Prolonged delivery of peptides

Claim 2

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a polymer capable of prolonging the action of said compound to achieve sustained glycemic control, said polymer selected from the group consisting of polyethylene glycol, polyvinylpyrrolidone, polyvinylalcohol, polyoxyethylenepolyoxypropylene copolymers, polysaccharides selected from the group consisting of cellulose, cellulose derivatives, chitosan, acacia gum, karaya gum, guar gum, xanthan gum, tragacanth, alginic acid, carrageenan, agarose, and furcellarans, dextran, starch, starch derivatives, hyaluronic acid, polyesters, polyamides, polyanhydrides, and polyortho esters.

Claim 3

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3)a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a pharmaceutically acceptable water-immiscible oil suspension capable of prolonging action of said compound to achieve sustained glycemic control; said oil selected from the group consisting of peanut oil, sesame oil, almond oil, castor oil, camellia oil, cotton seed oil, olive oil, corn oil, soy oil, safflower oil, coconut oil, esters of fatty acids, and esters of fatty alcohols.

Claim 4

A composition according to claim 3 further comprising a wetting agent, wherein said wetting agent is a nonionic surfactant and said composition also containing a suspending agent.

Claim 5

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) zinc (II), which is complexed with the peptide, said composition capable of achieving sustained glycemic control and in a form which is amorphous, crystalline, or an aqueous suspension.

Claim 6

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a metal selected from the group consisting of Ni (II), Co (II), Mg (II), Ca (II), K (I), Mn (II), Fe(II), and Cu(II), said composition capable of achieving sustained glycemic control.

Claim 7

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a basic polypeptide, wherein said composition is an aqueous suspension capable of sustained glycemic control.

Claim 8

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a phenolic compound, wherein said composition is an aqueous suspension capable of sustained glycemic control, said phenolic compound selected from the group consisting of phenol, cresol, resorcinol, and methyl paraben.

Claim 9

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a basic polypeptide and a phenolic compound, wherein such composition is an aqueous suspension capable of sustained glycemic control.

Claim 10

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1)a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a basic polypeptide, a phenolic compound, and a metal ion wherein said composition is an aqueous suspension capable of sustained glycemic control.

Claim 11

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) said peptides and derivatives thereof having being subjected to conditions resulting in amorphous or crystalline material formation; wherein said conditions are high shear, exposure to salts; or combinations thereof.

Claim 12

A composition according to claim 11 wherein said salt is selected from the group consisting of ammonium sulfate, sodium sulfate, lithium sulfate, lithium chloride, sodium citrate, ammonium citrate, sodium phosphate, potassium phosphate, sodium chloride, potassium chloride, ammonium chloride, sodium acetate, ammonium acetate, magnesium sulfate, calcium chloride, ammonium nitrate, and sodium formate; and combinations thereof.

Claim 13

A composition of matter comprising; (i) a compound selected from the group consisting of: (a) a peptide having the amino acid sequence: (b) a peptide having the amino acid sequence: wherein X is selected from the group consisting of: (A) Lys, (B) Lys-Gly, and (C) Lys-Gly-Arg; (c) a derivative of a polypeptide comprising the primary structure H₂N-W-COOH wherein W is an amino acid sequence selected from the group consisting of which derivative when processed in a mammal results in a polypeptide derivative having an insulinotropic activity; (d) a derivative of a polypeptide comprising the primary structure H₂N-R-COOH wherein R is an amino acid sequence selected from the group consisting of and a derivative of said peptides (a) through (d) wherein said derivative is selected from the group consisting of: (1) a pharmaceutically acceptable acid addition salt of said peptides; (2) a pharmaceutically acceptable carboxylate salt of said peptides; (3) a pharmaceutically acceptable alkali addition salt of said peptides; (4) a pharmaceutically acceptable lower alkyl ester of said peptides; and (5) a pharmaceutically acceptable amide of said peptides wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide, and (ii) a liposome delivery system capable of sustained glycemic control.