LU86068A1 - PERCUTANEOUS ANESTHETIC COMPOSITION FOR TOPICAL USE AND METHOD OF APPLICATION - Google Patents
PERCUTANEOUS ANESTHETIC COMPOSITION FOR TOPICAL USE AND METHOD OF APPLICATION Download PDFInfo
- Publication number
- LU86068A1 LU86068A1 LU86068A LU86068A LU86068A1 LU 86068 A1 LU86068 A1 LU 86068A1 LU 86068 A LU86068 A LU 86068A LU 86068 A LU86068 A LU 86068A LU 86068 A1 LU86068 A1 LU 86068A1
- Authority
- LU
- Luxembourg
- Prior art keywords
- composition
- composition according
- amethocaine
- anesthetic
- weight
- Prior art date
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- 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
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
Abstract
Description
te * 1 L'invention concerne des compositions pharmaceutiques contenant de 1'améthocaine.The invention relates to pharmaceutical compositions containing amethocaine.
L'améthocaine ou p-bytylamino benzoate de 2-diméthylamino éthyle, est utilisée en préparations topiques pour produire une anesthésie de surface. Les précédentes tentatives d’obtention d'une anesthésie percutanée topique, dans laquelle l'agent anesthésique doit pénétrer le stratum corneum, se sont heurtées à de nombreuses difficultés : . > 1) de hautes concentrations en principe actif (pouvant attein- * dre 33 %) étaient nécessaires.Amethocaine or 2-dimethylamino ethyl p-bytylamino benzoate, is used in topical preparations to produce surface anesthesia. Previous attempts to obtain topical percutaneous anesthesia, into which the anesthetic agent must penetrate the stratum corneum, have encountered many difficulties:. > 1) high concentrations of active ingredient (up to * 33%) were necessary.
2) les compositions précédemment obtenues étaient inséparables d'effets secondaires inacceptables.2) the compositions previously obtained were inseparable from unacceptable side effects.
3) les compositions précédemment obtenues exigeaient l'emploi de pansements occlusifs.3) the compositions previously obtained required the use of occlusive dressings.
4) les compositions précédemment obtenues nécessitaient une période d'attente prolongée avant de conférer l'anesthésie percutanée attendue.4) the compositions previously obtained required an extended waiting period before imparting the expected percutaneous anesthesia.
L'améthocaine a été jusqu'ici dispersée, soit dans un mélange d'éthanol ou d'isopropanol (45 %), de glycérine (10 %) et d'eau (45 %), soit dans une pommade hydrophile^ (95 %) ou dans de la · vaseline (95 %) ou encore dans lë DMSO (diméthylsulfoxyde).Amethocaine has so far been dispersed, either in a mixture of ethanol or isopropanol (45%), glycerin (10%) and water (45%), or in a hydrophilic ointment ^ (95% ) or in vaseline (95%) or in DMSO (dimethyl sulfoxide).
Les formulations contenant le mélange éthanol-(ou isopropanol)-glycérine-eau ont tendance à être très "mobiles" de nature et, par conséquent, la délimitation du site à traiter est difficile. De plus ces solutions ne possèdent qu'une stabilité limitée.Formulations containing the ethanol- (or isopropanol) -glycerin-water mixture tend to be very "mobile" in nature and, therefore, delimitation of the site to be treated is difficult. In addition, these solutions have only limited stability.
Les autres formulations possèdent des inconvénients similaires.The other formulations have similar drawbacks.
i * 2 >i * 2>
Celles qui contiennent des pommades hydrophiles ou de la vase-’ line, retardent l'action de l'effet anesthésique, tandis que les compositions contenant du DMSO provoquent une douloureuse dislocation à la surface de l'épiderme.Those containing hydrophilic ointments or mud-line, delay the action of the anesthetic effect, while the compositions containing DMSO cause a painful dislocation on the surface of the epidermis.
Selon un aspect de l'invention, il est proposé une composition pour l'application locale, comprenant : de 1'améthocaine, un agent gélifiant aqueux et de l'eau dans laquelle se forme le . gel, 1'améthocaine étant fortement et complètement maintenue en phase solide discontinue, de telle façon‘que dans ladite composition 1 *améthocaine soit protégée de l'hydrolyse pendant ’ le stockage, mais que lorsque la composition est appliquée sur la peau, 11améthocaine fonde et devienne disponible pour l'ab-sorDtion.According to one aspect of the invention, there is provided a composition for local application, comprising: amethocaine, an aqueous gelling agent and water in which it is formed. gel, the amethocaine being strongly and completely maintained in the discontinuous solid phase, in such a way that in said composition the amethocaine is protected from hydrolysis during storage, but that when the composition is applied to the skin, the amethocaine melts and become available for ab-sorDtion.
ss
Selon un autre aspect de la présente invention, il est proposé une composition à usage d'anesthésique local percutané, comprenant un anesthésique, un agent gélifiant aqueux pour stabiliser l'anesthésique et· de l'eau, la composition étant telle que, lors de l'emploi, l'anesthésique fonde et se disperse à travers le gel pour provoquer la pénétration cutanée.According to another aspect of the present invention, there is provided a composition for use in percutaneous local anesthetic, comprising an anesthetic, an aqueous gelling agent for stabilizing the anesthetic and · water, the composition being such that, when use, the anesthetic melts and disperses through the gel to cause skin penetration.
L'invention comprend également le procédé, pour produire 1'anesthésie locale percutanée à l'aide de la composition ci-dessus définie, en quantité efficace, sur une région intacte de la peau.The invention also includes the method for producing local percutaneous anesthesia using the above defined composition, in an effective amount, on an intact region of the skin.
La présente invention propose une composition contenant de 1 'améthocaine qui s'étale peu ou pas du tout après l'application sur la peau. La formulation est protégée par l'application d'un pansement non absorbant convenable (occlusif ou non) et laissée en contact avec la peau pendant une période minimum c de 20 minutes. Puis le pansement et l’application sont retirés avant de procéder à l'acte chirurgical. La composition produit un effet anesthésique profond, suffisamment pénétrant pour Λ / /7 ’ 3 t , bloquer les récepteurs nociceptifs sous-jacents (récepteurs de la douleur), procurant ainsi la possibilité d'actes indolores : prélèvements de greffes épidermiques dans toute leur épaisseur, pénétration de la peau par des aiguilles à injection (par exemple, prise de sang) et autres procédés chirurgicaux mineurs.The present invention provides a composition containing 1 amethocaine which spreads little or not at all after application to the skin. The formulation is protected by the application of a suitable non-absorbent dressing (occlusive or not) and left in contact with the skin for a minimum period of 20 minutes. Then the dressing and application are removed before performing the surgical procedure. The composition produces a deep anesthetic effect, sufficiently penetrating for Λ / / 7 '3 t, blocking the underlying nociceptive receptors (pain receptors), thus providing the possibility of painless acts: samples of epidermal grafts throughout their thickness , penetration of the skin by injection needles (eg, blood test) and other minor surgical procedures.
La composition évite l'usage d'infiltrations anesthésiques locales dans de telles circonstances, et peut être aisément appliquée par un personnel non médical.. 'The composition avoids the use of local anesthetic infiltrations in such circumstances, and can be easily applied by non-medical personnel.
Selon la présente invention, la composition contenant de 1 ' améthocaine pour l'anesthésie locale percutanée, peut comprendre là 7 ÿ, et de préférence 4 %, d'améthocaine dispersée dans un gel aqueux, tel que 0,5 à 2 % -de carbomère * ou 3 à 10 % de méthyl cellulose et 81 à 94,5 % d'eau ; ces pourcentages sont exprimés en poids, par rapport au poids total de la composition.According to the present invention, the composition containing 1 amethocaine for percutaneous local anesthesia, can comprise there 7 ÿ, and preferably 4%, of amethocaine dispersed in an aqueous gel, such as 0.5 to 2%. carbomer * or 3 to 10% methyl cellulose and 81 to 94.5% water; these percentages are expressed by weight, relative to the total weight of the composition.
» L ' améthocaine en poudre est répartie dans le gel qui ne doit pas contenir d'autre phase lipophile. La structure cristalline (gros cristaux) dans un support de gel visqueux, stabilise 1 ' améthocaine en retardant sa dissolution et donc l'hydrolyse alcaline de son groupement ester, sous réserve que l'on n'excède pas une température de 30 °C. L'améthocaine fond aux environs de 41 °C, mais dans la composition, son point de fusion est abaissé à 30-32° C.The amethocaine powder is distributed in the gel which must not contain any other lipophilic phase. The crystalline structure (large crystals) in a viscous gel support stabilizes the amethocaine by delaying its dissolution and therefore the alkaline hydrolysis of its ester group, provided that a temperature of 30 ° C. is not exceeded. Amethocaine melts around 41 ° C, but in the composition, its melting point is lowered to 30-32 ° C.
vv
La température cutanée est habituellement aux environs de ' 32° C. Quand la composition est appliquée à la surface de la peau, les gros cristaux d'améthocaine fondent lentement et se dispersent sous forme de minuscules gouttelettes huileuses, dans le gel. L'améthocaine est ainsi présente sous forme moléculaire, et sous réserve qu'aucune autre phase lipophile ne soit présente, ces gouttelettes huileuses sont hautement pénétrantes dans la peau et dans se‘s sous-structures.The skin temperature is usually around 32 ° C. When the composition is applied to the surface of the skin, the large amethocaine crystals slowly melt and disperse as tiny oily droplets in the gel. Amethocaine is thus present in molecular form, and provided that no other lipophilic phase is present, these oily droplets are highly penetrating in the skin and in its substructures.
> λ 4 *> λ 4 *
La présence de phases lipophiles étrangères obligerait à augmenter les concentrations en améthocaine pour maintenr une efficacité thérapeutique similaire.The presence of foreign lipophilic phases would make it necessary to increase the concentrations of amethocaine in order to maintain a similar therapeutic efficacy.
Il n'est pas nécessaire d'inclure un conservateur dans la composition, en raison de la propriété antimicrobienne de 1'améthocaine.It is not necessary to include a preservative in the composition, due to the antimicrobial property of amethocaine.
La composition peut être préparée par. des .moyens techniques conventionnels. Par exemple, 1'améthocaine peut être ajoutée à un gel formé de carbomère ou de méthyl cellulose, et soi-• gneusement mélangée. Alternativement, on peut former le sel de sodium du carbomère, selon les instructions du fabricant. Dans ces conditions, la composition peut être préparée comme ‘ précédemment, ou bien, 1'améthocaine peut être ajoutée et dispersée dans l'eau, avant l'addition du sel de sodium du carbopol, le tout étant soigneusement mélangé jusqu'à formation du gel.The composition can be prepared by. conventional technical means. For example, amethocaine can be added to a gel made of carbomer or methyl cellulose, and thoroughly mixed. Alternatively, the sodium salt of the carbomer can be formed, according to the manufacturer's instructions. Under these conditions, the composition can be prepared as above, or else, amethocaine can be added and dispersed in water, before the addition of the sodium salt of carbopol, the whole being thoroughly mixed until formation of the gel.
I ,I,
Les compositions selon l'invention sont aussi facilement étalées que retirées de la peau, n'y laissant pas de traces grasses, en raison de la base aqueuse du produit.The compositions according to the invention are as easily spread as removed from the skin, leaving no greasy traces there, because of the aqueous base of the product.
Les formulations suivantes sont données a titre d'exemples préférentiels, en accord avec la présente invention : _ % » Exemple 1The following formulations are given as preferred examples, in accordance with the present invention: _% "Example 1
On mélange, comme précédemment décrit, les ingrédients suivants :The following ingredients are mixed, as previously described:
Améthocaine 4 %Amethocaine 4%
Carbopol sodique 934 1,2 %Carbopol sodium 934 1.2%
Eau 94,8 % t 3 · , 5 .Water 94.8% t3.5.
èè
Exemple 2 j I Améthocaine 4 % i 1 Méthylcellulose 450 7 % j Eau 89 % i i i Les compositions selon l'invention sont appliquées sur la peau intacte en couche épaisse, protégée par un pansement non absorbant. La composition est laissée en place.pendant une période minimum de 20 minutes, pouvant aller jusqu'à une heure, mais se . . situant de préférence - autour de 30 minutes, après quoi le pan- | ’ sement et la composition sont retirés. A ce moment, selon les j variations individuelles, l'anesthésie complète soit est ins tallée, soit nécessite une attente complémentaire (jusqu’à *=· 50 minutes) pour être pleinement développée. L'effet anesthé- ! , sique persiste pendant 2 à 8 heures, en fonction également des variations individuelles.Example 2 j I Amethocaine 4% i 1 Methylcellulose 450 7% j Water 89% i i i The compositions according to the invention are applied to intact skin in a thick layer, protected by a non-absorbent dressing. The composition is left in place for a minimum period of 20 minutes, which can go up to an hour, but is. . preferably - around 30 minutes, after which the pan- | Ement and composition are removed. At this time, depending on the individual variations, complete anesthesia is either installed or requires additional waiting (up to * = · 50 minutes) to be fully developed. The anesthetic effect! , sique persists for 2 to 8 hours, depending also on individual variations.
/* ’/ * ’
! A! AT
! i « · Ä « :>! i "· Ä":>
Claims (11)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08422759A GB2163956B (en) | 1984-09-08 | 1984-09-08 | Percutaneous anaesthetic composition for topical application |
| GB8422759 | 1984-09-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU86068A1 true LU86068A1 (en) | 1986-03-11 |
Family
ID=10566481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU86068A LU86068A1 (en) | 1984-09-08 | 1985-09-04 | PERCUTANEOUS ANESTHETIC COMPOSITION FOR TOPICAL USE AND METHOD OF APPLICATION |
Country Status (31)
| Country | Link |
|---|---|
| EP (1) | EP0175609B1 (en) |
| JP (1) | JPS6185316A (en) |
| KR (1) | KR860002267A (en) |
| AT (1) | ATE73352T1 (en) |
| AU (1) | AU581246B2 (en) |
| BE (1) | BE903186A (en) |
| CH (1) | CH666815A5 (en) |
| CS (1) | CS261887B2 (en) |
| DD (1) | DD236876A5 (en) |
| DE (2) | DE3531002A1 (en) |
| DK (1) | DK406785A (en) |
| FI (1) | FI853416L (en) |
| FR (1) | FR2569982B1 (en) |
| GB (1) | GB2163956B (en) |
| GR (1) | GR852142B (en) |
| HU (1) | HU193611B (en) |
| IL (1) | IL76092A0 (en) |
| IN (1) | IN165072B (en) |
| IS (1) | IS3035A7 (en) |
| IT (1) | IT1182854B (en) |
| LU (1) | LU86068A1 (en) |
| MA (1) | MA20519A1 (en) |
| NO (1) | NO853504L (en) |
| NZ (1) | NZ213325A (en) |
| OA (1) | OA08158A (en) |
| PH (1) | PH21731A (en) |
| PL (1) | PL255285A1 (en) |
| PT (1) | PT81079B (en) |
| ZA (1) | ZA856501B (en) |
| ZM (1) | ZM6185A1 (en) |
| ZW (1) | ZW14285A1 (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8712518D0 (en) * | 1987-05-28 | 1987-07-01 | Univ Belfast | Unit-dose film composition |
| GB8729855D0 (en) * | 1987-12-22 | 1988-02-03 | Drythanol Ltd | New dithranol compositions |
| GB9101986D0 (en) * | 1991-01-30 | 1991-03-13 | Smith & Nephew | Pharmaceutical compositions |
| SE9402453D0 (en) * | 1994-07-12 | 1994-07-12 | Astra Ab | New pharmaceutical preparation |
| US6245347B1 (en) | 1995-07-28 | 2001-06-12 | Zars, Inc. | Methods and apparatus for improved administration of pharmaceutically active compounds |
| US6284266B1 (en) | 1995-07-28 | 2001-09-04 | Zars, Inc. | Methods and apparatus for improved administration of fentanyl and sufentanil |
| US5658583A (en) * | 1995-07-28 | 1997-08-19 | Zhang; Jie | Apparatus and methods for improved noninvasive dermal administration of pharmaceuticals |
| US6955819B2 (en) | 1998-09-29 | 2005-10-18 | Zars, Inc. | Methods and apparatus for using controlled heat to regulate transdermal and controlled release delivery of fentanyl, other analgesics, and other medical substances |
| US6453648B1 (en) | 1999-07-06 | 2002-09-24 | Zars, Inc. | Method for manufacturing a heat generating apparatus |
| US6261595B1 (en) | 2000-02-29 | 2001-07-17 | Zars, Inc. | Transdermal drug patch with attached pocket for controlled heating device |
| KR20030083316A (en) * | 2002-04-20 | 2003-10-30 | 김성수 | Solid lidocaine pharmaceutical for local anesthesia of pharynx |
| ES2388355T3 (en) | 2006-11-03 | 2012-10-11 | Durect Corporation | Transdemic delivery systems comprising bupivacaine |
| CN102427792A (en) | 2009-05-04 | 2012-04-25 | 扎斯制药公司 | Methods of treating pains associated with neuroma, nerve entrapment, and other conditions |
| US9186334B2 (en) | 2009-05-04 | 2015-11-17 | Nuvo Research Inc. | Heat assisted lidocaine and tetracaine for transdermal analgesia |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB633062A (en) * | 1945-02-01 | 1949-12-12 | Benjamin Clayton | Improvements in or relating to ointment bases |
| GB948838A (en) * | 1961-12-04 | 1964-02-05 | Lucien Harnist | Hemorrhoidal compositions containing topical anesthetics |
| US3337406A (en) * | 1963-12-12 | 1967-08-22 | Mar Sal Inc | Treatment of arteriosclerotic diseases |
| SE387536B (en) * | 1973-03-13 | 1976-09-13 | Astra Laekemedel Ab | PROCEDURE FOR PREPARING A LOCAL AESTHETIC PREPARATION |
| DE2413143A1 (en) * | 1974-03-19 | 1975-10-09 | Inst Chimii Drevesiny Akademii | Local anaesthetic soln or ointment - contains high molecular deriv of para-amino-benzoic acid 2-diethyl-amino ethyl ester hydrochloride |
| JPS5467022A (en) * | 1977-11-07 | 1979-05-30 | Toko Yakuhin Kogyo Kk | Topical agent and production thereof |
| SE7713618L (en) * | 1977-12-01 | 1979-06-02 | Astra Laekemedel Ab | LOCAL ANESTHETIC MIXTURE |
| DE3234350A1 (en) * | 1982-09-16 | 1984-03-22 | Roland 3400 Göttingen Hemmann | Process for the preparation of a germicidal and surface-anaesthetic medicinal composition |
-
1984
- 1984-09-08 GB GB08422759A patent/GB2163956B/en not_active Expired
-
1985
- 1985-08-13 IS IS3035A patent/IS3035A7/en unknown
- 1985-08-14 IL IL76092A patent/IL76092A0/en unknown
- 1985-08-16 IN IN643/MAS/85A patent/IN165072B/en unknown
- 1985-08-26 PH PH32693A patent/PH21731A/en unknown
- 1985-08-27 ZA ZA856501A patent/ZA856501B/en unknown
- 1985-08-30 DE DE19853531002 patent/DE3531002A1/en not_active Withdrawn
- 1985-09-02 NZ NZ213325A patent/NZ213325A/en unknown
- 1985-09-03 PT PT81079A patent/PT81079B/en not_active IP Right Cessation
- 1985-09-03 AU AU47006/85A patent/AU581246B2/en not_active Ceased
- 1985-09-04 ZW ZW142/85A patent/ZW14285A1/en unknown
- 1985-09-04 LU LU86068A patent/LU86068A1/en unknown
- 1985-09-04 KR KR1019850006446A patent/KR860002267A/en not_active Application Discontinuation
- 1985-09-04 GR GR852142A patent/GR852142B/el unknown
- 1985-09-05 IT IT48529/85A patent/IT1182854B/en active
- 1985-09-05 EP EP85401721A patent/EP0175609B1/en not_active Expired - Lifetime
- 1985-09-05 BE BE0/215548A patent/BE903186A/en not_active IP Right Cessation
- 1985-09-05 ZM ZM61/85A patent/ZM6185A1/en unknown
- 1985-09-05 DD DD85280366A patent/DD236876A5/en unknown
- 1985-09-05 AT AT85401721T patent/ATE73352T1/en not_active IP Right Cessation
- 1985-09-05 DE DE8585401721T patent/DE3585580D1/en not_active Revoked
- 1985-09-05 FR FR8513184A patent/FR2569982B1/en not_active Expired
- 1985-09-05 CS CS856356A patent/CS261887B2/en unknown
- 1985-09-06 PL PL25528585A patent/PL255285A1/en unknown
- 1985-09-06 NO NO853504A patent/NO853504L/en unknown
- 1985-09-06 DK DK406785A patent/DK406785A/en unknown
- 1985-09-06 CH CH3849/85A patent/CH666815A5/en not_active IP Right Cessation
- 1985-09-06 OA OA58673A patent/OA08158A/en unknown
- 1985-09-06 HU HU853378A patent/HU193611B/en not_active IP Right Cessation
- 1985-09-06 MA MA20745A patent/MA20519A1/en unknown
- 1985-09-06 FI FI853416A patent/FI853416L/en not_active Application Discontinuation
- 1985-09-06 JP JP60197484A patent/JPS6185316A/en active Pending
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