PROCESSES FOR PREPARING PIPERAZINIUM SALTS OF KMUP AND USE THEREOF

• US 20110136767A1
• Filed: 09/09/2010
• Published: 06/09/2011
• Est. Priority Date: 04/30/2009
• Status: Active Grant

• Current Assignee: Kaohsiung Medical University
• Original Assignee: Kaohsiung Medical University
• Inventors: Chen, Ing-Jun
• Granted Patent: US 8,470,805 B2
• Time in Patent Office: Days
• US Class Current: 514/161
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

A series of monoquarternary piperazium salts including a structure of a formula I or II are provided. In formula I or II, R₁, R_a, and RX are as defined in the specification. The monoquarternary piperazium salt of KMUP or piperazine disclosed in the present invention is characterized by being presented in a pro-drug form and having various pharmaceutical functions.

Claims

1. A complex compound, comprising a structure being one of

2. A compound as claimed in claim 1, wherein the halogen atom is one of a chlorine atom and a fluorine atom.

3. A compound as claimed in claim 1, wherein RX is a mineral acid being one selected from a group consisting of HCl, HBr, HI, H₂SO₄, HNO₃, H₃PO₄, H₃PO₂, Na₂HPO₄ and NaH₂PO₄.

4. A compound as claimed in claim 1, wherein RX is an organic acid being one selected from a group consisting of a citric acid, a fumaric acid, a maleic acid, a nicotinic acid, an isonicotinic acid, a tartaric acid, a succinic acid, an adipic acid, a fatty acid, a methanesulfonic acid and a phenoxylevulinic acid.

5. A compound as claimed in claim 1, wherein RX is a statin being one selected from a group consisting of atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pravastatin, rosuvastatin, pitavastatin and simvastatin.

6. A compound as claimed in claim 1, wherein RX is an NSAID being one selected from a group consisting of Aspirin, Salicylic acid, indomethacin, diclofenac, meclofenamic acid, tolmetin, ketoprofen, methotrexate, flurbiprofen, fenoprofen, tiaprofen, diflunisal, etodolac, ibuprofen and prostacyclin.

7. A compound as claimed in claim 1, wherein RX is an anti-asthmatic drug being one selected from a group consisting of a montelukast, a cromolyn sodium and a nedocromil.

8. A compound as claimed in claim 1, wherein RX is a fabric acid derivative being one of a gemfibrozil and a fenofibrate.

9. A compound as claimed in claim 1, wherein RX is an anti-diabetic drug being one selected from a group consisting of an alginate sodium, a γ

-polyglutamic acid, a sodium polyglutamate, a calcium polyglutamate-alginate sodium, a repaglinide and a nateglinide.

10. A method for preparing a complex compound, comprising :

providing one of a KMUP salt and a piperazinium salt;

reacting one of the KMUP salt and the piperazinium salt with a reacting compound containing a carboxylic group donated from one selected from a group consisting of a statin, a fibric acid, a fibric acid derivative, a non-steroid anti-inflammatory (NSAIDs), an anti-allergy drug, an anti-diabetic drug and an anti-asthmatic drug; and

forming the complex compound being a quaternary ammonium salt.

11. A method as claimed in claim 10, wherein the piperazinium salt is one of a mineral acid salt and an organic acid salt.

12. A method as claimed in claim 10, wherein the KMUP salt is one of a mineral acid salt and an organic acid salt.

13. A pharmaceutical composition, comprising :

an effective amount of one of a KMUP salt and a piperazinium salt; and

an effective amount of a compound containing a carboxylic group donated from one selected from a group consisting of a statin, a non-steroid anti-inflammatory (NSAIDs), an anti-allergy drug, an anti-diabetic drug and an anti-asthmatic drug.

14. A pharmaceutical composition as claimed in claim 13, wherein the KMUP salt is one of a mineral acid salt and an organic acid salt.

15. A pharmaceutical composition as claimed in claim 13, wherein the piperazinium salt is one of a mineral acid salt and an organic acid salt.

16. A pharmaceutical composition as claimed in claim 13, further comprising a pharmaceutically accepted carrier.