US4137307A
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Process for preparing haptoglobin aqueous solution using strong anion exchanger
Assignee: Tanabe Pharma Corp
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Filing: 1977-04-19
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Granted: 1979-01-30
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Expires: 1997-04-19
Abstract
Abstract An aqueous solution of haptoglobin is obtained by subjecting an aqueous solution of alpha and beta -globulin fractions of human blood plasma to further fractionation by use of ammonium sulfate, collecting fractions precipitated at a concentration between 30% and 40% saturation of ammonium sulfate, contacting a reconstituted aqueous solution of the collected fractions with an anion exchanger to adsorb haptoglobin on said anion exchanger, selectively eluting the haptoglobin from the anion exchanger, and then concentrating the resulting aqueous eluate solution. The aqueous solution of haptoglobin is subjected to heat treatment in the presence of a selected stabilizing agent for inactivating hepatitis B virus at an optional step of the process.
Inventors
- 👤 Satoshi Funakoshi
- 👤 Takao Omura
- 👤 Takeshi Ohshiro
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 15:43
CPC Classifications
A; A61; A61K; A61K38/00; A61L; A61L2/00; A61L2/02; A61L2/04; C; C07; C07K; C07K14/00; C07K14/435; C07K14/46; C07K14/47; A61L2103/00; A61L2103/05; A61L2103/09; Y; Y10; Y10S; Y10S530/00; Y10S530/806; Y10S530/827; Y10S530/829; Y10S530/83; Y10S530/831
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
100 words
A process for preparing a solution of human serum haptoglobin, characterized by subjecting an aqueous solution of α- and β-globulin fractions of human blood plasma to further fractionation by use of ammonium sulfate, collecting the fractions precipitated at an ammonium sulfate concentration between 30% W/V and 40% W/V saturation, contacting an aqueous reconstituted solution of the collected fractions with a strong anion exchanger which is epichlorhydrin-crosslinked diethyl (2-hydroxypropyl) aminoethyldextran or guanidoethyl cellulose to absorb haptoglobin onto said anion exchanger, eluting haptoglobin from the anion exchanger, concentrating the resulting eluate and forming the concentrated solution into a physiologically acceptable aqueous solution.
Claim 2
Dependent Claim
100 words
A process for preparing a solution of human serum haptoglobin, characterized by subjecting an aqueous solution of α- and β-globulin fractions of human blood plasma to further fractionation by use of ammonium sulfate, collecting the fractions precipitated at an ammonium sulfate concentration between 30% W/V and 40% W/V saturation, contacting an aqueous reconstituted solution of the collected fractions with a strong anion exchanger which is epichlorhydrin-crosslinked diethyl (2-hydroxypropyl) aminoethyldextran or guanidoethyl cellulose to absorb haptoglobin onto said anion exchanger, eluting haptoglobin from the anion exchanger, concentrating the resulting eluate and forming the concentrated solution into a physiologically acceptable aqueous solution.
Claim 3
Dependent Claim
37 words
A process according to claim 1, comprising clarifying aqueous solution of α- and β-globulin fractions or the ammonium sulfate-precipitate by adding rivanol to the solution, separating the precipitates formed and then removing residual rivanol from the solution.
Claim 4
Dependent Claim
47 words
A process according to claim 1 comprising adding to the aqueous solution of haptoglobin at least one stabilizer selected from the group consisting of neutral amino acids, monosaccharides, disaccharides and soluble sugar alcohols, heating until the HB-Ag is inactivated and then freeing the solution from the stabilizer.
Claim 5
Dependent Claim
14 words
A process according to claim 1, wherein the strong anion exchanger is epichlorohydrin-crosslinked diethyl(2-hydroxypropyl)aminoethyldextran.
Claim 6
Dependent Claim
19 words
A process according to claim 1, wherein the aqueous eluate is concentrated by precipitating with ammonium sulfate precipitation method.
Claim 7
Dependent Claim
17 words
A process according to claim 1, wherein the aqueous eluate is concentrated by dialysis under reduced pressure.
Claim 8
Dependent Claim
22 words
A process according to claim 1, wherein the physiologically acceptable aqueous solution is in the form of an isotonic sodium chloride solution.
Claim 9
Dependent Claim
17 words
A process according to claim 2, wherein the residual rivanol is removed by dialysis against buffer solution.
Claim 10
Dependent Claim
21 words
A process according to claim 2, wherein the residual rivanol is removed by adsorption on bentonite, terra alba or active carbon.
Claim 11
Dependent Claim
23 words
A process according to claim 3, wherein the stabilizing agent is a neutral amino acid and is glycine, alanine, valine, leucine or isoleucine.
Claim 12
Dependent Claim
20 words
A process according to claim 3, wherein the stabilizing agent is a monosaccharide and is glucose, mannose, galactose or fructose.
Claim 13
Dependent Claim
19 words
A process according to claim 3, wherein the stabilizing agent is a disaccharide and is sucrose, maltose or lactose.
Claim 14
Dependent Claim
21 words
A process according to claim 3, wherein the stabilizing agent is a soluble sugar alcohol and is mannitol, sorbitol or xylitol.
Claim 15
Dependent Claim
20 words
A process according to claim 3, wherein the aqueous solution of haptoglobin is heated at 60° C. for 10 hours.
Claim 16
Dependent Claim
13 words
A process according to claim 3, wherein the stabilizer is removed by dialysis.
Claim 17
Dependent Claim
26 words
A process according to claim 3, wherein the amount of the stabilizer added is at least 5% by weight based on the volume of the solution.
Claim 18
Dependent Claim
26 words
A process according to claim 3, wherein the amount of the stabilizer added is 15 to 20% by weight based on the volume of the solution.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1982-01-29 | 1982-07-31 | 1983-01-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1986-01-29 | 1986-07-31 | 1987-01-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1990-01-29 | 1990-07-31 | 1991-01-30 | $7700.00 | Window Closed / Lapsed |