Musk blood-activating and orifice-opening mixture and preparation process thereof

Abstract

The invention discloses a musk blood-activating and orifice-opening mixture and a preparation process thereof, and belongs to the field of traditional Chinese medicine preparations. The traditional Chinese medicine composition is prepared from the following raw materials in parts by mass: 0.15 to 0.8 part of musk, 60 to 200 parts of radix paeoniae rubra, 80 to 200 parts of rhizoma chuanxiong or radix salviae miltiorrhizae, 60 to 150 parts of semen persicae and 60 to 150 parts of flos carthami. The preparation method comprises the following steps: carrying out alcohol extraction on musk to obtain a musk extract, and carrying out inclusion and nanocrystallization treatment on the musk extract and beta-cyclodextrin to obtain a nanosuspension; carrying out dynamic circulating ultrasonic countercurrent extraction, membrane separation, macroporous resin column adsorption and elution on other raw materials except the musk to obtain an eluent; and finally, combining the nano suspension and the eluent, adding a flavoring agent and a stabilizer, filling, and sterilizing to obtain the musk blood-activating and orifice-opening mixture. Besides, other traditional Chinese medicine components or additives can be introduced in the process to prepare syrup, dripping pills, gels, film agents, patches, tinctures, freeze-dried powder injections, sprays and capsules, and the traditional Chinese medicine composition has the advantages of being more remarkable in curative effect, more controllable in quality and higher in medicine availability clinically.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparations, specifically relating to a musk-based blood-activating and orifice-clearing compound and its preparation process. Background Technology

[0002] In recent years, cardiovascular and cerebrovascular diseases (such as coronary heart disease, angina pectoris, and sequelae of cerebral infarction) and headaches and dizziness caused by blood stasis have become common and frequently occurring diseases in clinical practice. However, traditional Chinese medicine preparations for promoting blood circulation and clearing the orifices are highly dependent on: ① the origin of raw materials and the experience of the decocters, resulting in significant batch-to-batch variations and uncontrollable quality; ② extremely prone to mold growth, requiring immediate decoction and administration, making permanent preservation impossible, and ordinary Chinese medicine compound preparations are prone to precipitation; ③ may contain small molecule impurities or large molecule colloids, increasing the risk of allergies or intestinal discomfort for patients; ④ bitter taste and turbid odor, resulting in poor palatability and low patient compliance, especially for children; ⑤ low concentration of active ingredients, and potential poor absorption due to solubility issues; ⑥ highly volatile and easily lost active ingredients; ⑦ unable to achieve large-scale standardized production and inconvenient for storage and transportation; ⑧ requiring a cumbersome process of dispensing, soaking, and decocting, which is time-consuming and labor-intensive.

[0003] In addition, natural musk raw materials are extremely scarce and their sources are limited, so most of them are synthesized artificially. Therefore, improving their utilization rate is particularly important. Furthermore, the components of traditional Chinese medicine for promoting blood circulation and clearing the orifices are relatively complex and have poor stability. The active ingredients involved are easily volatilized and lost, and some active ingredients have poor water solubility, which affects the efficacy. The preparation process of traditional Chinese medicine for promoting blood circulation and clearing the orifices is complicated and time-consuming, and mostly involves conventional water decoction or alcohol precipitation processes, which can result in high loss rate of active ingredients, low transfer rate, poor stability between batches of products, and problems such as slow onset of action and low bioavailability.

[0004] In view of this, there is an urgent need to develop a musk-based oral cavity clearing compound and its preparation process that can make the drug take effect faster, be more stable, have more controllable quality, and have higher safety, compliance, and drug utilization rate, so as to meet the urgent clinical needs. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and propose a musk-based blood-activating and orifice-clearing compound containing the following raw materials in parts by weight: 0.15-0.8 parts musk, 60-200 parts red peony root, 80-200 parts chuanxiong or danshen, 60-150 parts peach kernel, and 60-150 parts safflower.

[0006] Furthermore, this invention also provides a preparation process for a musk-based blood-activating and orifice-clearing compound: prepared according to the process flow of "decoction → concentration → alcohol precipitation → blending → sterilization," wherein, In the decoction process: Musk and β-cyclodextrin are encapsulated to form an inclusion complex, which is then nano-sized to form nano-suspension A; In the concentration process: Red peony root, Sichuan lovage rhizome or salvia miltiorrhiza, peach kernel, and safflower are placed in a dynamic circulating ultrasonic countercurrent device to extract extract B; In the alcohol precipitation process: extract B is separated by membrane to obtain filtrate C, and filtrate C is adsorbed and eluted onto a macroporous adsorption resin column to obtain eluent D.

[0007] Specifically, such as Figure 1 As shown, the preparation process of Musk Blood-Activating and Orifice-Clearing Compound includes the following steps: Step 1: Weigh the raw materials according to the set mass proportions. Wash the red peony root, chuanxiong rhizome or danshen root, and safflower, then slice and dry them. Wash the peach kernels and grind them into a paste. Step 2: First, extract the musk extract using alcohol extraction; then, treat the extracted musk extract with β-cyclodextrin inclusion and low-temperature nano-dispersion to obtain nano-suspension A; then, extract the other raw materials except musk using dynamic circulating ultrasonic countercurrent extraction to obtain extract B; extract B is then separated by membrane separation through a ceramic microfiltration membrane or ultrafiltration membrane to form filtrate C; then, filtrate C is adsorbed and eluted onto a macroporous adsorption resin column to obtain eluent D. Step 3: Mix nano-suspension A and eluent D to form solution E. Add flavoring agent and stabilizer to solution E to finally form solution F. Step 4: Fill and sterilize solution F sequentially to complete the preparation of Musk Blood-Activating and Orifice-Clearing Compound.

[0008] Furthermore, in step 2, the mass ratio of musk to ethanol is 1:5 to 1:10; the molar ratio of musk extract to β-cyclodextrin inclusion is 1:1 to 1:2.

[0009] Furthermore, the temperature for the inclusion process in step 2 is 50℃~80℃.

[0010] Furthermore, in step 2, the nano-dispersion equipment for low-temperature nano-dispersion is a high-pressure homogenizer, and the specific process parameters are as follows: reaction temperature is 0℃~15℃, high-pressure homogenization pressure is 500~1500 bar, and homogenization cycle number is 5~15 times. Furthermore, the concentration of nanosuspension A is 1% to 5% w / v, and the pH value is 6 to 8.

[0011] Furthermore, during the dynamic circulating ultrasonic countercurrent extraction in step 2, the mass ratio of raw materials other than musk to solvent is 1:8 to 1:15.

[0012] Furthermore, the specific process of elution in step 2 is as follows: First, wash with 2-5 column volumes of purified water to remove unadsorbed water-soluble impurities; then elute once with 2-3 column volumes of 70% ethanol, and then elute a second time with 3-5 column volumes of 70%-95% ethanol until the eluent is colorless.

[0013] Furthermore, the present invention is applied in the preparation of syrups, pellets, gels, films, patches, tinctures, lyophilized powder injections, sprays, and capsules.

[0014] Optionally, adding 6-30 parts of old scallions (white part), 9-90 parts of ginger, 15-100 parts of jujubes, and 50-250 parts of rice wine to the ingredients can enhance the medicinal effect. Depending on the type of disease, appropriate amounts of astragalus, earthworm, notoginseng, angelica, tribulus, polygala, and acorus can also be added to optimize the composition of the ingredients.

[0015] Compared with the prior art, the present invention has the following beneficial effects: This invention is the first to combine "β-cyclodextrin inclusion" with "low-temperature nano-dispersion" processes, using standardized modern Chinese medicine preparation technology. This ensures batch-to-batch stability and quality control of the compound. Gradient elution with purified water and ethanol-water solution effectively removes unstable impurities such as starch, protein, and mucilage, reducing the possibility of precipitation and deterioration at the source. It also removes some potentially irritating impurities, improving medication safety. The addition of flavoring agents significantly improves patient compliance. Macroporous adsorption resin technology can selectively adsorb and enrich the effective components in the aqueous extract. Furthermore, the nano-sized musk has a significantly increased specific surface area, resulting in increased dissolution rate and extent in vivo, making it easier to permeate biological membranes, thereby significantly improving bioavailability and ensuring the onset rate and duration of the core efficacy. This invention integrates multiple modern separation and purification technologies, including dynamic circulation, ultrasound, countercurrent extraction, membrane separation, and resin adsorption, to construct a highly efficient, energy-saving, and precise platform for the extraction and purification of traditional Chinese medicine compound preparations. Specifically, the "dynamic circulation + ultrasound + countercurrent extraction" method can shorten extraction time by approximately 40% compared to traditional processes, increase the transfer rate of active ingredients by more than 15%, and reduce solvent usage while protecting the active ingredients. The "membrane separation + resin adsorption" method, compared to traditional alcohol precipitation, can enrich the active ingredients, remove impurities more thoroughly, and obtain a more refined formulation. Therefore, it can improve patient medication adherence, reduce the volume of medication per dose, avoid the use of large amounts of ethanol, save energy, and make the production process safer and more efficient.

[0016] The musk-invigorating and orifice-clearing compound prepared using the process of this invention has a faster onset of action, stronger stability, more controllable quality, higher safety and compliance, and better drug utilization. Moreover, it can relatively reduce the amount of precious medicinal musk while ensuring the same efficacy, and has important economic and social value. Attached Figure Description

[0017] The accompanying drawings are incorporated in and form part of this specification, and together with the description serve to explain the principles of the invention.

[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 This is a flowchart illustrating the preparation process of a musk-based blood-activating and orifice-clearing compound according to the present invention. Detailed Implementation

[0020] Exemplary embodiments will now be described in detail. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Rather, they are merely examples consistent with some aspects of the invention as detailed in the appended claims.

[0021] Example 1 This embodiment 1 provides a musk-based blood-activating and orifice-clearing compound and its preparation process, mainly including the following steps: Step 1: Weigh the raw materials: 0.15 g musk, 150 g red peony root, 120 g chuanxiong rhizome, 120 g peach kernel, 100 g safflower, 30 g old scallion (white part), 90 g ginger, 100 g jujube, 50 ml rice wine (as a medicinal guide, added when concentrating the paste). Wash the red peony root, chuanxiong rhizome, and safflower, cut them into slices, and dry them. Wash the peach kernel and grind it into a paste. Wash the jujube and remove the pits. Wash the old scallion and cut it into sections. Wash the ginger and slice it. Step 2: Extract musk extract using a musk:ethanol ratio of 1:5 (mass ratio); form inclusion complex by stirring at 50°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 10 cycles at 500 bar pressure and 0°C using a high-pressure homogenizer to obtain a 3% w / v nano-suspension A with a pH of 6. The processed red peony root, chuanxiong rhizome, peach kernel, safflower, jujube, ginger, and scallion were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent, and the mass-to-volume ratio of raw materials (except musk) to solvent was 1:9. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 minutes to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a flow rate of 2 BV / h, and loaded onto the column. After adsorption, the sample was washed with 2 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the sample was eluted once with 2 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 3 BV of 70% ethanol at a flow rate of 2 BV / h. The eluent D was prepared by a second elution at a flow rate of BV / h to obtain a colorless eluent. Step 3: Dilute the eluent D, monosaccharide syrup, glycerol, steviol glycoside aqueous solution, and sodium benzoate aqueous solution with purified water to about 9.5L, stir well, and slowly add nano suspension A and orange flavor while stirring. Add about 50ml of rice wine and adjust the total volume to 10L with purified water. Stir well to form solution F. Step 4: After the solution F is left to stand for 24 hours, it is filtered through a 0.45μm microporous membrane and filled into a 10ml oral liquid bottle. The solution is then sterilized by flowing steam at 100℃ for 30 minutes. After labeling and packaging, the preparation of Musk Blood-Activating and Orifice-Clearing Compound is completed.

[0022] Comparative Example Step 1: Weigh out 0.1g of natural musk, 15g of chuanxiong rhizome, 10g of peach kernel, 10g of safflower, 10g of red peony root, 10g of ginger, 7 jujubes, and 250ml of rice wine (to be used as a medicinal guide for oral administration). Step 2: Place the natural musk in a mortar, add a small amount of water or rice wine, and grind it repeatedly and slowly for at least 30 minutes until it is fully dissolved and dispersed, forming a turbid liquid; mix the chuanxiong, peach kernel, safflower, red peony root, ginger, and jujube (cut open), place them in a ceramic jar or earthenware pot, add cold water and soak for 30 minutes, the water level should be enough to cover the herbs and be 2-3 cm above them; Step 3: Preparing the First Decoction: Bring all the soaked herbs except musk to a boil over high heat. After boiling, reduce to a simmer and start timing. Simmering time: 40-50 minutes, stirring occasionally to prevent sticking and burning. After 40 minutes, filter the liquid through gauze and collect the filtrate. Step 4: Decocting the second batch of medicine: Return the dregs to the pot, add warm water again, slightly less than the first time. Bring to a boil over high heat, then reduce to a simmer. Decoct for 30-40 minutes. After 30 minutes, filter again and collect the filtrate. Step 5: Combine the first and second decoctions, let stand for a while to allow the sediment to settle, pour the supernatant into a pot, add 250ml of rice wine, and heat gently until just before boiling to prevent alcohol from evaporating. Step 6: Slowly pour in the pre-ground musk solution when the temperature of the medicinal liquid is about 60-70℃, and stir quickly and thoroughly.

[0023] The modern integrated technology used in Example 1 represents a significant improvement in preparation efficiency, scale, and standardization compared to the traditional manual, experience-based, and time-consuming processes used in the comparative example, and can retain the core components to the greatest extent. The musk-invigorating and orifice-clearing compound prepared in Example 1, compared to the traditional decoction prepared in the comparative example, is used to treat migraines of the qi stagnation and blood stasis type. The diagnostic criteria refer to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines." Patients present with stabbing headaches, fixed pain locations, prolonged duration, recurrent attacks, or accompanied by a sallow complexion, purplish-dark tongue, petechiae or ecchymosis, and a wiry or hesitant pulse.

[0024] Treatment methods: The treatment group took 20ml of natural musk blood-activating and orifice-clearing compound orally three times a day; the control group took traditional decoction twice a day, morning and evening, warm after meals. This decoction is very easy to spoil and must be placed in a cool place or refrigerated and consumed within 24 hours.

[0025] Treatment effect: Because the compound is a liquid and has been refined, the active ingredients are more easily absorbed. Patients reported that headache relief time was on average about 30 minutes earlier than that of traditional decoctions, and the effect was rapid.

[0026] Stable therapeutic effect: Due to the use of standardized extraction process, the content of effective ingredients in each batch and each bottle of medicine is uniform, which ensures the stability and repeatability of clinical efficacy and avoids the problem of different efficacy of traditional decoctions due to different people who decoct them.

[0027] High compliance: It can be used immediately after opening, without the need for decoction, and the taste is controllable. It is easy to carry and store, which greatly improves patients' compliance with long-term treatment.

[0028] Good safety: Through purification steps such as alcohol precipitation and filtration, a large number of impurities are removed, reducing the incidence of gastrointestinal adverse reactions. It is fast-acting and has a long-lasting effect. The extraction time is shortened by 40%, and the transfer rate of effective ingredients is increased by more than 15%.

[0029] Clinical application The clinical observation case report of the musk-invigorating and orifice-opening compound prepared in Example 1 above for treating migraine of qi stagnation and blood stasis type is as follows: I. Patient Basic Information: Wang, female, 42 years old, visited the hospital on October 10, 2023.

[0030] II. Medical History and Diagnosis Chief complaint: Recurrent throbbing pain in the right temporal region for 5 years, which has worsened in the past 3 months.

[0031] Present Illness: The patient began experiencing right-sided headaches without any obvious cause 5 years ago, occurring 1-2 times per month, which could be relieved by self-medicating with "Sanlitong". In the past 3 months, due to high work stress, the frequency of attacks has increased to 1-2 times per week, the pain has intensified, and nausea and photophobia have also occurred, severely affecting work and sleep. Oral analgesics have become less effective.

[0032] Traditional Chinese medicine examination: dull complexion, depressed mood, dark red tongue with petechiae on the edges, thin white coating, and wiry and hesitant pulse.

[0033] Traditional Chinese Medicine diagnosis: migraine (Qi stagnation and blood stasis syndrome); Western medicine diagnosis: migraine without aura (chronic phase).

[0034] III. Treatment Methods Medication: Musk-infused Orifice-Clearing and Blood-Activating Mixture, Specification: 100ml per bottle Dosage and administration: Oral administration, 20ml each time, 3 times a day (taken after breakfast, lunch and meals).

[0035] Treatment course: One course of treatment consists of continuous medication for 4 weeks (28 days). This study observed one course of treatment.

[0036] Contraindications: Discontinue use of other pain medications during treatment, avoid raw, cold, and spicy foods, and maintain emotional well-being.

[0037] IV. Observation Indicators and Efficacy Evaluation Criteria 1. Primary therapeutic endpoints: Headache Visual Analogue Scale (VAS): 0 (no pain) to 10 (severe pain), frequency of headaches (times / week), duration of each headache (hours / time).

[0038] 2. Secondary efficacy endpoints: Accompanying symptoms (nausea, photophobia) score: 0, 1, 2, and 3 points respectively for none, mild, moderate, and severe.

[0039] Traditional Chinese Medicine syndrome scoring: Scored based on symptoms such as headache, complexion, tongue, and pulse.

[0040] 3. Efficacy evaluation criteria (refer to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines"): Clinical cure: efficacy index ≥ 95%.

[0041] Significant efficacy: efficacy index ≥70% and <95%.

[0042] Effective: The efficacy index is ≥30% and <70%.

[0043] Ineffective: Therapeutic index <30%.

[0044] Therapeutic effect index = [(Pre-treatment score - Post-treatment score) ÷ Pre-treatment score] × 100% V. Treatment Results and Data Observation indicators Before treatment (baseline) Two weeks after treatment Four weeks after treatment (end of treatment) Remark VAS score (points) 8 4 2 The pain level was significantly reduced, from severe pain to mild pain. Attack frequency (times / week) 2 1 0.5 The frequency of attacks decreased significantly, with only one attack occurring in the second half of the treatment course. Duration (hours / time) 12 6 3 The duration of headaches was significantly shortened. Nausea symptom score 2 1 0 The accompanying symptoms have largely disappeared. Photophobia symptom score 2 1 0 The accompanying symptoms have largely disappeared. Total score of TCM syndrome 18 10 5 Used to calculate the efficacy index. VI. Calculation and Conclusion of Therapeutic Effect Therapeutic effect index calculation: Therapeutic effect index = [(18 - 5) ÷ 18] × 100% = 72.2% Final efficacy evaluation: Based on an efficacy index of 72.2%, the patient's efficacy was evaluated as "significantly effective" after one course of treatment.

[0045] Conclusion: The data from this case study show that after two weeks of taking the Musk Blood-Activating and Orifice-Clearing Compound, the patient's various indicators began to show significant improvement. After four weeks of continuous medication, the severity (VAS), frequency, and duration of headaches were fundamentally controlled, and accompanying symptoms disappeared. The treatment course was well-designed, and the efficacy steadily improved with the extension of medication time, demonstrating the definite therapeutic effect of this compound on migraine caused by qi stagnation and blood stasis. Furthermore, the compound had a relatively rapid onset of action and a stable and sustained therapeutic effect. Throughout the treatment process, the patient did not report any gastrointestinal discomfort or other adverse reactions, and their vital signs remained stable, demonstrating the good safety profile of the compound.

[0046] Example 2 This embodiment provides a musk-based blood sugar-regulating and scalp-opening syrup and its preparation process. To improve medication adherence for children and some patients with high taste preferences, this invention mainly includes the following steps: Step 1: Weigh the raw materials: 0.5g musk, 100g salvia miltiorrhiza, 80g peach kernel, 80g safflower, 80g red peony root, 20g old scallion, 50g ginger, and 50g jujube; Step 2: Extract musk extract using a musk:ethanol ratio of 1:8 (mass ratio); form inclusion complex by stirring at 60°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 8 cycles using a high-pressure homogenizer at 1200 bar and 5°C to obtain a 5% w / v inclusion suspension A with a pH of 8 nanometers. The processed raw materials, excluding musk, were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent. The mass-to-volume ratio of raw materials (excluding musk) to solvent was 1:10. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 min to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a column volume of 3 BV (column volume) and loaded onto the column at a flow rate of 2 BV / h. After adsorption, the column was washed with 5 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the column was first washed with 3 BV of 70% ethanol at a flow rate of 2 BV / h. The solution was eluted once with a flow rate of BV / h, and then eluted a second time with 4 BV of 95% ethanol at a flow rate of 2 BV / h to obtain a colorless eluent D. Step 3: Dissolve sucrose in boiling purified water to prepare a 65% simple sugar syrup, and filter while hot; mix the fluid extract, 400ml of simple sugar syrup and 100g of honey in a preparation tank and stir well, then add nano suspension A, stir thoroughly, add 1g of potassium sorbate as a preservative, and add purified water to adjust the total volume to 1L, stir well to form solution F; Step 4: Filter the solution F through an ultrafiltration membrane to ensure that the solution is clear and sterile, and finally fill it into sterilized syrup bottles under aseptic conditions.

[0047] Example 2 is used to treat pediatric migraine of the Qi stagnation and blood stasis type. The dosage is finely adjusted according to the child's age or weight: 3-6 years old, weight <20kg, 5ml each time, twice a day; 7-12 years old, weight 20-40kg, 10ml each time, twice a day; 13 years and older, 10ml each time, three times a day, with 4 weeks as one course of treatment. Patients often experience recurrent headaches due to exam stress, emotional fluctuations, and lack of sleep, resulting in a pale complexion, irritability or depression, a dark tongue or petechiae, and a wiry and thready pulse.

[0048] Treatment method: Based on age and weight standards, the treatment group received oral administration of natural musk blood-activating and orifice-clearing syrup.

[0049] Treatment efficacy: The results showed that the frequency, duration and severity of headache attacks in the children were significantly improved compared with before treatment.

[0050] High compliance: The sweet taste of the syrup completely masks the bitterness of the traditional Chinese medicine. All children expressed their willingness to accept the medicine and there was no refusal. Parents reported that the difficulty of administering the medicine was reduced to zero.

[0051] Good safety profile: The use of rice wine as a medicinal ingredient has been removed, avoiding the effects of alcohol on children's nervous system. Through a refined processing method, impurities are reduced, and no significant gastrointestinal adverse reactions have been observed.

[0052] Example 3 This embodiment 3 provides a musk-invigorating and blood-activating pill and its preparation process, mainly including the following steps: Step 1: Weigh the raw materials: 0.3 g of musk, 100 g of red peony root, 150 g of chuanxiong rhizome, 100 g of peach kernel, and 100 g of safflower. Wash the red peony root, chuanxiong rhizome, and safflower, cut them into 3 mm slices, and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:10 (mass ratio); form inclusion complex by stirring at 70°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 9 cycles using a high-pressure homogenizer at 1000 bar and 10°C to obtain a 2% w / v nano-suspension A with a pH of 7; The processed red peony root, chuanxiong rhizome, peach kernel, and safflower were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent. The mass-to-volume ratio of raw materials (except musk) to solvent was 1:8. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 min to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a flow rate of 2 BV / h, and loaded onto the column. After adsorption, the column was washed with 3 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the column was eluted once with 3 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 5 BV of 85% ethanol at a flow rate of 2 BV / h. The eluent was eluted twice at a flow rate of BV / h to obtain a colorless eluent D. The eluent D was then dried into a dry extract powder using spray drying technology. Step 3: Heat and melt PEG 4000 and PEG 6000 in a specific ratio in the mixing tank of the pelleting machine to form a uniform liquid matrix; under a constant temperature of 80~90℃, fully and uniformly disperse the nano-suspension A and dry extract powder into the liquid matrix to form a drug-matrix mixed melt. Step 4: Turn on the pelleting machine. Through a precisely controlled dropper, the mixed molten liquid is dripped at a specific rate and distance into the low-temperature dimethyl silicone oil flowing in the cooling column. The droplets shrink into pellets due to surface tension in the condensate and rapidly cool and solidify into solid pellets. The pellets flow out with the condensate, are separated by a sieve, and the surface silicone oil is washed off with a non-toxic solvent. They are then dried in a fluidized bed to obtain dry, round pellets.

[0053] The droplet formulation in Example 3 utilizes the rich blood vessels in the sublingual mucosa, allowing the active ingredients of the drug to be directly absorbed into the bloodstream, bypassing the first-pass effect of the liver, thereby achieving rapid onset of action. It also boasts advantages such as small size, portability, and discreet administration. This dosage form can be used to treat patients experiencing acute attacks of migraine due to qi stagnation and blood stasis.

[0054] Treatment method: During the prodromal phase of a migraine attack or at the onset of pain, immediately take 5-8 pills of this product and place them under the tongue. Allow them to dissolve naturally with saliva. Instruct the patient to close their mouth, breathe through their nose, and try not to swallow, so that the drug components can be quickly absorbed through the sublingual mucosa. If the pain is not completely relieved, another dose can be taken after 30 minutes.

[0055] Clinical efficacy observation: The onset of action is significantly improved. The drug is absorbed through the sublingual mucosa and enters the systemic circulation directly, shortening the onset time to 10-15 minutes, which is far longer than that of oral compound preparations (about 30-60 minutes), providing convenience for patients.

[0056] High bioavailability: By avoiding the first-pass effect of the liver, the bioavailability of musk is improved, which means that smaller doses can be used to achieve the same or even better therapeutic effects.

[0057] Ultimate portability and privacy: A small bottle of drops can be easily put into a pocket or wallet, allowing patients to take their medication discreetly and without water in any situation, greatly facilitating patients who are traveling or working.

[0058] Flexible dosage: The number of pills can be adjusted according to the severity of pain, enabling individualized and immediate treatment.

[0059] Example 4 This embodiment 4 provides a musk-based transdermal patch for promoting blood circulation and clearing the orifices, and its preparation process, mainly including the following steps: Step 1: Weigh the raw materials: 0.5 g of musk, 120 g of red peony root, 200 g of chuanxiong rhizome, 120 g of peach kernel, and 120 g of safflower. Wash the red peony root, chuanxiong rhizome, and safflower, cut them into 3 mm slices, and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:6 (mass ratio); form inclusion complex by stirring at 80°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 5 cycles using a high-pressure homogenizer at 1300 bar and 15°C to obtain a 1.5% w / v nano-suspension A with a pH of 6.5; The processed red peony root, chuanxiong rhizome, peach kernel, and safflower were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent. The mass-to-volume ratio of raw materials (except musk) to solvent was 1:12. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 min to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a column volume of 2 BV (column volume) and loaded onto the column at a flow rate of 2 BV / h. After adsorption, the sample was washed with 5 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the sample was eluted once with 3 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 4 BV of 80% ethanol at a flow rate of 2 BV / h. The eluent was eluted twice at a flow rate of BV / h to obtain a colorless eluent D. The eluent D was then dried into a dry extract powder using spray drying technology. Step 3: Grind and mix the nano suspension A, dry extract powder and 10g azone (penetration enhancer) thoroughly; slowly add this mixture to the pressure-sensitive adhesive matrix that has been dissolved in polyacrylate, and use a high-speed homogenizer to shear and disperse it to form a uniform, viscous drug-containing colloid. Step 4: Using a precision coating machine, the drug-containing colloid is evenly coated onto the anti-adhesive layer (silicified polyester film) to a thickness of 100μm. The coated material is then passed through a segmented heating drying channel to allow the organic solvent to completely evaporate, forming a stable drug reservoir layer. The backing layer (polyester composite film) is then laminated and rolled with the dried drug reservoir layer to form a sandwich structure of "backing layer-drug reservoir layer-anti-adhesive layer". The laminated material is then cut into specified sizes (e.g., 5cm x 7cm) using a die-cutting machine. Finally, the material is packaged in aluminum foil bags in a clean environment to obtain the musk-invigorating transdermal patch.

[0060] Example 5 This embodiment 5 provides a musk-based blood-activating and orifice-clearing nanogel and its preparation process, which mainly includes the following steps: Step 1: Weigh the raw materials: 0.15 g of musk, 60 g of red peony root, 80 g of chuanxiong rhizome, 60 g of peach kernel, and 60 g of safflower. Wash the red peony root, chuanxiong rhizome, and safflower, cut them into 3 mm slices, and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:7 (mass ratio); form inclusion complex by stirring at 50°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 9 cycles using a high-pressure homogenizer at 1000 bar and 10°C to obtain a 2% w / v nano-suspension A with a pH of 7. The processed red peony root, chuanxiong rhizome, peach kernel, and safflower were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent. The mass-to-volume ratio of raw materials (except musk) to solvent was 1:8. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 min to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a flow rate of 2 BV / h, and loaded onto the column. After adsorption, the column was washed with 5 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the column was eluted once with 3 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 4 BV of 95% ethanol at a flow rate of 2 BV / h. The eluent was eluted twice at a flow rate of BV / h to obtain a colorless eluent D. The eluent D was then dried into a dry extract powder using spray drying technology. Step 3: Dissolve nano-suspension A, dry extract powder, phospholipids, and cholesterol together in an organic solvent, and prepare a drug-loaded NLC suspension using a thin-film evaporation-high pressure homogenization method or a microemulsification method; determine the particle size, zeta potential, and encapsulation efficiency of the obtained NLC to ensure quality uniformity; slowly disperse poloxamer 407 in the sterile suspension containing NLC at 0~4℃ to allow it to fully swell and form a free-flowing sol solution; Step 4: Add sodium chloride as an osmotic pressure regulator and phosphate buffer as a pH regulator to the sol solution to adjust the pH value to 7.3; under sterile conditions, filter and sterilize through a 0.22μm microporous membrane, and dispense into sterile eye drop bottles to complete the preparation of musk blood-activating and nasal-clearing nanogel.

[0061] The dosage form prepared in Example 5 is administered topically to the eye and utilizes nanotechnology to enhance the drug's penetration through the corneal barrier and its residence time within the eye, directly targeting the retinal lesion site for targeted ocular therapy. This dosage form is liquid at room temperature, making it easy to instill into the eye. After instillation, it transforms into a semi-solid gel within seconds, triggered by corneal surface temperature. This dosage form is used to treat retinal vein occlusion (RVO) due to qi stagnation and blood stasis, where patients exhibit symptoms such as tortuous and dilated retinal veins, fundus hemorrhage, and edema.

[0062] Treatment method: The patient lies supine and drops 1-2 drops of this product into the conjunctival sac of the affected eye 3-4 times a day.

[0063] Therapeutic effects: ① High targeting and local concentration: It breaks through the blood-retinal barrier, allowing the blood-activating and nasal-clearing drugs to act directly and efficiently on retinal blood vessels, which is difficult to achieve with oral or injection administration; ② Long-lasting effect and reasonable dosing frequency: The thermosensitive gel system extends the duration of drug action in the eye from a few minutes to several hours, ensuring continuous therapeutic effects; ③ Promotes hemorrhage absorption and improves circulation: Clinical observations show that RVO patients using this product have significantly faster absorption of retinal hemorrhage and exudate than the conventional treatment group, reduced macular edema, and effective improvement in vision in some patients; ④ Minimal systemic side effects: Due to local administration and the negligible amount absorbed into the system through the nasolacrimal duct, the potential impact of the drug on other systems (such as cardiovascular and coagulation functions) is almost avoided, resulting in extremely high safety.

[0064] Example 6 This embodiment 6 provides a musk-infused oral cavity quick-dissolving film for promoting blood circulation and clearing nasal passages, and its preparation process, which mainly includes the following steps: Step 1: Weigh the raw materials: 0.2 g of musk, 80 g of red peony root, 100 g of chuanxiong rhizome, 80 g of peach kernel, 80 g of safflower, and 150 g of astragalus root. Wash the red peony root, chuanxiong rhizome, safflower, and astragalus root, cut them into 3 mm slices, and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:9 (mass ratio); form inclusion complex by stirring at 50°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 7 cycles using a high-pressure homogenizer at 1300 bar and 10°C to obtain a 4% w / v nano-suspension A with a pH of 7. The processed red peony root, chuanxiong rhizome, peach kernel, safflower, and astragalus root were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent. The mass-to-volume ratio of raw materials (except musk) to solvent was 1:10. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 min to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a column volume of 2 BV (column volume) and loaded onto the column at a flow rate of 2 BV / h. After adsorption, the sample was washed with 5 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the sample was eluted once with 3 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 4 BV of 85% ethanol at a flow rate of 2 BV / h. The eluent was eluted twice at a flow rate of BV / h to obtain a colorless eluent D. The eluent D was then dried into a dry extract powder using spray drying technology. Step 3: The dry extract powder is processed by nano-grinding technology to obtain nanoparticles with a particle size of less than 400 nanometers; HPMC and amylopectin are dissolved in purified water to form a gel; then glycerol is added in sequence as a plasticizer, eluent D, nano suspension A, aspartame, and menthol (flavoring agent), and emulsified by high-speed shearing to form a uniform, bubble-free drug-loaded film solution. Step 4: Using a precision automatic casting coating machine, the film liquid is coated onto a moving stainless steel belt to a thickness of 3mm; after drying in a low-temperature hot air circulating drying oven, a flexible drug film is formed; finally, a laser precision cutting machine is used to cut the drug film into square thin sheets of a specified size (such as 2cm x 2cm) to obtain the musk blood-activating and orifice-clearing oral quick-dissolving film.

[0065] When this dosage form (Example 6) is placed on the tongue, it dissolves and releases the drug rapidly within seconds without the need for water. It can be absorbed through the sublingual and oral mucosa for rapid onset of action, or absorbed through the gastrointestinal tract via swallowing for long-lasting effect. This perfectly solves the drug administration problem for patients with dysphagia and greatly improves the convenience of medication use. It can be used to treat post-stroke sequelae (qi deficiency and blood stasis syndrome). Specific case reports are as follows: Patient Information: Mr. Zhang, male, 68 years old, presented with left-sided limb movement impairment and speech difficulties for more than 3 months. Three months prior, the patient suffered a sudden cerebral infarction, and after hospital resuscitation, was left with left-sided hemiplegia, occasional choking when drinking, and slurred speech.

[0066] Traditional Chinese medicine diagnosis: Stroke - Affecting the meridians (Qi deficiency and blood stasis syndrome) Treatment process: On the basis of routine rehabilitation training, the original oral Chinese patent medicine was discontinued, and natural musk blood-activating and nasal-clearing oral quick-dissolving film was given.

[0067] Dosage and administration: 1 tablet each time, 3 times a day. Instruct the patient to clean their mouth after each meal, place the medicated film under the tongue, close their mouth, and wait for it to dissolve naturally.

[0068] Observation Results: Week 1 of Medication: Family members reported that the patient found taking the medication extremely convenient, with no risk of choking. The patient reported improved mental state. Week 4 of Medication: The rehabilitation therapist assessed that the proximal muscle strength of the left upper limb had improved to grade III, allowing the patient to perform a few assisted movements. Speech clarity improved. Week 8 of Medication: The patient could walk short distances with assistance. During the treatment period, the patient's liver and kidney function and blood routine tests showed no abnormal changes, and there were no allergic reactions or gastrointestinal discomfort.

[0069] Example 7 This embodiment 7 provides a musk-infused nasal spray for promoting blood circulation and clearing nasal passages, and its preparation process, which mainly includes the following steps: Step 1: Weigh the raw materials: 0.2 g of musk, 120 g of red peony root, 140 g of chuanxiong rhizome, 120 g of peach kernel, and 120 g of safflower. Wash the red peony root, chuanxiong rhizome, and safflower, cut them into 3 mm slices, and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:7 (mass ratio); form inclusion complex by stirring at 50°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 10 cycles using a high-pressure homogenizer at 800 bar and 10°C to obtain a 3% w / v nano-suspension A with a pH of 6. The processed red peony root, chuanxiong rhizome, peach kernel, and safflower were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent. The mass-to-volume ratio of raw materials (except musk) to solvent was 1:9. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 min to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a flow rate of 2 BV / h, and loaded onto the column. After adsorption, the sample was washed with 3 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the sample was eluted once with 2 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 3 BV of 90% ethanol at a flow rate of 2 BV / h. The eluent D was prepared by a second elution at a flow rate of BV / h to obtain a colorless eluent. Step 3: Add about 800 ml of phosphate buffer solution with a pH of 6 to a sterile preparation vessel. After mixing the eluent D and nano suspension A evenly, add sodium chloride, disodium EDTA, and benzalkonium chloride in sequence, and then add the mixture F to 1 L with phosphate buffer solution. Step 4: After the solution F is left to stand for 24 hours, it is filtered and sterilized using a 0.1μm microporous membrane, and then filled into a specially designed nasal spray device to complete the preparation of the musk-invigorating and nasal-clearing nasal spray.

[0070] This embodiment 7 provides a nasal drug delivery system that utilizes the rich capillaries of the nasal cavity and avoids the first-pass effect of the liver to achieve rapid onset of action, making it particularly suitable for acute symptoms requiring rapid relief. A case report of treatment in a patient with an acute migraine attack with aura is as follows: The patient is a 35-year-old female. Western medicine diagnosis: acute migraine attack; prior to the attack, she experienced blurred vision and flashes of light, followed by throbbing pain in the right temporal region, accompanied by nausea, vomiting, photophobia, phonophobia, facial flushing, a red tongue with petechiae on the edges, and a wiry and rapid pulse.

[0071] Treatment: During the prodromal phase of an acute migraine attack, the treatment group used a natural musk nasal spray to promote blood circulation and clear the nasal passages, while the control group took an oral medication.

[0072] Dosage and administration: 1 spray per nostril each time. If necessary, repeat once after 15 minutes. Do not exceed 4 times in 24 hours.

[0073] Efficacy observation: Pain relief rate within 2 hours (pain reduced from moderate to severe to mild or no pain): 85% in the treatment group and 60% in the control group; Pain disappearance rate within 2 hours: 45% in the treatment group and 25% in the control group; Average onset time was 15±5 minutes, with significant improvement in symptoms such as nausea and photophobia; Recurrence rate within 24 hours: 20% in the treatment group and 40% in the control group; The proportion of patients who could resume normal activity within 1 hour after medication was significantly higher in the treatment group than in the control group; Local adverse reactions were mild (transient nasal burning sensation, incidence <5%), and there were no serious systemic adverse reactions.

[0074] Example 8 This embodiment 8 provides a natural musk-invigorating, blood-activating, orifice-clearing, and vitiligo-removing tincture and its preparation process, specifically including the following steps: Step 1: Weigh the raw materials: 0.3 g musk, 120 g red peony root, 140 g chuanxiong rhizome, 120 g peach kernel, 120 g safflower, 50 g angelica root, and 100 g tribulus terrestris. Wash the red peony root, chuanxiong rhizome, safflower, and angelica root, cut them into 3 mm slices, and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:8 (mass ratio); form inclusion complex by stirring at 50°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 10 cycles using a high-pressure homogenizer at 1100 bar and 8°C to obtain a 2.5% w / v nano-suspension A with a pH of 6.2; The processed red peony root, chuanxiong rhizome, peach kernel, safflower, angelica root, and tribulus terrestris were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent, and the mass-to-volume ratio of raw materials (except musk) to solvent was 1:14. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. After extraction for 45min, extract B was obtained. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a flow rate of 2 BV / h, and loaded onto the column. After adsorption, the sample was washed with 3 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the sample was eluted once with 2 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 3 BV of 90% ethanol at a flow rate of 2 BV / h. The eluent D was prepared by a second elution at a flow rate of BV / h to obtain a colorless eluent. Step 3: Place 600ml of 75% ethanol in a light-proof preparation container, add menthol, azone, and propylene glycol in sequence, and stir to dissolve; add psoralen to eluent D and stir until completely dissolved; then slowly add nano suspension A and mix well, and add 75% ethanol to make up to 1L of mixture F. Step 4: Store the solution F in a sealed, light-protected container and age for 7 days. Then, use a 0.1μm microporous membrane for fine filtration to sterilize, thus completing the preparation of the musk-invigorating, blood-activating, orifice-clearing, and leukorrhea-removing tincture.

[0075] In this embodiment 8, the Tongqiao Huoxue Decoction was modified into a topical tincture. Local administration stimulates the activation of hair follicle melanocytes, improves local microcirculation, and promotes pigment recovery. It was used to treat patients with staged vitiligo. A case report is as follows: The patient is a 28-year-old female, diagnosed by Western medicine with segmental vitiligo (stable phase).

[0076] Symptoms: Well-defined, porcelain-white patches appear on the right side of the face along the distribution area of ​​the trigeminal nerve. Hair within the white patches turns white. The disease has lasted for 2 years and has not recently expanded. Accompanying symptoms include emotional depression, dark menstrual blood with clots, a purplish-dark tongue, and a wiry, hesitant pulse.

[0077] Skin lesion characteristics: Venous-associated dermatitis score of 8, bright blue-white fluorescence observed under Wood's lamp.

[0078] Treatment: The natural musk tincture prepared in this embodiment for promoting blood circulation, clearing the orifices, and removing leukorrhea was combined with narrow-spectrum medium-wave ultraviolet (NB-UVB) therapy.

[0079] Dosage and administration: Apply the tincture to the vitiligo area twice daily. After application, massage gently until absorbed. Receive NB-UVB irradiation twice a week, starting at 280 mJ / cm², increasing by 10%-15% each time.

[0080] Therapeutic effect observation: Pigmentation recovery rate after 6 months of treatment: 76.8% in the treatment group (tincture + NB-UVB) and 52.3% in the control group (NB-UVB alone); VASI 50 improvement rate: 85.0% in the treatment group and 60.0% in the control group; Time to follicular repigmentation: 3.2 weeks in the treatment group and 5.8 weeks in the control group; Repigmentation uniformity score: the treatment group was significantly better than the control group; Serum immune indicators: IL-17 and IFN-γ levels decreased significantly. Imaging observation: Dermoscopy showed more pronounced repigmentation around the hair follicles in the treatment group; confocal microscopy revealed a significant increase in the number of melanocytes in the basal layer. Relapse rate: 12 months after discontinuation of medication, the relapse rate was 18.2% in the treatment group and 41.7% in the control group. Safety evaluation: The incidence of mild local irritation was 12.5% ​​(tolerable), with no phototoxic reactions and no abnormal changes in liver and kidney function.

[0081] Example 9 This embodiment provides a musk-based lyophilized powder injection formulation for promoting blood circulation and clearing the orifices, and its preparation process, including the following steps: Step 1: Weigh the raw materials: 0.8 g of musk, 150 g of red peony root, 120 g of chuanxiong rhizome, 150 g of peach kernel, 150 g of safflower, and 150 g of notoginseng. Wash the red peony root, chuanxiong rhizome, and safflower, cut them into 3 mm slices, and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:8 (mass ratio); form inclusion complex by stirring at 50°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 12 cycles using a high-pressure homogenizer at 1400 bar and 13°C to obtain a 3.5% w / v nano-suspension A with a pH of 7.3; The processed red peony root, chuanxiong rhizome, peach kernel, safflower, and notoginseng were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent. The mass-to-volume ratio of raw materials (except musk) to solvent was 1:11. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. Extraction was carried out for 45 min to obtain extract B. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a flow rate of 2 BV / h, and loaded onto the column. After adsorption, the sample was washed with 3 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the sample was eluted once with 2 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 3 BV of 75% ethanol at a flow rate of 2 BV / h. The eluent D was prepared by a second elution at a flow rate of BV / h to obtain a colorless eluent. Step 3: In a sterile preparation vessel, add approximately 800 mL of water for injection and cool to 2-8°C. Under nitrogen protection, dissolve the prescribed amounts of mannitol, polysorbate 80, and disodium edetate sequentially. While stirring at high speed, add eluent D and nano-suspension A, which has been solubilized with 1 g of polysorbate 80. Adjust the total volume to 1000 mL with water for injection and adjust the pH to 6.9 with 0.1 mol / L HCl or NaOH. Step 4: Filter the solution sequentially through 0.45μm and 0.22μm microporous membranes for sterilization. Under Class A laminar flow protection, fill 2.0 mL of the filtrate into 7 mL sterile vials, partially stoppering each vial. Cool the filtrate to -45°C using a sterile freeze dryer and maintain this temperature for 2 hours. Then, lower the condenser temperature to -55°C, apply a vacuum, and control the pressure at 30 Pa. Slowly raise the temperature to -20°C and maintain it for 20 hours, then gradually raise it to 25°C and maintain it for 6 hours, ensuring the moisture content is below 2.0%. Finally, fully stopper and crimp seal the vial under vacuum or nitrogen purging conditions to obtain the lyophilized powder for injection.

[0082] Example 9 of this study was used to treat acute ischemic stroke: The treatment group received thrombolytic therapy plus lyophilized musk powder for promoting blood circulation and clearing the orifices, 600ml each time, dissolved in 250 mL of 0.9% sodium chloride injection, administered intravenously once daily for 14 days; the control group received thrombolytic therapy alone. After 90 days of treatment: the improvement rate of neurological deficit scores in the treatment group was 85%, significantly higher than the 70% in the control group; the proportion of good functional prognosis in the treatment group was 78%, significantly higher than the 65% in the control group. The results indicate that, in addition to standard thrombolytic therapy, the combined use of lyophilized musk powder for promoting blood circulation and clearing the orifices can more effectively promote neurological function recovery, improve prognosis, and does not increase the risk of bleeding, demonstrating its value in the acute treatment of promoting blood circulation, removing blood stasis, clearing the orifices, and awakening the brain.

[0083] Example 10 This embodiment provides a musk-infused capsule for promoting blood circulation, clearing the orifices, and improving intelligence, and its preparation process, including the following steps: Step 1: Weigh the raw materials: 0.8 g musk, 200 g red peony root, 150 g chuanxiong rhizome, 120 g peach kernel, 120 g safflower, 100 g polygala root, 60 g acorus tatarinowii rhizome, and 120 g notoginseng. Wash the red peony root, chuanxiong rhizome, peach kernel, safflower, polygala root, acorus tatarinowii rhizome, and notoginseng, then cut them into 3 mm slices and dry them. Wash the peach kernel and grind it into a paste. Step 2: Extract musk extract using a musk:ethanol ratio of 1:10 (mass ratio); form inclusion complex by stirring at 50°C for 3 hours using a saturated aqueous solution method with a musk extract:β-cyclodextrin molar ratio of 1:1; disperse the inclusion complex in an aqueous solution containing 0.5% poloxamer 188, and homogenize for 15 cycles using a high-pressure homogenizer at 1500 bar and 15°C to obtain a 4% w / v nano-suspension A with a pH of 5.8; The processed red peony root, chuanxiong rhizome, peach kernel, safflower, polygala root, acorus tatarinowii rhizome, and notoginseng were placed in the extraction column of a dynamic circulating ultrasonic countercurrent device. 60% ethanol was used as the solvent, and the mass-to-volume ratio of raw materials (except musk) to solvent was 1:15. The extraction temperature was 60℃, the ultrasonic power was set to 500W (pulse mode: 3s working, 2s intermittent), the ultrasonic frequency was 28Hz, and the solvent flow rate was 1.5 L / min. After extraction for 45min, extract B was obtained. Extract B was subjected to reduced pressure at 60℃ and -0.08 MPa to recover ethanol, and concentrated to a fragrance paste with a relative density of 1.10~1.15 (measured at 60℃). Then, three times the volume of 95% ethanol was slowly added to the fragrance paste while stirring, until the alcohol content reached approximately 70%. The mixture was then allowed to stand at 4℃ for 24 hours to allow impurities to precipitate completely. The supernatant was then collected, filtered, and the ethanol was recovered and concentrated to a thick paste with a relative density of 1.20~1.25 (measured at 60℃). The thick paste was dispersed in water using an HPD-100 macroporous adsorption resin column with a flow rate of 2 BV / h, and loaded onto the column. After adsorption, the column was washed with 5 BV of purified water at a flow rate of 3 BV / h. After discarding the washings, the column was eluted once with 3 BV of 70% ethanol at a flow rate of 2 BV / h, followed by elution with 4 BV of 95% ethanol at a flow rate of 2 BV / h. The eluent was eluted twice at a flow rate of BV / h to obtain a colorless eluent D. The eluent D was then dried into a dry extract powder using spray drying technology. Step 3: Mix eluent D and nano suspension A in a mixer, and add microcrystalline cellulose as a filler and micronized silica gel as a flow aid. Mix thoroughly for more than 30 minutes to ensure uniformity. Step 4: Using a fully automatic capsule filling machine, in an environment of 18~26℃ and relative humidity below 45%, select No. 1 empty capsules for metering and filling; polish the filled capsules to remove surface powder; then seal them with aluminum-plastic blister packs to complete the preparation of Musk Blood Activating and Orifice Clearing and Intelligence-Enhancing Capsules.

[0084] Example 10 was used to treat mild vascular cognitive impairment: the treatment group took 2 capsules three times a day for 24 weeks, while the control group took the basic drug nicergoline. After one course of treatment, the MoCA score of the treatment group was 5.2±1.3, which was significantly higher than that of the control group (2.8±1.1). The improvement rate in the treatment group (42.5%) was 16.7% higher than that in the control group (25.8%). These results indicate that the Musk-Invigorating-Blood-Activating-Intelligence Capsules can significantly improve the cognitive function of patients with vascular cognitive impairment and provide effective clinical application value.

[0085] The above description is merely a specific embodiment of the present invention, enabling those skilled in the art to understand or implement the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention.

[0086] It should be understood that the present invention is not limited to the content already described above, and various modifications and changes can be made without departing from its scope. The scope of the present invention is limited only by the appended claims.

Claims

1. A musk-based blood-activating and orifice-clearing compound, characterized in that, The ingredients include the following parts by weight: 0.15-0.8 parts musk, 60-200 parts red peony root, 80-200 parts chuanxiong or danshen, 60-150 parts peach kernel, and 60-150 parts safflower.

2. A preparation process for a musk-based blood-activating and orifice-clearing compound, characterized in that, Prepared according to the process flow of "decoction → concentration → alcohol precipitation → blending → sterilization", among which, In the decoction process: Musk and β-cyclodextrin are encapsulated to form an inclusion complex, which is then nano-sized to form nano-suspension A; In the concentration process: Red peony root, Sichuan lovage rhizome or salvia miltiorrhiza, peach kernel, and safflower are placed in a dynamic circulating ultrasonic countercurrent device to extract extract B; In the alcohol precipitation process: the extract B is separated by membrane separation to obtain filtrate C, and the filtrate C is adsorbed and eluted onto a macroporous adsorption resin column to obtain eluent D.

3. The preparation process of the musk-invigorating and orifice-clearing compound according to claim 2, characterized in that, Includes the following steps: Step 1: Weigh the raw materials according to the set mass proportions. Wash the red peony root, chuanxiong rhizome or danshen root, and safflower, then slice and dry them. Wash the peach kernels and grind them into a paste. Step 2: First, extract musk extract using alcohol extraction; then, treat the extracted musk extract with β-cyclodextrin inclusion and low-temperature nano-dispersion to obtain nano-suspension A; then, extract other raw materials except musk by dynamic circulation ultrasonic countercurrent extraction to obtain extract B; extract B is then separated by membrane separation through ceramic microfiltration membrane or ultrafiltration membrane to form filtrate C; then, filtrate C is adsorbed and eluted onto a macroporous adsorption resin column to obtain eluent D; Step 3: Mix the nano suspension A and the eluent D to form solution E, and add flavoring agent and stabilizer to solution E to finally form solution F; Step 4: Fill and sterilize the solution F sequentially to complete the preparation of the musk blood-activating and orifice-clearing compound.

4. The preparation process of the musk-invigorating and orifice-clearing compound according to claim 2, characterized in that, In step 2, the mass ratio of musk to ethanol is 1:5 to 1:10; the molar ratio of musk extract to β-cyclodextrin inclusion is 1:1 to 1:

2.

5. The preparation process of the musk-invigorating and orifice-clearing compound according to claim 2, characterized in that, The temperature for the encapsulation process in step 2 is 50℃~80℃.

6. The preparation process of the musk-invigorating and orifice-clearing compound according to claim 2, characterized in that, In step 2, the low-temperature nano-dispersion nano-scale equipment is a high-pressure homogenizer, and the specific process parameters are as follows: reaction temperature is 0℃~15℃, high-pressure homogenization pressure is 500~1500 bar, and homogenization cycle number is 5~15 times.

7. The preparation process of the musk-invigorating and orifice-clearing compound according to claim 2, characterized in that, The concentration of the nano-suspension A is 1%~5% w / v, and the pH value is 6~8.

8. The preparation process of the musk-invigorating and orifice-clearing compound according to claim 2, characterized in that, In step 2, during dynamic circulating ultrasonic countercurrent extraction, the mass ratio of raw materials other than musk to solvent is 1:8 to 1:

15.

9. The preparation process of the musk-invigorating and orifice-clearing compound according to claim 2, characterized in that, The specific process of elution in step 2 is as follows: First, wash with 2-5 column volumes of purified water to remove unadsorbed water-soluble impurities; then elute once with 2-3 column volumes of 70% ethanol, and then elute a second time with 3-5 column volumes of 70%-95% ethanol until the eluent is colorless.

10. The preparation process of the musk-invigorating and orifice-clearing compound according to any one of claims 2 to 9, for use in the preparation of syrups, pills, gels, films, patches, tinctures, lyophilized powder injections, sprays, and capsules.

Images