AU705718B2 - Antibacterial compositions - Google Patents
Antibacterial compositions Download PDFInfo
- Publication number
- AU705718B2 AU705718B2 AU27621/95A AU2762195A AU705718B2 AU 705718 B2 AU705718 B2 AU 705718B2 AU 27621/95 A AU27621/95 A AU 27621/95A AU 2762195 A AU2762195 A AU 2762195A AU 705718 B2 AU705718 B2 AU 705718B2
- Authority
- AU
- Australia
- Prior art keywords
- composition
- ciprofloxacin
- sulfonic acid
- polystyrene sulfonic
- acid polymer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/795—Polymers containing sulfur
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61K47/585—Ion exchange resins, e.g. polystyrene sulfonic acid resin
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
0 *0 ANTIBACTERIAL COMPOSITIONS
S
@0 Field of the Invention The present invention relates to pharmaceutical compositions comprising a combination of a quinolone, specifically ciprofloxacin, and a polystyrene sulfonic acid polymer.
0 0 "Background of the Invention Ciprofloxacin (CiloxanTM, Alcon Laboratories, Inc., Fort Worth, Texas, is being used to treat ocular bacterial infections. However, because of the poor solubility of ciprofloxacin at physiological or higher pH, ciprofloxacin formulations were developed at acidic pHs. When these formulations are *0 0 administered topically to the eye, they can be uncomfortable for some individuals.
Summary of the Invention The present invention is directed to improved topical ophthalmic or otic compositions containing ciprofloxacin and a polystyrene sulfonic acid polymer.
The compositions are formulated such that the solubility of ciprofloxacin at a higher pH is increased by the use of an ionic polymer (namely, polystyrene sulfonic acid polymer) which binds with the ciprofloxacin. The binding between the polymer and the ciprofloxacin additionally provides for both initial and continual comfort upon instillation in the eye, as there is less free drug to irritate the tissues of the eye. Another added benefit to the compositions of the present invention is that there is sustained release of the ciprofloxacmn.
Detailed Descdrtion of the Invention The pharmaceutical compositions of the present invention contain a combination of ciprofloxacin having antibacterial activity and a 0 polystyrene sulfonic acid polymer, preferably at physiological or near- .:physiological pH. These compositions are especially useful in thle eye, as thle compositions are comfortable upon topical administration to the eye and provide as for sustained release of ciprofloxacin.
The polystyrene sulfonic acid polymers (and their salts) which are used in the formulations of the present invention have the following formula: 909L X* nitge uhta th moear egto h oytrn 0rfral les thnaot501% WO 96/37191 PCT/US95/06587 3 Ciprofloxacin, its preparation and use as an antimicrobial, are disclosed in U.S. Patent No. 4,670,444 (Grohe, et The entire contents of that patent is incorporated herein by reference.
Ciprofloxacin has the following structure: HN- V 0 The chemical name for ciprofloxacin is l-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl)-3-quinoline carboxylic acid.
The ciprofloxacin concentration in the formulations is less than or about wt% of the total composition, preferably between about 0.1 wt% and 0.75 wt%.
The most preferred concentration is between about 0.2 and 0.4 wt%.
The compositions of the present invention are prepared by combining the ciprofloxacin with the polystyrene sulfonic acid polymer in aqueous media and adjusting the pH, if necessary. The compositions of the present invention may also include one or more ingredients conventionally found in ophthalmic or otic formulations, such as preservatives benzalkonium chloride or thimerosal), is viscosity-imparting agents polyvinyl alcohol or hydroxypropylmethylcellulose), and tonicity agents sodium chloride or mannitol). The compositions will also normally include buffering agents, such as phosphates and citrates, to maintain the pH within the range of physiological pH (pH between and Hydrochloric acid or sodium hydroxide will typically be used to adjust the pH of the resultant composition.
WO 96/37191 PCT/US95/06587 4 The compositions are useful in treating ophthalmic and otic bacterial infections and are administered one to four times daily according to the discretion of a skilled clinician.
The following example is presented to illustrate the preferred formulation of this invention.
EXAMPLE
Ingredient Ciprofloxacin HC1, Monohydrate PSSA 78-7063 (Available from National Starch) Amount w/v% 0.35* 50 ml** Mannitol Boric Acid NaOH and/or HCI Purified Water 4.4 0.3 to pH 6.70 Q.S. to 100 ml l x li!Valent 11:0 U. b aS r rquvalent to u.J3% as Dase PSSA solution in water COMPOUNDING
PROCEDURE
1. Into an agitator-equipped compounding vessel, add approximately 50% of the batch volume of Purified Water at 20-30 0
C.
2. While maintaining moderate agitation, dissolve the PSSA.
3. Into an agitator-equipped compounding vessel, add approximately 30% of the batch volume of Purified Water at 20-30 0
C.
4. While maintaining moderate agitation, dissolve the following: Mannitol Boric Acid Ciprofloxacin HC1, Monohydrate Add the Ciprofloxacin solution from Step 4 to the PSSA Solution slowly with mixing (Note: A precipitate may form briefly, but should dissolve in a few minutes.) 6. Rinse the Ciprofloxacin compounding vessel and transfer lines with 10% of batch volume of cool Purified Water and add to the PSSA/Ciprofloxacin Solution.
7. Check and record the pH. Adjust the pH to interim target of 6.50 using 6N NaOH solution or 1N HC1 solution (requires approximately 800mL 6N NaOH per 100L of batch volume). (Note: NaOH must be added slowly.) 8. Q.S. to 100% total batch weight with room temperature Purified Water.
Mix until homogeneous.
9. Check and record the pH. Adjust the pH, if necessary, to 6.70 0.1 using 6N NaOH solution or 1N HC1 solution.
Filter solution through a 6pm or smaller polishing filter into the receiving reactor.
11. Sterilize the product in the reactor for a minimum of 30 minutes at a minimum of 121°C.
12. Cool the product to approximately room temperature with stirring by introducing cool water into the reactor jacket.
13. If batch weight is less than 99% of the weight measured in Step 10, adjust to the weight in Step 10 with Purified Water through the hydrophilic sterilizing filter. Mix to homogeneity (minimum of 15 minutes).
The invention has been described by reference to certain preferred embodiments; however, it should be understood that it may be embodied in other specific forms or variations thereof without departing from its spirit or essential characteristics. The embodiments described above are therefore considered to be illustrative in all respects and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description.
Throughout the description and claims of the specification the word "comprise" and variations of the word, such as "comprising" and "comprises" is not intended to exclude other additives, components, integers or steps.
Claims (7)
1. A topical otic or ophthalmic sustained release aqueous composition useful in the treatment of bacterial infections which comprises a pharmaceutically effective amount of ciprofloxacin present at a concentration of 0.1wt% and 0.75wt% based on the total weight of the composition and a polystyrene sulfonic acid polymer to which the cirpofloxacin is bound wherein the polystyrene sulfonic acid polymer has the following formula: CH 3 -c SO 3 wherein R H or CH 3 and X an integer such that the molecular weight of the polystyrene sulfonic acid polymer may vary from about 10,000 to 1.6 million.
2. The composition of Claim 1, wherein the ciprofloxacin is present at a concentration between about 0.2 to about 0.4wt%.
3. The composition of Claim 2, wherein the ciprofloxacin is present at a concentration of about 0.3wt%.
4. The composition of any one of the preceding claims, wherein the concentration of the polystyrene sulfonic acid polymer is less than about The composition of Claim 4, wherein the concentration of the polystyrene sulfonic acid polymer is less than about C:\WINWORD'ANNANODELETESPECIES\7621
6. The composition of any one of the preceding claims wherein R is H and the molecular weight is between about 500,000 and 1,000,000.
7. The composition of claim 6, wherein the molecular weight is about 600,000.
8. A composition according to Claim 1 substantially as hereinbefore described with reference to any of the examples. DATED: 22 March 1999 PHILLIPS ORMONDE FITZPATRICK Attorneys for: ALCON LABORATORIES, INC. 4 4. 4 4 .4 4 S.. 0S 0 @4 4 9* 4 .4 4 4* 9 4 C:\WINWORD\ANNANODELETESPECIESW7621
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1995/006587 WO1996037191A1 (en) | 1995-05-24 | 1995-05-24 | Antibacterial compositions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2762195A AU2762195A (en) | 1996-12-11 |
| AU705718B2 true AU705718B2 (en) | 1999-05-27 |
Family
ID=22249170
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU27621/95A Ceased AU705718B2 (en) | 1995-05-24 | 1995-05-24 | Antibacterial compositions |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP2944759B2 (en) |
| AU (1) | AU705718B2 (en) |
| WO (1) | WO1996037191A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60008234T2 (en) * | 1999-04-29 | 2004-12-30 | Alza Corp., Mountain View | LIPOSOME COMPOSITIONS FOR IMPROVED ACTIVE SUBSTANCE |
| US8357385B2 (en) * | 2008-04-07 | 2013-01-22 | Interface Biologics Inc. | Combination therapy for the treatment of bacterial infections |
| JP5624281B2 (en) * | 2009-04-21 | 2014-11-12 | 東亜薬品株式会社 | Liquid formulation containing quinolone antibacterial agent with excellent photostability |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4670444B1 (en) * | 1980-09-03 | 1999-02-09 | Bayer Ag | and-naphthyridine-3-carboxylic acids and antibacte7-amino-1-cyclopropyl-4-oxo-1,4-dihydro-quinoline-rial agents containing these compounds |
| DE3142854A1 (en) * | 1981-10-29 | 1983-05-11 | Bayer Ag, 5090 Leverkusen | 1-CYCLOPROPYL-6-FLUOR-1,4-DIHYDRO-4-OXO-7-PIPERAZINO-CHINOLINE-3-CARBONIC ACIDS, METHOD FOR THE PRODUCTION THEREOF AND THEIR CONTAINING ANTIBACTERIAL AGENTS |
| US5104649A (en) * | 1988-05-11 | 1992-04-14 | Monsanto Company | Surface-functionalized biocidal polymers |
| JP2536806B2 (en) * | 1991-03-27 | 1996-09-25 | アルコン ラボラトリーズ インコーポレイテッド | Topical ophthalmic composition combining gelled polysaccharide and finely divided drug carrier |
-
1995
- 1995-05-24 JP JP52719495A patent/JP2944759B2/en not_active Expired - Fee Related
- 1995-05-24 AU AU27621/95A patent/AU705718B2/en not_active Ceased
- 1995-05-24 WO PCT/US1995/006587 patent/WO1996037191A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| JPH09507679A (en) | 1997-08-05 |
| WO1996037191A1 (en) | 1996-11-28 |
| JP2944759B2 (en) | 1999-09-06 |
| AU2762195A (en) | 1996-12-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |