Liquid preparation of physiologically active peptide
An effective liquid preparation achieves high bioavailability (BA) of physiologically active peptides or proteins, including ghrelins, that are administered as drugs. Also provided is a method for improving the BA of physiologically active peptides or proteins, including ghrelins, that are subcutaneously injected in aqueous solutions. The liquid preparation contains: a physiologically active peptide or protein, such as ghrelins, as an active ingredient; an acid solution including one or a combination of two or more selected form the group consisting of acetic acid, lactic acid, phosphoric acid, glycine, citric acid, hydrochloric acid, propionic acid, butyric acid, benzoic acid and salts thereof; an alcohol; and a polar organic liquid including one or a combination of two or more selected from the group consisting of N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide and methylparaben.
1. A method for improving bioavailability of one or more ghrelins, comprising,
(a) adding an acidic solution and a polar organic liquid to an aqueous solution of said one or more ghrelins, or
(b) adding a polar organic liquid alone to an aqueous solution of said one or more ghrelins,
wherein the one or more ghrelins is human ghrelin, rat ghrelin, human des-octanoyl ghrelin, human [L-2-aminododecanoic acid 3 ]ghrelin or combinations thereof;
wherein the acidic solution is acetic acid, lactic acid, phosphoric acid, propionic acid, butyric acid, salts thereof, or combinations thereof; and
wherein the polar organic liquid is benzyl alcohol, phenol, tert-butanol, N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide, or combinations thereof.
2. The method according to claim 1 , wherein the concentration of the polar organic liquid is from 0.1 to 10% (w/v).
3. The method according to claim 1 , further comprising adding a sugar of mannitol, sucrose, glucose, cyclodextrin, or combinations thereof.
4. The method according to claim 3 , wherein the sugar is cyclodextrin.
5. The method according to claim 3 , wherein the concentration of the sugar is from 1 to 10% (w/v).
6. The method according to claim 1 , wherein the ghrelin is human ghrelin.
7. The method according to claim 1 , wherein the concentration of the one or more ghrelins is from 50 to 2000 μg/mL.
8. A method for preparing a liquid preparation in order to improve a bioavailability of one or more ghrelins, comprising,
(a) adding an acidic solution and a polar organic liquid to an aqueous solution of said one or more ghrelins, or
(b) adding a polar organic liquid alone to an aqueous solution of said one or more ghrelins,
wherein the ghrelins is human ghrelin, rat ghrelin, human des-octanoyl ghrelin, human [L-2-aminododecanoic acid 3 ]ghrelin, or combinations thereof;
wherein the acidic solution is acetic acid, lactic acid, phosphoric acid, propionic acid, butyric acid, salts thereof, or combinations thereof; and
wherein the polar organic liquid is benzyl alcohol, phenol, tert-butanol, N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide, or combinations thereof.
9. The method of claim 8 , wherein the ghrelin is human ghrelin.
10. A method for improving bioavailability of one or more ghrelins, comprising,
(a) adding an acidic solution and a polar organic liquid to an aqueous solution of said one or more ghrelins, or
(b) adding a polar organic liquid alone to an aqueous solution of said one or more ghrelins,
wherein the polar organic liquid is benzyl alcohol, phenol, tert-butanol, N-methyl-2-pyrrolidone, dimethylformamide, dimethylsulfoxide, or combinations thereof.