KR20000017706A - New pharmaceutical composition of gel preparation containing local anaesthetic agents - Google Patents
New pharmaceutical composition of gel preparation containing local anaesthetic agents Download PDFInfo
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- KR20000017706A KR20000017706A KR1019990027503A KR19990027503A KR20000017706A KR 20000017706 A KR20000017706 A KR 20000017706A KR 1019990027503 A KR1019990027503 A KR 1019990027503A KR 19990027503 A KR19990027503 A KR 19990027503A KR 20000017706 A KR20000017706 A KR 20000017706A
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- South Korea
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- hydrochloride
- local anesthetic
- anesthetic composition
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- 238000002360 preparation method Methods 0.000 title claims description 4
- 229960005015 local anesthetics Drugs 0.000 title claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 title description 4
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 239000003589 local anesthetic agent Substances 0.000 claims abstract description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003381 stabilizer Substances 0.000 claims abstract description 10
- 239000003002 pH adjusting agent Substances 0.000 claims abstract description 8
- 239000003755 preservative agent Substances 0.000 claims abstract description 8
- 230000002335 preservative effect Effects 0.000 claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 23
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 18
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 10
- 229960004194 lidocaine Drugs 0.000 claims description 9
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 8
- 230000003444 anaesthetic effect Effects 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 8
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 7
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 7
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 7
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 7
- 229940068977 polysorbate 20 Drugs 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 6
- 229960004217 benzyl alcohol Drugs 0.000 claims description 6
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 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
- 229960001807 prilocaine Drugs 0.000 claims description 5
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 4
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 4
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 claims description 4
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 claims description 4
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 4
- 229960002372 tetracaine Drugs 0.000 claims description 4
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 claims description 4
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 3
- 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
- 229960003920 cocaine Drugs 0.000 claims description 3
- -1 polyoxyethylene nonylphenyl ether Polymers 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 2
- 229960005274 benzocaine Drugs 0.000 claims description 2
- 229940067596 butylparaben Drugs 0.000 claims description 2
- 229940096529 carboxypolymethylene Drugs 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 2
- 229960002216 methylparaben Drugs 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
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 2
- 229960003415 propylparaben Drugs 0.000 claims description 2
- 229940037001 sodium edetate Drugs 0.000 claims description 2
- 235000010384 tocopherol Nutrition 0.000 claims description 2
- 229960001295 tocopherol Drugs 0.000 claims description 2
- 229930003799 tocopherol Natural products 0.000 claims description 2
- 239000011732 tocopherol Substances 0.000 claims description 2
- 229940042585 tocopherol acetate Drugs 0.000 claims description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 10
- 238000010521 absorption reaction Methods 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 22
- 210000003491 skin Anatomy 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 206010002091 Anaesthesia Diseases 0.000 description 9
- 230000037005 anaesthesia Effects 0.000 description 9
- 241000700199 Cavia porcellus Species 0.000 description 7
- 229920002125 Sokalan® Polymers 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 229960001631 carbomer Drugs 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 4
- 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 4
- 239000002674 ointment Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- OMOVVBIIQSXZSZ-UHFFFAOYSA-N [6-(4-acetyloxy-5,9a-dimethyl-2,7-dioxo-4,5a,6,9-tetrahydro-3h-pyrano[3,4-b]oxepin-5-yl)-5-formyloxy-3-(furan-3-yl)-3a-methyl-7-methylidene-1a,2,3,4,5,6-hexahydroindeno[1,7a-b]oxiren-4-yl] 2-hydroxy-3-methylpentanoate Chemical compound CC12C(OC(=O)C(O)C(C)CC)C(OC=O)C(C3(C)C(CC(=O)OC4(C)COC(=O)CC43)OC(C)=O)C(=C)C32OC3CC1C=1C=COC=1 OMOVVBIIQSXZSZ-UHFFFAOYSA-N 0.000 description 3
- 238000000586 desensitisation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000008252 pharmaceutical gel Substances 0.000 description 3
- 241000208340 Araliaceae Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 2
- 235000003140 Panax quinquefolius Nutrition 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000002421 anti-septic effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000008434 ginseng Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BJPJNTKRKALCPP-UHFFFAOYSA-N prilocaine hydrochloride Chemical compound [Cl-].CCC[NH2+]C(C)C(=O)NC1=CC=CC=C1C BJPJNTKRKALCPP-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 206010059313 Anogenital warts Diseases 0.000 description 1
- 206010008531 Chills Diseases 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 240000002045 Guettarda speciosa Species 0.000 description 1
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- 235000016639 Syzygium aromaticum Nutrition 0.000 description 1
- 244000223014 Syzygium aromaticum Species 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000002692 epidural anesthesia Methods 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 239000000374 eutectic mixture Substances 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 206010036596 premature ejaculation Diseases 0.000 description 1
- 229960005094 prilocaine hydrochloride Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000010181 skin prick test Methods 0.000 description 1
- 238000002693 spinal anesthesia Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 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
- 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
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
본 발명은 국소마취제를 함유한 약용겔제 조성물로, 국소마취제 0.25∼10.0 중량부, 겔기제 0.5∼2.5 중량부, pH 조정제 0.5∼2.0 중량부, 안정화제 0.3∼3.0중량부, 보존제 0.1∼2.0 중량부, 에탄올 및 물로 구성되며, 경피흡수율을 현저히 개선시키고, 효과발현이 빠르며, 신속히 흡수되도록 설계하였고 사용시 끈적거림이 없는 약용겔제 조성물이다.The present invention is a medicinal gel composition containing a local anesthetic, 0.25 to 10.0 parts by weight of a local anesthetic, 0.5 to 2.5 parts by weight of gel, 0.5 to 2.0 parts by weight of pH adjuster, 0.3 to 3.0 parts by weight of stabilizer, 0.1 to 2.0 parts by weight of preservative Consisting of ethanol and water, it is a medicinal gel composition that significantly improves transdermal absorption, is fast in effect expression, designed to be absorbed quickly, and has no stickiness in use.
Description
본 발명은 국소마취제를 함유한 약용겔제 조성물에 관한 것으로, 보다 상세히는 국소마취제 0.25∼10.0 중량부, 겔기제 0.5∼2.5 중량부, pH 조정제 0.5∼2.0 중량부, 안정화제 0.3∼3.0 중량부, 보존제 0.1∼2.0 중량부, 에탄올 및 물로 구성된 겔제형의 국소마취제 조성물 및 그 제조방법에 관한 것이다.The present invention relates to a medicinal gel composition containing a local anesthetic, more specifically, 0.25 to 10.0 parts by weight of a local anesthetic, 0.5 to 2.5 parts by weight of a gel base, 0.5 to 2.0 parts by weight of a pH adjuster, 0.3 to 3.0 parts by weight of a stabilizer, It relates to a gel-type local anesthetic composition composed of 0.1 to 2.0 parts by weight of a preservative, ethanol and water, and a preparation method thereof.
국소마취제는 대뇌피질의 지각령에 작용하지 않고, 다만 말초지각신경에 작용하여 신경전달을 차단하므로서 국소의 지각, 특히 가역적으로 통각을 둔화 또는 소실시킨다. 적용방법에 따라 표면마취, 침윤마취, 전도마취, 척추마취, 경막외마취 등이 있다. 더욱 상세하게는 주사바늘삽입(정맥상관, 혈액시료채취등) 및 표재성 외과적 처치에 따른 피부의 표면마취, 생식기 점막의 표면마취(예: 콘딜롬제거)와 조루증(남성성기 촉각의 예민성감소) 등에 사용되도록 국소마취제를 약용량 첨가하여 만든 약제의 조성물이 최근 개발의 주류이다.Local anesthetics do not affect the perceptual cortex of the cerebral cortex, but act on the peripheral perceptual nerve to block neurotransmission, thereby slowing or losing local perception, particularly reversibly pain. Depending on the application method, there are surface anesthesia, infiltration anesthesia, conduction anesthesia, spinal anesthesia, epidural anesthesia. More specifically, surface anesthesia of the skin following injection needle insertion (vein coronary, blood sample, etc.) and superficial surgical procedures, surface anesthesia of genital mucosa (e.g., removal of condyloma) and premature ejaculation (decrease in sensitivity In recent years, the composition of a medicament made by adding a small amount of a local anesthetic is used.
종래의 국소마취제의 제형으로는 주사제, 액제, 크림제등이 소개되어 있고, 리도카인, 푸릴로카인, 테트라카인, 푸로카인, 디브카인등 단독 또는 배합제가 다수 시판되고 있음도 사실이다. 그중에 ELMA(등록상표) 크림제는 온전한 피부에 마취효과를 제공한다고 알려져 있는 제품이다.Conventional local anesthetic formulations include injections, solutions, creams, and the like, and it is also true that a large number of single or combination agents, such as lidocaine, furilocaine, tetracaine, furokine, and dibcaine, are commercially available. Among them, ELMA® creams are known to provide anesthetic effects on intact skin.
그러나, 주사제는 투여방법에서 자가투여하기가 곤란하다는 제약조건이 따르고, 액제나 크림제는 끈적거림등이 있어 적용에 불편한 단점이 있다.However, injectables have a constraint that it is difficult to self-administer in the method of administration, liquids or creams, such as sticky there is a disadvantage in that it is inconvenient to apply.
특허문헌으로는 미국특허 제4529601호(1985.7.16.등록) 및 제4562060호 (1985.12.31.등록)등에, 백색크림제로서, 프릴로카인 염기와 리도카인 염기의 42:58 내지 80:20 중량비의 공융혼합물로하여 에물젼, 연고 또는 크림 제형이 알려져 있고, WO 96/01637(1996.1.25.공개)에는 마취개시시간을 신속하게 하고, 피부에 자극이 적으며 마취효과가 장시간 지속성의 국소마취제를 얻기 위하여, 기제로서 극성지질(polar lipid)과 트리아실 글리세롤(triacyl glycerol)을 특징적으로 사용하여 연고제나 크림제를 얻고 있다.As a patent document, US Pat. No. 4,529,601 (registered on July 6, 1985) and 4,520,60 (registered on Dec. 31, 1985), etc., are used as a white cream agent and have a 42:58 to 80:20 weight ratio of a prilocaine base and a lidocaine base. Emulsions, ointments or cream formulations are known as eutectic mixtures, and WO 96/01637 (published on January 25, 1996) has a rapid onset of anesthesia, less irritation to the skin and a long-lasting topical anesthetic. In order to obtain, as a base, polar lipids and triacyl glycerol are characteristically used to obtain ointments or creams.
국소마취제의 제형은 주사제, 액제, 크림제, 연고제 또는 패치제등이 주종인바, 상기에서 거론된 바와같이 이들 제형으로는 투여시 제형상의 문제점이 있고, 투여후에는 끈적거림등의 불쾌한 사용감을 느끼게 되어, 이들 문제점을 해소하고자 기존의 제형들과는 다른 겔제로하여, 경피흡수율을 현저히 개선시키고, 효과발현시까지의 시간도 기존의 약제조성물보다 짧고, 신속히 흡수되도록 하고, 사용시 끈적거림이 없이 산뜻한 사용감을 느끼에 할 수 있는 약용겔제 조성물을 개발하고 특허로서 출원하는 바이다.Formulations of topical anesthetics are mainly injections, solutions, creams, ointments or patches, and as discussed above, these formulations have problems in formulation when administered, and unpleasant feelings such as stickiness after administration. In order to solve these problems, the gel is different from the existing formulations, which significantly improves the transdermal absorption rate, and the time until the effect is expressed is shorter than the conventional pharmaceutical composition, so as to be absorbed quickly, and there is no stickiness in use. It is intended to develop a medicinal gel composition capable of feeling and to apply as a patent.
본 발명의 국소마취제를 함유한 약용겔제 조성물은, 국소마취제 0.25∼10.0 중량부, 겔기제 0.5∼2.5 중량부, pH 조정제 0.5∼2.0 중량부, 안정화제 0.3∼3.0중량부, 보존제 0.1∼2.0 중량부, 에탄올 및 물로 구성된다.The pharmaceutical gel composition containing the local anesthetic agent of the present invention comprises 0.25 to 10.0 parts by weight of a local anesthetic, 0.5 to 2.5 parts by weight of a gel base, 0.5 to 2.0 parts by weight of a pH adjuster, 0.3 to 3.0 parts by weight of a stabilizer, and 0.1 to 2.0 parts by weight of a preservative. It consists of parts, ethanol and water.
본 발명의 약용겔제 조성물중 국소마취제로는 리도카인(Lidocaine) 및 그의 염산염, 염산 베녹시네이트(Benoxinate·HCl), 프릴로카인(Prilocaine) 및 그의 염산염, 테트라카인(Tetracaine) 및 그의 염산염, 디부카인(Dibucaine) 및 그의 염산염, 벤조카인(Benzocaine), 코카인(Cocaine) 및 그의 염산염, 염산 프라녹신 (Pranoxine·HCl), 염산 다이크로민(Dyclomine·HCl), 염산 푸로파코카인 (Propacocaine·HCl) 중에서 선택한 1종이상의 화합물을 함유하며, 겔제 조성물에 대하여 0.25∼10.0 중량부를 함유하는 것이 좋다.The local anesthetic agent of the pharmaceutical composition of the present invention is Lidocaine (Lidocaine) and its hydrochloride, Benoxinate (HCl) hydrochloride, Prilocaine (Prilocaine) and its hydrochloride, Tetracaine (Tetracaine) and its hydrochloride, Dibucaine (Dibucaine and its hydrochloride, Benzocaine, Cocaine and its hydrochloride, Pranoxine hydrochloride (Pranoxine HCl), diclomine hydrochloride (Dyclomine HCl), Propacocaine hydrochloride (Propacocaine HCl) It is preferable to contain the selected 1 or more types of compounds, and to contain 0.25-10.0 weight part with respect to a gel composition.
본 발명의 핵심적인 겔기제로는 아크릴산폴리머(Acrylic acid polymer)로서 카르복실기를 갖는 비닐폴리머를 사용하며, 바람직하게는 카르복시 폴리 메틸렌(일면, 카보머)을 0.5∼2.5 중량부 함유하는 것이 바람직하다. 겔기제의 함유량이 0.5 중량부 이하에서는 점도가 생성되지 않아 피부적용시 흘러내려 사용시 불편하게 되고, 2.5 중량부 이상에서는 점도가 너무 높아 피부적용시 뭉글뭉글하고 산뜻한 사용감이 없다.As the core gel base of the present invention, a vinyl polymer having a carboxyl group is used as an acrylic acid polymer, and preferably 0.5 to 2.5 parts by weight of carboxy polymethylene (one side, carbomer) is used. When the content of the gel base is 0.5 parts by weight or less, the viscosity is not produced, so it is uncomfortable during use when flowing down the skin, and the viscosity is too high at 2.5 parts by weight or more, there is no lumpy and fresh feeling when applying the skin.
본 발명의 pH 조정제로는 트리에탄올아민 또는 수산화나트륨중에서 선택사용하여, 그 사용량은 0.5∼2.0 중량부가 바람직하다. 만약 0.5 중량부 이하를 사용하면 전질균등한 겔형성이 어렵고, 2.0 중량부이상 사용시에도 역시 전질 균등한 겔이 형성되지 않는다.As a pH adjuster of this invention, it selects and uses among triethanolamine or sodium hydroxide, and the usage-amount is 0.5-2.0 weight part. If 0.5 parts by weight or less is used, it is difficult to form a homogeneous gel, and even when used in an amount of 2.0 parts by weight or more, a gel is not formed even.
또한, 본 발명에서는 유효성분의 안정화를 위하여 안정화제를 사용하며, 사용가능한 안정화제로는 에데트산나트륨, 토코페롤, 초산토코페롤, 폴리소르베이트 20, 폴리옥시에틸렌노닐페닐에테르, 부틸화하이드록시톨루엔(B.H.T.)중에서 1종 또는 2종이상을 선택하여 사용하며, 사용량은 겔조성물에 대하여 0.3∼3.0 중량부를 사용하는 것이 바람직하다. 안정화제의 사용량이 0.3 중량부 이하에서는 겔의 유화가 되지 않아 유상과 수상이 층을 이뤄 겔이 형성되지 않고, 3.0 중량부 이상에서는 유화는 이루어지나 과량투여시 과민증상 및 부작용이 우려된다.In addition, the present invention uses a stabilizer for the stabilization of the active ingredient, usable stabilizers include sodium edetate, tocopherol, tocopherol acetate, polysorbate 20, polyoxyethylene nonylphenyl ether, butylated hydroxytoluene (BHT ) Select one kind or two or more kinds and use the amount of 0.3 to 3.0 parts by weight based on the gel composition. If the amount of the stabilizer is 0.3 parts by weight or less, the gel is not emulsified, so that the oil phase and the water phase form a layer, and the gel is not formed. The emulsification is carried out at 3.0 parts by weight or more, but there is concern about hypersensitivity symptoms and side effects upon overdose.
본 발명의 보존제로는 메칠파라벤, 프로필파라벤, 부틸파라벤 및 벤질알콜중에서 선택사용하며, 그 사용량은 겔중량에 대하여 0.1∼2.0 중량부되게 사용하는 것이 바람직하다. 0.1 중량부 이하일 경우 방부력이 떨어져 미생물에 대한 오염가능성이 커지며, 2.0 중량부 이상일 경우에는 방부력이 증가하지 않고 피부에 적용시 과민증상 및 부작용 발현이 우려된다.The preservative of the present invention is selected from methyl paraben, propyl paraben, butyl paraben and benzyl alcohol, the amount of which is preferably used 0.1 to 2.0 parts by weight relative to the gel weight. If the amount is less than 0.1 parts by weight, the antiseptic potential is reduced and the possibility of contamination with microorganisms is increased. If the amount is more than 2.0 parts by weight, the antiseptic power does not increase, and when applied to the skin, hypersensitivity and side effects may be expressed.
본 발명의 약용겔제 조성물은 그 밖에 에탄올 및 물 외에도 약제학적으로 가능한 피부외용제류에 통상적으로 사용되는 보습제나 기타 첨가제 성분등을 함유할 수 있다.In addition to ethanol and water, the pharmaceutical gel composition of the present invention may contain a moisturizing agent or other additive components commonly used in pharmacologically available external skin preparations.
본 발명의 약용겔제 조성물은 통상적인 연고류 제조방법에 따라 제조될 수 있으며, 예를들면 일정용량 혼합기에 유효성분과 기제, 안정화제, 보존제, pH 조정제, 보습제 및 기타 첨가제를 첨가한후, 혼합기를 가동시켜 전질균등하게 한후, 진공하 제조할 수 있다.The pharmaceutical gel composition of the present invention may be prepared according to a conventional ointment manufacturing method, for example, after adding an active ingredient, a base, a stabilizer, a preservative, a pH adjuster, a humectant, and other additives to a constant volume mixer, and then operating the mixer. After homogenization, it can be prepared in vacuo.
이하 실시예에 의거하여 본 발명을 구체적으로 설명하며, 이들 실시예로 본 발명의 보호범위가 제한되는 것은 아니다.The present invention will be described in detail with reference to the following Examples, which are not intended to limit the scope of the present invention.
(실시예 1)(Example 1)
중량부Parts by weight
리도카인(Lidocaine) 9.6Lidocaine 9.6
카보머(Carbomer) 1.1Carbomer 1.1
폴리솔베이트 20(Polysorbate 20) 2.0Polysorbate 20 2.0
벤질알콜(Benzyl Alcohol) 1.0Benzyl Alcohol 1.0
트리에탄올아민(Triethanolamine) 1.3Triethanolamine 1.3
에탄올(Ethanol) 41.5Ethanol 41.5
정제수 to 100Purified Water to 100
상기 성분들을 혼합기에서 전질균등하게 혼합한 후, 겔제 조성물을 제조하였다.After mixing the above ingredients homogeneously in a mixer, a gel composition was prepared.
(실시예 2)(Example 2)
중량부Parts by weight
리도카인(Lidocaine) 2.5Lidocaine 2.5
프릴로카인(Prilocaine) 2.5Prilocaine 2.5
카보머(Carbomer) 1.1Carbomer 1.1
폴리솔베이트 20(Polysorbate 20) 2.0Polysorbate 20 2.0
벤질알콜(Benzyl Alcohol) 1.0Benzyl Alcohol 1.0
트리에탄올아민(Triethanolamine) 1.3Triethanolamine 1.3
에탄올(Ethanol) 43.8Ethanol 43.8
정제수 to 100Purified Water to 100
상기 성분들을 혼합기에서 전질균등하게 혼합한 후 겔제 조성물을 제조하였다.After mixing the ingredients homogeneously in a mixer to prepare a gel composition.
(실시예 3)(Example 3)
중량부Parts by weight
염산리도카인(Lidocaine·HCl) 9.6Lidocaine Hydrochloride (LidocaineHCl) 9.6
카보머(Carbomer) 1.1Carbomer 1.1
폴리솔베이트 20(Polysorbate 20) 2.0Polysorbate 20 2.0
벤질알콜(Benzyl Alcohol) 1.0Benzyl Alcohol 1.0
트리에탄올아민(Triethanolamine) 1.3Triethanolamine 1.3
에탄올(Ethanol) 41.5Ethanol 41.5
정제수 to 100Purified Water to 100
상기 성분들을 혼합기에서 전질균등하게 혼합한 후 겔제 조성물을 제조하였다.After mixing the ingredients homogeneously in a mixer to prepare a gel composition.
(실시예 4)(Example 4)
중량부Parts by weight
염산리도카인(Lidocaine·HCl) 2.5Lidocaine Hydrochloride (LidocaineHCl) 2.5
프릴로카인(Prilocaine) 2.5Prilocaine 2.5
카보머(Carbomer) 1.1Carbomer 1.1
폴리솔베이트 20(Polysorbate 20) 2.0Polysorbate 20 2.0
벤질알콜(Benzyl Alcohol) 1.0Benzyl Alcohol 1.0
트리에탄올아민(Triethanolamine) 1.3Triethanolamine 1.3
에탄올(Ethanol) 43.8Ethanol 43.8
정제수 to 100Purified Water to 100
상기 성분들을 혼합기에서 전질균등하게 혼합한 후 겔제 조성물을 제조하였다.After mixing the ingredients homogeneously in a mixer to prepare a gel composition.
(실시예 5)(Example 5)
중량부Parts by weight
염산프릴로카인(Prilocaine·HCl) 5.0Prilocaine hydrochloride (Prilocaine, HCl) 5.0
카보머(Carbomer) 1.1Carbomer 1.1
폴리솔베이트 20(Polysorbate 20) 2.0Polysorbate 20 2.0
벤질알콜(Benzyl Alcohol) 1.0Benzyl Alcohol 1.0
트리에탄올아민(Triethanolamine) 1.3Triethanolamine 1.3
에탄올(Ethanol) 43.8Ethanol 43.8
정제수 to 100Purified Water to 100
상기 성분들을 혼합기에서 전질균등하게 혼합한 후 겔제 조성물을 제조하였다.After mixing the ingredients homogeneously in a mixer to prepare a gel composition.
(실험예)Experimental Example
상기 실시예에서 제조한 약용겔제 조성물의 국소마취효과를 확인하기 위하여 다음과 같이 시험을 실시하였다.In order to confirm the local anesthetic effect of the medicinal gel composition prepared in the above example, the test was carried out as follows.
실험 : 국소마취 효과 비교실험(Pin Prink Test)Experiment: Pin Prink Test
국소마취제 함유 약용 겔제(실시예 1)의 국소마취효과를 평가하기 위하여 기니픽(giniea pig)의 등피부를 이용한 "Skin Prick Test"를 실시하였다. Hartle계 백색 기니픽(giniea pig)의 등피부를 제모하고, 10㎠ 면적에 실시예 1의 샘플을 30 분간 적용한 후, 경시별로 자극에 대한 반응을 점수화 하였다.In order to evaluate the local anesthetic effect of the local anesthetic-containing medicinal gel (Example 1), a "Skin Prick Test" was performed using the back skin of a guinea pig. Hartle-based white guinea pig (giniea pig) is the epidermis, the sample of Example 1 was applied to the area of 10 cm 2 for 30 minutes, and the response to the stimulus was scored over time.
대조물질로는 A, B 두가지를 사용하였다.A and B were used as a control material.
- 실험방법은 다음과 같다.-Experimental method is as follows.
1)실험동물 : 실험에 사용한 기니픽(giniea pig)은 체중 300∼350 g 정도의 Hartle계 백색 수컷 기니픽으로서 (주)삼육실험동물센타(경기도 오산)에서 공급받아 실험전 1주일 이상 실험실 환경에 순화시켰다. 실험기간 동안 사료와 음수는 자유 섭식시켰다.1) Experimental animal: The guinea pig (giniea pig) used in the experiment is a Hartle-based white male guinea pig with a weight of 300-350 g, supplied by Samyuk Experiment Animal Center (Osan, Gyeonggi-do) and purified to laboratory environment for more than one week before the experiment. I was. Feed and water were fed freely during the experiment.
2)실험물질2) Experimental substance
①실시예 1 : 1 g 중 리도케인(K.P) 96 mgExample 1 96 mg of lidocaine (K.P) in 1 g
②대조물질 A(액제) : 1g 중 리도케인(K.P) 96 mg② Control substance A (liquid): 96 mg of lidocaine (K.P) in 1 g
③대조물질 B(크림제) : 1 g중 섬수 70 % 에탄올엑스 10 mg, 육종용, 당귀, 백삼, 사상자, 산초 혼합엑스 100 mg, 세신, 계피, 정향 혼합엑스 100 mg③ Control substance B (creaming agent): 1 mg of ginseng 70% ethanol extract 10 mg, breeding, Angelica, white ginseng, saengsaeng, sancho mixed extract 100 mg, sessin, cinnamon, clove mixed extract 100 mg
3)실험방법 : Nagarsenker & Joshi의 방법(1)을 일부 변형하여 실시함.3) Experimental method: Nagarsenker & Joshi's method (1) was partially modified.
①기니픽의 등피부를 애니몰 클립퍼(Animal Clipper)를 사용하여 5×5 ㎠ 넓이로 제모한다.(1) The back skin of the guinea pig is epilated 5 × 5 cm 2 using an animal clipper.
②약물을 10 ㎠의 제모한 등피부에 적용하였다. 약물의 적용량은 각 동물당 실시예 1 약 1 g, 대조물질 A 약 1 g, 대조물질 B 4.0 g을 사용하였으며, 기니픽의 피부 적용부위가 충분히 약물로 덮히도록 하였다.② The drug was applied to the back skin of 10 cm 2 epilation. The amount of drug applied was about 1 g of Example 1, about 1 g of Control A, and 4.0 g of Control B, so that the skin application area of the guinea pig was sufficiently covered with the drug.
③약물 적용 직후를 0 분으로 하고, 초기에는 매 2.5-5 분 간격으로(2.5, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 분) 60 분간 측정하고, 이후 30-60 분 간격으로(90, 120, 150, 180, 240, 300, 360 분) pin prick test를 실시하였다. 각 적용약물은 기니픽 피부적용 30 분 후 생리식염수로 닦아 제거하였다.③ Immediately after drug application is 0 minutes, initially 60 minutes every 2.5-5 minutes (2.5, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 minutes) Then, a pin prick test was performed at intervals of 30 to 60 minutes (90, 120, 150, 180, 240, 300, 360 minutes). Each applied drug was removed by physiological saline 30 minutes after guinea pig skin application.
④Prick test는 surgical pin을 사용하여 피부를 관통하지 않을 정도의 강도로 찔러서 shivering 반응이 일어나는 횟수를 측정하였으며, 자극횟수는 각 시간대별 1 개체 10 회로 하였다.④Prick test measured the number of times the shivering reaction occurred by sticking to the strength that does not penetrate the skin by using the surgical pin, the number of stimulation was 1 subject 10 times each time period.
4)실험횟수 : 3)의 실험을 동일하게 2 회 반복한다.4) Number of experiments: Repeat the same experiment 2 times.
5)계산 : 탈감각율(% of desensitization)은 다음과 같은 공식을 사용하여 계산산다.5) Calculation: The percentage of desensitization is calculated using the following formula.
군당 무반응 회수No reaction count per group
탈감각율 = ------------------------ × 100Desensitization rate = ------------------------ × 100
군당 자극 회수Stimulus count per group
-실험결과는 다음 표 1과 같다.-The test results are shown in Table 1 below.
(표 1)Table 1
실험약물의 경시별 평균 탈감각율Average Desensitization Rate of Test Drugs with Time
(unit : %)(unit:%)
- 결과의 해석-Interpretation of the results;
①실시예 1은 약물적용 약 15 분 후부터 국소마취효가가 나타나기 시작하였으며, 약물적용 60 분에 최고도에 달하였고, 이러한 작용은 약 150 분 까지 지속되었다.① In Example 1, local anesthetic efficacy began to appear after about 15 minutes of drug application, and reached a maximum at 60 minutes of drug application, and this action lasted up to about 150 minutes.
②대조물질 A의 경우 마취효과는 비교적 신속하게 나타나서 약물 적용 45 분 후에 최고도에 달하고, 이후 점차 회복되는 경향을 나타내어 비교적 적용시간이 짧았다.② For control substance A, the anesthesia effect appeared relatively quickly, reached the highest level after 45 minutes of drug application, and then gradually recovered.
③대조물질 B는 국소마취효능이 비교적 미약하여 최대효능발현 시간대(40 분)에서 실시예 1 및 대조물질 A 처치군의 약 50 %에 달하는 효능을 나타내었다.③ The control substance B exhibited an effect of about 50% of the Example 1 and the control substance A treatment group at the time of maximum efficacy expression (40 minutes) because the local anesthetic effect was relatively weak.
- 고찰- Review
국소마취 효과의 강도만을 비교할 경우, 그 정도의 순서는 실시예 1대조물질 A > 대조물질 B 이었다.When only the intensity of the local anesthetic effect is compared, the order of the degree is Example 1 Control A> Control B.
용도별 적절한 효과발현 및 부작용에 대한 비교자료는 현재 ○○○병원에서 실시하고 있는 간이임상실험이 완료되면 명백히 밝혀지겠지만, 지금까지의 실험내용은 매우 바람직하였고, 표 1의 동물(기니픽)에 대한 국소마취효과 비교실험에서 볼 수 있는 바와같이, 본 발명품(실시예 1등)은 약물적용 15분후 부터 국소마취효과가 나타났으며, 60분후에 최고도에 달하였고, 그 강도는 150분까지 계속되었음도 볼수 있어, 본 발명품은 대조물질 A나 B 보다 발현시간이 빠르고 마취강도가 강하게 오래 지속되며 겔제제로서 피부에 끈적거림이 없어 적용시 산뜻한 감을 줄 수 있는 제형적으로 우수한 약제임이 입증되었다.The comparative data on the effects and side effects of each application will be clear when the simple clinical trials conducted at the ○○○ hospital are completed. As can be seen in the comparative anesthesia effect experiment, the present invention (Example 1, etc.) showed local anesthesia effect after 15 minutes of drug application, reached the highest level after 60 minutes, and the intensity continued up to 150 minutes. As can be seen, the present invention is faster than the control material A or B, the anesthesia strength is strongly long lasting, and as a gel formulation, it has been proved to be an excellent pharmaceutical formulation that can give a fresh feeling when applied as there is no stickiness on the skin.
Claims (7)
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| KR1019990027503A KR100347883B1 (en) | 1999-07-08 | 1999-07-08 | New pharmaceutical composition of gel preparation containing local anaesthetic agents |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20010007724A (en) * | 2000-07-04 | 2001-02-05 | 임준기 | The band with an anesthesia effect and sterilization |
| KR20020006555A (en) * | 2000-07-03 | 2002-01-23 | 김수지 | External gel preparation containing local anesthetics |
| CN112516074A (en) * | 2020-12-11 | 2021-03-19 | 南京斯泰尔医药科技有限公司 | Benzocaine medicinal preparation and preparation method thereof |
-
1999
- 1999-07-08 KR KR1019990027503A patent/KR100347883B1/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020006555A (en) * | 2000-07-03 | 2002-01-23 | 김수지 | External gel preparation containing local anesthetics |
| KR20010007724A (en) * | 2000-07-04 | 2001-02-05 | 임준기 | The band with an anesthesia effect and sterilization |
| CN112516074A (en) * | 2020-12-11 | 2021-03-19 | 南京斯泰尔医药科技有限公司 | Benzocaine medicinal preparation and preparation method thereof |
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