wherein the gamma globulin precipitate is resolved in an aqueous solution in which macromolecular substances shield-ing the globulin molecules from each other and displacing them from the solution are present. Such shielding substan-ces are hydroxylethyl starch, gelatine, dextranes, albumin, plyalcohols or polyvinyls. Especially hydroxylethyl starch (HES) in that said aqueous solution from which the gamma globulin is subsequently precipitated, yields good results.
The gamma globuline is than re-dissolved, particularly in a physiological normal saline solution.
The gamma globuline is than re-dissolved, particularly in a physiological normal saline solution.
Description
5~
Process of improvin~ the compatibilit~ of gamma globulins .,~
The present invention relates to a prscess of improving the intravenous compatibility of gamma globulins precipitated from blood or blood products.
,, .
- Blood is a liquid which consists of solid and liquid com-ponents. The solid components include the red and white blood corpuscles as well as the blood platelets---~r throm-bocytes. The plasma, i.e. the liquid portion of the blood, contains about 90% of water and 10% of solids. The sub-stances dissolved in the plasma include, among other sub-;. .
stances, the gamma globulin which is used for the therapy and prophylaxe of infections. For the isolation of gamma - globulin, all of the other substances contained in the . .
plasma must be removed as far as possible, in order that as pure as possible a gamma globulin is provided.
For the precipitation and isolation of gamma globulin from blood, there is used particularly a process which is known by the name "COHN-Method." (COHN et al., J. Amer. Chem. Soc., -; Vol. 68, pp. 459... 475, and Vol. 72, pp. 465... 474). This process starts with a plasma mixed from various blood samples. Principally, this involves a ~ractionated pre-,~, ;........................ .. .
~ cipitation under various conditions. In a first stage, ~
,,.,. , , ~
as the first sediment there is initially separated mainly fibrinogen at a temperature of minus 3~C and at a pH of 7.2 with an ethanol addition of 8%. The supernatant .....
liquid is precipitated in a second stage with about 19% of ethanol at a pH of 5.6. The precipitate contains mainly , . .
gamma globulin. For the purification of this precipitate ~ I .
~designated as COHN-Fraction II-XII), this precipitate is :; _ ~ 30 re-dissolved and thereafter initially re~recipitated at a ;;~, ':
! ~ - 2 -~5~ S
pH of 5 and with 8% of ethanol. The remaining supernatant phase is thereafter again precipitated with 25~ of ethanol, ' and at a pH of 7.2 b The resul~ing precipitate comprises at least 90% of gamma globulin. The precipi~ate is received by a suitable buffer solution, and after the sterile filtration this precipitate is ready for application to human beings.
~', - , .
It has been found that in numerous instances the gamma globulin preparations which have been obtained in the above-indicated or in another manner9 are of anticomplementary activity such that complications result from corporeal re-actions in the case of intravenous application.
, ::
. , .
Accordingly, it has already been attempted to increase or improve the intravenous compatibility of gamma globulins.
As examples, the following methods or processes known from literature may be mentioned:
1) Treatment with suitable enzymes;
Z) hydrolysis at high hydrogen ions concentration (e.g.
at a pH of 4.0);
3~ modification by means of beta-propiolactone.
., .
However, it has been found that the known processes act to ~` modify *he gamma globulin molecules_and to vary them in ~heir chemical structu~e to such degree that their activity ~ is reduced and their average retention time in th~ organism `:~ is shortened.
~ Therefore 9 the present invention has.as its object the ,i:
r.," provision~of a novel process for increasing or improving ,........................................................................... .
. the intravenous compa~ibility of gamma globulins, which ` ~ process, on the one hand, avoids the disadvantages of the .,. .:
_ 3 ~ -.`''' "` ,' , . . . .
.,....................................................................... ~
, .. , ..... - , . . . . .
~ ~ 5 ~ ~7~i conventional processes and, on the other hand, provides the following improvements:.
- The st~ucture of the existing gamma globulin molecules is varied to minimum degree, - the anticomplementary activity should be greatly reduced as compared wi~h conventional gamma globulin preparations;
- the retention period in ~he organism should be increased9 whereby the preparation should be more compatible than conventional preparations.
These objects are solved by a process for impro~ing the intravenous compatibility, wherein the gamma globulin precipitated from blood or from blood products is introduced into an aqueous solution in the presence of macromolecular substances which shield the globulin molecules from each other and which displace these molecules from the solution, such as hydroxyethyl starch (HES), gelatine, destranes, ~ t albumin, polyalcohols, poli~inyls, whereupon the gamma globulin is precipitated and re-dLissolved, particularly in a phisiologic~l normal saline solution.
;, .
Acco~ding to present knowledge, the effecti~ity of HES is at an optimum; however, it is likew*se possible to obtain ~;~ a similar effect by the adtition of the other substances specified above.
, .... .
Preferably, the precipitate is introduced into a buffered - aqueous HES solution having a pH of from 3.5 to 8Ø A
`; particularly fa~orable practical value has been found to --r,., -be within the range of pH from 6.5 to 609.
~¦ The contents of HES in the aqueous solution may range ;~
between 1 ~nd 30~; a particula~ly good practical Yalue ~ ~ ;
amounts to f~om 8 ~o 10% of H~S.
.
.. , . ~ - .
, ~L058~) 75 Preferably, it is operated with HES having a molecular weight of between 1,000 and 900,000.
.. . .
Upon redissolving of the gamma globulin precipitate in the buffered HES solution - is added to the mixture (10~ of polyethylene glycol). The mixture is made free of unwanted precipitan~s by centrifugation. In the place of the poly-ethylene glycol as the precipitation agent~ other polymerized polyvalent alcohols may be used well. The remaining super-natant phase after centrifugation is mixed with 20~ of poly-....
ethylene glycol at a pH of from 7.Q to 7.2 and then centri-fuged anew. Expediently, the thus obtained precipitate is dissolved in a physiological normal saline solution and adjusted to a concentration of about 5% of albumin or ~, protein. After the sterile centrifugation, the solution is ready for therapeutical use.
r'; Below, the individual process steps are explained again in ; an Example.
` Separation of the gamma globulin:
;i T~e process starts with a collected plasma which is blended ,; 20 with 8~ of ethanol and precipitated at a pH of 7.2 at a temperature o minus 3C. Hereby, Fraction I is separated.
The recovered liquid is thereafter mixed with 19% of ethanol a~ a temperature of minus 5C and a pH of 5.8. Hereby, Fraction II-III is separated which consists of gamma globulins.
The precipitate is re-dissolved and again precipitated at a pH of 5 with 8% of ethanol. The remaining supe~natant phase is then again preclpitated with 25~ of ethanol at a pH of ,.:, ~ 7.2. The precipitatè obtained in this stage (= Fraction II) , , ~; comprises at least 90% of gamma globulin. ~
., . ~ .
~,J
~; - 5 - ~
, . . .
.
. : . . . . . .
~5~17S
Reduction of t~e anti`complementary activity:
The gamma globulin precipita~e is resolved in a buffered - aqueous solution at a pH of 6.7, in a concentration of about 6%, whereby the aqueous solu~ion has added thereto - about 10~ of hydroxylethyl starch ~HES). The HES renders ` possible a separation of already existing aggregates and ,. ..
i simultaneously protects non-aggregated gamma globulins.
Introduction into a Physiolo~ical normal saline solution:
After the addition of 10~ of polyethylene glycol 7 the . .
mixture is centrifuged. The remaining supernatant phase is mixed with 20% of polyethylene glycol at a pH of 7.2, and centrifuged. The thus obtained precipitate is adjusted to a concentration of 5.2~ of albumin in a physiological ; normal saline solution, and subsequently filtered under sterile conditions. Thereupon, the precipitate is ready ,~
~ for therapeutical use.
.~':; . .
~ The accompanying drawing shows in Figure 1 thereof the ~-, .
structural formula of hydroxyethyl starch (HES), and in Figure 2 thereof immune electrophoresis diagrams ~IEP) of various gamma globulins or of normal sera, respectively, . which have been prepared in accordance with the conventional ~ -, .; . . .
: and novel processes.
~, ,~. .
', The upper half of the diagrams of fig. 2 each shows IEP
diagrams of normal blood sera, whereas the lower half shows diagrams of:
(a) standard gamma globulin~
: ".
;~1 (b) proteolytically modified gamma globulin, ~
~. j .
`' ~c~ beta-p~opiolactone-modified gamma globulin, j (d~ gamma globuline as prepared in accordance with the : . 30 noveI process. . ~ -',.. , ' . '. "~ . ., . ~ :, . , ,. ~., . , ,. ~ :
~ S~7 5 Samples (a) to (c) each represent a commercially available modified preparation. In addition to the gamma globulin line (elongated crescen~-shaped line in the right hand portion of the diagram), ~hese samples also show additional -albumin or protein components of the human blood. Owing to the chemical modification, the gamma globulin lines of samples (a) and (b) are shown blurred. Sample (c) exhibits a varied position as compared with the gamma globulin line of the cont TO 1 S erum.
In contrast, it is clearly evident that sample (d) consists substantially exclusively of pure gamma globuline as the crescent-shaped line of the spectrum is distinctly present in the normal.serum.
:~.
9 It can be concluded from the diagrams that the gamma globulin obtained by the novel process has a purity of substantially 100% so as to completely correspond to the ' gamma globulin of the original blood serum. The la~ter fact means that the molecules are not modified or chemically ~ Yaried. These characteristics result in the further advan-; 20 tageous properties of the gamma globulin according to the ; novel process which have also been verified by tests, namely `` its absolutely positive intravenous compatibility and its greatly reduced anticomplementary activity to intracorporeal ; antibodies, which properties could be clearly demonstrated ;~, in in-vitro tests.
As another advantage, storage tests nave shown a particularly high stability of gamma globulins prepared in the above disclosed manne~, using the steps of invention.
:.'; ` -3~
,.................................................. . . . ..
Process of improvin~ the compatibilit~ of gamma globulins .,~
The present invention relates to a prscess of improving the intravenous compatibility of gamma globulins precipitated from blood or blood products.
,, .
- Blood is a liquid which consists of solid and liquid com-ponents. The solid components include the red and white blood corpuscles as well as the blood platelets---~r throm-bocytes. The plasma, i.e. the liquid portion of the blood, contains about 90% of water and 10% of solids. The sub-stances dissolved in the plasma include, among other sub-;. .
stances, the gamma globulin which is used for the therapy and prophylaxe of infections. For the isolation of gamma - globulin, all of the other substances contained in the . .
plasma must be removed as far as possible, in order that as pure as possible a gamma globulin is provided.
For the precipitation and isolation of gamma globulin from blood, there is used particularly a process which is known by the name "COHN-Method." (COHN et al., J. Amer. Chem. Soc., -; Vol. 68, pp. 459... 475, and Vol. 72, pp. 465... 474). This process starts with a plasma mixed from various blood samples. Principally, this involves a ~ractionated pre-,~, ;........................ .. .
~ cipitation under various conditions. In a first stage, ~
,,.,. , , ~
as the first sediment there is initially separated mainly fibrinogen at a temperature of minus 3~C and at a pH of 7.2 with an ethanol addition of 8%. The supernatant .....
liquid is precipitated in a second stage with about 19% of ethanol at a pH of 5.6. The precipitate contains mainly , . .
gamma globulin. For the purification of this precipitate ~ I .
~designated as COHN-Fraction II-XII), this precipitate is :; _ ~ 30 re-dissolved and thereafter initially re~recipitated at a ;;~, ':
! ~ - 2 -~5~ S
pH of 5 and with 8% of ethanol. The remaining supernatant phase is thereafter again precipitated with 25~ of ethanol, ' and at a pH of 7.2 b The resul~ing precipitate comprises at least 90% of gamma globulin. The precipi~ate is received by a suitable buffer solution, and after the sterile filtration this precipitate is ready for application to human beings.
~', - , .
It has been found that in numerous instances the gamma globulin preparations which have been obtained in the above-indicated or in another manner9 are of anticomplementary activity such that complications result from corporeal re-actions in the case of intravenous application.
, ::
. , .
Accordingly, it has already been attempted to increase or improve the intravenous compatibility of gamma globulins.
As examples, the following methods or processes known from literature may be mentioned:
1) Treatment with suitable enzymes;
Z) hydrolysis at high hydrogen ions concentration (e.g.
at a pH of 4.0);
3~ modification by means of beta-propiolactone.
., .
However, it has been found that the known processes act to ~` modify *he gamma globulin molecules_and to vary them in ~heir chemical structu~e to such degree that their activity ~ is reduced and their average retention time in th~ organism `:~ is shortened.
~ Therefore 9 the present invention has.as its object the ,i:
r.," provision~of a novel process for increasing or improving ,........................................................................... .
. the intravenous compa~ibility of gamma globulins, which ` ~ process, on the one hand, avoids the disadvantages of the .,. .:
_ 3 ~ -.`''' "` ,' , . . . .
.,....................................................................... ~
, .. , ..... - , . . . . .
~ ~ 5 ~ ~7~i conventional processes and, on the other hand, provides the following improvements:.
- The st~ucture of the existing gamma globulin molecules is varied to minimum degree, - the anticomplementary activity should be greatly reduced as compared wi~h conventional gamma globulin preparations;
- the retention period in ~he organism should be increased9 whereby the preparation should be more compatible than conventional preparations.
These objects are solved by a process for impro~ing the intravenous compatibility, wherein the gamma globulin precipitated from blood or from blood products is introduced into an aqueous solution in the presence of macromolecular substances which shield the globulin molecules from each other and which displace these molecules from the solution, such as hydroxyethyl starch (HES), gelatine, destranes, ~ t albumin, polyalcohols, poli~inyls, whereupon the gamma globulin is precipitated and re-dLissolved, particularly in a phisiologic~l normal saline solution.
;, .
Acco~ding to present knowledge, the effecti~ity of HES is at an optimum; however, it is likew*se possible to obtain ~;~ a similar effect by the adtition of the other substances specified above.
, .... .
Preferably, the precipitate is introduced into a buffered - aqueous HES solution having a pH of from 3.5 to 8Ø A
`; particularly fa~orable practical value has been found to --r,., -be within the range of pH from 6.5 to 609.
~¦ The contents of HES in the aqueous solution may range ;~
between 1 ~nd 30~; a particula~ly good practical Yalue ~ ~ ;
amounts to f~om 8 ~o 10% of H~S.
.
.. , . ~ - .
, ~L058~) 75 Preferably, it is operated with HES having a molecular weight of between 1,000 and 900,000.
.. . .
Upon redissolving of the gamma globulin precipitate in the buffered HES solution - is added to the mixture (10~ of polyethylene glycol). The mixture is made free of unwanted precipitan~s by centrifugation. In the place of the poly-ethylene glycol as the precipitation agent~ other polymerized polyvalent alcohols may be used well. The remaining super-natant phase after centrifugation is mixed with 20~ of poly-....
ethylene glycol at a pH of from 7.Q to 7.2 and then centri-fuged anew. Expediently, the thus obtained precipitate is dissolved in a physiological normal saline solution and adjusted to a concentration of about 5% of albumin or ~, protein. After the sterile centrifugation, the solution is ready for therapeutical use.
r'; Below, the individual process steps are explained again in ; an Example.
` Separation of the gamma globulin:
;i T~e process starts with a collected plasma which is blended ,; 20 with 8~ of ethanol and precipitated at a pH of 7.2 at a temperature o minus 3C. Hereby, Fraction I is separated.
The recovered liquid is thereafter mixed with 19% of ethanol a~ a temperature of minus 5C and a pH of 5.8. Hereby, Fraction II-III is separated which consists of gamma globulins.
The precipitate is re-dissolved and again precipitated at a pH of 5 with 8% of ethanol. The remaining supe~natant phase is then again preclpitated with 25~ of ethanol at a pH of ,.:, ~ 7.2. The precipitatè obtained in this stage (= Fraction II) , , ~; comprises at least 90% of gamma globulin. ~
., . ~ .
~,J
~; - 5 - ~
, . . .
.
. : . . . . . .
~5~17S
Reduction of t~e anti`complementary activity:
The gamma globulin precipita~e is resolved in a buffered - aqueous solution at a pH of 6.7, in a concentration of about 6%, whereby the aqueous solu~ion has added thereto - about 10~ of hydroxylethyl starch ~HES). The HES renders ` possible a separation of already existing aggregates and ,. ..
i simultaneously protects non-aggregated gamma globulins.
Introduction into a Physiolo~ical normal saline solution:
After the addition of 10~ of polyethylene glycol 7 the . .
mixture is centrifuged. The remaining supernatant phase is mixed with 20% of polyethylene glycol at a pH of 7.2, and centrifuged. The thus obtained precipitate is adjusted to a concentration of 5.2~ of albumin in a physiological ; normal saline solution, and subsequently filtered under sterile conditions. Thereupon, the precipitate is ready ,~
~ for therapeutical use.
.~':; . .
~ The accompanying drawing shows in Figure 1 thereof the ~-, .
structural formula of hydroxyethyl starch (HES), and in Figure 2 thereof immune electrophoresis diagrams ~IEP) of various gamma globulins or of normal sera, respectively, . which have been prepared in accordance with the conventional ~ -, .; . . .
: and novel processes.
~, ,~. .
', The upper half of the diagrams of fig. 2 each shows IEP
diagrams of normal blood sera, whereas the lower half shows diagrams of:
(a) standard gamma globulin~
: ".
;~1 (b) proteolytically modified gamma globulin, ~
~. j .
`' ~c~ beta-p~opiolactone-modified gamma globulin, j (d~ gamma globuline as prepared in accordance with the : . 30 noveI process. . ~ -',.. , ' . '. "~ . ., . ~ :, . , ,. ~., . , ,. ~ :
~ S~7 5 Samples (a) to (c) each represent a commercially available modified preparation. In addition to the gamma globulin line (elongated crescen~-shaped line in the right hand portion of the diagram), ~hese samples also show additional -albumin or protein components of the human blood. Owing to the chemical modification, the gamma globulin lines of samples (a) and (b) are shown blurred. Sample (c) exhibits a varied position as compared with the gamma globulin line of the cont TO 1 S erum.
In contrast, it is clearly evident that sample (d) consists substantially exclusively of pure gamma globuline as the crescent-shaped line of the spectrum is distinctly present in the normal.serum.
:~.
9 It can be concluded from the diagrams that the gamma globulin obtained by the novel process has a purity of substantially 100% so as to completely correspond to the ' gamma globulin of the original blood serum. The la~ter fact means that the molecules are not modified or chemically ~ Yaried. These characteristics result in the further advan-; 20 tageous properties of the gamma globulin according to the ; novel process which have also been verified by tests, namely `` its absolutely positive intravenous compatibility and its greatly reduced anticomplementary activity to intracorporeal ; antibodies, which properties could be clearly demonstrated ;~, in in-vitro tests.
As another advantage, storage tests nave shown a particularly high stability of gamma globulins prepared in the above disclosed manne~, using the steps of invention.
:.'; ` -3~
,.................................................. . . . ..
Claims (10)
1. In a process for preparing purified gamma globulin wherein impure gamma globulin precipitated from blood or blood products and containing component(s) having anti-complementary activity is re-dissolved in an aqueous medium and subsequently purified gamma globulin is precipitated therefrom, the improvement comprising including in said solution from 1-30% by weight of a hydroxyethyl starch having a molecular weight of 1000-900,000, preferentially precipitating said gamma globulin component(s) having anti-comple-mentary activity from said solution, and subsequently recovering gamma globulin substantially free of anti-complementary activity from said solution.
2. In a process for preparing purified gamma globulin wherein impure gamma globulin precipitated from blood or blood products and containing component(s) having anti-complementary activity is re-dissolved in an aqueous medium and subsequently purified gamma globulin is precipitated therefrom, the improvement comprising including in said solution from 1-30% by weight of a hydroxyethyl starch having a molecular weight of 1000-900,000, preferentially precipitating said gamma globulin component(s) having anti-comple-mentary activity from said solution by the addition of a precipitating agent, and subsequently recovering gamma globulin substantially free of anti-complementary activity from said solution.
3. In a process for preparing purified gamma globulin wherein impure gamma globulin precipitated from blood or blood produces and containing component(s) having anti-complementary activity is re-dissolved in an aqueous medium and subsequently purified gamma globulin is preciptitated thereform, the improvement comprising including in said solution from 1-30% by weight of a hydroxyethyl starch having a molecular weight of 1000-900,000 preferentially precipitating said gamma globulin component(s) having anti-comple-mentary activity from said solution by the addition of a precipitating agent, removing the so-formed precipitate, adding further precipitating agent to the residual solution to precipitate the gamma globulin substantially free of anti-complementary activity subsequently recovering same.
4. A process according to Claim 1, 2 or 3, wherein the HES solution is buffered and has a pH of from 3.5-8.
5. A process according to Claim 1, 2 or 3, wherein the HES solution is buffered and has a pH of from 6.5-6.9.
6. A process according to Claim 1, 2 or 3, wherein the solution contains from 8-10% by weight of HES.
7. A process according to Claim 1, 2 or 3, wherein the solution contains about 10% HES and about 6% impure gamma globulin.
8. A process according to Claim 1, 2 or 3, wherein the recovered purified gamma globulin is re-dissolved in a physiological normal saline solution.
9. A process according to Claim 1, 2 or 3, wherein the precipitating agent is a polymerized polyvalent alcohol.
10. A process according to Claim 2 or 3, wherein the precipitating agent is polyethylene glycol.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2500076A DE2500076C3 (en) | 1975-01-02 | 1975-01-02 | Process for the production of intravenously tolerated gamma globulins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1058075A true CA1058075A (en) | 1979-07-10 |
Family
ID=5935911
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA242,734A Expired CA1058075A (en) | 1975-01-02 | 1975-12-30 | Process of improving the compatibility of gamma globulins |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS5512001B2 (en) |
| AT (1) | AT344883B (en) |
| AU (1) | AU505416B2 (en) |
| BE (1) | BE837211A (en) |
| CA (1) | CA1058075A (en) |
| DD (1) | DD121875A5 (en) |
| DE (1) | DE2500076C3 (en) |
| DK (1) | DK144679C (en) |
| EG (1) | EG11987A (en) |
| ES (1) | ES443982A1 (en) |
| FR (1) | FR2296429A1 (en) |
| GB (1) | GB1495159A (en) |
| IE (1) | IE43449B1 (en) |
| IL (1) | IL48766A (en) |
| IN (1) | IN143525B (en) |
| NL (1) | NL179824C (en) |
| PL (1) | PL99599B1 (en) |
| SE (1) | SE437470B (en) |
| SU (1) | SU576898A3 (en) |
| ZA (1) | ZA758050B (en) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2604759C2 (en) * | 1976-02-07 | 1983-06-01 | SCHURA Blutderivate GmbH & Co KG, 4150 Krefeld | Method of Obtaining IV Compatible Gamma Globulins |
| JPS6016406B2 (en) * | 1976-08-06 | 1985-04-25 | マイヤ−、ル−イス、コ−バル | Method for producing intravenously administrable gamma globulin and gamma globulin prepared thereby |
| US4124576A (en) * | 1976-12-03 | 1978-11-07 | Coval M L | Method of producing intravenously injectable gamma globulin |
| GB1603244A (en) * | 1977-05-20 | 1981-11-18 | Max Planck Gesellschaft | Medicaments for the suppression of pathological processes |
| JPS5822085B2 (en) * | 1977-07-19 | 1983-05-06 | 株式会社ミドリ十字 | Intravenous gamma globulin preparations |
| AT359641B (en) * | 1978-09-19 | 1980-11-25 | Immuno Ag | METHOD FOR PRODUCING AN INTRAVENOUS ADMINISTRABLE ANTIBODY-CONTAINING IMMUNOGLOBULIN PREPARATE |
| EP0019403B1 (en) * | 1979-05-10 | 1985-07-31 | American Hospital Supply Corporation | Hydroxyalkyl-starch drug carrier |
| US4396608A (en) * | 1981-08-24 | 1983-08-02 | Cutter Laboratories | Intravenously injectable immune serum globulin |
| EP0085747B2 (en) * | 1982-02-08 | 1990-05-30 | Schweizerisches Serum- und Impfinstitut und Institut zur Erforschung der Infektionskrankheiten | Intravenously administrable human immunoglobuline and process for its preparation |
| US4482483A (en) * | 1983-04-06 | 1984-11-13 | Armour Pharmceutical Company | Composition of intravenous immune globulin |
| SE8302483L (en) * | 1983-05-02 | 1984-11-03 | Pharmacia Ind | PROCEDURE FOR PURIFICATION OF BIOLOGICALLY ACTIVE SUBSTANCES |
| US5945098A (en) * | 1990-02-01 | 1999-08-31 | Baxter International Inc. | Stable intravenously-administrable immune globulin preparation |
| DE19907257A1 (en) * | 1999-02-21 | 2000-09-14 | Bernd Horst Meier | Means for controlling the diffusion of injection solutions |
| DE10040707A1 (en) * | 2000-08-17 | 2002-03-14 | Braun Melsungen Ag | Injectable aqueous medicament, containing colloid, e.g. hydroxyethyl starch, to modulate mobility, diffusion, pharmacokinetic and electrophoretic properties of active agent and improve effectiveness |
| DE10303974A1 (en) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid β (1-42) oligomers, process for their preparation and their use |
| PT1954718E (en) | 2005-11-30 | 2014-12-16 | Abbvie Inc | Anti-a globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies |
| DK1976877T4 (en) | 2005-11-30 | 2017-01-16 | Abbvie Inc | Monoclonal antibodies to amyloid beta protein and uses thereof |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| WO2008104386A2 (en) | 2007-02-27 | 2008-09-04 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
| MX360403B (en) | 2010-04-15 | 2018-10-31 | Abbvie Inc | Amyloid-beta binding proteins. |
| EP2603524A1 (en) | 2010-08-14 | 2013-06-19 | AbbVie Inc. | Amyloid-beta binding proteins |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE348942B (en) * | 1970-06-02 | 1972-09-18 | Statens Bakteriologiska Labor | |
| DE2234069A1 (en) * | 1971-07-16 | 1973-02-08 | South African Inventions | METHOD OF MANUFACTURING A PURIFIED GAMMA GLOBULIN |
| ZA738779B (en) * | 1972-11-27 | 1974-10-30 | Baxter Laboratories Inc | Production of gamma globulin |
| JPS49101516A (en) * | 1973-01-13 | 1974-09-25 |
-
1975
- 1975-01-02 DE DE2500076A patent/DE2500076C3/en not_active Expired
- 1975-12-16 NL NLAANVRAGE7514627,A patent/NL179824C/en not_active IP Right Cessation
- 1975-12-18 SE SE7514388A patent/SE437470B/en not_active IP Right Cessation
- 1975-12-22 DK DK584375A patent/DK144679C/en active
- 1975-12-23 AT AT981675A patent/AT344883B/en active
- 1975-12-26 FR FR7539814A patent/FR2296429A1/en active Granted
- 1975-12-27 JP JP15974275A patent/JPS5512001B2/en not_active Expired
- 1975-12-29 DD DD190614A patent/DD121875A5/xx unknown
- 1975-12-29 GB GB53020/75A patent/GB1495159A/en not_active Expired
- 1975-12-30 IE IE2826/75A patent/IE43449B1/en unknown
- 1975-12-30 IL IL48766A patent/IL48766A/en unknown
- 1975-12-30 AU AU87921/75A patent/AU505416B2/en not_active Expired
- 1975-12-30 ZA ZA00758050A patent/ZA758050B/en unknown
- 1975-12-30 IN IN2413/CAL/75A patent/IN143525B/en unknown
- 1975-12-30 BE BE6045314A patent/BE837211A/en not_active IP Right Cessation
- 1975-12-30 EG EG775/75A patent/EG11987A/en active
- 1975-12-30 CA CA242,734A patent/CA1058075A/en not_active Expired
- 1975-12-30 ES ES443982A patent/ES443982A1/en not_active Expired
- 1975-12-31 SU SU7502306354A patent/SU576898A3/en active
-
1976
- 1976-01-01 PL PL1976186289A patent/PL99599B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5191321A (en) | 1976-08-10 |
| PL99599B1 (en) | 1978-07-31 |
| ATA981675A (en) | 1977-12-15 |
| SU576898A3 (en) | 1977-10-15 |
| DE2500076A1 (en) | 1976-07-08 |
| GB1495159A (en) | 1977-12-14 |
| ZA758050B (en) | 1976-12-29 |
| EG11987A (en) | 1981-12-31 |
| DD121875A5 (en) | 1976-09-05 |
| IL48766A (en) | 1979-11-30 |
| NL7514627A (en) | 1976-07-06 |
| DE2500076B2 (en) | 1979-02-22 |
| SE7514388L (en) | 1976-07-05 |
| ES443982A1 (en) | 1977-07-16 |
| FR2296429B1 (en) | 1978-12-01 |
| AT344883B (en) | 1978-08-10 |
| DK144679C (en) | 1982-10-11 |
| IE43449B1 (en) | 1981-02-25 |
| FR2296429A1 (en) | 1976-07-30 |
| SE437470B (en) | 1985-03-04 |
| BE837211A (en) | 1976-06-30 |
| JPS5512001B2 (en) | 1980-03-29 |
| IE43449L (en) | 1976-07-02 |
| NL179824B (en) | 1986-06-16 |
| IL48766A0 (en) | 1976-02-29 |
| IN143525B (en) | 1977-12-17 |
| NL179824C (en) | 1986-11-17 |
| DE2500076C3 (en) | 1982-11-18 |
| DK584375A (en) | 1976-07-03 |
| AU505416B2 (en) | 1979-11-22 |
| DK144679B (en) | 1982-05-10 |
| AU8792175A (en) | 1977-07-14 |
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