An external use traditional Chinese medicine formula for treating ankylosing spondylitis and a preparation method thereof
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SHANDONG PROVINCIAL HOSPITAL AFFILIATED TO SHANDONG FIRST MEDICAL UNIVERSITY (SHANDONG PROVINCIAL HOSPITAL)
- Filing Date
- 2026-06-09
- Publication Date
- 2026-07-14
Smart Images
Figure CN122376692A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of topical drug synthesis technology, specifically, it relates to a topical traditional Chinese medicine formula for treating ankylosing spondylitis and its preparation method. Background Technology
[0002] Ankylosing spondylitis (AS) is a chronic, progressive autoimmune disease characterized primarily by inflammation of the sacroiliac joints and spinal entheses. Its core pathological mechanism involves a cascade of inflammatory reactions mediated by excessive activation of Th17 cells, coupled with abnormal bone metabolism: the excessive secretion of inflammatory factors such as IL-17 triggers inflammation of the synovial membrane and soft tissue damage. Simultaneously, an imbalance between osteoblasts and osteoclasts leads to heterotopic ossification and spinal ankylosis, ultimately resulting in loss of joint function. Current clinical treatment primarily involves oral nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressants, and biologics. However, these treatments suffer from drawbacks such as gastrointestinal irritation, significant systemic toxicity, low local drug concentrations in the joints, and poor long-term adherence.
[0003] Topical preparations, due to their direct application to the lesion and avoidance of systemic adverse reactions, have become an important direction for the local treatment of ankylosing spondylitis (AS). However, existing topical Chinese medicine preparations still face three major technical bottlenecks: First, they mostly employ traditional herbal extraction processes, leading to interference between different polar active ingredients, easy degradation of heat-sensitive components, and a lack of precise formulation design tailored to the pathological characteristics of AS, making it difficult to simultaneously achieve synergistic effects of anti-inflammation and osteogenic repair. Second, transdermal penetration enhancement methods are often limited, relying heavily on chemical penetration enhancers that damage the skin barrier, easily causing skin irritation. Furthermore, the drugs have short retention times on the skin surface, uncontrollable release, and cannot maintain long-term therapeutic concentrations. Third, the carrier design is disconnected from the drug characteristics. Conventional single carriers cannot simultaneously meet the loading and release requirements of multi-scale, transpolar active ingredients such as water-soluble polysaccharides, lipid-soluble terpenes, and alkaloids in Chinese medicine compound preparations. Moreover, there is a common contradiction between transdermal efficiency and skin comfort, which can easily lead to adverse reactions such as skin irritation and allergies with long-term use.
[0004] Therefore, developing a topical traditional Chinese medicine preparation that combines multi-target synergistic anti-inflammatory and osteogenic effects, high-efficiency transdermal absorption, comfortable skin feel, and long-lasting sustained release is of great clinical significance for improving the treatment of ankylosing spondylitis. Summary of the Invention
[0005] To address the shortcomings of existing technologies, this invention discloses a topical traditional Chinese medicine formula for treating ankylosing spondylitis. Using seven medicinal herbs—white peony root, artemisia annua, turmeric, coptis chinensis, astragalus membranaceus, salvia miltiorrhiza, and drynaria fortunei—as the base material, a differentiated extraction process is employed to enrich transpolar active ingredients, forming a bidirectional therapeutic basis that inhibits Th17 differentiation and IL-17 secretion while promoting osteoblast differentiation. By introducing a compound system of calcined oyster shell powder and multiple oils, the alkaline properties of oyster shell powder neutralize acidic metabolites from lesions and optimize transdermal penetration. Its hygroscopic and exothermic properties, combined with oleic acid, jojoba oil, white oil, and oleic acid oleyl alcohol esters, construct transdermal channels and a moisturizing sealing membrane. Furthermore, the fatty acid salts generated by the weak saponification reaction of alkaline inorganic salts and free fatty acids synergistically solidify the membrane layer, enhancing the stability of the skin barrier. Further, calcium hydrogen phosphate is introduced, whose calcium ions form ionic coordination bonds with sodium alginate carboxyl groups and anchor to the polysaccharide gel framework, constituting an inorganic-organic composite drug-carrying matrix. The micropores of calcium hydrogen phosphate and the mesopores of oyster shell powder form a multi-level pore system to achieve differentiated drug loading. The two work together to form a warm but not dry, moist but not stuffy drug delivery microenvironment, promoting stratum corneum hydration and blood circulation, maintaining sweat evaporation and gas exchange, reducing the risk of stuffiness and allergies, and achieving a continuous drug delivery effect of integrated drug efficacy, transdermal enhancement and sustained release regulation.
[0006] To achieve the above objectives, the technical solution adopted by this invention is a topical traditional Chinese medicine formula for treating ankylosing spondylitis, comprising the following raw materials in parts by weight: 7-10 parts of traditional Chinese medicine compound powder, 3.5-4.5 parts of transdermal gel, 0.2-0.4 parts of beeswax, 0.3 parts of oyster shell powder, 0.5-1 parts of glycerol, 0.02-0.05 parts of polyethylene glycol, 0.01-0.03 parts of EDTA-2Na, 0.3-0.5 parts of chondroitin sulfate, 0.15-0.35 parts of xanthan gum, 0.2-0.5 parts of menthol, 0.5-1 parts of chitosan, and 0.5-1 parts of montmorillonite; Furthermore, the method for preparing the polymeric oil includes the following steps: S11. Weigh 3-5 parts of activated carbon (sieved using a 200-mesh screen) and 0.5-1 parts of dicalcium phosphate and dry them at 60°C for 24 hours. Then grind and mix them evenly, sieve them using a 200-mesh screen, and obtain solid carrier powder. S12. Weigh 8-12 parts of oleic acid and add it to 8-10 parts of oleyl alcohol. Stir at 500 r / min for 10 min. Weigh 0.05 parts of citric acid and add it to the mixture. Continue stirring at the same speed for 10 min. Heat at 60-80℃ and keep warm for 4 h. The vacuum degree of the heat preservation is -0.06 MPa. Cool naturally to room temperature to obtain oleic acid oleyl alcohol ester. S13. Weigh 6-10 parts of jojoba oil and 15-25 parts of white oil, stir at 500 r / min for 30 min, then heat at 60-80℃ for 1.5 h to obtain an oil phase matrix. Add the oleic acid oleyl alcohol ester obtained in step S12 to the oil phase matrix, stir at 300 r / min, and keep at the above temperature for 2 h to obtain a composite oil phase. S14. Add the solid carrier powder obtained in step S11 to the composite oil phase obtained in step S13, heat at 110℃ for 30 min, stir at 500 r / min, degas at a vacuum of -0.1 MPa for 20 min, and let stand and mature at room temperature for 12 h to obtain the polymerized oil.
[0007] The esterification reaction process in step S12 is as follows: C 18 H 34 O2 (oleic acid) + C 18 H 37 OH (oleyl alcohol) → C 36 H 70 O2 (oleic acid oleyl alcohol ester) + H2O Furthermore, the preparation method of the transdermal gel includes the following steps: S21. Weigh 0.3-1 parts of hyaluronic acid and add it to 30 parts of deionized water. Stir at 500 r / min for 30 min to obtain a hyaluronic acid gel dispersion. Weigh 1.5-3 parts of sodium carboxymethyl cellulose and add it to 20 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 1-2.5 parts of sodium alginate and add it to the mixture. Then heat at 80℃ for 2 h and stir at 500 r / min to obtain a polysaccharide colloidal solution. S22. Add the polysaccharide colloidal solution obtained in step S21 to the prepared hyaluronic acid gel dispersion, stir at a speed of 800 r / min, heat at a temperature of 65-75℃ for 30 min, and then cool naturally to room temperature to obtain an aqueous gel matrix. S23. Weigh 2-5 parts of Tween-80 and add them to 12-15 parts of polymerized oil. Emulsify the mixture for 20 minutes at a speed of 8000 r / min to obtain a polymerized oil dispersion. S24. Add the polymerized oil dispersion obtained in step S23 to the aqueous gel matrix obtained in step S22, stir at 500 r / min for 30 min, and heat at 50°C to obtain a gel emulsion. Weigh 1 part of triethanolamine and add it to the obtained gel emulsion. Continue stirring at the above speed for 30 min and maintain the above temperature. Then cool naturally to room temperature to obtain a transdermal gel solution.
[0008] Furthermore, the preparation method of the traditional Chinese medicine compound powder includes the following steps: S31. Weigh 3-6 parts of white peony root, 1.5 parts of artemisia annua, 1-2 parts of turmeric, 0.5-1.2 parts of coptis chinensis, 0.5-1.5 parts of astragalus membranaceus, 1 part of salvia miltiorrhiza, and 0.8-1.2 parts of drynaria fortunei, wash them, and pre-dry them at 50℃ for 24 hours. Mix and grind the pre-treated white peony root, artemisia annua, and astragalus membranaceus for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder A. Mix and grind the pre-treated salvia miltiorrhiza and coptis chinensis for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder B. Mix and grind the pre-treated turmeric and drynaria fortunei for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder C. S32. Add the coarse powder A obtained in step S31 to 30 parts of deionized water, reflux at 110°C for 30 min, collect filtrate I and filter residue, add 30 parts of deionized water to the filter residue, reflux at 130°C for 10 min, collect filtrate II, mix filtrate I and filtrate II, stir at 500 r / min for 10 min, and naturally cool to room temperature to obtain a mixed filtrate. Add the coarse powder B obtained in step S31 to the mixture. Add 20 parts of alcohol solution, wherein the alcohol solution is composed of the following mass ratio of materials: water:ethanol = 7:3, and reflux at 110℃ for 30 min, and then naturally cool to room temperature to obtain alcohol extract. Add the crude powder C obtained in step 31 to 20 parts of composite extract, wherein the composite extract is composed of the following mass ratio of materials: water:ethanol:propylene glycol = 5:2:3, and reflux at 110℃ for 30 min, and then naturally cool to room temperature to obtain extract. S33. Add the alcohol extract obtained in step S32 to the obtained extract, stir at 650 r / min for 15 min, and then perform vacuum treatment at 50℃ and -0.08 MPa for 30 min to obtain the alcohol extract concentrate. Slowly add the mixed filtrate obtained in step S32, stir at 650 r / min for 15 min, and then perform vacuum treatment at 60℃ and -0.1 MPa for 30 min to obtain the water extract concentrate. S34. Add the water extract concentrate obtained in step S33 to the alcohol extract concentrate, stir at 500 r / min for 20 min, let stand at 4℃ for 48 h, then perform vacuum treatment at 45℃ and -0.12 MPa for 1 h, dry at 65℃ for 48 h, then grind and sieve through a 200 mesh screen to obtain the traditional Chinese medicine compound powder.
[0009] This invention also provides a method for preparing a topical traditional Chinese medicine formula for treating ankylosing spondylitis, comprising the following steps: S41. Weigh 0.01-0.03 parts of EDTA-2Na and add it to 25 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 0.5-1 parts of glycerol, 0.02-0.05 parts of polyethylene glycol and 0.3-0.5 parts of chondroitin sulfate and add them. Sonicate at 25 kHz for 20 min. Heat at 50℃ for 30 min. Cool naturally to room temperature to obtain a suspension. S42. Weigh 0.15-0.35 parts xanthan gum and add it to 30 parts deionized water. Stir at 500 r / min for 10 min. Weigh 0.5-1 parts chitosan and 0.5-1 parts montmorillonite (sieved using a 200 mesh screen) and add them to the mixture. Continue stirring at the above speed for 30 min to obtain the drug-loaded matrix. S43. Weigh 0.2-0.4 parts of beeswax and 0.2-0.5 parts of menthol and add them to the suspension obtained in step S41. Stir at 500 r / min for 30 min to obtain an oil phase alcohol solution. Add the drug-loaded matrix obtained in step S42 to the solution and continue stirring at the above speed for 30 min. Then, heat and reflux at 110°C to obtain a composite drug matrix. S44. Add 3.5-4.5 parts of the transdermal gel solution to the composite drug matrix prepared in step S43, stir at 500 r / min for 30 min, weigh 7-10 parts of the traditional Chinese medicine compound powder and add it, sonicate at 30 kHz for 15 min, heat at 60℃ for 30 min to obtain the gel solution, weigh 0.3 parts of oyster shell powder, calcine at 850℃ for 2 h, then cool naturally to room temperature, sieve using a 200 mesh screen, add to the gel solution, continue stirring at the above speed for 30 min, then let stand at 4℃ for 12 h to obtain the external traditional Chinese medicine formula for treating ankylosing spondylitis.
[0010] The beneficial effects achieved by this invention are as follows: The topical traditional Chinese medicine formula for treating ankylosing spondylitis prepared in this application uses seven medicinal herbs with suitable efficacy—white peony root, artemisia annua, turmeric, coptis chinensis, astragalus membranaceus, salvia miltiorrhiza, and drynaria fortunei—as the base material. A differentiated extraction process combining water extraction, alcohol extraction, and compound solvent extraction is employed to directionally separate and enrich active ingredients with different polarity ranges, followed by low-temperature precipitation to form a complex pharmacodynamic component. Among these, paeoniflorin, curcumin, and berberine synergistically inhibit Th17 differentiation and IL-17 secretion, suppressing the cascade amplification of synovial inflammation; drynaria fortunei naringin and tanshinone promote osteoblast differentiation and inhibit osteoclast activation, forming a dual therapeutic basis for inflammation control and bone repair.
[0011] The topical traditional Chinese medicine formula for treating ankylosing spondylitis prepared in this application introduces a synergistic transdermal channel constructed from calcined oyster shell powder and a multi-oil compound system. Calcined oyster shell powder is alkaline, which can neutralize acidic metabolites accumulated in inflammatory lesions, optimizing the dissociation state of drug molecules to enhance transdermal penetration. Its hygroscopic and exothermic properties create a micro-warming effect on the epidermis, promoting subcutaneous blood circulation. Based on this microenvironment, oleic acid reconstructs the lipid bilayer structure of the stratum corneum and activates epidermal cells. Jojoba oil, with its highly homologous structure to human sebum, carries the active ingredients deep into the skin. White oil and oleyl alcohol act as a flexible matrix to prolong the skin's retention time. Oleic acid and oleyl alcohol esterify to form oleic acid-oleyl alcohol ester, forming a moisturizing and sealing film on the skin surface, delaying drug release. In addition, the alkaline inorganic salts dissolved in calcined oyster shell powder can undergo a weak saponification reaction with trace amounts of free fatty acids in the system. The resulting fatty acid salts and oleic acid oleyl alcohol esters work together to form a dense and stable composite film, which enhances the uniformity and durability of the skin barrier, giving oyster shell powder multiple functions such as transdermal absorption, temperature regulation, and film curing.
[0012] The topical traditional Chinese medicine formula for treating ankylosing spondylitis prepared in this application introduces dicalcium phosphate as the basic material for epidermal drug loading. The calcium ions in dicalcium phosphate can form ionic coordination bonds with the carboxyl groups of sodium alginate in the gel system, firmly anchoring dicalcium phosphate particles within the polysaccharide gel framework, forming an inorganic and organic composite drug-loaded matrix. The micropores of dicalcium phosphate and the mesopores of calcined oyster shell powder constitute a multi-level pore system, each adapting to drug molecules of different sizes to achieve differentiated loading. Simultaneously, the hygroscopic and exothermic properties of calcined oyster shell powder are efficiently coupled with the breathability of the dicalcium phosphate micropores, creating a warm yet not dry, moist yet not stuffy microenvironment at the drug delivery site. This promotes stratum corneum hydration and blood circulation to facilitate rapid drug efficacy, while maintaining normal sweat evaporation and gas exchange through the pores, reducing skin dampness and the risk of allergies, achieving a continuous drug delivery effect of integrated efficacy, transdermal enhancement, and sustained-release regulation. Attached Figure Description
[0013] Figure 1 A simplified diagram illustrating the preparation method of the topical traditional Chinese medicine formula for treating ankylosing spondylitis proposed in this application; Figure 2pH test graphs of topical Chinese medicine formulas for treating ankylosing spondylitis prepared in the examples and comparative examples; Figure 3 Viscosity and RSD test graphs of the topical Chinese medicine formulas for treating ankylosing spondylitis prepared in the examples and comparative examples; Figure 4 The images show the total aerobic bacterial count, mold count, and yeast count of the topical Chinese medicine formulas for treating ankylosing spondylitis prepared in the examples and comparative examples. Figure 5 The transdermal absorption rate and steady-state transdermal rate of the topical Chinese medicine formulations for treating ankylosing spondylitis prepared in the examples and comparative examples are shown in the figure. Figure 6 The cumulative average release rate and film-forming time of the topical Chinese medicine formulations for treating ankylosing spondylitis prepared in the examples and comparative examples are shown in the graphs. Figure 7 The graphs show the inhibition rate, ALP, and osteoclast formation inhibition rate of the topical Chinese medicine formulas for treating ankylosing spondylitis prepared in the examples and comparative examples. Figure 8 Infrared thermography of the human epidermis of the topical Chinese medicine formula for treating ankylosing spondylitis prepared in Example 2.
[0014] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation
[0015] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.
[0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.
[0017] The preparation methods and related tests in the following examples are as follows: Figures 1-8 Unless otherwise specified, all methods are conventional. Unless otherwise specified, all parts of the materials used in the following examples are by mass. The alcohol solution is composed of the following mass ratio of materials: water:ethanol = 7:3. The compound extract is composed of the following mass ratio of materials: water:ethanol:propylene glycol = 5:2:3. All materials used are medical grade.
[0018] Example 1: A topical traditional Chinese medicine formula for treating ankylosing spondylitis, comprising the following raw materials in parts by weight: 7 parts of traditional Chinese medicine compound powder, 3.5 parts of transdermal gel, 0.2 parts of beeswax, 0.3 parts of oyster shell powder, 0.5 parts of glycerol, 0.02 parts of polyethylene glycol, 0.01 parts of EDTA-2Na, 0.3 parts of chondroitin sulfate, 0.15 parts of xanthan gum, 0.2 parts of menthol, 0.5 parts of chitosan, and 0.5 parts of montmorillonite; The method for preparing polymeric oils includes the following steps: S11. Weigh 3 parts activated carbon and 0.5 parts dicalcium phosphate and dry them at 60°C for 24 hours. Then grind and mix them evenly and sieve them with a 200-mesh screen to obtain solid carrier powder. S12. Weigh 8 parts of oleic acid and add it to 8 parts of oleyl alcohol. Stir at 500 r / min for 10 min. Weigh 0.05 parts of citric acid and add it to the mixture. Continue stirring at the same speed for 10 min. Heat at 60℃ and keep warm for 4 h. The vacuum degree of the heat preservation is -0.06 MPa. Cool naturally to room temperature to obtain oleic acid oleyl alcohol ester. S13. Weigh 6 parts of jojoba oil and 15 parts of white oil, stir at 500 r / min for 30 min, then heat at 60℃ for 1.5 h to obtain an oil phase matrix. Add the oleic acid oleyl alcohol ester obtained in step S12 to the oil phase matrix, stir at 300 r / min, and keep at the above temperature for 2 h to obtain a composite oil phase. S14. Add the solid carrier powder obtained in step S11 to the composite oil phase obtained in step S13, heat at 110℃ for 30 min, stir at 500 r / min, degas at a vacuum of -0.1 MPa for 20 min, and let stand and mature at room temperature for 12 h to obtain the polymerized oil.
[0019] The preparation method of the transdermal gel includes the following steps: S21. Weigh 0.3 parts of hyaluronic acid and add it to 30 parts of deionized water. Stir at 500 r / min for 30 min to obtain hyaluronic acid gel dispersion. Weigh 1.5 parts of sodium carboxymethyl cellulose and add it to 20 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 1 part of sodium alginate and add it to the mixture. Then heat at 80℃ for 2 h and stir at 500 r / min to obtain polysaccharide colloidal solution. S22. The polysaccharide colloidal solution obtained in step S21 is added to the hyaluronic acid gel dispersion, stirred at a speed of 800 r / min, heated at a temperature of 65℃ for 30 min, and then naturally cooled to room temperature to obtain an aqueous gel matrix. S23. Weigh 2 parts of Tween-80 and add them to 12 parts of polymerized oil. Emulsify the mixture for 20 minutes at a speed of 8000 r / min to obtain a polymerized oil dispersion. S24. Add the polymerized oil dispersion obtained in step S23 to the aqueous gel matrix obtained in step S22, stir at 500 r / min for 30 min, and heat at 50°C to obtain a gel emulsion. Weigh 1 part of triethanolamine and add it to the obtained gel emulsion. Continue stirring at the above speed for 30 min and maintain the above temperature. Then cool naturally to room temperature to obtain a transdermal gel solution.
[0020] The preparation method of traditional Chinese medicine compound powder is as follows: S31. Weigh 3 parts of white peony root, 1.5 parts of artemisia annua, 1 part of turmeric, 0.5 parts of coptis chinensis, 0.5 parts of astragalus membranaceus, 1 part of salvia miltiorrhiza, and 0.8 parts of drynaria fortunei. Wash them and pre-dry them at 50℃ for 24 hours. Mix and grind the pre-treated white peony root, artemisia annua, and astragalus membranaceus for 30 minutes and sieve them using a 200-mesh screen to obtain coarse powder A. Mix and grind the pre-treated salvia miltiorrhiza and coptis chinensis for 30 minutes and sieve them using a 200-mesh screen to obtain coarse powder B. Mix and grind the pre-treated turmeric and drynaria fortunei for 30 minutes and sieve them using a 200-mesh screen to obtain coarse powder C. S32. Add the coarse powder A obtained in step S31 to 30 parts of deionized water, reflux at 110°C for 30 min, collect filtrate I and filter residue, add 30 parts of deionized water to the filter residue, reflux at 130°C for 10 min, collect filtrate II, mix filtrate I and filtrate II, stir at 500 r / min for 10 min, and naturally cool to room temperature to obtain a mixed filtrate. Add the coarse powder B obtained in step S31 to 20 parts of alcohol solution, reflux at 110°C for 30 min, and naturally cool to room temperature to obtain an alcohol extract. Add the coarse powder C obtained in step S31 to 20 parts of the composite extract, reflux at 110°C for 30 min, and naturally cool to room temperature to obtain an extract. S33. Add the alcohol extract obtained in step S32 to the obtained extract, stir at 650 r / min for 15 min, and then perform vacuum treatment at 50℃ and -0.08 MPa for 30 min to obtain the alcohol extract concentrate. Slowly add the mixed filtrate obtained in step S32, stir at 650 r / min for 15 min, and then perform vacuum treatment at 60℃ and -0.1 MPa for 30 min to obtain the water extract concentrate. S34. Add the water extract concentrate obtained in step S33 to the alcohol extract concentrate, stir at 500 r / min for 20 min, let stand at 4℃ for 48 h, then perform vacuum treatment at 45℃ and -0.12 MPa for 1 h, dry at 65℃ for 48 h, then grind and sieve through a 200 mesh screen to obtain the traditional Chinese medicine compound powder.
[0021] This embodiment also provides a method for preparing a topical traditional Chinese medicine formula for treating ankylosing spondylitis, including the following steps: S41. Weigh 0.01 parts of EDTA-2Na and add it to 25 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 0.5 parts of glycerol, 0.02 parts of polyethylene glycol and 0.3 parts of chondroitin sulfate and add them. Sonicate at 25 kHz for 20 min. Heat at 50℃ for 30 min. Allow to cool naturally to room temperature to obtain a suspension. S42. Weigh 0.15 parts xanthan gum and add it to 30 parts deionized water. Stir for 10 minutes at a speed of 500 r / min. Weigh 0.5 parts chitosan and 0.5 parts montmorillonite and add them to the mixture. Continue stirring at the speed mentioned above for 30 minutes to obtain the drug-loaded matrix. S43. Weigh 0.2 parts beeswax and 0.2 parts menthol and add them to the suspension obtained in step S41. Stir at 500 r / min for 30 min to obtain an oil phase alcohol solution. Add the drug-loaded matrix obtained in step S42 to the solution and continue stirring at the above speed for 30 min. Then, heat and reflux at 110°C to obtain a composite drug matrix. S44. Add 3.5 parts of the transdermal gel solution to the composite drug matrix prepared in step S43, stir at 500 r / min for 30 min, weigh 7 parts of the traditional Chinese medicine compound powder and add it, sonicate at 30 kHz for 15 min, heat at 60℃ for 30 min, weigh 0.3 parts of oyster shell powder, calcine at 850℃ for 2 h, then cool naturally to room temperature, add it to the gel solution, continue stirring at the above speed for 30 min, and then let it stand at 4℃ for 12 h to obtain the external traditional Chinese medicine formula for treating ankylosing spondylitis.
[0022] Example 2: A topical traditional Chinese medicine formula for treating ankylosing spondylitis, comprising the following raw materials in parts by weight: 9 parts of traditional Chinese medicine compound powder, 4 parts of transdermal gel, 0.3 parts of beeswax, 0.3 parts of oyster shell powder, 0.8 parts of glycerol, 0.035 parts of polyethylene glycol, 0.02 parts of EDTA-2Na, 0.4 parts of chondroitin sulfate, 0.25 parts of xanthan gum, 0.35 parts of menthol, 0.8 parts of chitosan, and 0.8 parts of montmorillonite; The method for preparing polymeric oils includes the following steps: S11. Weigh 4 parts activated carbon and 0.8 parts dicalcium phosphate and dry them at 60°C for 24 hours. Then grind and mix them evenly and sieve them with a 200-mesh screen to obtain solid carrier powder. S12. Weigh 10 parts of oleic acid and add it to 9 parts of oleyl alcohol. Stir at 500 r / min for 10 min. Weigh 0.05 parts of citric acid and add it to the mixture. Continue stirring at the same speed for 10 min. Heat at 70℃ and keep warm for 4 h. The vacuum degree of the heat preservation is -0.06 MPa. Cool naturally to room temperature to obtain oleic acid oleyl alcohol ester. S13. Weigh 8 parts of jojoba oil and 20 parts of white oil, stir at 500 r / min for 30 min, then heat at 70℃ for 1.5 h to obtain an oil phase matrix. Add the oleic acid oleyl alcohol ester obtained in step S12 to the oil phase matrix, stir at 300 r / min, and keep at the above temperature for 2 h to obtain a composite oil phase. S14. Add the solid carrier powder obtained in step S11 to the composite oil phase obtained in step S13, heat at 110℃ for 30 min, stir at 500 r / min, degas at a vacuum of -0.1 MPa for 20 min, and let stand and mature at room temperature for 12 h to obtain the polymerized oil.
[0023] The preparation method of the transdermal gel includes the following steps: S21. Weigh 0.7 parts of hyaluronic acid and add it to 30 parts of deionized water. Stir at 500 r / min for 30 min to obtain a hyaluronic acid gel dispersion. Weigh 2.3 parts of sodium carboxymethyl cellulose and add it to 20 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 1.8 parts of sodium alginate and add it to the mixture. Then heat at 80℃ for 2 h and stir at 500 r / min to obtain a polysaccharide colloidal solution. S22. The polysaccharide colloidal solution obtained in step S21 is added to the hyaluronic acid gel dispersion, stirred at a speed of 800 r / min, heated at a temperature of 70℃ for 30 min, and then naturally cooled to room temperature to obtain an aqueous gel matrix. S23. Weigh 4 parts of Tween-80 and add them to 13.5 parts of polymeric oil. Emulsify the mixture for 20 minutes at a speed of 8000 r / min to obtain a polymeric oil dispersion. S24. Add the polymerized oil dispersion obtained in step S23 to the aqueous gel matrix obtained in step S22, stir at 500 r / min for 30 min, and heat at 50°C to obtain a gel emulsion. Weigh 1 part of triethanolamine and add it to the obtained gel emulsion. Continue stirring at the above speed for 30 min and maintain the above temperature. Then cool naturally to room temperature to obtain a transdermal gel solution.
[0024] The preparation method of traditional Chinese medicine compound powder is as follows: S31. Weigh 4.5 parts of white peony root, 1.5 parts of artemisia annua, 1.5 parts of turmeric, 0.9 parts of coptis chinensis, 1 part of astragalus membranaceus, 1 part of salvia miltiorrhiza, and 1 part of drynaria fortunei, wash them, and pre-dry them at 50℃ for 24 hours. Mix and grind the pre-treated white peony root, artemisia annua, and astragalus membranaceus for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder A. Mix and grind the pre-treated salvia miltiorrhiza and coptis chinensis for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder B. Mix and grind the pre-treated turmeric and drynaria fortunei for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder C. S32. Add the coarse powder A obtained in step S31 to 30 parts of deionized water, reflux at 110°C for 30 min, collect filtrate I and filter residue, add 30 parts of deionized water to the filter residue, reflux at 130°C for 10 min, collect filtrate II, mix filtrate I and filtrate II, stir at 500 r / min for 10 min, and naturally cool to room temperature to obtain a mixed filtrate. Add the coarse powder B obtained in step S31 to 20 parts of alcohol solution, reflux at 110°C for 30 min, and naturally cool to room temperature to obtain an alcohol extract. Add the coarse powder C obtained in step S31 to 20 parts of the composite extract, reflux at 110°C for 30 min, and naturally cool to room temperature to obtain an extract. S33. Add the alcohol extract obtained in step S32 to the obtained extract, stir at 650 r / min for 15 min, and then perform vacuum treatment at 50℃ and -0.08 MPa for 30 min to obtain the alcohol extract concentrate. Slowly add the mixed filtrate obtained in step S32, stir at 650 r / min for 15 min, and then perform vacuum treatment at 60℃ and -0.1 MPa for 30 min to obtain the water extract concentrate. S34. Add the water extract concentrate obtained in step S33 to the alcohol extract concentrate, stir at 500 r / min for 20 min, let stand at 4℃ for 48 h, then perform vacuum treatment at 45℃ and -0.12 MPa for 1 h, dry at 65℃ for 48 h, then grind and sieve through a 200 mesh screen to obtain the traditional Chinese medicine compound powder.
[0025] This embodiment also provides a method for preparing a topical traditional Chinese medicine formula for treating ankylosing spondylitis, including the following steps: S41. Weigh 0.02 parts of EDTA-2Na and add it to 25 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 0.8 parts of glycerol, 0.035 parts of polyethylene glycol and 0.4 parts of chondroitin sulfate and add them. Sonicate at 25 kHz for 20 min. Heat at 50℃ for 30 min. Allow to cool naturally to room temperature to obtain a suspension. S42. Weigh 0.25 parts xanthan gum and add it to 30 parts deionized water. Stir for 10 minutes at a speed of 500 r / min. Weigh 0.8 parts chitosan and 0.8 parts montmorillonite and add them to the mixture. Continue stirring at the speed mentioned above for 30 minutes to obtain the drug-loaded matrix. S43. Weigh 0.3 parts beeswax and 0.35 parts menthol and add them to the suspension obtained in step S41. Stir at 500 r / min for 30 min to obtain an oil phase alcohol solution. Add the drug-loaded matrix obtained in step S42 to the solution and continue stirring at the above speed for 30 min. Then, heat and reflux at 110°C to obtain a composite drug matrix. S44. Add 4 parts of the transdermal gel solution to the composite drug matrix prepared in step S43, stir for 30 minutes at a speed of 500 r / min, weigh 9 parts of the traditional Chinese medicine compound powder and add it, sonicate for 15 minutes at a frequency of 30 kHz, heat for 30 minutes at a temperature of 60℃, weigh 0.3 parts of oyster shell powder, calcine at a temperature of 850℃ for 2 hours, then cool naturally to room temperature, add it to the gel solution, continue stirring at the above speed for 30 minutes, and then let it stand at a low temperature of 4℃ for 12 hours to obtain the external traditional Chinese medicine formula for treating ankylosing spondylitis.
[0026] Example 3: A topical traditional Chinese medicine formula for treating ankylosing spondylitis, comprising the following raw materials in parts by weight: 10 parts of traditional Chinese medicine compound powder, 4.5 parts of transdermal gel, 0.4 parts of beeswax, 0.3 parts of oyster shell powder, 1 part of glycerol, 0.05 parts of polyethylene glycol, 0.03 parts of EDTA-2Na, 0.5 parts of chondroitin sulfate, 0.35 parts of xanthan gum, 0.5 parts of menthol, 1 part of chitosan, and 1 part of montmorillonite; The method for preparing polymeric oils includes the following steps: S11. Weigh 5 parts activated carbon and 1 part dicalcium phosphate and dry them at 60°C for 24 hours. Then grind and mix them evenly and sieve them with a 200-mesh screen to obtain solid carrier powder. S12. Weigh 12 parts of oleic acid and add it to 10 parts of oleyl alcohol. Stir at 500 r / min for 10 min. Weigh 0.05 parts of citric acid and add it to the mixture. Continue stirring at the same speed for 10 min. Heat at 60-80℃ and keep warm for 4 h. The vacuum degree of the heat preservation is -0.06 MPa. Cool naturally to room temperature to obtain oleic acid oleyl alcohol ester. S13. Weigh 10 parts of jojoba oil and 25 parts of white oil, stir at 500 r / min for 30 min, then heat at 80℃ for 1.5 h to obtain an oil phase matrix. Add the oleic acid oleyl alcohol ester obtained in step S12 to the oil phase matrix, stir at 300 r / min, and keep warm at the above temperature for 2 h to obtain a composite oil phase. S14. Add the solid carrier powder obtained in step S11 to the composite oil phase obtained in step S13, heat at 110℃ for 30 min, stir at 500 r / min, degas at a vacuum of -0.1 MPa for 20 min, and let stand and mature at room temperature for 12 h to obtain the polymerized oil.
[0027] The preparation method of the transdermal gel includes the following steps: S21. Weigh 1 part of hyaluronic acid and add it to 30 parts of deionized water. Stir at 500 r / min for 30 min to obtain hyaluronic acid gel dispersion. Weigh 3 parts of sodium carboxymethyl cellulose and add it to 20 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 2.5 parts of sodium alginate and add it to the mixture. Then heat at 80℃ for 2 h and stir at 500 r / min to obtain polysaccharide colloidal solution. S22. The polysaccharide colloidal solution obtained in step S21 is added to the hyaluronic acid gel dispersion, stirred at a speed of 800 r / min, heated at a temperature of 75℃ for 30 min, and then naturally cooled to room temperature to obtain an aqueous gel matrix. S23. Weigh 5 parts of Tween-80 and add them to 15 parts of polymerized oil. Emulsify the mixture for 20 minutes at a speed of 8000 r / min to obtain a polymerized oil dispersion. S24. Add the polymerized oil dispersion obtained in step S23 to the aqueous gel matrix obtained in step S22, stir at 500 r / min for 30 min, and heat at 50°C to obtain a gel emulsion. Weigh 1 part of triethanolamine and add it to the obtained gel emulsion. Continue stirring at the above speed for 30 min and maintain the above temperature. Then cool naturally to room temperature to obtain a transdermal gel solution.
[0028] The preparation method of traditional Chinese medicine compound powder is as follows: S31. Weigh 6 parts of white peony root, 1.5 parts of artemisia annua, 2 parts of turmeric, 1.2 parts of coptis chinensis, 1.5 parts of astragalus membranaceus, 1 part of salvia miltiorrhiza, and 1.2 parts of drynaria fortunei, wash them, and pre-dry them at 50℃ for 24 hours. Mix and grind the pre-treated white peony root, artemisia annua, and astragalus membranaceus for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder A. Mix and grind the pre-treated salvia miltiorrhiza and coptis chinensis for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder B. Mix and grind the pre-treated turmeric and drynaria fortunei for 30 minutes, and sieve them using a 200-mesh screen to obtain coarse powder C. S32. Add the coarse powder A obtained in step S31 to 30 parts of deionized water, reflux at 110°C for 30 min, collect filtrate I and filter residue, add 30 parts of deionized water to the filter residue, reflux at 130°C for 10 min, collect filtrate II, mix filtrate I and filtrate II, stir at 500 r / min for 10 min, and naturally cool to room temperature to obtain a mixed filtrate. Add the coarse powder B obtained in step S31 to 20 parts of alcohol solution, reflux at 110°C for 30 min, and naturally cool to room temperature to obtain an alcohol extract. Add the coarse powder C obtained in step S31 to 20 parts of the composite extract, reflux at 110°C for 30 min, and naturally cool to room temperature to obtain an extract. S33. Add the alcohol extract obtained in step S32 to the obtained extract, stir at 650 r / min for 15 min, and then perform vacuum treatment at 50℃ and -0.08 MPa for 30 min to obtain the alcohol extract concentrate. Slowly add the mixed filtrate obtained in step S32, stir at 650 r / min for 15 min, and then perform vacuum treatment at 60℃ and -0.1 MPa for 30 min to obtain the water extract concentrate. S34. Add the water extract concentrate obtained in step S33 to the alcohol extract concentrate, stir at 500 r / min for 20 min, let stand at 4℃ for 48 h, then perform vacuum treatment at 45℃ and -0.12 MPa for 1 h, dry at 65℃ for 48 h, then grind and sieve through a 200 mesh screen to obtain the traditional Chinese medicine compound powder.
[0029] This embodiment also provides a method for preparing a topical traditional Chinese medicine formula for treating ankylosing spondylitis, including the following steps: S41. Weigh 0.03 parts of EDTA-2Na and add it to 25 parts of deionized water. Stir at 500 r / min for 15 min. Weigh 1 part of glycerol, 0.05 parts of polyethylene glycol and 0.5 parts of chondroitin sulfate and add them. Sonicate at 25 kHz for 20 min. Heat at 50℃ for 30 min. Let it cool naturally to room temperature to obtain a suspension. S42. Weigh 0.35 parts xanthan gum and add it to 30 parts deionized water. Stir for 10 minutes at a speed of 500 r / min. Weigh 1 part chitosan and 1 part montmorillonite and add them to the mixture. Continue stirring at the speed mentioned above for 30 minutes to obtain the drug-loaded matrix. S43. Weigh 0.4 parts beeswax and 0.5 parts menthol and add them to the suspension obtained in step S41. Stir at 500 r / min for 30 min to obtain an oil phase alcohol solution. Add the drug-loaded matrix obtained in step S42 to the solution and continue stirring at the above speed for 30 min. Then, heat and reflux at 110°C to obtain a composite drug matrix. S44. Add 4.5 parts of the transdermal gel solution to the composite drug matrix prepared in step S43, stir at 500 r / min for 30 min, weigh 10 parts of the traditional Chinese medicine compound powder and add it, sonicate at 30 kHz for 15 min, heat at 60℃ for 30 min, weigh 0.3 parts of oyster shell powder, calcine at 850℃ for 2 h, then cool naturally to room temperature, add it to the gel solution, continue stirring at the above speed for 30 min, and then let it stand at 4℃ for 12 h to obtain the external traditional Chinese medicine formula for treating ankylosing spondylitis.
[0030] Comparative example: The difference between Comparative Example 1 and Example 2 is that no compound Chinese medicine powder was added; the rest of the parts are the same as Example 2. The difference between Comparative Example 2 and Example 2 is that no gel transdermal solution was added; the rest of the parts are the same as Example 2. The difference between Comparative Example 3 and Example 2 is that no traditional Chinese medicine compound powder and transdermal gel were added; the rest of the parts are the same as Example 2.
[0031] The following performance tests were conducted on the prepared topical traditional Chinese medicine formula for treating ankylosing spondylitis: Figure 2 The pH values of the formulations prepared in Examples 1-3 and Comparative Examples 1-3 are compared. The pH values of the examples were stable in the range of 6.15–6.45, which is within the physiologically tolerable pH range of human skin (4.5–6.5). This indicates that the citrate-triethanolamine buffer system can effectively regulate the pH of the system, maintaining the stability of the formulation while reducing the risk of skin irritation caused by abnormal pH. Figure 3 The results show the relative standard deviation (RSD) of viscosity and content uniformity of the formulations prepared in Examples 1-3 and Comparative Examples 1-3. The viscosity of the Examples is 25000–32000 mPa·s, which is higher than that of the Comparative Examples, thus prolonging the retention time of the drug on the skin surface. At the same time, the content uniformity RSD of the three indicative components, paeoniflorin, curcumin, and berberine hydrochloride, in the Examples is <3%, which is lower than the 5% threshold that is conventionally acceptable for topical semi-solid preparations, indicating that the drugs are uniformly dispersed and of stable quality in the inorganic-organic composite gel matrix. Figure 4The results show the microbial limit comparison between the preparations obtained in Examples 1-3 and Comparative Examples 1-3. In the examples, the total aerobic bacteria count was <500 cfu / g, and the total mold and yeast count was <100 cfu / g, meeting the microbial limit requirements for topical administration preparations in the 2025 edition of the Chinese Pharmacopoeia. This indicates that the antibacterial system of the present invention is effective and its microbial safety is qualified. Figure 5 The results show the comparison of the 24-hour cumulative transdermal absorption and steady-state transdermal absorption rate of the formulations prepared in Examples 1-3 and Comparative Examples 1-3. The 24-hour cumulative transdermal absorption and steady-state transdermal absorption rate of Examples 1-3 are higher than those of the comparative examples, indicating that the calcined oyster shell powder-multi-oil compound system can achieve synergistic transdermal enhancement by improving the permeability of the stratum corneum and increasing drug solubility. Figure 6 The results compare the cumulative release rate and film-forming time of the formulations prepared in Examples 1-3 and Comparative Examples 1-3 over 48 hours. The cumulative release rate of Example 2 over 48 hours was 69.4%, with no obvious burst release and the drug release was gradual and lasted for more than 48 hours. At the same time, the film-forming time of Example 2 was 3-4 minutes, which was shorter than that of the comparative examples (6-8 minutes), and the film formation was rapid and uniform, which is beneficial to prolonging the drug action time. Figure 7 The results show a comparison of the in vitro pharmacological activities of the formulations prepared in Examples 1-3 and Comparative Examples 1-3. Example 2 showed a 64.3% inhibition rate of IL-17 secretion, significantly better than the comparative examples; it increased osteoblast ALP activity to 61.2% and inhibited osteoclast differentiation by 70.4%. These results indicate that the formulations of this invention possess both significant anti-inflammatory activity and bidirectional osteogenic-osteoclast regulatory effects in vitro. Figure 8 The results are shown in the infrared thermal imaging test after the preparation obtained in Example 2 was applied to the human epidermis. The skin surface temperature reached 39.6°C 2 hours after application, indicating that the hygroscopic and exothermic properties of calcined oyster shell powder can create a mild warming effect on the local epidermis, which can promote local blood circulation, assist in transdermal drug absorption, and provide a mild and comfortable skin feel.
[0032] To further verify the efficacy of the topical traditional Chinese medicine formulations for treating ankylosing spondylitis prepared in the examples and comparative examples, the following safety tests were conducted. Table 1 shows the test results using rats as the safety verification subjects:
[0033] Table 1 shows the results of selecting healthy SPF-grade SD rats as experimental subjects. The formulations of Examples 1-3 and Comparative Examples 1-3 were applied to the shaved areas on the backs of the rats, and acute skin irritation tests, skin sensitization tests, transepidermal water loss (TEWL) measurements, and a long-term skin toxicity test lasting 90 days were conducted. In the acute skin irritation and sensitization tests, erythema, edema, irritation, and sensitization scores were observed and recorded after administration. TEWL was measured at 0 h before administration and 24 h after administration. In the long-term toxicity test, the rats were administered the drug daily, and their general condition was observed for 90 days. Hematological and serum biochemical indicators were measured at the end of the test. The results showed that no erythema or edema appeared on the skin of rats in Examples 1-3 groups, with irritation scores of 1-2 and sensitization scores of 0, indicating good skin barrier function. TEWL values increased from 18.5-18.7 g / (m²) before administration. 2 The concentration of ·h) decreased to 14.9-15.7 g / (m 2 The results (·h) indicate that the formulation can protect and repair the skin barrier. After 90 days of continuous application, the rats' diet, activity, and weight remained normal, and their blood and biochemical indicators were all within the normal range, with no abnormalities. Comparative examples 1-3 showed varying degrees of erythema, edema, sensitization reactions, and skin barrier damage. In summary, the topical Chinese medicine formulation prepared in these examples is non-irritating and non-sensitizing to the skin, can protect the skin barrier, and is safe and gentle for long-term topical use, meeting the safety requirements for clinical topical use.
[0034] Based on the above test results, the following clinical trials were conducted; Table 2 shows the experimental results of the topical Chinese medicine formula for treating ankylosing spondylitis prepared in Example 2:
[0035] Table 2 shows the clinical observation results of the topical traditional Chinese medicine formula for treating ankylosing spondylitis prepared in Example 2. This study selected 10 patients with ankylosing spondylitis, who applied the topical traditional Chinese medicine formula of Example 2 to the affected area daily and were followed up for 12 months. The results showed that after one month of use, patients experienced significant relief of local pain and a shorter morning stiffness duration; after 2-4 months of use, pain, stiffness, and limited mobility symptoms were significantly improved; and after 8-12 months of use, joint function was basically restored, and the inflammatory state was under long-term control. No redness, swelling, irritation, or allergic reactions occurred at the application site in any patient, indicating good skin tolerance and long-term safety and stability. In summary, the preparation of this invention can significantly improve the pain, stiffness, and limited mobility symptoms of patients with ankylosing spondylitis, improve their quality of life, and has good clinical application value.
[0036] Figure 8The results of the application are for patient 2. It should be noted that this study is a small-sample preliminary observational trial and no control group was set up. Note: Clinical efficacy is mainly evaluated by the improvement of patients' subjective pain, morning stiffness duration, joint range of motion, and inflammation-related symptoms.
[0037] Obviously, the above comparative examples and embodiments are only a part of the comparative examples and embodiments of the present invention, and they, along with the comparative examples and embodiments referenced based on such examples, are all within the scope of protection of this invention.
[0038] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
[0039] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.
Claims
1. A topical traditional Chinese medicine formula for treating ankylosing spondylitis, characterized in that, The preparation materials include the following parts by weight: 7-10 parts of traditional Chinese medicine compound powder, 3.5-4.5 parts of transdermal gel, 0.2-0.4 parts of beeswax, 0.3 parts of oyster shell powder, 0.5-1 parts of glycerol, 0.02-0.05 parts of polyethylene glycol, 0.01-0.03 parts of EDTA-2Na, 0.3-0.5 parts of chondroitin sulfate, 0.15-0.35 parts of xanthan gum, 0.2-0.5 parts of menthol, 0.5-1 parts of chitosan, and 0.5-1 parts of montmorillonite; The transdermal gel comprises materials in the following mass ratio: hyaluronic acid: Tween-80: sodium carboxymethyl cellulose: sodium alginate: triethanolamine: polymeric oil = 0.3-1: 2-5: 1.5-3: 1-2.5: 1: 12-15, and the polymeric oil comprises materials in the following mass ratio: activated carbon: dicalcium phosphate: oleic acid: jojoba oil: white oil: oleyl alcohol: citric acid = 3-5: 0.5-1: 8-12: 6-10: 15-25: 8-10: 0.05; The method for preparing the polymeric oil includes the following steps: S11. Activated carbon and calcium hydrogen phosphate are dried, ground, and then a solid carrier powder is obtained. S12. Add oleic acid to oleyl alcohol, stir, add citric acid, stir, heat, and keep warm to obtain oleic acid oleyl alcohol ester; S13. Weigh jojoba oil and white oil, stir, heat to obtain oil phase matrix, add oleic acid oleyl alcohol ester, stir, keep warm to obtain composite oil phase; S14. Add the solid carrier powder to the composite oil phase, stir, degas, and mature to obtain the polymerized oil.
2. The topical traditional Chinese medicine formula for treating ankylosing spondylitis according to claim 1, characterized in that, The heating temperature in step S12 is 60-80℃, and the vacuum degree of heat preservation is -0.06MPa. The heating temperature in step S13 is 60-80℃, and the vacuum degree of degassing in step S14 is -0.1MPa.
3. The topical traditional Chinese medicine formula for treating ankylosing spondylitis according to claim 1, characterized in that, The preparation method of the transdermal gel includes the following steps: S21. Hyaluronic acid is added to water and stirred to obtain a hyaluronic acid gel dispersion. Sodium carboxymethyl cellulose is added to water and stirred. Sodium alginate is added and stirred to obtain a polysaccharide colloidal solution. S22. Add the polysaccharide colloidal solution to the hyaluronic acid gel dispersion, stir, and heat to obtain an aqueous gel matrix; S23. Add Tween-80 to the polymerized oil, emulsify, and obtain the polymerized oil dispersion; S24. Add the polymerized oil dispersion to the aqueous gel matrix and stir to obtain a gel emulsion. Add triethanolamine to the gel emulsion and stir to obtain a transdermal gel solution.
4. The topical traditional Chinese medicine formula for treating ankylosing spondylitis according to claim 3, characterized in that, The heating temperature in step S22 is 65-75℃ and the heating time is 30 min. The emulsification speed in step 23 is 8000 r / min and the emulsification time is 20 min.
5. A topical traditional Chinese medicine formula for treating ankylosing spondylitis according to claim 1, characterized in that, The herbal compound powder comprises materials in the following mass ratio: white peony root: artemisia annua: turmeric: coptis chinensis: astragalus membranaceus: salvia miltiorrhiza: drynaria fortunei = 3-6: 1.5: 1~2: 0.5-1.2: 0.5~1.5: 1: 0.8-1.2; The preparation method of the traditional Chinese medicine compound powder includes the following steps: S31. Pre-treat white peony root, artemisia annua, turmeric, coptis chinensis, astragalus membranaceus, salvia miltiorrhiza, and drynaria fortunei. Mix and grind white peony root, artemisia annua, and astragalus membranaceus to obtain coarse powder A. Mix and grind salvia miltiorrhiza and coptis chinensis to obtain coarse powder B. Mix and grind turmeric coarse powder and drynaria fortunei to obtain coarse powder C. S32. Add coarse powder A to water, heat to obtain mixed filtrate, add coarse powder B to alcohol solution, reflux to obtain alcohol extract, add coarse powder C to compound extract, heat, reflux to obtain extract; S33. Add the alcohol extract to the extract, stir, reduce pressure to obtain the alcohol extract concentrate, add the mixed filtrate, stir, reduce pressure to obtain the water extract concentrate; S34. Add the water extract concentrate to the alcohol extract concentrate, stir, let stand at low temperature, reduce pressure, dry, grind, and sieve to obtain the traditional Chinese medicine compound powder.
6. A topical traditional Chinese medicine formula for treating ankylosing spondylitis according to claim 5, characterized in that, The alcohol solution in step S32 is composed of materials in the following mass ratio: water:ethanol = 7:
3. The composite extract is composed of materials in the following mass ratio: water:ethanol:propylene glycol = 5:2:
3. The vacuum degree of the alcohol extract concentrate in step S33 is -0.08MPa, and the vacuum temperature is 50℃. The vacuum degree of the water extract concentrate is -0.1MPa, and the vacuum temperature is 60℃. The vacuum degree of the vacuum in step S34 is -0.12MPa, and the vacuum temperature is 45℃.
7. A method for preparing a topical traditional Chinese medicine formula for treating ankylosing spondylitis as described in any one of claims 1-6, characterized in that, Includes the following steps: S41. Add EDTA-2Na to water and stir. Add glycerol, polyethylene glycol and chondroitin sulfate, sonicate and heat to obtain a suspension. S42. Add xanthan gum to water and stir. Add chitosan and montmorillonite and stir to obtain the drug-loaded matrix. S43. Add beeswax and menthol to a suspension to obtain an oil phase alcoholic solution. Add the drug-loaded matrix, stir, and heat to obtain a composite drug matrix. S44. Add the transdermal gel to the composite drug matrix, stir, add the Chinese herbal compound powder, sonicate, heat to obtain the gel solution, calcine the oyster shell powder, add it to the gel solution, stir, let stand at low temperature to obtain the external Chinese herbal medicine formula for treating ankylosing spondylitis.