WO1998032465A1 - Composition for the transdermal administration of steroid drugs - Google Patents
Composition for the transdermal administration of steroid drugs Download PDFInfo
- Publication number
- WO1998032465A1 WO1998032465A1 PCT/KR1998/000013 KR9800013W WO9832465A1 WO 1998032465 A1 WO1998032465 A1 WO 1998032465A1 KR 9800013 W KR9800013 W KR 9800013W WO 9832465 A1 WO9832465 A1 WO 9832465A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- drug
- diethylene glycol
- ranges
- absorption promoter
- Prior art date
Links
Classifications
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
Definitions
- the present invention relates to a composition for the transdermal administration of steroid drugs, wherein a mixture of a diethylene glycol ether and a sorbitan ester is used as an absorption promoter; and to a transdermal formulation containing same.
- transdermal drug administration alleviates the aforementioned problems and delivers a drug at a controlled rate for an extended period of prescribed time due to increased bioavailability of the drug which is degraded in the digestive tract.
- Diethyleneglycol monoethyl ether which has been used as a solubilizer in the formulation of naproxen, nitroglycerin, phenylbutazone and prazepa , was also reported to be effective as an absorption promoter in the transdermal administration of theophylline and prostaglandin E2 (Touitou, et al . , International Journal of Pharmaceutics, 20, 159-166(1991); and Watkinson, A. et al . , ibid, 74, 229- 236(1991) ) .
- absorption promoters disclosed in the prior art include: a mixture of linoleic acid and propyleneglycol (European Patent Publication No. 261429); and mixtures of N- (hydroxyethyl)pyrrolidone and methyl laurate, ethanol and glycerol monolaurate, diethylene glycol monoethyl ether and propyleneglycol monolaurate (US Patent Nos. 4,537,776; 4,764,379; and 4,973,468).
- the conventional transdermal formulations may be divided into three types: a reservoir type, a simple matrix type and a multi-layer lamination type.
- the simple matrix type formulation as disclosed in U.S. Patent Nos. 4,314,577; 4,438,139; and 4,839,174, comprises a drug dispersed in a layer made of a pressure-sensitive adhesive matrix.
- Such formulation can be produced at a low cost by a simple process.
- it has the problem that the rate of drug release is high in the initial stage and tapers off sharply thereafter.
- a diethylene glycol monoalkyl ether and a sorbitan ester each of which has been individually known as an absorption promoter having a limited effectiveness, provide a synergistic effect when combined, i.e., a mixture of a diethylene glycol ether and a sorbitan ester has been found to be a remarkably efficient absorption promoter for the transdermal transport of steroid drugs .
- an object of the present invention to provide an improved composition for the transdermal administration of a steroid drug.
- composition for the transdermal administration of a steroid drug comprising: a therapeutically effective amount of the drug; an absorption promoter consisting essentially of a diethylene glycol ether and a sorbitan ester; and a pharmaceutically acceptable adhesive matrix.
- Fig. 1 shows a schematic cross-sectional view of an embodiment of the inventive pharmaceutical formulation for the transdermal delivery of a steroid drug
- Fig. 2 displays the time-dependent changes in the cumulative amount of estradiol transported across the skin of a hairless mouse as a function of the absorption promoter used;
- Fig. 3 depicts the time-dependent changes in the cumulative amount of norethisterone acetate transported across the skin of a hairless mouse as a function of the absorption promoter used;
- Fig. 4 illustrates the time-dependent changes in the cumulative amount of norethisterone acetate transported across human cadaver skin as a function of the absorption promoter used
- Fig. 5 exhibits the time-dependent changes in the cumulative amount of norethisterone acetate transported across human cadaver skin as a function of the contents of sorbitan monolaurate and diethylene glycol monoethyl ether.
- the present invention provides a composition for the transdermal administration of a steroid drug, comprising: the steroid drug; a mixture of diethylene glycol ether and sorbitan ester which is used as an absorption promoter; and a pharmaceutically acceptable adhesive matrix.
- Exemplary steroid drugs for use in the composition of the present invention include estrogens, e.g., estradiol, ethynyl estradiol and estradiol ester; progestogens, e.g., norethisterone, norethisterone acetate, medroxyprogesterone acetate, desogestrel, gestaten and levonorgestrel; androgens, e.g., testosterone, testosterone propionate, testosterone enanthate, testosterone cypionate, methyltestosterone and dihydroepiandrosterone; and a mixture thereof.
- estrogens e.g., estradiol, ethynyl estradiol and estradiol ester
- progestogens e.g., norethisterone, norethisterone acetate, medroxyprogesterone acetate, desogestrel, gestaten and levonorgestrel
- the total amount of the steroid drug used in the inventive composition may range from 0.05 to 30 wt%, preferably, from 0.1 to 10 wt% based on the total weight of the composition.
- the absorption promoter of the present invention is composed of a diethylene glycol monoalkylether and a sorbitan ester mixed in a weight ratio ranging from 1:4 to 4:1, preferably, from 1:2 to 2:1.
- Diethyleneglycol monoalkyl ethers which may be suitably used in the present invention include diethylene glycol monoethyl ether and diethylene glycol monomethyl ether, and suitable sorbitan esters include sorbitan monolaurate and sorbitan monooleate.
- the total amount of the mixture of diethylene glycol ether and sorbitan ester used in the inventive composition may range from 5 to 30 wt%, preferably, from 5 to 25 wt% based on the total weight of the composition, wherein the weight ratio of said two components is kept within the aforementioned range.
- the pharmaceutically acceptable adhesive matrix used in the present invention may be any of those known in the art, e.g., polyacrylate adhesives such as ethyl-, butyl- and 2- ethylhexyl acrylate, polyisobutylene and silicon rubber.
- the composition of the present invention may further comprise flavoring agents, preservatives, anti-oxidants, stabilizers and pigments.
- the transdermal formulation of a steroid drug in accordance with another aspect of the present invention may be constructed using: a protective backing layer which is impermeable to the steroid drug; a drug reservoir layer containing the aforementioned composition of the present invention, one side of which is laminated on the protective backing layer; and a peel layer attached to the other side of the drug reservoir layer, said peel layer being capable of protecting the composition from the environment until it is removed to bring the drug reservoir layer into contact with the skin.
- the formulation of the present invention may further comprise a supplementary adhesive layer which is selected from those known in the art, e.g., a ring-shaped adhesive layer sealably attached to the periphery of the drug reservoir layer and the protective backing layer.
- a supplementary adhesive layer which is selected from those known in the art, e.g., a ring-shaped adhesive layer sealably attached to the periphery of the drug reservoir layer and the protective backing layer.
- Fig. 1 shows a schematic cross-sectional view of an embodiment of the transdermal formulation of the present invention, which comprises peel layer(1), drug reservoir layer(2), protective backing layer(3) and supplementary adhesive layer(4).
- the inventive composition for the transdermal delivery of a steroid drug has advantages in that: it is a simple matrix-type which can be prepared at a low cost; the use of the improved absorption promoter disclosed above makes it possible to maintain a high flux of the drug for an extended period, the apparent drug permeation rate following zero- order kinetics; and the formation of drug crystals is inhibited even at a high drug loading level owing to the use of said improved absorption promoter.
- the dosage administered to a patient by using the composition of the present invention can be controlled by adjusting the contents of the drug and the absorption promoter.
- the flux, or the skin permeation rate (SPR), of a drug through a skin sample was determined by the following procedure.
- a skin sample either human cadaver skin or a skin piece excised from 6 week-old female hairless mouse, was installed in Valia-Chien diffusion cell(Crown Glass, U.S.A. ) such that the stratum corneum of the skin faced outward from the cell, and then a transdermal formulation containing one or more steroid drugs was fixed on the skin.
- 3.4 m-2 of physiological saline solution containing 40% of polyethyleneglycol 400 (Sigma Scientific Co.) was added to the cell and stirred for the whole period of experiment.
- the skin permeation rate (SPR) of the drug through the skin was calculated by regression analysis of the time-dependent cumulative amounts of the drug( ⁇ g/cm 2 /hr) .
- the mixture thus obtained was poured onto an impermeable protective backing layer (Scotchpak 1109, 3M Co . ) to coat a matrix layer having a thickness of lOOO ⁇ m.
- the resulting material consisting of the protective backing layer coated with the matrix layer was dried in an oven by raising the temperature stepwise from 60°C to 120°C.
- the resulting material was cured in open air for 1 hour and a peel layer (Scotchpak 1012, 3M Co.) was laminated thereon.
- the resulting transdermal formulation was stored at room temperature .
- Figs . 2 and 3 show the time-dependent cumulative amounts of estradiol and norethisterone acetate transported across the skin as function of absorption promoter used.
- transdermal delivery compositions were prepared and tested by the procedure of Reference Example 1, except that human cadaver skin was employed in place of the mouse skin, and 4 wt% of norethisterone acetate (NETA) was employed together with the absorption promoter listed in Table 2. The results are shown in Table 2 and Fig. 4.
- NETA norethisterone acetate
- transdermal delivery compositions were prepared and tested by the procedure of Reference Example 1, except that human cadaver skin as well as 0.4 wt% of estradiol and
- the inventive compositions containing a mixture of diethylene glycol monoethyl ether (TC) and sorbitan monolaurate (SML) having a TC to SML weight ratio in the range of 0.5 to 2 (Examples 1, 2 and 3 ) as the absorption promoter exhibited markedly enhanced permeation rates of the drugs across human cadaver skin, as compared with those observed in Comparative Examples 1-6. The permeation rates follow apparent zero- order kinetics. Further, drug crystals were not observed in Examples 1 , 2 and 3.
- transdermal delivery compositions were prepared and tested by the procedure of Reference Example 1, except that human cadaver skin and 3.5 wt% of testosterone were employed together with the absorption promoters listed Table 4.
- transdermal delivery compositions were prepared and tested by the procedure of Reference Example 1, except that human cadaver skin and 0.8 wt% of estradiol were employed together with the absorption promoters listed Table
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU58820/98A AU727811B2 (en) | 1997-01-27 | 1998-01-23 | Composition for the transdermal administration of steroid drugs |
BR9807009-6A BR9807009A (en) | 1997-01-27 | 1998-01-23 | Composition for administration of steroid drug transfer |
EP98902269A EP1001812A1 (en) | 1997-01-27 | 1998-01-23 | Composition for the transdermal administration of steroid drugs |
JP10531848A JP2000508349A (en) | 1997-01-27 | 1998-01-23 | Composition for transdermal administration of steroid drug |
CA002277970A CA2277970A1 (en) | 1997-01-27 | 1998-01-23 | Composition for the transdermal administration of steroid drugs |
US09/746,448 US20010023261A1 (en) | 1997-01-27 | 2000-12-12 | Novel composition for the transdermal administration of drugs |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1019970002233A KR100215027B1 (en) | 1997-01-27 | 1997-01-27 | Composition for transdermal administration of steroid drugs and formulation containing same |
KR1997/2233 | 1997-01-27 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US29325599A Continuation-In-Part | 1997-01-27 | 1999-04-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998032465A1 true WO1998032465A1 (en) | 1998-07-30 |
Family
ID=19495561
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR1998/000013 WO1998032465A1 (en) | 1997-01-27 | 1998-01-23 | Composition for the transdermal administration of steroid drugs |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP1001812A1 (en) |
JP (1) | JP2000508349A (en) |
KR (1) | KR100215027B1 (en) |
CN (1) | CN1244806A (en) |
AR (1) | AR011577A1 (en) |
AU (1) | AU727811B2 (en) |
BR (1) | BR9807009A (en) |
CA (1) | CA2277970A1 (en) |
ID (1) | ID19755A (en) |
RU (1) | RU2176499C2 (en) |
TW (1) | TW537899B (en) |
WO (1) | WO1998032465A1 (en) |
Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
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WO1999062557A1 (en) * | 1998-06-02 | 1999-12-09 | Lg Chemical Limited | Composition for the transdermal administration of non-steroidal anti-inflammatory drugs |
WO2000040230A2 (en) * | 1999-01-06 | 2000-07-13 | Cedars-Sinai Medical Center | Hormone replacement for breast cancer patients |
WO2002066018A2 (en) * | 2001-02-19 | 2002-08-29 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing testosterone and method for the production thereof |
FR2848112A1 (en) * | 2002-12-10 | 2004-06-11 | Besins Int Belgique | PHARMACEUTICAL COMPOSITION FOR TRANSDERMAL OR TRANSMUCTIVE DELIVERY COMPRISING AT LEAST ONE PROGESTATIVE AND / OR AT LEAST ONE OESTROGEN, PREPARATION METHOD AND USES THEREOF |
WO2004054544A1 (en) * | 2002-12-10 | 2004-07-01 | Besins International Belgique | Pharmaceutical composition for transdermal or transmucous administration comprising a progestin or an estrogen, method for preparing same and uses thereof |
WO2006061340A2 (en) * | 2004-12-10 | 2006-06-15 | Grünenthal GmbH | Stable, hormone-containing (intermediate) product |
US7611727B2 (en) | 2003-02-20 | 2009-11-03 | Besins International Belgique | Pharmaceutical composition for transdermal or transmucous administration |
US8633178B2 (en) | 2011-11-23 | 2014-01-21 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US8933059B2 (en) | 2012-06-18 | 2015-01-13 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US9125816B2 (en) | 2000-08-30 | 2015-09-08 | Besins Healthcare Inc. | Pharmaceutical composition and method for treating hypogonadism |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US9289382B2 (en) | 2012-06-18 | 2016-03-22 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US9931349B2 (en) | 2016-04-01 | 2018-04-03 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
US10052386B2 (en) | 2012-06-18 | 2018-08-21 | Therapeuticsmd, Inc. | Progesterone formulations |
US10080760B2 (en) | 2009-10-27 | 2018-09-25 | Besins Healthcare Luxembourg Sarl | Transdermal pharmaceutical compositions comprising active agents |
US10206932B2 (en) | 2014-05-22 | 2019-02-19 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US10258630B2 (en) | 2014-10-22 | 2019-04-16 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10286077B2 (en) | 2016-04-01 | 2019-05-14 | Therapeuticsmd, Inc. | Steroid hormone compositions in medium chain oils |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
US10471148B2 (en) | 2012-06-18 | 2019-11-12 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable PK profile |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
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KR100403051B1 (en) * | 2000-07-25 | 2003-10-23 | 일양약품주식회사 | Composition of matrix type patch for transdermal testosterone delivery and process for preparing the same |
JP4422430B2 (en) * | 2003-05-14 | 2010-02-24 | 帝國製薬株式会社 | External patch containing estrogen and / or progestogen |
GB0409498D0 (en) * | 2004-04-28 | 2004-06-02 | Hunter Fleming Ltd | Transdermal steroid formulation |
CN1313084C (en) * | 2004-11-05 | 2007-05-02 | 郑会义 | Percutaneous contraceptive drugs delivery system and method |
JP4969050B2 (en) * | 2005-01-07 | 2012-07-04 | ロート製薬株式会社 | Topical skin preparation |
JP2007045808A (en) * | 2005-01-07 | 2007-02-22 | Rohto Pharmaceut Co Ltd | Skin care preparation |
WO2013054809A1 (en) * | 2011-10-14 | 2013-04-18 | 大正製薬株式会社 | External preparation for skin |
JP5521025B2 (en) * | 2012-12-21 | 2014-06-11 | 日本精化株式会社 | Penetration enhancer |
KR101968873B1 (en) * | 2018-09-21 | 2019-04-29 | 아이큐어 주식회사 | Cosmetic composition comprising peptide derived from Botulinum toxin having improved cell penetrating ability |
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- 1997-01-27 KR KR1019970002233A patent/KR100215027B1/en not_active IP Right Cessation
-
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- 1998-01-23 BR BR9807009-6A patent/BR9807009A/en not_active Application Discontinuation
- 1998-01-23 RU RU99118582/14A patent/RU2176499C2/en not_active IP Right Cessation
- 1998-01-23 JP JP10531848A patent/JP2000508349A/en active Pending
- 1998-01-23 CA CA002277970A patent/CA2277970A1/en not_active Abandoned
- 1998-01-23 EP EP98902269A patent/EP1001812A1/en not_active Withdrawn
- 1998-01-23 AU AU58820/98A patent/AU727811B2/en not_active Ceased
- 1998-01-23 CN CN98802010A patent/CN1244806A/en active Pending
- 1998-01-23 WO PCT/KR1998/000013 patent/WO1998032465A1/en not_active Application Discontinuation
- 1998-01-26 TW TW087101089A patent/TW537899B/en active
- 1998-01-27 ID IDP980113A patent/ID19755A/en unknown
- 1998-01-27 AR ARP980100352A patent/AR011577A1/en not_active Application Discontinuation
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Cited By (66)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999062557A1 (en) * | 1998-06-02 | 1999-12-09 | Lg Chemical Limited | Composition for the transdermal administration of non-steroidal anti-inflammatory drugs |
WO2000040230A2 (en) * | 1999-01-06 | 2000-07-13 | Cedars-Sinai Medical Center | Hormone replacement for breast cancer patients |
WO2000040230A3 (en) * | 1999-01-06 | 2001-05-17 | Cedars Sinai Medical Center | Hormone replacement for breast cancer patients |
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Also Published As
Publication number | Publication date |
---|---|
JP2000508349A (en) | 2000-07-04 |
BR9807009A (en) | 2000-03-14 |
AU727811B2 (en) | 2000-12-21 |
TW537899B (en) | 2003-06-21 |
CA2277970A1 (en) | 1998-07-30 |
KR19980066583A (en) | 1998-10-15 |
CN1244806A (en) | 2000-02-16 |
EP1001812A1 (en) | 2000-05-24 |
RU2176499C2 (en) | 2001-12-10 |
ID19755A (en) | 1998-07-30 |
AU5882098A (en) | 1998-08-18 |
KR100215027B1 (en) | 1999-08-16 |
AR011577A1 (en) | 2000-08-30 |
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