Stabilized peptide composition

Abstract

Provided herein is a peptide composition that is highly stable and can be stored long term, said composition containing one or more types of peptides having an amino acid sequence represented by any of SEQ ID Nos. 1-5, or a peptide in which one or two of the amino acids of the abovementioned peptides are independent and may be substituted, deleted or added, and saccharides and an inorganic salt.

1 . A composition comprising one or more peptides, a saccharide and an inorganic salt, wherein said peptide consists of an amino acid sequence selected from SEQ ID NOs: 1 to 5, or an amino acid sequence, wherein one or two amino acid(s) may be each independently substituted, deleted or added in the amino acid sequence selected from SEQ ID NOs: 1 to 5. 
     
     
         2 . The composition of  claim 1 , wherein the second amino acid from the N-terminus of the amino acid sequence of the peptide is phenylalanine, tyrosine, methionine, tryptophan or threonine. 
     
     
         3 . The composition according to  claim 1 , wherein the C-terminal amino acid of the amino acid sequence of the peptide is phenylalanine, leucine, isoleucine, tryptophan or methionine. 
     
     
         4 . The composition according to  claim 1 , which comprises:
 a first peptide consisting of the amino acid sequence of SEQ ID NO: 1;   a second peptide consisting of the amino acid sequence of SEQ ID NO: 2;   a third peptide consisting of the amino acid sequence of SEQ ID NO: 3;   a fourth peptide consisting of the amino acid sequence of SEQ ID NO: 4; and   a fifth peptide consisting of the amino acid sequence of SEQ ID NO: 5.   
     
     
         5 . The composition according to  claim 1 , wherein the saccharide is one or more selected from the group consisting of monosaccharide, disaccharides and polysaccharide. 
     
     
         6 . The composition according to  claim 5 , wherein the saccharide is one or more selected from the group consisting of glucose, galactose, fructose, sucrose, lactose, maltose, trehalose, dextran and glycerol. 
     
     
         7 . The composition according to  claim 6 , wherein the saccharide is sucrose. 
     
     
         8 . The composition according to  claim 1 , wherein the inorganic salt is one or more selected from the group consisting of sodium chloride, potassium chloride, magnesium chloride, sodium sulfite and sodium metabisulfite. 
     
     
         9 . The composition according to  claim 8 , wherein the inorganic salt is sodium chloride. 
     
     
         10 . The composition according to  claim 1 , which is a lyophilized formulation. 
     
     
         11 . The composition according to  claim 10 , wherein the weight of the one or more peptides is 1.0 to 20 mg. 
     
     
         12 . The composition according to  claim 10 , wherein the concentration of the one or more peptides is 0.05 to 1.0% by weight when the total amount is 2.0 g by dissolving the composition in water. 
     
     
         13 . The composition according to  claim 10 , wherein the weight of the saccharide is 20 to 70 mg. 
     
     
         14 . The composition according to  claim 10 , wherein the weight ratio of the one or more peptides and the saccharide in the composition is 1:1.7 to 1:29.2. 
     
     
         15 . The composition according to  claim 10 , wherein the concentration of the saccharide is 1.0 to 3.5% by weight when the total amount is 2.0 g by dissolving the composition with water. 
     
     
         16 . The composition according to  claim 10 , wherein the weight of the inorganic salt is 0.1 to 3.0 mg. 
     
     
         17 . The composition according to  claim 10 , wherein the weight ratio of the one or more peptides and the inorganic salt is 1:0.008 to 1:1.25. 
     
     
         18 . The composition according to  claim 10 , wherein the concentration of the inorganic salt is 0.01 to 0.3% by weight when the total amount is 2.0 g by dissolving the composition in water. 
     
     
         19 . The composition according to  claim 10 , having a pH 7.0 to 9.5 when the composition is dissolved in water. 
     
     
         20 . The composition according to  claim 1 , which is a water-in-oil emulsion formulation. 
     
     
         21 . The composition according to  claim 19 , which is a water-in-oil formulation. 
     
     
         22 . The composition according to  claim 1 , which is suitable for injection. 
     
     
         23 . The composition according to  claim 10 , wherein the composition is in a vial and the concentration of oxygen is 0.01% to 3.0% in the vial. 
     
     
         24 . A method of preparation of an emulsion by mixing the composition according to  claim 10  and an adjuvant. 
     
     
         25 . A kit comprising the composition according to  claim 1 . 
     
     
         26 . A method of manufacturing a lyophilized formulation which comprises at least the following steps:
 a) mixing one or more stable peptides, a saccharide and an inorganic salt in a solution having a pH of 12.0 to 13.0,   b) adjusting the pH of the solution prepared by said step a) to pH 10.0 to pH 12.0,   c) mixing one or more less stable peptides in the solution prepared by said step b),   d) adjusting the pH of the solution prepared by said step c) to pH 7.0 to pH 9.0, and   e) lyophilizing the mixture prepared by said step d).   
     
     
         27 . The method according to  claim 26 ,
 wherein in step a) the one or more stable peptides comprise a first peptide consisting of an amino acid sequence of SEQ ID NO: 1 and a second peptide consisting of an amino acid sequence of SEQ ID NO: 4, the saccharide is sucrose, and the inorganic salt is sodium chloride,   wherein in step b) the pH of the solution prepared by said step a) is adjusted to pH 10.0 to pH 12.0 with an acid substance,   wherein in step c) the one or more less stable peptides comprise a third peptide consisting of an amino acid sequence of SEQ ID NO: 2, a fourth peptide consisting of an amino acid sequence of SEQ ID NO: 3 and a fifth peptide consisting of an amino acid sequence of SEQ ID NO: 5, and   wherein in step d) the pH of the solution prepared by said step c) is adjusted to pH 7.0 to pH 9.0 with an acid substance.   
     
     
         28 . The method according to  claim 26 ,
 wherein in step a) the one or more stable peptides comprise a first peptide consisting of an amino acid sequence of SEQ ID NO: 1 and a second peptide consisting of an amino acid sequence of SEQ ID NO: 4, the saccharide is sucrose, and the inorganic salt is sodium chloride,   wherein in step b) the pH of the solution prepared by said step a) is adjusted to pH 11.0 to pH 12.0 with an acid substance,   wherein in step c) the one or more less stable peptides comprise a third peptide consisting of an amino acid sequence of SEQ ID NO: 2 and a fourth peptide consisting of an amino acid sequence of SEQ ID NO: 3,   wherein the method further comprises the steps of:   c1) adjusting the pH of the solution prepared by said step c) to pH 9.0 to pH 11.0 with an acid substance,   c2) mixing a fifth peptide consisting of an amino acid sequence of SEQ ID NO: 5 to the solution prepared by said step c1, and   wherein in step d) the solution prepared by said step c2) is adjusted to pH 7.0 to pH 9.0 with an acid substance.   
     
     
         29 . The method according to  claim 26 , wherein the lyophilized formulation prepared by step e) is stored in a vial and wherein the method further comprises the step of controlling the oxygen concentration to 0.01% to 3.0% in the vial. 
     
     
         30 . A lyophilized formation prepared by the method according to  claim 26 . 
     
     
         31 . A composition comprising a peptide consisting of an amino acid sequence of SEQ ID NO: 3, or an amino acid sequence wherein one or two amino acid(s) may be substituted, deleted or added in the amino acid sequence of SEQ ID NO: 3, wherein the composition is in a vial and the oxygen concentration is 0.01% to 3.0% in the vial.