US4428942A
Expired / Lapsed
US
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Analogs of somatostatin
Assignee: Salk Institute for Biological Studies
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Filing: 1982-05-17
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Granted: 1984-01-31
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Expires: 2002-05-17
Abstract
Abstract Somatostatin-14 has the formula: <IMAGE> Analogs that are more potent than somatostatin-14 in increasing electrolyte absorption in the gut without suppressing the secretion of GH, insulin and glucagon, or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals in the same manner as somatostatin to increase absorbtion of electrolytes for the treatment of diarrhea. In particular of the analogs, certain substitutions are made for Phe in the 11-position, sometimes in combination with deletions in the 4- and 5-positions and in the 12- and 13-positions. D-Cys may also be substituted in the 3- or 14-position. There may be some substitutions in the 6- and 10-positions, and the residues in the 1- and/or 2-positions may also be deleted or substituted.
Inventors
- 👤 Jean E. F. Rivier
- 👤 Wylie W. Vale, Jr.
- 👤 Marvin R. Brown
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 19:28
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/655; C07K14/6555; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/16; Y10S930/26
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
174 words
A method for the treatment of mammals to increase electrolyte absorption in the gut comprising administering an effective amount of a somatostatin analog having the formula: ##STR6## wherein: R is hydrogen; R 1 is Ala or des R 1 ; R 2 is Gly or des R 2 ; R 4 is Lys or D-Lys or des R 4 ; R 5 is Asn or des R 5 ; R 6 is Phe or D-Phe or Ala; R 10 is Thr or Ala or des R 10 ; R 11 is Ala, Arg, Trp, Val, Ile, Ser, Thr, Glu, His, β-Nal, Lys Pro or des R 11 ; R 12 is Thr or Ala or des R 12 ; and R 13 is Ser or D-Ser or des R 13 ; provided that not more than two of R 10 , R 11 , R 12 and R 13 are deleted and provided that if R 4 is deleted, either R 12 or R 13 is also deleted; or a nontoxic addition salt thereof.
Claim 2
Independent Claim
174 words
A method for the treatment of mammals to increase electrolyte absorption in the gut comprising administering an effective amount of a somatostatin analog having the formula: ##STR6## wherein: R is hydrogen; R 1 is Ala or des R 1 ; R 2 is Gly or des R 2 ; R 4 is Lys or D-Lys or des R 4 ; R 5 is Asn or des R 5 ; R 6 is Phe or D-Phe or Ala; R 10 is Thr or Ala or des R 10 ; R 11 is Ala, Arg, Trp, Val, Ile, Ser, Thr, Glu, His, β-Nal, Lys Pro or des R 11 ; R 12 is Thr or Ala or des R 12 ; and R 13 is Ser or D-Ser or des R 13 ; provided that not more than two of R 10 , R 11 , R 12 and R 13 are deleted and provided that if R 4 is deleted, either R 12 or R 13 is also deleted; or a nontoxic addition salt thereof.
Claim 3
Dependent Claim
10 words
The method of claim 1 wherein R 11 is Trp.
Claim 4
Dependent Claim
10 words
The method of claim 1 wherein R 11 is Arg.
Claim 5
Dependent Claim
10 words
The method of claim 1 wherein R 11 is β-Nal.
Claim 6
Dependent Claim
10 words
The method of claim 1 wherein R 11 is His.
Claim 7
Dependent Claim
12 words
The method of claim 2 wherein Trp in the 8-position is D-Trp.
Claim 8
Dependent Claim
20 words
The method in accordance with claim 1 wherein said administering is carried out either orally, intravenously, subcutaneously, intranasally or intramuscularly.
Claim 9
Dependent Claim
22 words
The method in accordance with claim 1 where said administering is carried out intravenously at between 25 and 300 μg per hour.
Claim 10
Dependent Claim
169 words
A pharmaceutical composition for administration to mammals for the treatment of diarrhea, which comprises an effective amount of a somatostatin analog having the formula: ##STR7## wherein: R 4 is Lys or D-Lys or des R 4 ; R 6 is Phe or D-Phe or Ala; R 10 is Thr or Ala or des R 10 ; R 11 is Arg, Trp, His, Glu, β-Nal or Phe; R 12 is Thr or Ala or des R 12 ; and R 13 is Ser or D-Ser or des R 13 ; provided that (a) Ala, Gly and/or Asn can be deleted; (b) D-Trp can be substituted for Trp and D-Cys can be substituted for either or both Cys residues; (c) when R 11 is Phe, then R 4 is D-Lys; (d) not all R 10 , R 12 and R 13 are deleted; and (e) if R 4 is deleted, either R 12 or R 13 is deleted; or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
Claim 11
Dependent Claim
169 words
A pharmaceutical composition for administration to mammals for the treatment of diarrhea, which comprises an effective amount of a somatostatin analog having the formula: ##STR7## wherein: R 4 is Lys or D-Lys or des R 4 ; R 6 is Phe or D-Phe or Ala; R 10 is Thr or Ala or des R 10 ; R 11 is Arg, Trp, His, Glu, β-Nal or Phe; R 12 is Thr or Ala or des R 12 ; and R 13 is Ser or D-Ser or des R 13 ; provided that (a) Ala, Gly and/or Asn can be deleted; (b) D-Trp can be substituted for Trp and D-Cys can be substituted for either or both Cys residues; (c) when R 11 is Phe, then R 4 is D-Lys; (d) not all R 10 , R 12 and R 13 are deleted; and (e) if R 4 is deleted, either R 12 or R 13 is deleted; or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
Claim 12
Dependent Claim
10 words
The composition of claim 9 wherein R 11 is Trp.
Claim 13
Dependent Claim
10 words
The composition of claim 9 wherein R 11 is Arg.
Claim 14
Dependent Claim
10 words
The composition of claim 9 wherein R 11 is β-Nal.
Claim 15
Dependent Claim
10 words
The composition of claim 9 wherein R 4 is D-Lys.
Claim 16
Dependent Claim
90 words
A somatostatin analog having the formula: ##STR8## wherein: R 11 is Arg, Trp, His, Glu or β-Nal; provided that (a) Ala, Gly and one or two of the residues in positions 10, 12 and 13 can be deleted; (b) Lys 4 and/or Asn can be deleted; and (c) D-Trp can be substituted for Trp, D-Lys can be substituted for Lys 4 , D-Ser can be substituted for Ser, D-Cys can be substituted for Cys 14 and/or D-Phe can be substituted for Phe 6 ; or a nontoxic addition salt thereof.
Claim 17
Dependent Claim
90 words
A somatostatin analog having the formula: ##STR8## wherein: R 11 is Arg, Trp, His, Glu or β-Nal; provided that (a) Ala, Gly and one or two of the residues in positions 10, 12 and 13 can be deleted; (b) Lys 4 and/or Asn can be deleted; and (c) D-Trp can be substituted for Trp, D-Lys can be substituted for Lys 4 , D-Ser can be substituted for Ser, D-Cys can be substituted for Cys 14 and/or D-Phe can be substituted for Phe 6 ; or a nontoxic addition salt thereof.
Claim 18
Dependent Claim
10 words
The analog of claim 14 wherein R 11 is Trp.
Claim 19
Dependent Claim
10 words
The analog of claim 15 which is [Trp 11 ]-SS.
Claim 20
Dependent Claim
13 words
The analog of claim 15 which is des-AA 1 ,2, [Trp 11 ]-SS.
Claim 21
Dependent Claim
10 words
The analog of claim 14 wherein R 11 is β-Nal.
Claim 22
Dependent Claim
10 words
The analog of claim 18 which is [Arg 11 ]-SS.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-01-30 | 1987-08-01 | 1988-01-31 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-01-30 | 1991-08-01 | 1992-01-31 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-01-30 | 1995-08-01 | 1996-01-31 | $7700.00 | Window Closed / Lapsed |