US4183849A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Therapeutic insulin preparation and a process for the production of a stable insulin preparation with protracted effect
Assignee: Nordisk Insulinlaboratorium
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Filing: 1977-12-08
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Granted: 1980-01-15
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Expires: 1997-12-08
Abstract
Abstract Novel stable insulin preparations with protracted action and reduced or no antigenicity are obtained by reacting insulin free of antigenic impurities with an organic compound having basic amino groups, preferably a basic polypeptide or a cleavage product of a basic polypeptide, such as protamine, in a buffered protein dissociating or protein depolymerizing aqueous medium. Examples of preferred protein dissociating or protein depolymerizing media are aqueous solutions containing urea, a lower alkanol dialkylformamide, acetamide, N-alkyl-acetamide or acetonitrile.
Inventors
- 👤 Bruno A. Hansen
- 👤 Finn H. Andresen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 04:38
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/58; A61K47/585; C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/62; C07K14/625; A61K38/00
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
106 words
In a process for producing a stable insulin preparation with protracted action, wherein insulin is purified to a state of reduced or no antigenicity and then is reacted with an organic base containing amino groups in an aqueous medium maintained at a pH of about 6 to about 9, and the insulin preparation is isolated, the improvement comprising utilizing for said reaction with said organic base a medium containing a protein depolymerizing or protein dissociating stabilizer to maintain said purified insulin in a dissolved monomeric or loosely aggregated form during said reaction, thereby producing a stable insulin preparation with protracted action and reduced or no antigencity.
Claim 2
Dependent Claim
106 words
In a process for producing a stable insulin preparation with protracted action, wherein insulin is purified to a state of reduced or no antigenicity and then is reacted with an organic base containing amino groups in an aqueous medium maintained at a pH of about 6 to about 9, and the insulin preparation is isolated, the improvement comprising utilizing for said reaction with said organic base a medium containing a protein depolymerizing or protein dissociating stabilizer to maintain said purified insulin in a dissolved monomeric or loosely aggregated form during said reaction, thereby producing a stable insulin preparation with protracted action and reduced or no antigencity.
Claim 3
Dependent Claim
12 words
A process according to claim 1, wherein the insulin is bovine insulin.
Claim 4
Dependent Claim
16 words
A process according to claim 1, wherein the medium is a buffered aqueous solution of urea.
Claim 5
Dependent Claim
31 words
A process according to claim 1, wherein the medium is a buffered aqueous solution containing a compound selected from the group consisting of a lower alkanol, dialkylformamide, acetamide, N-alkyl-acetamide and acetonitrile.
Claim 6
Dependent Claim
31 words
A process according to claim 1, wherein the medium is a buffered aqueous solution containing about 7 mol urea, and the reaction product is precipitated by dilution of the reaction mixture.
Claim 7
Dependent Claim
21 words
A process according to claim 1, wherein the organic base containing amino groups is a polypeptide or a cleavage product thereof.
Claim 8
Dependent Claim
11 words
A process according to claim 6, wherein the polypeptide is protamine.
Claim 9
Dependent Claim
68 words
A process according to claim 1, the improvement comprising the steps of subjecting insulin to a chromatographic purification using a buffered eluent containing a protein dissociating or protein depolymerizing stabilizer, isolating a fraction of the eluted product containing highly purified insulin, adding an aqueous solution of an organic base containing amino groups to said fraction, maintaining a pH of 6 to 9 and isolating the produced insulin preparation.
Claim 10
Dependent Claim
12 words
A process according to claim 8, wherein the insulin is bovine insulin.
Claim 11
Dependent Claim
16 words
A process according to claim 8, wherein the eluent is a buffered aqueous solution of urea.
Claim 12
Dependent Claim
31 words
A process according to claim 8, wherein the eluent is a buffered aqueous solution of a compound selected from the group consisting of a lower alkanol, dialkylformamide, acetamide, N-alkyl-acetamide and acetonitrile.
Claim 13
Dependent Claim
31 words
A process according to claim 8, wherein the eluent is a buffered aqueous solution containing about 7 mol urea, and the reaction product is precipitated by dilution of the reaction mixture.
Claim 14
Dependent Claim
21 words
A process according to claim 8, wherein the organic base containing amino groups is a polypeptide or a cleavage product thereof.
Claim 15
Dependent Claim
11 words
A process according to claim 13, wherein the polypeptide is protamine.
Claim 16
Dependent Claim
18 words
A process according to claim 8, wherein the eluent is an aqueous buffered solution containing 50-70% lower alkanol.
Claim 17
Dependent Claim
12 words
A process according to claim 15, wherein the lower alkanol is ethanol.
Claim 18
Dependent Claim
26 words
A process according to claim 8, wherein the insulin is also subjected to a gel filtration before the reaction with the organic base containing amino groups.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-01-14 | 1983-07-16 | 1984-01-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-01-14 | 1987-07-16 | 1988-01-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-01-14 | 1991-07-16 | 1992-01-15 | $7700.00 | Window Closed / Lapsed |