阅读说明：本技术 一种高活性缓释止痛贴及其制备工艺 (High-activity sustained-release analgesic patch and preparation process thereof ) 是由 徐建峰 施利群 左伟平 倪斌斌 张利华 付茂琦 朗古特 徐忠贤 姜成炜 于 2021-08-16 设计创作，主要内容包括：本发明涉及一种高活性缓释止痛贴及其制备工艺,高活性缓释止痛贴包括依次叠加的背衬层、主体层和隔离层；其中,主体层包括以下组分：基质,包括骨架材料30～50wt％和助剂12～28wt％；活性成分,包括水杨酸甲酯6～12wt％、薄荷醇5～8wt％和樟脑1～4wt％；活性成分缓释包合料6～18wt％。本发明选用具有高活性、高挥发性药物,即水杨酸甲酯、薄荷醇和樟脑作为高活性缓释止痛贴的主体,主体中的活性成分采用缓释包合材料包合,使各活性成分的含量保留达到最大化并持续稳定释放,确保药物有效性；选用用低致敏亲水性的基质材料且制备工艺采用创新的无溶剂生产工艺技术,使透皮贴剂用于人体不易过敏,从而保证药物安全性。(The invention relates to a high-activity slow-release analgesic patch and a preparation process thereof, wherein the high-activity slow-release analgesic patch comprises a back lining layer, a main body layer and an isolation layer which are sequentially overlapped; wherein the main body layer comprises the following components: the matrix comprises 30-50 wt% of framework material and 12-28 wt% of auxiliary agent; the active ingredients comprise 6-12 wt% of methyl salicylate, 5-8 wt% of menthol and 1-4 wt% of camphor; 6-18 wt% of active ingredient slow-release inclusion material. The invention selects the medicines with high activity and high volatility, namely methyl salicylate, menthol and camphor as the main body of the high-activity slow-release analgesic plaster, and the active ingredients in the main body are included by adopting slow-release inclusion materials, so that the content retention of each active ingredient reaches the maximum and is continuously and stably released, and the effectiveness of the medicine is ensured; the transdermal patch is not easy to be allergic when being used for human body by selecting a low-sensitization hydrophilic matrix material and adopting an innovative solvent-free production process technology in the preparation process, thereby ensuring the safety of the medicine.)

1. A high-activity slow-release analgesic patch is characterized by comprising a back lining layer, a main body layer and an isolation layer which are sequentially overlapped;

wherein the main body layer comprises the following components:

the matrix comprises 30-50 wt% of framework material and 12-28 wt% of auxiliary agent;

the active ingredients comprise 6-12 wt% of methyl salicylate, 5-8 wt% of menthol and 1-4 wt% of camphor;

6-18 wt% of active ingredient slow-release inclusion material.

2. The patch according to claim 1, wherein the matrix material comprises at least one of natural rubber, synthetic rubber, and thermoplastic rubber.

3. The patch as claimed in claim 1, wherein the matrix further comprises polyisobutylene 1-3 wt%.

4. The patch as claimed in claim 1, wherein the active ingredient slow-release coating material comprises at least one of Ewing, cyclodextrin, and Kaolin.

5. The patch as claimed in any one of claims 1 to 4, wherein the adjuvant comprises 1 to 10 wt% of filler, 2 to 4 wt% of plasticizer, 3 to 4 wt% of softener and 6 to 10 wt% of tackifier.

6. The patch as claimed in claim 5, wherein the filler comprises at least one of lithopone, zinc oxide, and aluminum silicate.

7. The patch as claimed in claim 5, wherein the plasticizer comprises at least one of liquid paraffin and solid paraffin.

8. The patch as claimed in claim 5, wherein said emollient comprises at least one of lanolin and vaseline.

9. The patch as claimed in claim 5, wherein the viscosity increasing agent comprises at least one of rosin glycerin ester and sodium carboxymethyl cellulose.

10. The process for preparing a high-activity sustained-release analgesic patch as claimed in any one of claims 1 to 9, which comprises the following steps:

(1) kneading each component contained in the matrix to obtain the matrix;

(2) mixing the active ingredient and the active ingredient slow-release inclusion material to obtain an inclusion material;

(3) adding the inclusion material into the matrix for mixing to obtain paste; then filtering the paste to obtain paste;

(4) and heating the paste to coat on the back lining layer, covering the isolation layer, rolling and slicing through the cooling channel to obtain the high-activity slow-release pain relieving plaster.

Technical Field

The invention belongs to the technical field of a preparation process of a medicine transdermal patch, and particularly relates to a high-activity sustained-release analgesic patch and a preparation process thereof.

Background

The transdermal patch has remarkable curative effect in treating diseases, especially rheumatic arthralgia, myalgia, sprain, cervical vertebra lumbocrural pain and the like, and occupies a great proportion in clinical use. Transdermal administration is the third main route of administration, except oral administration and injection. Traditional analgesic transdermal drug delivery preparations such as black plaster and rubber plaster have strong irritation and sensitization, and the drug-loading rate is small, so that the further development of the transdermal drug delivery preparation is greatly limited.

At present, the traditional production method of domestic transdermal patches is a solvent method, for example, patent document with publication number CN107375891A discloses a preparation method of external patches for dispelling wind-damp; since the solvent method uses gasoline as a solvent in a large amount, there are 3 major disadvantages: 1. the gasoline is inflammable and explosive, the requirements on explosion-proof and fire-proof measures are strict, and the safety and environmental protection cost is extremely high; 2. because the traditional solvent method production process needs high-temperature drying to remove the solvent, the active ingredients of the high-activity volatile medicine are lost along with the drying of the solvent, and the effectiveness of the medicine is seriously influenced; 3. gasoline has anesthetic effect on central nervous system, is harmful to skin, and is easy to cause skin allergy.

Disclosure of Invention

Based on the defects in the prior art, the invention aims to provide an innovative high-activity sustained-release analgesic patch and a preparation process thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

a high-activity sustained-release analgesic patch comprises a back lining layer, a main body layer and an isolation layer which are sequentially stacked;

wherein the main body layer comprises the following components:

the matrix comprises 30-50 wt% of framework material and 12-28 wt% of auxiliary agent;

the active ingredients comprise 6-12 wt% of methyl salicylate, 5-8 wt% of menthol and 1-4 wt% of camphor;

6-18 wt% of active ingredient slow-release inclusion material.

Preferably, the framework material comprises at least one of natural rubber, synthetic rubber and thermoplastic rubber.

Preferably, the substrate further comprises 1-3 wt% of polyisobutylene.

Preferably, the active ingredient slow-release coating material comprises at least one of Ewing, cyclodextrin and kaolin.

Wherein the Eudragit comprises at least one of ethyl acrylate and methyl methacrylate copolymer.

Preferably, the auxiliary agent comprises 1-10 wt% of filler, 2-4 wt% of plasticizer, 3-4 wt% of softener and 6-10 wt% of tackifier.

Preferably, the filler includes at least one of lithopone, zinc oxide, and aluminum silicate.

Preferably, the plasticizer includes at least one of liquid paraffin and solid paraffin.

Preferably, the softener comprises at least one of lanolin and vaseline.

Preferably, the tackifier comprises at least one of rosin glycerin ester and sodium carboxymethyl cellulose.

The invention also provides a preparation process of the high-activity slow-release analgesic patch, which comprises the following steps:

(1) kneading each component contained in the matrix to obtain the matrix;

(2) firstly, performing inclusion on the active ingredient and the slow-release inclusion ingredient to obtain a slow-release inclusion material;

(3) adding the inclusion material into the matrix for mixing, and filtering the paste after mixing to obtain paste;

(4) and heating the paste to coat on the back lining layer, covering the isolation layer, rolling and slicing through the cooling channel to obtain the high-activity slow-release pain relieving plaster.

Compared with the prior art, the invention has the beneficial effects that:

the invention selects high-activity and high-volatility medicines, namely methyl salicylate, menthol and camphor as the main body of the high-activity slow-release analgesic patch, and active ingredients in the main body are included by adopting an active ingredient slow-release inclusion material, so that the content retention of each active ingredient reaches the maximum and is continuously and stably released, and the effectiveness of the medicine can be ensured.

The invention adopts a solvent-free clean production process technology, does not need to use a solvent, greatly reduces the production cost, has no potential safety hazard, does not pollute the environment, reduces sensitization factors, reduces anaphylactic reaction of a human body, can obviously improve the production safety and the drug safety, and is a revolution of the traditional production process.

Detailed Description

The technical solution of the present invention is further explained by the following specific examples.

Example 1:

the preparation process of the high-activity slow-release analgesic patch comprises the following steps:

(1) adding 30 wt% of skeleton material natural rubber, 16 wt% of thermoplastic rubber SIS and 2 wt% of PB2400 polyisobutylene into a mixing and dispersing machine for fully mixing and dispersing, and adding 2 wt% of lanolin, 1 wt% of vaseline, 2 wt% of liquid paraffin, 10 wt% of rosin glyceride and 7 wt% of zinc oxide, kneading and dispersing uniformly to obtain a matrix;

(2) uniformly stirring 10 wt% of methyl salicylate, 6.5 wt% of menthol, 3.5 wt% of camphor and 10 wt% of cyclodextrin, adding the mixture into the matrix for kneading, filtering and refining the paste slurry through a filter to fully mix all the components uniformly, and discharging;

(3) heating the paste to 80 deg.C by coating machine, cooling the cover isolation layer to 5 deg.C by cooling tunnel, rolling, and slicing to obtain pieces of per 100cm²The high-activity slow-release pain relieving plaster contains 1.6-1.9 g of plaster.

Wherein, the high-activity slow-release analgesic patch comprises a back lining layer, a main body layer and an isolation layer which are sequentially overlapped.

Example 2:

the preparation process of the high-activity slow-release analgesic patch comprises the following steps:

(1) adding 15 wt% of framework material natural rubber, 10 wt% of synthetic rubber, 15 wt% of thermoplastic rubber SIS and 2 wt% of PB2400 polyisobutylene into a mixing and dispersing machine for fully mixing and dispersing, and then adding 2 wt% of wool grease, 1 wt% of vaseline, 5 wt% of liquid paraffin, 10 wt% of rosin glyceride, 3 wt% of lithopone and 6 wt% of zinc oxide, kneading and dispersing uniformly to obtain a matrix;

(2) uniformly stirring 10 wt% of methyl salicylate, 6.5 wt% of menthol, 3.5 wt% of camphor and 11 wt% of kaolin, adding the mixture into the matrix, mixing, filtering and refining the paste slurry through a filter to fully mix the components, and discharging;

(3) heating the paste to 80 deg.C by coating machine, cooling the cover isolation layer to 5 deg.C by cooling tunnel, rolling, and slicing to obtain pieces of per 100cm²The high-activity slow-release pain relieving plaster contains 1.6-1.9 g of plaster.

Wherein, the high-activity slow-release analgesic patch comprises a back lining layer, a main body layer and an isolation layer which are sequentially overlapped.

Example 3:

the preparation process of the high-activity slow-release analgesic patch comprises the following steps:

(1) adding 15 wt% of framework material natural rubber, 10 wt% of synthetic rubber, 15 wt% of thermoplastic rubber SIS and 505 wt% of polyisobutylene B into a mixing and dispersing machine for fully mixing and dispersing, and then adding 2 wt% of wool fat, 1 wt% of vaseline, 5 wt% of liquid paraffin, 10 wt% of sodium carboxymethylcellulose, 1 wt% of aluminum silicate and 6 wt% of zinc oxide, kneading and dispersing uniformly to obtain a matrix;

(2) uniformly stirring 10 wt% of methyl salicylate, 6.5 wt% of menthol, 3.5 wt% of camphor and 10 wt% of Eudragit (copolymer of ethyl acrylate and methyl methacrylate), adding the mixture into the matrix for kneading, filtering and refining the paste by a filter to fully mix all the components uniformly, and discharging;

(3) heating the paste to 80 deg.C by coating machine, coating on the back lining layer, cooling the cover isolation layer to 5 deg.C by cooling tunnel, rolling and slicing to obtain pieces of per 100cm²The high-activity slow-release pain relieving plaster contains 1.6-1.9 g of plaster.

Wherein, the high-activity slow-release analgesic patch comprises a back lining layer, a main body layer and an isolation layer which are sequentially overlapped.

Comparative example 1:

the preparation process of the pain relieving plaster comprises the following steps:

(1) soaking 25 wt% of natural rubber and 10 wt% of synthetic rubber in gasoline for 24 hours to fully swell, then putting the natural rubber and the synthetic rubber into a double-shaft stirrer for fully stirring, and then adding 2 wt% of lanolin, 2 wt% of vaseline, 20 wt% of zinc oxide, 20 wt% of rosin and 1 wt% of liquid paraffin for fully stirring and mixing to obtain a matrix;

(2) adding 10 wt% of methyl salicylate, 6.5 wt% of menthol and 3.5 wt% of camphor into the matrix, uniformly stirring, filtering and discharging;

(3) finally coating the paste on the back lining layer, heating to 120 deg.C to remove solvent gasoline, covering with an isolation layer, and slicing to obtain pieces per 100cm²The analgesic patch contains 1.6-1.9 g of ointment.

Wherein, the analgesic plaster comprises a back lining layer, a main body layer and an isolating layer which are sequentially overlapped.

Firstly, the content of the active ingredients in the main body layer of the analgesic patches obtained in examples 1 to 3 and comparative example 1 is measured, and the specific operation is as follows:

the analgesic patch is peeled off the isolation layer and then placed into a flask filled with 100mL of purified water to be heated and refluxed for extraction for 3 hours, the extracting solution is toluene, the diluent is ethyl acetate, the internal standard is naphthalene solution, and the detection is carried out by a gas chromatograph, and the detection results are shown in Table 1.

Table 1 results of active ingredient contents of main layer of analgesic patches of examples 1 to 3 and comparative example 1

	10 percent of methyl salicylate	6.5 percent of menthol	3.5 percent of camphor
				Example 1	9.12％	6.04％	3.07％
Example 2	9.30％	6.25％	3.21％
				Example 3	9.82％	6.32％	3.42％
Comparative example 1	7.65％	4.87％	2.50％

Secondly, the analgesic patches obtained in examples 1 to 3 and comparative example 1 were subjected to a heat resistance test, which was specifically performed as follows:

for examples 1-3 and comparative example 1, 2 analgesic patches were each taken, the cover liner was removed, and the patch was placed in an oven at 120 ℃ for 30 minutes, left to cool, and observed.

The test results were as follows:

(1) the back surfaces of the pain relieving plasters of the examples 1 to 3 have no yellowing and oil seepage phenomena, and the surfaces of the plasters are still sticky when touched by fingers; the tack of example 1 is slightly worse than that of examples 2 and 3.

(2) The patch of comparative example 1 had a slight yellowing on the back side.

In addition, the content of 6-12 wt% of methyl salicylate, 5-8 wt% of menthol and 1-4 wt% of camphor is tested and compared, and when the content of each active ingredient is less than the lower limit, the drug effect is not good; when the content is higher than the upper limit, the retention of the active ingredients is poor and the volatilization is high.

In the embodiment and the alternative scheme thereof, the content of the framework material is 30-50 wt%, the auxiliary agent is 12-28 wt%, the methyl salicylate is 6-12 wt%, the menthol is 5-8 wt%, the camphor is 1-4 wt%, the active ingredient slow-release coating material is 6-18 wt%, the filling agent is 1-10 wt%, the plasticizer is 2-4 wt%, the softener is 3-4 wt%, and the tackifier is 6-10 wt%, and the content of each component can be determined within a corresponding range according to actual needs.

In the above embodiments and alternatives, the filler may also be at least one of lithopone, zinc oxide, and aluminum silicate, the plasticizer may also be at least one of liquid paraffin and solid paraffin, and the softener may also be at least one of lanolin and vaseline, which are determined according to the actual application requirements.

The foregoing has outlined rather broadly the preferred embodiments and principles of the present invention and it will be appreciated that those skilled in the art may devise variations of the present invention that are within the spirit and scope of the appended claims.