CN117338698A - Compound lidocaine gel and preparation method thereof - Google Patents

Compound lidocaine gel and preparation method thereof Download PDF

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Publication number
CN117338698A
CN117338698A CN202311448789.2A CN202311448789A CN117338698A CN 117338698 A CN117338698 A CN 117338698A CN 202311448789 A CN202311448789 A CN 202311448789A CN 117338698 A CN117338698 A CN 117338698A
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parts
gel
compound lidocaine
agent
acid
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Inventor
马保臣
杨青春
何金艳
冯秀娟
胡楠
黄学林
吴秋萍
乔秋萍
李祥健
尼健君
闫旭亮
张丽娜
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China Animal Husbandry Industry And Commerce Group Co ltd
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China Animal Husbandry Industry And Commerce Group Co ltd
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Priority to CN202311448789.2A priority Critical patent/CN117338698A/en
Publication of CN117338698A publication Critical patent/CN117338698A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K47/08—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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Anesthesiology (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention provides a compound lidocaine gel and a preparation method thereof, which belong to the technical field of medical preparations, and the compound lidocaine gel comprises the following components in parts by weight: 0.02-0.04 part of prednisolone acetate, 0.08-0.2 part of lidocaine hydrochloride, 10-25 parts of dimethyl sulfoxide, 0.05-3 parts of cross-linking agent, 0.01-3 parts of pH regulator, 0.02-2 parts of stabilizer, 0.02-0.05 part of preservative, 0.4-2 parts of penetrating agent, 0.5-5 parts of tackifier, 5-8 parts of gel skeleton material, 10-20 parts of humectant and 20-50 parts of purified water. The compound lidocaine gel provided by the invention has the characteristics of good bioavailability, quick absorption, stable quality, no skin irritation and the like, and meanwhile, the preparation process of the compound lidocaine gel is simple, and the compound lidocaine gel is suitable for large-scale production application.

Description

Compound lidocaine gel and preparation method thereof
Technical Field
The invention relates to the technical field of medicinal preparations, in particular to a compound lidocaine gel and a preparation method thereof.
Background
Musculoskeletal diseases are one of the common types of diseases in veterinary clinics, and are usually caused by structural injury or dysfunction of bones, muscles, surrounding soft tissues and the like of affected animals, and common causes include trauma, stress injury, arthritis, developmental bone diseases and the like, which are easy to cause local inflammation and pain of animal bodies, further cause lameness and cause adverse effects on the health and athletic performances of the affected animals. Therefore, an external gel having both analgesic and anti-inflammatory effects is required to directly act on the affected parts of animals to relieve body injuries and pains caused by such diseases.
Lidocaine hydrochloride is amide type middle-effect local anesthetic with chemical formula of C 14 H 23 ClN 2 O has obvious excitation and inhibition dual-phase effect on the central nervous system after blood absorption or intravenous administration, can be excited without precursor, and has the advantages of strong penetrating power, quick effect, wide spreading, stable property and the like. The medicine is widely applied to external analgesic preparations clinically, has high anesthesia strength, quick response and strong dispersion force, and takes about 2 hours for local elimination of the medicine. Prednisolone acetate, also known as prednisone, prednisone acetate, prednisolone acetate, and the like, and has the chemical name: 11 beta, 17 alpha, 21-trihydroxy pregna-1, 4-diene-3, 20-diketone-21-acetate belongs to glucocorticoids, can resist the stimulation reaction of bacterial endotoxin to organisms, lighten cell injury and play a role in protecting the organisms. Is used for treating allergic and noninfectious dermatosis and some hyperplastic dermatosis by clinical external application.
The existing registered veterinary drugs of lidocaine hydrochloride injection and prednisone acetate tablet in China have no related compound veterinary drug, but the development of a compound preparation of lidocaine hydrochloride and prednisolone acetate is urgent, the combined application effect of the two drugs can be synergistically exerted, and the development of an external gel formulation which has good bioavailability, quick absorption and easy application is very important for solving the related pain and inflammation caused by common local musculoskeletal diseases of animals in combination with clinical practice.
Disclosure of Invention
In view of the above, the invention aims to provide a compound lidocaine gel agent which has the advantages of good bioavailability, quick absorption, stable quality and no irritation to skin, and the preparation process of the compound lidocaine gel agent is simple and is suitable for the application of amplified production.
The first aim of the invention is to provide a compound lidocaine gel agent, which comprises the following components in parts by weight: 0.02-0.04 part of prednisolone acetate, 0.08-0.2 part of lidocaine hydrochloride, 10-25 parts of dimethyl sulfoxide, 0.05-3 parts of cross-linking agent, 0.01-3 parts of pH regulator, 0.02-2 parts of stabilizer, 0.02-0.05 part of preservative, 0.4-2 parts of penetrating agent, 0.5-5 parts of tackifier, 5-8 parts of gel skeleton material, 10-20 parts of humectant and 20-50 parts of purified water.
Preferably, the crosslinking agent is at least one selected from aluminum trichloride, calcium hydroxide, aluminum sulfate and zinc hydroxide.
Preferably, the pH regulator is at least one selected from lactic acid, citric acid and tartaric acid.
Preferably, the stabilizer is a 10% aqueous solution of formic acid.
Preferably, the preservative is at least one selected from benzoic acid, parahydroxybenzoic acid and propyl hydroxybenzoate.
Preferably, the penetrating agent is selected from at least one of azone, propylene glycol, menthol, salicylic acid and oleic acid.
Preferably, the tackifier is at least one selected from sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, gelatin and hydroxyethyl cellulose.
Preferably, the gel skeleton material is selected from at least one of carbomer (acrylic acid cross-linked resin), ammonium polyacrylate and diethanolamine polyacrylate.
Preferably, the humectant is at least one selected from sorbitol, polyethylene glycol, glycerin, isopropyl myristate, isopropyl palmitate.
The second aim of the invention is to provide a preparation method of the compound lidocaine gel agent, which comprises the following steps:
(1) Weighing the components according to a proportion;
(2) Dissolving a tackifier with purified water, wherein the mass ratio of the tackifier to the purified water is 1:1, the rotating speed of a stirrer is 80-100 r/min, adding prednisolone acetate, lidocaine hydrochloride, dimethyl sulfoxide, a stabilizer, a preservative and a penetrating agent while stirring at room temperature, and continuing stirring for 20-30min after the addition is finished to obtain a mixture A for later use;
(3) Uniformly mixing a cross-linking agent, a gel framework material, a humectant and the rest purified water to obtain a mixture B for later use;
(4) Starting a stirrer, stirring at a rotating speed of 100-200 r/min, adding the mixture A obtained in the step (2) into the mixture B obtained in the step (3), adding the mixture A in a small amount for multiple times, uniformly mixing, adding a pH regulator, regulating the pH value to 7.5-8.0, ensuring the temperature of the system to be in a range of 70-90 ℃, preserving heat and reacting for 1-2h, and cooling to room temperature to obtain the finished product.
Compared with the prior art, the invention has the following beneficial effects: the lidocaine hydrochloride is an amide type middle-effect local anesthetic, has obvious excitation and inhibition dual-phase effects on a central nervous system after blood absorption or intravenous administration, has the advantages of strong penetrating power, quick effect, wide spreading, stable property and the like, but can generate toxic impurities after in vivo degradation; in addition, the transdermal enhancer with specific types and proportions is selected, so that the release of the active ingredients of lidocaine hydrochloride and prednisolone acetate can be improved, and the curative effect can be improved; the traditional emulsifiable paste has the defects of easy erasure, short acting time, inapplicability in chronic pain and the like, and the gel provided by the invention can obviously reduce the administration frequency and has important clinical value.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be clearly and completely described below. It will be apparent that the described embodiments are only some, but not all, embodiments of the invention. All other embodiments, which can be made by one of ordinary skill in the art without undue burden from the invention, are within the scope of the invention.
The test methods or test methods described in the following examples are all conventional methods unless otherwise specified; the starting materials and auxiliaries, unless otherwise specified, are obtained commercially from conventional sources or are prepared in conventional manner.
Example 1
A preparation method of a compound lidocaine gel agent comprises the following steps:
(1) Weighing raw materials, namely 0.02 part of prednisolone acetate, 0.08 part of lidocaine hydrochloride, 10 parts of dimethyl sulfoxide, 0.08 part of aluminum hydroxide, 1 part of tartaric acid, 2 parts of 10% formic acid aqueous solution, 0.02 part of benzoic acid, 1 part of salicylic acid, 2 parts of hydroxyethyl cellulose, 6 parts of ammonium polyacrylate, 15 parts of isopropyl myristate and 35 parts of purified water;
(2) Dissolving hydroxyethyl cellulose with purified water, wherein the mass ratio of the hydroxyethyl cellulose to the purified water is 1:1, the rotating speed of a stirrer is 80 revolutions per minute, adding prednisolone acetate, lidocaine hydrochloride, dimethyl sulfoxide, 10% formic acid aqueous solution, benzoic acid and salicylic acid while stirring at room temperature, and continuing stirring for 30 minutes after the addition is finished to obtain a mixture A for later use;
(3) Uniformly mixing aluminum hydroxide, ammonium polyacrylate, isopropyl myristate and the rest purified water to obtain a mixture B for later use;
(4) Starting a stirrer, stirring at a rotating speed of 200 revolutions per minute, adding the mixture A obtained in the step (2) into the mixture B obtained in the step (3), adding a small amount of tartaric acid for multiple times while stirring, uniformly mixing, adding tartaric acid, adjusting the pH value to 8.0, ensuring the temperature of the system to be within the range of 80 ℃, preserving heat and reacting for 2 hours, and cooling to room temperature to obtain a finished product.
Example 2
The difference from example 1 is that: the formula of the compound lidocaine gel agent is as follows: 0.04 part of prednisolone acetate, 0.2 part of lidocaine hydrochloride, 25 parts of dimethyl sulfoxide, 3 parts of aluminum sulfate, 3 parts of citric acid, 2 parts of 10% formic acid aqueous solution, 0.05 part of parahydroxybenzoic acid, 1 part of oleic acid, 3 parts of sodium carboxymethyl cellulose, 8 parts of polyacrylic acid diethanolamine, 20 parts of polyethylene glycol and 50 parts of purified water.
Example 3
The difference from example 1 is that: the formula of the compound lidocaine gel agent is as follows: 0.03 part of prednisolone acetate, 0.15 part of lidocaine hydrochloride, 18 parts of dimethyl sulfoxide, 2 parts of aluminum trichloride, 2 parts of lactic acid, 2 parts of 10% formic acid aqueous solution, 0.04 part of propyl hydroxybenzoate, 2 parts of propylene glycol, 4 parts of polyvinylpyrrolidone, 6 parts of carbomer, 15 parts of sorbitol and 45 parts of purified water.
In other embodiments, the cross-linking agent may be one or more of aluminum trichloride, calcium hydroxide, aluminum sulfate, and zinc hydroxide.
In other embodiments, the pH adjuster may be one or a mixture of more than two of lactic acid, citric acid, and tartaric acid.
In other embodiments, the preservative may be one or more of benzoic acid, parahydroxybenzoic acid, and propyl hydroxybenzoate.
In other embodiments, the penetrating agent may be one or a mixture of more than two of azone, propylene glycol, menthol, salicylic acid and oleic acid.
In other embodiments, the tackifier may be sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, gelatin, or hydroxyethyl cellulose.
In other embodiments, the gel skeleton material may be one or more of acrylic acid cross-linked resin, ammonium polyacrylate, and diethanolamine polyacrylate.
In other embodiments, the humectant may be one or more of sorbitol, polyethylene glycol, glycerol, isopropyl myristate, and isopropyl palmitate.
Comparative example 1
The difference from example 1 is that: the prednisolone acetate is not added in the formula of the compound lidocaine gel agent.
Comparative example 2
The difference from example 1 is that: the lidocaine hydrochloride is not added in the prescription of the compound lidocaine gel agent.
Comparative example 3
The difference from example 1 is that: the compound lidocaine gel is prepared by adding 0.01 part by weight of prednisolone acetate.
Comparative example 4
The difference from example 1 is that: the compound lidocaine gel is prepared by adding 0.06 parts by weight of prednisolone acetate.
Comparative example 5
The difference from example 1 is that: the compound lidocaine gel agent is prepared by adding 0.05 part by weight of lidocaine hydrochloride.
Comparative example 6
The difference from example 1 is that: the compound lidocaine gel agent is prepared by adding 0.25 part by weight of lidocaine hydrochloride.
The gels prepared in examples 1-3 and comparative examples 1-6 were subjected to bioavailability, chemical stability during storage, and skin toxicity and irritation test studies, respectively, and the results showed that:
1) The gel provided in the examples 1-3 can well enhance the absorption of lidocaine hydrochloride and prednisolone acetate by human body, and has good bioavailability, and further the gel provided in the examples 1-3 is expected to have remarkable curative effect in the clinical use process, and the use effect of the gel prepared in the comparative examples 1-6 is remarkably poor;
2) The compound lidocaine gel provided in examples 1-3 can still maintain good chemical stability after long-term placement at room temperature;
3) The gels provided in examples 1-3 and comparative examples 1-6 were tested for safety, and the specific experimental procedure was: the gel provided in examples 1-3 and comparative examples 1-6 were respectively applied to the skin of SD rats in each group (the hair on both sides of the spine of SD rats was removed with a depilatory agent one day before administration, and no water was inhibited by feeding for 12 hours before administration), and the results showed that the skin at the administration site of examples 1-3 had no adverse reaction, and the effect of comparative examples 1-6 was slightly poor, thus proving that the compound lidocaine gel provided by the present invention had good non-irritating safety, and the components and contents in the formulation had specificity.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.

Claims (10)

1. The compound lidocaine gel is characterized by comprising the following components in parts by weight: 0.02-0.04 part of prednisolone acetate, 0.08-0.2 part of lidocaine hydrochloride, 10-25 parts of dimethyl sulfoxide, 0.05-3 parts of cross-linking agent, 0.01-3 parts of pH regulator, 0.02-2 parts of stabilizer, 0.02-0.05 part of preservative, 0.4-2 parts of penetrating agent, 0.5-5 parts of tackifier, 5-8 parts of gel skeleton material, 10-20 parts of humectant and 20-50 parts of purified water.
2. The compound lidocaine gel agent of claim 1, wherein the cross-linking agent is selected from at least one of aluminum trichloride, calcium hydroxide, aluminum sulfate, zinc hydroxide.
3. The compound lidocaine gel agent of claim 1, wherein the pH adjuster is selected from at least one of lactic acid, citric acid, tartaric acid.
4. The compound lidocaine gel agent of claim 1, wherein the stabilizer is a 10% aqueous solution of formic acid.
5. The compound lidocaine gel according to claim 1, wherein the preservative is at least one selected from benzoic acid, parahydroxybenzoic acid, propyl hydroxybenzoate.
6. The compound lidocaine gel of claim 1, wherein the osmotic agent is selected from at least one of azone, propylene glycol, menthol, salicylic acid, and oleic acid.
7. The compound lidocaine gel according to claim 1, wherein the tackifier is at least one selected from sodium carboxymethyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, gelatin, and hydroxyethyl cellulose.
8. The compound lidocaine gel according to claim 1, wherein the gel skeleton material is selected from at least one of acrylic acid cross-linked resin, ammonium polyacrylate, and diethanolamine polyacrylate.
9. The compound lidocaine gel according to claim 1, wherein the humectant is at least one selected from sorbitol, polyethylene glycol, glycerin, isopropyl myristate, isopropyl palmitate.
10. The method for preparing the compound lidocaine gel agent according to claim 1, characterized by comprising the following steps:
(1) Weighing the components according to a proportion;
(2) Dissolving a tackifier with purified water, wherein the mass ratio of the tackifier to the purified water is 1:1, the rotating speed of a stirrer is 80-100 r/min, adding prednisolone acetate, lidocaine hydrochloride, dimethyl sulfoxide, a stabilizer, a preservative and a penetrating agent while stirring at room temperature, and continuing stirring for 20-30min after the addition is finished to obtain a mixture A for later use;
(3) Uniformly mixing a cross-linking agent, a gel framework material, a humectant and the rest purified water to obtain a mixture B for later use;
(4) Starting a stirrer, stirring at a rotating speed of 100-200 r/min, adding the mixture A obtained in the step (2) into the mixture B obtained in the step (3), adding the mixture A in a small amount for multiple times, uniformly mixing, adding a pH regulator, regulating the pH value to 7.5-8.0, ensuring the temperature of the system to be in a range of 70-90 ℃, preserving heat and reacting for 1-2h, and cooling to room temperature to obtain the finished product.
CN202311448789.2A 2023-11-02 2023-11-02 Compound lidocaine gel and preparation method thereof Pending CN117338698A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0739748A (en) * 1993-07-30 1995-02-10 Kiyuukiyuu Yakuhin Kogyo Kk Low temperature crosslinked type gel agent
JPH09143060A (en) * 1995-11-16 1997-06-03 Showa Denko Kk Composition for water-containing gel plaster base
KR20050071436A (en) * 2005-06-16 2005-07-07 주식회사이-글벳 Pharmaceutical composition for an animal
WO2007072923A1 (en) * 2005-12-22 2007-06-28 Kowa Company, Ltd. Preparation for external use having improved temporal stability of steroid
CN104147035A (en) * 2014-07-30 2014-11-19 上海新亚药业闵行有限公司 Lincomycin hydrochloride gel and preparation method thereof
CN110946846A (en) * 2018-09-27 2020-04-03 湖南九典制药股份有限公司 Loxoprofen sodium gel cream matrix without transdermal penetration enhancer and preparation method thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0739748A (en) * 1993-07-30 1995-02-10 Kiyuukiyuu Yakuhin Kogyo Kk Low temperature crosslinked type gel agent
JPH09143060A (en) * 1995-11-16 1997-06-03 Showa Denko Kk Composition for water-containing gel plaster base
KR20050071436A (en) * 2005-06-16 2005-07-07 주식회사이-글벳 Pharmaceutical composition for an animal
WO2007072923A1 (en) * 2005-12-22 2007-06-28 Kowa Company, Ltd. Preparation for external use having improved temporal stability of steroid
CN104147035A (en) * 2014-07-30 2014-11-19 上海新亚药业闵行有限公司 Lincomycin hydrochloride gel and preparation method thereof
CN110946846A (en) * 2018-09-27 2020-04-03 湖南九典制药股份有限公司 Loxoprofen sodium gel cream matrix without transdermal penetration enhancer and preparation method thereof

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