SI9300115A - Topical use of local anaesthetic agents and a pharmaceutical preparation for rheumatoid arthritis and a method for the treatment thereof - Google Patents
Topical use of local anaesthetic agents and a pharmaceutical preparation for rheumatoid arthritis and a method for the treatment thereof Download PDFInfo
- Publication number
- SI9300115A SI9300115A SI19939300115A SI9300115A SI9300115A SI 9300115 A SI9300115 A SI 9300115A SI 19939300115 A SI19939300115 A SI 19939300115A SI 9300115 A SI9300115 A SI 9300115A SI 9300115 A SI9300115 A SI 9300115A
- Authority
- SI
- Slovenia
- Prior art keywords
- rheumatoid arthritis
- lidocaine
- pharmaceutical preparation
- topical
- treatment
- Prior art date
Links
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 25
- 230000000699 topical effect Effects 0.000 title claims abstract description 14
- 229960005015 local anesthetics Drugs 0.000 title claims abstract description 9
- 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims description 8
- WZSPWMATVLBWRS-UHFFFAOYSA-N 2-(diethylamino)-n-(2,6-dimethylphenyl)acetamide;n-(2-methylphenyl)-2-(propylamino)propanamide Chemical compound CCCNC(C)C(=O)NC1=CC=CC=C1C.CCN(CC)CC(=O)NC1=C(C)C=CC=C1C WZSPWMATVLBWRS-UHFFFAOYSA-N 0.000 claims abstract 3
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 239000003589 local anesthetic agent Substances 0.000 claims description 25
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 12
- 229960004194 lidocaine Drugs 0.000 claims description 11
- 230000003444 anaesthetic effect Effects 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000000374 eutectic mixture Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 238000004381 surface treatment Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000006071 cream Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 229920002125 Sokalan® Polymers 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 210000001503 joint Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 230000028709 inflammatory response Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000030214 innervation Effects 0.000 description 3
- 230000002889 sympathetic effect Effects 0.000 description 3
- 229940019097 EMLA Drugs 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- -1 fatty acid ester Chemical class 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 description 1
- 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 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- 235000000832 Ayote Nutrition 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 235000009854 Cucurbita moschata Nutrition 0.000 description 1
- 240000001980 Cucurbita pepo Species 0.000 description 1
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960003150 bupivacaine Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 210000002310 elbow joint Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- XPXMKIXDFWLRAA-UHFFFAOYSA-N hydrazinide Chemical compound [NH-]N XPXMKIXDFWLRAA-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 229960001807 prilocaine Drugs 0.000 description 1
- MVFGUOIZUNYYSO-UHFFFAOYSA-N prilocaine Chemical compound CCCNC(C)C(=O)NC1=CC=CC=C1C MVFGUOIZUNYYSO-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000015136 pumpkin Nutrition 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000006335 response to radiation Effects 0.000 description 1
- 229960001549 ropivacaine Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229920002554 vinyl polymer Polymers 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
- 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
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
POVRŠINSKA UPORABA LOKALNIH ANESTETIKOV IN FARMACEVTSKEGA PRIPRAVKA PRI REVMATOIDNEM ARTRITISU, TER NAČIN NJEGOVEGA ZDRAVLJENJASURFACE USE OF LOCAL ANESTHETICS AND PHARMACEUTICAL PREPARATION IN RHEUMATOID ARTHRITIS AND THE METHOD OF ITS TREATMENT
P 1132-1P 1132-1
1993-02-081993-02-08
POVRŠINSKA UPORABA LOKALNIH ANESTETIKOV IN FARMACEVTSKEGA PRIPRAVKA PRI REVMATOIDNEM ARTRITISU, TER NAČIN NJEGOVEGA ZDRAVLJENJASURFACE USE OF LOCAL ANESTHETICS AND PHARMACEUTICAL PREPARATION IN RHEUMATOID ARTHRITIS AND THE METHOD OF ITS TREATMENT
Področje patentne zahteveClaim area
Predložena patentna zahteva se nanaša na uporabo pripravka, za lokalno aplikacijo na kožo, in vsebuje enega ali več lokalnih anestetikov, ali njihovih farmacevtsko sprejemljivih soli, za zdravljenje revmatoidnega artritisa, in z njim povezanim vneljem.The present claim relates to the use of a preparation for topical application to the skin and contains one or more topical anesthetics, or pharmaceutically acceptable salts thereof, for the treatment of rheumatoid arthritis, and related inflammation.
Osnova za patentno zahtevoThe basis of the claim
Revmatoidni artritis je bolezen, s pretežno neznano etiologijo. V večini primerov je to kronično obolenje, ki ga spremlja bolečina in invalidnost, posebaj v poznejših stadijih obolenja. Revmatoidni artritis (RA) obravnavamo kot vnetno obolenje, pri katerem pride do simetričnega povečanja sklepov in kit Widenfalk B. je odkril več znakov, ki nakazujejo da je debli povzročitelj RA tudi živčni sistem.Rheumatoid arthritis is a disease with a largely unknown etiology. In most cases, this is a chronic illness accompanied by pain and disability, especially in the later stages of the disease. Rheumatoid arthritis (RA) is considered to be an inflammatory condition in which there is a symmetric enlargement of the joints and the Widenfalk B. kit has detected several signs suggesting that the obese RA is also a nervous system.
Widenfalk B. Spinalno stična povezava za simetrično refleksni odgovor.”, Scand. J. Plast Reconstr. Hand. Surg. 24: str. 207212, (1990), in Simpatična inervacija normalnega in revmatoidno sinergičnega tkiva.”, Scand. J. Plast Reconstr. Hand. Surg. 25: str. 31-31, (1991), Widenfalk B. et al. Izvor simpatične in senzorne inervacije komolčnega sklepa pri podganah: Retrogradna študija aksona, označenega z aglutinini iz pšeničnih kalčkov konjugiranimi s hrenovo peroksidazo.”, The J. of Comparative Neurology 271: str. 313-318, (1988) m Widenfalk B., Wiberg M. Izvor simpatične in senzorne inervacije kolenskega sklepa.”,Widenfalk B. Spin-joint connection for symmetrically reflex response. ”, Scand. J. Plast Reconstr. Hand. Surg. 24: p. 207212, (1990), and Sympathetic innervation of normal and rheumatoid synergistic tissue. ”, Scand. J. Plast Reconstr. Hand. Surg. 25: p. 31-31, (1991), Widenfalk B. et al. Origin of sympathetic and sensory innervation of the elbow joint in rats: A retrograde study of an axon labeled with horseradish peroxidase-conjugated wheat germ agglutinins. ”, The J. of Comparative Neurology 271: p. 313-318, (1988) m Widenfalk B., Wiberg M. The origin of sympathetic and sensory innervation of the knee joint. ”,
Anat EmbryoL 180: str. 317-323, (1989). Znak, ki kaže, da je RA povzročen na ta način, je ugotovitev, da pri pacientu, kiAnat EmbryoL 180: p. 317-323 (1989). A sign indicating that RA is caused in this way is the finding that in a patient who
P 1132-1 trpi, zaradi tega obolenja in istočasno boleha za cerebrovasularno ležijo z delno paralizo telesa, v paraliziranem delu telesa, kjer je moten živčni prenos, ne opazimo vnetnega procesa. Po vbrizganju protivnetne učinkovine, npr. steroida, v sklep pacientu, obolelim za RA, po tovrstni opazimo vidno izboljšanje bolezni, zato smatramo, da je to terapija izbire za taka obolenja. Injiciranje v sklep je boleč klinični postopek, in v primeru RA je na več mestih, npr. na rokah, potrebnih mnogo injekcij. Zato, da bi zmanjšali bolečine pri tem postopku, pogosto steroidu dodamo lokalni anestetik, da zmanjšamo ali odstranimo bolečino, zaradi lokalnega draženja steroidne raztopine. Raztopni dodajamo lokalni anestetik predvsem z namenom blokade bolečine na mestu injiciranja. Ugotovili so, da lokalni anestetik vpliva na nastanek tkivnega vnetnega odgovora, kot je opisano v mnogih publikacijah.P 1132-1 suffers from this disease and, at the same time, suffers from cerebrovascular disease with partial paralysis of the body, no inflammatory process is observed in the paralyzed part of the body where the nervous transmission is impaired. After injection of an anti-inflammatory agent, e.g. of steroids, in the joint of a patient with RA, a marked improvement in the disease is observed after this, so we consider it to be the therapy of choice for such diseases. Injection into the joint is a painful clinical procedure, and in the case of RA it is in several places, e.g. on the hands, many injections are needed. Therefore, to reduce pain in this procedure, a steroid anesthetic is often added to the steroid to reduce or eliminate pain, due to local irritation of the steroid solution. A topical anesthetic is added to the solution mainly to block the injection site pain. A local anesthetic has been found to influence the formation of a tissue inflammatory response, as described in many publications.
Mehanizem protivnetnega delovanja lokalnih anstetikov je v glavnem neznan, in je definiran kot rezultat kombinacije blokade živčnega prenosa in učinka na lokalne mediatorje vnetja. Opazen zaščitni učinek lokalnih anestetikov, napram standardizirani poskusni poškodbi, je raziskal Ohlsen at el., Lokalni anestetiki, ki modificirajo dermalni odgovor na žarčenje. Acta Oncologica 26, (1987), Fasc. 6, str. 467-476.The mechanism of anti-inflammatory action of local anesthetics is largely unknown and is defined as the result of a combination of blockage of nerve transmission and effect on local inflammatory mediators. The observed protective effect of local anesthetics against standardized trial injury was investigated by Ohlsen at el., Local anesthetics modifying the dermal response to radiation. Acta Oncologica 26, (1987), Fasc. 6, p. 467-476.
V poskusni študiji na zajcih, je avtor ugotovil, da vnetni odgovor v kožnem tkivu živali, ki ga povzroči visoko energetsko sevanje, lahko opazno modificiramo aU celo popolnoma preprečimo s površinsko aplikacijo lokalnega anestetika (krema Emla), nanesenega na kožo poskusnih živaU pred in po poškodbi tkiva z žarčenjem. Rezultati te študije kažejo, da je po površinski aplikaciji možno zagotoviti zadostno tkivno koncentracijo lokalnega anestetika, da se zmanjša vnetni odgovor celo v globjih plasteh pod površinsko, na kožo, nanešenim pripravkom.In an experimental study in rabbits, the author found that the inflammatory response in the skin tissue of an animal caused by high energy radiation can be markedly modified aU even completely prevented by topical application of a local anesthetic (Emla cream) applied to the skin of experimental live before and after tissue damage by irradiation. The results of this study show that after surface application, it is possible to provide sufficient tissue concentration of a local anesthetic to reduce the inflammatory response even in deeper layers beneath the superficial, skin-applied preparation.
P 1132P 1132
Opis patentne zahteveDescription of the claim
Pri tej raziskavi nas je zanimalo, če mogoče ima površinsko apliciran lokalni anestetik ugodne učinke tudi v primerih RA, ali zmanjša vnetni odgovor v sklepih, ki so oddaljeni od zdravljene kože na rokah pacienta, obolelim za RA. Pacientom s prodromalnim simptomom RA, ki ga spremljata Še bolečina in zmanjšana gibljivost obeh rok, so aplicirali pripravek z lokalnim anestetikom (krema Emla) na sklepe in okoliške kožne površine. Površinski anestetik so nanesli pod okluzivno obvezo in levo neposredno na kožo za dve uri. To terapijo so ponavljali dvakrat dnevno dva dni. Po tej terapiji, je bolečina popolnoma izginila, gibljivost zdravljene roke se je normalizirala. Izboljšanje po tej terapiji je trajalo dlje kot teden dni, kar kaže, da trajanje pozitivnega učinka ni neposredno povezano z učinkom lokalnega anestetika, če smo tak učinek, preiskušali s tehniko zbadanja z buciko, je trajal le okrog 5 ur, Juhlin L. & Evers H.In this study, we were interested in whether a topically applied topical anesthetic may also have beneficial effects in RA cases, or reduce the inflammatory response in joints distant from the treated skin on the hands of a patient with RA. Patients with prodromal RA symptom, accompanied by pain and decreased mobility of both hands, were administered a local anesthetic preparation (Emla cream) to the joints and surrounding skin surfaces. The surface anesthetic was applied under occlusive dressing and left directly on the skin for two hours. This therapy was repeated twice daily for two days. After this therapy, the pain disappeared completely, the mobility of the treated arm returned to normal. Improvement after this therapy lasted longer than a week, suggesting that the duration of the positive effect was not directly related to the effect of local anesthetic, if we tested this effect with the pumpkin piercing technique, it only lasted about 5 hours, Juhlin L. & Evers H.
'EMLA: nov površinski anestetik., Adv. Dermatol. 5. str. 75-92, (1990). Pozitivni učinek, ki ga izzove lokalni anestetik pri takem pacientu, je potemtakem verjetno povezan z začasno prekinitvijo reakcije, ki teče v začaranem krogu, in jo drugače povzroči vnetno obolenje (RA).'EMLA: a new surface anesthetic., Adv. Dermatol. 5. p. 75-92 (1990). The positive effect elicited by a local anesthetic on such a patient is therefore likely to be associated with a temporary interruption of the reaction in the vicious cycle and otherwise caused by inflammatory disease (RA).
Zato, da bi še bolj utemeljili ugodne učinke, ki se kažejo po površinskem zdravljenju pacientov z RA, po aplikacijo sestave z lokalnim anestetikom, smo zdravili roke petih pacientov, z diagnosticiranim revmatoidnim artritisom.In order to further substantiate the beneficial effects of superficial treatment of RA patients following the administration of a topical anesthetic, we treated the hands of five patients with diagnosed rheumatoid arthritis.
Eksperimentalni podatkiExperimental data
Pet pacientov, z diagnosticiranim aktivnim revmatoidnim artritisom, smo zdravili lokalno, z nanašanjem EMLA na kožo, dva tedna. Pri vseh petih pacientih smo zasledil pozitiven učinek zdravljenja, zmanjšala se je bolečina in nastajanje otekline na prizadetih sklepih. Opaziti je bilo izboljšano gibljivost sklepovFive patients diagnosed with active rheumatoid arthritis were treated locally with EMLA application to the skin for two weeks. All five patients experienced a positive treatment effect, reducing pain and swelling on the affected joints. Improved joint motility was observed
P 1132-1 objektivo in subjektivno. Pri vseh pacientih je učinek trajal več kot dva tedna, vendar je le pri enem pacientu, tudi šest mesecev po terapiji, otekanje popolnoma izginilo.P 1132-1 lens and subjective. In all patients, the effect lasted for more than two weeks, but in only one patient, even six months after therapy, did the swelling disappear completely.
Farmacevtski pripravki, označeni s tem, da se zanje zahteva patentna zaščitaPharmaceutical preparations characterized in that they are subject to patent protection
Površinski pripravek z lokalnim anestetikom, je označen s tem, da ima sposobnost prodirati skozi nepoškodovano kožo, zaradi svojih farmacevtskih lastnosti, ali prehajati v kožo in pod njo ležeča tkiva, s pomočjo iontoforeze, ali dodatka pospeševalca penetracije (npr. DMSO, DMA ali Azone®),Topical preparation with a local anesthetic, characterized in that it has the ability to penetrate intact skin due to its pharmaceutical properties, or to penetrate into and into underlying skin through iontophoresis, or the addition of a penetration enhancer (eg DMSO, DMA or Azone ®),
Pripravek naj vsebuje najmanj en lokalni anestetik v obliki baze ali njegove farmacevtsko sprejemljive soli, ali evtektične zmesi lokalnih anestetikov aminoamidnega tipa (npr. lidokain, prilokain, bupivakain, ropivakain, itd.).The preparation should contain at least one local anesthetic in the form of a base or a pharmaceutically acceptable salt thereof, or an eutectic mixture of local aminoamide type anesthetics (eg lidocaine, prilocaine, bupivacaine, ropivacaine, etc.).
Lokalni anestetik(i) je (so) vgrajeni v gel, emulzijo, kremo, mazilo, raztopino za razprševanje ali pripravek, ki tvori film na koži.The topical anesthetic (s) is (are) embedded in a gel, emulsion, cream, ointment, spray solution or film-forming preparation on the skin.
Lokalni anestetik(e) je možno vgraditi v farmacevtski pripravek s podaljšanim sproščanjem aktivne učinkovin(e). Na tak način dosežemo dovolj visoko koncentracijo aktivne spojine skozi daljši Čas, zato pogostejše menjavnju obvez ni potrebno.The topical anesthetic (s) can be incorporated into a sustained release pharmaceutical ingredient (s). In this way, a sufficiently high concentration of the active compound is achieved over a longer period of time, so a more frequent change of commitments is not necessary.
Dodaten način aplikacije pripravka z lokalnim anestetikom je, uporaba sterilnega ali nesterilnega obliža prepojenega s pripravkom, ki vsebuje lokalni anestetik.An additional method of administering the preparation with a local anesthetic is to use a sterile or non-sterile patch soaked with a preparation containing a local anesthetic.
Pripravek, z lokalnim anestetikom, vsebuje med 0.25 utežnih % in 20 utežnih % lokalnega(ih) anestetika(ov), najbolj zažeijeno med 5% in 10%.The preparation, with a local anesthetic, contains between 0.25% by weight and 20% by weight of local anesthetic (s), most preferably between 5% and 10%.
P 1132-1P 1132-1
Farmacevtski pripravkiPharmaceutical preparations
Primer 1: 1% GELExample 1: 1% GEL
Lidokinijev klorid monohidrat Hidroksipropilmetilceluloza 400 cps 2M natrijev hidroksid do pH 6.3-6.7Lidokinium chloride monohydrate Hydroxypropyl methylcellulose 400 cps 2M sodium hydroxide up to pH 6.3-6.7
10.8 kg 24.5 kg10.8 kg 24.5 kg
Voda za injekcijeWater for injections
q.s. adq.s. ad
1000 11000 1
Lidokainijev klorid monohidrat in hidroksipropilmetilcelulozo raztopimo v vodi za injekcije. pH uravnamo na 6.3 do 6.7 z natrijevim hidroksidom in dopolnimo z vodo do 1000 litrov.Lidocaine chloride monohydrate and hydroxypropylmethylcellulose are dissolved in water for injection. Adjust the pH to 6.3 to 6.7 with sodium hydroxide and make up to 1000 liters with water.
Primer 2: 2% GELExample 2: 2% GEL
Lidokainijev klorid monohidrat Hidroksipropilmetilceluloza 4000 cps 2M natrijev hidroksid do pH 6.2-6.6Lidocaine hydrochloride monohydrate Hydroxypropyl methylcellulose 4000 cps 2M sodium hydroxide to pH 6.2-6.6
8.65 kg 9.8 kg8.65 kg 9.8 kg
Voda za injekcijeWater for injections
q.s. adq.s. ad
400 1400 1
Lidokainijev klorid monohidrat in hidroksipropilmetilcelulozo raztopimo v vodi za injekcije. pH uravnamo na 6.2 do 6.6 z natrijevim hidroksidom in dopolnimo z vodo do 400 1. Nastali gel avtoklaviramo.Lidocaine chloride monohydrate and hydroxypropylmethylcellulose are dissolved in water for injection. The pH was adjusted to 6.2 to 6.6 with sodium hydroxide and made up to 400 with water. The resulting gel was autoclaved.
Primer 3: RAZTOPINA 40 mg/mlExample 3: 40 mg / ml solution
Lidokainijev klorid monohidrat 4.28 kgLidocaine hydrochloride monohydrate 4.28 kg
2M natrijev hidroksid do pH 6.5-6.7 « 0.46 kg2M sodium hydroxide to pH 6.5-6.7 «0.46 kg
Prečiščena voda q.s ad 95.56 kgPurified water q.s ad 95.56 kg
Lidokain raztopimo v vodi. Dodamo natrijev hidroksid, da uravnamo pH na 6.5-6.7. Pripravljeno raztopino avtokalviramo.Dissolve lidocaine in water. Sodium hydroxide was added to adjust the pH to 6.5-6.7. The prepared solution is autocalibrated.
P 1132-1P 1132-1
Primer 4: EMULZIJSKA KREMAExample 4: EMULSION CREAM
LidokainLidocaine
Miglyol® 812 Arlatone® 289 Carbopol® 934 VodaMiglyol® 812 Arlatone® 289 Carbopol® 934 Water
10-0 g 27.6 g 9.0 g10-0 g 27.6 g 9.0 g
1.0 g ad 100.0 g1.0 g ad 100.0 g
Emulzijo pripravimo tako, da lidokain raztopimo v olju (Miglyol® 812), ter raztalimo skupaj z emulgatorjem (Arlatone® 289). Vroči mešanici dodamo manjšo količino vode. Nastalo mešanico ohladimo in dodamo gel, ki ga tvorita sredstvo za zgoščevanje (Carbopol® 934) in voda. Nastalo kremo homogeniziramo do premera velikosti oljnih kapljic < 3 μ.The emulsion was prepared by dissolving lidocaine in oil (Miglyol® 812) and melted together with the emulsifier (Arlatone® 289). Add a small amount of water to the hot mixture. The resulting mixture was cooled and a gel formed by the thickening agent (Carbopol® 934) and water was added. The resulting cream is homogenized to an oil droplet size <3 μ.
Miglyol® 812 je trdna kokosova maščoba z srednje dolgimi verigami. Arlatone® 289 je ester maščobne kisline z polioksietilenom in Carbopol® 934 je vinilni polimer z aktivnimi karboksilnimi skupinamiMiglyol® 812 is a medium-chain solid coconut fat. Arlatone® 289 is a fatty acid ester with polyoxyethylene and Carbopol® 934 is a vinyl polymer with active carboxyl groups
Primer 5:Example 5:
LidokainLidocaine
Miglyol® 812 Arlatone® 289 Carbopol® 934 Voda adMiglyol® 812 Arlatone® 289 Carbopol® 934 Water ad
5.0 g 13.8 g 4.5 g 1-0 g5.0 g 13.8 g 4.5 g 1-0 g
100.0 g100.0 g
Emulzijsko kremo pripravimo kot je opisano pri primeru 4.The emulsion cream was prepared as described in Example 4.
ΊΊ
Emulzijsko kremo pripravimo kot je opisano pri primeru 4.The emulsion cream was prepared as described in Example 4.
Primer 7:Example 7:
Prilokain, baza 52 gPriloocaine, base 52 g
Lidokain 48 gLidocaine 48 g
Dve kristalinični spojini z lokalno anestetičnim delovanjem natehtamo skupaj, in jih segrejemo na 30°C, da se spojini raztaliti in tvorita homogeno olje. Mešanica kristalov ima tališče pri 22°C. Nato mešanico nanesemo na papirnat nosilec,The two crystalline compounds with locally anesthetic action are weighed together and heated to 30 ° C to melt the compounds to form a homogeneous oil. The crystalline mixture has a melting point at 22 ° C. The mixture is then applied to a paper carrier,
1.5 mg/cm2 Primemo velik nosilec, apliciramo na prizadete sklepe. Do sedaj poznan najboljši način uporabe te inovacije je uporaba preparata, označenega v primeru 7.1.5 mg / cm 2 A large carrier is applied, applied to the affected joints. The best way to use this innovation so far is to use the preparation indicated in Example 7.
P 1132-1P 1132-1
ZaključkiConclusions
Glede na predloženo inovacijo, smo ugotovili, da so bili pacienti, z revmatoidnim artritisom, uspešno zdravljeni, kar se tiče bolečine in gibljivosti rok, z ekskluzivno uporabo površinsko apliciranege pripravka z lokalnim anestetikom. Paciente so opazovali še šest mesecev, po končani lokalni terapiji z lokalnim anestetikom.According to the proposed innovation, we have found that patients with rheumatoid arthritis have been successfully treated with regard to pain and motility of the hands with the exclusive use of a topically applied topical preparation with a local anesthetic. Patients were monitored for six months after completing topical local anesthetic therapy.
Claims (7)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9200762A SE9200762D0 (en) | 1992-03-12 | 1992-03-12 | NEW TOPICAL USE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI9300115A true SI9300115A (en) | 1993-09-30 |
Family
ID=20385599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI19939300115A SI9300115A (en) | 1992-03-12 | 1993-03-11 | Topical use of local anaesthetic agents and a pharmaceutical preparation for rheumatoid arthritis and a method for the treatment thereof |
Country Status (5)
| Country | Link |
|---|---|
| IS (1) | IS3984A (en) |
| SE (1) | SE9200762D0 (en) |
| SI (1) | SI9300115A (en) |
| WO (1) | WO1993017674A1 (en) |
| ZA (1) | ZA931079B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19526031A1 (en) * | 1995-07-17 | 1997-01-23 | Liedtke Pharmed Gmbh | Method and composition of a topical therapy for back pain and muscle tension |
| US5993836A (en) * | 1998-04-28 | 1999-11-30 | Castillo; James G. | Topical anesthetic formulation |
| AU7847800A (en) | 1999-10-15 | 2001-04-30 | Mayo Foundation For Medical Education And Research | Topical anesthetics useful for treating cancer, autoimmune diseases and ischemia |
| US8119694B2 (en) | 2008-08-15 | 2012-02-21 | Arcion Therapeutics, Inc. | High concentration local anesthetic formulations |
| WO2011074015A2 (en) | 2009-12-17 | 2011-06-23 | Themis Medicare Limited | Novel composition of pharmaceutical product to treat sexual dysfunction |
| EP3775116A4 (en) * | 2018-04-05 | 2022-03-23 | Bausch Health Ireland Limited | Polymeric emulsion delivery systems |
| CN111840553A (en) * | 2019-04-15 | 2020-10-30 | 湖州依诺唯新药物制剂有限公司 | Lipid pharmaceutical preparation and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4628052A (en) * | 1985-05-28 | 1986-12-09 | Peat Raymond F | Pharmaceutical compositions containing dehydroepiandrosterone and other anesthetic steroids in the treatment of arthritis and other joint disabilities |
| SE8802040D0 (en) * | 1988-06-01 | 1988-06-01 | Astra Ab | NEW USE |
-
1992
- 1992-03-12 SE SE9200762A patent/SE9200762D0/en unknown
-
1993
- 1993-02-16 ZA ZA931079A patent/ZA931079B/en unknown
- 1993-03-10 WO PCT/SE1993/000208 patent/WO1993017674A1/en not_active Ceased
- 1993-03-11 SI SI19939300115A patent/SI9300115A/en unknown
- 1993-03-11 IS IS3984A patent/IS3984A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE9200762D0 (en) | 1992-03-12 |
| WO1993017674A1 (en) | 1993-09-16 |
| IS3984A (en) | 1993-09-13 |
| ZA931079B (en) | 1993-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003232828B2 (en) | Topically applicable pharmaceutical preparation | |
| AU3417595A (en) | Topical anti-inflammatory composition and method | |
| US20120149779A1 (en) | High concentration local anesthetic formulations | |
| RU2095060C1 (en) | Composition showing analgetic or antiinflammatory activity, a method of analgia or treatment of allergic diseases | |
| CN103079552A (en) | Topical pharmaceutical composition comprising flurbiprofen | |
| Wells | Comparision of ici 35868, etomidate and methohexitone for day-case anaesthesia | |
| SI9300115A (en) | Topical use of local anaesthetic agents and a pharmaceutical preparation for rheumatoid arthritis and a method for the treatment thereof | |
| US20040081702A1 (en) | Bee venom treatment without the sting | |
| US20220249470A1 (en) | Treatment of skin disorders by topical administration of vegf inhibitors | |
| CA1169774A (en) | Medication having penetration through cutaneous surfaces into articular and muscular areas | |
| WO2015024420A1 (en) | Local anesthesia pain-relieving time-delay agent | |
| CA2145968A1 (en) | Topical antipruritic composition | |
| JPH0640947A (en) | Composition for percutaneous absorption preparation and percutaneous absorption preparation | |
| SK48896A3 (en) | Application of ibuprofen and flurbiprofen as anti-pruritic agents and and pharmaceutical compositions for this use | |
| US5444076A (en) | Pharmaceutical preparation for topical application | |
| EP0492747B1 (en) | Pharmaceutical preparation for topical application | |
| ES2444398T3 (en) | Topical pharmaceutical compositions of ketoprofen and methylsulfonylmethane | |
| WO2007099559A2 (en) | Method of preparation for novel composition of 2-{(2,6 dichlorophenyl) amino] benzeneacetic acid carboxymethyl ester or 2-[2-[2-(2,6-dichlorophenyl) amino] phenylacetoxyacetic acid and method of its use | |
| US20230190719A1 (en) | Topical formulations of (1s)-1-phenyl-2-pyridin-2-ylethanamine | |
| JPH03236330A (en) | Therapeutic agent for inflammation | |
| BR112021008677A2 (en) | topical pharmaceutical compositions of teriflunomide, process of preparation and use | |
| WO1989011853A1 (en) | Use of local anaesthetic agents in the manufacture of preparations with wound healing effect | |
| KR930701994A (en) | How to provide improved pain relief | |
| EP2298280A2 (en) | Gel comprising a combination of flurbiprofen and muscle relaxant | |
| WO2018063876A1 (en) | Transdermal and/or topical delivery systems comprising cetirizine dihydrochloride |