An active complex preparation having joint soothing effect and a method for preparing the same

Abstract

This invention discloses an active compound preparation with joint-relieving effects and its preparation method, belonging to the technical field of external care preparations. The active compound preparation, by mass percentage, comprises 0.5-5.0% acetyl glucosamine, 0.1-2.0% chondroitin sulfate, 0.1-0.5% anti-inflammatory and analgesic modifier, 0.1-2.0% menthol, 0.1-1.0% vanillin butyl ether, 0.05-2.0% magnesium sulfate, and the balance excipients; wherein the anti-inflammatory and analgesic modifier is composed of curcumin, white willow bark extract, Belamcanda chinensis leaf extract, licorice root extract, and Anemarrhena asphodeloides root extract in a specific ratio. This invention, through the synergistic effect of multiple components, combines immediate analgesia and relief, deep anti-inflammatory effects, and long-lasting cartilage protection. The preparation process is simple, the active ingredients have good stability, and it can be widely used in the preparation of joint care preparations for sports-relieving, anti-inflammatory, analgesic, and soothing purposes.

Description

Technical Field

[0001] This invention belongs to the technical field of topical care preparations, specifically relating to an active compound preparation with joint-relieving effects and its preparation method. Background Technology

[0002] Currently, intervention products for joint discomfort are mainly divided into two categories: oral preparations and topical preparations. Oral preparations mainly consist of nonsteroidal anti-inflammatory drugs (NSAIDs), glucosamine, and chondroitin sulfate. Although they can relieve symptoms to some extent, they have significant limitations: long-term use of NSAIDs can easily cause systemic adverse reactions such as gastrointestinal mucosal damage and burden on liver and kidney function; glucosamine, chondroitin sulfate, and other cartilage nutrients have extremely low oral bioavailability, making it difficult to achieve an effective concentration at the joint site, resulting in slow onset of action and limited intervention effects.

[0003] Topical preparations can act directly on the joint, avoiding the first-pass effect and systemic adverse reactions of oral administration. However, existing topical joint relief products still face several technical bottlenecks: First, most products only provide immediate cooling / warming sensory relief with menthol and capsaicin-like ingredients, which can only temporarily mask pain and cannot address the root cause of joint inflammation and cartilage damage, thus treating the symptoms but not the underlying cause; Second, some products with added anti-inflammatory active ingredients suffer from problems such as single active ingredient and unreasonable formulation, which can only block inflammatory pathways at a single target, resulting in limited anti-inflammatory and analgesic effects and failing to achieve multi-pathway synergistic intervention; Third, existing products struggle to balance "immediate relief" and "long-lasting repair," failing to simultaneously achieve the triple core effects of analgesia, anti-inflammation, and cartilage protection, and generally suffer from poor transdermal absorption, easy inactivation of active ingredients, and short local residence time, making it difficult to achieve ideal joint care results.

[0004] Therefore, developing a topical active compound preparation that combines immediate analgesia and relief, deep anti-inflammatory effects, long-lasting cartilage protection, good transdermal properties, stable activity, and high safety has significant scientific research value and market application prospects. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide an active compound preparation with joint-relieving effects and its preparation method.

[0006] To achieve the above objectives, the present invention discloses the following technical solutions: In a first aspect, the present invention provides an active compound preparation for relieving joint pain, the active compound preparation containing the following components in weight percentages: acetyl glucosamine 0.5-5.0%, chondroitin sulfate 0.1-2.0%, anti-inflammatory and analgesic modulator 0.1-0.5%, menthol 0.1-2.0%, vanillyl butyl ether 0.1-1.0%, magnesium sulfate 0.05-2.0%; and the balance being excipients; The anti-inflammatory and analgesic modifier is a compound of curcumin, white willow bark extract, belamcanda leaf extract, licorice root extract and anemarrhena root extract.

[0007] Preferably, the anti-inflammatory and analgesic conditioning agent is composed of curcumin, white willow bark extract, belamcanda leaf extract, licorice root extract and anemarrhena root extract in a mass ratio of (10-12):(1-3):(3-5):(2-4):(0.5-2.5).

[0008] More preferably, the preparation method of the white willow bark extract includes the following steps: Step 1: Dry the white willow bark and pulverize it through a 30-60 mesh sieve to obtain white willow bark powder. Mix the white willow bark powder with an 80 v / v% ethanol solution at a material-to-liquid ratio of 1:(3-5) g / mL. Perform hot reflux extraction at 70-80℃, extract twice, each time for 1-2 hours. After extraction, filter while hot and combine the two filtrates. Step 2: Concentrate the filtrate under reduced pressure to remove ethanol, and dilute it with 5-10 times the mass of pure water. Then, load the concentrated solution onto an AB-8 macroporous adsorption resin column at a rate of 1.1 BV / h. After loading to 1 BV, allow it to stand for adsorption for 1.2-1.6 h. Elute impurities with pure water at a rate of 2-3 BV / h for 2 h. Finally, elute with 80 v / v% ethanol solution at a rate of 1.1-1.5 BV / h for 2-3 h and collect the eluent. Step 3: Concentrate the eluent under reduced pressure and freeze-dry it under vacuum to obtain white willow bark extract.

[0009] More preferably, the preparation method of the Belamcanda chinensis leaf extract includes the following steps: After drying the leaves of Belamcanda chinensis, pulverize them and pass them through a 40-60 mesh sieve. Add 70-80 v / v% ethanol solution at a material-to-liquid ratio of 1:(5-10) g / mL and soak for 1-2 hours. Then, heat to 70-80℃ and reflux for extraction 2-3 times, 1-2 hours each time. Combine the filtrates and concentrate under reduced pressure to remove ethanol to obtain an extract. Extract with ethyl acetate and remove ethyl acetate to obtain Belamcanda chinensis leaf extract.

[0010] More preferably, the preparation method of the licorice root extract includes the following steps: After drying, licorice root is pulverized and passed through a 30-60 mesh sieve to obtain licorice root powder. Then, the licorice root powder is extracted three times at 70-80℃ with 80-90 v / v% ethanol solution at a material-to-liquid ratio of 1:(10-15) g / mL for 1-2 hours each time. The extracts are combined and concentrated under reduced pressure and dried under vacuum to obtain licorice root extract.

[0011] More preferably, the preparation method of the Anemarrhena asphodeloides root extract includes the following steps: Step 1: After drying the Anemarrhena asphodeloides root, pulverize it through a 30-60 mesh sieve to obtain Anemarrhena asphodeloides root powder. Add 70-80 v / v% ethanol solution at a ratio of 1:(5-10) g / mL and extract by hot reflux at 70-80℃ for 1-2 hours. After filtration, collect the filtrate. Add 70-80 v / v% ethanol solution to the residue at a ratio of 1:(5-10) g / mL and extract by hot reflux at 70-80℃ for 1-2 hours. After filtration, collect the filtrate. Combine the two filtrates and concentrate under reduced pressure to remove ethanol to obtain a concentrated solution. Step 2: Dilute the concentrate with 15 times its weight of pure water. Load the diluted solution onto a D101 macroporous adsorption resin column at a flow rate of 1.3 BV / h. Load to 1 BV and allow to stand for 2 hours. Then, elute with pure water at a flow rate of 1.5-1.7 BV / h for 2 hours to remove impurities. Next, elute with 80 v / v% ethanol at a flow rate of 1-1.2 BV / h for 2-3 hours. Collect the eluent, concentrate under reduced pressure to recover the ethanol, and freeze-dry to obtain the mother root extract.

[0012] Preferably, the excipients are at least one selected from humectants, penetration enhancers, emulsifiers, natural oils, synthetic oils, film-forming agents, thickeners, pH adjusters, preservatives, and solvents.

[0013] More preferably, the excipients are glycerin, butylene glycol, glyceryl stearate, stearyl alcohol polyether-21, stearyl alcohol polyether-2, petrolatum, cyclodimethylsiloxane, carbomer, aminomethylpropanol, preservatives, and deionized water; The mixed preservative is obtained by combining phenoxyethanol, ethylhexylglycerin and octyl glycol.

[0014] Secondly, the present invention provides a method for preparing the active compound formulation described in the first aspect, the method comprising the following steps: Step 1: Add deionized water, glycerol, butylene glycol, and carbomer to the aqueous phase pot, stir well, heat to 85-90℃, stir until completely dissolved, keep warm for later use, and obtain an aqueous phase mixture; Step 2: Add glyceryl stearate, stearyl alcohol polyether-21, stearyl alcohol polyether-2, petrolatum, and cyclodimethylsiloxane to the oil phase pot, stir evenly, heat to 85-90℃, stir until completely dissolved, keep warm for later use, and obtain the oil phase mixture. Step 3: Slowly pump the oil phase mixture into the water phase mixture, homogenize and emulsify at 85-90℃ and 2500-2800rpm for 5-10min, add aminomethylpropanol, and homogenize and emulsify again at 2500-2800rpm for 5-10min to obtain a homogeneous emulsion. Step 4: Add acetyl glucosamine, chondroitin sulfate, magnesium sulfate, licorice root extract, anemarrhena root extract, white willow bark extract, menthol, vanillyl butyl ether, curcumin, and belamcanda leaf extract, and homogenize and emulsify at 2500-2800 rpm for 5-10 minutes. Step 5: Cool the homogenized emulsion to 40-45℃, add preservatives, adjust the pH to 6.0-7.0, stir evenly, and degas under vacuum to obtain the active composite preparation.

[0015] Thirdly, the present invention provides the application of the active compound preparation described in the first aspect in the preparation of joint-residual preparations with anti-inflammatory, analgesic, and soothing effects.

[0016] Preferably, the joint retention preparation is a patch, emulsion, liquid, cream, or ointment.

[0017] The beneficial effects of this invention are: 1. This invention optimizes the composition and ratio of a soothing, anti-inflammatory and analgesic conditioning agent. It is formulated with curcumin as the core, combined with extracts of white willow bark, Belamcanda chinensis leaf, licorice root, and Anemarrhena asphodeloides root. The five ingredients work synergistically through multiple targets and pathways to achieve extremely strong anti-inflammatory and analgesic effects.

[0018] 2. This invention constructs a triple-action system of "immediate sensory relief - deep inflammation intervention - long-term cartilage protection," breaking through the bottleneck of existing products that "treat the symptoms but not the root cause": ① The scientific combination of menthol, vanillyl butyl ether, and magnesium sulfate can quickly improve local microcirculation in the joint, block the transmission of pain nerves, and achieve immediate cooling, soothing, and analgesic effects, rapidly relieving joint pain, stiffness, and discomfort; ② The anti-inflammatory and analgesic modulator can significantly inhibit the release of pro-inflammatory factors, block the inflammatory cascade reaction, improve synovial inflammation from the root cause, and solve the problem of joint damage caused by repeated inflammation; ③ The combination of acetyl glucosamine and chondroitin sulfate with the anti-inflammatory and analgesic modulator can bidirectionally regulate cartilage metabolism. On the one hand, it inhibits the expression of cartilage-degrading enzymes such as MMP-3, reducing cartilage matrix degradation; on the other hand, it supplements the core raw materials for the synthesis of type II collagen and glycosaminoglycans, promoting cartilage tissue repair and achieving long-term joint protection. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. However, the following embodiments are merely preferred embodiments of this invention and not all of them. For clarity, not all features of the actual embodiments are described.

[0020] Based on the embodiments described in the implementation plan, other embodiments obtained by those skilled in the art without creative effort are all within the scope of protection of this invention.

[0021] I. In this invention Acetyl glucosamine: purchased from Baijun (Guangdong) New Materials Technology Co., Ltd.; Chondroitin sulfate: purchased from Baijun (Guangdong) New Materials Technology Co., Ltd.; Menthol: Purchased from Guangzhou Wuzhitang Biotechnology Co., Ltd. Vanillyl butyl ether: purchased from Guangzhou Wuzhitang Biotechnology Co., Ltd.; Magnesium sulfate: purchased from Xilong Scientific Co., Ltd. Curcumin: Purchased from Baijun (Guangdong) New Materials Technology Co., Ltd.; The remaining raw materials are commercially available.

[0022] II. Anti-inflammatory and analgesic conditioning agents 1. Raw material preparation 1.1 White willow bark extract The specific method is as follows: Step 1: Dry the white willow bark and pulverize it through a 40-mesh sieve to obtain white willow bark powder. Mix the white willow bark powder with an 80 v / v% ethanol solution at a material-to-liquid ratio of 1:4 g / mL. Perform hot reflux extraction at 75℃, extract twice, each time for 2 hours. After extraction, filter while hot and combine the two filtrates. Step 2: Concentrate the filtrate under reduced pressure to remove ethanol, and dilute it with 6 times the mass of pure water. Then, load the concentrated solution onto an AB-8 macroporous adsorption resin column at a rate of 1.1 BV / h. After loading to 1 BV, allow it to stand for 1.5 h for adsorption. Elute impurities with pure water at a rate of 2.5 BV / h for 2 h. Finally, elute with 80 v / v% ethanol solution at a rate of 1.4 BV / h for 2.5 h and collect the eluent. Step 3: Concentrate the eluent under reduced pressure and freeze-dry it under vacuum to obtain white willow bark extract.

[0023] 1.2. Belamcanda chinensis leaf extract The specific method is as follows: After drying, the leaves of *Belamcanda chinensis* were pulverized and passed through a 60-mesh sieve. They were then soaked in 75% v / v% ethanol solution at a ratio of 1:8 g / mL for 1 hour, followed by reflux extraction at 80°C twice for 2 hours each time. The filtrates were combined and concentrated under reduced pressure to remove ethanol, yielding an extract. The extract was dispersed and mixed with pure water at a ratio of 1:2 g / mL, transferred to a separatory container, and an equal volume of ethyl acetate was added. After thorough mixing and standing, the layers were separated, and the upper ethyl acetate phase was collected. This process was repeated twice more. The resulting ethyl acetate extracts were combined and concentrated under reduced pressure at 50°C to remove ethyl acetate, yielding the *Belamcanda chinensis* leaf extract.

[0024] 1.3 Licorice root extract The specific method is as follows: After drying, licorice root was pulverized and passed through a 40-mesh sieve to obtain licorice root powder. Then, the licorice root powder was extracted three times at 80°C with 85 v / v% ethanol solution at a material-to-liquid ratio of 1:10 g / mL for 2 hours each time. The extracts were combined and concentrated under reduced pressure and dried under vacuum to obtain licorice root extract.

[0025] 1.4 Anemarrhena asphodeloides root extract The specific method is as follows: Step 1: After drying the Anemarrhena asphodeloides root, pulverize it through a 40-mesh sieve to obtain Anemarrhena asphodeloides root powder. Add 75 v / v% ethanol solution at a ratio of 1:8 g / mL and extract by hot reflux at 80℃ for 1 hour. After filtration, collect the filtrate. Add 75 v / v% ethanol solution to the residue at a ratio of 1:6 g / mL and extract by hot reflux at 80℃ for 1 hour. After filtration, collect the filtrate. Combine the two filtrates and concentrate under reduced pressure to remove ethanol to obtain a concentrated solution. Step 2: Dilute the concentrate with 15 times its weight of pure water. Load the diluted solution onto a D101 macroporous adsorption resin column at a flow rate of 1.3 BV / h. Load to 1 BV and allow to stand for 2 hours. Then, elute with pure water at 1.6 BV / h for 2 hours to remove impurities. Next, elute with 80 v / v% ethanol at a flow rate of 1.1 BV / h for 2.5 hours. Collect the eluent, concentrate under reduced pressure to recover the ethanol, and freeze-dry after concentration to obtain the mother root extract.

[0026] 2. Preparation of anti-inflammatory and analgesic modulators The components of the anti-inflammatory and analgesic conditioning agent are compounded and added according to the mass ratio in Table 1; Table 1. Mass ratio of each component in the anti-inflammatory and analgesic conditioning agent Raw material name Conditioner 1 Conditioner 2 Conditioner 3 Curcumin 10 11 12 White willow bark extract 1 2 3 Belamcanda chinensis leaf extract 3 4 5 Licorice root extract 2 3 4 Anemarrhena asphodeloides root extract 0.5 1.5 2.5 3. Performance Testing 3.1 Control Group Setup Based on the aforementioned formula of conditioner 2, adjustments were made to obtain the control group shown in Table 2 below: Table 2. Mass ratio of each component in the control group Raw material name Control group 1 Control group 2 Control group 3 Control group 4 Control group 5 Control group 6 Control group 7 Curcumin / 11 11 11 11 4 3 White willow bark extract 2 / 2 2 2 11 2 Belamcanda chinensis leaf extract 4 4 / 4 4 2 4 Licorice root extract 3 3 3 / 3 3 11 Anemarrhena asphodeloides root extract 1.5 1.5 1.5 1.5 / 1.5 1.5 Note: " / " in the table indicates no addition.

[0027] 3.2 In vitro anti-inflammatory effect test An inflammation model was constructed using RAW264.7 macrophages induced by LPS. The macrophages were divided into a blank group, a model group, and a test group. The specific grouping is detailed in Table 3. After co-incubation with the drug for 24 h, the levels of TNF-α and IL-1β in the cell supernatant were detected by ELISA. The inflammation inhibition rate was calculated according to the following formula. The results are detailed in Table 4.

[0028] Inhibition rate / % = [1 - (A1 - A0) / (A2 - A0)] × 100%; Where: A1—concentration of inflammatory factors in each test group; A2 – Concentration of inflammatory factors in the model group; A0 – Concentration of inflammatory factors in the blank control group.

[0029] Table 3 Grouping and Processing

[0030] Note: DMSO can be added to the preparation of the drug delivery system to aid dissolution, but the amount of DMSO in the system should be <0.1wt% to avoid affecting the cells.

[0031] Table 4 Results of the effects of each group on inflammatory factors Group TNF-α inhibition rate (%) IL-1β inhibition rate (%) Conditioner 1 set 86.35 82.47 Conditioner 2 sets 87.12 83.15 3 sets of conditioning agents 85.91 81.43 Control group 1 42.63 39.72 Control group 2 51.28 48.36 Control group 3 38.75 35.64 Control group 4 35.26 32.58 Control group 5 56.32 54.47 Control group 6 72.53 69.84 Control group 7 69.71 66.37 3.3 Analgesic effect test 3.3.1 Preparation of the test substance The base cream is prepared by weight percentage from 5% glycerin, 3% butylene glycol, 2.0% glyceryl stearate, 4% squalane, 1.5% stearyl alcohol polyether-21 and the balance water; Test substance: It is prepared by mass percentage from 0.5% of the test sample of the corresponding group (conditioner 1-3 and control group 1-7) with 5% glycerol, 3% butylene glycol, 2.0% glyceryl stearate, 4% squalane, 1.5% stearyl alcohol polyether-21 and the balance water.

[0032] 3.3.2 Test Plan The acetic acid writhing test was performed using 55 SPF-grade Kunming mice, which were randomly divided into 11 groups: a model control group and a test group. The model control group received 0.5g of a base cream after abdominal hair removal, while the test group received 0.5g of the test substance after abdominal hair removal. After 30 minutes, mice were injected intraperitoneally with 0.1mL / 10g of 0.6% acetic acid solution. The writhing response was observed within 15 minutes (indicating abdominal retraction and extension of both hind limbs). The number of writhing events within 15 minutes was recorded, and the analgesic inhibition rate was calculated using the following formula. The results are shown in Table 5.

[0033] Inhibition rate (%) = (T1 - T2) / T1 × 100% Where: T1—number of torsional responses in the model control group; T2 – Number of writhing responses in the drug-treated group.

[0034] 3.3.3 Test Results Table 5. Number of writhing episodes and analgesic inhibition rate in each group of mice ( (n=10)

[0035] 3.4 Results Analysis The in vitro anti-inflammatory experiments showed that opsonants 1, 2, and 3 all exhibited strong inhibitory effects on TNF-α and IL-1β inflammatory factors induced by LPS in RAW264.7 macrophages. Opsonant 2 showed the best effect, with an inhibition rate of 87.12% for TNF-α and 83.15% for IL-1β. The inhibition rates of inflammatory factors in all three opsonants remained consistently above 81%. In contrast, controls 1-5, after omitting a single component of the opsonant, showed a decrease in their inhibition rates of both inflammatory factors. Controls 6 and 7, after adjusting the proportions of the components in the opsonant, deviating from the specified range of this invention, also showed a significant decrease in their anti-inflammatory inhibition rates, reaching only 72.53% and 69.71%, respectively. The above results fully demonstrate that the five components of the anti-inflammatory and analgesic conditioning agent of the present invention—curcumin, white willow bark extract, belamcanda leaf extract, licorice root extract, and anemarrhena root extract—have a synergistic anti-inflammatory and enhancing effect. Each component is indispensable, and the mass ratio specified in the present invention is the key to achieving the optimal anti-inflammatory effect.

[0036] The results of the acetic acid-induced writhing analgesia experiment in mice showed that opsonants 1, 2, and 3 all exhibited strong inhibitory effects on acetic acid-induced writhing responses in mice, with opsonant 2 showing the highest inhibition rate of 86.88%. The analgesic inhibition rates of controls 1-5 were all below 50%, and the analgesic inhibition rates of controls 6 and 7 were only 69.23% and 60.41%, respectively, showing a trend completely consistent with the anti-inflammatory experiment results. These results further verify that the components and ratios of the anti-inflammatory and analgesic opsonant of this invention have a significant synergistic analgesic effect, achieving highly effective analgesia by inhibiting the inflammatory response, and its effect is far superior to compositions lacking a single component or with suboptimal ratios.

[0037] III. Active compound preparations for joint relief 1. Preparation of active compound formulations S1. Add deionized water, glycerol, butylene glycol, and carbomer to an aqueous phase pot, stir well, heat to 90°C, stir until completely dissolved, keep warm for later use, and obtain an aqueous phase mixture. S2. Add glyceryl stearate, stearyl alcohol polyether-21, stearyl alcohol polyether-2, petrolatum, and cyclodimethylsiloxane to the oil phase pot, stir evenly, heat to 90°C, stir until completely dissolved, keep warm for later use, and obtain the oil phase mixture. S3. Slowly pump the oil phase mixture into the water phase mixture, homogenize and emulsify at 90°C and 2500 rpm for 10 min, add aminomethylpropanol, and homogenize and emulsify again at 2500 rpm for 10 min to obtain a homogeneous emulsion. S4. Add acetyl glucosamine, chondroitin sulfate, magnesium sulfate, licorice root extract, anemarrhena root extract, white willow bark extract, menthol, vanillyl butyl ether, curcumin, and belamcanda leaf extract, and homogenize and emulsify at 2500 rpm for 10 min. S5. Cool the homogenized emulsion to 40°C, add a mixture of phenoxyethanol, ethylhexylglycerin and caprylyl glycol as preservatives, adjust the pH to 6.5, stir evenly, and degas under vacuum to obtain the active compound preparation in cream form.

[0038] Table 6. Percentage of each raw material in the active compound formulation by mass

[0039] Note: " / " in the table indicates no addition.

[0040] 2. Cartilage protection effect test 2.1 Test Plan and Results Sixty SPF-grade SD rats were randomly divided into six groups: sham-operated group, model group, Example 1 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group. Except for the sham-operated group, all other groups underwent left knee anterior cruciate ligament transection to establish a rat osteoarthritis model. Rats were anesthetized with 40 mg / kg sodium pentobarbital via intraperitoneal injection and locally infiltrated with lidocaine hydrochloride. The anterior cruciate ligament was transected via a midline approach to the anterior knee joint and then sutured. In the sham-operated group, only patellar dislocation reduction was performed. Postoperatively, rats received intraperitoneal injections of penicillin and streptomycin for 3 consecutive days to prevent infection. The rearing environment was (23±2)℃, humidity 40%-60%, and 12-hour light-dark cycle. The rats were observed for 4 weeks. Once the modeling criteria were met during the observation period, subsequent experiments were conducted.

[0041] From week 5 to week 12, rats in the sham-operated group and the model group had 0.5g of matrix emulsion applied to the hair-removed area of ​​the knee joint daily, while rats in the other groups had 0.5g of the corresponding test substance (Example 1 and Comparative Examples 1-3) applied to the hair-removed area of ​​the knee joint daily. After 8 weeks of continuous administration, the rats were sacrificed, and the synovial fluid and cartilage tissue were collected. The core indicators of MMP-3 and Col-II in the synovial fluid and GAG content in the cartilage tissue were detected. The results are shown in Table 7.

[0042] Table 7 Core indicators of cartilage protection in rats of each group ( (n=10) Group MMP-3 (ng / mL) Col-II (ng / mL) GAG (μg / mg) Sham surgery group 8.26±2.85 42.53±3.12 85.62±15.35 Model group 36.24±8.18 12.47±1.25 28.35±6.76 Example 1 Group 9.85±1.63 39.74±7.98 78.46±16.92 Comparative Example 1 29.52±5.06** 17.26±4.32** 36.17±9.33** Comparative Example 2 31.18±7.15** 19.85±3.30** 41.64±9.81** Comparative Example 3 Groups 26.86±6.12** 23.24±5.28** 49.08±12.72** Note: MMP-3 is a core marker of cartilage degradation; the lower the content, the less cartilage degradation. Col-II (type II collagen) and GAG (glycosaminoglycans) are core components of the cartilage matrix; the higher the content, the better the cartilage repair effect. * indicates a significant difference between the comparative example and the actual example, and ** indicates P < 0.01.

[0043] 2.2 Results Analysis After 8 weeks of continuous administration in Example 1, the MMP-3 content in the synovial fluid of rats decreased to 9.85 ng / mL, close to the 8.26 ng / mL in the sham-operated group, and decreased by 72.8% compared to the 36.24 ng / mL in the model group. Simultaneously, the Col-II content increased to 39.74 ng / mL, and the GAG ​​content increased to 78.46 μg / mg, both recovering to levels close to the normal levels of the sham-operated group, showing a significant rebound compared to the model group. These results demonstrate that the active compound formulation of the present invention can effectively inhibit cartilage degradation, promote cartilage matrix synthesis, and achieve excellent cartilage protection and repair effects.

[0044] Although the indicators of Comparative Example 1 (lacking acetyl glucosamine), Comparative Example 2 (lacking chondroitin sulfate), and Comparative Example 3 (lacking anti-inflammatory and analgesic modulator) showed some improvement compared to the model group, they were still significantly different from the Example 1 group (P < 0.01). These results indicate that in the active compound formulation of this invention, acetyl glucosamine, chondroitin sulfate, and the anti-inflammatory and analgesic modulator have an irreplaceable synergistic cartilage protective effect: the anti-inflammatory and analgesic modulator can inhibit local joint inflammation and reduce the expression of chondrodegrading enzymes mediated by inflammatory factors, thus blocking the degradation of the cartilage matrix at its source; acetyl glucosamine and chondroitin sulfate, as core precursors for cartilage matrix synthesis, can directly promote the synthesis of Col-II and GAG, repairing damaged cartilage tissue; the three synergistically regulate cartilage metabolism through a two-way regulation of "inhibiting degradation and promoting synthesis," achieving excellent cartilage protective effects. Simultaneously, the addition of menthol, vanillyl butyl ether, and magnesium sulfate can further promote the transdermal absorption of the active ingredients, increase the concentration of active ingredients in the joint area, and ensure the full efficacy of the formulation.

[0045] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. An active complex preparation having joint movement soothing, characterized by, The active compound formulation contains the following components by weight percentage: acetyl glucosamine 0.5-5.0%, chondroitin sulfate 0.1-2.0%, anti-inflammatory and analgesic modulator 0.1-0.5%, menthol 0.1-2.0%, vanillyl butyl ether 0.1-1.0%, magnesium sulfate 0.05-2.0%; and the balance being excipients; The anti-inflammatory and analgesic modifier is a compound of curcumin, white willow bark extract, belamcanda leaf extract, licorice root extract and anemarrhena root extract.

2. The active compound formulation according to claim 1, characterized in that, The anti-inflammatory and analgesic conditioning agent is composed of curcumin, white willow bark extract, belamcanda leaf extract, licorice root extract and anemarrhena root extract in a mass ratio of (10-12):(1-3):(3-5):(2-4):(0.5-2.5).

3. The active compound formulation according to claim 2, characterized in that, The preparation method of the white willow bark extract includes the following steps: Step 1: Dry the white willow bark and pulverize it through a 30-60 mesh sieve to obtain white willow bark powder. Mix the white willow bark powder with an 80 v / v% ethanol solution at a material-to-liquid ratio of 1:(3-5) g / mL. Perform hot reflux extraction at 70-80℃, extract twice, each time for 1-2 hours. After extraction, filter while hot and combine the two filtrates. Step 2: Concentrate the filtrate under reduced pressure to remove ethanol, and dilute it with 5-10 times the mass of pure water. Then, load the concentrated solution onto an AB-8 macroporous adsorption resin column at a rate of 1.1 BV / h. After loading to 1 BV, allow it to stand for adsorption for 1.2-1.6 h. Elute impurities with pure water at a rate of 2-3 BV / h for 2 h. Finally, elute with 80 v / v% ethanol solution at a rate of 1.1-1.5 BV / h for 2-3 h and collect the eluent. Step 3: Concentrate the eluent under reduced pressure and freeze-dry it under vacuum to obtain white willow bark extract.

4. The active compound formulation according to claim 2, characterized in that, The preparation method of the Belamcanda chinensis leaf extract includes the following steps: After drying the leaves of Belamcanda chinensis, pulverize them and pass them through a 40-60 mesh sieve. Add 70-80 v / v% ethanol solution at a material-to-liquid ratio of 1:(5-10) g / mL and soak for 1-2 hours. Then, heat to 70-80℃ and reflux for extraction 2-3 times, 1-2 hours each time. Combine the filtrates and concentrate under reduced pressure to remove ethanol to obtain an extract. Extract with ethyl acetate and remove ethyl acetate to obtain Belamcanda chinensis leaf extract.

5. The active compound formulation according to claim 2, characterized in that, The preparation method of the licorice root extract includes the following steps: After drying, licorice root is pulverized and passed through a 30-60 mesh sieve to obtain licorice root powder. Then, the licorice root powder is extracted three times at 70-80℃ with 80-90 v / v% ethanol solution at a material-to-liquid ratio of 1:(10-15) g / mL for 1-2 hours each time. The extracts are combined and concentrated under reduced pressure and dried under vacuum to obtain licorice root extract.

6. The active compound formulation according to claim 2, characterized in that, The preparation method of the Anemarrhena asphodeloides root extract includes the following steps: Step 1: After drying the Anemarrhena asphodeloides root, pulverize it through a 30-60 mesh sieve to obtain Anemarrhena asphodeloides root powder. Add 70-80 v / v% ethanol solution at a ratio of 1:(5-10) g / mL and extract by hot reflux at 70-80℃ for 1-2 hours. After filtration, collect the filtrate. Add 70-80 v / v% ethanol solution to the residue at a ratio of 1:(5-10) g / mL and extract by hot reflux at 70-80℃ for 1-2 hours. After filtration, collect the filtrate. Combine the two filtrates and concentrate under reduced pressure to remove ethanol to obtain a concentrated solution. Step 2: Dilute the concentrate with 15 times its weight of pure water. Load the diluted solution onto a D101 macroporous adsorption resin column at a flow rate of 1.3 BV / h. Load to 1 BV and allow to stand for 2 hours. Then, elute with pure water at a flow rate of 1.5-1.7 BV / h for 2 hours to remove impurities. Next, elute with 80 v / v% ethanol at a flow rate of 1-1.2 BV / h for 2-3 hours. Collect the eluent, concentrate under reduced pressure to recover the ethanol, and freeze-dry to obtain the mother root extract.

7. The active compound formulation according to claim 1, characterized in that, The excipients are at least one of the following: humectant, penetration enhancer, emulsifier, natural oil, synthetic oil, film-forming agent, thickener, pH adjuster, preservative, and solvent.

8. The active compound formulation according to claim 7, characterized in that, The excipients are glycerin, butylene glycol, glyceryl stearate, stearyl alcohol polyether-21, stearyl alcohol polyether-2, petrolatum, cyclodimethylsiloxane, carbomer, aminomethylpropanol, mixed preservatives and deionized water; The mixed preservative is obtained by combining phenoxyethanol, ethylhexylglycerin and octyl glycol.

9. The method for preparing the active compound formulation according to claim 8, characterized in that, The preparation method includes the following steps: Step 1: Add deionized water, glycerol, butylene glycol, and carbomer to the aqueous phase pot, stir well, heat to 85-90℃, stir until completely dissolved, keep warm for later use, and obtain an aqueous phase mixture; Step 2: Add glyceryl stearate, stearyl alcohol polyether-21, stearyl alcohol polyether-2, petrolatum, and cyclodimethylsiloxane to the oil phase pot, stir evenly, heat to 85-90℃, stir until completely dissolved, keep warm for later use, and obtain the oil phase mixture. Step 3: Slowly pump the oil phase mixture into the water phase mixture, homogenize and emulsify at 85-90℃ and 2500-2800rpm for 5-10min, add aminomethylpropanol, and homogenize and emulsify again at 2500-2800rpm for 5-10min to obtain a homogeneous emulsion. Step 4: Add acetyl glucosamine, chondroitin sulfate, magnesium sulfate, licorice root extract, anemarrhena root extract, white willow bark extract, menthol, vanillyl butyl ether, curcumin, and belamcanda leaf extract, and homogenize and emulsify at 2500-2800 rpm for 5-10 minutes. Step 5: Cool the homogenized emulsion to 40-45℃, add the mixed preservative, adjust the pH to 6.0-7.0, stir evenly, and degas under vacuum to obtain the active composite preparation.

10. The use of the active compound preparation according to any one of claims 1-8 in the preparation of a joint care stay-in preparation having the effects of exercise relief, anti-inflammation, analgesia and joint relaxation.

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