WO1997045102A1 - Novel therapeutic use of ophthalmic gels - Google Patents
Novel therapeutic use of ophthalmic gels Download PDFInfo
- Publication number
- WO1997045102A1 WO1997045102A1 PCT/FR1996/000827 FR9600827W WO9745102A1 WO 1997045102 A1 WO1997045102 A1 WO 1997045102A1 FR 9600827 W FR9600827 W FR 9600827W WO 9745102 A1 WO9745102 A1 WO 9745102A1
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- Prior art keywords
- gel
- water
- polymer
- viscosity
- use according
- 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.)
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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
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
Definitions
- the present invention relates to the field of therapeutic chemistry and more particularly to that of pharmacotechnology.
- viscous solutions intended to be instilled in the eye based on a gelling polymer characterized in that said polymer is a dispersion of a carboxyvinyl polymer in water which gels by neutralization.
- the document EP A.105 338 36 (Allergan) describes the production of a reversible aqueous gel which manifests the thermosensitive properties of a reversible gelling agent by simultaneous modification of the temperature (0-60 ° C) and the pH (2, 5 to 7.5).
- This gelling agent is typically a mixture of 1% methylcellulose and 0.3% of acrylic polymer (Carbopol 940). It is therefore a complex mixture, the instillation of which is not without problems.
- the problem of the present invention is to produce an aqueous gel which can be instilled in the eye with optimal fluidity so as to achieve both the ability to flow during instillation, and the ability to adhere to the eyeball. by progressive gelation in contact with the mucous membranes.
- Bioadhesion is due to the interpenetration of polymer chains and mucus from the ocular surface via the carboxyvinyl functions.
- a pseudosolution that is too concentrated in polymers (viscosity> 1000 mPa.s) makes the wound molecules not very solvent and the carboxyvinyl groups little available, unlike a more dilute solution.
- This problem is solved according to the invention by dispersing a carboxyvinyl polymer in water and neutralizing this dispersion up to an optimal pH of between 7.0 and 7.5 using a mineral or organic base of so as to obtain a fluid gel having a viscosity of not more than 1000 mPa.s.
- the resulting gel can also be supplemented with one or more isotonizers such as mineral salts, sugars (sorbitol, mannitoi), pH stabilizers such as buffer solutions, preservatives such as quaternary ammoniums (cetrimide), parabens or sorbic acid, antioxidants like ascorbic acid.
- isotonizers such as mineral salts, sugars (sorbitol, mannitoi), pH stabilizers such as buffer solutions, preservatives such as quaternary ammoniums (cetrimide), parabens or sorbic acid, antioxidants like ascorbic acid.
- the carboxyvinyl polymer is present at a concentration which ranges from 0.05 to 0.15% by weight.
- the preferred carboxyvinyl polymers are those sold under the brand name Carbopol (Goodrich) 934 P, 940, 941 and 980.
- the viscosity of such a gel is limited so that the gel can flow freely at the end of the instillation device without however risking to flow from the eye. For this reason, the viscosity at ordinary temperature of such a gel can be situated between 300 and 1000 mPa.s.
- the gel can, in addition, be added with flavoring substances without risk of being irritating. Rose water or witch hazel water, blueberry water, mallow water, meet this condition.
- the gel finds use in ophthalmology for the treatment of red eyes or dry eyes.
- the following examples illustrate the invention without however limiting it:
- This gel has a viscosity of 900 mPas and a pH of 7.1
- This gel has a viscosity of 600 mPas and a pH of 7.2
- This gel has a viscosity of 400 mPas and a pH of 7.1
- This gel has a viscosity of 600 mPas and a p H of 7.2
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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)
Abstract
La présente invention se rapporte au domaine de la chimie thérapeutique et plus spécialement à celui de la pharmacotechnie. Elle a pour objet l'utilisation d'un gel fluide destiné à être instillé dans l'oeil à base d'un polymère gélifiant caractérisé en ce que ledit polymère est une dispersion aqueuse de polymère carboxyvinylique qui se gélifie par neutralisation à l'aide d'une base minérale ou organique. Les gels fluides selon l'invention trouvent un emploi en ophtalmologie pour le traitement des yeux rouges ou des yeux secs.The present invention relates to the field of therapeutic chemistry and more particularly to that of pharmacotechnology. It relates to the use of a fluid gel intended to be instilled in the eye based on a gelling polymer characterized in that said polymer is an aqueous dispersion of carboxyvinyl polymer which gels by neutralization using 'a mineral or organic base. The fluid gels according to the invention find use in ophthalmology for the treatment of red eyes or dry eyes.
Description
NOUVELLE UTILISATION THERAPEUTIQUE DE GELS OPHTALMIQUES NEW THERAPEUTIC USE OF OPHTHALMIC GELS
La présente invention se rapporte au domaine de la chimie thérapeutique et plus spécialement à celui de la pharmacotechnie.The present invention relates to the field of therapeutic chemistry and more particularly to that of pharmacotechnology.
Elle a notamment pour objet des solutions visqueuses destinées à être instillées dans l'oeil et à assurer une bonne couverture du globe oculaire dans les cas où le film lacrymal est absent ou défectueux..Its particular object is viscous solutions intended to be instilled into the eye and to ensure good coverage of the eyeball in cases where the tear film is absent or defective.
Elle a pour objet des solutions visqueuses destinées à être instillées dans l'oeil, à base d'un polymère gélifiant caractérisées en ce que ledit polymère est une dispersion d'un polymère carboxyvinylique dans l'eau qui se gélifie par neutralisation.It relates to viscous solutions intended to be instilled in the eye, based on a gelling polymer characterized in that said polymer is a dispersion of a carboxyvinyl polymer in water which gels by neutralization.
On connaissait déjà, par la demande de brevet européen 0.536.255 du 14 Avril 1993, la possibilité de réaliser un gel auto gélifiant à base de 0, 1 à 6,5% en poids de polymère qui a une valeur de pH comprise entre 9,0 et 6,5 pour une viscosité de 1000 à 30 000 CPS. Le polymère utilisé est dénommé Polycarbophil ou Carbopol 976 (Goodrich). La dispersion de ce polymère peut être envisagée pour traiter le syndrome de l'oeil sec, sans qu'il soit nécessaire d'adjoindre un médicament.We already knew, from European patent application 0.536.255 of April 14, 1993, the possibility of producing a self-gelling gel based on 0.1 to 6.5% by weight of polymer which has a pH value between 9 , 0 and 6.5 for a viscosity of 1000 to 30,000 CPS. The polymer used is called Polycarbophil or Carbopol 976 (Goodrich). The dispersion of this polymer can be considered to treat dry eye syndrome, without the need to add a drug.
Le document EP A.105 338 36 (Allergan) décrit la production d'un gel aqueux réversible qui manifeste les propriétés thermosensibles d'un agent gélifiant réversible par modification simultanée de la température (0-60°C) et du pH (2,5 à 7,5). Cet agent gélifiant est typiquement un mélange de 1 % de méthylcellulose et de 0,3% de polymère acrylique (Carbopol 940). Il s'agit de ce fait, d'un mélange complexe dont l'instillation ne se fait pas sans problème.The document EP A.105 338 36 (Allergan) describes the production of a reversible aqueous gel which manifests the thermosensitive properties of a reversible gelling agent by simultaneous modification of the temperature (0-60 ° C) and the pH (2, 5 to 7.5). This gelling agent is typically a mixture of 1% methylcellulose and 0.3% of acrylic polymer (Carbopol 940). It is therefore a complex mixture, the instillation of which is not without problems.
Le brevet US 5.075.104 (Alcon) décrit la préparation d'un gel ophtalmique aqueux destiné au traitement du syndrome de l'oeil sec dans lequel on disperse dans de l'eau, un polymère carboxyvinylique de manière à obtenir une préparation présentant une viscosité élevée s'échelonnant de 1 500 à 20US Pat. No. 5,075,104 (Alcon) describes the preparation of an aqueous ophthalmic gel intended for the treatment of dry eye syndrome in which a carboxyvinyl polymer is dispersed in water so as to obtain a preparation having a viscosity high ranging from 1,500 to 20
000 dynes/cm2. Le problème de la présente invention est de réaliser un gel aqueux instillable dans l'oeil présentant une fluidité optimale de façon à réaliser à la fois l'aptitude à l'écoulement lors de l'instillation, et la capacité d'adhésion au globe oculaire par gélification progressive au contact des muqueuses.000 dynes / cm 2 . The problem of the present invention is to produce an aqueous gel which can be instilled in the eye with optimal fluidity so as to achieve both the ability to flow during instillation, and the ability to adhere to the eyeball. by progressive gelation in contact with the mucous membranes.
La bioadhésion est due à l'interpénétration des chaînes de polymères et du mucus de la surface oculaire par l'intermédiaire des fonctions carboxyvinyliques. Au contraire, une pseudosolution trop concentrée en polymères (viscosité > 1000 mPa.s) rend les molécules enroulées peu solvatrices et les groupements carboxyvinyliques peu disponibles, au contraire d'une solution plus diluée.Bioadhesion is due to the interpenetration of polymer chains and mucus from the ocular surface via the carboxyvinyl functions. On the contrary, a pseudosolution that is too concentrated in polymers (viscosity> 1000 mPa.s) makes the wound molecules not very solvent and the carboxyvinyl groups little available, unlike a more dilute solution.
Ce problème se trouve résolu selon l'invention en dispersant dans l'eau un polymère carboxyvinylique et en neutralisant cette dispersion jusqu'à un pH optimal compris entre 7,0 et 7,5 à l'aide d'une base minérale ou organique de façon à obtenir un gel fluide présentant une viscosité qui n'est pas supérieure à 1000 mPa.s.This problem is solved according to the invention by dispersing a carboxyvinyl polymer in water and neutralizing this dispersion up to an optimal pH of between 7.0 and 7.5 using a mineral or organic base of so as to obtain a fluid gel having a viscosity of not more than 1000 mPa.s.
Le gel résultant peut également être additionné d'un ou plusieurs isotonisants comme des sels minéraux, des sucres (sorbitol, mannitoi), d'agents stabilisants le pH comme des solutions tampons, des agents conservateurs comme des ammoniums quaternaires (cétrimide), les parabens ou l'acide sorbique, des agents antioxydants comme l'acide ascorbique.The resulting gel can also be supplemented with one or more isotonizers such as mineral salts, sugars (sorbitol, mannitoi), pH stabilizers such as buffer solutions, preservatives such as quaternary ammoniums (cetrimide), parabens or sorbic acid, antioxidants like ascorbic acid.
D'une manière préférée, le polymère carboxyvinylique est présent à une concentration qui s'échelonne de 0,05 à 0, 1 5% en poids. Les polymères carboxyvinyliques préférés sont ceux vendus sous la marque Carbopol (Goodrich) 934 P, 940, 941 et 980.Preferably, the carboxyvinyl polymer is present at a concentration which ranges from 0.05 to 0.15% by weight. The preferred carboxyvinyl polymers are those sold under the brand name Carbopol (Goodrich) 934 P, 940, 941 and 980.
La viscosité d'un tel gel est limitée de façon à ce que le gel puisse s'écouler librement à l'extrémité du dispositif d'instillation sans toutefois risquer de couler de l'oeil. Pour cette raison, on peut situer la viscosité à température ordinaire d'un tel gel entre 300 et 1000 mPa.s.The viscosity of such a gel is limited so that the gel can flow freely at the end of the instillation device without however risking to flow from the eye. For this reason, the viscosity at ordinary temperature of such a gel can be situated between 300 and 1000 mPa.s.
Le gel peut, en outre, être additionné de substances aromatisantes sans risque d'être irritant. L'eau de roses ou l'eau d'Hamamélis, l'eau de bleuet, l'eau de Mauve, remplissent cette condition. Le gel trouve une utilisation en ophtalmologie pour le traitement des yeux rouges ou des yeux secs. Les exemples suivants illustrent l'invention sans toutefois la limiter :The gel can, in addition, be added with flavoring substances without risk of being irritating. Rose water or witch hazel water, blueberry water, mallow water, meet this condition. The gel finds use in ophthalmology for the treatment of red eyes or dry eyes. The following examples illustrate the invention without however limiting it:
EXEMPLE I Gel fluide à 0, 1 %EXAMPLE I Fluid gel at 0.1%
- Polymère carboxyvinylique commercialisé sous la marque Carbopol 934P (Goodrich) 1 g- Carboxyvinyl polymer marketed under the brand Carbopol 934P (Goodrich) 1 g
- Triéthanolamine 0,45 g - Méthylparaben 0,01 15 g- Triethanolamine 0.45 g - Methylparaben 0.01 15 g
- Mannitoi 4,5 g- Mannitoi 4.5 g
- Eau distillée qsp 1000 ml- Distilled water qs 1000 ml
Ce gel présente une viscosité de 900 mPas et un pH de 7, 1This gel has a viscosity of 900 mPas and a pH of 7.1
EXEMPLE IIEXAMPLE II
Gel fluide à 0,08%0.08% fluid gel
- Polymère carboxyvinylique commercialisé sous la marque Carbopol 940 (Goodrich) 0,8 g- Carboxyvinyl polymer marketed under the brand Carbopol 940 (Goodrich) 0.8 g
- Carbonate de lithium 0,28 g- Lithium carbonate 0.28 g
- Méthylparaben 0,01 1 5 g- Methylparaben 0.01 1 5 g
- Acide éthylènediamino tétracétique 0,02 g- Ethylenediamino tetracetic acid 0.02 g
- Sorbitol 5,4 g - Eau distillée de roses qsp 1000 ml- Sorbitol 5.4 g - Distilled water from roses qs 1000 ml
Ce gel présente une viscosité de 600 mPas et un pH de 7,2This gel has a viscosity of 600 mPas and a pH of 7.2
EXEMPLE III Gel fluide de 0, 15%EXAMPLE III 0.15% fluid gel
- Polymère carboxyvinylique commercialisé sous la marque Carbopol 940 (Goodrich) 1 ,5 g- Carboxyvinyl polymer marketed under the brand Carbopol 940 (Goodrich) 1.5 g
- Hydroxyde de sodium en solution à 40% 0, 1 5 g - Méthylparaben 0,01 15 g- Sodium hydroxide in 40% solution 0.15 g - Methylparaben 0.01 15 g
- Sorbitol 5,4 g- Sorbitol 5.4 g
- Eau distillée de roses qsp 1000 ml Ce gel présente une viscosité de 800 mPas et un pH de 7,0- Distilled water of roses qs 1000 ml This gel has a viscosity of 800 mPas and a pH of 7.0
EXEMPLE IV Gel fluide à 0,05%EXAMPLE IV Fluid gel at 0.05%
- Polymère carboxyvinylique commercialisé sous la marque Carbopol 934P (Goodrich) 0,5 g- Carboxyvinyl polymer marketed under the brand Carbopol 934P (Goodrich) 0.5 g
- N-méthylglucamine 0,8 g- N-methylglucamine 0.8 g
- Acide sorbique 1,2 g - Acide éthylènediamino tétraacétique 0,05 g- Sorbic acid 1.2 g - Ethylenediamino tetraacetic acid 0.05 g
- Sorbitol 5,4 g- Sorbitol 5.4 g
- Eau distillée qsp 1000 ml- Distilled water qs 1000 ml
Ce gel présente une viscosité de 400 mPas et un pH de 7, 1This gel has a viscosity of 400 mPas and a pH of 7.1
EXEMPLE VEXAMPLE V
Gel fluide à 0,05%0.05% fluid gel
- Polymère carboxyvinylique commercialisé sous la marque Carbopol 940 (Goodrich) 0,5 g- Carboxyvinyl polymer marketed under the brand Carbopol 940 (Goodrich) 0.5 g
- Pipérazine (hydrate) 0,6 g- Piperazine (hydrate) 0.6 g
- Méthylparaben 0,01 15 g- Methylparaben 0.01 15 g
- Sorbitol 5,4 g- Sorbitol 5.4 g
- Eau distillée de roses qsp 1000 ml- Distilled water of roses qs 1000 ml
Ce gel présente une viscosité de 600 mPas et un p H de 7,2This gel has a viscosity of 600 mPas and a p H of 7.2
EXEMPLE VIEXAMPLE VI
Gel fluide à 0,08 %0.08% fluid gel
- Polymère carboxyvinylique commercialisé sous la marque Carbopol 941 (Goodrich) 0,8 g- Carboxyvinyl polymer marketed under the brand Carbopol 941 (Goodrich) 0.8 g
- Trométhamol 0,55 g- Tromethamol 0.55 g
- Ascorbate de sodium 0,4 g - Méthyl paraben 0,01 1 5 g- Sodium ascorbate 0.4 g - Methyl paraben 0.01 1 5 g
- Sorbitol 2,7 g- Sorbitol 2.7 g
- Eau distillée qsp 1000 ml- Distilled water qs 1000 ml
Le gel résultant à une viscosité de 600 mPas et un pH de 7,4 The resulting gel at a viscosity of 600 mPas and a pH of 7.4
Claims
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/FR1996/000827 WO1997045102A1 (en) | 1996-05-31 | 1996-05-31 | Novel therapeutic use of ophthalmic gels |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/FR1996/000827 WO1997045102A1 (en) | 1996-05-31 | 1996-05-31 | Novel therapeutic use of ophthalmic gels |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997045102A1 true WO1997045102A1 (en) | 1997-12-04 |
Family
ID=9488440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/FR1996/000827 Ceased WO1997045102A1 (en) | 1996-05-31 | 1996-05-31 | Novel therapeutic use of ophthalmic gels |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1997045102A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19938668A1 (en) * | 1999-08-14 | 2001-02-22 | Pharm Pur Gmbh | Tear substitute |
| KR100775065B1 (en) | 2006-06-13 | 2007-11-08 | 주식회사태준제약 | Long-lasting effect eye drop composition and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984004681A1 (en) * | 1983-05-25 | 1984-12-06 | Alcon Lab Inc | Ophthalmic solution |
| GB2196255A (en) * | 1986-10-14 | 1988-04-27 | Res & Dev Co Ltd | Eyedrops |
| EP0365427A1 (en) * | 1988-10-18 | 1990-04-25 | Laboratoire Chauvin Sa | Eyelid compresses, process for soaking same and resultant products |
| FR2717691A1 (en) * | 1994-03-22 | 1995-09-29 | Europhta Laboratoire | Fluid gel esp. for ophthalmic use by instillation |
-
1996
- 1996-05-31 WO PCT/FR1996/000827 patent/WO1997045102A1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984004681A1 (en) * | 1983-05-25 | 1984-12-06 | Alcon Lab Inc | Ophthalmic solution |
| GB2196255A (en) * | 1986-10-14 | 1988-04-27 | Res & Dev Co Ltd | Eyedrops |
| EP0365427A1 (en) * | 1988-10-18 | 1990-04-25 | Laboratoire Chauvin Sa | Eyelid compresses, process for soaking same and resultant products |
| FR2717691A1 (en) * | 1994-03-22 | 1995-09-29 | Europhta Laboratoire | Fluid gel esp. for ophthalmic use by instillation |
Non-Patent Citations (1)
| Title |
|---|
| REYNOLDS J.: "Martindale", 1982, THE PHARMACEUTICAL PRESS, LONDON, XP002025193 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19938668A1 (en) * | 1999-08-14 | 2001-02-22 | Pharm Pur Gmbh | Tear substitute |
| DE19938668B4 (en) * | 1999-08-14 | 2006-01-26 | Bausch & Lomb Inc. | Artificial tears |
| KR100775065B1 (en) | 2006-06-13 | 2007-11-08 | 주식회사태준제약 | Long-lasting effect eye drop composition and preparation method thereof |
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