Medical compositions containing ghrelin

Abstract

It is provided a pharmaceutical composition stably containing ghrelin or its derivative, which is an endogenous growth hormone secretagogue (GHS) to a growth hormone secretagogue-receptor (GHS-R), comprising a aqueous solution containing the ghrelins having pH range of 2 to 7, wherein the aqueous solution having pH range of 2 to 7 is a buffer solution, especially, glycine hydrochloride buffer, acetate buffer, citrate buffer, lactate buffer, phosphate buffer, citric acid-phosphate buffer, phosphate-acetate-borate buffer or phthalate buffer, and the concentration of the ghrelins in the solution is from 0.03 nmol/mL to 61 μmol/mL.

1 . A pharmaceutical composition comprising ghrelin or its derivative and an aqueous solution which dissolves the ghrelin, wherein the pH of the aqueous solution dissolving the ghrelins is from 2 to 7.  
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein said pH is from 3 to 6.  
     
     
         3 . A pharmaceutical composition according to claims  1  or  2 , further comprising a pH adjuster or a buffer agent.  
     
     
         4 . A pharmaceutical composition according to  claim 3 , wherein the pH adjuster is hydrochloric acid, sulfuric acid, nitric acid, boric acid, carbonic acid, bicarbonic acid, gluconic acid, sodium hydroxide, potassium hydroxide, aqueous ammonia, citric acid, monoethanolamine, lactic acid, acetic acid, succinic acid, fumaric acid, maleic acid, phosphoric acid, methanesulfonic acid, malic acid, propionic acid, trifluoroacetic acid, a salt thereof or mixtures thereof.  
     
     
         5 . A pharmaceutical composition according to  claim 3 , wherein the buffer agent is glycine, acetic acid, citric acid, boric acid, phthalic acid, phosphoric acid, succinic acid, lactic acid, tartaric acid, carbonic acid, hydrochloric acid, sodium hydroxide, the salt thereof, or mixtures thereof.  
     
     
         6 . A pharmaceutical composition according to  claim 3 , wherein the concentration of the pH adjuster or the buffer agent in the solution is in the range of from 0.01 mM to 1000 mM.  
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein the solution is buffer solution.  
     
     
         8 . A pharmaceutical composition according to  claim 7 , wherein the buffer solution is glycine hydrochloride buffer, acetate buffer, citrate buffer, lactate buffer, phosphate buffer, citric acid-phosphate buffer, phosphate-acetate-borate buffer or phthalate buffer or mixtures thereof.  
     
     
         9 . A pharmaceutical composition according to  claim 1 , wherein the concentration of the ghrelins in the solution is in the range of 0.03 nmol/mL to 6 μmol/mL.  
     
     
         10 . A pharmaceutical composition according to  claim 1 , wherein the ghrelins is acetic acid salt.  
     
     
         11 . A pharmaceutical composition according to  claim 1 , wherein the ghrelins is human ghrelin.  
     
     
         12 . A pharmaceutical composition according to  claim 1 , further comprising an anti-adsorbent.  
     
     
         13 . A pharmaceutical composition according to  claim 12 , wherein the concentration of the anti-adsorbent is in the range of from 0.001% to 5%.  
     
     
         14 . A pharmaceutical composition according to  claim 12  or  13 , wherein the anti-adsorbent is a surfactant.  
     
     
         15 . A pharmaceutical composition comprising the ghrelins of  claim 1  in the form of a dried powder obtained from a solution.  
     
     
         16 . A pharmaceutical composition according to  claim 15 , wherein the powder is a lyophilized powder.  
     
     
         17 . A method for preventing degradation of a hydrophobic group of ghrelin or its derivative in a solution comprising the ghrelins which method comprises adjusting the pH of the solution in the range of from 2 to 7.  
     
     
         18 . A method according to  claim 17 , wherein said pH of the solution is adjusted to 3 to 6.  
     
     
         19 . A method according to claims  17  or  18 , further comprising a pH adjuster or a buffer agent.  
     
     
         20 . A method according to  claim 19 , further comprising a pH adjuster selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, boric acid, carbonic acid, bicarbonic acid, gluconic acid, sodium hydroxide, potassium hydroxide, aqueous ammonia, citric acid, monoethanolamine, lactic acid, acetic acid, succinic acid, fumaric acid, maleic acid, phosphoric acid, methanesulfonic acid, malic acid, propionic acid, trifluoroacetic acid, a salt thereof and mixtures thereof.  
     
     
         21 . A method according to  claim 19 , further comprising a buffer agent selected from the group consisting of glycin, acetic acid, citric acid, boric acid, phthalic acid, phosphoric acid, succinic acid, lactic acid, tartaric acid, carbonic acid, hydrochloric acid, sodium hydroxide the salt thereof, and mixtures thereof.  
     
     
         22 . A method according to  claim 19 , wherein the concentration of the pH adjuster or the buffer agent in the solution is in the range of 0.01 mM to 1000 mM.  
     
     
         23 . A method according to  claim 17 , wherein the solution is buffer solution.  
     
     
         24 . A method according to  claim 23 , wherein the buffer solution is glycine hydrochloride buffer, acetate buffer, citrate buffer, lactate buffer, phosphate buffer, citric acid-phosphate buffer, phosphate-acetate-borate buffer, phthalate buffer, or mixtures thereof.  
     
     
         25 . A method according to  claim 17 , wherein the concentration of the ghrelins in the solution is in the range of from 0.03 nmol/mL to 6 μmol/mL.  
     
     
         26 . A method according to  claim 17 , wherein the ghrelins is an acetic acid salt.  
     
     
         27 . A method according to  claim 17 , wherein the ghrelins is a human ghrelin.