WO1993002663A1 - Ophthalmic compositions based on polyhydric alcohols - Google Patents
Ophthalmic compositions based on polyhydric alcohols Download PDFInfo
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- WO1993002663A1 WO1993002663A1 PCT/GB1992/001407 GB9201407W WO9302663A1 WO 1993002663 A1 WO1993002663 A1 WO 1993002663A1 GB 9201407 W GB9201407 W GB 9201407W WO 9302663 A1 WO9302663 A1 WO 9302663A1
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- Prior art keywords
- composition
- osmotic agent
- antimicrobial activity
- ophthalmic
- ophthalmically acceptable
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
Definitions
- the present invention relates to ophthalmic compositions, and concerns more especially the preservatives contained in ophthalmic compositions.
- Ophthalmic compositions generally consist of at least one active principle, and an excipient containing at least one inorganic or organic osmotic agent which imparts to the preparation an osmotic pressure corresponding to that of the lachrymal fluid.
- the osmotic pressure of the lachrymal fluid is equivalent to that of a 0.93% NaCl solution.
- An inorganic osmotic agent commonly employed in ophthalmic preparations is sodium chloride.
- organic osmotic agents commonly employed in ophthalmic formulations include hydrogenated hexoses such as mannitol and sorbitol. Ophthalmic compositions must also be sterile when used.
- the hydrogenated hexoses generally employed as excipients tend to promote microorganism growth. It is hence necessary either to prepare sterile single doses which are discarded after each use, thereby increasing production costs, or to incorporate into the ophthalmic composition preservatives which are microorganism growth inhibitors.
- the preservatives generally employed have many drawbacks. In particular, they might exhibit some degree of toxicity through the corneal epithelium, or else they might induce allergic reactions if used at excessively high concentrations. Alternatively, if used at too low concentrations, certain preservatives may not be sufficiently active against some microorganisms.
- osmotic agents namely those having antimicrobial activity
- a class of acceptable osmotic agents of particular value in this regard includes the hydrogenated pentose derivatives such as xylitol and related compounds of the xylitol type.
- the present invention accordingly relates to an ophthalmic composition
- an ophthalmic composition comprising at least one active principle and an excipient, characterised in that the excipient contains at least one ophthalmically acceptable osmotic agent having antimicrobial activity, preferably a hydrogenated pentose derivative such as xylitol.
- ophthalmically acceptable osmotic agent is meant a compound which imparts to an ophthalmic composition an osmotic pressure corresponding to that of a NaCl solution which is acceptable to the eye? in other words, a composition which neither irritates nor adversly affects the parts of the eye with which it will come into contact.
- the limits imposed by the USP for acceptable ophthalmic solutions are from 0.6 to 2% by weight of NaCl.
- the hydrogenated pentose derivatives such as xylitol or related compounds of the xylitol type, may be employed alone or mixed with at least one other osmotic agent suitably selected from sodium chloride, annitol, sorbitol and mixtures thereof.
- agent having antimicrobial activity is meant a compound which inhibits microorganism growth or destroys microorganisms, such microorganisms typically including bacteria and fungi.
- the composition according to the invention may also advantageously incorporate at least one standard preservative.
- preservatives examples include benzalkonium chloride, thimerosal, benzododecinium bromide, parabens and their sodium salts, chlorobutanol, aromatic alcohols, chlorhexidine, and mercury derivatives, as well as other preservatives well known to those skilled in the art, and mixtures thereof.
- the ophthalmic composition according to the present invention may suitably take the form of a solution, a gel, a suspension or an emulsion, preferably an aqueous solution.
- the ophthalmically acceptable osmotic agent having antimicrobial activity such as a hydrogenated pentose derivative, e.g. xylitol, is employed therein as a replacement for the osmotic agents commonly used in known preparations of the prior art.
- the ophthalmically acceptable osmotic agent having antimicrobial activity is incorporated into the preparations of the present invention such that these preparations display a cryoscopic lowering property of between -0.34°C and -1.16°C.
- An ophthalmic composition in accordance with the present invention capable of showing such a cryoscopic lowering typically comprises from 0.1 to 9%, preferably from 2.0 to 9%, by weight of xylitol. It is possible to use in the composition according to the invention a wide variety of active principles.
- - antibacterial substances such as beta-lactam antibiotics, for example cefoxitin, n- forma idoylthienamycin and other thienamycin derivatives, tetracyclines, chloramphenicol , neomycin, carbenicillin, colistin, penicillin G, polymyxin B, vancomycin, cefazolin, cephaloridine, chibrorifamycin, gramicidin, bacitracin and sulfonamides; aminoglycoside antibiotics such as gentamycin, kanamycin, amikacin, sisomicin and tobramycin; nalidixic acid and its analogues such as norfloxacin and the antimicrobial combination fluoroalanine/pentizidone, nitrofurazones and analogues thereof;
- beta-lactam antibiotics for example cefoxitin, n- forma idoylthienamycin and other thienamycin derivatives, te
- - antihistamines and decon ⁇ estants such as pyrilamine, chlorpheniramine, tetrahydrazoline, antazoline and analogues thereof;
- anti-inf1animatories such as cortisone, hydrocortisone, hydrocortisone acetate, betamethasone, dexamethasone, dexamethasone sodium phosphate, prednisone, methylprednisolone, edrysone, fluorometholone, prednisolone, prednisolone sodium phosphate, triamcinolone, indomethacin, sulindac, its salts and corresponding sulphides, and analogues thereof;
- - miotics and anticholiner ⁇ ics such as echothiopate, pilocarpine, physostigmine salicylate, diisopropyl- fluorophosphate, epinephrine, dipivaloylepinephrine, neostigmine, echothiopate iodide, demecarium bromide, carbamoyl choline chloride, methacholine, bethanechol and analogues thereof;
- - mydriatics such as atropine, homatropine, scopolamine, hydroxyamphetamine, ephedrine, cocaine, tropicamide, phenylephrine, cyclopentolate, oxyphenonium, eucatropine and analogues thereof;
- timolol timolol
- R-timolol and a combination of timolol or R-timolol with pilocarpine, as well as many other adrenergic agonists and/or antagonists
- epinephrine, and epinephrine complexes or prodrugs dipivefrine derivatives and hyperosmotic agents such as glycerol, mannitol and urea
- carbonic anhydrase inhibitors such as acetazolamide, dichlorphenamide, 2-(p-hydroxyphenyl)thio-5- thiophenesulphonamide, 6-pivaloyloxy-2- benzothiazolesulphonamide, MK-927 and MK-417
- - antiparasitic compounds and/or antiprotozoal compounds such as ivermectin, pyrimethamine
- - compounds having antiviral activity such as acyclovir, 5-iodo-2'-deoxyuridine (IDU), adenosine arabinoside (Ara- A) , trifluorothymidine, and interferon and interferon- inducing agents such as polyl.polyC;
- antifungal agents such as amphotericin B, nystatin, flucytosine, natamycin and miconazole;
- - anaesthetic agents such as etidocaine, cocaine, benoxinate, dibucaine hydrochloride, dyclonine hydrochloride, naepaine, phenacaine hydrochloride, piperocaine, proparacaine hydrochloride, tetracaine hydrochloride, hexylcaine, bupivacaine, lidocaine, mepivacaine and prilocaine
- - ophthalmic diagnostic agents such as: a) those which are used for examining the retina, such as fluorescein sodium; b) those which are used for examining the conjunctiva, cornea and lachrymal apparatus, such as fluorescein and rose bengal; and c) those which are used for examining abnormal responses of the pupil, such as methacholine, cocaine, adrenaline, atropine, hydroxyamphetamine and pilocarpine; - ophthalmic agents used as surgical aids, such as alpha- chymotryp
- - chelating agents such as ethylenediaminetetraacetic acid (ETDA) and deferoxamine
- - immunosuppressants and antimetabolites such as methotrexate, cyclophosphamide, 6-mercaptopurine and azathioprine
- antibiotic/anti-inflammatory combinations such as the combination neomycin sulphate/dexamethasone sodium phosphate, and combinations concomitantly treating glaucoma, for example a timolol maleate/aceclidine combination.
- the active principle may typically be present in the ophthalmic composition according to the invention in an amount of from about 0.001% to about 5% by weight, suitably from 0.1% to 2% by weight.
- gelling or viscosifying agents may be advantageously incorporated into the preparations of the present invention.
- agents include in particular polysaccharides such as gellan gum, especially the product sold by the Kelco company under the trade name
- Gelrite Gelrite; carboxylic polymers such as those designated by the trade mark Carbopol; cellulose derivatives, for example carboxymethylcellulose or hydroxyethylcellulose (HEC) ; polyvinyl alcohols (PVA) ; polyvinylpyrrolidone (PVP) ; and mixtures thereof.
- carboxylic polymers such as those designated by the trade mark Carbopol
- cellulose derivatives for example carboxymethylcellulose or hydroxyethylcellulose (HEC)
- PVA polyvinyl alcohols
- PVP polyvinylpyrrolidone
- the present invention also concerns a process for preparing the above-described composition, characterised in that an ophthalmically acceptable osmotic agent having antimicrobial activity is mixed with the other components constituting the composition under agitation in an aqueous solution and then sterilized.
- Table I describes the composition of two dilute ophthalmic solutions, one being rendered isotonic with xylitol according to the present invention (Example 1) , the other being rendered isotonic in a conventional manner with mannitol (Example 2) .
- the proportions are given in percentages by weight relative to the total weight of the composition.
- Both solutions are prepared in an identical way by dissolving the different compounds in water under agitation, the gelling or viscosifying agent being incorporated last. After dissolving all the components, the ophthalmic solutions are sterilized in an autoclave.
- compositions have an identical concentration of preservative (0.01% benzododecinium bromide) , and differ only in the tonicity agent employed.
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- Health & Medical Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to an ophthalmic composition comprising at least one active principle and at least one ophthalmically acceptable osmotic agent having antimicrobial activity, typically xylitol; and to a process for the preparation thereof.
Description
OPHTHALMIC COMPOSITIONS BASED ON POLYHYDRIC ALCOHOLS
The present invention relates to ophthalmic compositions, and concerns more especially the preservatives contained in ophthalmic compositions.
Ophthalmic compositions generally consist of at least one active principle, and an excipient containing at least one inorganic or organic osmotic agent which imparts to the preparation an osmotic pressure corresponding to that of the lachrymal fluid. The osmotic pressure of the lachrymal fluid is equivalent to that of a 0.93% NaCl solution. An inorganic osmotic agent commonly employed in ophthalmic preparations is sodium chloride. Examples of organic osmotic agents commonly employed in ophthalmic formulations include hydrogenated hexoses such as mannitol and sorbitol. Ophthalmic compositions must also be sterile when used. However, whilst sodium chloride remains neutral with respect to bacterial growth, the hydrogenated hexoses generally employed as excipients tend to promote microorganism growth. It is hence necessary either to prepare sterile single doses which are discarded after each use, thereby increasing production costs, or to incorporate into the ophthalmic composition preservatives which are microorganism growth inhibitors. The preservatives generally employed have many drawbacks. In particular, they might exhibit some degree of toxicity through the corneal epithelium, or else they might induce allergic reactions if used at excessively high concentrations. Alternatively, if used at too low
concentrations, certain preservatives may not be sufficiently active against some microorganisms.
We have now found unexpectedly that certain acceptable osmotic agents, namely those having antimicrobial activity, may advantageously replace, partially or wholly, the osmotic agents commonly used in ophthalmic compositions, thereby enabling the use of possibly toxic or irritant preservatives to be decreased or even excluded and the spectrum of microorganisms eliminated to be broadened. A class of acceptable osmotic agents of particular value in this regard includes the hydrogenated pentose derivatives such as xylitol and related compounds of the xylitol type.
The present invention accordingly relates to an ophthalmic composition comprising at least one active principle and an excipient, characterised in that the excipient contains at least one ophthalmically acceptable osmotic agent having antimicrobial activity, preferably a hydrogenated pentose derivative such as xylitol. By the expression "ophthalmically acceptable osmotic agent" is meant a compound which imparts to an ophthalmic composition an osmotic pressure corresponding to that of a NaCl solution which is acceptable to the eye? in other words, a composition which neither irritates nor adversly affects the parts of the eye with which it will come into contact. By way of guidance, it is to be noted that the limits imposed by the USP for acceptable ophthalmic solutions are from 0.6 to 2% by weight of NaCl. The hydrogenated pentose derivatives, such as xylitol or related compounds of the xylitol type, may be employed alone or mixed with at least one other osmotic agent suitably selected from sodium chloride, annitol, sorbitol and mixtures thereof.
By the expression "agent having antimicrobial activity" is meant a compound which inhibits microorganism growth or destroys microorganisms, such microorganisms typically including bacteria and fungi. The composition according to the invention may also advantageously incorporate at least one standard preservative. Examples of suitable preservatives include benzalkonium chloride, thimerosal, benzododecinium bromide, parabens and their sodium salts, chlorobutanol, aromatic alcohols, chlorhexidine, and mercury derivatives, as well as other preservatives well known to those skilled in the art, and mixtures thereof.
The ophthalmic composition according to the present invention may suitably take the form of a solution, a gel, a suspension or an emulsion, preferably an aqueous solution. The ophthalmically acceptable osmotic agent having antimicrobial activity such as a hydrogenated pentose derivative, e.g. xylitol, is employed therein as a replacement for the osmotic agents commonly used in known preparations of the prior art.
The ophthalmically acceptable osmotic agent having antimicrobial activity is incorporated into the preparations of the present invention such that these preparations display a cryoscopic lowering property of between -0.34°C and -1.16°C. An ophthalmic composition in accordance with the present invention capable of showing such a cryoscopic lowering typically comprises from 0.1 to 9%, preferably from 2.0 to 9%, by weight of xylitol. It is possible to use in the composition according to the invention a wide variety of active principles. They may typically be selected from the following pharmaceutical compounds:
- antibacterial substances such as beta-lactam antibiotics, for example cefoxitin, n- forma idoylthienamycin and other thienamycin derivatives, tetracyclines, chloramphenicol , neomycin, carbenicillin, colistin, penicillin G, polymyxin B, vancomycin, cefazolin, cephaloridine, chibrorifamycin, gramicidin, bacitracin and sulfonamides; aminoglycoside antibiotics such as gentamycin, kanamycin, amikacin, sisomicin and tobramycin; nalidixic acid and its analogues such as norfloxacin and the antimicrobial combination fluoroalanine/pentizidone, nitrofurazones and analogues thereof;
- antihistamines and deconσestants such as pyrilamine, chlorpheniramine, tetrahydrazoline, antazoline and analogues thereof;
- anti-inf1animatories such as cortisone, hydrocortisone, hydrocortisone acetate, betamethasone, dexamethasone, dexamethasone sodium phosphate, prednisone, methylprednisolone, edrysone, fluorometholone, prednisolone, prednisolone sodium phosphate, triamcinolone, indomethacin, sulindac, its salts and corresponding sulphides, and analogues thereof;
- miotics and anticholinerσics such as echothiopate, pilocarpine, physostigmine salicylate, diisopropyl- fluorophosphate, epinephrine, dipivaloylepinephrine, neostigmine, echothiopate iodide, demecarium bromide, carbamoyl choline chloride, methacholine, bethanechol and analogues thereof;
- mydriatics such as atropine, homatropine, scopolamine, hydroxyamphetamine, ephedrine, cocaine, tropicamide, phenylephrine, cyclopentolate, oxyphenonium, eucatropine and analogues thereof;
- other druσs used in the treatment of eye conditions and lesions, such as antiglaucoma drugs, for example timolol.
R-timolol, and a combination of timolol or R-timolol with pilocarpine, as well as many other adrenergic agonists and/or antagonists; epinephrine, and epinephrine complexes or prodrugs, and dipivefrine derivatives and hyperosmotic agents such as glycerol, mannitol and urea; and carbonic anhydrase inhibitors such as acetazolamide, dichlorphenamide, 2-(p-hydroxyphenyl)thio-5- thiophenesulphonamide, 6-pivaloyloxy-2- benzothiazolesulphonamide, MK-927 and MK-417; - antiparasitic compounds and/or antiprotozoal compounds such as ivermectin, pyrimethamine, trisulphapyrimidine, clindamycin and corticosteroid preparations;
- compounds having antiviral activity such as acyclovir, 5-iodo-2'-deoxyuridine (IDU), adenosine arabinoside (Ara- A) , trifluorothymidine, and interferon and interferon- inducing agents such as polyl.polyC;
- antifungal agents such as amphotericin B, nystatin, flucytosine, natamycin and miconazole;
- anaesthetic agents such as etidocaine, cocaine, benoxinate, dibucaine hydrochloride, dyclonine hydrochloride, naepaine, phenacaine hydrochloride, piperocaine, proparacaine hydrochloride, tetracaine hydrochloride, hexylcaine, bupivacaine, lidocaine, mepivacaine and prilocaine; - ophthalmic diagnostic agents such as: a) those which are used for examining the retina, such as fluorescein sodium; b) those which are used for examining the conjunctiva, cornea and lachrymal apparatus, such as fluorescein and rose bengal; and c) those which are used for examining abnormal responses of the pupil, such as methacholine, cocaine, adrenaline, atropine, hydroxyamphetamine and pilocarpine;
- ophthalmic agents used as surgical aids, such as alpha- chymotrypsin and hyaluronidase;
- chelating agents such as ethylenediaminetetraacetic acid (ETDA) and deferoxamine; - immunosuppressants and antimetabolites such as methotrexate, cyclophosphamide, 6-mercaptopurine and azathioprine; and antibiotic/anti-inflammatory combinations such as the combination neomycin sulphate/dexamethasone sodium phosphate, and combinations concomitantly treating glaucoma, for example a timolol maleate/aceclidine combination.
The active principle may typically be present in the ophthalmic composition according to the invention in an amount of from about 0.001% to about 5% by weight, suitably from 0.1% to 2% by weight.
Finally, gelling or viscosifying agents may be advantageously incorporated into the preparations of the present invention. Such agents include in particular polysaccharides such as gellan gum, especially the product sold by the Kelco company under the trade name
Gelrite; carboxylic polymers such as those designated by the trade mark Carbopol; cellulose derivatives, for example carboxymethylcellulose or hydroxyethylcellulose (HEC) ; polyvinyl alcohols (PVA) ; polyvinylpyrrolidone (PVP) ; and mixtures thereof.
It will be appreciated that, in practice, certain gelling or viscosifying agents have a tendency to be incompatible with certain mineral osmotic agents. For example, GelriteR interacts rapidly with sodium chloride to form a gel, and CarbopolR gives an unwanted precipitate in the presence of sodium chloride. Combinations of gelling or viscosifying agents and mineral osmotic agents which interact undesirably in this way are consequently best avoided. The person skilled in
the art will either be already aware of which combinations to avoid, or be capable of ascertaining such incompatible combinations on the basis of simple trial and error. The present invention also concerns a process for preparing the above-described composition, characterised in that an ophthalmically acceptable osmotic agent having antimicrobial activity is mixed with the other components constituting the composition under agitation in an aqueous solution and then sterilized.
Table I below describes the composition of two dilute ophthalmic solutions, one being rendered isotonic with xylitol according to the present invention (Example 1) , the other being rendered isotonic in a conventional manner with mannitol (Example 2) . The proportions are given in percentages by weight relative to the total weight of the composition.
Both solutions are prepared in an identical way by dissolving the different compounds in water under agitation, the gelling or viscosifying agent being incorporated last. After dissolving all the components, the ophthalmic solutions are sterilized in an autoclave.
Both compositions have an identical concentration of preservative (0.01% benzododecinium bromide) , and differ only in the tonicity agent employed.
TABLE 1
A simplified test of efficacy of preservatives according to the British Pharmacopoeia (1988, Appendix XVI C) was performed for the two compositions, with respect to Aspergillus niger.
The results of these comparative tests, as displayed in Table II below, show clearly the major advantage of incorporating xylitol into a composition of this type.
TABLE II
Aspergillus niger count according to the B.P.. 1988
Claims
1. An ophthalmic composition comprising at least one active principle and an excipient, characterised in that the excipient contains at least one ophthalmically acceptable osmotic agent having antimicrobial activity.
2. A composition as claimed in claim 1, characterised in that the ophthalmically acceptable osmotic agent having antimicrobial activity is a hydrogenated pentose derivative.
3. A composition as claimed in claim 2, characterised in that the ophthalmically acceptable osmotic agent having antimicrobial activity is xylitol.
4. A composition as claimed in any one of the preceding claims, characterised in that it further contains at least one other osmotic agent selected from sodium chloride, mannitol, sorbitol and mixtures thereof.
5. A composition as claimed in any one of the preceding claims, characterised in that it further contains at least one standard preservative.
6. A composition as claimed in any one of the preceding claims, characterised in that it comprises from 0.1 to 9% by weight of xylitol.
7. A composition as claimed in any one of the preceding claims, characterised in that it further comprises a gelling or viscosifying agent.
8. A composition as claimed in claim 7, characterised in that the gelling or viscosifying agent is selected from polysaccharides , carboxylic polymers, cellulose derivatives, and mixtures thereof.
9. A composition as claimed in any one of the preceding claims, characterised in that the active principle is selected from antiglaucoma drugs, antibiotics and compounds having antiviral activity.
10. A process for preparing an ophthalmic composition as claimed in any one of the preceding claims, characterised in that an ophthalmically acceptable osmotic agent having antimicrobial activity is mixed with the other components constituting the composition under agitation in an aqueous solution and then sterilized.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR91/09651 | 1991-07-30 | ||
FR9109651A FR2679773A1 (en) | 1991-07-30 | 1991-07-30 | Ophthalmic preparation containing an acceptable antimicrobial osmotic agent |
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Publication Number | Publication Date |
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WO1993002663A1 true WO1993002663A1 (en) | 1993-02-18 |
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Application Number | Title | Priority Date | Filing Date |
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PCT/GB1992/001407 WO1993002663A1 (en) | 1991-07-30 | 1992-07-29 | Ophthalmic compositions based on polyhydric alcohols |
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WO (1) | WO1993002663A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995015149A1 (en) * | 1993-12-02 | 1995-06-08 | Sederma S.A. | Novel cosmetic compositions containing simple polyols |
WO2000049990A2 (en) * | 1999-02-03 | 2000-08-31 | Bakulesh Mafatlal Khamar | The process for manufacturing topical ophthalmic preparations without systemic effects |
US6414035B1 (en) | 1997-12-01 | 2002-07-02 | Xyrofin Oy | Use of polyols in combating yeast infection and polyol preparations for said use |
US6503497B2 (en) | 1992-05-06 | 2003-01-07 | Alcon Manufacturing, Ltd. | Use of borate-polyol complexes in ophthalmic compositions |
US20130251697A1 (en) * | 2008-06-13 | 2013-09-26 | Ford D. Albritton, IV | Novel nasal spray |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19614823A1 (en) | 1996-04-15 | 1997-10-16 | Mann Gerhard Chem Pharm Fab | Ophthalmic composition with prolonged retention time on the eye |
US7619008B2 (en) * | 2004-11-12 | 2009-11-17 | Kimberly-Clark Worldwide, Inc. | Xylitol for treatment of vaginal infections |
US7786176B2 (en) | 2005-07-29 | 2010-08-31 | Kimberly-Clark Worldwide, Inc. | Vaginal treatment composition containing xylitol |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0080879A2 (en) * | 1981-11-28 | 1983-06-08 | Sunstar Kabushiki Kaisha | Pharmaceutical composition containing interferon in stable state |
JPS62277323A (en) * | 1986-02-19 | 1987-12-02 | Sankyo Co Ltd | Production of eye drop containing ketotifen fumarate |
GB2199745A (en) * | 1987-01-14 | 1988-07-20 | Hokuriku Pharmaceutical | Isotonic aqueous solution of quinolone carboxylic biocide |
-
1991
- 1991-07-30 FR FR9109651A patent/FR2679773A1/en active Pending
-
1992
- 1992-07-29 WO PCT/GB1992/001407 patent/WO1993002663A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0080879A2 (en) * | 1981-11-28 | 1983-06-08 | Sunstar Kabushiki Kaisha | Pharmaceutical composition containing interferon in stable state |
JPS62277323A (en) * | 1986-02-19 | 1987-12-02 | Sankyo Co Ltd | Production of eye drop containing ketotifen fumarate |
GB2199745A (en) * | 1987-01-14 | 1988-07-20 | Hokuriku Pharmaceutical | Isotonic aqueous solution of quinolone carboxylic biocide |
Non-Patent Citations (1)
Title |
---|
Database: WPIL, accession no. 88-016591 (03), Derwent Publications Ltd, London, GB, & JP,A,62277323 (SANKYO K.K.) 2 December 1987, see abstract * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6503497B2 (en) | 1992-05-06 | 2003-01-07 | Alcon Manufacturing, Ltd. | Use of borate-polyol complexes in ophthalmic compositions |
US6849253B2 (en) | 1992-05-06 | 2005-02-01 | Alcon Manufacturing, Ltd. | Use of borate-polyol complexes in ophthalmic compositions |
WO1995015149A1 (en) * | 1993-12-02 | 1995-06-08 | Sederma S.A. | Novel cosmetic compositions containing simple polyols |
FR2713086A1 (en) * | 1993-12-02 | 1995-06-09 | Sederma Sa | New cosmetic compositions containing simple polyols. |
US6414035B1 (en) | 1997-12-01 | 2002-07-02 | Xyrofin Oy | Use of polyols in combating yeast infection and polyol preparations for said use |
EP1600155A1 (en) * | 1997-12-01 | 2005-11-30 | Danisco Sweeteners Oy | The use of polyols in combating yeast infection and polyol preparations for said use |
WO2000049990A2 (en) * | 1999-02-03 | 2000-08-31 | Bakulesh Mafatlal Khamar | The process for manufacturing topical ophthalmic preparations without systemic effects |
WO2000049990A3 (en) * | 1999-02-03 | 2001-07-26 | Bakulesh Mafatlal Khamar | The process for manufacturing topical ophthalmic preparations without systemic effects |
US20130251697A1 (en) * | 2008-06-13 | 2013-09-26 | Ford D. Albritton, IV | Novel nasal spray |
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FR2679773A1 (en) | 1993-02-05 |
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