Back to results
US 2019/0216883 A1Published application
Use of peptide compounds in treating acute pancreatitis
AssigneeShenzhen HighTide Biopharmaceutical, Ltd.
InventorsLiping LIU, Ru BAI
Life of this patent
Estimating the term…
Abstract
This invention discloses certain method of use of peptides and their analogs in the treatment of acute pancreatitis. The disclosed peptides and analogs can significantly lower the elevated blood amylase and lipase levels caused by acute pancreatitis, reduce the degree of injury observed in pancreatic histopathology caused by pancreatitis, and significantly lower the mortality rate of acute pancreatitis.
Claims7
1-13. (canceled)
A pharmaceutical composition comprising an INGAP-PP peptide, HIP peptide, or analog thereof, the peptide or analog thereof comprising a formula selected of (1)-(7):
- (1)
- (SEQ ID NO:
- 111)
- X1GLHX2PX3X4GTX5PX6GS
- wherein, X1 is selected from Isoleucine (I), D-Isoleucine, L-NorValine or L-NorLeucine;
- X2 is selected from Alanine (A) or Aspartic Acid (D);
- X3 is selected from Serine(S) or Threonine (T);
- X4 is selected from Histidine (H) or Glutamine (Q);
- X5 is selected from Leucine (L) or Glutamic acid (E);
- and
- when it is established that X1 is Isoleucine (I), X2 is Aspartic Acid (D), X3 is Serine(S), X4 is Histidine (H), and X5 is Leucine (L), then X6 is selected from either Alanine (A), α-Amino-isobutyric acid or N-methyl-L-Alanine;
- and
- when it is not established that X1 is Isoleucine (I), X2 is Aspartic Acid (D), X3 is Serine(S), X4 is Histidine (H) and X5 is Leucine (L), then X6 is selected from either Alanine (A), Asparagine (N), α-Amino-isobutyric acid or N-methyl-L-Alanine;
- (2)
- (SEQ ID NO:
- 112)
- R1-IGLHDPSHGTLPNGX1(C)m-R2
- wherein, m is 0 or 1;
- R1 is selected from —H or —Ac;
- R2 is selected from —OH or —NH2;
- and
- when it is established that R1 is —H, R2 is —OH and m is 0, then X1 is selected from Glutamic acid (E), Cysteine (C) or Lysine (K);
- and
- when it is not established that R1 is —H, R2 is —OH and m is 0, then X1 is selected from Serine(S), Glutamic acid (E), Cysteine (C) or Lysine (K);
- (3)
- (SEQ ID NO:
- 113)
- (R1-IGLHDPSHGTLPAG(X1)m-R2
- wherein, m is 0 or 1;
- R1 is selected from —H or —Ac;
- R2 is selected from —OH or —NH2;
- and
- when it is established that R1 is —H, R2 is —OH and m is 1, then X1 is selected from Glutamic acid (E), Cysteine (C) or Lysine (K);
- and
- when it is not established that R1 is —H, R2 is —OH and m is 1, then X1 is selected from Serine(S), Glutamic acid (E), Cysteine (C) or Lysine (K);
- (4)
- (SEQ ID NO:
- 114)
- R1-IGLHDPSHGTLPAGSX2-R2
- wherein, X2 is selected from Lysine (K) or Cysteine (C), R1 is selected from —H or —Ac, R2 is selected from —OH or —NH2;
- (5)
- (SEQ ID NO:
- 115)
- X1GLHDPTQGTX2PX3GE
- wherein, X1 is selected from Isoleucine (I) or D-Isoleucine;
- X2 is selected from Glutamic acid (E) or Leucine (L);
- and
- when it is established that X1 is Isoleucine (I) and X2 is Glutamic acid (E), then X3 is selected from Alanine (A) or α-Amino-isobutyric acid;
- and
- when it is not established that X1 is Isoleucine (I) and X2 is Glutamic acid (E), then X3 is selected from Alanine (A), Asparagine (N) or α-Amino-isobutyric acid;
- (6)
- (SEQ ID NO:
- 116)
- R1-IGLHDPTQGTEPNGX1-R2
- wherein, X1 is selected from —H or —Ac;
- X2 is selected from —OH or —NH2;
- and
- when it is established that R1 is —H and R2 is —OH, then X1 is selected from Serine(S) or Cysteine (C);
- and
- when it is not established that R1 is —H and R2 is —OH, then X1 is selected from Serine(S), Glutamic acid (E) or Cysteine (C);
- and
- (7)
- (SEQ ID NO:
- 117)
- R1-IGLHDPTQGTEPAG(X1)n-R2
- wherein, R1 is selected from —H or —Ac;
- R2 is selected from —OH or —NH2, n is 0 or 1;
- X1 is selected from Serine(S) or Cysteine (C),
- or
- an INGAP-PP peptide, HIP peptide, or analog thereof, selected from the INGAP-PP and HIP peptides of Table 1, the INGAP-PP analogs of Table 2, and the HIP peptide analogs of Table 3,
- TABLE 1
- INGAP-PP peptide and HIP peptide
- Peptide ID/SEQ ID NO.
- Sequence
- 1 (INGAP-PP)
- H-IGLHDPSHGTLPNGS-OH
- 2 (HIP)
- H-IGLHDPTQGTEPNGE-OH
- TABLE 2
- Exemplary INGAP-PP Analogs
- Peptide ID/
- SEQ ID NO.
- Sequence
- 1
- H-IGLHDPSHGTLPNGS-OH
- 6
- H-IGLHAPSHGTLPNGS-OH
- 7
- H-IGLHDPSHGTLPAGS-OH
- 8
- H-IGLHAPSHGTLPAGS-OH
- 9
- H-IGLHDPSHGTLPAGSK-OH
- 10
- H-IGLHDPSHGTLP(Aib)GS-OH
- 11
- H-IGLHDPSHGTLP(N-methyl-L-
- Alanine)GS-OH
- 12
- Ac-IGLHDPSHGTLPAGS-OH
- 13
- H-(D-Isoleucine)GLHDPSHGTLPAGS-OH
- 14
- H-(L-NorValine)GLHDPSHGTLPAGS-OH
- 15
- H-(L-NorLeucine)GLHDPSHGTLPAGS-OH
- 16
- Ac-IGLHDPSHGTLPNGS-OH
- 17
- H-(D-Isoleucine)GLHDPSHGTLPNGS-OH
- 18
- H-IGLHDPSHGTEPNGS-OH
- 19
- H-IGLHDPSQGTLPNGS-OH
- 20
- H-IGLHDPTHGTLPNGS-OH
- 21
- H-IGLHDPSHGTLPNGE-OH
- 22
- H-IGLHDPSHGTLPNGK-OH
- 23
- H-IGLHDPSHGTLPAGK-OH
- 24
- H-IGLHDPSHGTEPAGS-OH
- 25
- H-IGLHDPSQGTLPAGS-OH
- 26
- H-IGLHDPTHGTLPAGS-OH
- 27
- H-IGLHDPSHGTLPAGE-OH
- 28
- H-IGLHDPSHGTLPAG-NH2
- 29
- Ac-IGLHDPSHGTLPAGS-NH2
- 30
- Ac-IGLHDPSHGTLPAG-NH2
- 31
- Ac-IGLHDPSHGTLPNGS-NH2
- 32
- H-IGLHDPSHGTLPNGS-NH2
- 33
- H-IGLHDPSHGTLPNGSC-OH
- 34
- Ac-IGLHDPSHGTLPNGSC-OH
- 35
- H-IGLHDPSHGTLPNGSC-NH2
- 36
- Ac-IGLHDPSHGTLPNGSC-NH2
- 37
- H-IGLHDPSHGTLPNGC-OH
- 38
- Ac-IGLHDPSHGTLPNGC-OH
- 39
- H-IGLHDPSHGTLPNGC-NH2
- 40
- Ac-IGLHDPSHGTLPNGC-NH2
- 41
- H-IGLHDPSHGTLPAGS-NH2
- 42
- H-IGLHDPSHGTLPAGSC-OH
- 43
- Ac-IGLHDPSHGTLPAGSC-OH
- 44
- H-IGLHDPSHGTLPAGSC-NH2
- 45
- Ac-IGLHDPSHGTLPAGSC-NH2
- 46
- H-IGLHDPSHGTLPAGC-OH
- 47
- Ac-IGLHDPSHGTLPAGC-OH
- 48
- H-IGLHDPSHGTLPAGC-NH2
- 49
- Ac-IGLHDPSHGTLPAGC-NH2
- 73
- IGLHDPSHGTLPAG
- 74
- IGLHDPSHGTLPNG
- 75
- Ac-IGLHDPSHGTLPNG
- 76
- IGLHDPSHGTLPNG-NH2
- 77
- Ac-IGLHDPSHGTLPNG-NH2
- 78
- H-IGLHDPSHGTLPQGS-OH
- 79
- H-IGLHDPSHGTLPDGS-OH
- 80
- H-IGLHDPSHGTLPEGS-OH
- 81
- H-IGLHEPSHGTLPNGS-OH
- 82
- H-IGLHQPSHGTLPNGS-OH
- 83
- H-IGLHNPSHGTLPNGS-OH
- 84
- H-IGLHEPSHGTLPAGS-OH
- 85
- H-IGLHQPSHGTLPAGS-OH
- 86
- H-IGLHNPSHGTLPAGS-OH
- 87
- H-IGLHDPSHGTLPQGSC-OH
- 88
- H-IGLHDPSHGTLPDGSC-OH
- 89
- H-IGLHDPSHGTLPEGSC-OH
- 90
- H-IGLHEPSHGTLPNGSC-OH
- 91
- H-IGLHQPSHGTLPNGSC-OH
- 92
- H-IGLHNPSHGTLPNGSC-OH
- 93
- H-IGLHDPSHGTLPQG-OH
- 94
- H-IGLHDPSHGTLPDG-OH
- 95
- H-IGLHDPSHGTLPEG-OH
- 96
- H-IGLHEPSHGTLPNG-OH
- 97
- H-IGLHQPSHGTLPNG-OH
- 98
- H-IGLHNPSHGTLPNG-OH
- 99
- H-IGLHEPSHGTLPAG-OH
- 100
- H-IGLHQPSHGTLPAG-OH
- 101
- H-IGLHNPSHGTLPAG-OH
- 102
- H-IGLHDPSHGTLPQGE-OH
- 103
- H-IGLHDPSHGTLPDGE-OH
- 104
- H-IGLHDPSHGTLPEGE-OH
- 105
- H-IGLHEPSHGTLPNGE-OH
- 106
- H-IGLHQPSHGTLPNGE-OH
- 107
- H-IGLHNPSHGTLPNGE-OH
- 108
- H-IGLHEPSHGTLPAGE-OH
- 109
- H-IGLHQPSHGTLPAGE-OH
- 110
- H-IGLHNPSHGTLPAGE-OH
- TABLE 3
- Exemplary HIP Analogs
- Peptide ID/
- SEQ ID NO.
- Sequence
- 2
- H-IGLHDPTQGTEPNGE-OH
- 50
- H-IGLHDPTQGTEPAGE-OH
- 51
- H-IGLHDPTQGTEP(Aib)GE-OH
- 52
- Ac-IGLHDPTQGTEPAGE-OH
- 53
- H-(D-Isoleucine)GLHDPTQGTEPAGE-OH
- 54
- Ac-IGLHDPTQGTEPNGE-OH
- 55
- H-(D-Isoleucine)GLHDPTQGTEPNGE-OH
- 56
- H-IGLHDPTQGTEPNGS-OH
- 57
- H-IGLHDPTQGTEPAGS-OH
- 58
- H-IGLHDPTQGTLPNGE-OH
- 59
- H-IGLHDPTQGTLPAGE-OH
- 60
- Ac-IGLHDPTQGTEPAG-NH2
- 61
- Ac-IGLHDPTQGTEPNGE-NH2
- 62
- Ac-IGLHDPTQGTEPAGE-NH2
- 63
- H-IGLHDPTQGTEPNGE-NH2
- 64
- H-IGLHDPTQGTEPNGC-OH
- 65
- Ac-IGLHDPTQGTEPNGC-OH
- 66
- H-IGLHDPTQGTEPNGC-NH2
- 67
- Ac-IGLHDPTQGTEPNGC-NH2
- 68
- H-IGLHDPTQGTEPAGE-NH2
- 69
- H-IGLHDPTQGTEPAGC-OH
- 70
- Ac-IGLHDPTQGTEPAGC-OH
- 71
- H-IGLHDPTQGTEPAGC-NH2
- 72
- Ac-IGLHDPTQGTEPAGC-NH2
300 more elements
Dependencies are inferred from the claim text.