Suppository preparation having excellent absorption property

• US 4,873,087 A
• Filed: 03/08/1982
• Issued: 10/10/1989
• Est. Priority Date: 01/14/1982
• Status: Expired due to Fees

• Current Assignee: Toyo Jozo Co., Ltd.
• Original Assignee: Toyo Jozo Co., Ltd.
• Inventors: Yamamoto, Yoshiaki, Aikawa, Renji, Sugimoto, Kenichi, Morishita, Masataka, Katsuragi, Shigeo
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US06/355,887
• Time in Patent Office: 2,773 Days
• Field of Search: 514/563, 514/613, 514/617, 514/946, 514/947, 514/966, 514/967, 424/430, 424/433, 424/436
• US Class Current: 424/433
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00

Abstract

A preparation containing an absorption promoter selected from N-acyl amino acid derivatives or N-acyl peptide derivatives represented by the formula: R-CO-A (R is an aliphatic hydrocarbon group, an aromatic hydrocarbon group or an aryl-substituted lower hydrocarbon group which may optionally be substituted, and A is an amino acid residue or a peptide residue), preferably in the presence of a salt at a concentation exhibiting higher osmotic pressure than isotonic sodium chloride solution, and a medicine is found to promote absorption of the medicine through a gastrointestinal organ such as the colon and rectum, and through the vagina.

Claims

1. A suppository having excellent absorption property, comprising (1) a water-soluble medicine, (2) a water-soluble substance selected from the group consisting of water-soluble salts and water-soluble saccharides at a concentration exhibiting 1.5-6.0 fold of osmotic pressure of isotonic sodium chloride solution, and (3) at least 0.01 W/W % of an absorption promoter which is at least one N-acyl amino acid derivative or N-acyl peptide derivative represented by the formula:

space="preserve" listing-type="equation">R--CO--A,

wherein R is an aliphatic hydrocarbon group, a substituted aliphatic hydrocarbon group, an aromatic hydrocarbon group, a substituted aromatic hydrocarbon group, an aryl-substituted lower hydrocarbon group or a substituted aryl-substituted lower hydrocarbon group;

wherein said substituted aliphatic hydrocarbon group, said substituted aromatic hydrocarbon group or said substituted aryl-substituted lower hydrocarbon group is substituted with a member selected from the group consisting of a lower alkyl group, a hydroxyI group, a carboxylic acid group, an alkoxy group, a phosphoric acid group, an amino group, an imino group and a halogen; and

A is an amino acid residue or a peptide residue.

2. A suppository according to claim 1, wherein said water-soluble substance is 1 W.W % or more of a water-soluble salt of an alkali metal.

3. A suppository according to claim 2, wherein said water-soluble salt of an alkali metal is a halide, a sulfate, a phosphate or a carbonate of sodium, potassium or lithium.

4. A suppository according to claim 1, wherein said water-soluble substance is 0.25M or more of a water-soluble saccharide.

5. A suppository according to claim 4, wherein said water-soluble saccharide is sorbitol, glucose, mannitol, lactose or sucrose.

6. A suppository according to claim 1, wherein said water-soluble medicine has a partition coefficeint of 50 or less in chloroform/water.

7. A suppository according to claim 1, further comprising an oily vehicle or a water-soluble vehicle.

8. A suppository according to claim 1, wherein R is a member selected from the group consisting of acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, hexanoic acid, enathic acid, octanoic acid, pelargonic acid, decanoic acid, undecylic acid, lauric acid, myristic acid, palmitic acid, stearic acid, acrylic acid, crotonic acid, vinylacetic acid, 4-pentenoic acid, oleic acid, linoleic acid, linolenic acid, sorbic acid, benzoic acid, alkylbenzoic acid, phthalic acid, isophthalic acid, o-aminobenzoic acid, a m-aminobenzoic acid, p-aminobenzoic acid, o-hydroxybenzoic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, o-alkoxybenzoic acid, m-alkoxybenzoic acid, p-alkoxybenzoic acid, dihydroxybenzoic acid, phenylacetic acid, phenylpropionic acid, o-hydroxy phenylacetic acid, m-hydroxy phenylacetic acid, p-hydroxy phenylacetic acid, phenylmalonic acid, phenylsuccinic acid, cinnamic acid, phenylpyruvic acid and benzoylacetic acid or is an acid substituted with a member selected from the group consisting of a lower alkyl group, a hydroxyl group, a carboxylic acid group, an alkoxy group, a phosphoric acid group, an amino group, an imino group and a halogen, said acid being selected from the group consisting of acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, hexanoic acid, enathic acid, octanoic acid, pelargonic acid, decanoic acid, undecylic acid, lauric acid, myristic acid, palmitic acid, stearic acid, acrylic acid, crotonic acid, vinylacetic acid, 4-pentenoic acid, oleic acid, linoleic acid, linolenic acid, sorbic acid, benzoic acid, alkylbenzoic acid, phthalic acid, isophthalic acid, o-aminobenzoic acid, m-aminobenzoic acid, p-aminobenzoic acid, o-hydroxybenzoic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, o-alkoxybenzoic acid, m-alkoxybenzoic acid, p-alkoxybenzoic acid, dihydroxybenzoic acid, phenylacetic acid, phenylpropionic acid, o-hydroxy phenylacetic acid, m-hydroxy pehnylacetic acid, p-hydroxy phenylacetic acid, phenylmalonic acid, phenylsuccinic acid, cinnamic acid, phenylpyruvic acid and benzoylacetic acid.

9. A suppository according to claim 1, wherein said N-acyl amino acid derivative or N-acyl peptide derivative is incorporated in said suppository in the form of an alkali metal salt or an ammonium salt.