Formula for relieving and treating osteoarthropathy and preparation method

Abstract

The invention relates to the technical field of medicines, and discloses a formula for relieving and treating osteoarthropathy, which comprises the following components in parts by weight: 10-20 parts of ligusticum wallichii extract; 10 to 15 parts of frankincense extract; 5 to 10 parts of myrrh extract; 5 to 15 parts of non-denatured type II collagen; 5-15 parts of a teasel root extract; 2 to 5 parts of curcumin; 10 to 20 parts of a penetration enhancer; 1-5 parts of a targeted response material; the invention further provides a preparation method of the formula, and the preparation method comprises the following steps: extracting and purifying the main medicinal components; preparing a targeted response carrier; compounding a penetration enhancer; integration of the medicinal components and the auxiliary materials; preparing an ointment matrix; and preparing an ointment finished product. Through optimal design of the penetration enhancer, the targeting carrier and the stable emulsion matrix, deep penetration, accurate release, uniform distribution and high-efficiency stability during use of the medicine are realized.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to a formula for relieving and treating osteoarthritis and a preparation method thereof. Background Art

[0002] With the extension of human life span and changes in lifestyle, the incidence of bone and joint diseases continues to rise, and has become a major issue threatening public health. The pain and inconvenience caused by joint degeneration in the elderly, as well as the acute inflammation caused by sports injuries in young people, have caused great troubles in daily life and work. At present, topical ointments have become a common choice for relieving the symptoms of bone and joint diseases due to their convenience, concentrated site of action, and low irritation.

[0003] In the prior art, topical preparations for relieving osteoarthritis have achieved certain results. For example, by adding ointments with Chinese herbal extracts, it can play a certain anti-inflammatory, analgesic and blood circulation and blood stasis effects; some preparations can effectively relieve local joint stiffness and pain through physical massage combined with drug penetration. In addition, some improved ointment products use transdermal absorption technology to improve the utilization rate of drugs, so that the active ingredients can be quickly released on the skin surface and reach the superficial tissue. These methods meet the use needs of some patients to a certain extent, and also provide good effects on the symptom relief of existing osteoarthritis.

[0004] However, these existing technologies still have shortcomings in practical applications. First, most products lack targeted design, and drug ingredients tend to stagnate at the skin barrier and have difficulty penetrating into the joints, limiting the therapeutic effect on deep tissues. Second, preparations that lack targeted response function often cause drugs to diffuse throughout the epidermis and fail to concentrate at the site of inflammation, reducing the utilization rate of the drug efficacy. In addition, some products have unreasonable matrix design, ointment stratification, or uneven drug distribution, which seriously affects the user experience. Summary of the invention

[0005] In view of the deficiencies of the prior art, the present invention provides a formula and a preparation method for alleviating the function of treating osteoarthritis, which solves the problems of insufficient drug penetration, poor targeting, uneven drug distribution and low stability in use in the prior art.

[0006] To achieve the above objectives, the present invention is implemented by the following technical scheme: a formula for relieving and treating osteoarthritis, the formula comprising the following components in parts by weight: Chuanxiong extract: 10-20 parts; The main active ingredient of Chuanxiong extract is ligustrazine, which can promote microcirculation and has a significant effect of promoting blood circulation and removing blood stasis. In addition, Chuanxiong extract can also inhibit the release of inflammatory factors in the synovial membrane of the joints, thereby reducing the inflammatory response in osteoarthritis. Ligustrazine improves local microcirculation, reduces the level of hypoxia in the inflammatory area, reduces the inflammatory response, and promotes the supply of nutrients around the lesions. In addition, Chuanxiong extract can reduce the generation of free radicals, prevent oxidative damage to cartilage tissue, and provide favorable conditions for joint recovery. Frankincense extract: 10-15 parts; Frankincense extract contains active ingredients such as β-amyric acid and α-amyric acid, which have strong anti-inflammatory effects. They can reduce joint inflammation by inhibiting the activity of cyclooxygenase and 5-lipoxygenase, blocking the inflammatory signal transduction pathway. β-Amyric acid can effectively relieve joint pain and swelling by inhibiting the synthesis of inflammatory mediators such as prostaglandin E2 and leukotrienes, reducing the accumulation of local inflammatory factors in the joints.

[0007] Myrrh extract: 5-10 parts; Myrrh extracts can reduce the production of inflammatory factors such as tumor necrosis factor-α and interleukin-6 by inhibiting the nuclear factor κB signaling pathway, thereby alleviating the inflammatory response of joint soft tissues. At the same time, myrrh ingredients can also reduce cartilage damage caused by osteoarthritis by inhibiting the tyrosine kinase signaling pathway. Non-denatured type II collagen: 5-15 parts; By introducing non-denatured type II collagen, the ointment’s precise action on cartilage repair is enhanced and inflammation-induced joint pain is reduced, while providing direct cartilage regeneration support for longer-lasting results; Dipsacus asper extract: 5-15 parts; Dipsacus root extract can enhance the gene expression level of chondrocytes, improve the efficiency of cartilage repair, and further slow down the progression of osteoarthritis. At the same time, Dipsacus root extract can also reduce the release of cartilage-degrading enzymes by inhibiting the activity of matrix metalloproteinases. Curcumin: 2-5 parts; Curcumin can reduce oxidative stress by removing reactive oxygen species from the inflamed joints. At the same time, it can inhibit the NF-κB pathway and reduce the release of inflammatory factors such as TNF-α and IL-6. In addition, curcumin can promote the synthesis of hyaluronic acid in the cartilage matrix and enhance the lubrication of the joints. Penetration enhancer: 10-20 parts; Targeted response materials: 1 to 5 copies; Ointment base: 35-50 parts; The use of penetration enhancers and targeted response materials solves the technical problems of drug transdermal absorption and target aggregation. Combined with a stable ointment base, the formula has the comprehensive advantages of high efficiency, targeting and stability.

[0008] Preferably, the penetration enhancer comprises: Palmitoylethanolamide: 2-5 parts; The addition of palmitoylethanolamide can enhance the anti-inflammatory and analgesic effects of the ointment, improve storage stability and bioavailability, and increase the rate and depth of drug transdermal absorption through its fat-soluble properties; Propylene glycol: 3-8 parts; Propylene glycol is a commonly used transdermal adjuvant and moisturizer. It can reduce the skin barrier resistance by dissolving the lipid components in the stratum corneum. It also has a good dissolution and penetration promoting effect on both water-soluble and fat-soluble drugs. Propylene glycol destroys the integrity of the lipid bilayer of the stratum corneum, allowing drug molecules to more easily pass through the skin barrier and enter the dermis. In addition, the moisturizing effect of propylene glycol can keep the skin soft and moist, reduce the barrier dysfunction caused by dry skin, and improve the drug absorption rate. Ethanol: 5-10 parts; Ethanol is a small molecule organic solvent with good volatility and penetrability. It can be used as the main transdermal enhancer. Ethanol changes the structural integrity of the stratum corneum and increases the fluidity of the stratum corneum through dehydration and dissolving lipids in the stratum corneum, thereby reducing the resistance to transdermal diffusion of drugs. In addition, ethanol has a strong solubility and can dissolve certain fat-soluble drugs and bring drug molecules into the deep layers of the skin in the form of a solvent.

[0009] Preferably, the targeted response material comprises: Chitosan-curcumin composite particles: 1-3 parts; Chitosan-curcumin composite particles are prepared by self-assembly of chitosan and curcumin. They are a pH-responsive nanocomposite material. Chitosan is a natural polymer material with biocompatibility, degradability and low toxicity. It has a large number of amino groups and can partially dissociate and release the loaded active substances in an acidic environment. Curcumin is a polyphenol compound with anti-inflammatory, antioxidant and immunomodulatory effects. It is an important ingredient in the treatment of osteoarthritis. Hyaluronic acid: 0.5-2 parts; Hyaluronic acid is a natural polysaccharide that is widely present in human connective tissue, especially in synovial fluid where it has a high concentration. In this formula, hyaluronic acid plays a role in lubricating joints, protecting articular cartilage, and promoting drug dispersion. At the same time, its polymer structure can enhance the residence time of the drug at the site of inflammation. Chitosan releases curcumin in response to the inflammatory microenvironment, effectively alleviating inflammation and oxidative damage. At the same time, hyaluronic acid enhances the stability and efficacy of the formula through lubrication and drug delivery.

[0010] Preferably, the ointment base comprises: Vaseline: 35-50 parts; Vaseline is mainly used as a carrier component of drugs to provide a suitable matrix structure, ensure the physical stability of the ointment, and form a protective film to reduce the evaporation of drugs and the impact of external stimuli on the skin; Lanolin: 10-15 parts; Lanolin contains hydrophilic groups and lipophilic groups in its structure, which can play an emulsifying role in the ointment, stably combining the hydrophilic components with the lipophilic components to form a uniform ointment structure, ensuring the uniform distribution of the drug components, and also has a moisturizing effect; Purified water: 10-20 parts; Purified water is an important solvent component in this formula. Purified water can effectively dissolve hydrophilic components and fully mix them with lipophilic components through the action of emulsifiers, thereby ensuring that all drug ingredients in the ointment are evenly distributed and avoiding the phenomenon of excessively high or low local drug concentrations.

[0011] The present invention also provides a method for preparing the formula, comprising the following steps: Extraction and purification of main active ingredients; Preparation of targeted response vectors; Compounding of penetration enhancers; Integration of active ingredients and auxiliary materials; Preparation of particle matrix; Integration and preparation of particles.

[0012] Preferably, the extraction and purification of the main active ingredients includes: Wash and dry Chuanxiong, frankincense, myrrh, Eucommia ulmoides and Dipsacus asper respectively, and control the moisture content to ≤10%; Excessive water content in medicinal materials will lead to solvent dilution during extraction, affecting the extraction efficiency of active ingredients, and accelerating microbial reproduction, causing the medicinal materials to deteriorate. Drying treatment can reduce the moisture content of medicinal materials, ensure the physical stability of medicinal materials, and provide a stable material basis for the subsequent extraction process. Use 70% ethanol solvent, with a weight ratio of medicinal material to solvent of 1:10, extract at 50℃~70℃ for 12 hours, and filter the extract; 70% ethanol has good solubility for polar and non-polar molecules, and can extract hydrophilic and fat-soluble components at the same time, ensuring comprehensiveness and efficiency of extraction. This temperature can not only increase the solubility rate of the solute, but also avoid the decomposition or inactivation of active ingredients caused by high temperature. It uses the cavitation effect of ultrasound to destroy the cell wall, increase the contact area between the solvent and the medicinal material, and accelerate the dissolution of the active ingredients. The extract is concentrated to 1 / 5 of the original volume by vacuum rotary evaporation. The vacuum condition is used to reduce the boiling point, so that ethanol and water evaporate at low temperature to avoid high temperature damage to active ingredients, such as curcumin, ligustrazine, etc.; The target components are collected by gradient ethanol elution using macroporous adsorption resin. The macroporous adsorption resin selectively adsorbs the active ingredients in the drug through its porous structure and polar groups to remove impurities and inactive substances. The eluate is freeze-dried to obtain the main active ingredient in powder form; Freeze-drying technology is completed under low-temperature conditions, avoiding the oxidation, decomposition or inactivation of active ingredients that may occur during high-temperature drying. The powdered ingredients are highly stable and easy to store and transport. They are also easy to disperse and dissolve in subsequent ointment preparation.

[0013] Preferably, the preparation of the targeted response vector comprises: Prepare 0.5-1 parts by weight of chitosan solution, dissolve chitosan in 2-3 parts by weight of acetic acid solution, and stir at 25-30°C for 2-4 hours. Chitosan is a natural polysaccharide polymer with biocompatibility and biodegradability. A large number of amino groups in its molecular structure undergo protonation reaction in an acidic environment, so that chitosan dissolves in aqueous solution to form a stable cationic solution. Chitosan molecules carry positive charges and have good ability to interact with cell membranes and biomacromolecules, making it an ideal drug carrier material; Prepare 1 to 3 parts by weight of curcumin solution, dissolve curcumin in anhydrous ethanol, and ultrasonically vibrate for 15 to 30 minutes; curcumin is a hydrophobic polyphenol compound that is difficult to dissolve in water, but has good ethanol solubility. Through ultrasonic vibration technology, the cavitation effect is used to destroy the aggregated crystal structure of curcumin, accelerate its dissolution process, and thus form a stable molecular dispersed solution. The uniformity of curcumin dissolution is crucial for the subsequent combination with chitosan solution; Slowly add the curcumin solution to the chitosan solution at a volume ratio of 1:10 to 1:20, maintain a stirring speed of 300 to 500 rpm, adjust the pH to 5.5 to 6.0, and stir for 2 to 3 hours; After the curcumin solution is added to the chitosan solution, it combines with the protonated amino groups in the chitosan molecules through electrostatic interaction, and at the same time relies on the hydrophobic interaction of the chitosan molecules to wrap the curcumin molecules to form a nanoparticle complex. This pH can help maintain the partial protonation state of the chitosan solution and prevent the inactivation of curcumin in an environment with too low pH, thereby obtaining uniform and stable nanoparticles. The nanoparticles were collected by centrifugation and freeze-dried for later use; High-speed centrifugation uses the density difference of the particles to separate the nanoparticles from the solution, while removing excess chitosan and unbound curcumin molecules from the solution. Freeze-drying technology is used to directly sublimate the water content of the nanoparticles, avoiding the destruction of curcumin activity by high-temperature drying, while protecting the microstructure and particle stability of the particles, making them suitable for long-term storage and subsequent use; The particles obtained after freeze-drying can be directly used as the core active ingredients of the finished particles, avoiding subsequent secondary processing and ensuring targeting performance.

[0014] Preferably, the compound of the penetration enhancer comprises: Dissolve palmitoylethanolamide in propylene glycol at a concentration of 2 to 5 parts by weight, stirring at a speed of 300 to 500 rpm for 10 to 15 minutes; Palmitoylethanolamide is a naturally occurring phospholipid molecule that contains a hydrophilic head and two hydrophobic fatty acid tails. Propylene glycol, as a polar organic solvent, can effectively dissolve palmitoylethanolamide molecules and stably disperse them in the solution. The stirring process promotes the dissolution efficiency and dispersion uniformity of palmitoylethanolamide by enhancing the contact between the solvent and the phospholipid molecules, while avoiding molecular aggregation; Add 5 to 10 parts by weight of ethanol and continue stirring for 10 to 15 minutes to ensure that the solution is uniform and transparent; Ethanol is a small molecule polar solvent with strong solubility and penetration-promoting effects. During the mixing process, ethanol can form hydrogen bonds with palmitoylethanolamide molecules and further destroy the self-aggregation tendency of phospholipid molecules, enhancing the uniformity of phospholipid dispersion in the solution; in addition, the addition of ethanol can also reduce the viscosity of the phospholipid solution, improve its mixing performance in subsequent formula integration, and give the solution good penetration-promoting properties; The prepared penetration enhancer is spray-dried into powder, or directly mixed with the active ingredient and used as a functional excipient of the particles to increase the absorption performance of the ingredient.

[0015] Preferably, the preparation of the particle matrix comprises: Evenly mix the extract powder and the penetration enhancer powder according to the formula ratio; Gradually add the granular matrix powder to the mixture to ensure that the main drug and the matrix are fully mixed; Spray an appropriate amount of adhesive solution, stirring while spraying until the mixture is evenly mixed; The granulation operation is carried out by a wet granulator, and the particle size is controlled at 200-500 μm; Place the wet granules in a 60°C hot air dryer and dry until the moisture content is ≤5%; After drying, the particles are sieved to remove unqualified particles and collect qualified particles for later use.

[0016] Preferably, the integration and preparation of the particles comprises: Preparation of empty capsules: Use hard gelatin empty capsules as packaging materials to ensure non-toxicity and easy solubility; Filling process: The prepared granules are passed through a capsule filling machine and filled into size 0 capsules; Sealing: The filled capsules are sealed by a sealing machine to complete the preparation; Post-processing: After the finished capsules are screened for appearance, they are placed in a drying oven and stored in sealed packages to avoid moisture.

[0017] The present invention provides a formula and preparation method for relieving and treating osteoarthritis. It has the following beneficial effects: 1. The present invention uses a composite permeation enhancer of palmitoylethanolamide, propylene glycol and ethanol to optimize the transdermal absorption path and promote the drug to penetrate the skin barrier into the deep tissue through synergistic effects. Compared with the existing technology, it solves the problem of insufficient penetration and difficulty in exerting deep drug efficacy.

[0018] 2. The present invention constructs a responsive drug delivery system through chitosan-curcumin composite particles, utilizes the acidic microenvironment of the inflammatory site to achieve targeted release, and at the same time improves the stability of the active ingredient. Compared with the non-targeted release method, it solves the problems of low drug utilization and insufficient target concentration.

[0019] 3. The present invention makes the drug distribution more uniform and the ointment application performance better by using an emulsified matrix and a reasonable temperature control stirring process. Compared with the problem of ointment stratification and uneven use, it solves the defects of uneven distribution of traditional ointments and poor patient experience.

[0020] 4. The present invention integrates a variety of active Chinese medicine extracts and combines targeting and sustained-release technology to form a treatment system that integrates anti-inflammatory, analgesic, repair and lubrication. Compared with single-function treatment plans, it solves the problem of one-sided treatment effects for osteoarthritis and is more comprehensive and effective. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a flow chart of the preparation method of the present invention. DETAILED DESCRIPTION

[0022] The following will be combined with the drawings in the specification of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0023] Please refer to the attached Figure 1 : Example 1: Preparation of granular capsules (standard formula) Extraction of main active ingredients Rhizoma Chuanxiong, frankincense, myrrh, Eucommia ulmoides, and Dipsacus asper are mixed in a weight ratio of 5:3:2:3:3. After washing, dry and control the moisture content to 8%. Use 70% ethanol solution, with a ratio of 1:10 between medicinal materials and solvent, and extract continuously at 60°C for 12 hours. Filter the extract through gauze to obtain a clear solution. After the extract is concentrated to 1 / 5 of the original volume, use macroporous adsorption resin to elute with gradient ethanol (50%, 70%, 90%) to collect the main active ingredients. The eluate is vacuum freeze-dried to obtain a powdered extract for use.

[0024] Preparation of targeted response vector Chitosan was dissolved in 2.5 parts by weight of acetic acid solution to prepare 0.8 parts by weight of chitosan solution, which was stirred at 25°C for 3 hours. Curcumin was dissolved in anhydrous ethanol at a concentration of 2 parts by weight, and ultrasonically vibrated for 20 minutes to ensure complete dissolution. The curcumin solution was added dropwise to the chitosan solution at a ratio of 1:15, the stirring speed was controlled at 400 rpm, the pH was adjusted to 5.7, and the particles were centrifuged after 2 hours of reaction. The final nanoparticles were freeze-dried and collected for later use.

[0025] Combination of penetration enhancers Dissolve 3 parts by weight of palmitoylethanolamide in 5 parts by weight of propylene glycol, stir at 400 rpm for 12 minutes. Add 8 parts by weight of ethanol, and continue stirring until the solution is transparent. The prepared solution is dried into powder by spray drying equipment and used as an auxiliary material in granule preparation.

[0026] Preparation of particle matrix The extract powder, the targeted response material, and the penetration enhancer powder are mixed evenly in a weight ratio of 2:1:1. 20 parts by weight of lactose and 10 parts by weight of microcrystalline cellulose are added, and after mixing, 3 parts by weight of sodium carboxymethyl cellulose solution is added, and the binder is sprayed while stirring until the particles are formed. The wet granules are granulated by a wet granulator, and the particle size is controlled to be about 300 μm. After the granulation is completed, the particles are placed in a 60°C hot air dryer and dried until the moisture content is less than 5%.

[0027] Capsule filling and packaging The dried particles are screened to remove fine powder and coarse particles, and qualified particles are collected for use. The particles are filled into No. 0 hard gelatin capsules by a capsule filling machine, with each capsule filling 400 mg. After filling, the capsules are sealed and stored in a drying oven.

[0028] Example 2: Preparation of granular capsules containing non-denatured type II collagen Extraction of medicinal ingredients Rhizoma Chuanxiong, frankincense, myrrh, and Radix Dipsaci were mixed in a weight ratio of 4:3:2:3, washed, and dried to a moisture content of 9%. 70% ethanol solution was used at a ratio of 1:8 between medicinal materials and solvent, and extracted at 50°C for 10 hours. The extract was filtered and concentrated to 1 / 6 of the original volume. A macroporous resin column was used to elute with 70% ethanol, and the extract powder was obtained after freeze-drying.

[0029] Targeted material preparation The concentration of chitosan solution was adjusted to 1 part by weight, and the concentration of curcumin solution was prepared to 1.5 parts by weight. The curcumin solution was slowly added to the chitosan solution at a ratio of 1:12, stirred at 300 rpm, the pH was adjusted to 5.5, reacted for 3 hours, and the nanoparticles were collected by freeze drying.

[0030] Contains non-denatured type II collagen Non-denatured type II collagen is added at 15% of the total weight of the extract and mixed evenly with the extract powder and targeted response material to ensure that it is not affected by high temperature.

[0031] Particle preparation Add 10 parts by weight of microcrystalline cellulose and 5 parts by weight of lactose, mix well and add a small amount of binder (2% sodium carboxymethyl cellulose solution). Granulate with a wet granulator to control the particle size to 200-500 μm and dry to a moisture content of 4%.

[0032] Capsule filling The prepared granules were filled into No. 1 hard gelatin capsules, 300 mg per capsule, and sealed for storage.

[0033] Example 3: Granular capsules with adjusted hyaluronic acid ratio Extraction of medicinal ingredients Chuanxiong, frankincense and Eucommia ulmoides are mixed in a ratio of 5:4:3, extracted with 70% ethanol solution in a ratio of 1:10, the extraction temperature is 65°C, the extraction time is 12 hours, concentrated to 1 / 5 volume, and freeze-dried to obtain a powder extract.

[0034] Targeted material preparation The concentration of hyaluronic acid was adjusted to 1.5 parts by weight, and the hyaluronic acid was evenly mixed with chitosan nanoparticles at a ratio of 1:2, and further spray-dried to obtain targeted particles.

[0035] Combination of penetration enhancers Palmitoylethanolamide, propylene glycol and ethanol are prepared in a ratio of 3:6:9 and spray-dried into powder for later use.

[0036] Particle Matrix and Preparation The extract powder, targeting particles and permeation enhancer were mixed in a ratio of 2:1:1, 20 parts by weight of lactose and 15 parts by weight of microcrystalline cellulose were added, granulated by a wet granulator, and dried to a moisture content of less than 4%.

[0037] Capsule filling The dried granules are filled into No. 2 gelatin capsules, with each capsule containing 250 mg. After filling, the capsules are sealed and stored.

[0038] Example 4: Optimized targeted particle capsule Medicinal Extraction Chuanxiong, frankincense and myrrh were mixed in a ratio of 3:2:2 for extraction, and extracted with 70% ethanol at 60°C for 8 hours. After concentration, the extract was gradient eluted with macroporous resin and dried to obtain the extract powder.

[0039] Targeted material preparation The chitosan solution was prepared with a concentration of 0.7 parts by weight, and the curcumin solution was prepared with a concentration of 2.5 parts by weight, and the mixture was mixed at a ratio of 1:20, and freeze-dried to obtain targeted nanoparticles.

[0040] The penetration enhancer is prepared in the proportion of 4 parts by weight of palmitoylethanolamide, 6 parts by weight of propylene glycol, and 8 parts by weight of ethanol, and is directly added to the particle matrix after mixing.

[0041] Particle preparation The extract powder, the penetration enhancer and the targeting particles are mixed in a ratio of 3:1:1, added with a binder solution, granulated by a granulator, and screened after drying.

[0042] Capsule filling Each capsule is filled with 400 mg of granules and filled into No. 0 gelatin capsules, which are then sealed and packaged.

[0043] Ratio 1: Adjustment of the extraction process of active ingredients (Comparative Example 1) the difference: Extraction solvent: Use 90% ethanol solvent instead of 70% ethanol.

[0044] Extraction time: reduced to 6 hours (compared to 12 hours in Example 1).

[0045] The macroporous adsorption resin elution process is not used, and the extract is directly concentrated into powder.

[0046] Preparation process: According to the ratio in Example 1, rhizome of Chuanxiong, frankincense, myrrh, eucommia and dipsaci were mixed, washed and dried, and the moisture content was controlled at 8%.

[0047] The medicinal materials were mixed with 90% ethanol in a ratio of 1:10, extracted at 60 °C for 6 h, and the extract was filtered through gauze.

[0048] The extract was directly concentrated to 1 / 6 of the original volume by vacuum rotary evaporation and freeze-dried to obtain the extract powder.

[0049] There is no purification step, the extraction is done only by filtration and concentration.

[0050] Comparative Example 2: Preparation and Adjustment of Targeted Response Vector (Comparative Example 2) the difference: The concentration of the chitosan solution was reduced to 0.3 parts by weight (lower than 0.8 parts by weight in the example).

[0051] The concentration of the curcumin solution was reduced to 0.5 parts by weight.

[0052] The pH was not adjusted to keep the solution naturally acidic (pH < 4.0).

[0053] The particles were not freeze-dried but collected by natural drying.

[0054] Preparation process: Chitosan was dissolved in 2 parts by weight of acetic acid solution to adjust the concentration to 0.3 parts by weight, and stirred for 3 hours.

[0055] Curcumin was dissolved in anhydrous ethanol at a concentration of 0.5 parts by weight and ultrasonically shaken for 15 minutes to ensure dissolution.

[0056] The curcumin solution was slowly added to the chitosan solution at a ratio of 1:20, the stirring speed was set at 300 rpm, and the pH value was not adjusted.

[0057] After reacting for 2 hours, the particles were separated by centrifugation, collected and dried naturally.

[0058] Comparative Example 3: Compounding and Adjustment of Penetration Enhancer (Comparative Example 3) the difference: Palmitoylethanolamide was not used, only propylene glycol and ethanol were used.

[0059] The ratio of propylene glycol to ethanol was changed to 1:1.

[0060] No spray drying was performed, and the particles were directly mixed in liquid form.

[0061] Preparation process: 5 parts by weight of propylene glycol and 5 parts by weight of ethanol were mixed, and the stirring speed was controlled to 200 rpm for 10 minutes.

[0062] No hexadecyl ethanolamide was added, and the mixed solution was used directly after it became transparent without the spray drying step.

[0063] For subsequent direct mixing with extract powder.

[0064] Comparative Example 4: Process Adjustment of Particle Preparation (Comparative Example 4) the difference: No penetration enhancers were added, and only the extract powder and matrix were used to prepare the granules.

[0065] The binder was changed to a plain aqueous solution (sodium carboxymethyl cellulose was removed).

[0066] The particle size is not strictly controlled and does not pass the screening.

[0067] Preparation process: The extract powder is directly mixed with the particle matrix (lactose, microcrystalline cellulose) according to the ratio of Example 4 and stirred evenly.

[0068] Use ordinary water as a binder, gradually spray it into the mixture and stir until the particles are initially formed.

[0069] Granulation was performed by wet granulation, the particle size was not strictly controlled (no sieving step), and the granules were directly dried to a moisture content of less than 8%.

[0070] Comparative Example 5: Capsule filling and packaging adjustment (Comparative Example 5) the difference: The moisture content of the particles is not strictly controlled and the degree of drying is insufficient.

[0071] The capsules are filled without undergoing a visual screening and sealing process.

[0072] Use non-standard capsules (vegetable capsules).

[0073] Preparation process: The prepared granules were directly filled into No. 1 plant empty capsules by a capsule filling machine, with each capsule filling 350 mg.

[0074] If the capsules are not stored in a dry box, particles may be attached to the surface of the capsules.

[0075] No sealing is performed and the packaging is completed directly.

[0076] Experiment 1: Purity test of extraction of active ingredients Purpose The effects of the extraction processes of Example 1 and Comparative Example 1 on the purity of the active ingredients were verified, with a focus on evaluating the differences in the extraction time and purification process on the target ingredient content and impurity content in the extract.

[0077] Experimental procedures Sample preparation: Example 1 Sample: According to the extraction process of Example 1, 70% ethanol solution was used, and the weight ratio of medicinal materials to solvent was 1:10. The extraction was carried out continuously at 60°C for 12 hours. The extract was purified by macroporous adsorption resin and then freeze-dried to obtain an extract powder.

[0078] Comparative Example 1 Sample: According to the extraction process of Comparative Example 1, 90% ethanol solution was used, and the weight ratio of medicinal materials to solvent was 1:10. The extraction was carried out at 60°C for 6 hours. The extract was directly concentrated and freeze-dried to obtain an extract powder.

[0079] Solution preparation: 100 mg of extract was weighed from each group of samples, added to 10 mL of anhydrous ethanol, and placed in an ultrasonicator for 30 minutes to ensure that the samples were completely dissolved.

[0080] The dissolved sample was filtered through a 0.22 μm microporous filter membrane, and the filtrate was used as a sample for HPLC detection.

[0081] High Performance Liquid Chromatography (HPLC) Detection: Testing conditions: Chromatographic column: C18 reverse phase column; Mobile phase: acetonitrile-water (60:40, volume ratio); Flow rate: 1 mL / min; Detection wavelength: 280nm.

[0082] Target components: Determine the contents of ligustrazine, aromatic acid and chlorogenic acid in the extract, and calculate their total purity (the percentage of the total amount of target components in the mass of the extract).

[0083] Impurity detection: record the peak area of ​​non-target components and calculate the impurity content (the percentage of impurity peak area to total peak area).

[0084] Experimental replication: Each group of samples was tested 5 times, the data were recorded, and the mean and standard deviation were calculated.

[0085] Purity and impurity content of extracts in Example 1 and Comparative Example 1 The optimization of the extraction process has a key impact on the purity of the target component. It can be seen from the experiment that the purification process using macroporous adsorption resin in Example 1 significantly improved the purity of the extract. The total purity of ligustrazine, balsamic acid and chlorogenic acid in Example 1 is close to 70%, while that in Comparative Example 1 is only about 40%. The selective separation effect of the macroporous adsorption resin obviously reduces the interference of non-target components, making the extract more concentrated. In addition, the extension of the extraction time also helps to fully release the active ingredients and ensure the extraction efficiency of the target ingredients.

[0086] The difference in impurity content further demonstrates the importance of the purification step. In Comparative Example 1, due to the lack of a purification process, the proportion of impurities exceeded 8%, while the impurity content in Example 1 was controlled below 3%. The accumulation of such impurities may adversely affect the quality stability of subsequent products, such as accelerating degradation during storage, or introducing unnecessary side effects. Obviously, removing impurities through adsorption resin not only improves the quality of the extract, but also provides higher quality raw materials for subsequent preparation.

[0087] From a mechanistic point of view, the adjustment of extraction time and solvent concentration also plays an important role. Although the use of 90% ethanol extraction in Comparative Example 1 improves the initial release of some fat-soluble components, it may also lead to the loss of some water-soluble active substances (such as chlorogenic acid). In addition, the shorter extraction time does not completely release the active ingredients in the medicinal materials, resulting in insufficient overall activity of the extract. However, Example 1 ensures the balanced extraction of multiple active ingredients through a more reasonable solvent ratio and an extension of the extraction time, so that the extract shows obvious advantages in both quality and stability.

[0088] Experiment 2: Targeted response vector performance test Purpose The release performance of the targeted carriers in Example 2 and Comparative Example 2, especially the release difference of the targeted responsive carriers under different pH conditions, was verified, reflecting the innovation of the present invention in targeted release and responsiveness.

[0089] Experimental procedures Sample preparation: Example 2: Chitosan-curcumin composite particles and hyaluronic acid were prepared according to the process of Example 2 to obtain a targeted response carrier.

[0090] Comparative Example 2: Chitosan-curcumin composite particles were prepared according to the process of Comparative Example 2 without using hyaluronic acid.

[0091] Release Experiment Setup: Two buffers were prepared: pH = 5.5 (simulating an inflammatory environment) and pH = 7.4 (simulating normal body fluids).

[0092] 10 mg of the targeting vector was added to each buffer, and the mixture was placed in a constant temperature oscillator with the temperature set at 37° C. and the shaking speed at 100 rpm for 24 hours.

[0093] 2 mL of sample was taken every 2 hours, filtered and stored for subsequent curcumin concentration detection.

[0094] Sample Analysis: The concentration of curcumin was determined by high performance liquid chromatography (HPLC), and the cumulative release amount was recorded at different time points.

[0095] The cumulative release rate of curcumin under two pH environments was calculated, and the release curves were analyzed.

[0096] Data Records: The release amount at each time point was recorded, the release curve was drawn, and the release characteristics of the two carriers under different pH conditions were compared.

[0097] Curcumin release under different pH conditions in Example 2 and Comparative Example 2 By comparing the experimental data of Example 2 and Comparative Example 2, it can be clearly seen that the responsiveness difference of the targeted carrier in different pH environments. The carrier in Example 2 shows a higher release rate at pH = 5.5 (simulating an inflammatory environment), and the release amount in 6 hours has significantly exceeded that of Comparative Example 2. This difference is closely related to the addition of hyaluronic acid, which not only increases the hydrophilicity of the carrier, but also improves the swelling of the carrier through interaction with chitosan, making it easier to release curcumin in an acidic environment, thereby enhancing the targeting and therapeutic effect of the drug. In contrast, the carrier in Comparative Example 2 has a lower release rate due to the lack of hyaluronic acid, especially in an acidic environment, where the release of curcumin is limited.

[0098] Another significant difference is that under the condition of pH = 7.4 (normal body fluid), Example 2 still maintains a relatively stable release curve, while the release rate of Comparative Example 2 decreases significantly. This shows that the addition of hyaluronic acid not only enhances the release in an inflammatory environment, but also provides a sustained drug release effect in a normal body fluid environment. This mechanism is related to the responsive swelling effect of the chitosan-curcumin complex at low pH, and the synergistic effect of hyaluronic acid enables the drug to maintain a higher bioavailability.

[0099] From a mechanistic point of view, the effect of hyaluronic acid on the chitosan-curcumin complex is crucial. In a low pH environment, the hyaluronic acid molecule carries a negative charge and interacts with the cationic part of the chitosan molecule, promoting the expansion of the carrier and accelerating the release of the drug. In contrast, the expansion and release rates of a single chitosan-curcumin composite carrier under the same conditions are lower, and the speed and total amount of drug release are limited. Therefore, the introduction of hyaluronic acid not only increases the targeting of the drug, but also improves the therapeutic effect of the drug in an inflammatory environment.

[0100] Experiment 3: Effect of penetration enhancers on absorption performance Purpose The effects of the permeation enhancer formulations in Example 3 and Comparative Example 3 on the transdermal absorption performance of the drug were verified, with a focus on analyzing the effect of the addition of palmitoylethanolamide on the enhancement of the permeation efficiency.

[0101] Experimental procedures Sample preparation: Example 3: A penetration enhancer was prepared according to the process of Example 3, comprising palmitoylethanolamide, propylene glycol, and ethanol in a ratio of 3:6:9, and was made into powder by spray drying, and then mixed with the extract powder to form granules.

[0102] Comparative Example 3: A penetration enhancer was prepared according to the process of Comparative Example 3, using only propylene glycol and ethanol in a ratio of 5:5, without spray drying, and directly participating in particle preparation.

[0103] Skin model preparation: Take fresh and healthy pig ear skin, separate the epidermis and dermis with a scalpel, cut into 1cm² skin samples, wash with physiological saline, remove surface impurities, and set aside.

[0104] Franz diffusion experimental apparatus setup: The skin sample was fixed between the test cell and the receiving cell of the Franz diffusion cell, with the stratum corneum facing the test cell and the dermis facing the receiving cell.

[0105] 6 mL of phosphate buffered saline (PBS) with a pH of 7.4 was added to the receiving cell, the temperature was maintained at 37°C, and the stirring speed was set to 50 rpm to simulate the human skin environment.

[0106] Sample coating and experiment start: 5 mg of the particle sample (Example 3 or Comparative Example 3) was evenly coated in the test cell to ensure that the skin surface was covered, and the transdermal absorption experiment was started.

[0107] Every 2 hours, 0.5 mL of sample was taken from the receiving pool and an equal amount of PBS was added to prevent the influence of volume change on the absorption amount.

[0108] Sample testing: The collected samples were tested for the concentration of curcumin by HPLC, and the transdermal absorption (μg / cm 2 ).

[0109] Experimental replication: Five parallel samples were set up for each group of experiments, and the experiments were repeated three times, and the average values ​​were recorded and calculated.

[0110] Transdermal absorption experimental data of Example 3 and Comparative Example 3 The enhancing effect of palmitoylethanolamide on transdermal absorption is obvious. In the experiment, the absorption curve of Example 3 is always higher than that of Comparative Example 3, especially in the first 8 hours, the absorption rate is almost doubled. This difference is attributed to the dual effect of palmitoylethanolamide on the skin barrier. It reduces the density of the stratum corneum by interacting with the lipids in the stratum corneum of the skin, allowing drug molecules to penetrate the surface of the skin faster. At the same time, it can also stabilize the diffusion path of drug molecules and reduce molecular losses during the absorption process. However, due to the lack of palmitoylethanolamide in Comparative Example 3, the penetration effect appears to be relatively limited, relying only on the physical effects of propylene glycol and ethanol.

[0111] Moreover, the introduction of palmitoylethanolamide also significantly changed the absorption depth of the drug. The absorption amount of Example 3 continued to grow within 24 hours, indicating that its penetration ability is not limited to the epidermis, but can penetrate into deeper tissues. This property is particularly suitable for the treatment of diseases such as osteoarthritis, because the drug needs to penetrate multiple layers of skin to reach the site of inflammation. However, the absorption rate of Comparative Example 3 gradually slowed down after 6 hours, indicating that its absorption is mainly concentrated in the surface layer of the skin and deep delivery cannot be achieved.

[0112] From a mechanistic point of view, the fat-soluble structure of palmitoylethanolamide plays a key role. It can fuse with skin cell lipids, thereby temporarily reducing the skin barrier function and enhancing the penetration ability of drug molecules. Propylene glycol and ethanol mainly play a role by dissolving stratum corneum proteins or lipids, but their persistence is poor and they cannot effectively maintain the efficient diffusion path of drugs. Therefore, the optimized combination of penetration enhancers in Example 3 significantly improves the efficiency and depth of transdermal absorption, providing a stronger therapeutic effect for alleviating osteoarthritis.

[0113] Experiment 4: Particle uniformity and long-term stability test Purpose The effects of the particle preparation processes of Example 4 and Comparative Example 4 on the uniformity and long-term stability of the particles were verified, and the effects of the particle distribution uniformity and the storage environment on the particle quality and the stability of the active ingredient were analyzed.

[0114] Experimental procedures Sample preparation: Example 4: Particles were prepared according to the process of Example 4, with the addition of a penetration enhancer and sodium carboxymethyl cellulose as a binder, strict control of particle size (200-500 μm), and screening to remove unqualified particles.

[0115] Comparative Example 4: Particles were prepared according to the process of Comparative Example 4, without adding a permeation enhancer, using a common aqueous solution as the binder, and without screening the particle size.

[0116] Uniformity test: Five groups of samples were randomly selected from the particles prepared in Example 4 and Comparative Example 4, each group containing 10 mg.

[0117] Each group of samples was dissolved in 10 mL of anhydrous ethanol and ultrasonically shaken for 20 minutes to ensure that the drug components were fully dissolved.

[0118] The concentration of curcumin was detected by high performance liquid chromatography (HPLC), the concentration value of each group of samples was recorded, and the standard deviation was calculated.

[0119] Long-term stability test: The particle samples were stored under three conditions: 40℃ (high temperature environment); 25℃ (room temperature); 4℃ (refrigerated).

[0120] The storage time was set to 30 days, and samples were taken on the 0th, 10th, 20th, and 30th days.

[0121] The appearance changes of the samples (such as delamination, breakage, color change) and curcumin content were detected, and the degradation rate was calculated.

[0122] Data Records: Each group of samples was tested 5 times, and the uniformity data and degradation rate changes were recorded.

[0123] Particle uniformity and stability test data of Example 4 and Comparative Example 4 Long-term stability test data The uniformity of the particles directly reflects the refinement of the preparation process. In this experiment, the particles of Example 4 showed significantly higher uniformity. The standard deviation of the curcumin concentration was within 0.1, indicating that the drug distribution in the particles was relatively uniform. This result was mainly due to the strict screening and uniform mixing process. However, Comparative Example 4 did not screen the particle size, and the drug distribution in the particles was uneven, resulting in large fluctuations in the curcumin concentration. This unevenness may lead to uncontrollability of drug dosage in actual use, affecting the therapeutic effect.

[0124] The results of the long-term stability experiment further highlight the impact of the particle preparation process on drug quality. The particles in Example 4 can still maintain a low degradation rate under high temperature conditions, reaching only 9.6% at 30 days. In contrast, the degradation rate of the particles in Comparative Example 4 exceeded 10% after 10 days, and was close to 30% at 30 days. This difference is directly related to the use of penetration enhancers and adhesives. The synergistic effect of the penetration enhancer and sodium carboxymethyl cellulose in Example 4 not only improves the physical stability of the particles, but also slows down the degradation of the active ingredients. However, in Comparative Example 4, only ordinary water is used as a binder, and the particle structure is loose, which is easily affected by temperature and humidity during storage and causes breakage and stratification.

[0125] From the perspective of mechanism analysis, the role of penetration enhancer in particle stability cannot be ignored. The introduction of palmitic acid ethanolamide and propylene glycol not only enhances the uniformity of the particles, but also reduces the water migration rate to a certain extent, reducing the humidity change inside the particles. In addition, the high viscosity characteristics of sodium carboxymethyl cellulose enable the particles to form a more stable internal network structure, thereby effectively resisting the erosion of high temperature and humidity. In contrast, due to the lack of enhancer and high-quality adhesive in Comparative Example 4, the internal structure of the particles appears more fragile, showing poor uniformity and stability. This shows that the process optimization of Example 4 not only improves the uniformity of drug distribution of the particles, but also significantly improves its stability during storage.

[0126] Experiment 5: Effect of capsule filling and packaging process on the stability of finished products Purpose The effects of the capsule filling and packaging processes of Example 5 and Comparative Example 5 on the stability and appearance retention of the finished capsules were verified, and the effects of moisture control and packaging treatment on long-term storage quality were especially analyzed.

[0127] Experimental procedures Sample preparation: Example 5: According to the process of Example 5, the moisture content of the dried particles is controlled at ≤5%, and No. 0 hard gelatin capsules are used for filling, packaging, and sealing for storage.

[0128] Comparative Example 5: According to the process of Comparative Example 5, the moisture content of the granules was not strictly controlled, and the granules were directly filled into No. 1 vegetable capsules without being sealed.

[0129] Storage condition settings: The filled capsules are stored in three different environments: High humidity environment: humidity 90%, temperature 40℃; Normal temperature environment: humidity 50%, temperature 25℃; Low temperature environment: humidity 30%, temperature 4°C.

[0130] The storage time is 30 days. The appearance changes of the samples are recorded every 7 days, and capsules are randomly selected for testing.

[0131] Sample testing: Appearance inspection: Observe whether the capsule has any abnormal conditions such as rupture, adhesion, discoloration, etc.

[0132] Ingredient testing: 10 capsules were randomly selected, the internal particles were taken out and dissolved in anhydrous ethanol, ultrasonically shaken for 30 minutes, and the curcumin content was detected by HPLC, and the degradation rate was calculated.

[0133] Experimental replication: Set up 5 sets of samples for each storage condition, record the average value and analyze Storage stability test data of capsules of Example 5 and Comparative Example 5 Appearance change data The filling and packaging process of the capsule plays a vital role in the product quality during long-term storage. The experimental results show that even if the capsules in Example 5 are stored in a high humidity and high temperature environment for 30 days, the degradation rate of curcumin is still controlled within 10%, the appearance remains intact, and only a slight color change. The key to this performance lies in the strict control of the moisture of the particles and the sealing treatment of the capsules, which significantly reduces the erosion of the particles by external humidity and oxygen. The capsules in Comparative Example 5 showed significant degradation under the same conditions, with a degradation rate of nearly 40% after 30 days, and serious cracking and adhesion problems in appearance. This shows that the role of particle moisture control and capsule encapsulation treatment in improving storage stability cannot be ignored.

[0134] From a mechanistic point of view, the moisture content of the particles is one of the core factors affecting the stability of the capsule. In Example 5, the moisture content of the particles is ≤5%, which effectively reduces the fluctuation of internal humidity and reduces the possibility of adhesion and disintegration of the particles. However, in Comparative Example 5, the moisture content is not strictly controlled, resulting in the hygroscopic expansion of the particles in a high humidity environment, further exacerbating the rupture of the capsule. In addition, the sealing of the hard gelatin capsule also provides an additional protective barrier for the particles, effectively blocking external moisture and oxygen. In Comparative Example 5, no sealing treatment was performed, and the hygroscopicity of the plant capsule was high, which exposed the particles directly to the environment, thereby accelerating the degradation of the active ingredients.

[0135] It is worth noting that the sealing treatment of capsule packaging has a particularly significant effect on maintaining the appearance. In a high humidity environment, the capsules in Comparative Example 5 generally showed adhesion and deformation, indicating that the stability of the plant capsule material in humidity changes is insufficient. However, through a strict packaging process in Example 5, the capsules can maintain good structural integrity during storage, with only slight surface color changes. This shows that the optimization of the packaging process can not only improve the long-term stability of the active ingredients, but also significantly improve the appearance and user experience of the product.

[0136] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A formula for relieving and treating osteoarthritis, characterized in that: The formulation includes the following components in parts by weight: Chuanxiong extract: 10-20 parts; Frankincense extract: 10-15 parts; Myrrh extract: 5-10 parts; Non-denatured type II collagen: 5-15 parts; Dipsacus asper extract: 5-15 parts; Curcumin: 2-5 parts; Penetration enhancer: 10-20 parts; Targeted response materials: 1 to 5 copies; Ointment base: 35-50 parts.

2. A formula for relieving and treating osteoarthritis according to claim 1, characterized in that: The penetration enhancers include: Palmitoylethanolamide: 2-5 parts; Propylene glycol: 3-8 parts; Ethanol: 5-10 parts.

3. A formula for relieving and treating osteoarthritis according to claim 1, characterized in that: The targeted response material comprises: Chitosan-curcumin composite particles: 1-3 parts; Hyaluronic acid: 0.5-2 parts.

4. The formula for relieving and treating osteoarthritis according to claim 1, characterized in that: The ointment base comprises: Vaseline: 35-50 parts; Lanolin: 10-15 parts; Purified water: 10-20 parts.

5. A method for preparing a formulation, characterized in that: The method of using the formulation for relieving and treating osteoarthritis according to any one of claims 1 to 4 comprises the following steps: Extraction and purification of main active ingredients; Preparation of targeted response vectors; Compounding of penetration enhancers; Integration of active ingredients and auxiliary materials; Preparation of particle matrix; Integration and preparation of particles.

6. The method for preparing the formulation according to claim 5, characterized in that: The extraction and purification of the main active ingredients include: Wash and dry Chuanxiong, frankincense, myrrh, Eucommia ulmoides and Dipsacus asper respectively, and control the moisture content to ≤10%; Use 70% ethanol solvent, with a weight ratio of medicinal material to solvent of 1:10, extract at 50℃~70℃ for 12 hours, and filter the extract; The extract was concentrated to 1 / 5 of the original volume by vacuum rotary evaporation; The target components were collected by gradient ethanol elution using macroporous adsorption resin; The eluate is freeze-dried to obtain the main active ingredient in powder form.

7. The method for preparing the formulation according to claim 5, characterized in that: The preparation of the targeted response vector includes: Prepare 0.5-1 parts by weight of chitosan solution, dissolve chitosan in 2-3 parts by weight of acetic acid solution, and stir at 25-30° C. for 2-4 hours; Prepare 1 to 3 parts by weight of a curcumin solution by dissolving curcumin in anhydrous ethanol and ultrasonically vibrating for 15 to 30 minutes; Slowly add the curcumin solution to the chitosan solution at a volume ratio of 1:10 to 1:20, maintain a stirring speed of 300 to 500 rpm, adjust the pH to 5.5 to 6.0, and stir for 2 to 3 hours; The particles obtained after freeze-drying can be directly used as the core active ingredients of the finished particles, avoiding subsequent secondary processing and ensuring targeting performance.

8. The method for preparing the formulation according to claim 5, characterized in that: The compound of the penetration enhancer comprises: Dissolve palmitoylethanolamide in propylene glycol at a concentration of 2 to 5 parts by weight, stirring at a speed of 300 to 500 rpm for 10 to 15 minutes; Add 5 to 10 parts by weight of ethanol and continue stirring for 10 to 15 minutes to ensure that the solution is uniform and transparent; The prepared penetration enhancer is spray-dried into powder, or directly mixed with the active ingredient and used as a functional excipient of the particles to increase the absorption performance of the ingredient.

9. The method for preparing the formulation according to claim 5, characterized in that: The preparation of the particle matrix comprises: Evenly mix the extract powder and the penetration enhancer powder according to the formula ratio; Gradually add the granular matrix powder to the mixture to ensure that the main drug and the matrix are fully mixed; Spray an appropriate amount of adhesive solution, stirring while spraying until the mixture is evenly mixed; The granulation operation is carried out by a wet granulator, and the particle size is controlled at 200-500 μm; Place the wet granules in a 60°C hot air dryer and dry until the moisture content is ≤5%; After drying, the particles are sieved to remove unqualified particles and collect qualified particles for later use.

10. The method for preparing the formulation according to claim 5, characterized in that: The integration and preparation of the particles include: Preparation of empty capsules: Use hard gelatin empty capsules as packaging materials to ensure non-toxicity and easy solubility; Filling process: The prepared granules are passed through a capsule filling machine and filled into size 0 capsules; Sealing: The filled capsules are sealed by a sealing machine to complete the preparation; Post-processing: After the finished capsules are screened for appearance, they are placed in a drying oven and stored in sealed packages to avoid moisture.

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