External preparation of traumatic injury composition and its preparation method and application

Abstract

The present application relates to traditional Chinese medicine composition and production process technology and treatment field, specifically relates to a kind of external preparation of composition for bruise and injury and application.A kind of external preparation of composition for bruise and injury, including solid medicament part and liquid medicament part;The raw materials of solid medicament part include: 2.5~3.5 parts of musk, 15~25 parts of borneol, 50~60 parts of dragon's blood, 100~110 parts of myrrh, 120~140 parts of catechu, 20~40 parts of sanqi, 150~170 parts of safflower, 260~280 parts of angelica, 120~140 parts of cinnabar and 100~120 parts of frankincense;The raw materials of liquid medicament part include: 40~60 parts of menthol, 40~60 parts of camphor, 25~35 parts of sylvestrene butyl ether, 35~45 parts of methyl salicylate, 40~60 parts of glycerol, 30~40 parts of light liquid paraffin.The composition is clinically used for bone injury swelling and pain and fracture healing.

Description

Technical Field

[0001] This invention relates to the fields of traditional Chinese medicine compositions, production processes and their clinical applications, specifically to a topical preparation of a traumatic injury composition, its preparation method and application. Background Technology

[0002] For bone injuries, swelling reduction, fracture healing, and sprains, topical medications such as blood-activating and pain-relieving plasters, safflower oil, and swelling-reducing and pain-relieving tinctures can generally be used. For example, blood-activating and pain-relieving plasters contain rhubarb and raw pinellia, among other medicinal herbs, which can promote blood circulation, relieve pain, and relax muscles and tendons, effectively treating swelling and pain caused by sprains. Applying safflower oil directly to the affected area and massaging it in can promote absorption, accelerate local blood circulation, and relieve swelling and pain. Swelling-reducing and pain-relieving tinctures typically relax muscles and tendons, reduce swelling and relieve pain, and can be used to treat sprains, rheumatic bone pain, and other conditions. The medication can be applied directly to the affected area, but should be used as directed by a doctor. However, the effectiveness of these existing medications in treating bone injuries, swelling, fracture healing, and sprains is limited and cannot meet clinical application needs.

[0003] Cinnabar, dragon's blood, myrrh, catechu, Panax notoginseng, Angelica sinensis, frankincense, and other traditional Chinese medicinal herbs all have certain therapeutic effects on bruises and sprains. Currently, these herbs are typically prepared into oral formulations. However, some of these herbs have slight toxicity and are not suitable for long-term use. These oral formulations are generally prescription drugs and must be used under the guidance of a doctor. If these active ingredients could be prepared into topical formulations, the aforementioned side effects could be greatly avoided. The active ingredients would act directly on the affected area through transdermal absorption to achieve the therapeutic effect, avoiding the damage to liver and kidney function caused by long-term medication. Currently, there are no relevant topical formulations on the market. How to ensure the effectiveness of these herbs in topical formulations still requires further research by relevant researchers. There is an urgent need to develop a method to prepare these active ingredients into topical formulations that meet the requirements for stability and therapeutic efficacy. Summary of the Invention

[0004] The present invention aims to provide a topical formulation of a bruise and sprain composition to solve the technical problem of the lack of topical formulations in the prior art for effectively treating bone injuries, reducing swelling, promoting fracture healing, and treating bruises and sprains.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A topical formulation for sprains and bruises, comprising a solid pharmaceutical portion and a liquid pharmaceutical portion;

[0007] By weight, the raw materials for the solid medicine portion include: 2.5-3.5 parts musk, 15-25 parts borneol, 50-60 parts dragon's blood, 100-110 parts myrrh, 120-140 parts catechu, 20-40 parts Panax notoginseng, 150-170 parts safflower, 260-280 parts angelica, 120-140 parts cinnabar, and 100-120 parts frankincense;

[0008] By weight, the raw materials for the liquid pharmaceutical portion include: 40-60 parts menthol, 40-60 parts camphor, 25-35 parts vanillyl butyl ether, 35-45 parts methyl salicylate, 40-60 parts glycerin, and 30-40 parts light liquid paraffin.

[0009] This technical solution also provides a method for preparing a topical formulation of a traumatic injury composition, characterized by comprising the following steps performed sequentially:

[0010] Preparation of S1 solid pharmaceutical portion: Cinnabar, dragon's blood, myrrh, catechu, Panax notoginseng, safflower, angelica, and frankincense were mixed, coarsely pulverized and sieved, and then ultra-finely pulverized to obtain a mixed ultra-fine powder; Musk, borneol, and micronized silica gel were mixed, ground, and sieved to obtain a musk-borneol-micronized silica gel mixture; The mixed ultra-fine powder and the musk-borneol-micronized silica gel mixture were mixed evenly using an equal-volume incremental addition method to obtain the solid pharmaceutical portion;

[0011] Preparation of the S2 liquid pharmaceutical component: Menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin were stirred and dissolved to obtain the liquid pharmaceutical component;

[0012] The ratio of solid to liquid dosage is 1.5g:2g.

[0013] This technical solution also provides the application of a topical preparation of a traumatic injury composition in the preparation of drugs for treating bone injuries and drugs for reducing swelling and relieving pain.

[0014] Furthermore, the solid pharmaceutical component is prepared by the following method: cinnabar, dragon's blood, myrrh, catechu, notoginseng, safflower, angelica, and frankincense are mixed, coarsely pulverized, and sieved, then ultra-finely pulverized to obtain a mixed ultra-fine powder; musk, borneol, and micronized silica gel are mixed, ground, and sieved to obtain a musk-borneol-micronized silica gel mixture; the mixed ultra-fine powder and the musk-borneol-micronized silica gel mixture are mixed evenly using an equal-volume incremental addition method to obtain the solid pharmaceutical component.

[0015] Furthermore, cinnabar, dragon's blood, myrrh, catechu, notoginseng, safflower, angelica, and frankincense are mixed, coarsely pulverized, and then subjected to ultrafine pulverization; the particle size D of the mixed ultrafine powder is... 90 The size should be controlled between 50 and 100 μm.

[0016] Further, musk, borneol, and micronized silica gel are mixed and ground through a 100-200 mesh sieve to obtain a musk-micronized silica gel mixture.

[0017] Furthermore, the amount of micronized silica gel used is 2-3% of the total mass of the raw materials in the solid pharmaceutical part.

[0018] Furthermore, the solid medicine is partially packaged into non-woven bags to obtain solid medicine packets; the specifications of the solid medicine packets are 1.5g / bag.

[0019] Furthermore, the liquid pharmaceutical portion is prepared by the following method: menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin are stirred and dissolved to obtain the liquid pharmaceutical portion.

[0020] Furthermore, the liquid medicine portion is further packaged to obtain liquid medicine packets; the specifications of the liquid medicine packets are 2g / bag; the liquid medicine portion is used to soak the solid medicine portion during use.

[0021] In summary, the beneficial effects of this technical solution are as follows:

[0022] (1) This technical solution is the first to combine cinnabar, dragon's blood, myrrh, catechu, notoginseng, angelica, frankincense, and other traditional Chinese medicinal materials to prepare a topical preparation. Although the above-mentioned traditional Chinese medicinal materials all have certain therapeutic effects on bruises and sprains, in the existing technology, these medicinal materials are usually prepared into oral preparations. However, some of these medicinal materials have slight toxicity and are not suitable for long-term use. The above-mentioned oral preparations are generally prescription drugs and must be used under the guidance of a doctor. This technical solution can greatly avoid the above-mentioned side effects. The active ingredients of the drug achieve therapeutic effects through transdermal absorption, avoiding damage to liver and kidney function caused by long-term drug use.

[0023] (2) In this technical solution, musk, borneol, dragon's blood, myrrh, catechu, notoginseng, safflower, angelica, cinnabar, and frankincense are prepared as the solid pharmaceutical component, and menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin are prepared as the liquid pharmaceutical component. When used, the two components are mixed to ensure sufficient content of the marker components and therapeutic effect of the drug.

[0024] (3) In the process of preparing musk, borneol, dragon's blood, myrrh, catechu, Panax notoginseng, safflower, angelica, cinnabar and frankincense into solid pharmaceutical parts, musk and borneol need to be mixed with micronized silica gel and then mixed with the pulverized materials of other medicinal materials. This can ensure that the content of the marker components muscone and dragon's blood in the prescription is high, avoid the loss of these two substances due to electrostatic adsorption during the production process, and ensure the flowability of the overall powder, making the production process smoother and avoiding the difference in the amount of filling. Attached Figure Description

[0025] Figure 1This is a schematic diagram of the usage process of the topical preparation in this plan. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to embodiments, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following embodiments and experimental examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used are all commercially available. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art.

[0027] Example 1

[0028] (1) Preparation process of topical formulation for sprains and bruises

[0029] A topical formulation for sprains and bruises, comprising a solid pharmaceutical portion and a liquid pharmaceutical portion.

[0030] The solid dosage form contains the following ingredients (by weight): 2.5–3.5 parts musk (artificial musk was used in subsequent examples and comparative examples), 15–25 parts borneol, 50–60 parts dragon's blood, 100–110 parts myrrh (vinegar-processed in subsequent examples and comparative examples, i.e., vinegar-processed myrrh), 120–140 parts catechu, 20–40 parts Panax notoginseng, 150–170 parts safflower, 260–280 parts Angelica sinensis (wine-processed in subsequent examples and comparative examples, i.e., wine-processed myrrh), 120–140 parts cinnabar, and 100–120 parts frankincense (vinegar-processed in subsequent examples and comparative examples, i.e., vinegar-processed frankincense). All the above-mentioned medicinal materials conform to the standards of Part I of the Chinese Pharmacopoeia 2020.

[0031] The liquid formulation is as follows (by weight): 40-60 parts menthol, 40-60 parts camphor, 25-35 parts vanillyl butyl ether, 35-45 parts methyl salicylate, 40-60 parts glycerin, and 30-40 parts light liquid paraffin. Menthol conforms to the standards of Part I of the Chinese Pharmacopoeia 2020; light liquid paraffin conforms to the standards of Part IV of the Chinese Pharmacopoeia 2020; and glycerin and camphor conform to the standards of Part II of the Chinese Pharmacopoeia 2020.

[0032] The solid and liquid components are packaged separately into medicine bags of a certain size to form the finished product.

[0033] The solid pharmaceutical portion is prepared in the following manner:

[0034] After coarsely mixing cinnabar, dragon's blood, myrrh, catechu, notoginseng, safflower, angelica, and frankincense slices, the mixture is pulverized through a 100-200 mesh sieve using a universal pulverizer. The mixture is then further pulverized into ultrafine powder (D90 between 50-100 μm) using an air jet mill to obtain a mixed ultrafine powder. The prescribed amounts of artificial musk and borneol are mixed with 2.0%–3.0% of a total amount of micronized silica gel (prepared by gas phase method, fineness 1000 mesh) prepared from the solid drug portion. The mixture is then ground through a 100-200 mesh sieve and homogenized to obtain a musk-borneol-micronized silica gel mixture. Using a conventional equal-volume incremental addition method, the mixed ultrafine powder and the musk-borneol-micronized silica gel mixture are mixed, then added to a three-dimensional motion mixer and mixed for 10–20 minutes. The mixture is then packaged into 7cm × 10cm non-woven fabric or cotton bags, with a specification of 1.5g / bag, to obtain a solid medicine packet. The medicine packet is attached to adhesive tape with release paper around the edges, and then individually packaged in an aluminum-plastic composite bag to obtain a solid medicine packet. The equal-volume incremental addition method is a conventional operating procedure in existing technology. This involves first taking a small amount of the component, adding an equal amount of the larger component, then taking another equal amount of the larger component and mixing thoroughly, and so on, increasing the amount in multiples until all components are mixed evenly and have a uniform color.

[0035] The liquid pharmaceutical portion is prepared in the following manner:

[0036] Menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin are mixed and dissolved into a solution, which is then packaged into individually packaged aluminum-plastic composite bags (2g / bag), i.e., liquid medicine packs.

[0037] The specific method of using the topical preparation for sprains and bruises in this formula is as follows:

[0038] Open the individually packaged liniment containing aluminum-plastic composite bag, take out the non-woven fabric medicine bag (solid medicine bag), open the individually packaged liquid medicine bag, evenly moisten the liquid medicine onto the non-woven fabric medicine bag, and then apply it to the affected area, pressing gently.

[0039] (2) Specific preparation method of topical preparation of traumatic injury composition

[0040] This embodiment uses the following specific formulation:

[0041] The formula for the solid medicine portion is as follows (by weight): 2 parts artificial musk, 20 parts borneol, 55 parts dragon's blood, 105 parts vinegar-processed myrrh, 130 parts catechu, 30 parts Panax notoginseng, 160 parts safflower, 270 parts wine-processed angelica, 130 parts cinnabar, and 110 parts vinegar-processed frankincense.

[0042] The liquid formulation is as follows (by weight): 50 parts menthol, 50 parts camphor, 30 parts vanillyl butyl ether, 40 parts methyl salicylate, 50 parts glycerin, and 35 parts light liquid paraffin.

[0043] The specific preparation process used in this embodiment is as follows:

[0044] Cinnabar, dragon's blood, vinegar-processed myrrh, catechu, Panax notoginseng, safflower, wine-processed angelica, and vinegar-processed frankincense are coarsely mixed, then pulverized through a 100-mesh sieve using a universal pulverizer. The mixture is then further pulverized into ultrafine powder (D...) using an air jet mill. 90 The particle size was approximately 50 μm, with particles <50 μm accounting for 90%, to obtain a mixed ultrafine powder. The prescribed amounts of artificial musk and borneol were mixed with 2.0% of the total amount of micronized silica gel (gas phase method) and ground through a 100-mesh sieve to obtain a musk-borneol-micronized silica gel mixture. The mixed ultrafine powder and the musk-borneol-micronized silica gel mixture were then mixed using a conventional equal-volume incremental addition method, and then added to a three-dimensional motion mixer and mixed for 10 minutes to obtain the solid pharmaceutical portion.

[0045] Menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin are mixed and dissolved to form a solution, thereby obtaining the liquid pharmaceutical portion.

[0046] Example 2

[0047] This embodiment is basically the same as Embodiment 1, except for the formulation:

[0048] The formula for the solid medicine portion is as follows (by weight): 2.5 parts artificial musk, 15 parts borneol, 50 parts dragon's blood, 100 parts vinegar-processed myrrh, 120 parts catechu, 20 parts Panax notoginseng, 150 parts safflower, 260 parts wine-processed Angelica sinensis, 120 parts cinnabar, and 100 parts vinegar-processed frankincense.

[0049] The liquid formulation is as follows (by weight): 40 parts menthol, 40 parts camphor, 25 parts vanillyl butyl ether, 35 parts methyl salicylate, 40 parts glycerin, and 30 parts light liquid paraffin (light liquid paraffin).

[0050] Example 3

[0051] This embodiment is basically the same as Embodiment 1, except for the formulation:

[0052] The formula for the solid medicine portion is as follows (by weight): 3.5 parts artificial musk, 25 parts borneol, 60 parts dragon's blood, 110 parts vinegar-processed myrrh, 140 parts catechu, 40 parts Panax notoginseng, 170 parts safflower, 280 parts wine-processed Angelica sinensis, 140 parts cinnabar, and 120 parts vinegar-processed frankincense.

[0053] The liquid formulation is as follows (by weight): 60 parts menthol, 60 parts camphor, 35 parts vanillyl butyl ether, 45 parts methyl salicylate, 60 parts glycerin, and 40 parts light liquid paraffin (light liquid paraffin).

[0054] Example 4

[0055] This embodiment is basically the same as Embodiment 1, except for the preparation process:

[0056] Cinnabar, dragon's blood, vinegar-processed myrrh, catechu, Panax notoginseng, safflower, wine-processed angelica, and vinegar-processed frankincense are coarsely mixed, then pulverized through a 200-mesh sieve using a universal pulverizer. The mixture is then further pulverized into ultrafine powder (D...) using an air jet mill. 90 To obtain a mixed ultrafine powder (approximately 100 μm in size), the prescribed amounts of artificial musk and borneol were mixed with 3.0% of the total amount of micronized silica gel and ground through a 200-mesh sieve to obtain a musk-borneol-micronized silica gel mixture. The mixed ultrafine powder and the musk-borneol-micronized silica gel mixture were then mixed using a conventional equal-volume incremental addition method, and finally added to a three-dimensional motion mixer and mixed for 20 minutes to obtain the solid pharmaceutical fraction.

[0057] Experimental Example 1: Collection of Experiences on the Use of Topical Preparations for Traumatic Injuries in Humans

[0058] 1. Case source and grouping

[0059] Sixty-four patients with closed lower limb fractures admitted between April 2020 and April 2023 were included in this human experience study. They were divided into a control group and a study group, with 32 patients in each group, based on their treatment regimens. In the control group, there were 17 males and 15 females, aged 25–68 years (mean 44.0 ± 6.2 years), with a disease duration of 1–3 days (mean 1.5 ± 0.8 days). The fractures included 20 cases of tibial fracture, 9 cases of fibular fracture, and 3 cases of femoral fracture. Twelve cases were caused by traffic accidents, 14 by falls from heights, 2 by injuries from falling objects, and 4 by falls. In the study group, there were 18 males and 14 females; their ages ranged from 21 to 67 years, with a mean age of (44.2 ± 6.2) years; the duration of illness ranged from 1 to 3 days, with a mean duration of (1.5 ± 0.7) days; there were 15 cases of tibial fractures, 9 cases of fibular fractures, and 8 cases of femoral fractures; 12 cases were caused by traffic accidents, 13 cases by falls from heights, 3 cases by being struck by heavy objects, and 4 cases by falls. There were no significant differences in baseline characteristics (gender, age, duration of illness, fracture type, and cause of injury) between the two groups (P > 0.05), making them comparable.

[0060] 2. Treatment methods

[0061] 2.1 Control Group

[0062] Standard external fixation conservative treatment is performed. Local anesthesia is administered, and X-rays are used to confirm successful reduction. Once reduction is successful, the fracture site is externally fixed with a splint. During fixation, soft materials such as towels, cotton, and cloth are placed on the splint to prevent skin damage. A bandage is then applied to secure the splint, starting at the lower part of the fracture and securing each joint above and below it, ensuring appropriate tightness. Continuous fixation treatment lasts for 6 weeks.

[0063] 2.2 Research Group

[0064] In addition to the treatment given to the control group, the patient was treated with the topical application of the medication from Example 2. After successful manual reduction, the solid medicated patch (solid medicated patch) containing the traumatic injury treatment was removed. The liquid medicated patch was then cut open, and the liquid was poured onto its surface. Once fully absorbed, the patch was applied to the fracture site. The patch was changed daily, with 10 applications constituting one course of treatment. Two consecutive courses of treatment were administered, and X-rays were regularly reviewed to observe fracture healing and alignment. A schematic diagram of the general usage process of the topical preparations in this treatment plan can be found [link to schematic diagram]. Figure 1 .

[0065] 3. Efficacy Analysis

[0066] 3.1 Observation Indicators

[0067] ① Pain status of the two groups of patients was assessed using the Visual Analogue Scale (VAS). The method involved measuring with a 10cm sliding ruler with 10 markings, the two ends being 0 and 10 points respectively. A score of 0 indicates no pain, and a score of 10 indicates severe pain; that is, the higher the score, the more intense the patient's pain.

[0068] ② Measure the swelling circumference of both groups of patients, and statistically compare the treatment time and fracture healing time. The criteria for judging fracture healing are: no local tenderness or longitudinal percussion pain; no abnormal movement in the local area; blurred fracture line on X-ray with continuous callus passing through the fracture line; and no fracture deformation during continuous observation for 2 weeks. The time elapsed from the start of observation to the last follow-up day is defined as the healing time.

[0069] 3.2 Efficacy Criteria

[0070] The recovery of limb function in the two groups of patients was assessed according to the Johner-Wruhs evaluation criteria. Excellent: Complete recovery of limb function, without affecting daily life; Good: Basic recovery of limb function, without excessively affecting daily life; Fair: Some improvement in limb function, but affecting daily life; Poor: Poor limb function, significantly impacting daily life. Excellent / Good Rate = (Number of Excellent Cases + Number of Good Cases) / Total Number of Cases × 100%.

[0071] 3.3 Statistical Methods

[0072] Data analysis was performed using SPSS 23.0 statistical software. t-tests were used for measurement data. This indicates that the count data uses X 2 The test is expressed as a percentage, with α = 0.05 as the research test standard, and p < 0.05 as the statistical significance of the difference.

[0073] 3.4 Treatment Results

[0074] 3.4.1 Comparison of limb function recovery between the two groups of patients

[0075] The excellent and good rate was 71.88% in the control group and 93.75% in the study group. The difference between the two groups was statistically significant (P<0.05). See Table 1.

[0076] Table 1: Comparison of limb function recovery status between the two groups (%)

[0077]

[0078] 3.4.2 Comparison of pain and swelling circumference between the two groups of patients

[0079] Compared with the control group, the patients in the study group had lower VAS scores and shorter swelling circumferences, and the differences were statistically significant (P<0.05). See Table 2.

[0080] Table 2: Comparison of pain and swelling circumference between the two groups of patients

[0081]

[0082] 3.4.3 Comparison of treatment and fracture healing time between the two groups: The hospital stay and fracture healing time in the treatment group were significantly shorter than those in the control group. The difference was statistically significant (P<0.05). See Table 3.

[0083] Table 3: Comparison of treatment time and fracture healing time between the two groups of patients

[0084]

[0085] The results of the human experience collection showed that the effective rate of limb function recovery in the experimental group (93.75%) was significantly higher than that in the control group (71.88%). In terms of pain and swelling circumference, the VAS score of the experimental group (1.24) was significantly lower than that of the control group (3.42). The swelling circumference of the experimental group (mean 30.11 cm) was significantly lower than that of the control group (mean 38.57 cm). The treatment time of the patients in the experimental group (mean 20.11 days) was significantly shorter than that of the control group (mean 41.32 days). The fracture healing time (mean 9.52 weeks) was significantly shorter than that of the control group (mean 17.02 weeks). The results showed that the traumatic injury composition of the present invention has good functions of reducing swelling, relieving pain, and accelerating fracture healing.

[0086] Comparative Example 1:

[0087] To prepare a topical formulation from ten traditional Chinese medicines—borneol, musk, dragon's blood, myrrh, catechu, notoginseng, safflower, angelica, cinnabar, and frankincense—plasters are the most common form. Conventional plasters are made by adding a wetting agent to powdered medicinal materials, then sealing the moistened powder and applying it to the affected area before use. In this comparative example, the inventors attempted a premixing method for the liquid and solid components, as follows (formulation same as Example 2):

[0088] Cinnabar, dragon's blood, vinegar-processed myrrh, catechu, Panax notoginseng, safflower, wine-processed angelica, and vinegar-processed frankincense were coarsely mixed, then pulverized through a 100-mesh sieve using a universal pulverizer. The mixture was then further pulverized into ultrafine powder (D90 approximately 50 μm) using an air jet mill to obtain a mixed ultrafine powder. The prescribed amounts of artificial musk and borneol were mixed with 2.0% of the total amount of micronized silica gel and ground through a 100-mesh sieve to obtain a musk-borneol-micronized silica gel mixture. Using a conventional equal-volume incremental addition method, the mixed ultrafine powder and the musk-borneol-micronized silica gel mixture were mixed, then added to a three-dimensional motion mixer and mixed for 10 minutes to obtain a total mixed solid powder. Finally, menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin were mixed and dissolved to form a solution. The total mixed solid powder and the above solution were mixed evenly to obtain an ointment (total mixed solid powder: solution = 1.5g: 2g). The ointment was packaged in a 7cm × 10cm non-woven fabric or cotton bag, and the bag was attached to adhesive tape with release paper around the edges. It was then individually packaged in an aluminum-plastic composite bag. Each package contained one patch (each patch contained 3.5g of ointment made from the mixture of total mixed solid powder and solution). After preparing the ointment according to this method, the contents of the two markers, daphne and muscone, were detected using conventional high-performance liquid chromatography (HPLC). The results were expressed as the mass of daphne and muscone contained in each patch. Each patch contained 0.83mg of daphne and 64μg of muscone. Compared with the solid ointment package of Example 2, the contents of these two markers, daphne and muscone, were significantly reduced. In the solid dosage form of Example 2, the content of dragon's blood extract and muscone was tested and expressed as the mass of dragon's blood extract and muscone contained in each patch (each patch includes 1.5g of solid dosage form and 2g of liquid dosage form; since the liquid dosage form does not contain musk and dragon's blood extract, only the content of dragon's blood extract and muscone in the solid dosage form was measured, and the mass of dragon's blood extract and muscone was calculated). Each patch contains 1.25mg of dragon's blood extract and 96μg of muscone. The inventors analyzed that the reason for the above phenomenon is that dragon's blood extract and musk become unstable in the liquid dosage form of this solution, requiring immediate mixing and immediate use.

[0089] Comparative Example 2

[0090] The inventors attempted to package the solid portion (containing dragon's blood extract and muscone) separately from the liquid portion, mixing them immediately upon use. This was carried out according to Example 2, with the difference that: dragon's blood extract, vinegar-processed myrrh, catechu, Panax notoginseng, safflower, wine-processed angelica, cinnabar, and vinegar-processed frankincense were directly coarsely mixed and pulverized, then pulverized through a 100-mesh sieve using a universal pulverizer, and finally pulverized into ultrafine powder (D) using an air jet mill. 90 The mixture (approximately 50 μm thick) is mixed with artificial musk powder and borneol powder (ground through a 100-mesh sieve), and then packaged into solid drug packets (solid drug portion). Menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin are used as the liquid portion. In this case, the content of thiamethoxam and muscone in the finished product is increased (compared to Comparative Example 1), but the increase is limited, and the flowability of the solid portion is problematic, leading to variations in fill weight.

[0091] Testing revealed that each patch contained 0.90 mg of dracoside and 46 μg of muscone. In contrast, Example 2 showed dracoside and muscone contents of 1.25 mg / patch and 96 μg / patch, respectively. This comparison demonstrates that the absence of differential silica gel in this technical solution leads to the electrostatic adsorption of dracoside and muscone onto the equipment surface during the mixing process, resulting in a significant reduction in the content of muscone and dracoside in the product and affecting its efficacy.

[0092] Regarding the flowability of the solid pharmaceutical portion, the inventors also tested the angle of repose of the solid pharmaceutical portion of Example 2 and the solid pharmaceutical portion of this comparative example, which were 38.4° (Example 2) and 45.2° (this comparative example), respectively. The angle of repose refers to the maximum angle formed by the free inclined plane of the powder accumulation layer and the horizontal plane. The smaller the angle of repose, the lower the friction and the better the flowability. When θ≤40°, the flowability requirements in the production process can be met, and the smaller the angle, the more ideal it is. This indicates that the powder of Example 2 has better flowability, is less likely to cause large differences in filling weight, and can improve the smoothness of the process. This technical solution can improve the flowability of the powder by adding micronized silica gel.

[0093] Comparative Example 3

[0094] To increase the stability and content of bloodwort extract and muscone, the inventors experimented with adding hydrogenated castor oil to the powder (the applicant's prior patent "2021111359291 A method for preparing a stable liniment for traumatic injuries" uses hydrogenated castor oil to increase the stability of the active ingredients). Based on Comparative Example 2, artificial musk and borneol were first ground and mixed with hydrogenated castor oil (the amount of hydrogenated castor oil added was 2% of the total amount of medicinal materials), and then other materials were added to the mixture (ultrafine powders of bloodwort extract, vinegar-processed myrrh, catechu, Panax notoginseng, safflower, wine-processed angelica, cinnabar, and vinegar-processed frankincense). The mixture was then packaged to obtain the solid pharmaceutical portion. The remaining operations were the same as in Comparative Example 2.

[0095] Testing revealed that the flowability of the solid formulation was further deteriorated compared to Comparative Example 2, with an angle of repose of 48.2°, which could easily lead to variations in fill weight and affect process continuity. Due to the decreased flowability after the addition of hydrogenated castor oil, the electrostatic adsorption of daphne and muscone remained significant, therefore, marker component and efficacy testing was not performed. While hydrogenated castor oil may improve the stability of daphne and other substances, under the process conditions of this technical solution, the negative effects of hydrogenated castor oil are difficult to overcome, therefore it cannot be used in the production of the topical formulation in this solution.

[0096] Comparative Example 4

[0097] Based on the study of Comparative Example 3, the inventors found that they needed to employ other methods to prevent the adsorption of bloodwort extract and muscone by the production equipment and to improve the flowability of the powder. The inventors attempted to add various substances such as micronized silica gel, magnesium stearate, calcium stearate, and talc to improve the flowability of the powder, and found that these substances all helped to improve the flowability of the powder to some extent. However, using magnesium stearate, calcium stearate, talc, etc., it was difficult to achieve the required high-quality product (low content of active ingredients).

[0098] The procedure was carried out according to Example 2, except that the micronized silica gel was replaced in equal amounts with magnesium stearate, calcium stearate, or talc. After the finished product was prepared, the content of dracoside and muscone in the solid drug was tested. When magnesium stearate was used, the content of dracoside was 1.04 mg / patch and muscone was 68 μg / patch; when calcium stearate was used, the content of dracoside was 1.02 mg / patch and muscone was 60 μg / patch. When talc was used, the content of dracoside was 1.08 mg / patch and muscone was 66 μg / patch. Compared with Example 2, in this comparative example, regardless of whether magnesium stearate, calcium stearate, or talc was used, the production equipment adsorbed dracoside and muscone to a certain extent, resulting in a decrease in content and affecting the quality of the product. The above data shows that the use of micronized silica gel is most effective in aiding flow and protecting the active ingredients from adsorption by the production equipment. When using micronized silica gel, it not only prevents the adsorption of bloodwort extract and muscone by production equipment, but also improves the flowability of the total mixture, enhances the smoothness of industrialization, and ensures the efficacy of the product.

[0099] Comparative Example 5

[0100] This comparative example is based on Example 2, with the difference being that: Dragon's blood, vinegar-processed myrrh, catechu, Panax notoginseng, safflower, wine-processed angelica, cinnabar, and vinegar-processed frankincense were directly coarsely mixed, and then finely mixed with silica gel powder, pulverized, and passed through a 100-mesh sieve using a universal pulverizer. The mixture was then further pulverized into ultrafine powder (D...) using an air jet mill. 90The silica gel (approximately 50 μm in size) was mixed with artificial musk and borneol (ground through a 100-mesh sieve), and then packaged into solid medicine packets (solid medicine portion). Menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin were used as the liquid portion. After preparation, the contents of malathion and muscone in the solid medicine were tested. The contents of malathion and muscone were 1.24 mg / patch and 61 μg / patch, respectively. The malathion content showed no significant change compared to Example 2, while the muscone content decreased significantly. The inventors also tested the angle of repose of the solid medicine portion, which was 42.3°, worse than in Example 2, potentially causing variations in fill weight and affecting process continuity. This indicates that adding the mixture of micronized silica gel and musk to the overall mix can effectively improve the flowability of the mixture and prevent adsorption of muscone and other substances by the equipment.

[0101] Comparative Example 6

[0102] This comparative example is basically the same as Example 2, except that the micronized silica gel used is precipitated micronized silica gel (mesh size 300-400 mesh; both precipitated and fumed micronized silica gels are conventional raw materials in the art and can be obtained commercially). Otherwise, it is completely consistent with the example. The test results showed that the content of surface thalassemia and muscone was 1.12 mg / patch and 80.2 μg / patch, respectively. This indicates that the antistatic adhesion ability of precipitated micronized silica gel is not as good as that of fumed micronized silica gel. Compared with other comparative examples, precipitated micronized silica gel also has a significant antistatic adsorption ability, but the effect is inferior to that of fumed micronized silica gel.

[0103] Based on the experimental data from the above embodiments and comparative examples, the conclusions are as follows:

[0104] Preparing ten traditional Chinese medicines—musk, dragon's blood, myrrh, catechu, notoginseng, safflower, angelica, cinnabar, and frankincense—into an effective external preparation presents certain technical challenges. It requires ensuring the stability of the active ingredients in the preparation and their rapid dissolution during use to achieve therapeutic effects. This technical solution employs separate preparation of the solid and liquid components to avoid adverse effects on musk and dragon's blood caused by prolonged immersion in the liquid component. Furthermore, to further increase the content of muscone and dragon's blood in the formula and improve the flowability of the solid component (avoiding variations in dosage), the inventors separated musk from the other medicinal materials, mixed it with micronized silica gel, and ground it into powder. These operations not only increased the content of muscone and dragon's blood but also improved the flowability of the solid component.

[0105] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A topical preparation for treating sprains and bruises, characterized in that, Includes solid and liquid pharmaceutical portions; By weight, the solid medicine portion is made from the following raw materials: 2.5 parts artificial musk, 15 parts borneol, 50 parts dragon's blood, 100 parts vinegar myrrh, 120 parts catechu, 20 parts Panax notoginseng, 150 parts safflower, 260 parts wine-processed angelica, 120 parts cinnabar and 100 parts vinegar frankincense. The liquid pharmaceutical portion is made from the following ingredients by weight: 40 parts menthol, 40 parts camphor, 25 parts vanillyl butyl ether, 35 parts methyl salicylate, 40 parts glycerin, and 30 parts light liquid paraffin. The solid pharmaceutical component is prepared by the following method: Cinnabar, dragon's blood, myrrh, catechu, Panax notoginseng, safflower, angelica, and frankincense are mixed, coarsely pulverized and sieved, then subjected to ultrafine pulverization to obtain a mixed ultrafine powder; the particle size D of the mixed ultrafine powder is... 90 The particle size is controlled at approximately 50 μm. Artificial musk, borneol, and fumed silica are mixed, ground, and sieved to obtain an artificial musk-borneol-fumed silica mixture. This mixture is used to improve the flowability of the solid drug fraction and ensure the content of the marker components muscone and daphne. The mixed ultrafine powder and the artificial musk-borneol-fumed silica mixture are then uniformly mixed using an equal-volume incremental addition method to obtain the solid drug fraction. The amount of fumed silica used is 2% of the total mass of the raw materials for the solid drug fraction. The solid and liquid formulations are designed for immediate mixing and use.

2. The topical preparation for treating sprains and bruises according to claim 1, characterized in that, Cinnabar, dragon's blood, myrrh, catechu, Panax notoginseng, safflower, angelica, and frankincense are mixed, coarsely ground, and then passed through a 100-200 mesh sieve before being ultra-finely ground; the particle size of the mixed ultra-fine powder is D. 90 The size should be controlled between 50 and 100 μm.

3. The topical preparation for treating sprains and bruises according to claim 1, characterized in that, Artificial musk, borneol, and fumed silica gel were mixed and ground through a 100-200 mesh sieve to obtain an artificial musk-borneol-fumed silica gel mixture.

4. The topical preparation for treating sprains and bruises according to claim 1, characterized in that, The solid medicine is partially packaged into non-woven bags to obtain solid medicine packets; the specifications of the solid medicine packets are 1.5g / bag.

5. The topical preparation for treating sprains and bruises according to claim 1, characterized in that, The liquid pharmaceutical component is prepared by the following method: menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin are stirred and dissolved to obtain the liquid pharmaceutical component.

6. The topical preparation for treating sprains and bruises according to claim 5, characterized in that, The liquid medicine portion is dispensed to obtain liquid medicine packets; the liquid medicine packets are 2g / packet; the liquid medicine portion is used to soak the solid medicine portion during use.

7. The method for preparing a topical preparation for treating sprains and bruises as described in claim 1, characterized in that, The following steps are performed sequentially: Preparation of S1 solid pharmaceutical preparation: Cinnabar, dragon's blood, myrrh, catechu, Panax notoginseng, safflower, angelica, and frankincense are mixed, coarsely pulverized and sieved, then subjected to ultrafine pulverization to obtain a mixed ultrafine powder; the particle size D of the mixed ultrafine powder is... 90 The particle size is controlled at around 50 μm; artificial musk, borneol and fumed silica are mixed, ground and sieved to obtain artificial musk-borneol-fumed silica mixture; the mixed ultrafine powder and artificial musk-borneol-fumed silica mixture are mixed evenly by equal incremental addition method to obtain solid drug fraction; Preparation of the S2 liquid pharmaceutical portion: Menthol, camphor, vanillyl butyl ether, methyl salicylate, glycerin, and light liquid paraffin are stirred and dissolved to obtain the liquid pharmaceutical portion; The ratio of solid to liquid dosage is 1.5g:2g; By weight, the raw materials for the solid medicine portion include: 2.5 parts artificial musk, 15 parts borneol, 50 parts dragon's blood, 100 parts vinegar-processed myrrh, 120 parts catechu, 20 parts Panax notoginseng, 150 parts safflower, 260 parts wine-processed Angelica sinensis, 120 parts cinnabar, and 100 parts vinegar-processed frankincense. By weight, the raw materials for the liquid pharmaceutical portion include: 40 parts menthol, 40 parts camphor, 25 parts vanillyl butyl ether, 35 parts methyl salicylate, 40 parts glycerin, and 30 parts light liquid paraffin. The amount of fumed silica gel used is 2% of the total mass of the raw materials in the solid pharmaceutical part.

8. The use of any one of the topical preparations for treating sprains and bruises according to any one of claims 1-6 in the preparation of drugs for treating bone injuries and drugs for reducing swelling and relieving pain.

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