Borneolum syntheticum inclusion compound, ostalgia tincture gel emplastrum and preparation method and application of ostalgia tincture gel emplastrum

Abstract

The invention discloses a borneol inclusion compound, a bone pain relieving tincture gel emplastrum and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicine preparation preparation. The preparation process of the borneol clathrate compound comprises the following steps: adding borneol into ethanol, and dissolving, so as to obtain a borneol ethanol solution; the preparation method comprises the following steps: adding water into hydroxypropyl beta-cyclodextrin to prepare hydroxypropyl beta-cyclodextrin paste; adding the borneol ethanol solution into the hydroxypropyl-beta-cyclodextrin paste, mixing, adding water in a room temperature environment, and grinding until the hydroxypropyl-beta-cyclodextrin is a saturated aqueous solution; carrying out ultrasonic treatment on the saturated aqueous solution to obtain an inclusion solution, carrying out spray drying on the inclusion solution, and washing to obtain the borneol inclusion compound; the mass ratio of the hydroxypropyl beta-cyclodextrin to the borneol is 4: (0.3-0.7). According to the invention, the medicinal effect of the original dosage form is ensured, the extraction efficiency of the decoction pieces is greatly improved, and the liquid dosage form is changed into the solid dosage form, so that the medication comfort and compliance are improved.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of traditional Chinese medicine preparations, and more specifically to a borneol inclusion compound, a bone pain relieving tincture gel plaster, and a preparation method and application thereof. Background Art

[0002] Gutongling tincture is widely used in clinical applications. This Chinese medicine compound preparation is composed of a variety of medicinal materials, including Artemisia annua, frankincense, myrrh, dragon's blood, dried ginger, and borneol.

[0003] Gutongling tincture is a Chinese Pharmacopoeia variety. This variety was proposed by Dianhong Pharmaceutical Group Co., Ltd. It has now been included in the national protected Chinese medicine variety, the national medical insurance catalog variety, and the national essential medicine catalog variety. Gutongling tincture is a very commonly used external pure Chinese medicine preparation, which uses Yunnan's unique precious medicinal materials and is made by using modern technology. The research of Feng Tao et al. shows that Gutongling tincture can play analgesic, anti-inflammatory, and detumescent effects, and can also achieve the expansion of capillaries, ultimately achieving the purpose of improving microcirculation. It can play a good role in the clinical treatment of bone hyperplasia, osteoarthritis, and rheumatoid arthritis. However, the borneol component contained in the formula of Gutongling tincture preparation is volatile and irritating. In the prior art, borneol is usually directly dissolved in ethanol and mixed with other drug percolation solutions. The processing method of borneol is not good, and the defects of borneol being volatile and irritating cannot be solved. Summary of the invention

[0004] To solve the above problems, the present invention provides a borneol inclusion compound, a bone pain tincture gel plaster, and a preparation method and application thereof, so as to solve the defect problem that borneol is volatile and irritating.

[0005] The present invention is achieved through the following technical solutions:

[0006] In one aspect, the present invention provides a borneol inclusion compound, the preparation process of which comprises the following steps:

[0007] The borneol is added into ethanol to dissolve, thereby obtaining a borneol ethanol solution.

[0008] Hydroxypropyl-beta-cyclodextrin is added with water to prepare hydroxypropyl-beta-cyclodextrin paste.

[0009] Add borneol ethanol solution to hydroxypropyl beta-cyclodextrin paste and mix, add water and grind at room temperature to obtain a saturated aqueous solution of hydroxypropyl beta-cyclodextrin, ultrasonically treat the saturated aqueous solution to obtain an inclusion liquid, spray-dry the inclusion liquid, and wash to obtain a borneol inclusion compound.

[0010] The mass ratio of hydroxypropyl-beta-cyclodextrin to borneol is 4:0.3-0.7.

[0011] Another aspect of the present invention provides a Gutongling tincture gel plaster, which is prepared from a borneol inclusion compound, other drugs in a formula and auxiliary materials.

[0012] The auxiliary materials are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0013] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:13.75-18.75:0-2.5:0.5-1:2.5:0.5:0.1:2.2.

[0014] Preferably, the mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:18.75:2.5:1:2.5:0.5:0.1:2.2.

[0015] The preparation method of the Gutongling tincture gel plaster specifically comprises the following steps:

[0016] Prepare the borneol inclusion compound, other drugs and excipients in the formula of Gutongling tincture gel patch according to the mass ratio.

[0017] Grind Artemisia annua, dried ginger, myrrh and frankincense into powder, mix well, soak in ethanol, perform ultrasonic extraction, collect the supernatant and concentrate to obtain a thick paste.

[0018] Add water to Carbomer to make it swell, let it stand for 12 to 13 hours, and adjust the pH value to 7 to form a gel.

[0019] Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound are fully mixed with glycerin in sequence, stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0020] The thick paste is added into the mixture of the drug-containing gel and glycerin, fully stirred, applied, dried, left to stand for aging, covered and cut to obtain the Gutongling tincture gel plaster.

[0021] The amount of water added is 19 to 21 times that of carbomer.

[0022] The volume ratio of the gel, glycerin mixture and thick paste is 4-5:4:5 。

[0023] Preferably, the relative density of the thick paste at 70° C. is 1.20-1.40.

[0024] Preferably, the particle size of the powder is 24 mesh to 65 mesh.

[0025] Preferably, the volume concentration of the ethanol is 50% to 70%.

[0026] Preferably, the ultrasonic extraction time is 65 min to 85 min.

[0027] Preferably, the cutting size is (6cm-8cm) x (10cm-12cm) per patch, 60cm per patch 2 ~96cm 2 Drug loading.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The present invention provides a borneol inclusion compound preparation process, which adopts grinding and ultrasonic method, and uses a spray dryer to spray dry to prepare the borneol inclusion compound, so as to improve the stability of borneol and reduce the irritation of borneol; finally, the bone pain tincture extract and the borneol inclusion compound are used as raw materials, and the bone pain tincture gel patch is prepared by adding a suitable matrix and then coating. While ensuring the efficacy of the original dosage form, the extraction efficiency can be greatly improved, the extraction time is greatly shortened, and the production efficiency is improved. In addition, the comfort and compliance of medication will be improved to varying degrees. At the same time, this can provide certain ideas and basis for other external preparations, and its own application value is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0031] Figure 1 The effect of different particle sizes of medicinal materials on the extraction rate of artemisinin A in the present invention;

[0032] Figure 2 The effect of different ethanol concentrations on the extraction rate of artemisinin A in the present invention;

[0033] Figure 3 The effect of different ultrasonic times on the extraction rate of artemisinin A in the present invention;

[0034] Figure 4 The effect of different ethanol dosages on the extraction rate of artemisinin A in the present invention;

[0035] Figure 5 This is a high performance liquid chromatogram of methanol of the present invention;

[0036] Figure 6 This is the standard spectrum of artemisinin A of the present invention;

[0037] Figure 7 This is a sample diagram of the Gutongling tincture thick paste of the present invention. DETAILED DESCRIPTION

[0038] In order to facilitate the understanding of the present invention, the present invention will be described more comprehensively below, and preferred embodiments of the present invention are provided. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0039] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0040] In order to better illustrate the present invention, the technical solution of the present invention will be further described below in conjunction with specific embodiments.

[0041] The sources of materials, reagents, equipment and instruments used in the present invention are as follows:

[0042] 1. Materials and reagents.

[0043] Table 1 Materials and reagents

[0044]

[0045]

[0046] 2. Equipment and instruments.

[0047] Table 2 Equipment and instruments

[0048] name model factory Laboratory spray dryer YC-2100 Shanghai Yacheng Instrument Equipment Co., Ltd. Ultrasonic Cleaner KQ-500B Kunshan Ultrasonic Instrument Co., Ltd. Electric blast drying oven XGQ-2000 Zhejiang Lichen Instrument Technology Co., Ltd. High-speed refrigerated centrifuge GL-12MS Shanghai Luxiangyi Centrifuge Instrument Co., Ltd. Purified water machine UPT-60 Suzhou Jiazhou Purification Equipment Co., Ltd. Circulating water multi-purpose vacuum pump SHZ-DIII Henan Yuhua Instrument Co., Ltd. Gas Chromatograph Agilent-7890A Agilent Technologies High performance liquid chromatography L600-DP6 Beijing Puxi General Instrument Co., Ltd. Electric constant temperature water bath DZKW-17-4 Beijing Yongguangming Medical Instrument Co., Ltd. Electronic analytical balance, 0.001g WT10002 Hangzhou Wante Weighing Instrument Co., Ltd. Electronic analytical balance, 0.0001g FA2104B Shanghai Yueping Scientific Instrument Co., Ltd. pH Meter PHS-3C Shanghai INESA Scientific Instrument Co., Ltd. Speed ​​digital display constant temperature magnetic stirrer 85-2A Shanghai Meixiang Instrument Co., Ltd. Purified water machine UPT-60 Suzhou Jiazhou Purification Equipment Co., Ltd. High speed multifunctional pulverizer JP-800C Yongkang Jiupin Industry and Trade Co., Ltd.

[0049] The inventive concept of the present invention is as follows:

[0050] The borneol contained in the formula of Gutongling tincture is volatile and irritating, which has caused some patients to report that their skin will have allergic reactions after using Gutongling tincture, usually showing symptoms such as redness, itching, and papules, which has an adverse effect on the patient's medication experience.

[0051] In view of this, the present invention proposes a borneol inclusion compound, the preparation process of which includes: adding borneol to ethanol to dissolve to obtain a borneol ethanol solution; adding water to hydroxypropyl beta-cyclodextrin to prepare hydroxypropyl beta-cyclodextrin paste; adding the borneol ethanol solution to the hydroxypropyl beta-cyclodextrin paste and mixing, adding water and grinding at room temperature to obtain a saturated aqueous solution of hydroxypropyl beta-cyclodextrin; ultrasonically treating the saturated aqueous solution to obtain an inclusion liquid, spray-drying the inclusion liquid, and washing to obtain a borneol inclusion compound. The preparation process can improve the stability of borneol, reduce the irritation of borneol, solve the defect problem that borneol is volatile and irritating, and improve the comfort of patients taking medicine. In addition, due to the use of a highly water-soluble inclusion material, the absorption of borneol is promoted, and the bioavailability of borneol can be improved. Ultrasonic extraction can greatly shorten the extraction time and improve production efficiency. The inclusion liquid is dried by a spray drying device, which shortens the drying time and improves production efficiency. The dry solid powder prepared can be more convenient for storage and subsequent production.

[0052] Based on the same inventive concept, the present invention also provides a Gutongling tincture gel patch, which is prepared from the borneol inclusion compound, other drugs in the formula and excipients.

[0053] The specific steps include:

[0054] Prepare the borneol inclusion compound, other drugs and excipients in the formula of Gutongling tincture gel patch according to the mass ratio.

[0055] Grind Artemisia annua, dried ginger, myrrh and frankincense into powder, mix well, soak in ethanol, perform ultrasonic extraction, collect the supernatant and concentrate to obtain a thick paste.

[0056] Add water to Carbomer to make it swell, let it stand for 12 to 13 hours, and adjust the pH value to 7 to form a gel.

[0057] Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound are fully mixed with glycerin in sequence, stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0058] The thick paste is added into the mixture of the drug-containing gel and glycerin, fully stirred, applied, dried, left to stand for aging, covered and cut to obtain the Gutongling tincture gel plaster.

[0059] The preparation method of the bone pain tincture gel patch uses ultrasonic extraction, which greatly shortens the extraction time and improves production efficiency compared to traditional percolation extraction. In addition, in the actual extraction process, it also shows the characteristics of low cost and simple operation. In addition, the gel patch has very good performance, its own drug loading is large, and the drug absorption rate is relatively high, and it can maintain a high affinity with the skin. The patient's medication comfort is further improved, and it is relatively simple to use without causing pollution to clothing.

[0060] The technical solution of the present invention will be further described below in conjunction with specific embodiments.

[0061] Example 1: Process for preparing a borneol inclusion compound

[0062] Add appropriate amount of ethanol to borneol and grind until borneol is completely dissolved to obtain borneol ethanol solution; place hydroxypropyl beta-cyclodextrin in a mortar, add appropriate amount of purified water until hydroxypropyl beta-cyclodextrin paste is prepared; slowly add borneol ethanol solution to hydroxypropyl beta-cyclodextrin paste and mix, add purified water at room temperature and grind for 1.5 hours until hydroxypropyl beta-cyclodextrin is a saturated aqueous solution; ultrasonically treat the saturated aqueous solution to obtain inclusion liquid, the ultrasonic treatment power is 250W, the frequency is 33kHz, and the time is 30 minutes; spray dry the inclusion liquid, wash it with anhydrous ethanol 3 times, 5 ml each time, and place it in a dryer for drying to obtain borneol inclusion compound. Wherein, the mass ratio of hydroxypropyl beta-cyclodextrin to borneol is 4:0.3.

[0063] Example 2: Process for preparing a borneol inclusion compound

[0064] Add appropriate amount of ethanol to borneol and grind until borneol is completely dissolved to obtain borneol ethanol solution; place hydroxypropyl beta-cyclodextrin in a mortar, add appropriate amount of purified water until hydroxypropyl beta-cyclodextrin paste is prepared; slowly add borneol ethanol solution to hydroxypropyl beta-cyclodextrin paste and mix, add purified water at room temperature and grind for 1.5 hours until hydroxypropyl beta-cyclodextrin is a saturated aqueous solution; ultrasonically treat the saturated aqueous solution to obtain inclusion liquid, the ultrasonic treatment power is 250W, the frequency is 33kHz, and the time is 30 minutes; spray dry the inclusion liquid, wash it with anhydrous ethanol 3 times, 5 ml each time, and place it in a dryer for drying to obtain borneol inclusion compound. Wherein, the mass ratio of hydroxypropyl beta-cyclodextrin to borneol is 4:0.5.

[0065] Example 3: Process for preparing a borneol inclusion compound

[0066] Add appropriate amount of ethanol to borneol and grind until the borneol is completely dissolved to obtain borneol ethanol solution; place hydroxypropyl beta-cyclodextrin in a mortar, add appropriate amount of purified water until hydroxypropyl beta-cyclodextrin paste is prepared; slowly add borneol ethanol solution to hydroxypropyl beta-cyclodextrin paste and mix, add purified water at room temperature and grind for 1.5 hours until hydroxypropyl beta-cyclodextrin is a saturated aqueous solution; ultrasonically treat the saturated aqueous solution to obtain inclusion liquid, the power of ultrasonic treatment is 250W, the frequency is 33kHz, and the time is 30 minutes; after spray drying the inclusion liquid, wash it with anhydrous ethanol 3 times, 5 ml each time, and place it in a dryer for drying to obtain borneol inclusion compound. Wherein, the mass ratio of hydroxypropyl beta-cyclodextrin to borneol is 4:0.7.

[0067] The content of the borneol inclusion complex prepared in Examples 1 to 3 was determined.

[0068] Chromatographic conditions: The present invention uses PEG-20M polyethylene glycol 20000 as the stationary phase, with a coating concentration of 10%; the column temperature is 140°C, and the injection volume is 1 μl. Based on the calculation of the borneol peak, the theoretical plate number should be no less than 2000.

[0069] Preparation of reference solution: Accurately weigh an appropriate amount of borneol reference, add ethyl acetate to prepare a solution containing 5 mg per 1 ml.

[0070] Preparation of sample solution: Accurately weigh 1.5 g of the borneol inclusion compound in Example 1, 0.85 g of the borneol inclusion compound in Example 2, and 0.7 g of the borneol inclusion compound in Example 3, respectively, and place them in a separating funnel, add about 9 ml of ethyl acetate, make up to 10 ml with purified water, shake, take the ethyl acetate layer and place it in a 10 ml volumetric flask, add ethyl acetate to make up to the volume, let it stand, filter, and take the filtrate to obtain.

[0071] Determination method: Accurately take 20 μl of the reference solution and 10 μl of the sample solution, respectively, inject them into the gas chromatograph, determine the borneol content, and calculate the borneol encapsulation rate based on the borneol content, in g, and the calculation formula is as follows:

[0072] Borneol encapsulation rate = borneol content in borneol inclusion compound / actual amount of borneol in borneol × 100%.

[0073] (3) Orthogonal experimental design

[0074] Table 3 Factor level table of orthogonal experimental design of borneol inclusion compound

[0075]

[0076] The orthogonal test was designed as shown in Table 3, where A is the feed ratio of hydroxypropyl beta-cyclodextrin to borneol, unit: g / g; B is the peristaltic speed of the spray dryer peristaltic pump, unit: RPM; C is the air inlet temperature, unit: °C. 4 ) orthogonal test, see Table 4 and Table 5. The orthogonal test results and variance analysis show that the air inlet temperature C has a greater impact on the encapsulation rate, followed by the feed ratio A and the peristaltic speed B. The best process combination is C2A2B2, that is, the feed ratio of hydroxypropyl beta-cyclodextrin: borneol is 4:0.5, the peristaltic speed of the spray dryer peristaltic pump is 20RPM, and the air inlet temperature is 45℃, which is the encapsulation process of borneol inclusion compound.

[0077] Table 4 Borneol inclusion compound orthogonal test results

[0078]

[0079]

[0080] Note: “ / ” means no item.

[0081] When α was 0.05, the variance analysis was performed, F 0.05 (2, 2) = 19.000, see Table 5 below for details.

[0082] Table 5 Analysis of variance

[0083] factor Sum of Squared Deviations Degrees of Freedom F-number A 58.621 2 8.172 B 60.111 2 8.380 C 535.340 2 74.633* error 7.17 2 /

[0084] Note: “ / ” means no such item; * means it is significant when α is 0.05.

[0085] (4) Repeated confirmatory test

[0086] According to the preparation process of the best inclusion compound obtained by orthogonal test, parallel experiments were conducted, as shown in Table 6. Three parallel verifications were conducted according to the experimental scheme C2A2B2, and the average encapsulation rate of the borneol inclusion compound was 68.72%, which indicated that the scheme was feasible.

[0087] Table 6 Results of repeated validation tests

[0088] Number of trials 1 2 3 Mean Encapsulation rate of borneol inclusion compound, % 68.60 68.84 68.71 68.72

[0089] Example 4: A method for preparing a Gutongling tincture gel plaster

[0090] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0091] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0092] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0093] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:13.75:0:0.5:2.5:0.5:0.1:2.2.

[0094] The specific steps include:

[0095] Prepare the borneol inclusion compound, other drugs and excipients in the formula of Gutongling tincture gel patch according to the mass ratio.

[0096] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 24 mesh, mix well, add 50% ethanol to soak for 24 hours, ultrasonically extract for 65 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.20 using a rotary evaporator at 70°C.

[0097] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 19 times that of carbomer.

[0098] (3) Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0099] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 6 cm×10 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 60 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0100] The volume ratio of the gel, glycerin mixture and thick paste is 4:4:5.

[0101] Example 5: A method for preparing a Gutongling tincture gel plaster

[0102] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0103] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0104] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0105] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:13.75:1.25:1:2.5:0.5:0.1:2.2.

[0106] The specific steps include:

[0107] Prepare the borneol inclusion compound, other drugs and excipients in the formula of Gutongling tincture gel patch according to the mass ratio.

[0108] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 50 mesh, mix well, add 60% ethanol to soak for 24 hours, ultrasonically extract for 75 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.30 at 70°C using a rotary evaporator.

[0109] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 20 times that of carbomer.

[0110] (3) Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0111] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 7 cm×11 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 77 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0112] The volume ratio of the gel, glycerin mixture and thick paste is 4.5:4:5.

[0113] Example 6: A method for preparing a Gutongling tincture gel plaster

[0114] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0115] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0116] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0117] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:13.75:2.5:1.5:2.5:0.5:0.1:2.2.

[0118] The specific steps include:

[0119] Prepare the borneol inclusion compound, other drugs and excipients in the formula of Gutongling tincture gel patch according to the mass ratio.

[0120] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 65 mesh, mix well, soak in 70% ethanol for 24 hours, perform ultrasonic extraction for 85 minutes, the ultrasonic power is 250 W, the frequency is 33 kHz, vacuum filter is performed with filter paper with a pore size of 70 μm, ultrasonic extraction is performed 4 times, and the filtrate is combined; centrifuge, collect the supernatant; and use a rotary evaporator to concentrate at 70°C to a thick paste with a relative density of 1.40.

[0121] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 21 times that of carbomer.

[0122] (3) Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0123] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 7 cm×11 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 77 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0124] The volume ratio of the gel, glycerin mixture and thick paste is 5:4:5.

[0125] Example 7: A method for preparing a Gutongling tincture gel plaster

[0126] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0127] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0128] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0129] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:16.25:0:1:2.5:0.5:0.1:2.2.

[0130] The specific steps include:

[0131] Prepare the borneol inclusion compound, other drugs and excipients in the formula of Gutongling tincture gel patch according to the mass ratio.

[0132] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 50 mesh, mix well, add 60% ethanol to soak for 24 hours, ultrasonically extract for 75 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.30 at 70°C using a rotary evaporator.

[0133] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 20 times that of carbomer.

[0134] (3) Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0135] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 8 cm×12 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 96 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0136] The volume ratio of the gel, glycerin mixture and thick paste is 5:4:5.

[0137] Example 8: A method for preparing a Gutongling tincture gel plaster

[0138] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0139] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0140] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0141] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:16.25:1.25:1.5:2.5:0.5:0.1:2.2.

[0142] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 50 mesh, mix well, add 60% ethanol to soak for 24 hours, ultrasonically extract for 75 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.30 at 70°C using a rotary evaporator.

[0143] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 20 times that of carbomer.

[0144] (3) Propylene glycol 2, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0145] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 7 cm×11 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 77 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0146] The volume ratio of the gel, glycerin mixture and thick paste is 5:4:5.

[0147] Example 9: A method for preparing a Gutongling tincture gel plaster

[0148] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0149] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0150] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0151] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:16.25:2.5:0.5:2.5:0.5:0.1:2.2.

[0152] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 50 mesh, mix well, add 60% ethanol to soak for 24 hours, ultrasonically extract for 75 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.30 at 70°C using a rotary evaporator.

[0153] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 20 times that of carbomer.

[0154] (3) Propylene glycol 2, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0155] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 7 cm×11 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 77 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0156] The volume ratio of the gel, glycerin mixture and thick paste is 5:4:5.

[0157] Example 10: A method for preparing a Gutongling tincture gel plaster

[0158] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0159] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0160] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0161] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:18.75:0:1.5:2.5:0.5:0.1:2.2.

[0162] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 50 mesh, mix well, add 60% ethanol to soak for 24 hours, ultrasonically extract for 75 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.30 at 70°C using a rotary evaporator.

[0163] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 20 times that of carbomer.

[0164] (3) Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0165] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 7 cm×11 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 77 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0166] The volume ratio of the gel, glycerin mixture and thick paste is 5:4:5.

[0167] Example 11: A method for preparing a Gutongling tincture gel plaster

[0168] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0169] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0170] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0171] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:18.75:1.25:0.5:2.5:0.5:0.1:2.2.

[0172] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 50 mesh, mix well, add 60% ethanol to soak for 24 hours, ultrasonically extract for 75 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.30 at 70°C using a rotary evaporator.

[0173] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 20 times that of carbomer.

[0174] (3) Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0175] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 7 cm×11 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 77 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0176] The volume ratio of the gel, glycerin mixture and thick paste is 5:4:5.

[0177] Example 12: A method for preparing a Gutongling tincture gel plaster

[0178] The Gutongling tincture gel plaster is prepared from borneol inclusion compound, other drugs in the formula and auxiliary materials.

[0179] The other medicines in the formula are Artemisia snow alkekengi, dried ginger, dragon's blood, frankincense and myrrh.

[0180] The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid.

[0181] The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:18.75:2.5:1:2.5:0.5:0.1:2.2.

[0182] (1) Grind Artemisia annua, dried ginger, myrrh, and frankincense into powder with a particle size of 50 mesh, mix well, add 60% ethanol to soak for 24 hours, ultrasonically extract for 75 minutes, with an ultrasonic power of 250 W and a frequency of 33 kHz, vacuum filter with a filter paper of 70 μm pore size, ultrasonically extract 4 times, combine the filtrate, centrifuge, collect the supernatant, and concentrate to a thick paste with a relative density of 1.30 at 70°C using a rotary evaporator.

[0183] (2) Carbomer is fully swollen with purified water, left to stand for 12 hours, and triethanolamine is added, and stirring is continued to keep the pH value stably at 7 to form a gel. The amount of water added is 20 times that of carbomer.

[0184] (3) Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are mixed in sequence and stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with the gel to obtain a drug-containing gel and glycerin mixture.

[0185] (4) Add the thick paste to the mixture of the drug-containing gel and glycerin, and after sufficient stirring, obtain a drug material with suitable viscosity, which is the drug material to be coated on the Gutongling Tincture Gel Patch; apply the drug material to be coated, place it in an electric hot air drying oven at 35° C. for 12 hours, let it stand for aging, cover it with a liner, cut it into a size of 7 cm×11 cm per patch, and seal it for storage, thereby obtaining the Gutongling Tincture Gel Patch, with a drug loading of 77 cm per patch. 2 Equivalent to 10ml of tincture, i.e. a single dose.

[0186] The volume ratio of the gel, glycerin mixture and thick paste is 5:4:5.

[0187] The quality of the Gutongling tincture gel patch prepared in Example 4 to Example 12 was evaluated, and the evaluation criteria were as shown in Table 7. Based on the items and standards in Table 3, the quality scores of the Gutongling tincture gel patches prepared in Example 2 to Example 12 were then calculated, and the comprehensive scores were calculated. The results are shown in Table 8, and the scores were between 32 and 43 points, among which Example 12 had the highest total score of 43 points. Therefore, when the preparation method of the Gutongling tincture gel patch of the present invention is used, the obtained finished product has good adhesion, cohesion, initial adhesion and adhesion base strength. In addition, no residue will appear on the skin surface, and its own formability and process reproducibility are relatively good.

[0188] Table 7 Scoring criteria

[0189]

[0190] Table 8 Quality evaluation table of Gutongling tincture gel plaster

[0191]

[0192] Example 13, determination of the extraction process of Gutongling tincture gel plaster

[0193] This example compares the extraction efficiency of the percolation method and the ultrasonic method.

[0194] Recipe: Artemisia snow alkekengi 80g, dried ginger 110g, Sanguisorba officinalis 1g, frankincense 5g, myrrh 5g, and borneol 1.5g.

[0195] (1) Percolation method

[0196] For the above six ingredients, grind the formulated amount of Artemisia annua, dried ginger, myrrh and frankincense into powder, mix well, and soak in 50% ethanol for 24 hours according to the percolation method under the fluid extract and extract items. Percolate and collect the percolate, a total of 950 ml; at the same time, dissolve the formulated amount of Sanguisorba officinalis and borneol in 50 ml of 95% ethanol, combine with the percolate, shake well, let stand for 48 hours, take the supernatant and make it into 1000 ml.

[0197] (2) Ultrasonic method

[0198] Take the above six ingredients, grind the formulated amount of Artemisia annua, dried ginger, myrrh and frankincense into powder, mix well, add 50% ethanol to soak for 24 hours, ultrasonically extract, vacuum filter, and ultrasonically extract 4 times, combine the filtrate; centrifuge to collect 950ml of filtrate; at the same time, dissolve the formulated amount of Sanguisorba officinalis and borneol in 50ml of ethanol, combine with the above filtrate, shake well, centrifuge, take the supernatant, and make it into 1000ml.

[0199] (3) Determination of extraction content by percolation and ultrasonic method

[0200] Chromatographic conditions: octadecylsilane bonded silica gel as filler; methanol-phosphate buffer solution as mobile phase, detection wavelength 210nm. Based on the peak of artemisinin, the number of theoretical plates is not less than 1500. The preparation method of methanol-phosphate buffer solution is to take 1.97g of disodium hydrogen phosphate and 0.22g of potassium dihydrogen phosphate, dissolve in water and dilute to 1000ml, adjust the pH value to 7.3 with 80% phosphoric acid solution, and the volume ratio of methanol to phosphate solution is 72:28.

[0201] Preparation of standard solution: Take an appropriate amount of artemisinin A standard, weigh accurately, add chromatographic methanol, and make a solution containing 300 μg per 1 ml for later use. Figure 5 shown.

[0202] Preparation of test solution: accurately measure 25 ml of sample solution prepared by percolation method and ultrasonic method, place in an evaporating dish, evaporate to about 10 ml in a water bath, adjust pH value to 2-3 with dilute hydrochloric acid, transfer to a separatory funnel, wash the container with an appropriate amount of 0.1 mol / L hydrochloric acid, add the washing liquid into the separatory funnel, dissolve with a small amount of chloroform if necessary, make the total amount of acid solution about 25 ml, wash twice with chloroform, the volume of chloroform used is 10 ml and 5 ml respectively, combine the chloroform solution, wash twice with 0.1 mol / L hydrochloric acid, the volume of hydrochloric acid used is 5 ml and 3 ml respectively, combine the above acid aqueous solution, add 2 g of sodium chloride, shake gently to dissolve, Adjust the pH value to 9-10 with ammonia test solution, extract with chloroform by shaking for 5 times, the volumes of chloroform used are 25ml, 15ml, 10ml, 10ml and 10ml respectively, combine the chloroform solutions, add appropriate amount of anhydrous sodium sulfate for dehydration, filter, collect the filtrate, wash the residue with chloroform twice, 5ml each time, combine the filtrate, evaporate to nearly dryness in a 60℃ water bath, add 1ml of anhydrous ethanol, evaporate naturally, dissolve in methanol and transfer to a 25ml volumetric flask, add methanol to the scale, ultrasonically treat with a power of 250W and a frequency of 33kHz for 5 minutes, cool, add methanol to the scale, shake well, let stand, filter, and take the filtrate to obtain.

[0203] Determination method: Accurately pipette 20μl of standard solution and 10μl of test solution respectively, inject into liquid chromatograph, and determine. The spectrum of artemisinin A standard is as follows: Figure 6 As shown in the figure, the spectrum of the test sample of Artemisinin A is as follows Figure 7 As shown. The content of artemisinin A was calculated respectively, and the formula is:

[0204]

[0205] C r is the concentration of artemisinin A in the standard solution; A X A is the peak area of ​​artemisinin A in the chromatogram of the test product; r It is the peak area of ​​artemisinin A in the chromatogram of the standard solution.

[0206] The results are shown in Table 9.

[0207] Table 9 Comparison of content extracted by percolation and ultrasonic method

[0208] method Artemisinin content in snow stalk, unit: μg / mL Percolation 81.46 Ultrasonic method 64.48

[0209] After comparison, the content of artemisinin A extracted by ultrasonic method was 64.48 μg / ml, which was in line with the requirement of pharmacopoeia that 1 ml of Artemisia selengensis contained 10.5 μg / ml of Artemisia selengensis A. 22 H 33Calculated in terms of NO2, it should be 60μg~170μg.

[0210] Example 14, determination of extraction conditions of Gutongling tincture gel plaster

[0211] In this example, single-factor experiments were conducted on the particle size of medicinal materials, ethanol concentration, ultrasonic time, and ethanol dosage to investigate the effects of the above factors on the extraction rate of artemisinin A.

[0212] (1) Influence of medicinal material particle size

[0213] The particle size of the medicinal materials was set to 10, 24, 50, 65, and 80 meshes. The formula amount of Artemisia sutchuenensis, dried ginger, myrrh, and frankincense were taken, soaked in 50% ethanol for 0.5 hours, ultrasonically extracted, vacuum filtered, and ultrasonically extracted 4 times, and the filtrates were combined; 1 / 10 of the formula amount of Sanguisorba officinalis and Borneol were dissolved in 95% ethanol, combined with the above filtrates, mixed, centrifuged, and made into 100 ml. According to the determination method of Example 13, the effect of the particle size of the medicinal materials on the extraction rate was explored, and the results are shown in FIG. Figure 1 When the particle size of the medicinal material is in the range of 24-65 mesh, the extraction rate of the active ingredient is higher, and when the particle size of the medicinal material is 50 mesh, the extraction rate is the highest, which can reach 64.14 μg / ml. Therefore, after comprehensive comparison, the best particle size of the medicinal material is 50 mesh.

[0214] (2) Effect of ethanol concentration

[0215] Take the formula amount of Artemisia sibiricum, dried ginger, myrrh, and frankincense, add ethanol concentrations of 30%, 40%, 50%, 60%, and 70% respectively, soak for 0.5 hours, perform ultrasonic, vacuum filtration, and ultrasonic extraction 4 times, and combine the filtrates; add 95% ethanol to dissolve 1 / 10 of the formula amount of Sanguisorba officinalis and Borneol, combine with the above filtrates, centrifuge, and prepare 100ml. According to the determination of Example 13, the effect of ethanol concentration on the extraction rate was explored, and the results are shown in Figure 2 When the ethanol concentration reaches 50% to 70%, a better extraction rate can be obtained. When the ethanol concentration is 60%, the extraction rate is the highest, reaching 59.82μg / ml, and then the optimal ethanol concentration is determined to be 60%.

[0216] (3) Effect of ultrasound time

[0217] Take the formula amount of Artemisia sibiricum, dried ginger, myrrh, and frankincense, set the ultrasonic time to 45, 55, 65, 75, and 85 minutes respectively, add 50% ethanol to soak for 0.5 hours, ultrasonic extraction, vacuum filtration, ultrasonic extraction 4 times, and combine the filtrate; dissolve 1 / 10 of the formula amount of dragon's blood and borneol in 95% ethanol, combine with the above filtrate, centrifuge, and prepare 100ml. According to the determination of Example 13, the effect of ultrasonic time on the extraction rate was explored, and the results are shown in FIG. Figure 3As the ultrasonic time increases, the content of active ingredients increases continuously. When the ultrasonic time is in the range of 65min to 85min, the extraction rate of active ingredients is better. When the ultrasonic time is 75min, the extraction rate is the highest, which can reach 62.5μg / ml. Then the optimal ultrasonic time is determined to be 75min.

[0218] (4) Effect of ethanol dosage

[0219] Take the formula amount of Artemisia annua, dried ginger, myrrh, and frankincense, set the ethanol dosage to 75ml, 85ml, 95ml, 105ml, and 115ml respectively, add 40ml of 50% ethanol to moisten for 70 minutes, then add 50% ethanol to ultrasonically filter, vacuum filter, repeat four times, combine the filtrate, centrifuge, and collect the supernatant; at the same time, dissolve 1 / 10 of the formula amount of dragon's blood and borneol in ethanol, and combine with the obtained filtrate, after mixing, let it stand for 48 hours, and after filtering, it is obtained. According to the determination of Example 13, the effect of ethanol dosage on the extraction rate is explored, and the results are shown in FIG. Figure 4 As the amount of ethanol increased, there was no significant difference in the content of the active ingredient, so it was not used as an investigation factor in the orthogonal test.

[0220] (5) Orthogonal experimental design

[0221] Table 10 Factor level table of orthogonal test design for medicinal material extraction

[0222]

[0223] The orthogonal test was designed as shown in Table 10, where a is the particle size of the medicinal material, unit: mesh, b is the ethanol concentration, unit: %, and c is the ultrasonic time, unit: min. Based on the extraction method proposed in the preliminary experiment, L9(3 4 ) Orthogonal optimization test, see Table 11, Table 12, after orthogonal test, variance analysis, according to the results obtained, the particle size of the medicinal material a and the extraction rate have the most significant influence relationship, followed by ultrasonic time c, ethanol concentration b. A1C3B2 is the best process combination, the medicinal material particle size of 24 mesh, ethanol concentration of 70%, ultrasonic time of 75min is the best extraction process of artemisinin A.

[0224] Table 11 Results of orthogonal test of artemisinin A on snow

[0225]

[0226] Note: “ / ” means no item.

[0227] When α is 0.05, the ethanol concentration b is selected as the error, and then the variance analysis is carried out. 0.05 (2, 4) = 6.940, see Table 12 below for details.

[0228] Table 12 Analysis of variance

[0229] factor Sum of Squared Deviations Degrees of Freedom F Ratio a 1667.909 2 18.649*7.019 b 58.745 2 0.6570.247 c 242.079 2 2.7071.019 error 178.87 4 /

[0230] Note: " / " means no such item; * means it is significant when α is 0.05.

[0231] In summary, the present invention, in order to reduce the irritation of borneol, applies inclusion technology to carry out inclusion treatment when conducting experimental research, and makes borneol inclusion compound, which not only significantly reduces the irritation of borneol to the skin, but also avoids the volatilization of borneol, and can promote the absorption of borneol. The bone pain tincture gel plaster prepared by using the borneol inclusion compound and the remaining drugs in the formula is extracted by ultrasonic method, which greatly shortens the extraction time, and the content of the effective ingredient is in line with the pharmacopoeia specified range compared with the percolation method. The alcohol-containing liquid preparation is developed into an alcohol-free solid gel plaster, which is convenient for patients to use, reduces adverse reactions, and is convenient for storage and transportation. This product is a brown external application patch. Various inspection items of the gel plaster all meet the requirements of the pharmacopoeia. It can play a good effect in the treatment of bone hyperplasia, osteoarthritis, and rheumatoid arthritis. By preparing the bone pain tincture into the gel plaster dosage form, the market gap is filled, and more choices are provided for the clinical medication of patients.

[0232] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0233] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A process for preparing a borneol inclusion compound, characterized in that: include: Add borneol to ethanol and dissolve it to obtain borneol ethanol solution; Adding water to hydroxypropyl beta-cyclodextrin to prepare hydroxypropyl beta-cyclodextrin paste; Adding borneol ethanol solution to hydroxypropyl beta-cyclodextrin paste and mixing, adding water and grinding at room temperature until hydroxypropyl beta-cyclodextrin is a saturated aqueous solution; subjecting the saturated aqueous solution to ultrasonic treatment to obtain an inclusion liquid, spray drying the inclusion liquid, and washing to obtain a borneol inclusion compound; The mass ratio of hydroxypropyl-beta-cyclodextrin to borneol is 4:0.3-0.

7.

2. The borneol inclusion compound prepared by the borneol inclusion compound preparation process as claimed in claim 1.

3. A Gutongling tincture gel plaster, characterized in that: The Gutongling tincture gel plaster is prepared from the borneol inclusion compound in claim 2, the remaining drugs in the formula and excipients; The remaining drugs in the formula are Artemisia sibiricum, dried ginger, dragon's blood, frankincense, and myrrh; The excipients are carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth and tartaric acid; The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:13.75-18.75:0-2.5:0.5-1:2.5:0.5:0.1:2.

2.

4. The Gutongling tincture gel plaster as claimed in claim 3, characterized in that: The mass ratio of the Artemisia annua, dried ginger, frankincense, myrrh, carbomer, glycerin, propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glyoxylate, diatomaceous earth, tartaric acid, dragon's blood, and borneol inclusion compound is 8:11:0.5:0.5:5:90:22.5:18.75:2.5:1:2.5:0.5:0.1:2.

2.

5. The method for preparing the Gutongling tincture gel plaster as claimed in claim 3, characterized in that: The specific steps include: Prepare the borneol inclusion compound of Gutongling tincture gel patch, other drugs and excipients in the formula according to the mass ratio; The Artemisia annua, dried ginger, myrrh and frankincense are crushed into powder, mixed, soaked in ethanol, extracted by ultrasonic, the supernatant is collected, and concentrated to obtain a thick paste; Add water to carbomer to make it swell, let it stand for 12 to 13 hours, and adjust the pH value to 7 to form a gel; Propylene glycol, sodium polyacrylate, tragacanth gum, aluminum glycolate, diatomaceous earth, tartaric acid, dragon's blood, borneol inclusion compound, and glycerin are fully mixed in sequence, stirred evenly to obtain a glycerin mixture, and the glycerin mixture is mixed with gel to obtain a drug-containing gel and glycerin mixture; The thick paste is added into the mixture of the drug-containing gel and glycerin, fully stirred, applied, dried, left to stand for aging, covered with a lining, and cut to obtain the bone pain tincture gel plaster; The amount of water added is 19 to 21 times that of carbomer; The volume ratio of the gel, glycerin mixture and thick paste is 4-5:4:5 。 6. The method for preparing the Gutongling tincture gel plaster as claimed in claim 4, characterized in that: The relative density of the thick paste at 70° C. is 1.20-1.

40.

7. The method for preparing the Gutongling tincture gel plaster as claimed in claim 4, characterized in that: The particle size of the powder is 24 mesh to 65 mesh.

8. The method for preparing the Gutongling tincture gel plaster as claimed in claim 4, characterized in that: The volume concentration of the ethanol is 50% to 70%.

9. The method for preparing the Gutongling tincture gel plaster as claimed in claim 4, characterized in that: The ultrasonic extraction time is 65 min to 85 min.

10. The method for preparing the Gutongling tincture gel plaster as claimed in claim 4, characterized in that: The cutting size is (6cm~8cm)×(10cm~12cm) per patch, 60cm per patch 2 ~96cm 2 Drug loading.

Images