CS261887B2 - Method of amethocaine containing aqueous agent stabilization - Google Patents
Method of amethocaine containing aqueous agent stabilization Download PDFInfo
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- CS261887B2 CS261887B2 CS856356A CS635685A CS261887B2 CS 261887 B2 CS261887 B2 CS 261887B2 CS 856356 A CS856356 A CS 856356A CS 635685 A CS635685 A CS 635685A CS 261887 B2 CS261887 B2 CS 261887B2
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- amethocaine
- composition
- weight
- gel
- améthocaïne
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- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 title claims description 24
- 229960002372 tetracaine Drugs 0.000 title claims description 24
- 238000000034 method Methods 0.000 title claims description 7
- 230000006641 stabilisation Effects 0.000 title description 2
- 238000011105 stabilization Methods 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 229920002125 Sokalan® Polymers 0.000 claims description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
- 229960001631 carbomer Drugs 0.000 claims description 7
- 229920000609 methyl cellulose Polymers 0.000 claims description 7
- 239000001923 methylcellulose Substances 0.000 claims description 7
- 239000003349 gelling agent Substances 0.000 claims description 5
- 230000000087 stabilizing effect Effects 0.000 claims description 4
- 210000003491 skin Anatomy 0.000 description 12
- 230000003444 anaesthetic effect Effects 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 206010002091 Anaesthesia Diseases 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 230000037005 anaesthesia Effects 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 230000002745 absorbent Effects 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000008311 hydrophilic ointment Substances 0.000 description 2
- 210000000929 nociceptor Anatomy 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229940099259 vaseline Drugs 0.000 description 2
- LQTVYXHMXITZSJ-UHFFFAOYSA-N 2-amino-4-butyl-3-[2-(dimethylamino)ethyl]benzoic acid Chemical compound CCCCC1=C(C(=C(C=C1)C(=O)O)N)CCN(C)C LQTVYXHMXITZSJ-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 229940086737 allyl sucrose Drugs 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 108091008700 nociceptors Proteins 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Emergency Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pipeline Systems (AREA)
- Vehicle Body Suspensions (AREA)
- Indication And Recording Devices For Special Purposes And Tariff Metering Devices (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
Řešení se týká způsobu stabilizace vodného prostředku, obsahujícího amethokain s obsahem 1 až 7 % hmotnostních amethokainu a 81 až 95 % hmotnostních vody, vyznačující se tím, že se jako stabilizační přísada použije 0,5 až 10 % hmotnostních vodného gelujícího činidla, kterým je carbomer nebo methylcelulóza.The invention relates to a process for stabilizing an aqueous composition comprising amethocaine containing 1-7% by weight of amethocaine and 81-95% by weight of water, characterized in that 0.5-10% by weight of an aqueous gelling agent, which is a carbomer, is used as stabilizing additive. or methylcellulose.
Vynález se týká způsobu výroby prostředku, obsahujícího amethokain.The invention relates to a process for the preparation of a composition comprising amethocaine.
Ámethokain (2-dimethy laminoethyl-p-butyl-aminobenzoát) je používán v lokálních preparátech к vyvolání povrchové anesthesie. Snahy vyvolat lokální perkutánní anesthesii, při které je anesthetické činidlo nuceno pronikat skrze stratům corneum, trpěly řadou nevýhod:Amethocaine (2-dimethylamino-ethyl-p-butyl-aminobenzoate) is used in topical preparations to induce surface anesthesia. Attempts to induce local percutaneous anesthesia in which the anesthetic agent is forced to penetrate the stratum corneum have suffered from a number of disadvantages:
1. bylo třeba vysokých koncentrací farmak (až 33 °/o)1. high concentrations of pharmaceuticals (up to 33 ° / o) were required
2. předchozí směsi vyvolávaly nepřijatelné vedlejší účinky2. the previous mixtures produced unacceptable side effects
3. předchozí směsi vyžadovaly použití oklusivních obvazů3. previous mixtures required the use of occlusive dressings
4. předchozí směsi vyžadovaly prodloužení časových období nutných к vyvolání účinné perkutánní anesthesie.4. previous compositions required prolongation of the time periods required to induce effective percutaneous anesthesia.
Dříve amethokain byl dispergován v ethanolu nebo isopropylalkoholu (45 °/o) a vodě (45 %), glycerolu (10 °/o) a vodě (45 °/o) nebo hydrofilním masťovém základu (95 °/o) nebo vaselině (95 %) nebo DMSO (dimethylsulphoxid).Previously, amethocaine was dispersed in ethanol or isopropyl alcohol (45%) and water (45%), glycerol (10%) and water (45%) or hydrophilic ointment base (95%) or vaseline (95%). %) or DMSO (dimethylsulphoxide).
Směsi obsahující ethanol nebo isopropylalkohol, glycerol a vodu mají tendenci mít velmi pohyblivou povahu a tak ohraničení místa účinku je obtížné. Nadto tyto roztoky mají jenom omezenou stabilitu. Ostatní směsi trpí stejnými nevýhodami. Směsi obsahující hydrofilní masťový základ nebo vaselinu zpomalují nástup anesthetického účinku, zatímco směsi obsahující DMSO vyvolávají bolestivé poškození povrchu kůže. Podle jednoho provedení vynálezu je vyráběna směs pro lokální aplikaci sestávající z amethokainu, vodného gelujícího činidla a vody, ve které jsou zmíněné gely vytvářeny; amethokain je v podstatě úplně zadržován jako diskontinuální pevná fáze, přičemž v zmíněné směsi je amethokain chráněn před hydrolysou v průběhu skladování, ale je-li směs aplikována na kůže, amethokain taje a je к dispozici pro vstřebání.Mixtures containing ethanol or isopropyl alcohol, glycerol and water tend to be highly mobile in nature and thus delimiting the site of action is difficult. Moreover, these solutions have only limited stability. Other mixtures suffer from the same disadvantages. Compositions containing a hydrophilic ointment base or vaseline slow the onset of anesthetic effect, while compositions containing DMSO cause painful damage to the skin surface. According to one embodiment of the invention, a topical composition is prepared consisting of amethocaine, an aqueous gelling agent and the water in which said gels are formed; amethocaine is substantially completely retained as a discontinuous solid phase, in which said amethocaine is protected from hydrolysis during storage, but when applied to the skin, amethocaine melts and is available for absorption.
Podle jiného provedení vynálezu je vyráběna směs к použití jako místní perkutánní anesthetikum sestávající z anesthetika, vodného gelujícího činidla pro stabilizaci anesthetika a vody, přičemž směs je taková, že při použití anesthetikum taje a rozptyluje se v gelu к usnadnění průniku kůží.According to another embodiment of the invention, a composition for use as a local percutaneous anesthetic is produced comprising an anesthetic, an aqueous gelling agent to stabilize the anesthetic and water, wherein the composition is such that it melts and disperses in the gel to facilitate penetration through the skin.
Pomocí prostředku, získaného způsobem podle vynálezu, lze provádět lokální perkutánní anesthesii aplikací účinného množství svrchu definované směsi na nepoškozenou kožní oblast.By means of a composition according to the invention, local percutaneous anesthesia can be performed by applying an effective amount of the above defined composition to an undamaged skin area.
Vynález tedy poskytuje amethokain obsahující prostředek, který se málo nebo vůbec neroztéká po aplikaci na povrch kůže. Prostředek je chráněn aplikací vhodného neabsorpčního obvazu (oklusivního nebo neoklusivního) a je ponechán v kontaktu s kůží po minimální období 20 minut. Potom se obvaz a prostředek odstraní, předtím než začne chirurgický výkon. Směs se vyznačuje silným anesthetickým účinkem dostatečně hlubokým pro blokování pod povrchem ležících nociceptoru (receptorů bolesti) atak umožňuje bezbolestné odnětí velkých kusů kožních transplantátů v plné tloušťce kůže, pronikání injekčních jehel (např. venepunkce) a ostatní podobné menší chirurgické procedury. Směs se odstraňuje užitím lokální infiltrační anestesie za těchto podmínek a může být snadno aplikována medicínsky netrénovanými osobami. Amethokain obsahující prostředek pro lokální perkutánní aplikaci může obsahovat od 1 do 7 %,s výhodou 4 % amethokainu dispergovaného ve vodním gelu, jako 0,5 až 2 % carbomeru nebo 3 až 10 % methylcelulosy v 81 až 94,5 % vody; zmíněná procenta jsou hmotnostní, vztažená na celkovou hmotnost směsi. Amethokainový prášek je distribuován skrze gel, který nesmí obsahovat žádné cizorodé lipofilní fáze. Velká krystalová struktura ve viskosní gelové matrici stabilizuje amethokain zpomalením jeho rozpouštění s následnou alkalickou hydrolysou esterových skupin, za předpokladu, že není překročena teplota 30 stupňů Celsia. Amethokain taje přibližně při 41 stupních Celsia, avšak ve směsi je jeho teplota tání snížena na 30 až 32 stupňů Celsia. Teplota kůže je obvykle kolem 32 stupňů Celsia. Je-li směs aplikována na povrch kůže, velké krystaly amethokainu se postupně taví a rozptylují se jako malé olejové kapičky v gelu. Amethokain je proto přítomen v molekulární formě a za předpokladu, že není přítomna další lipofilní fáze, tyto olejové kapičky jsou vysoce penetrativní, pokud jde o kůži a její pod povrchem ležící struktury. Přítomnost ciz ch lipofilních fází bude vyžadovat zvýšené koncentrace amethokainu tak, aby se dosáhlo podobného therapeutického účinku. Není třeba zahrnovat do směsi konservační činidlo, s ohledem na vlastní antimikrobiální vlastnosti amethokainu.Accordingly, the present invention provides an amethocaine containing composition that does not flow, if any, upon application to the skin surface. The composition is protected by applying a suitable non-absorbent dressing (occlusive or non-occlusive) and is left in contact with the skin for a minimum period of 20 minutes. Then, the dressing and the device are removed before the surgical procedure begins. The composition is characterized by a strong anesthetic effect deep enough to block the underlying nociceptor (pain receptors), thus allowing painless removal of large pieces of skin grafts in full skin thickness, injection needle penetration (eg venipuncture) and other similar minor surgical procedures. The composition is removed using local infiltration anesthesia under these conditions and can be easily administered by medically untrained persons. The amethocaine-containing composition for topical percutaneous administration may comprise from 1 to 7%, preferably 4% of amethocaine dispersed in a water gel, such as 0.5 to 2% carbomer or 3 to 10% methylcellulose in 81 to 94.5% water; said percentages are by weight based on the total weight of the composition. Amethocaine powder is distributed through a gel that must not contain any foreign lipophilic phases. The large crystal structure in the viscous gel matrix stabilizes amethocaine by retarding its dissolution followed by alkaline hydrolysis of the ester groups, provided the temperature is not exceeded 30 degrees Celsius. Amethocaine melts at approximately 41 degrees Celsius, but in the mixture its melting point is reduced to 30 to 32 degrees Celsius. Skin temperature is usually around 32 degrees Celsius. When the mixture is applied to the skin surface, large amethocaine crystals gradually melt and disperse as small oil droplets in the gel. Amethocaine is therefore present in molecular form, and provided that no other lipophilic phase is present, these oil droplets are highly penetrative with respect to the skin and its underlying surface. The presence of foreign lipophilic phases will require elevated concentrations of amethocaine to achieve a similar therapeutic effect. There is no need to include a preservative in the composition because of the intrinsic antimicrobial properties of amethocaine.
Předmětem vynálezu je způsob stabilizace vodného prostředku, obsahujícího amethokain s obsahem 1 až 7 hmotnostních % amethokainu a 81 až 95 hmotnostních % vody, vyznačující se tím, že se jako stabilizační přísada použije 0,5 až 10 hmotnostních % vodného gelujícího činidla, kterým je carbomer nebo methylcelulóza.SUMMARY OF THE INVENTION The present invention provides a process for the stabilization of an aqueous composition comprising amethocaine containing 1-7% by weight amethocaine and 81-95% by weight water, characterized in that 0.5-10% by weight aqueous gelling agent, which is a carbomer, is used as a stabilizing additive. or methylcellulose.
Vynález bude osvětlen následujícími příklady:The invention will be illustrated by the following examples:
Prostředek carbomer je polymer kyseliny akrylové, zesítěný allylsacharózou, s obsahem 56 až 68 % karboxylových skupin.The carbomer is an acrylic acid polymer cross-linked with allyl sucrose containing 56 to 68% carboxyl groups.
Carbipol 934, užitý v příkladu 1 je carbomer se střední molekulovou hmotností 3 000 000.Carbipol 934 used in Example 1 is a carbomer with an average molecular weight of 3,000,000.
Methylcelulóza je methylether celulózy s obsahem 29 % methoxyskupin. Je charakterizována viskositou svého 2% roztoku při teplotě 20 CC.Methylcellulose is a methyl ether of cellulose containing 29% methoxy groups. It is characterized by the viscosity of its 2% solution at 20 ° C.
Methylcelulóza-450, užitá v příkladu 2, má viskositu 350 až 550 cSt.The methylcellulose-450 used in Example 2 has a viscosity of 350 to 550 cSt.
Příklad 1Example 1
Následující složky se spolu smíchají svrchu popsaným způsobem:The following ingredients are mixed together as described above:
Amethokain 4,0 %Amethokain 4,0%
Sodná sůl Carbipolu 934 1,2 °/oCarbipol sodium 934 1.2 ° / o
Voda 94,8 %Water 94.8%
Příklad 2Example 2
Amethokain 4,0 %Amethokain 4,0%
Methylcelulosa 450 7,0 %Methylcellulose 450 7.0%
Voda 89,0 %Water 89.0%
Prostředky podle vynálezu se aplikují na nepoškozenou kůži jako silné překrytí, Ikteré je pak chráněno neabsorbčním obvazem. Sloučenina má být ponechána na místě po minimální období 20 minut až do jedné hodiny, s výhodou 30 minut, potom obvaz a prostředek mohou být odstraněny. Úplný anesthetický účinek může nastoupit po této době nebo může vyžadovat další časové období (do 50 minut) v závislosti na individuálních variacích, к tomu, aby se plně projevil. Anesthetický účinek přetrvává od 2 do 8 hodin opět v závislosti na individuálních variacích.The compositions of the invention are applied to undamaged skin as a strong overlay, which is then protected by a non-absorbent dressing. The compound should be left in place for a minimum period of 20 minutes up to one hour, preferably 30 minutes, then the dressing and the composition may be removed. A complete anesthetic effect may occur after this time or may require an additional period of time (up to 50 minutes), depending on individual variations, to fully manifest. The anesthetic effect persists from 2 to 8 hours again depending on individual variations.
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08422759A GB2163956B (en) | 1984-09-08 | 1984-09-08 | Percutaneous anaesthetic composition for topical application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS635685A2 CS635685A2 (en) | 1988-06-15 |
| CS261887B2 true CS261887B2 (en) | 1989-02-10 |
Family
ID=10566481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS856356A CS261887B2 (en) | 1984-09-08 | 1985-09-05 | Method of amethocaine containing aqueous agent stabilization |
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) | FI853416A7 (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 |
| 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 |
| US6245347B1 (en) | 1995-07-28 | 2001-06-12 | Zars, Inc. | Methods and apparatus for improved administration of pharmaceutically active compounds |
| 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 |
| EP2117521B1 (en) | 2006-11-03 | 2012-06-27 | Durect Corporation | Transdermal delivery systems comprising bupivacaine |
| WO2010129542A1 (en) | 2009-05-04 | 2010-11-11 | Jie Zhang | 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 KR KR1019850006446A patent/KR860002267A/en not_active Withdrawn
- 1985-09-04 ZW ZW142/85A patent/ZW14285A1/en unknown
- 1985-09-04 GR GR852142A patent/GR852142B/el unknown
- 1985-09-04 LU LU86068A patent/LU86068A1/en unknown
- 1985-09-05 EP EP85401721A patent/EP0175609B1/en not_active Expired - Lifetime
- 1985-09-05 IT IT48529/85A patent/IT1182854B/en active
- 1985-09-05 CS CS856356A patent/CS261887B2/en unknown
- 1985-09-05 DD DD85280366A patent/DD236876A5/en unknown
- 1985-09-05 BE BE0/215548A patent/BE903186A/en not_active IP Right Cessation
- 1985-09-05 FR FR8513184A patent/FR2569982B1/en not_active Expired
- 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 ZM ZM61/85A patent/ZM6185A1/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 PL PL25528585A patent/PL255285A1/en unknown
- 1985-09-06 MA MA20745A patent/MA20519A1/en unknown
- 1985-09-06 DK DK406785A patent/DK406785A/en unknown
- 1985-09-06 FI FI853416A patent/FI853416A7/en not_active Application Discontinuation
- 1985-09-06 HU HU853378A patent/HU193611B/en not_active IP Right Cessation
- 1985-09-06 JP JP60197484A patent/JPS6185316A/en active Pending
- 1985-09-06 NO NO853504A patent/NO853504L/en unknown
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