WO2001041771A2 - Acetylsalicylsäure enthaltendes transdermales system zur behandlung von migräne - Google Patents
Acetylsalicylsäure enthaltendes transdermales system zur behandlung von migräne Download PDFInfo
- Publication number
- WO2001041771A2 WO2001041771A2 PCT/EP2000/012092 EP0012092W WO0141771A2 WO 2001041771 A2 WO2001041771 A2 WO 2001041771A2 EP 0012092 W EP0012092 W EP 0012092W WO 0141771 A2 WO0141771 A2 WO 0141771A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acetylsalicylic acid
- tts
- migraine
- treatment
- serotonin
- 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
- 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
-
- 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
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- Transdermal system for the treatment of migraines containing acetylsalicylic acid.
- the present invention relates to the use of acetylsalicylic acid for the treatment of migraines and other serotonin-dependent, platelet-mediated diseases, the administration of the active ingredient taking place transdermally.
- the invention encompasses processes in which acetylsalicylic acid is administered to the human skin by a transdermal therapeutic system for the purpose of prophylactic treatment of the migraine.
- the invention further relates to the use of acetylsalicylic acid for the production of transdermal therapeutic systems for migraine prophylaxis, and transdermal therapeutic systems containing acetylsalicylic acid which are suitable for migraine prophylaxis.
- Migraines are a multifactorial occurrence, triggered by different exogenous and endogenous causes.
- the underlying biochemical processes are largely known, although the pathophysiological processes as a whole have not been clarified.
- a central role in migraines is attributed to the abnormal regulation of cerebral blood flow. The latter is controlled by a number of different factors, e.g. B. biogenic
- NSAIDs non-steroidal anti-inflammatory drugs
- serotonin antagonists serotonin antagonists
- acetylsalicylic acid ASA
- ASA acetylsalicylic acid
- the use of ASA for migraine prophylaxis is based on the assumption that ASA as a prostaglandin synthesis inhibitor influences the metabolism of certain cellular blood components, especially thrombocytes, and reduces their biochemical reactivity. In this way, there can be a quantitative change in the neurotransmitters and hormones produced by these blood cells come. An increased thrombocytic serotonin release, such as occurs at the beginning of a migraine attack, could be favorably influenced by active ingredients such as ASA.
- Oral administration of ASA has several disadvantages.
- SS salicylic acid
- the inhibition of platelet function - which is also important in migraine therapy - is mediated by ASA and not by SS (W. Horsch, "Die Salicylate", Pharmazie 34, 585-604, 1979). This leaves a significant portion of the dose administered unused.
- oral administration of ASA especially if it extends over long periods, often leads to gastrointestinal side effects, e.g. B. gastric bleeding.
- ASA-containing transdermal therapeutic systems which allow the application of ASA bypassing the gastrointestinal tract, have already been described.
- TTS transdermal therapeutic systems
- the last-mentioned publication primarily refers to the use in antithrombotic therapy and in colon cancer prophylaxis.
- ASA topical or transdermal use of ASA, also in the form of ointments, gels and. the like , also described for the therapeutic treatment of various other disease states.
- the object of the present invention was to demonstrate a method for the medicinal prophylaxis of migraines which has few side effects and is therefore suitable for long-term use, which is simple and patient-friendly to use and at the same time effective in preventing migraine conditions, but which on the other hand does not have the known disadvantages associated with oral administration of ASA.
- acetylsalicylic acid is administered transdermally, preferably using a transdermal therapeutic system according to the invention.
- the migraine frequency is significantly reduced. It is significant that - unlike with oral administration - the ASA level in the blood plasma remains low and does not exceed 0.5 ⁇ g / l (cf. Example 3). Average acetylsalicylic acid plasma levels of less than 10 ng / ml can be achieved during the day.
- an increase in the trigger threshold for migraine attacks was surprisingly found. Avoiding high ASA plasma levels also reduces the risk of systemic side effects.
- average salicylate blood plasma levels of at least 20 ng / l, preferably from 100 to 400 ng / ml, can be achieved in humans during the course of the day (cf. Example 3). These values indirectly indicate a very efficient absorption of ASA through the skin.
- the present invention provides an effective, cost-effective, low-side effect and patient- or patient- user-friendly treatment method for migraine prophylaxis.
- the therapy method proposed by the invention is suitable for both long-term prophylaxis and one
- Acute prophylaxis of migraines is also possible to combine the transdermal administration of TTS according to the invention with conventional migraine prophylaxis and other therapeutic regimens. Even if the present invention is primarily aimed at the treatment or prophylaxis of migraines, this does not exclude that it is also applicable to the treatment of other serotonin-dependent, platelet-mediated diseases.
- acetylsalicylic acid is administered in combination with one or more other active substances and / or in combination with auxiliary substances.
- Particularly suitable as further active substances are those which likewise have an analgesic effect and can be absorbed transdermally.
- Active substances from the following groups are preferably considered for a combined administration with ASA in a TTS: serotonin antagonists, non-selective serotonin derivatives, simple analgesics, analgesic combinations, ergotamine derivatives, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, Phenothiazines, opiate analgesics, beta blockers, calcium channel blockers, tricyclic antidepressants, antiepileptics and monoamine oxidase inhibitors.
- serotonin antagonists non-selective serotonin derivatives
- simple analgesics simple analgesics
- analgesic combinations ergotamine derivatives
- non-steroidal anti-inflammatory drugs (NSAIDs) non-steroidal anti-inflammatory drugs
- Phenothiazines corticosteroids
- Phenothiazines Phenothiazines
- opiate analgesics beta blockers
- calcium channel blockers
- the ASA-containing TTS is preferably used in such a way that the application time, based on a single TTS, is at most one week, preferably 1 to 3 days. A continuous daily application over a NEN period of at least 16 hours is particularly advantageous.
- the amount of ASA released to the skin by the TTS within one day is preferably in a range between 1 mg and 100 mg.
- TTS particularly suitable as TTS, which according to the invention can be used for migraine prophylaxis using the active ingredient ASS, are TTS of the matrix type, which are composed of a backing layer which is essentially impermeable to active ingredients and moisture, one or more active ingredient-containing matrix layer (s), and have a removable protective layer.
- TTS of the matrix type which are composed of a backing layer which is essentially impermeable to active ingredients and moisture, one or more active ingredient-containing matrix layer (s), and have a removable protective layer.
- acetylsalicylic acid is predominantly present in crystalline form in at least one of the matrix layers and in which at least part of the active ingredient acetylsalicylic acid is present in crystalline form as a stable
- anhydrous modification which melts at above 132 ° C. can advantageously be used.
- ASS crystals with a diameter of less than about 50-100 ⁇ m are particularly advantageous.
- the TTS according to the invention can contain further active ingredients which have already been mentioned above. These can either be located together with acetylsalicylic acid in the same matrix layer or in one or more separate matrix layers. Embodiments are particularly preferred in which the active substances are present in at least two matrices that are separate from one another and are released at mutually independent release rates.
- the skin permeation rates that can be achieved with the TTS according to the invention, based on ASA, are preferably in the range of 0.02-2 mg / cm 2 d, particularly preferably in the range of 0.1-0.4 mg / cm 2 d ,
- the matrix base material of the TTS according to the invention is primarily copolymers containing acrylic acid esters, and also mixtures of rubbers and resins, polyvinyl acetate, silicone polymers and many other materials, the use of which is harmless to human skin.
- the active ingredient-containing polymer matrix can additionally contain auxiliary substances and additives, e.g. B. fillers such as titanium dioxide, zinc oxide, chalk, activated carbon, finely divided silicon dioxide, and skin permeation-promoting additives which are known to the person skilled in the art.
- auxiliary substances and additives e.g. B. fillers such as titanium dioxide, zinc oxide, chalk, activated carbon, finely divided silicon dioxide, and skin permeation-promoting additives which are known to the person skilled in the art.
- liquid additives such as short-chain alcohols, triglycerides, cholesterol, cineol, delta-tocopherol, diethylene glycol, diethylene glycol monoethyl ether, diisopropyl adipate, dimethyldecylphosphoxide, dimethylisosorbide, dimethyllauroylamide, dodecylsulfoxide, ethylacetylsulfoxide, ethylacetylsulfoxide, and other ethylenethylacid sulfates and aliphatic esters, ethylene glycol, ethylene glycol monolaurate and other esters and ethers of ethylene glycol and propylene glycol, 2-octyldodecanol, low-viscosity paraffin, glycerol, glycerol monooleate, glycerol monostearate, hydrogenated castor oil, isopropyl myristate, isopropyl palmitate, lauric
- the reactivity of the active ingredient acetylsalicylic acid with esters and acids as well as alcohols must be taken into account in individual cases, which limits the use of these substances.
- Numerous plastic materials which are characterized by strength and diffusion resistance are suitable for the formation of the backing layer, especially polyester, polyvinyl chloride, ethylene vinyl acetate, vinyl acetate, polyethylene, polypropylene, cellulose dervates and many others.
- the back layer can be vapor-coated with metals or other diffusion-blocking additives, such as silicon dioxide, aluminum oxide or the like.
- the rear layer can also be painted skin-colored on the outside to improve acceptance, or it can be treated in some other way to improve the external appearance.
- the removable protective layer to be removed before the application of the TTS to the skin can be made from polyester material, but also from any other plastics suitable for use on the skin, e.g. B. from polyvinyl chloride, ethylene vinyl acetate, vinyl acetate, polyethylene, polypropylene, cellulose derivatives and many others. As with the production of the backing layer, additional vapor deposition with diffusion-blocking substances can also take place in the protective layer.
- Plastoid ® B 8.25% The details indicate the respective proportions by mass, based on the total mass of the active substance matrix.
- the ASA release was determined using the "paddle-over-disk" method of the USP.
- the content of acetylsalicylic acid and salicylic acid in the blood plasma was determined by GC-MS. While the acetylsalicylic acid content remained below the detection limit of 6 ng / ml at both times, the salicylic acid level was 72 ⁇ 18 ng / ml on day 10 and 157 ng / ml on day 14.
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002393748A CA2393748A1 (en) | 1999-12-11 | 2000-12-01 | Transdermal system containing acetylsalicylic acid for treatment of migraine |
EP00987336A EP1235580A2 (de) | 1999-12-11 | 2000-12-01 | Acetylsalicylsäure enthaltendes transdermales system zur behandlung von migräne |
KR1020027007228A KR20020058087A (ko) | 1999-12-11 | 2000-12-01 | 편두통 치료용 아세틸살리실산 함유 경피 치료 시스템 |
AU23618/01A AU2361801A (en) | 1999-12-11 | 2000-12-01 | Transdermal system containing acetylsalicylic acid for treatment of migraine |
JP2001543116A JP2003516356A (ja) | 1999-12-11 | 2000-12-01 | 偏頭痛の処置のためのアセチルサリチル酸含有経皮システム |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19959913A DE19959913A1 (de) | 1999-12-11 | 1999-12-11 | Acetylsalicylsäure enthaltendes transdermales System zur Behandlung von Migräne |
DE19959913.0 | 1999-12-11 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001041771A2 true WO2001041771A2 (de) | 2001-06-14 |
WO2001041771A3 WO2001041771A3 (de) | 2001-12-27 |
Family
ID=7932378
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2000/012092 WO2001041771A2 (de) | 1999-12-11 | 2000-12-01 | Acetylsalicylsäure enthaltendes transdermales system zur behandlung von migräne |
Country Status (8)
Country | Link |
---|---|
US (1) | US20030008852A1 (de) |
EP (1) | EP1235580A2 (de) |
JP (1) | JP2003516356A (de) |
KR (1) | KR20020058087A (de) |
AU (1) | AU2361801A (de) |
CA (1) | CA2393748A1 (de) |
DE (1) | DE19959913A1 (de) |
WO (1) | WO2001041771A2 (de) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1962837A4 (de) * | 2005-12-20 | 2011-12-14 | Teikoku Pharma Usa Inc | Verfahren zur transdermalen verabreichung eines indol-serotonin-rezeptoragonisten und transdermale zusammensetzungen zur verwendung darin |
PL2493457T3 (pl) | 2009-10-30 | 2018-01-31 | Ix Biopharma Ltd | Szybko rozpuszczalna stała postać dawkowana |
US20140083878A1 (en) * | 2012-09-21 | 2014-03-27 | Mylan Inc. | Transdermal drug delivery device |
KR20160001419A (ko) * | 2014-06-27 | 2016-01-06 | 포항공과대학교 산학협력단 | 양이온성 분자 수송체 및 음이온성 생리활성 물질을 포함하는 피부 투과용 조성물 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4218445A (en) * | 1978-05-08 | 1980-08-19 | Kasthuri Thirumalachar Mandaya | N,N'Dibenzylethylenediamine-diacetylsalicylate, a novel chemotherapeutic agent for pain relief by external application |
DE4332093A1 (de) * | 1993-09-22 | 1995-03-23 | Lohmann Therapie Syst Lts | Transdermales therapeutisches System mit dem Wirkstoff Acetylsalicylsäure |
US5401730A (en) * | 1990-07-06 | 1995-03-28 | The Hope Heart Institute | Method for reducing platelet aggregation |
WO1997004759A1 (en) * | 1995-07-27 | 1997-02-13 | Cal International Limited | Transdermal patch containing aspirin |
US5736126A (en) * | 1996-03-15 | 1998-04-07 | Van Engelen; H. Wayne | Liquid transdermal analgesic |
WO2001002015A1 (en) * | 1999-07-01 | 2001-01-11 | The University Of Georgia Research Foundation, Inc. | Composition and method for enhanced transdermal absorption of nonsteroidal anti-inflammatory drugs |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3598122A (en) * | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
US4219548A (en) * | 1978-09-01 | 1980-08-26 | The Procter & Gamble Company | Topical anti-inflammatory composition |
DE4416927C1 (de) * | 1994-05-13 | 1995-08-31 | Lohmann Therapie Syst Lts | Vorrichtung zur Abgabe von Wirkstoffen aus Haftschmelzklebern, Verfahren zu ihrer Herstellung und ihre Verwendung |
DE19701059C2 (de) * | 1997-01-15 | 2000-12-21 | Lohmann Therapie Syst Lts | Acetylsalicylsäure enthaltendes transdermales therapeutisches System mit Resorptionsverstärkung |
US5855907A (en) * | 1997-03-24 | 1999-01-05 | Peyman; Gholam A. | Method of treatment of migraine |
-
1999
- 1999-12-11 DE DE19959913A patent/DE19959913A1/de not_active Withdrawn
-
2000
- 2000-12-01 CA CA002393748A patent/CA2393748A1/en not_active Abandoned
- 2000-12-01 JP JP2001543116A patent/JP2003516356A/ja active Pending
- 2000-12-01 EP EP00987336A patent/EP1235580A2/de not_active Withdrawn
- 2000-12-01 WO PCT/EP2000/012092 patent/WO2001041771A2/de not_active Application Discontinuation
- 2000-12-01 US US10/149,205 patent/US20030008852A1/en not_active Abandoned
- 2000-12-01 AU AU23618/01A patent/AU2361801A/en not_active Abandoned
- 2000-12-01 KR KR1020027007228A patent/KR20020058087A/ko not_active Application Discontinuation
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4218445A (en) * | 1978-05-08 | 1980-08-19 | Kasthuri Thirumalachar Mandaya | N,N'Dibenzylethylenediamine-diacetylsalicylate, a novel chemotherapeutic agent for pain relief by external application |
US5401730A (en) * | 1990-07-06 | 1995-03-28 | The Hope Heart Institute | Method for reducing platelet aggregation |
DE4332093A1 (de) * | 1993-09-22 | 1995-03-23 | Lohmann Therapie Syst Lts | Transdermales therapeutisches System mit dem Wirkstoff Acetylsalicylsäure |
WO1997004759A1 (en) * | 1995-07-27 | 1997-02-13 | Cal International Limited | Transdermal patch containing aspirin |
US5736126A (en) * | 1996-03-15 | 1998-04-07 | Van Engelen; H. Wayne | Liquid transdermal analgesic |
WO2001002015A1 (en) * | 1999-07-01 | 2001-01-11 | The University Of Georgia Research Foundation, Inc. | Composition and method for enhanced transdermal absorption of nonsteroidal anti-inflammatory drugs |
Also Published As
Publication number | Publication date |
---|---|
DE19959913A1 (de) | 2001-06-28 |
CA2393748A1 (en) | 2001-06-14 |
JP2003516356A (ja) | 2003-05-13 |
KR20020058087A (ko) | 2002-07-12 |
WO2001041771A3 (de) | 2001-12-27 |
EP1235580A2 (de) | 2002-09-04 |
US20030008852A1 (en) | 2003-01-09 |
AU2361801A (en) | 2001-06-18 |
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