Sustained release medicinal compositions

• US 6,328,979 B1
• Filed: 06/23/2000
• Issued: 12/11/2001
• Est. Priority Date: 12/26/1997
• Status: Expired due to Fees

• Current Assignee: Astellas Pharma Incorporated
• Original Assignee: Yamanouchi Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
• Inventors: Takahashi, Yutaka, Yamashita, Noboru, Takagi, Akira, Saito, Katsumi, Takaishi, Yuuki, Katsuma, Masataka, Yasuda, Tatsuo, Mitomi, Mitsuo
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/582,384
• Time in Patent Office: 536 Days
• Field of Search: 424/451, 424/489, 424/454, 424/480, 424/50, 424/486, 424/502, 424/487, 424/488, 424/400, 424/468, 424/457, 424/426, 424/423, 424/DIG.15, 514/937
• US Class Current: 424/400
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 31/5585 having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• 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 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system

Abstract

The present invention relates to sustained-release pharmaceutical compositions for ionic pharmaceutically active substances (excluding ionic prostanoic acid derivatives) containing ionic compounds having opposite charges to those of the active substances and increasing hydrophobicity of the active substances. More specifically, the invention relates to sustained-release pharmaceutical compositions comprising the ionic pharmaceutically active substances and the ionic compounds having opposite charges to those of the active substances and increasing hydrophobicity of the active substances that contain hydrophobic groups in the molecule thereof. The pharmaceutical composition of the invention can exhibit excellent sustained release effect of the active substance, irrespective of water solubility possessed by the ionic pharmaceutically active substances.

Claims

1. A sustained-release pharmaceutical composition for an ionic pharmaceutically active substance comprising an ionic pharmaceutically active substance (excluding an ionic prostanoic acid derivative) and an ionic compound having an opposite charge to that of the ionic pharmaceutically active substance and increasing hydrophobicity of the active substance, wherein the ionic compound is incorporated at least in an equimolar amount based on the pharmaceutically active substance in terms of a charge ratio.

2. A sustained-release pharmaceutical composition according to claim 1, wherein the ionic compound having an opposite charge to the ionic pharmaceutically active substance and increasing the hydrophobic property of the active substance contains a hydrophobic group in the molecule thereof.

3. A sustained-release pharmaceutical composition according to claim 1, wherein the ionic compound increases an oil/water partition coefficient of the ionic pharmaceutically active substance.

4. A sustained-release pharmaceutical composition according to claim 1, wherein the ionic pharmaceutically active substance is anionic.

5. A sustained-release pharmaceutical composition according to claim 4, wherein the ionic compound is a compound containing a group selected from an ammonium, pyridinium, phosphonium and sulfonium group in the molecule thereof, or a salt thereof.

6. A sustained-release pharmaceutical composition according to claim 5, wherein the ionic compound contains at least one member selected from the group consisting of an alkyldimethylbenzylammonium salt, an alkyltrimethylammonium salt, an alkylpyridinium salt, an alkylamine salt and an alkylphosphonium salt.

7. A sustained-release pharmaceutical composition according to claim 1, wherein the ionic compound is benzalkonium chloride.

8. A sustained-release pharmaceutical composition according to claim 4, wherein the ionic pharmaceutically active substance is a synthetic ionic pharmaceutically active substance.

9. A sustained-release pharmaceutical composition according to claim 1, wherein the ionic pharmaceutically active substance is cationic.

10. A sustained-release pharmaceutical composition according to claim 9, wherein the ionic compound is a compound containing a group selected from a carboxyl, sulfate, sulfonate and phosphate groups in the molecule thereof, or a salt thereof.

11. A sustained-release pharmaceutical composition according to claim 10, wherein the ionic compound is sodium lauryl sulfate and/or sodium oleate.

12. A sustained-release pharmaceutical composition according to claim 9, wherein the ionic pharmaceutically active substance is a synthetic ionic pharmaceutically active substance.