US 12,544,349 B1Granted

Compositions comprising pemvidutide and an acylated amino acid

AssigneeAdocia

InventorsUlysse Naessens, Romain Noel

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Abstract

The invention relates to a pharmaceutical composition, in particular a solid composition, including a compound of (i), which is a permeation enhancer according to Formula I, said permeation enhancer being an acylated aminoacid substituted on the amine function, also called AC-aa-NS, and a compound of (ii) having at least 90% sequence identity to SEQ ID NOS: 1-23. Also disclosed are methods of preparing the pharmaceutical composition, formulations, and their use in medicine.

Claims30

Dependent claims

A pharmaceutical composition comprising of (i) a compound comprising a structure of:

wherein R1 is an alkyl comprising 5 to 15 carbon atoms, an alkyl comprising 7 to 17 carbon atoms and a carboxyl group, or an alkyl comprising 7 to 17 carbon atoms and a hydroxyl group;
and R3 is hydrogen or a cation;
and
(ii) a compound comprising a sequence having at least 90% sequence identity to:
(SEQ ID NO:
1)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Lys20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
2)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
3)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-
Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
4)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-
Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
5)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-octadecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-
Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
6)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-dodecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys(N-
omega(1-dodecyl beta-D-glucouronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
7)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-
Lys(N-omega(1-tetradecyl beta-D-glucouronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
8)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-
Lys(N-omega(1-hexadecyl beta-D-glucouronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
9)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-
Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
10)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Lys20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
11)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17Ala18-Ala19-Lys20Glu21-Phe22-Ile23-Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
12)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
13)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys(N-omega(1-(17-carboxyl-pentadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
14)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-
Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Gln20-Glu21-Phe22-
Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
15)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-
Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Gln20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
16)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-
Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Gln20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
17)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
18)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
19)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
20)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
21)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
22)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Lys17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
or
(SEQ ID NO:
23)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
and
a pharmaceutically acceptable carrier or excipient.

114 more elements

Dependencies are inferred from the claim text.

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Abstract

A pharmaceutical composition comprising of (i) a compound comprising a structure of:

wherein R1 is an alkyl comprising 5 to 15 carbon atoms, an alkyl comprising 7 to 17 carbon atoms and a carboxyl group, or an alkyl comprising 7 to 17 carbon atoms and a hydroxyl group;
and R3 is hydrogen or a cation;
and
(ii) a compound comprising a sequence having at least 90% sequence identity to:
(SEQ ID NO:
1)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Lys20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
2)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
3)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-
Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
4)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-
Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
5)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-octadecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Gln24-
Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
6)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-dodecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys(N-
omega(1-dodecyl beta-D-glucouronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
7)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-
Lys(N-omega(1-tetradecyl beta-D-glucouronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
8)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-
Lys(N-omega(1-hexadecyl beta-D-glucouronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
9)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Lys20-Glu21-Phe22-
Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
10)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Lys20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
11)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17Ala18-Ala19-Lys20Glu21-Phe22-Ile23-Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
12)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
13)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys(N-omega(1-(17-carboxyl-pentadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
14)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-
Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Gln20-Glu21-Phe22-
Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
15)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-
Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Gln20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
16)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-
Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl))17-Ala18-Ala19-Gln20-Glu21-
Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
17)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
18)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
19)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-
glucuronyl))24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
20)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Lys17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
21)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Lys12-Tyr13-Leu14-Asp15-Glu16-
Gln17-Ala18-Ala19-Lys20-Glu21-Phe22-Ile23-Lys24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
(SEQ ID NO:
22)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Lys17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Gln24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
or
(SEQ ID NO:
23)
His1-Aib2-Gln3-Gly4-Thr5-Phe6-Thr7-Sers-Asp9-Glu10-Ser11-Lys12-Tyr13-Lys14-Asp15-Ser16-Gln17-
Ala18-Ala19-Gln20-Glu21-Phe22-Ile23-Lys24-Trp25-Leu26-Leu27-Gln28-Thr29-NH2;
and
a pharmaceutically acceptable carrier or excipient.

114 more elements