Preparation which promotes the absorption of peptides

• US 4,900,730 A
• Filed: 06/18/1987
• Issued: 02/13/1990
• Est. Priority Date: 01/14/1981
• Status: Expired due to Fees

• Current Assignee: Toyo Jozo Co., Ltd.
• Original Assignee: Toyo Jozo Co., Ltd.
• Inventors: Miyauchi, Yasuyo
• Primary Examiner(s): Stone, Jacqueline M.
• Application Number:
  US07/063,744
• Time in Patent Office: 971 Days
• Field of Search: 514/2, 514/8, 514/12, 514/808, 514/946, 514/966, 514/947, 514/553, 514/557, 514/558, 514/560, 514/561, 514/562, 514/564, 514/566, 424/153, 424/DIG. 15, 424/436
• US Class Current: 514/9.7
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/0031 Rectum, anus
• CPC Class Codes: B01F 25/80 Falling particle mixers, e.g. with repeated agitation along a vertical axis
• CPC Class Codes: Y10S 424/15 Suppositories

Abstract

Medicinal compositions containing a water soluble absorption promoter having chelating activity, preferably in the presence of a salt at a concentration exhibiting higher osmotic pressure than isotonic sodium chloride solution, to promote absorption of the medicine through a gastrointestinal organ such as colon or rectum, and through the vagina.

Claims

1. A rectal composition for promoting improved absorption of medicine through the rectum containing a therapeutically effective amount of water soluble peptide hormone, and additionally containing:

(a) from 0.1 to 50 w/w % of at least one water soluble chelating agent selected from the group consisting of oxalic acid, malonic acid, glutaric acid, maleic acid, adipic acid, fumaric acid, trans-asonitic acid, pimelic acid, ethylmalonic acid, iminodiacetic acid, nitrilotriacetic acid, malic acid, lactic acid, glycero-3-phosphoric acid, fructose-1,6-diphosphoric acid, glucuronic acid, galacturonic acid, glyoxylic acid, oxaloacetic acid, α

-ketobutyric acid, pyruvic acid, α

-ketoglutaric acid, levulinic acid, 3-phenylacetylacetone and ethylacetoacetate, and their salts and their esters, and

(b) at least 1 w/w % of a water soluble solute selected from the group consisting of halides, sulfates, phosphates, nitrates amd carbonates of alkali metals, the total concentration of the dissolved chelating agent and solute in an aqueous medium being sufficient so that the composition exhibits an osmotic pressure of 1.5 to 7 times greater than that of isotonic sodium chloride solution.

2. A rectal composition according to claim 1, wherein said water soluble peptide hormone is calcitonin.

3. A rectal composition according to claim 1, wherein said composition is in the form of a suppository which further comprises an oily vehicle or a water soluble vehicle.

4. A rectal composition according to claim 1, wherein said water soluble solute is selected from the group consisting of sulfates, phosphates, nitrates and carbonates of alkali metals.

9. A preparation according to claim 1 wherein the water-soluble peptide hormone has a partition coefficient of 50 or less in chloroform/water.

10. A preparation according to claim 1 wherein the amount of water soluble chelating agent is in the range from 1.0 to 30 W/W %.

11. A preparation according to claim 1 wherein the amount of water soluble is in the range of from about 2 to 30 W/W %.

5. A rectal composition according for promoting improved absorption of medicine through the rectum containing a therapeutically effective amount of water soluble peptide hormone, and additionally containing:

(a) from 0.1 to 50 w/w % of at least one water soluble chelating agent selected from the group consisting of oxalic acid, malonic acid, glutaric acid, maleic acid, adipic acid, fumaric acid, trans-aconitic acid, pimelic acid, ethylmalonic acid, iminodiacetic acid, nitrilotriacetic acid, malic acid, lactic acid, glycero-3-phosphoric acid, fructose-1,6-diphosphoric acid, glucuronic acid, galaturonic acid, glyoxylic acid, oxaloacetic acid, α

-ketobutyric acid, pyruvic acid, α

-ketoglutaric acid, levulinic acid, 3-phenylacetylacetone, and ethylacetoacetate, and their salts and their esters, and

(b) at least 0.25M of a water soluble solute selected from the group consisting of mono- and di-saccharides, the total concentration of dissolved chelating agents and solute in an aqueous medium being sufficient so that the composition exhibits an osmotic pressure of 1.5 to 7 times greater than that of isotonic sodium chloride solution.

6. A rectal composition according to claim 5, wherein said water soluble peptide hormone is calcitonin.

7. A rectal composition according to claim 5, wherein said composition is in the form of a suppository which further comprises an oily vehicle or a water soluble vehicle.

8. A preparation according to claim 5 wherein the water-soluble saccharide is sorbitol, glucose, mannitol, maltose, lactose or sucrose.

12. A preparation according to claim 5, wherein the water-soluble peptide hormone has a partition coefficient of 50 or less in chloroform/water.

13. A preparation according to claim 5 wherein the amount of water soluble chelating agent is in the range from 1.0 to 30 W/W %.