DD236876A5 - METHOD FOR PRODUCING A PERCUTANEOUS ANESTHETIC COMPOSITION - Google Patents
METHOD FOR PRODUCING A PERCUTANEOUS ANESTHETIC COMPOSITION Download PDFInfo
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- DD236876A5 DD236876A5 DD85280366A DD28036685A DD236876A5 DD 236876 A5 DD236876 A5 DD 236876A5 DD 85280366 A DD85280366 A DD 85280366A DD 28036685 A DD28036685 A DD 28036685A DD 236876 A5 DD236876 A5 DD 236876A5
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- German Democratic Republic
- Prior art keywords
- amethocaine
- composition
- anesthetic
- skin
- water
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- 239000000203 mixture Substances 0.000 title claims abstract description 36
- 230000003444 anaesthetic effect Effects 0.000 title claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229960002372 tetracaine Drugs 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229920002125 Sokalan® Polymers 0.000 claims description 7
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 6
- 229960001631 carbomer Drugs 0.000 claims description 6
- 229920000609 methyl cellulose Polymers 0.000 claims description 6
- 239000001923 methylcellulose Substances 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 8
- 239000003349 gelling agent Substances 0.000 claims 4
- 206010002091 Anaesthesia Diseases 0.000 abstract description 5
- 230000037005 anaesthesia Effects 0.000 abstract description 5
- 239000000155 melt Substances 0.000 abstract description 3
- 239000011159 matrix material Substances 0.000 abstract description 2
- 230000037368 penetrate the skin Effects 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000009472 formulation Methods 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 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 2
- 239000004264 Petrolatum Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ONQIULKITQJUDK-UHFFFAOYSA-N 2-[2-[di(propan-2-yl)amino]ethoxy]-1-phenylbutan-1-one Chemical compound CC(C)N(C(C)C)CCOC(CC)C(=O)C1=CC=CC=C1 ONQIULKITQJUDK-UHFFFAOYSA-N 0.000 description 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 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
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005360 alkyl sulfoxide group Chemical group 0.000 description 1
- 229940064734 aminobenzoate Drugs 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000008311 hydrophilic ointment Substances 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
- 238000002690 local anesthesia Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 230000035699 permeability 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
- 210000002265 sensory receptor cell Anatomy 0.000 description 1
- 102000027509 sensory receptors Human genes 0.000 description 1
- 108091008691 sensory receptors Proteins 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
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
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- 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
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- 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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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
Die Erfindung betrifft ein Verfahren zur Herstellung einer Zusammensetzung fuer die lokale perkutane Anaesthesie, bestehend aus 1 bis 7 Gew.-% 2-Dimethylaminoethyl-p-butylaminobenzoat (Amethocain), dispergiert in 0,5 bis 10 Gew.-% eines waessrigen Gels und 81 bis 94,5 Gew.-% Wasser. Die Amethocain-Stabilitaet wird durch die Gelmatrix gefoerdert. Beim Auftragen auf die Haut schmilzt das Amethocain und dispergiert in Gestalt von Oeltroepfchen durch das Gel hindurch. Diese Troepfchen durchdringen die Haut, um die anaesthetische Wirkung zu erzeugen.The invention relates to a method for producing a composition for local percutaneous anesthesia, consisting of 1 to 7 wt .-% 2-dimethylaminoethyl p-butylaminobenzoate (amethocaine) dispersed in 0.5 to 10 wt .-% of an aqueous gel and From 81 to 94.5% by weight of water. The amethocaine stability is promoted by the gel matrix. When applied to the skin melts the amethocaine and dispersed in the form of oil droplets through the gel. These trophies penetrate the skin to produce the anesthetic effect.
Description
Die Erfindung betrifft eine Zusammensetzung für die lokale Anwendung in der perkutanen Anästhesie.The invention relates to a composition for topical application in percutaneous anesthesia.
In der britischen Patentschrift 1464975 wird eine Zusammensetzung für die lokale Anästhesie beschrieben, die Diisopropylaminoethoxybutyrophenon als aktive Substanz und als Lösungsmittel eine Mischung aus Isopropanol (40 bis 70%), Glycerol (0 bis 60%) und andere inerte Mittel, wie z. B. Wasser, enthält.British Patent 1464975 describes a composition for local anesthesia containing diisopropylaminoethoxybutyrophenone as the active substance and as a solvent a mixture of isopropanol (40 to 70%), glycerol (0 to 60%) and other inert agents, such as e.g. As water contains.
Nach der US-Patentschrift 4091 090 wird als Mittel für die perkutane Anästhesie eine Mischung aus 0,5 bis 12% der anästhetischen Agenz, 1 bis 15% eines Eindringbeschleunigers für das Anästhetikum, wie Cyclohexylalkohol, und Rest Lösungsmittel wie Wasser, Ethanol und Propylenglycol verwandt.According to US Pat. No. 4,091,090, the percutaneous anesthetic agent used is a mixture of 0.5 to 12% of the anesthetic agent, 1 to 15% of an anesthetic penetration enhancer such as cyclohexyl alcohol, and remainder solvents such as water, ethanol and propylene glycol ,
In der US-Patentschrift 4148917 wird eine anästhetische Mischung beschrieben, die 0,1 bis 15% aktive Substanz, 0,1 bis 1 % eines Zuckeresters und 0,1 bis 10% Alkylsulfoxyd oder Phosphinoxyd, Rest Lösungsmittel enthält.US Pat. No. 4,147,917 describes an anesthetic mixture containing 0.1 to 15% active substance, 0.1 to 1% of a sugar ester and 0.1 to 10% alkyl sulfoxide or phosphine oxide, the remainder solvent.
Nach der US-Patentschrift 4052 513 wird als perkutanes Anästhetikum eine Mischung aus 0,5 bis 15% Benzocain, 5 bis 40% eines Dialkylesters einer Alkandionsäure als Lösungsvermittler, eines Emulgators und Wasser verwandt.According to US Pat. No. 4,052,513, a mixture of 0.5 to 15% benzocaine, 5 to 40% of a dialkyl ester of an alkanedioic acid as a solubilizer, an emulsifier and water is used as the percutaneous anesthetic.
Weiter wurde 2-Dimethylaminoethyl-p-butyl-amino-benzoat, bekannt unter dem Handelsnamen Amethocain, in lokalen Anästhetika eingesetzt.Further, 2-dimethylaminoethyl-p-butyl-amino-benzoate, known under the trade name amethocaine, has been used in local anesthetics.
Versuche zur Erzeugung einer lokalen perkutanen Anästhesie, bei der das Anästhetikum das Stratum corneum zu durchdringen hat, leiden unter einer Reihe von Nachteilen. So waren hohe Konzentrationen der Wirksubstanz erforderlich, bis zu 33%, die bisherigen Zusammensetzungen erzeugten unangenehme Nebenwirkungen, erforderten die Anwendung abschließender Verbände und lange Zeitspannen für eine wirksame perkutane Anästhesie.Attempts to create local percutaneous anesthesia, where the anesthetic has to penetrate the stratum corneum, suffer from a number of disadvantages. Thus, high concentrations of the active ingredient were required, up to 33%, the previous compositions produced unpleasant side effects, required the use of final dressings and long periods of effective percutaneous anesthesia.
Bislang wurde Amethocain in Ethanol oder Isopropylalkohol (45%), Glycerol (10%) und Wasser (45%) oder hydrophiler Salbe (95%) oder Petrolat (95%) oder in DMSO (Dimethylsulfoxid) dispergiert, eingesetzt. Die Ethanol oder Isopropylalkohol, Glycerol und Wasser enthaltenden Formulierungen neigen in ihrer Natur dazu, sehr mobil zu sein, wodurch eine räumliche Umgrenzung der Anwendungsstelle schwierig ist. Darüber hinaus weisen diese Lösungen nur eine begrenzte Stabilität auf. Die anderen Formulierungen leiden unter dem gleichen Nachteil. Hydrophile Sal be oder Roh vaseline enth alten de Formulierungen verzögern das Einsetzen der anästhetischen Wirkung, während DMSO enthaltende Zusammensetzungen schmerzhafte Risse in der Haut hervorrufen.Heretofore, amethocaine has been used in ethanol or isopropyl alcohol (45%), glycerol (10%) and water (45%) or hydrophilic ointment (95%) or petrolatum (95%) or dispersed in DMSO (dimethylsulfoxide). The formulations containing ethanol or isopropyl alcohol, glycerol and water tend to be very mobile in nature, making it difficult to spatially confine the site of application. In addition, these solutions have only limited stability. The other formulations suffer from the same disadvantage. Hydrophilic salves or crude petrolatum-containing formulations delay the onset of anesthetic activity, while compositions containing DMSO cause painful cracks in the skin.
Ziel der Erfindung ist ein perkutanes Anästhetikum, das bei seiner Anwendung unkompliziert ist und kurze Zeitspannen der Einwirkung auf die zu behandelnden Stellen erfordert.The aim of the invention is a percutaneous anesthetic which is uncomplicated in its application and requires short periods of exposure to the sites to be treated.
Der Erfindung liegt die Aufgabe zugrunde, ein Anästhetikum unter Einsatz von 2-Dimethylaminoethyl-p-butyl-aminobenzoat als wirksame Substanz zu entwickeln.The invention has for its object to develop an anesthetic using 2-dimethylaminoethyl-p-butyl-aminobenzoate as an effective substance.
Bei der Herstellung der perkutanen anästhetischen Zusammensetzung für eine lokale Anwendung wird erfindungsgemäß 2-Dimethylaminoethyl-p-butyl-aminobenzoat in einer Mischung aus einem Gel, wie Carbomer oder Methylcellulose und Wasser dispergiert.In the preparation of the percutaneous anesthetic composition for topical application, according to the present invention, 2-dimethylaminoethyl p-butyl aminobenzoate is dispersed in a mixture of a gel such as carbomer or methyl cellulose and water.
Für die erfindungsgemäße Zusammensetzung werden 1 bis 7 Gew.-%, vorzugsweise 4Gew.-% 2-Dimethylaminoethyl-p-butylaminobenzoat, nachfolgend Amethocain genannten 0,5 bis 2Gew.-% Carbomer oder 3 bis 10Gew.-% Methylcellulose und Rest Wasser dispergiert.For the composition according to the invention, 1 to 7% by weight, preferably 4% by weight, of 2-dimethylaminoethyl p-butylaminobenzoate, hereinafter referred to as amethocaine 0.5 to 2% by weight of carbomer or 3 to 10% by weight of methylcellulose and the remainder of water are dispersed ,
Das Amethocain wird im wesentlichen vollständig als die diskontinuierliche feste Phase zurückgehalten, wodurch das Amethocain während der Lagerung in der genannten Zusammensetzung vor Hydrolyse geschützt bleibt, wohingegen es beim Auftragen auf die Haut schmilzt und für die Sorption verfügbar gemacht wird.The amethocaine is substantially completely retained as the discontinuous solid phase, whereby the amethocaine remains protected from hydrolysis during storage in said composition, whereas it melts upon application to the skin and is made available for sorption.
Das Amethocain-Pulver wird durch das Gel hindurch verteilt, welches seinerseits keine fremde lipophile Phase zu enthalten braucht. Die großkristalline Struktur in der viskosen Gelmatrix stabilisiert das Amethocain durch Verzögerung seiner Auflösung sowie anschließende Hydrolyse der Estergruppe, sofern eine Temperatur von 30°C nicht überschritten wird. Amethocain schmilzt bei ungefähr410C, in der erfindungsgemäßen Zusammensetzung ist sein Schmelzpunkt jedoch auf 30 bis 32°C gesenkt. Die Hauttemperatur beträgt gewöhnlich etwa 32°C. Wird die Zusammensetzung auf die Hautoberfläche aufgetragen, dann schmelzen die großen Amethocain-Kristalle allmählich und werden als kleine Öltröpfchen durch das Gel dispergiert. Das Amethocain liegt dann in molekularer Form vor, und sofern keine andere lipophile Phase vorhanden ist, weisen diese Öltröpfchen eine hohe Durchdringungsfähigkeit für die Haut und ihrer darunterliegenden Strukturen auf. Liegen fremde lipophile Phasen vor, wird die Amethocain-Konzentration erhöht, so daß eine ähnliche therapeutische Wirksamkeit erreicht wird. Auf Grund der dem Amethocain innewohnenden antimikrobiellen Eigenschaften ist es erforderlich, ein Schutzmittel in die Zusammensetzung einzubeziehen. -""The amethocaine powder is distributed through the gel, which in turn need not contain any foreign lipophilic phase. The large crystalline structure in the viscous gel matrix stabilizes the amethocaine by delaying its dissolution and subsequent hydrolysis of the ester group, provided a temperature of 30 ° C is not exceeded. Amethocaine ungefähr41 melts at 0 C, in the inventive composition, however, its melting point is lowered to 30 to 32 ° C. The skin temperature is usually about 32 ° C. When the composition is applied to the skin surface, the large crystals of amethocaine gradually melt and are dispersed as small oil droplets through the gel. The amethocaine is then in molecular form, and unless other lipophilic phase is present, these oil droplets have a high permeability to the skin and its underlying structures. If foreign lipophilic phases are present, the concentration of amethocaine is increased, so that a similar therapeutic efficacy is achieved. Due to the inherent antimicrobial properties of the amethocaine, it is necessary to include a preservative in the composition. - ""
Die Zusammensetzung kann unter Anwendung konventioneller Techniken hergestellt werden. Amethocain wird dem gebildeten Carbomer- oder Methylcellulose-Gel zugesetzt, worauf innig vermischt wird. Ebenso kann das Natriumsalz des Carbomers, den Anweisungen des Herstellers entsprechend, verwendet werden. Es kann aber auch Amethocain in Wasser dispergiert werden, worauf das Natriumsalz von Carbopol zugesetzt und die Mischung gründlich durchgemischt wird, bis sich das Gel gebildet hat. Die erfindungsgemäßen Zusammensetzungen lassen sich sowohl auf der Haut leicht verteilen als auch leicht wieder von dieser entfernen, wobei auf Grund des wäßrigen Grundstoffes der Zusammensetzung keine Rückstände auf der Hautoberfläche zurückbleiben.The composition can be prepared using conventional techniques. Amethocaine is added to the formed carbomer or methylcellulose gel followed by intimate mixing. Similarly, the sodium salt of the carbomer can be used according to the manufacturer's instructions. However, it is also possible to disperse amethocaine in water, whereupon the Carbopol sodium salt is added and the mixture thoroughly mixed until the gel has formed. The compositions according to the invention can be easily distributed both on the skin and also readily removed therefrom, leaving no residue on the skin surface due to the aqueous base substance of the composition.
Die Zusammensetzungen der vorliegenden Erfindung werden der intakten Haut als dicke Beschichtung appliziert, die dann durch einen nicht absorbierenden Verband geschützt wird. Die Zusammensetzung verbleibt für 20 min bis zu einer Stunde, vorzugsweise 30 min auf der Haut, worauf Verband und Zusammensetzung entfernt werden. Die vollständige anästhetische Wirkung kann sich zu diesem Zeitpunkt bereits eingestellt haben, es kann aber auch, je nach individuller Variation, einer weiteren Zeitspanne (bis zu 50 min) bedürfen, bis sich die anästhetische Wirkung voll entfaltet hat. Wierderum in Abhängigkeit von der individuellen Reaktion hält der anästhetische Effekt 2 bis 8 Stunden lang an.The compositions of the present invention are applied to the intact skin as a thick coating, which is then protected by a non-absorbent dressing. The composition remains on the skin for 20 minutes to one hour, preferably 30 minutes, after which dressing and composition are removed. The complete anesthetic effect may have already stopped at this time, but it may also, depending on individual variation, require a further period of time (up to 50 minutes) until the anesthetic effect has fully developed. Wernderum depending on the individual reaction, the anesthetic effect lasts for 2 to 8 hours.
Die folgenden Ingredienzien werden in der bereits beschriebenen Weise miteinander vermischt: Amethocain 4,0%The following ingredients are mixed together in the manner already described: Amethocaine 4.0%
Natrium-Carbopoi934 1,2%Sodium carbopoi934 1.2%
Wasser 94,8%Water 94.8%
Die in den Beispielen genannten Formulierungen werden durch die Applikation eines geeigneten, nicht absorbierenden Verbandes (okklusiv oder nichtokklusiv) geschützt und mindestens 20 min in Kontakt mit der Haut belassen. Danach werden der Verband und das Anästhetikum entfernt, bevor die chirugische Operation stattfindet. Die Zusammensetzung bietet eine gründliche und ausreichende tiefe anästhetische Wirkung, um die darunterliegenden Schmerzempfindungsrezeptoren zu blockieren und ermöglicht damit die schmerzlose Entfernung von Hauttransplantaten in voller Hautdicke, das schmerzlose Durchdringen der Haut mit Injektionsnadeln (z.B. Venenpunktion) sowie die schmerzlose Durchführung anderer derartiger kleinerer chirugischer Eingriffe. Die Zusammensetzung erübrigt unter diesen Umständen die Anwendung einer lokalen Infiltrationsanästhesie und kann auch durch nichtmedizinisches Personal leicht ausgeführt werden.The formulations mentioned in the examples are protected by the application of a suitable non-absorbent dressing (occlusive or non-occlusive) and left in contact with the skin for at least 20 minutes. Thereafter, the bandage and anesthetic are removed before the surgical operation takes place. The composition provides a thorough and sufficient deep anesthetic effect to block the underlying pain sensory receptors, thereby enabling the painless removal of skin grafts in full thickness, the painless penetration of the skin with hypodermic needles (e.g., venipuncture), and the painless performance of other such minor surgical procedures. The composition in these circumstances eliminates the need for local infiltration anesthesia and can be easily performed by non-medical personnel.
Claims (8)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08422759A GB2163956B (en) | 1984-09-08 | 1984-09-08 | Percutaneous anaesthetic composition for topical application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD236876A5 true DD236876A5 (en) | 1986-06-25 |
Family
ID=10566481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD85280366A DD236876A5 (en) | 1984-09-08 | 1985-09-05 | METHOD FOR PRODUCING A PERCUTANEOUS ANESTHETIC COMPOSITION |
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 |
| US5658583A (en) * | 1995-07-28 | 1997-08-19 | Zhang; Jie | Apparatus and methods for improved noninvasive dermal administration of pharmaceuticals |
| US6284266B1 (en) | 1995-07-28 | 2001-09-04 | Zars, Inc. | Methods and apparatus for improved administration of fentanyl and sufentanil |
| 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 |
| AU2010246064A1 (en) | 2009-05-04 | 2011-12-22 | Zars Pharma, Inc. | 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 AU AU47006/85A patent/AU581246B2/en not_active Ceased
- 1985-09-03 PT PT81079A patent/PT81079B/en not_active IP Right Cessation
- 1985-09-04 GR GR852142A patent/GR852142B/el unknown
- 1985-09-04 KR KR1019850006446A patent/KR860002267A/en not_active Application Discontinuation
- 1985-09-04 LU LU86068A patent/LU86068A1/en unknown
- 1985-09-04 ZW ZW142/85A patent/ZW14285A1/en unknown
- 1985-09-05 AT AT85401721T patent/ATE73352T1/en not_active IP Right Cessation
- 1985-09-05 FR FR8513184A patent/FR2569982B1/en not_active Expired
- 1985-09-05 IT IT48529/85A patent/IT1182854B/en active
- 1985-09-05 ZM ZM61/85A patent/ZM6185A1/en unknown
- 1985-09-05 BE BE0/215548A patent/BE903186A/en not_active IP Right Cessation
- 1985-09-05 EP EP85401721A patent/EP0175609B1/en not_active Expired - Lifetime
- 1985-09-05 CS CS856356A patent/CS261887B2/en unknown
- 1985-09-05 DE DE8585401721T patent/DE3585580D1/en not_active Revoked
- 1985-09-05 DD DD85280366A patent/DD236876A5/en unknown
- 1985-09-06 CH CH3849/85A patent/CH666815A5/en not_active IP Right Cessation
- 1985-09-06 HU HU853378A patent/HU193611B/en not_active IP Right Cessation
- 1985-09-06 FI FI853416A patent/FI853416L/en not_active Application Discontinuation
- 1985-09-06 MA MA20745A patent/MA20519A1/en unknown
- 1985-09-06 OA OA58673A patent/OA08158A/en unknown
- 1985-09-06 DK DK406785A patent/DK406785A/en unknown
- 1985-09-06 JP JP60197484A patent/JPS6185316A/en active Pending
- 1985-09-06 PL PL25528585A patent/PL255285A1/en unknown
- 1985-09-06 NO NO853504A patent/NO853504L/en unknown
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