SE432192B - A LOCAL ANESTHETIC EMULSION ALVA FOR EXTERNAL USE OF THE TYPE OF OIL-IN-WATER EMULSION - Google Patents
A LOCAL ANESTHETIC EMULSION ALVA FOR EXTERNAL USE OF THE TYPE OF OIL-IN-WATER EMULSIONInfo
- Publication number
- SE432192B SE432192B SE7812020A SE7812020A SE432192B SE 432192 B SE432192 B SE 432192B SE 7812020 A SE7812020 A SE 7812020A SE 7812020 A SE7812020 A SE 7812020A SE 432192 B SE432192 B SE 432192B
- Authority
- SE
- Sweden
- Prior art keywords
- local anesthetic
- oil
- emulsion
- ointment
- weight
- Prior art date
Links
- 239000003589 local anesthetic agent Substances 0.000 title claims abstract description 44
- 239000000839 emulsion Substances 0.000 title claims abstract description 39
- 239000007764 o/w emulsion Substances 0.000 title claims abstract description 5
- 230000003444 anaesthetic effect Effects 0.000 claims abstract description 20
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 4
- 239000002674 ointment Substances 0.000 claims description 53
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 29
- 229960004194 lidocaine Drugs 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 14
- -1 butanilicain Chemical compound 0.000 claims description 11
- 239000003995 emulsifying agent Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- UXAWFWFJXIANHZ-UHFFFAOYSA-N 1-[2-[2-[di(propan-2-yl)amino]ethoxy]phenyl]butan-1-one Chemical compound CCCC(=O)C1=CC=CC=C1OCCN(C(C)C)C(C)C UXAWFWFJXIANHZ-UHFFFAOYSA-N 0.000 claims description 6
- 229950001903 ketocaine Drugs 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 229960001807 prilocaine Drugs 0.000 claims description 6
- MVFGUOIZUNYYSO-UHFFFAOYSA-N prilocaine Chemical compound CCCNC(C)C(=O)NC1=CC=CC=C1C MVFGUOIZUNYYSO-UHFFFAOYSA-N 0.000 claims description 6
- 229960002372 tetracaine Drugs 0.000 claims description 6
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 claims description 6
- 239000002562 thickening agent Substances 0.000 claims description 6
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 claims description 5
- 229960003150 bupivacaine Drugs 0.000 claims description 5
- 229960002409 mepivacaine Drugs 0.000 claims description 5
- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 claims description 5
- 229950002569 trimecaine Drugs 0.000 claims description 5
- GOZBHBFUQHMKQB-UHFFFAOYSA-N trimecaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=C(C)C=C1C GOZBHBFUQHMKQB-UHFFFAOYSA-N 0.000 claims description 5
- 229960001747 cinchocaine Drugs 0.000 claims description 3
- PUFQVTATUTYEAL-UHFFFAOYSA-N cinchocaine Chemical compound C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCCN(CC)CC)=C21 PUFQVTATUTYEAL-UHFFFAOYSA-N 0.000 claims description 3
- 230000001804 emulsifying effect Effects 0.000 claims description 3
- HQFWVSGBVLEQGA-UHFFFAOYSA-N 4-aminobenzoic acid 3-(dibutylamino)propyl ester Chemical compound CCCCN(CCCC)CCCOC(=O)C1=CC=C(N)C=C1 HQFWVSGBVLEQGA-UHFFFAOYSA-N 0.000 claims description 2
- 229960003369 butacaine Drugs 0.000 claims description 2
- 229960001290 butanilicaine Drugs 0.000 claims description 2
- VWYQKFLLGRBICZ-UHFFFAOYSA-N butanilicaine Chemical compound CCCCNCC(=O)NC1=C(C)C=CC=C1Cl VWYQKFLLGRBICZ-UHFFFAOYSA-N 0.000 claims description 2
- OECNHRSNFLARHZ-UHFFFAOYSA-N n-[2-(2-butoxyphenoxy)ethyl]-n-propan-2-ylpropan-2-amine Chemical compound CCCCOC1=CC=CC=C1OCCN(C(C)C)C(C)C OECNHRSNFLARHZ-UHFFFAOYSA-N 0.000 claims description 2
- 229960003502 oxybuprocaine Drugs 0.000 claims description 2
- CMHHMUWAYWTMGS-UHFFFAOYSA-N oxybuprocaine Chemical compound CCCCOC1=CC(C(=O)OCCN(CC)CC)=CC=C1N CMHHMUWAYWTMGS-UHFFFAOYSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
- 239000006071 cream Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 7
- 229920002125 Sokalan® Polymers 0.000 description 6
- 238000009472 formulation Methods 0.000 description 4
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- ARIWANIATODDMH-UHFFFAOYSA-N rac-1-monolauroylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- XNMYNYSCEJBRPZ-UHFFFAOYSA-N 2-[(3-butyl-1-isoquinolinyl)oxy]-N,N-dimethylethanamine Chemical compound C1=CC=C2C(OCCN(C)C)=NC(CCCC)=CC2=C1 XNMYNYSCEJBRPZ-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 208000006558 Dental Calculus Diseases 0.000 description 1
- 208000035859 Drug effect increased Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 208000012266 Needlestick injury Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940068939 glyceryl monolaurate Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000007388 punch biopsy Methods 0.000 description 1
- 229960005038 quinisocaine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 210000003454 tympanic membrane Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/113—Multiple emulsions, e.g. oil-in-water-in-oil
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
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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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q15/00—Anti-perspirants or body deodorants
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Abstract
Description
ïsïzozn-1 10 l5 20 25 30 Det har sålunda rests krav på en salva eller kräm, som ger anestesi genom intakt hud, varvid ett ytterligare sönskemål är att hålla koncentrationen av lokalanestetiskt medel låg för att undvika varje tendens till biverkningar. Thus, a requirement has been raised for an ointment or cream which provides anesthesia through intact skin, a further advantage being to keep the concentration of local anesthetic low to avoid any tendency to side effects.
Detta har nu överraskande blivit uppfyllt genom föreliggande uppfinning, som avser en emulsionssalvekomposition, inne- hållande från 0,5 viktprocent av åtminstone ett lokalaneste- tiskt medel och vilken kännetecknas av att det lokalaneste- tiska medlet i basform som sådan eller löst i en olja bildar oljefasen av en olja-i-vatten-emulsion, varvid koncentrationen av lokalanestetiskt medel i oljedropparna är sådan att oljan är huvudsakligen mättad med nämnda lokalanestetiska medel och att huvuddelen av oljedropparna har en storlek som inte överstiger l0 u, företrädesvis inte överstiger 3 p i diameter.This has now surprisingly been fulfilled by the present invention, which relates to an emulsion ointment composition, containing from 0.5% by weight of at least one local anesthetic and which is characterized in that the local anesthetic in base form as such or dissolved in an oil forms the oil phase of an oil-in-water emulsion, wherein the concentration of local anesthetic in the oil droplets is such that the oil is substantially saturated with said local anesthetic and that the majority of the oil droplets have a size not exceeding 10 μ, preferably not exceeding 3 μm in diameter.
En ytterligare fördel med en sådan emulsionssalva är att den i vissa fall kan steriliseras medelst autoklavering.A further advantage of such an emulsion ointment is that in some cases it can be sterilized by autoclaving.
Enligt en föredragen utföringsform av uppfinningen är det lokalanestetiska medlet valt ur den grupp som består av prilokain, lidokain, bupivakain, mepivakain, etidokain, ketocain, 2-(2-n-butoxifenoxi)-l-diisopropylaminoetan, tetrakain, butanilikain, trimekain, dibukain, quinisokain, butakain, oxybuprokain och tolykain.According to a preferred embodiment of the invention, the local anesthetic is selected from the group consisting of prilocaine, lidocaine, bupivacaine, mepivacaine, ethidocaine, ketocaine, 2- (2-n-butoxyphenoxy) -1-diisopropylaminoethane, tetracaine, butanilicaine, trimeca , quinisocaine, butacaine, oxybuprocaine and tolykain.
Blandningar av lokalanestetiska medel kan också användas, varvid en av prilokain, tetrakain, butinilakain och trimekain blandas med en av lidokain, bupivakain, mepivakain, etido- kain, dibukain, tetrakain, butinilakain och trimekain.Mixtures of local anesthetics may also be used, one of which is prilocaine, tetracaine, butinilacaine and trimecaine mixed with one of lidocaine, bupivacaine, mepivacaine, ethidocaine, dibucaine, tetracaine, butinilacaine and trimecaine.
Andra blandningar kan också användas. ' l0 l5 20 25 30 7812020-1 Den framställda emulsionssalvan består av en emulsion av olja i vatten, varvid den förutom det lokalanestetiska medlet i basform omfattar vatten, ett lösningsmedel för det lokalanestetiska medlet om nödvändigt, och en emulgator och ett förtjockningsmedel.Other mixtures can also be used. 7812020-1 The emulsion ointment prepared consists of an emulsion of oil in water, in addition to the local anesthetic in basic form comprising water, a solvent for the local anesthetic if necessary, and an emulsifier and a thickener.
Företrädesvis omfattar formuleringen Lokalanestetiskt medel l-20 viktprocent Lösningsmedel (olja) 0-72 " Emulgator 0.2-20 " Förtjockningsmedel 0.5-2 " Vatten l5-95 " I vissa fall består det lokalanestetiska medlet av en olja av vilken följer 0 viktprocent av lösningsmedlet.Preferably the formulation Local anesthetic comprises 1-20% by weight Solvent (oil) 0-72 "Emulsifier 0.2-20" Thickener 0.5-2 "Water l5-95" In some cases the local anesthetic consists of an oil of which follows 0% by weight of the solvent.
Lösningsmedlet skall vara ett lösningsmedel som är oblandbart med vatten. Lämpliga lösningsmedel är monoglycerider som har en fettsyrakomponent med 12-18 kolatomer, exempelvis glycerylmonolaurat, och triglycerider, såsom exempelvis en härdad växtglyceridblandning, exempelvis Miglyol®8l2 olja, som är ett härdat kokosfett med medelkedjelängd.The solvent must be a solvent that is immiscible with water. Suitable solvents are monoglycerides having a fatty acid component having 12-18 carbon atoms, for example glyceryl monolaurate, and triglycerides, such as, for example, a hardened plant glyceride mixture, for example Miglyol® 822 oil, which is a medium chain hardened coconut fat.
Den använda emulgatorn är av non-jonisk typ såsom polyoxy- etylenfettsyra-ester eller sorbitan-fettsyra-ester. Sådana emulgatorer är Arlaton®289 och Tween®80. Lecitin kan också användas.The emulsifier used is of the non-ionic type such as polyoxyethylene fatty acid ester or sorbitan fatty acid ester. Such emulsifiers are Arlaton®289 and Tween®80. Lecithin can also be used.
Det använda förtjockningsmedlet kan också ha emulgerande egenskaper. Carbopol®, Methocel®, Pluronic® och karboxi- metylcellulosa kan användas. Carbopol® och Pluronic® har också emulgerande egenskaper.The thickener used may also have emulsifying properties. Carbopol®, Methocel®, Pluronic® and carboxymethylcellulose can be used. Carbopol® and Pluronic® also have emulsifying properties.
Tål 2020-1 lÜ 15 2D 30 35 Emulsionen framställes genom att lösa den lokalanestetiska basen i oljan (Miglyolfi8l2) och smältes tillsammans med emulgatorn (Arlaton@2B9], varvid en mindre mängd vatten tillsättes medan blandningen är varm. Den resulterande blandningen kyles, varpå Förtjockningsmedlet (Carbopolm) blandat med resten av vattnet tillsättes som en gel. Denna resulterande blandning homogeniseras till en sådan grad att huvuddelen av oljedropparna har en diameter av <3 p.Withstands 2020-1 lU 15 2D 30 35 The emulsion is prepared by dissolving the local anesthetic base in the oil (Miglyol fi8 l2) and melted together with the emulsifier (Arlaton® 2B9], adding a small amount of water while the mixture is hot. The resulting mixture is cooled, then cooled. The thickener (Carbopolm) mixed with the rest of the water is added as a gel, this resulting mixture is homogenized to such an extent that the majority of the oil droplets have a diameter of <3 p.
Det lokalanestetiska medlet löses i oljan på sådant sätt att en mättad lösning, eller huvudsakligen mättad lösning av anestetiskt medel i oljan erhålles. Med användning av lidokain erhålles mättnad, då 27.6 % lidokainbas har lästs.The local anesthetic is dissolved in the oil in such a way that a saturated solution, or substantially saturated solution of anesthetic in the oil is obtained. With the use of lidocaine, saturation is obtained, as 27.6% lidocaine base has been read.
Enligt uppfinningen skall oljedropparna inte överstiga en diameter av 1D p, företrädesvis inte 3 p. Emellertid skall inte oljedropparna homogeniseras i sådan grad att en mikro- emulsion erhålles, då denna kommer att Förlora sin aktivitet.According to the invention, the oil droplets should not exceed a diameter of 1D p, preferably not 3 p. However, the oil droplets should not be homogenized to such an extent that a microemulsion is obtained, as this will lose its activity.
Dosen lokalanestetiskt medel beror på medlets potens men är som regel l-3DD mg/omz, mera vanligt 5-3D mg/omz.The dose of local anesthetic depends on the potency of the agent but is usually 1-3DD mg / omz, more usually 5-3D mg / omz.
Följande exempel illustrerar uppFinningen mera i detalj.The following examples illustrate the invention in more detail.
Exempel l Prilokain lD viktprocent Miglyufäslz 15.5 'f Arlatone@2B9 6 " Carbopol®934 1 " Vatten 64.5 " En emulsionssalva Framställdes enligt den allmänna bered- níngsprooeduren ovan. God lokalanestetisk effekt erhålles, då salvan appliceras på ytan av intakt hud. 5 FN lÜ f~ l5 ZÜ f* 25 f~ 30 Éyempel 2 Lidokain Mig1y@1“a12 Arlat0ne®2B9 Carbopol®934 Vatten 7§l2Û20-1 10 viktprocent 27.6 " 9.0 " l.Ü " 52.4 " En emulsionssalva Framställdes enligt den allmänna bered- ningsprpceduren ovan. God lokalanestetisk ettekt erhålles, då salvan appliceras på ytan av intakt hud.Example 1 Prilocaine 1% by weight Miglyufäslz 15.5 'f Arlatone® 2B9 6 "Carbopol®934 1" Water 64.5 "An emulsion ointment Prepared according to the general preparation procedure above. Good local anesthetic effect is obtained when the ointment is applied to the surface of intact skin. 5 FN lÜ f ~ l5 ZÜ f * 25 f ~ 30 Example 2 Lidocaine Mig1y @ 1 “a12 Arlat0ne®2B9 Carbopol®934 Water 7§l2Û20-1 10% by weight 27.6" 9.0 "l.Ü" 52.4 "An emulsion ointment Prepared according to the general preparation Good local anesthetic effect is obtained when the ointment is applied to the surface of intact skin.
Exempel 3 Lidokain M1g1y@1®a12 Arlatonem2B9 Carbopol@934 Vatten 5 víktprocent 13.8 " 4.5 " 1.0 " 75.7 " En emulsionesalva Framställdes enligt det allmänna törfarandet ovan. God lokalanestetisk eFFekt erhölls. IJFP tabell 3).Example 3 Lidocaine M1g1y @ 1®a12 Arlatonem2B9 Carbopol @ 934 Water 5% by weight 13.8 "4.5" 1.0 "75.7" An emulsion ointment Prepared according to the general dry procedure above. Good local anesthetic effect was obtained. IJFP Table 3).
Exempel 4 Lidpkain Mig1y@1®s12 Arlatone®289 Carb0pol®934 Vatten N) viktprocent B. 2.25 " l 67.35 ” En emulsionssalva tramställdes enligt det allmänna FörFarandet ovan. Bed anestetisk e¥¥ekt erhålles. IJFP tabell 3). .sfísjfzazo - 1 10 15 20 25 30 35 Exempel 5 Príldkain 5.04 víktprocent Lidokain 4.96 " Arlatonefizas 3.75 " Carbop0l®934 1.0 " Vatten 85.25 " En emulsidnssalva framställdes i enlighet med det allmänna Förtarandet ovan. God lekalaestetísk eF¥ekt erhålles då salvan applicerades på ytan.Example 4 Lidpkain Mig1y @ 1®s12 Arlatone®289 Carb0pol®934 Water N)% by weight B. 2.25 "l 67.35" An emulsion ointment was trampled according to the general Procedure above. Bed anesthetic is obtained. IJFP table 3). .Sfísjfzaz 1 5 15 20 25 30 35 Example 5 Príldkain 5.04% by weight Lidocaine 4.96 "Arlatone fi zas 3.75" Carbop0l®934 1.0 "Water 85.25" An emulsion ointment was prepared according to the general procedure above. Good medical aesthetic effect is obtained when the ointment is applied to the surface.
Exemgel 6 Prilokain 30.24 viktprocent Líddkain 29.76 ” Ar1at@ne®2a9 22.5 " Carbopol®934 1.0 " Vatten 16.5 " En emulsidnssalva Framställdes i enlighet med det allmänna törtarandet ovan. God lokalanestetísk efïekt erhölls, då salvan applicerades på ytan.Exemgel 6 Prilocaine 30.24% by weight Líddkain 29.76 "Ar1at® ne®2a9 22.5" Carbopol®934 1.0 "Water 16.5" An emulsion ointment Prepared according to the general tarring trend above. Good local anesthetic effect was obtained when the ointment was applied to the surface.
ExemEel 7 Prilukaín 2.52 víktprocent Lidokain 2.48 " Ar1at0ne®zß9 1.aaa " Carb0pol®934 1.0 " Vatten 92.12 ” En emulsionssalva Framställdes í enlighet med den allmänna proceduren ovan. God lokalanestetísk effekt erhölls, då salvan applícerades på ytan. 10 15 20 25 30 7'8Ü"{'202;0~ 1 7 Exempel B Ketocain 0.5 viktprocent Ar1at0n@®2e0 0.2 " Carb0pol@934 1.0 " Vatten 98.3 " En emulsionssalva framställdes i enlighet med den allmänna proceduren ovan. Lokalanestetísk eF¥ekt erhölls, då salvan applicerades på ytan.Example 7 Prilukaín 2.52% by weight Lidocaine 2.48 "Ar1at0ne®zß9 1.aaa" Carb0pol®934 1.0 "Water 92.12" An emulsion ointment Prepared according to the general procedure above. Good local anesthetic effect was obtained when the ointment was applied to the surface. 7'8Ü "{'202; 0 ~ 1 7 Example B Ketocaine 0.5% by weight Ar1at0n @ ®2e0 0.2" Carb0pol @ 934 1.0 "Water 98.3" An emulsion ointment was prepared according to the general procedure above. Local anesthetic effect was obtained when the ointment was obtained. was applied to the surface.
Exempel 9 Ketocaín 5 víktprocent Arlat0ne@2B9 2 " Carbopolm934 1 " Vatten 92 " En emulsionssalva Framställdes i enlighet med den allmänna proceduren ovan. Lokalanestetisk e¥Fekt erhölls, då salvan applicerades på ytan.Example 9 Ketocaine 5% by weight Arlatone® 2B9 2 "Carbopolm934 1" Water 92 "An emulsion ointment Prepared according to the general procedure above. Local anesthetic effect was obtained when the ointment was applied to the surface.
Exempel 10 Ketocaín 2.5 viktprocent Arlatßnefizas 1.0 " carbapnfssß. 1.0 " Vatten 95.5 " En emulsionssalva framställdes i enlighet med den allmänna proceduren som ovan givits. Lokalanestetisk e¥¥ekt erhölls då salvan applícerades på ytan. 7312020-1 10 l5 20 25 30 35 8 Exempel ll Ketocain l viktprocent Arlatone®2B9 0.4 " carbnp01®934 1.0 " Vatten 97.6 " En emulsionssalva erhölls i enlighet med den allmänna beskrivningen som givits ovan. Lokalanestetisk eFFekt erhölls, då salvan applicerades på yta.Example 10 Ketocaine 2.5% by weight Arlatzene as zas 1.0 "carbapnfssß. 1.0" Water 95.5 "An emulsion ointment was prepared according to the general procedure given above. Local anesthetic effect was obtained when the ointment was applied to the surface. 7312020-1 10 l5 20 25 30 35 8 Example 11 Ketocaine 1% by weight Arlatone®2B9 0.4 "carbnp01®934 1.0" Water 97.6 "An emulsion ointment was obtained according to the general description given above. Local anesthetic effect was obtained when the ointment was applied to the surface.
BIÜLÛGISK EFFEKT Material och metoder Marsvin (hanar, Dunkin-Hartley-stam), 6-8 veckor gamla, användes i denna studie. Håret på huden på ryggen hos mar- esvinen avlägsnades och en cirkelFormad yta av ungetär 4.5Cm2 skrapades med BUF-Putm (Riker). Testberedníngen gnuggades in i det skrubbade skinnet under 30 sekunder. Test tör anestetisk eftekt medelst prickning med nål utfördes sex gånger på olika platser på det behandlade området med regel- bundna intervall under och eFter tidpunkten ¥ör applicering intill dess att ingen anestetisk eF¥ekt kunde registreras.BIOLOGICAL EFFECT Materials and methods Guinea pigs (males, Dunkin-Hartley strain), 6-8 weeks old, were used in this study. The hair on the skin on the back of the guinea pig was removed and a circle-shaped surface of 4.5 cm2 was scraped with BUF-Putm (Riker). The test preparation was rubbed into the scrubbed skin for 30 seconds. Testing for anesthetic effect by needle puncture was performed six times at different sites on the treated area at regular intervals during and after the time before application until no anesthetic effect could be registered.
Testberedningen tvättades inte bort.The test preparation was not washed off.
Emulsionssalvor med 0.25-5.0 % lídokain och 5.0 % lidokain- salva studerades. De använda beredningarna är beskrivna i tabell l. Studien genomfördes dubbelblint. Student's t-test användes För att beräkna den statistiska signifikansen. En signiFikant skillnad hade ett P-värde av:í0.05.Emulsion ointments with 0.25-5.0% lidocaine and 5.0% lidocaine ointment were studied. The preparations used are described in Table 1. The study was conducted double-blind. Student's t-test was used to calculate the statistical significance. A significant difference had a P-value of: í0.05.
Resultat Emulsionssalva med 5 2 lidokainbas och den kommersiellt o tillgängliga 5 6 lidokainsalvan jämfördes i en Första serie experiment. Som Framgår av tabell 2 var emulsionssalvan klart 10 15 20 25 30 35 7312029-1 o mera effektiv än salvan. Maximumeffekterna var ungefär 60 4 blockad och 35 % blockad applicering. Fullständig och erhölls 15 minuter efter återgång inträffade inom två respek- tive en timme.Results Emulsion ointment with 5 2 lidocaine base and the commercially available 5 6 lidocaine ointment were compared in a First series of experiments. As shown in Table 2, the emulsion ointment was clearly more effective than the ointment. The maximum effects were approximately 60 4 blocked and 35% blocked application. Complete and obtained 15 minutes after return occurred within two and one hour respectively.
Ett dosresponsförhållande observerades med emulsionssalvan i en andra serie med experiment (tabell 3). Den uppnådda lído- blockad med formuler- maximumeffekten ökade från ca 20 % blockad med 1,0 % o kainemulsionssalva till omkring 90 4 ingen innehållande 5 % lidokainsalva (tabell 3) var ca 25 % effekt mellan 2,5 och 5,0 % 5,0 % effektivitet erhölls 5-15 minuter efter applícering. Full- Motsvarande värde med blockad. Skillnaden i lidokainemulsionssalva gentemot lidokain. lidokainsalva var statistiskt signifikant. Maximum ständig återhämtning från blockad uppträdde från ungefär 30 till 80 minuter efter applicering. Vehioklarna enbart hade ingen blockerande effekt.A dose-response relationship was observed with the emulsion ointment in a second series of experiments (Table 3). The achieved lido blockade with formula- maximum effect increased from about 20% blockade with 1.0% o cain emulsion ointment to about 90 4 none containing 5% lidocaine ointment (Table 3) was about 25% effect between 2.5 and 5.0% 5 .0% efficiency was obtained 5-15 minutes after application. Full- Corresponding value with blockade. The difference in lidocaine emulsion ointment versus lidocaine. lidocaine ointment was statistically significant. Maximum continuous recovery from blockade occurred from approximately 30 to 80 minutes after application. Vehicles alone had no blocking effect.
Sammanfattning Emuleionssalvor med lidokainbas var effektiva vid utplåning av svaret för pin-prick då de gnuggas in i skrapad hud hos 2,5 och 5,0 % potent än lidokain 5,0 %-salva. marsvin. emulsionssalva med lidokain var mera Tabell 1 A. Kompositioner av emulsionssalvor av lidokainbas.Summary Emulsion ointments with lidocaine base were effective in erasing the pin-dot response when rubbed into scraped skin at 2.5 and 5.0% potent than lidocaine 5.0% ointment. guinea pig. lidocaine emulsion ointment was more Table 1 A. Compositions of lidocaine base emulsion ointments.
Formulering nr I II III IV V Lidokainbas - 0.25 g 1.0 g 2.5 g 5.0 g Arlatoneßzse 2.25 g 0.23 g 0.90 g 2.25 g 4.5 g Miglyolæolja 6.9 g 0.69 g 2.75 g 6.9 g }3.8 g carbopøïfläesß, 1.0 g 1.0 g 1.0 g 1.0 g 1.0 g Natriumhydroxid + + + + + Vatten till 100 g 100 g 100 g 100 g 100 g TfšÛTZ-Ûâíl- 1 10 15 20 25 30 10 Tabell l B. Komposition av lídokaín 5 % salva och salvbas.Formulation No. I II III IV V Lidocaine base - 0.25 g 1.0 g 2.5 g 5.0 g Arlatone nectar 2.25 g 0.23 g 0.90 g 2.25 g 4.5 g Miglyole oil 6.9 g 0.69 g 2.75 g 6.9 g} 3.8 g carbopoeia, 1.0 g 1.0 g 1.0 g 1.0 g 1.0 g Sodium hydroxide + + + + + Water to 100 g 100 g 100 g 100 g 100 g TfšÛTZ-Ûâíl- 1 10 15 20 25 30 10 Table l B. Composition of lidocaine 5% ointment and ointment base.
Formulering nr VI VII Lidokainbas - - 5.0 g Propylenglykol 25.0 g 25.0 g Vatten '2.0 g 2.0 g ßarbøwaxæ) *C111 mn g mn g Tabell Z. E¥¥ekter av 5 % lídokain emulsionssalva (V) och 5 % lídokain salva, kommersiell (VII)- Varje värde är medelvärde i s.e.m. av anestetisk eF¥ekt till pín-prick med en nål sex gånger på olika platser i den behandlade ytan i grupper av 12 marsvin. p550.Ül = (xx), pfi0.001 = (xxx) Fprmuleríng I Lokalanestetisk effekt i % efter 5 10 15 30 45 60 75 90 105 120 minuter V 52 73 K 82 59 52 32 25 12 5 VII 15 27 27 B 3 l 0 0 0 ' t-test V/VII xx xxx xxx xxx xxx xxx - - - - E 10 15 20 25 35 lrfiifzozn- 1 11 Tabell 3. E¥Fekter av varierande koncentrationer av lido- kainemulsionssalvor och 5 % lidokainsalva (kommersiell). Varje värde som givits är medel- värde i s.e.m. anestetisk e¥Fekt till pin-prick med en nål sex gånger på olika platser i den behandlade ytan i grupper av 8 marsvin. i .Formulation No VI VII Lidocaine base - - 5.0 g Propylene glycol 25.0 g 25.0 g Water '2.0 g 2.0 g ßarbøwaxæ) * C111 mn g mn g Table Z. E ¥OB ekter of 5% lidocaine emulsion ointment (V) and 5% lidocaine ointment, commercial (VII) - Each value is the mean of sem of anesthetic effect to pin point with a needle six times in different places in the treated surface in groups of 12 guinea pigs. p550.Ül = (xx), p fi0.001 = (xxx) Formulation I Local anesthetic effect in% after 5 10 15 30 45 60 75 90 105 120 minutes V 52 73 K 82 59 52 32 25 12 5 VII 15 27 27 B 3 l 0 0 0 't test V / VII xx xxx xxx xxx xxx xxx - - - - E 10 15 20 25 35 lr fi ifzozn- 1 11 Table 3. E ¥ Effects of varying concentrations of lidocaine emulsion ointments and 5% lidocaine ointment (commercial ). Each value given is the mean value in s.e.m. anesthetic e ¥ Effective to pin-dot with a needle six times in different places in the treated surface in groups of 8 guinea pigs. i.
;Formuler1ng nr! Lokalanestetisk eF¥ekt i % eFter i 5 1n 15 sn sn 75 min. 1 n n n n i V1 n n n 11 15 1s n n n 4 111 25 25 15 4 n n Iv 55 75 67 47 25 12 v 52 az en se an 1n v11 12 21 í 27 n n n Föreliggande emulsionssalva kan användas var än en lokal- anestetisk e¥Fekt önskas och närhelst det är möjligt att erhålla detta medelst ytapplicering. Sålunda kan anestesi erhållas genom slemhinna och intakt och skadad hud. EFter anestesi kan Följande ingrepp göras.; Formulation1ng no! Local anesthetic effect in% after 5 1n 15 sn sn 75 min. 1 nnnni V1 nnn 11 15 1s nnn 4 111 25 25 15 4 nn Iv 55 75 67 47 25 12 v 52 az en se an 1n v11 12 21 í 27 nnn The present emulsion ointment can be used anywhere a local anesthetic e ¥ Effect is desired and whenever possible it is possible to obtain this by surface application. Thus, anesthesia can be obtained through mucosa and intact and damaged skin. After anesthesia, the following procedures can be performed.
Slemhinna: tagande av punch-biopsi, mindre ingrepp i under- liggande slemhinna, exempelvis kurettage eller gingivektomi, eller tandstensborttagning, elimineríng av nålstíckssmärta vid injektion. Ütolaryngologiska ingrepp i näsa och hals, exempelvis biopsi eller trepanation.Mucosa: taking a punch biopsy, minor surgery on the underlying mucosa, such as curettage or gingivectomy, or tartar removal, elimination of needle stick pain on injection. Ütolaryngological procedures in the nose and throat, such as biopsy or trepanation.
*Paracenteses av trumhinna. Érovtagning i det urogenitala området.* Paracentesis of the eardrum. Removal in the urogenital area.
Lokalanestesi av cervix vid Förlossning. fšfïjfiflíß- 1 12 Intakt hud: Mindre ingrepp i hud, exempelvis biopsí eller excision av naevi, elímínering av nålsmärta ¥öre injektion.Local anesthesia of the cervix at delivery. fšfïj fifl íß- 1 12 Intact skin: Minor skin interventions, such as biopsy or excision of the navel, elimination of needle pain ¥ öre injection.
Claims (5)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE7713617A SE7713617L (en) | 1977-12-01 | 1977-12-01 | ANTITRANSPIRATIVES |
| SE7713618A SE7713618L (en) | 1977-12-01 | 1977-12-01 | LOCAL ANESTHETIC MIXTURE |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7812020L SE7812020L (en) | 1979-06-02 |
| SE432192B true SE432192B (en) | 1984-03-26 |
Family
ID=26656921
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7812020A SE432192B (en) | 1977-12-01 | 1978-11-22 | A LOCAL ANESTHETIC EMULSION ALVA FOR EXTERNAL USE OF THE TYPE OF OIL-IN-WATER EMULSION |
Country Status (4)
| Country | Link |
|---|---|
| AU (1) | AU524406B2 (en) |
| DE (1) | DE2851369A1 (en) |
| GB (1) | GB2008946B (en) |
| SE (1) | SE432192B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3066859D1 (en) | 1979-10-26 | 1984-04-12 | Smith & Nephew Ass | Autoclavable emulsions |
| US5489426A (en) * | 1980-07-01 | 1996-02-06 | L'oreal | Cosmetic composition based on an aqueous dispersion of small lipid spheres |
| US5439672A (en) * | 1980-07-01 | 1995-08-08 | L'oreal | Cosmetic composition based on an aqueous dispersion of small lipid spheres |
| SE9704031D0 (en) * | 1997-11-05 | 1997-11-05 | Astra Ab | Novel formulation |
| US9642912B2 (en) | 2006-03-06 | 2017-05-09 | Crescita Therapeutics Inc. | Topical formulations for treating skin conditions |
| US9308181B2 (en) | 2006-03-06 | 2016-04-12 | Nuvo Research Inc. | Topical formulations, systems and methods |
| US9012477B2 (en) | 2009-01-06 | 2015-04-21 | Nuvo Research Inc. | Method of treating neuropathic pain |
| MX2012008168A (en) | 2010-01-14 | 2013-02-07 | Nuvo Res Inc | Solid-forming local anesthetic formulations for pain control. |
-
1978
- 1978-11-22 SE SE7812020A patent/SE432192B/en not_active IP Right Cessation
- 1978-11-28 DE DE19782851369 patent/DE2851369A1/en active Granted
- 1978-11-29 AU AU42028/78A patent/AU524406B2/en not_active Expired
- 1978-11-30 GB GB7846755A patent/GB2008946B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| AU524406B2 (en) | 1982-09-16 |
| DE2851369C2 (en) | 1988-04-28 |
| GB2008946A (en) | 1979-06-13 |
| GB2008946B (en) | 1982-06-30 |
| AU4202878A (en) | 1979-06-07 |
| DE2851369A1 (en) | 1979-06-07 |
| SE7812020L (en) | 1979-06-02 |
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