US4608364A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Pharmaceutical agent for the treatment of diabetes mellitus
Assignee: Hoechst AG
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Filing: 1984-07-20
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Granted: 1986-08-26
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Expires: 2004-07-20
Abstract
Abstract The invention relates to medicaments consisting of a physiologically acceptable excipient and an active compound combination of (a) an insulin derivative of the formula I ##STR1## in which R 1 denotes H or H--Phe, R 30 represents the radical of a neutral L-aminoacid and R 31 represents a physiologically acceptable organic group of basic character with up to 50 carbon atoms, with an isoelectric point between 5.8 and 8.5, and (b) an insulin of the formula I in which R 1 denotes H or H--Phe, R 30 represents Ala, Thr or Ser and R 31 denotes OH, and to its use for the treatment of diabetes mellitus.
Inventors
- 👤 Ulrich Grau
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 12:36
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/62; C07K14/625; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/26
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
253 words
A pharmaceutical composition stable on storing and being suitable for the treatment of diabetes mellitus consisting of a physiologically acceptable excipient and an active compound combination, which contains, as the active compound combination, (a) an insulin derivative of the formula I ##STR5## in which R 1 denotes H or H--Phe R 30 represents the radical of Ala, Thr or Ser and R 31 represents a physiologically acceptable organic group of basic character of the formula X n --S which has up to 50 carbon atoms, in which n is 0, 1, 2 or 3, X represents identical or different radicals of naturally occurring neutral or basic α-amino acids and S denotes OH or a physiologically acceptable group which blocks the carboxyl group but S being, if n is 0, a positively charged or protonatable basic radical or, if n is greater than 0, S can carry such a radical, or in which, if n is 2 or 3, the C-terminus X--S can also represent the homoserine-lapton radical and which contains or does not contain a terminal carboxyl function or an ester or an amide thereof, with an iso electric point between 5.8 and 8.5, and (b) an insulin of the formula I in which R 1 denotes H or H--Phe, R 30 represents Ala, Thr or Ser and R 31 denotes OH, or (b2) physiologically acceptable salts thereof, or (b3) proinsulin or (b4) C peptide or (b5) a combination thereof, component (a) being present in an amount of at least 1% by weight.
Claim 2
Dependent Claim
253 words
A pharmaceutical composition stable on storing and being suitable for the treatment of diabetes mellitus consisting of a physiologically acceptable excipient and an active compound combination, which contains, as the active compound combination, (a) an insulin derivative of the formula I ##STR5## in which R 1 denotes H or H--Phe R 30 represents the radical of Ala, Thr or Ser and R 31 represents a physiologically acceptable organic group of basic character of the formula X n --S which has up to 50 carbon atoms, in which n is 0, 1, 2 or 3, X represents identical or different radicals of naturally occurring neutral or basic α-amino acids and S denotes OH or a physiologically acceptable group which blocks the carboxyl group but S being, if n is 0, a positively charged or protonatable basic radical or, if n is greater than 0, S can carry such a radical, or in which, if n is 2 or 3, the C-terminus X--S can also represent the homoserine-lapton radical and which contains or does not contain a terminal carboxyl function or an ester or an amide thereof, with an iso electric point between 5.8 and 8.5, and (b) an insulin of the formula I in which R 1 denotes H or H--Phe, R 30 represents Ala, Thr or Ser and R 31 denotes OH, or (b2) physiologically acceptable salts thereof, or (b3) proinsulin or (b4) C peptide or (b5) a combination thereof, component (a) being present in an amount of at least 1% by weight.
Claim 3
Dependent Claim
25 words
A composition as claimed in claim 1, in which R 1 represents H--Phe in the insulin derivative and in the insulin of the formula I.
Claim 4
Dependent Claim
29 words
A composition as claimed in claim 1, in which the amino acid radicals X are in the L-configuration in the insulin derivative of the formula I, mentioned under (1a).
Claim 5
Dependent Claim
19 words
A composition as claimed in claim 1, in which S represents OH or (C 1 to C 6 )-alkoxy.
Claim 6
Dependent Claim
27 words
A composition as claimed in claim 1, in which X denotes Lys or Arg or both, in the insulin derivative of the formula I, mentioned under (1a).
Claim 7
Dependent Claim
12 words
A composition as claimed in claim 5, which contains insulin-B31--Arg--OH or insulin-B31--Arg--Arg--OH.
Claim 8
Dependent Claim
33 words
A composition as claimed in claim 1, which contains a plurality of (a) different insulin derivatives of the formula I or (b) different insulins of the formula I or of (a) and (b).
Claim 9
Dependent Claim
22 words
A composition as claimed in claim 1, which contains proinsulin or a proinsulin analogue or human C peptide or a combination thereof.
Claim 10
Dependent Claim
35 words
A composition as claimed in claim 1, which has a pH between 2.5 and 8.5 and is in the form of a solution or suspension, and contains a conventional isotonicity agent and a conventional preservative.
Claim 11
Dependent Claim
23 words
A composition as claimed in claim 1, which additionally contains a conventional buffer substance, if the pH value is between 5.0 and 8.5.
Claim 12
Dependent Claim
31 words
A composition as claimed in claim 1, wherein the formulation contains a conventional stabilizer which prevents precipitation of protein on exposure to heat or mechanical stress on contact with various materials.
Claim 13
Dependent Claim
23 words
A composition as claimed in claim 1, which contains a suitable amount of zinc, which can be between 0 and 100 μg/100 units.
Claim 14
Dependent Claim
45 words
A composition as claimed in claim 1, in which the insulin or proinsulin or des-Phe B1 -insulin or C peptide or a combination thereof and insulin derivative of the formula I are used in the form of an alkali metal salt or the ammonium salt.
Claim 15
Dependent Claim
53 words
A composition as claimed in claim 1, wherein the content of insulin or proinsulin or des-Phe B1 -insulin or C-peptide or a combination thereof and the content of insulin derivative of the formula I can in each case be, independently of one another, in dissolved, amorphous or crystalline form or a combination thereof.
Claim 16
Dependent Claim
123 words
A composition as claimed in claim 1, in which in each case any desired part of the content of insulin or proinsulin or des-Phe- B1 -insulin or C-peptide or a combination thereof and of the content of insulin derivative of the formula I is in crystalline form, in each case any other desired part of the content of insulin or proinsulin or des-Phe-insulin or C-peptide or a combination thereof and of the content of the insulin derivative of the formula I is in amorphous form, and in each case the remainder of the content of insulin or proinsulin or des-Phe-insulin or C peptide or a combination thereof and of the content of the insulin derivative of the formula I is in dissolved form.
Claim 17
Dependent Claim
16 words
A composition as claimed in claim 1, which contains a conventional auxiliary having a delaying action.
Claim 18
Dependent Claim
27 words
A composition as claimed in claim 16, in which this delayed action principle is used in combination with the entire active compound content or with parts thereof.
Claim 19
Dependent Claim
40 words
A composition as claimed in claim 16, which contains insulin or proinsulin or des-Phe-insulin or C peptide or a combination thereof and insulin derivative of the formula I in combination with a plurality of different auxiliaries having a delaying action.
Claim 20
Dependent Claim
41 words
A method of treating a patient suffering from diabetes mellitus which comprises administering an effective amount of an insulin derivative of the formula I and an insulin of the formula I according to claim 1 or a pharmaceutically acceptable salt thereof.
References Cited (Backward Citations)
GB2104381A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-08-25 | 1990-02-24 | 1990-08-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-08-25 | 1994-02-24 | 1994-08-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-08-25 | 1998-02-24 | 1998-08-26 | $7700.00 | Window Closed / Lapsed |