Drug composition

• US 5,474,989 A
• Filed: 03/01/1994
• Issued: 12/12/1995
• Est. Priority Date: 11/11/1988
• Status: Expired due to Fees

• Current Assignee: Kurita Water Industries Limited
• Original Assignee: Kurita Water Industries Limited
• Inventors: Hashimoto, Masanori, Otagiri, Masaki, Imai, Teruko
• Primary Examiner(s): Henley, III, Raymond
• Assistant Examiner(s): Weddington, Kevin E.
• Application Number:
  US08/203,863
• Time in Patent Office: 651 Days
• Field of Search: 514/55, 514/179, 514/420, 514/560, 514/570, 514/650, 514/458
• US Class Current: 514/55
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds

Abstract

The present invention relates to a drug composition in which the solubility and the dissolution rate of a drug having low water solubility are improved by incoroprating therein a low molecular weight chitosan in an amount of from 0.2 to 10 parts by weight per one part by weight of the poorly water-soluble drug. As the low molecular weight chitosan, those having a weight average molecular weight in the range from 500 to 50,000 and soluble in water were employed. This drug composition is prepared by mixing the components intimately so as to obtain a homogeneous dispersion of the low molecular weight chitosan with the mass of the composition.

The drug composition according to the invention can be worked up into various preparation forms, such as, granules etc., as medicaments for administration to living organisms in which the bioabsorptivity and biouptake are improved.

Claims

1. A medicinal pharmaceutical composition comprising a medicinal pharmaceutical component having a low water solubility and a water-soluble chitosan derivative having a weight average molecular weight in the range of from 500 to 50×

10³ and which is soluble in neutral and alkaline water, said water-soluble chitosan derivative being obtained by subjecting high molecular weight chitosan to a molecular weight degradation reaction with an enzyme, hydrogen peroxide, a nitrite ion or an alkali.

2. The medicinal pharmaceutical composition of claim 1, wherein said pharmaceutical component and said water-soluble chitosan derivative are contained in the composition in a proportion of one part of pharmaceutical component per 0.2 to 10 parts of water-soluble chitosan derivative.

3. The medicinal pharmaceutical composition of claim 1, wherein said medicinal pharmaceutical component is selected from the group consisting of betamethasone, diclofenac acid, dicumarol, digoxin, flurbiprofen, ibuprofen, indomethacin, ketoprofen, mefenamic acid, phenytoin, prednisolone, triamcinolone, vitamin E and vitamin K.

4. The medicinal pharmaceutical composition of claim 2, wherein said medicinal pharmaceutical component is selected from the group consisting of betamethasone, diclofenac acid, dicumarol, digoxin, flurbiprofen, ibuprofen, indomethacin, ketoprofen, mefenamic acid, phenytoin, prednisolone, triamcinolone, vitamin E and vitamin K.

5. The medicinal pharmaceutical composition of claim 1, wherein the water-soluble chitosan derivative has a weight average molecular weight of from 800 to 10×

10³.

6. A method for improving the solubility and rate of dissolution in water of a medicinal pharmaceutical component having a low water solubility comprising the step of mixing the medicinal pharmaceutical component with a water-soluble chitosan derivative having a weight average molecular weight in the range of from 500 to 50×

10³ and which is soluble in neutral and alkaline water, said water-soluble chitosan derivative being obtained by subjecting high molecular weight chitosan to a molecular weight degradation reaction with an enzyme, hydrogen peroxide, a nitrite ion or an alkali.

7. The method of claim 6, wherein said pharmaceutical component and said water-soluble chitosan derivative are mixed in a proportion of one part of pharmaceutical component per 0.2 to 10 parts of water-soluble chitosan.

8. The method of claim 6, wherein said medicinal pharmaceutical component is selected from the group consisting of betamethasone, diclofenac acid, dicumarol, digoxin, flurbiprofen, ibuprofen, indomethacin, ketoprofen, mefenamic acid, phenytoin, prednisolone, triamcinolone, vitamin E and vitamin K.

9. The method of claim 7, wherein said medicinal pharmaceutical component is selected from the group consisting of betamethasone, diclofenac acid, dicumarol, digoxin, flurbiprofen, ibuprofen, indomethacin, ketoprofen, mefenamic acid, phenytoin, prednisolone, triamcinolone, vitamin E and vitamin K.

10. The method of claim 6, wherein the water-soluble chitosan derivative product has a weight average molecular weight of from 800 to 10×

10³.