WO2003022278A1 - Contraceptifs - Google Patents
Contraceptifs Download PDFInfo
- Publication number
- WO2003022278A1 WO2003022278A1 PCT/JP2002/008961 JP0208961W WO03022278A1 WO 2003022278 A1 WO2003022278 A1 WO 2003022278A1 JP 0208961 W JP0208961 W JP 0208961W WO 03022278 A1 WO03022278 A1 WO 03022278A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- contraceptive
- acid
- present
- nicotinamide
- nicotinamides
- Prior art date
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
Definitions
- the present invention relates to a contraceptive composition containing nicotinamides.
- spermicides such as nonoxynol 9 or octoxinol 9 have been widely used as suppositories, creams and foams, mainly for contraception, alone and in conjunction with various contraceptive devices. It has been reported in the prior art that nonoxynol 9, in addition to sperm, has at least some bactericidal action in some in vitro tests and can also kill the human immunodeficiency virus (HIV).
- HAV human immunodeficiency virus
- a contraceptive composition that has low irritation to the inner layer of the mucous membrane of the vagina, has no side effects, and can easily perform contraception is desired. Disclosure of the invention
- An object of the present invention is to produce a sperm using a contraceptive composition containing nicotinamides. Inhibiting motor skills and obtaining a contraceptive effect.
- the present inventors have studied a wide variety of chemical substances.As a result, unexpectedly, nicotinamides, which conventionally belong to the category of the vitamin B group, use piyumin as a raw material, and therefore have toxicity. The present inventors have found that they have an excellent spermicidal activity, and as a result of further study, they have completed the present invention.
- a contraceptive composition comprising nicotinamides
- the nicotinamides are nicotinamide, nicotinic acid, pyrazine, pyrazinamide, pyrazine—2-rubilic acid, pyridoxine, pyridoxal, pyridoxamine, methylnicotinic acid, pyridine-3—virurubonic acid, hydrazine isonicotinate , 3-methylpyridine, NAD + , NAD H, NAD P + , NAD PH and at least one selected from the group consisting of salts thereof, the contraceptive composition according to (1),
- contraceptive composition according to (1) wherein the contraceptive composition is a vaginal effervescent tablet, jelly, or a film-form preparation.
- a spermicidal or contraceptive method which comprises contacting nicotinamides with sperm;
- nicotinamides used in the contraceptive composition of the present invention can be produced and obtained by a known method.
- nicotinamide can be produced and produced by passing ammonia gas through an ethanol solution of methyl nicotinate, or by partially hydrolyzing cyanopyridine.
- Nicochi Commercially available amides may be used. Examples of such commercially available products include nicotinamide (manufactured by Nakaraitex), nicotinic acid (manufactured by Nakaraitex), pyrazine (manufactured by Nakaraitex), and pyrazineamide (manufactured by Nakaraitex).
- the active ingredient of the contraceptive composition according to the present invention includes, for example, nicotinamide, nicotinic acid, pyrazine, pyrazinamide, pyrazine-2-pyruvic acid, pyridoxine, pyridoxal, pyridoxamine, methylnicotinic acid, and pyridine-13-carboxylic acid.
- NAD + (nicotinamide adenine dinucleotide), NADH (nicotinamide adenine dinucleotide reduced form), NAD P + (nicotinamide adenine dinucleotide phosphate), NAD PH (reduced form of nicotinamide adenine dinucleotide phosphate) and the like, and preferably, nicotinamide, pyrazinamide, nicotinic acid, methyl nicotinate, pyrazine-12-carboxylic acid and the like.
- active ingredients may be used alone or in combination of two or more.
- the active ingredient of the contraceptive composition according to the present invention may be a salt.
- pharmacologically acceptable salts of the above compounds that form salts are preferred.
- examples of such salts include salts with organic or inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and citric acid, and salts with bases such as ammonia, dimethylamine, and getylamine. .
- the contraceptive composition of the present invention can be obtained by formulating an effective amount of a nicotinamide in combination with a suitable pharmaceutical carrier or other adjuvant by a conventional method.
- effective amount means that sperm present in the mammal's vagina is brought into contact with nicotinamide to cut the flagella of the sperm and immobilize it to make fertilization impossible. The amount that can be done. In addition, an amount that produces the desired effect with few side effects is preferable.
- the concentration of the active ingredient is usually about 0.5 mM to 10 mM, preferably about 1 mM to 3 mM. Contraception can be achieved by vaginal administration 10 to 60 minutes before sexual intercourse.
- Examples of the form of the contraceptive composition of the present invention include, for example, ointments, dispersions, creams, vaginal effervescent tablets, jellies, film-form preparations, and the like.
- Examples include effervescent tablets, jellies, and film-form preparations, which are used alone when administered intravaginally or when applied to the vagina using a finger or an applicator.
- the form of the effervescent tablet in the vagina according to the present invention includes, for example, a circle, a rectangle, an ellipse, and a donut, but the form is not particularly limited and may be composed of several layers.
- Intravaginal effervescent tablets disintegrate rapidly in the vagina, producing a thick suspension.
- nicotinamides include, for example, glucose, saccharides, sorbitol, mannitol, an inert diluent such as polyvinylpyrrolidone, cellulose, a cellulose derivative exhibiting adhesiveness when contacted with a mucous membrane, A substance such as a lipoxyvinyl polymer, a derivative of a carboxyvinyl polymer, a lectin or a natural substance, or a mixture thereof, for example, lipoxyl polymethylene, carboxymethylcellulose, or acetic acid furic acid, which produces a storage effect. It is manufactured by a generally well-known method by mixing with materials such as polyethylene and polyvinyl acetate.
- the vaginal effervescent tablet according to the present invention may be formulated, if necessary, in addition to the above-mentioned drugs, for example, excipients, binders, disintegrants, lubricants, coloring agents, humectants, thickeners, preservatives It may be carried out by adding an agent, a flavoring agent, an antioxidant, an antibacterial preservative, a pH adjuster and the like.
- excipient include lactose, corn starch, sucrose, glucose, sorbitol, crystalline cellulose, silicon dioxide, and the like.
- the binder include, for example, starch, polyvinyl alcohol, polyvinyl ether, ethyl cellulose, and methyl cellulose.
- Disintegrants include, for example, starch, hydroxypropyl starch, Q! Maize starch, alginic acid, and lubricating agents, for example, talc powder, magnesium stearate, talc, polyethylene glycol, silica, hardened Vegetable oils and the like. Colorants that are permitted to be added to pharmaceuticals are used. Examples of humectants include glycerin, polyglycerin, 1,3_butylene glycol, sorby] ⁇ il, xylitol, mulch!
- Mucopolysaccharides hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, mucopolysaccharides such as heparin and keratan sulfate and their salts, collagen, elastin, keratin, etc. proteins and their derivatives, and Thickeners, such as carboxymethyl cellulose, agarose, methylcellulose, ethylcellulose, gum arabic, polyvinyl chloride, and the like, such as carboxymethyl cellulose, sorbyl, inositol, trehalose, urea, pyrrolidonecarboxylic acid and salts thereof.
- Thickeners such as carboxymethyl cellulose, agarose, methylcellulose, ethylcellulose, gum arabic, polyvinyl chloride, and the like, such as carboxymethyl cellulose, sorbyl, inositol, trehalose, urea,
- preservatives such as alcohol, montmorillonite, and labonite are, for example, ethyl ethyl parahydroxybenzoate (ethylparaben) and methyl paraoxybenzoate (methyl paraben).
- aromatic agents are menthols, fruit juice and other flavors.
- essential oils include vitamin A, such as vitamin A acetate and vitamin A palmitate, and their derivatives and their salts, vitamin B and their derivatives, their salts, and monophosphate phosphate.
- Vitamin C and its derivatives such as virmagnesium, sodium L-ascorbate sulfate, and vitamin C dipalmitate, and their salts, vitamins D and their derivatives, and their salts; and vitamin E and its salts such as vitamin E acetate Derivatives and their salts, daryuthione and its derivatives and their salts, butylated hydroxytoluene (BHT), and butylated hydroxyazole (BHA).
- the pH adjuster include bases such as sodium hydroxide, sodium carbonate and sodium hydrogen carbonate, and acids such as hydrochloric acid.
- the effervescent tablet in the vagina according to the present invention may be, for example, sugar-coated, gelatin-coated, or optionally coated as needed.
- additives are appropriately selected by those skilled in the art, and the mixing ratio with the active ingredient of the present invention can be appropriately adjusted according to known methods depending on the type and amount of the additives.
- the contraceptive jelly according to the present invention is manufactured by an ordinary method.
- the base material of the contraceptive jelly according to the present invention is not particularly limited as long as it is a commonly used base, and includes, for example, gelatin, pectin, xanthan gum, carrageenan, mouth-to-mouth bean gum, mannan, and cyclodextrin. One or more selected ones can be mentioned.
- the contraceptive jelly according to the present invention contains, for example, a pharmacologically acceptable carrier, a water-soluble polymer base material, and a solubilizing component.
- Pharmaceutically acceptable carriers include, for example, water, ethanol, glycerin, alcohols such as propylene glycol, or mixtures thereof.
- the water-soluble polymer matrix is preferably, for example, a polyethoxylate compound or a cellulose derivative, and most preferably a hydroxyalkyl cellulose containing a lower alkyl (c 2 to c 6 ) component such as ethyl, propyl, or butyl. .
- the contraceptive jelly according to the present invention comprises, for example, adding nicotinamides to a water-soluble polymer such as a cellulose derivative, adding a predetermined amount of a solubilizing agent to the obtained mixed solution, stirring and dissolving the mixture, and adding a predetermined amount of purified water. Stir and mix.
- the obtained contraceptive jelly preferably has a pH of about 3.0 to 5.5 for compatibility with vaginal mucosa.
- Formulation of the contraceptive jelly according to the present invention may be further performed, if necessary, similarly to the above-mentioned effervescent tablets, for example, excipients, binders, disintegrants, lubricants, coloring agents, humectants, thickeners, Preservatives, fragrances, antioxidants, antibacterial preservatives, pH adjusters, etc. may be added.
- excipients for example, excipients, binders, disintegrants, lubricants, coloring agents, humectants, thickeners, Preservatives, fragrances, antioxidants, antibacterial preservatives, pH adjusters, etc.
- the above additives are appropriately selected by those skilled in the art, and the mixing ratio with the active ingredient of the present invention can be appropriately adjusted according to a known method depending on the kind and amount of the additives.
- the contraceptive jelly according to the present invention uses a finger or an applicator to form, for example, a contraceptive device for a child (IUD), a condom for males, a condom for females, and a contraceptiveterrorism.
- a contraceptive device for a child IUD
- a condom for males a condom for females
- a contraceptive conspiracy a contraceptive conspiracy.
- nicotine in the manufacture of thin films by applying them to Z or surfaces or by processing the constituents of the thin films, such as polyethylene, nylon, latex and other similar elastic materials. Amides can also be used by kneading.
- the film-form preparation according to the present invention can be produced by a known method. For example, it can be produced by dissolving nicotinamides, a water-soluble polymer and a polyhydric alcohol in water, drying and solidifying a plurality of times at a predetermined temperature to form a film.
- the water-soluble polymer that constitutes the film layer of the film-form preparation include polyvinyl alcohol, polyethylene oxide, polyacrylamide, cellulose ether, polysaccharide, and soluble starch.
- a partially saponified polyvinyl alcohol having a degree of polymerization of about 300 to 500 is preferable. The lower the degree of polymerization, the lower the strength of the film, and the higher the degree of polymerization, the slower the dissolution rate in the vagina.
- a polyhydric alcohol as a humectant
- a plasticizer such as glycerin and ethylene glycol.
- glycerin and ethylene glycol polyethylene glycol and the like are used.
- Formulation of the film-form preparation according to the present invention may further include, if necessary, as in the case of the effervescent tablet, for example, excipients, binders, disintegrants, lubricants, coloring agents, humectants, thickeners, Preservatives, fragrances, antioxidants, antibacterial preservatives, PH regulators, etc. may be added.
- excipients for example, excipients, binders, disintegrants, lubricants, coloring agents, humectants, thickeners, Preservatives, fragrances, antioxidants, antibacterial preservatives, PH regulators, etc.
- binders for example, excipients, binders, disintegrants, lubricants, coloring agents, humectants, thickeners, Preservatives, fragrances, antioxidants, antibacterial preservatives, PH regulators, etc.
- coloring agents for example, coloring agents, humectants, thickeners, Preservatives
- the contraceptive composition of the present invention is prepared by passing nicotinamide, which is an essential component, according to a conventional method. It can be prepared by blending with various additives known as ordinary external compositions. Although the amount of the additive varies depending on the kind or the form of use of the contraceptive composition of the present invention, it cannot be determined unconditionally, but is prepared by an ordinary method.
- the contraceptive composition of the present invention contains nicotinamides as an active ingredient, and is preferably administered parenterally as a dosage form.
- nicotinamides as an active ingredient
- parenterally for example, vaginal effervescent tablets, jellies, films, vaginal suppositories, ointments, Dosage forms such as solutions, application solutions, and vaginal drops.
- the preferred dose of the contraceptive composition of the present invention cannot be said unconditionally because it differs depending on, for example, the method of administration, the type and activity of the formulated composition, the frequency of use, and the like. Is about 1 to 10 Omg Zkg per day.
- Fresh sperm was obtained from four healthy volunteers. Using this as a sample, lm1 of each sample is dispensed into a 5 ml volume centrifuge tube, and 1.61 nicotinamide solution is added so that the final concentration becomes 5 mM and 25 mM, respectively. did. After incubation for 1 or 2 hours, the detachment of the flagella was observed at a magnification of 600 times using a phase contrast microscope. Nicotinamide compounds 16 types are shown below.
- nicotinamide manufactured by Nacalai Tex Co.
- BSF BSF
- Cremophor RH-60 Pre-mix 2.0 g of the polyethoxylated castor oil at 50 ° C.
- 35 g of propylene glycol was taken, and 0.20 g of methylparaben and 0.20 g of sorbic acid were added thereto.
- the solution was heated to 80 ° C and stirred with a stir bar until the solution became clear. This solution was added to 76.08 g of water taken in another beaker.
- the nicotinamides of the present invention can cut sperm flagella or inhibit sperm motility by contact with sperm.
- the sperm whose flagella have been severed cannot swim up the uterus and cannot be fertilized to obtain a contraceptive effect.
- the contraceptive composition of the present invention does not need to be taken daily like a pill, so it can be used easily, and has no toxicity because it is made of biquinamine, which originally belongs to the vitamin B group. It is safe to use because of its low irritation to the vaginal mucosal lining.
Landscapes
- Health & Medical Sciences (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)
- Epidemiology (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001269485A JP2005053783A (ja) | 2001-09-05 | 2001-09-05 | 避妊薬 |
JP2001-269485 | 2001-09-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003022278A1 true WO2003022278A1 (fr) | 2003-03-20 |
Family
ID=19095296
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2002/008961 WO2003022278A1 (fr) | 2001-09-05 | 2002-09-03 | Contraceptifs |
Country Status (2)
Country | Link |
---|---|
JP (1) | JP2005053783A (fr) |
WO (1) | WO2003022278A1 (fr) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5020811B2 (ja) | 2005-03-16 | 2012-09-05 | 五十嵐 正雄 | 子宮内膜症および子宮腺筋症の治療剤および予防剤 |
CN116096376A (zh) * | 2020-09-08 | 2023-05-09 | 未来生物科学实验室株式会社 | 精子运动性改善剂以及精子运动性改善方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5750917A (en) * | 1980-09-04 | 1982-03-25 | Syntex Inc | Contraceptive composition containing imidazole derivative |
WO1998040057A1 (fr) * | 1997-03-12 | 1998-09-17 | Medical Research Council | Spermicide |
WO1999048902A1 (fr) * | 1998-03-25 | 1999-09-30 | Parker Hughes Institute | Derives de l'azt faisant preuve d'une activite spermicide et antivirale |
-
2001
- 2001-09-05 JP JP2001269485A patent/JP2005053783A/ja active Pending
-
2002
- 2002-09-03 WO PCT/JP2002/008961 patent/WO2003022278A1/fr active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5750917A (en) * | 1980-09-04 | 1982-03-25 | Syntex Inc | Contraceptive composition containing imidazole derivative |
WO1998040057A1 (fr) * | 1997-03-12 | 1998-09-17 | Medical Research Council | Spermicide |
WO1999048902A1 (fr) * | 1998-03-25 | 1999-09-30 | Parker Hughes Institute | Derives de l'azt faisant preuve d'une activite spermicide et antivirale |
Non-Patent Citations (6)
Title |
---|
AKUSHERSTVO I GINEKOL., vol. 35, no. 6, 1959, pages 28 - 30 * |
CHEMICAL ABSTRACTS, vol. 54, 1960, Columbus, Ohio, US; abstract no. 105481, GENIN D.I.: "Nicotinic acid as a spermacide component of chemical contraceptives" XP002904792 * |
CHEMICAL ABSTRACTS, vol. 57, 1962, Columbus, Ohio, US; abstract no. 4356, BRYKOVA Z.I. ET AL.: "Use of sodium bicarbonate and tartaric acid in tablets" XP002904793 * |
CHEMICAL ABSTRACTS, vol. 92, 1980, Columbus, Ohio, US; abstract no. 128683, LI MING-MEI ET AL.: "Synthesis and contraceptive characteristics of (SYM98)-pyridinecarboxamide" XP002904794 * |
MED. PROM. SSSR, vol. 15, no. 12, 1961, pages 43 - 44 * |
T' IEN-CHIN I YAO, vol. 7, no. 8, 1979, pages 354 - 356 * |
Also Published As
Publication number | Publication date |
---|---|
JP2005053783A (ja) | 2005-03-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0719137B1 (fr) | Compositions de tensioactifs visqueuses se presentant sous forme d'emulsions | |
DE69634171T2 (de) | Mikroverkapselte Kaktobacilli für medizinische Anwendungen | |
JP2002537070A (ja) | 生体接着性抗菌性創傷治癒用組成物 | |
EP0650354B1 (fr) | Solutions solides et liquides de substances medicamenteuses peu solubles dans l'eau | |
KR20110125660A (ko) | 가온성 및 무자극성 윤활제 항진균성 겔 조성물 | |
CA2417736A1 (fr) | Dispersions solides de citrate de sildenafil ayant une forte solubilite dans l'eau | |
WO1986006586A1 (fr) | Excipients pharmaceutiques reducteurs du flux transdermique | |
JPH10287588A (ja) | 医薬製剤 | |
JPH1160505A (ja) | 防腐組成物 | |
EP1620069B1 (fr) | Compositions lubrifiantes, fongicides, non-irritatives et chauffantes sous forme de gel | |
JP2523428B2 (ja) | 消炎鎮痛ゲル製剤 | |
JP5474033B2 (ja) | 置換イミダゾール誘導体を含む改良された製剤 | |
WO2005101982A2 (fr) | Composition ophtalmique stable | |
WO1999012545A2 (fr) | Medicaments contenant acyclovir | |
WO2003022278A1 (fr) | Contraceptifs | |
JP2905210B2 (ja) | 経皮、経粘膜吸収促進剤および経皮、経粘膜製剤 | |
JPH0597706A (ja) | アフタ性潰瘍および他の粘膜皮膚障害の処置方法 | |
US2939820A (en) | Aqueous vitamin and mineral compositions | |
IL129140A (en) | The use of an antifungal gel with the release of a high active ingredient for the preparation of a pharmaceutical preparation for the treatment and prevention of cutaneous fungus | |
CN116172888A (zh) | 用于调节肌肤微生态的含氨基酸衍生物的组合物 | |
JPH07118169A (ja) | 抗菌製剤及び抗真菌製剤 | |
CA2173964A1 (fr) | Prevention de l'infection par le vih | |
JPS6383023A (ja) | 薬剤調製物 | |
WO1988003799A1 (fr) | Vehicules pharmaceutiques de reduction du flux transdermique | |
CA2529860A1 (fr) | Composition ophtalmique |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AU AZ BA BB BR BY CA CN CO CR CU DM DZ EC GD GE HU ID IL IN IS JP KG KR KZ LC LK LR LV MA MD MG MK MN MX NO NZ PH PL RO RU SG SI TJ TM TN TT UA UZ VC VN YU |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ UG ZM ZW AM AZ BY KG KZ RU TJ TM AT BE BG CH CY CZ DK EE ES FI FR GB GR IE IT LU MC PT SE SK TR BF BJ CF CG CI GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 69(1) EPC (FORM 1205A OF 12-07-04 |
|
NENP | Non-entry into the national phase |
Ref country code: JP |
|
122 | Ep: pct application non-entry in european phase |