阅读说明：本技术 右酮洛芬氨丁三醇凝胶贴膏及其制备方法 (Deketoprofen trometamol gel plaster and preparation method thereof ) 是由 殷报云 肖稳定 文凤 谢超君 徐华庚 于 2020-08-18 设计创作，主要内容包括：本发明公开了一种右酮洛芬氨丁三醇凝胶贴膏及其制备方法,所述凝胶贴膏,以重量百分比计,包括有0.1%～3.0%右酮洛芬氨丁三醇及凝胶基质。本发明的右酮洛芬氨丁三醇凝胶贴膏,通过凝胶基质的处方改进,不含促渗剂,具有高强的渗透性,透皮吸收快,可持续给药24小时,质量稳定,符合药品上市要求,适用于类风湿关节炎、骨关节炎、强直性脊柱炎、痛风性关节炎,以及癌症疼痛、急性扭伤、软组织挫伤疼痛等各种急慢性疼痛,相比已上市的同类产品,疗效高,并且副作用小,安全可靠。(The invention discloses a dexketoprofen tromethamine gel plaster and a preparation method thereof, wherein the gel plaster comprises 0.1-3.0% of dexketoprofen tromethamine and a gel matrix by weight percentage. The dexketoprofen trometamol gel plaster is improved by a gel matrix prescription, does not contain a penetration enhancer, has high permeability, is quick in transdermal absorption, can be continuously administrated for 24 hours, has stable quality, meets the marketing requirement of medicines, is suitable for various acute and chronic pains such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gouty arthritis, cancer pain, acute sprain, soft tissue contusion pain and the like, and has high curative effect, small side effect, safety and reliability compared with similar products on the market.)

1. The dexketoprofen tromethamine gel plaster without a penetration enhancer is characterized by comprising the following components in percentage by weight:

0.1 to 3.0 percent of dexketoprofen tromethamine,

5.0 to 10.0 percent of water-based high molecular compound,

35.0 to 50.0 percent of solvent,

20.0 to 40.0 percent of humectant,

0.02 to 0.6 percent of cross-linking agent,

0.5 to 5.0 percent of surfactant,

0.1 to 1.0 percent of pH regulator.

2. The dexketoprofen trometamol gel patch without a penetration enhancer according to claim 1, wherein the gel patch comprises, in weight percent:

0.15 to 1.2 percent of dexketoprofen tromethamine,

5.0 to 10.0 percent of water-based high molecular compound,

35.0 to 50.0 percent of solvent,

20.0 to 40.0 percent of humectant,

0.02 to 0.6 percent of cross-linking agent,

0.5 to 5.0 percent of surfactant,

0.1 to 1.0 percent of pH regulator.

3. The dexketoprofen trometamol gel patch without penetration enhancer according to claim 1 or 2,

the gel plaster also comprises a preservative, and the dosage of the preservative is 0.1-0.5% by weight percentage.

4. The dexketoprofen trometamol gel patch without penetration enhancer according to claim 1 or 2,

the water-based high molecular compound is one or more of polyacrylic acid, sodium polyacrylate, polyacrylic acid aqueous solution, sodium polyacrylate aqueous solution, sodium carboxymethyl cellulose, carbomer and polyvinyl alcohol.

5. The dexketoprofen trometamol gel patch without penetration enhancer according to claim 1 or 2,

the solvent is one or two of purified water and ethanol.

6. The dexketoprofen trometamol gel patch without penetration enhancer according to claim 1 or 2,

the humectant is one or more of glycerol, sorbitol, urea and polyethylene glycol.

7. The dexketoprofen trometamol gel patch without penetration enhancer according to claim 1 or 2,

the surfactant is one or more of polysorbate 40, polysorbate 60, polysorbate 80, polyoxyethylene hydrogenated castor oil 40 and sorbitan oleate.

8. The dexketoprofen trometamol gel patch without penetration enhancer according to claim 1 or 2,

the pH regulator is one or more of L-tartaric acid, DL tartaric acid, citric acid and phosphoric acid.

9. The dexketoprofen trometamol gel patch without penetration enhancer according to claim 1 or 2,

the cross-linking agent is one or more of aluminium glycollate, aluminium hydroxide gel and aluminium trichloride.

10. The method for preparing a dexketoprofen tromethamine gel patch containing no penetration enhancer according to any one of claims 1 to 9, comprising the steps of:

adding pH regulator into purified water, stirring for dissolving,

adding dexketoprofen trometamol, crosslinking regulator, humectant, tackifier and surfactant into purified water, stirring for dissolving, adding part of aqueous high molecular compound, stirring and dispersing uniformly for later use to obtain an aqueous phase mixture,

adding filler and cross-linking agent into humectant solution, dispersing uniformly, adding the rest water-based high molecular compound, mixing uniformly to obtain oil phase mixture,

adding the preservative into the solvent, dissolving for standby,

mixing the above materials, coating, blanking, and packaging to obtain gel plaster.

Technical Field

The invention belongs to the technical field of medicinal preparations, and relates to an acrylic acid non-steroidal anti-inflammatory drug dexketoprofen tromethamine gel plaster and a preparation method thereof.

Background

Ketoprofen is an acrylic acid non-steroidal anti-inflammatory drug, and is mainly used for treating rheumatic or rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, postoperative pain and the like. Ketoprofen, which has a structural formula with one chiral carbon atom, has been used in the form of racemate for a long time. It was found that the levorotatory form of ketoprofen is almost inactive, while the dextrorotatory form has an anti-inflammatory effect 2 times that of the ketoprofen racemate. However, dexketoprofen, which has a lower solubility and a poorer absorption, is often used as tromethamine salt.

Dexketoprofen trometamol tablets were first developed by The Menarini Group company and first marketed in spain 1996. Dexketoprofen trometamol is currently marketed in the form of tablets, capsules, oral liquids and injections. Oral administration of dexketoprofen trometamol has a greater side effect, has a damaging effect on the gastrointestinal mucosa, and can cause gastrointestinal ulcers, and even gastrointestinal bleeding side effects. In addition, the half-life period of the dexketoprofen trometamol is short, and the dexketoprofen trometamol is generally taken 3 to 4 times a day, so that gastrointestinal dysfunction appears in many patients, particularly various arthritis patients need to receive long-term treatment, and the incidence rate of adverse reactions is higher. There is a need to develop a more patient-compliant dosage form.

The main indications of dexketoprofen tromethamine are the inflammation diminishing and pain easing of diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gouty arthritis, etc., and the symptoms of the diseases are mainly expressed on local joints, so the development of a percutaneous topical administration preparation of dexketoprofen tromethamine is very suitable. The transdermal drug delivery preparation can avoid the first-pass elimination effect and gastrointestinal irritation of the drug, realize the continuous controlled drug delivery of the drug with short half-life period, maintain constant blood concentration, enhance the treatment effect and reduce the occurrence of side effects. Meanwhile, the transdermal drug delivery preparation can reduce the drug delivery times, and for drugs with large drug delivery dose, the patient can stop taking the drug at any time by self-administration, so that the incidence rate of serious adverse reactions is reduced, and the patient compliance is better.

At present, no research report of the dexketoprofen tromethamine gel emplastrum preparation is searched.

Disclosure of Invention

The invention mainly aims to provide a dexketoprofen tromethamine gel emplastrum and a preparation method thereof, which are used for treating various acute and chronic pains such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gouty arthritis, cancer pain, acute sprain, soft tissue contusion pain and the like.

According to one aspect of the invention, the dexketoprofen trometamol gel plaster without a penetration enhancer is provided, and comprises the following components in percentage by weight

0.1 to 3.0 percent of dexketoprofen tromethamine,

5.0 to 10.0 percent of water-based high molecular compound,

35.0 to 50.0 percent of solvent,

20.0 to 40.0 percent of humectant,

0.02 to 0.6 percent of cross-linking agent,

0.5 to 5.0 percent of surfactant,

0.1 to 1.0 percent of pH regulator.

Further, the dexketoprofen tromethamine gel plaster without the penetration enhancer comprises the following components in percentage by weight:

0.15 to 1.2 percent of dexketoprofen tromethamine,

5.0 to 10.0 percent of water-based high molecular compound,

35.0 to 50.0 percent of solvent,

20.0 to 40.0 percent of humectant,

0.02 to 0.6 percent of cross-linking agent,

0.5 to 5.0 percent of surfactant,

0.1 to 1.0 percent of pH regulator.

Further, the dexketoprofen tromethamine gel plaster without the penetration enhancer also comprises a preservative, and the usage amount of the preservative is 0.1-0.5% by weight percentage.

Further, the water-based high molecular compound is one or more of polyacrylic acid, sodium polyacrylate, a polyacrylic acid aqueous solution, a sodium polyacrylate aqueous solution, sodium carboxymethyl cellulose, carbomer and polyvinyl alcohol.

Further, the solvent is one or two of purified water and ethanol.

Further, the humectant is one or two of glycerin, urea, sorbitol and polyethylene glycol.

Further, the surfactant is one or more of polysorbate 40, polysorbate 60, polysorbate 80, polyoxyethylene hydrogenated castor oil 40, and sorbitan oleate.

Further, the pH regulator is one or more of L-tartaric acid, DL tartaric acid, citric acid and phosphoric acid.

Further, the cross-linking agent is one or more of aluminum glycoxide, aluminum hydroxide gel and aluminum trichloride.

Furthermore, the gel plaster can also comprise other components such as a filler, a tackifier, a crosslinking regulator, a spice and the like. The filler may be selected from one or more of titanium dioxide, silica, talc, kaolin, diatomaceous earth. The tackifier can be one or two selected from polyvinylpyrrolidone and gelatin. The crosslinking regulator can be selected from disodium edetate or tetrasodium edetate, the perfume can be a perfume conventionally used in gel plaster, the above are only examples of various substances, and the actual preparation is not limited to the above substances.

According to another aspect of the invention, the preparation method of the dexketoprofen trometamol gel plaster without a penetration enhancer is also provided, and comprises the following steps:

adding pH regulator into purified water, stirring for dissolving,

adding dexketoprofen trometamol, crosslinking regulator, humectant, tackifier and surfactant into purified water, stirring for dissolving, adding part of aqueous high molecular compound, stirring and dispersing uniformly for later use to obtain an aqueous phase mixture,

adding filler and cross-linking agent into humectant solution, dispersing uniformly, adding the rest water-based high molecular compound, mixing uniformly to obtain oil phase mixture,

adding the preservative into the solvent, dissolving for standby,

mixing the above materials, coating, blanking, and packaging to obtain gel plaster.

The dexketoprofen trometamol as the main drug has larger water solubility than dexketoprofen, and can be added into purified water or added into a solvent for dissolution.

By adopting the technical scheme, the invention has the beneficial effects that:

(1) compared with the similar products (such as ketoprofen with the same concentration) on the market, the dexketoprofen tromethamine gel plaster has the advantages of doubled curative effect, small side effect, safety and reliability.

(2) The dexketoprofen tromethamine gel plaster is improved by a matrix prescription, does not contain a penetration enhancer, but has high permeability, and has stable percutaneous absorption and stable quality according to 12-month long-term stability investigation and rat skin external transdermal experiments, so that the dexketoprofen tromethamine gel plaster meets the medicinal standard.

Drawings

FIG. 1 is a schematic diagram showing the results of in vitro transdermal experimental investigation of dexketoprofen tromethamine gel patch.

Detailed Description

The present application will be described in further detail with reference to specific examples. The following examples are intended to be illustrative of the present application only and should not be construed as limiting the present application.

The reagents and raw materials used in the invention are commercially available.