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CN-122005443-A - Compound lidocaine emulsifiable paste and preparation method and application thereof

CN122005443ACN 122005443 ACN122005443 ACN 122005443ACN-122005443-A

Abstract

The application relates to the technical field of medicines, and particularly discloses a compound lidocaine emulsifiable paste and a preparation method and application thereof. The application provides a compound lidocaine emulsifiable paste, which specifically comprises, by weight, 22-26 parts of lidocaine, 22-26 parts of prilocaine, 13-17 parts of a solubilizer, 9-11 parts of carbomer, 3-5 parts of sodium hydroxide, 0.02-0.06 part of a penetration enhancer, and the balance of water added to 1000 parts, wherein the solubilizer is formed by mixing polyoxyethylene hydrogenated castor oil and poloxamer 188 in a weight ratio of 10-15:1-4, and the penetration enhancer is formed by mixing L-ethyl lactate and oleic acid in a weight ratio of 1-4:0.2-1. The compound lidocaine emulsifiable paste prepared by the application has good safety, and the compound lidocaine emulsifiable paste has the effects of quicker onset of action, deeper anesthetic effect and longer duration.

Inventors

  • HAN YU
  • HU NA
  • ZHAO XIN
  • YANG XINYAO
  • LIU DONG
  • Lu Linqiong
  • YU XINXING

Assignees

  • 同方药业集团有限公司

Dates

Publication Date
20260512
Application Date
20260317

Claims (10)

  1. 1. The compound lidocaine emulsifiable paste is characterized by comprising, by weight, 22-26 parts of lidocaine, 22-26 parts of prilocaine, 13-17 parts of solubilizer, 9-11 parts of carbomer, 3-5 parts of sodium hydroxide, 0.02-0.06 part of penetration enhancer, and the balance of water added to 1000 parts; the solubilizer is formed by mixing polyoxyethylene hydrogenated castor oil and poloxamer 188 in a weight ratio of 10-15:1-4; the penetration enhancer is formed by mixing L-ethyl lactate and oleic acid in a weight ratio of 1-4:0.2-1.
  2. 2. The compound lidocaine cream of claim 1, which is characterized by comprising, by weight, 23-25 parts of lidocaine, 23-25 parts of prilocaine, 14-16 parts of solubilizer, 9.5-10.5 parts of carbomer, 3.5-4.5 parts of sodium hydroxide, 0.03-0.05 part of penetration enhancer and the balance of water to 1000 parts.
  3. 3. The compound lidocaine cream of claim 1, which is characterized by comprising the following components, by weight, 24 parts of lidocaine, 24 parts of prilocaine, 15 parts of a solubilizer, 10 parts of carbomer, 4 parts of sodium hydroxide, 0.04 part of a penetration enhancer, and the balance of water added to 1000 parts.
  4. 4. The compound lidocaine cream of claim 1, wherein the solubilizer is composed of polyoxyethylene hydrogenated castor oil and poloxamer 188 in a weight ratio of 12-13:2-3.
  5. 5. The compound lidocaine cream of claim 1, wherein the polyoxyethylene hydrogenated castor oil is selected from polyoxyethylene hydrogenated castor oil PEG-40 or polyoxyethylene hydrogenated castor oil PEG-60.
  6. 6. The compound lidocaine cream of claim 1, wherein the penetration enhancer is composed of ethyl L-lactate and oleic acid in a weight ratio of 2-3:0.5-0.7.
  7. 7. A method for preparing a compound lidocaine cream according to any one of claims 1 to 6, comprising the following steps in sequence: (1) Adding carbomer into 250-350 parts by weight of water under stirring, stirring and soaking to obtain carbomer gel; (2) Uniformly mixing lidocaine and prilocaine under stirring, uniformly stirring at normal temperature, and nanocrystallizing by high-pressure homogenization to obtain a eutectic; (3) Mixing the solubilizer and the penetration enhancer, stirring at 55-60 ℃ until the mixture is completely melted, adding the mixture into the eutectic mixture, and stirring uniformly to obtain a water-in-oil phase mixture; (4) Mixing the carbomer gel with the oil phase mixture, and stirring to obtain an oil-in-water mixture; (5) Adding the rest water to the formula in a stirring container, stirring to obtain cream, homogenizing to stabilize the cream.
  8. 8. The method for preparing the compound lidocaine cream according to claim 7, wherein in the step (2), the technological parameters of the high-pressure homogenizing treatment are that the high-pressure homogenizing treatment is carried out for 15-30min under the conditions that the temperature is 30-40 ℃, the pressure is 60-80Mpa and the rotating speed is 2000-3000rpm, and then the high-pressure homogenizing treatment is carried out for 30-90min under the conditions that the temperature is 40-50 ℃, the pressure is 80-120Mpa and the rotating speed is 2000-3000 rpm.
  9. 9. The method for preparing the compound lidocaine cream according to claim 7, wherein in the step (5), the technological parameters of the homogenizing treatment are that the homogenizing is carried out for 20-90min under the conditions of 30-40 ℃ of temperature, 40-70Mpa of pressure and 2000-3000rpm of rotating speed.
  10. 10. Use of a compound lidocaine cream according to any one of claims 1 to 6 for the preparation of a medicament for use in anaesthesia.

Description

Compound lidocaine emulsifiable paste and preparation method and application thereof Technical Field The application relates to the technical field of medicines, in particular to a compound lidocaine emulsifiable paste and a preparation method and application thereof. Background Anesthesia is an indispensable part of the medical industry, and can help patients to relieve pain and discomfort in the process of surgery and treatment, and improve the success rate and effect of surgery and treatment. The related anesthetic is prepared by soaking carbomer 934 in purified water for at least 10 hr, adding polyoxyethylene hydrogenated castor oil directly into stirring container, stirring with low-melting co-solvent mixture to obtain water-in-oil phase mixture, and mixing with carbomer 934 to obtain unguent. The preparation method has the defects of high production cost, slow onset time, generally more than 1 hour and unsatisfactory percutaneous permeation effect. Disclosure of Invention In order to solve the technical problems, the application provides a compound lidocaine emulsifiable paste, and a preparation method and application thereof. The application provides a compound lidocaine emulsifiable paste, which comprises, by weight, 22-26 parts of lidocaine, 22-26 parts of prilocaine, 13-17 parts of solubilizer, 9-11 parts of carbomer, 3-5 parts of sodium hydroxide, 0.02-0.06 part of penetration enhancer, and the balance of water to 1000 parts; the solubilizer is formed by mixing polyoxyethylene hydrogenated castor oil and poloxamer 188 in a weight ratio of 10-15:1-4; the penetration enhancer is formed by mixing L-ethyl lactate and oleic acid in a weight ratio of 1-4:0.2-1. The application adopts the synergistic effect of the lidocaine and the prilocaine, and the drug is administrated through the skin or the mucosal surface, permeates to subcutaneous nerve endings, has paralytic and analgesic effects, and has quicker onset of action, deeper anesthetic effect and longer duration than single component. The polyoxyethylene hydrogenated castor oil and poloxamer 188 are mainly used as solubilizers in the compound lidocaine emulsifiable paste, and have the important effects that the polyoxyethylene hydrogenated castor oil and poloxamer 188 can be used as an emulsifying agent to reduce the interfacial tension of oil and water so as to uniformly disperse oil phases (lidocaine, prilocaine and the like) in water phases, thus forming a stable emulsifiable paste system. Solubilization, namely, the solubility of indissolvable drugs (lidocaine and prilocaine) in the water phase is increased, and the bioavailability of the drugs is improved. Penetration promoting effect, i.e. by changing the structure of lipid bilayer of horny layer, skin permeability is increased, percutaneous absorption of medicine is promoted, and onset time is shortened. The stability is that the physical stability of the cream is maintained, the oil-water separation is prevented, and the shelf life of the product is prolonged. Wetting, improving spreadability and spreadability of the cream, and making the drug more easily and uniformly distributed on the skin surface. The penetration enhancer composed of L-ethyl lactate and oleic acid can make the medicine pass through the stratum corneum barrier quickly, and can quickly reach effective concentration at skin nerve terminal, and the medicine retention in skin can be increased, local concentration can be quickly raised, and the anesthesia action time can be shortened. The L-ethyl lactate and the oleic acid have good biocompatibility, can play a penetration promoting effect under low concentration, have small skin irritation, and have higher safety compared with a chemical synthesis penetration promoter. Preferably, the compound lidocaine emulsifiable paste specifically comprises, by weight, 23-25 parts of lidocaine, 23-25 parts of prilocaine, 14-16 parts of solubilizer, 9.5-10.5 parts of carbomer, 3.5-4.5 parts of sodium hydroxide, 0.03-0.05 part of penetration enhancer and the balance of water to 1000 parts. Preferably, the compound lidocaine emulsifiable paste specifically comprises the following components in parts by weight of 24 parts of lidocaine, 24 parts of prilocaine, 15 parts of solubilizer, 10 parts of carbomer, 4 parts of sodium hydroxide, 0.04 part of penetration enhancer and the balance of water to 1000 parts. Preferably, the solubilizer is formed by mixing polyoxyethylene hydrogenated castor oil and poloxamer 188 in a weight ratio of 12-13:2-3. In a specific embodiment, the polyoxyethylene hydrogenated castor oil, poloxamer 188 may be present in a weight ratio of 12:2, 12.5:2, 13:2, 12:2.5, 12.5:2.5, 13:2.5, 12:3, 12.5:3, 13:3. Experimental analysis shows that the application adopts polyoxyethylene hydrogenated castor oil and poloxamer 188 with the weight ratio as solubilizer, so that the drug effect of the compound lidocaine emulsifiable paste can be further improved. Preferably, the polyoxyeth