Headache capsule and preparation method thereof

Abstract

The invention is applicable to the technical field of traditional Chinese medicine preparations, and provides a headache capsule and a preparation method thereof.The headache capsule is prepared from 11 parts of lemonfragrant angelica root, 25 parts of kudzuvine root, 25 parts of ligusticum wallichii, 15 parts of fructus forsythiae, 15 parts of cocklebur fruit, 7 parts of radix bupleuri and pharmaceutically acceptable auxiliary materials, and the formula follows the principle of monarch, minister, assistant and guide; the traditional Chinese medicine can be used for treating tension, vascular and wind-cold common cold and nasosinusitis related headache; the preparation method comprises the steps of raw material pretreatment, differential extraction (the ligusticum wallichii volatile oil is subjected to supercritical COextraction or steam distillation, and other medicinal materials are subjected to water extraction or alcohol extraction), concentration and drying, volatile oil inclusion, granulation and capsule filling. The capsule is scientific in formula, wide in application range, advanced in process, capable of retaining active ingredients and reducing the toxicity of the fructus xanthii, fast in effect taking and high in compliance, the clinical total effective rate is larger than or equal to 90%, the side effect incidence rate is smaller than or equal to 2%, and the capsule is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, and particularly relates to a headache capsule and a preparation method thereof. BACKGROUND

[0002] Headache is a common neurological symptom worldwide, among which tension headache and migraine are the main types, and there are also vascular headache and headache caused by nasal catarrh, which seriously affects the quality of life and work efficiency.

[0003] The existing treatment drugs have obvious defects: in terms of western medicine, non-steroidal anti-inflammatory drugs only relieve symptoms, and long-term use can easily cause gastrointestinal damage and drug overdose headache; triptans have a narrow application range and high cardiovascular risk, and are expensive; prophylactic western medicine has a slow effect, large side effects, and low patient compliance.

[0004] Although traditional Chinese medicine has the potential to treat both symptoms and root causes, it has significant defects: most prescriptions are targeted at a single type of headache, and have a narrow application range; the simple process does not take into account the poor solubility of effective components of medicinal materials, for example, the loss of volatile oil of Chuanxiong Rhizoma is more than 60% when decocted in water, and the extraction rate of puerarin and forsythoside is less than 50%; preparations containing Xiang'ezi do not control toxic components, which can easily cause liver damage; most of the dosage forms are decoctions or tablets, which are inconvenient to take, have a slow disintegration, and have low patient compliance.

[0005] In summary, there is an urgent need to develop headache treatment drugs with scientific prescription, advanced process, safety and effectiveness, and wide application. SUMMARY

[0006] The present application provides a headache capsule and a preparation method thereof, aiming to retain effective components and reduce the risk of toxicity through a differential extraction process.

[0007] The present application is implemented in the following manner: a headache capsule is prepared from the following weight parts of raw medicinal materials and auxiliary materials: The raw medicinal materials include: 11 parts of Xiangbaishi, 25 parts of Gegen, 25 parts of Chuanxiong Rhizoma, 15 parts of Lianqiao, 15 parts of Xiang'ezi, and 7 parts of Chaihu; The auxiliary materials include: a filler, a disintegrant, and a binder, the filler is selected from one or more of microcrystalline cellulose, lactose, and starch, the disintegrant is selected from one or more of crospovidone, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose, and the binder is selected from one or more of 80% ethanol solution and 5% hydroxypropyl methyl cellulose solution; the headache capsule is used for treating tension headache, vascular headache, headache caused by wind-cold cold and nasal catarrh-related headache, and the content of puerarin in each capsule is ≥7.8 mg, the content of Chuanxiongzhizine is ≥0.48 mg, and the content of Xiang'ezi glycoside is ≤0.05 mg / g (calculated based on the mass of the dry powder of the raw medicinal material extract).

[0008] Preferably, the amount of the auxiliary agent is in the range of 5%-15% of the amount of the dry powder of the raw medicinal material extract, 3%-8% of the amount of the dry powder of the raw medicinal material extract, and 10%-20% of the total amount of the dry powder of the raw medicinal material extract, the volatile oil inclusion compound, and the auxiliary agent; the capsule shell of the headache capsule is a hypromellose capsule shell, the specification is No. 0 or No. 1, the loading amount of each capsule is 0.25-0.35 g, the loading amount difference is within ±7.5%, and the disintegration time is less than or equal to 30 minutes.

[0009] The present application provides a preparation method of a headache capsule for preparing the headache capsule described above, comprising the following steps: S1, raw medicinal material pretreatment: taking Xiangbaishi, Gegen, Chuanxiong, Lianqiao, Cang'erzi, and Chaihu, respectively selecting and removing impurities, rapidly washing 2-3 times (10-15 seconds each time) with purified water, and then cutting Xiangbaishi, Gegen, Chuanxiong, Cang'erzi, and Chaihu into drinking pieces with a thickness of 2-4 mm, and placing them in a hot air circulation oven at 60-70°C for drying until the water content is less than or equal to 8%, for standby; S2, effective component extraction: a. Chuanxiong volatile oil extraction: taking the Chuanxiong drinking pieces pretreated in step S1, extracting the volatile oil by supercritical CO2 extraction or water vapor distillation; if supercritical CO2 extraction is used, the extraction conditions are: extraction pressure 25-35 MPa, extraction temperature 35-45°C, CO2 flow rate 20-30 L / h, and extraction time 1.5-2.5 h; if water vapor distillation is used, the extraction conditions are: adding 8-12 times the amount of purified water, and distillation time 2-4 h; collecting the volatile oil, storing it at 5-10°C in the dark, and standby; b. mixed medicinal material extraction: taking the Xiangbaishi, Gegen, Lianqiao, Cang'erzi, and Chaihu drinking pieces pretreated in step S1, mixing them evenly, adding 6-10 times the amount of purified water or 60%-80% ethanol, if water extraction, soaking for 0.5-1.5 h and then heating to boiling, and micro-boiling decoction 1-2 times (1-2 h for the first time and 1 h for the second time); if alcohol extraction, heating to reflux extraction 1-2 times (2 h for the first time and 1.5 h for the second time); combining the extraction liquid, filtering with 100-120 mesh filter cloth, collecting the filtrate, and standby; S3, concentration and drying: the filtrate collected in step S2b is placed in a vacuum concentration tank, and concentrated under reduced pressure at a vacuum degree of -0.08 to -0.09 MPa and a temperature of 50-60°C to obtain a clear paste with a relative density of 1.20-1.25 (hot measurement at 60°C); the clear paste is dried by spray drying or vacuum drying; if spray drying, the conditions are: inlet air temperature 170-190°C, outlet air temperature 75-85°C, and feed rate 10-15 mL / min; if vacuum drying, the conditions are: vacuum degree -0.09 MPa and temperature 55-65°C; after drying, the dry powder of the extract of the crude drug (moisture content ≤5%) is obtained and reserved for use; S4, volatile oil inclusion: the volatile oil collected in step S2a is taken, β-cyclodextrin is added, the mass ratio of the volatile oil to β-cyclodextrin is 1:5-1:8, and 3-5 times the amount of purified water is added, and then stirred at a speed of 300-500 r / min at 40-50°C for 1-2 h, and then placed in a 4°C refrigerator for cold storage for 12-24 h, and then filtered (0.45 μm microporous filter membrane), and the inclusion compound is collected, and dried at 60-70°C to a moisture content of ≤5% to obtain the volatile oil inclusion compound (inclusion rate ≥90%) and reserved for use; S5, granulation: the dry powder of the extract of the crude drug obtained in step S3 and the volatile oil inclusion compound obtained in step S4 are mixed with excipients (using a three-dimensional mixer, mixed at 200 r / min for 15-20 min), and a binder is added to prepare a soft material (the soft material is suitable to be formed into a ball by hand, and scattered by light pressure); the soft material is granulated through a 16-20 mesh screen to obtain wet granules; the wet granules are dried in a hot air circulation oven at 55-65°C to a moisture content of 3%-5%, and then sieved through a 14-18 mesh screen to obtain dry granules (18-40 mesh granules account for ≥90%); S6, filling capsules: the dry granules obtained in step S5 are filled into hydroxypropyl methylcellulose capsule shells, and each capsule contains 0.25-0.35 g, thereby obtaining headache capsules.

[0010] Preferably, in step S2a, when the volatile oil of Chuanxiong Rhizoma is extracted by supercritical CO2 extraction, the extraction pressure is 30 MPa, the extraction temperature is 40°C, the CO2 flow rate is 25 L / h, and the extraction time is 2 h; when extracted by steam distillation, 10 times the amount of purified water is added, and the distillation time is 3 h.

[0011] Preferably, in step S2b, when water extraction is used, 8 times the amount of purified water is added, soaked for 1 h, and decocted twice, with the first decoction for 1.5 h and the second decoction for 1 h; when alcohol extraction is used, 8 times the amount of 70% ethanol is added, and extracted by reflux twice, with the first reflux for 2 h and the second reflux for 1.5 h.

[0012] Preferably, in the step S4, the mass ratio of volatile oil to β-cyclodextrin is 1:6, 4 times of purified water is added, and the inclusion is stirred at 45℃ and 400r / min for 1.5h, and then the mixture is cooled and placed for 18h; in the step S5, the excipient is microcrystalline cellulose and crosslinked polyvinylpyrrolidone, the amount of microcrystalline cellulose is 10% of the mass of the dry powder of the extract of raw medicinal materials, the amount of crosslinked polyvinylpyrrolidone is 5% of the mass of the dry powder of the extract of raw medicinal materials, and the amount of the adhesive (80% ethanol solution) is 15% of the total mass of the dry powder of the extract of raw medicinal materials, the volatile oil inclusion and the excipient.

[0013] Preferably, in the step S5, the granulation is performed through an 18-mesh sieve, and the dried product is sieved through a 16-mesh sieve; in the step S6, the capsules are filled by using a full-automatic capsule filling machine at a filling speed of 400 capsules per minute, and then the capsules are subjected to appearance inspection, and the capsules with deformation or powder leakage are removed, and the microbial limit of the final product needs to meet the following requirements: total bacterial count ≤1000cfu / g, total mold and yeast count ≤100cfu / g, no Escherichia coli and Salmonella.

[0014] Compared with the related art, the headache capsule and the preparation method thereof have the following beneficial effects: 1. Scientific formula and significant curative effect: covering four types of headaches, the total effective rate is ≥90%, the cure rate is 35%-38%, and the recurrence rate after 3 months of drug withdrawal is only 8%-10%, which is much better than existing drugs; 2. Advanced process and high utilization rate: differential extraction makes the retention rate of volatile oil of Chuanxiong Rhizoma ≥85%, and the extraction rate of puerarin and forsythoside ≥80%; the inclusion of volatile oil improves the bioavailability by 30%-40%, and the capsule disintegration is ≤30 minutes; 3. Controllable toxicity and high safety: the extraction process of Xiang'e Zi is optimized, the content of Xiang'e Zi glycoside in the extract is ≤0.05mg / g, the incidence of side effects is only 1%-2%, and there is no serious adverse reaction; 4. Suitable dosage form and easy industrialization: the capsule masks the bitter taste, the dosage is accurate, the patient compliance is ≥90%, the process parameters are clear, the batch difference is small, the production cost is low, and it is suitable for large-scale production. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figure 1 The flowchart of the preparation method of the headache capsule provided by the present application is shown. DETAILED DESCRIPTION

[0016] The present application will be further described below in combination with the drawings and embodiments.

[0017] Example 1: Preparation of the headache capsule (supercritical CO2 extraction of volatile oil of Chuanxiong Rhizoma + water extraction) 1.1 Raw material preparation Raw medicinal materials: Angelica dahurica, Pueraria lobata, Ligusticum chuanxiong, Forsythia suspensa, Xanthium sibiricum, Bupleurum chinense; Excipients: Microcrystalline cellulose, crospovidone, β-cyclodextrin, 80% ethanol solution (prepared in-house, pharmaceutical grade ethanol + purified water), No. 0 hydroxypropyl methylcellulose capsule shell.

[0018] 1.2 Preparation steps 1. Raw material pretreatment: Take 110g of Angelica dahurica, 250g of Pueraria lobata, 250g of Ligusticum chuanxiong, 150g of Forsythia suspensa, 150g of Xanthium sibiricum, and 70g of Bupleurum chinense. Select and remove impurities from each ingredient (remove moldy pieces from Angelica dahurica, remove lignified parts from Pueraria lobata, and remove fibrous roots from Ligusticum chuanxiong). Rinse quickly three times with purified water (12 seconds each time), then cut into 3mm thick slices. The medicinal slices were placed in a hot air circulating oven (model: CT-CO) and dried at 65℃ for 4 hours. The moisture content was measured to be 6.8%, and the slices were then set aside for later use.

[0019] 2. Extraction of active ingredients: Extraction of volatile oil from Ligusticum chuanxiong: Take 250g of Ligusticum chuanxiong slices and place them in a supercritical CO2 extractor (model: HA221-50-06). Set the extraction pressure to 30MPa, extraction temperature to 40℃, CO2 flow rate to 25L / h, and extraction time to 2h. Collect 1.8mL of volatile oil (density 0.92g / mL, mass 1.656g), store it in a 5℃ refrigerator away from light, and use it later. Extraction of mixed medicinal materials: Take 110g of Angelica dahurica, 250g of Pueraria lobata, 150g of Forsythia suspensa, 150g of Xanthium sibiricum, and 70g of Bupleurum chinense, mix them evenly, add 8 times the amount (8×830g=6640mL) of purified water, and soak for 1 hour; then place them in a multi-functional extraction tank (model: TQ-50), heat to boiling, and simmer twice, the first time for 1.5 hours and the second time for 1 hour; combine the two decoctions, filter with a 100-mesh filter cloth, and collect about 5800mL of filtrate for later use.

[0020] 3. Concentration and drying: The filtrate was placed in a vacuum concentration tank (model: ZN-100), the vacuum degree was set to -0.085MPa, the temperature was 55℃, and the concentration was carried out under reduced pressure for 3 hours to obtain approximately 420g of clear extract with a relative density of 1.23 (measured at 60℃). The extract was placed in a spray dryer (model: LPG-5), the inlet air temperature was set to 180℃, the outlet air temperature to 80℃, the feed rate to 12mL / min, and the spray drying was carried out for 2.5h to obtain 89.5g of dry powder of extract (moisture content 4.2%), which was then set aside for later use.

[0021] 4. Inclusion of volatile oils: Take 1.656g of volatile oil from Ligusticum chuanxiong, add 9.936g of β-cyclodextrin (volatile oil to β-cyclodextrin mass ratio 1:6), and then add 4 times the amount of purified water (4×11.592g=46.368mL); Place it in a constant temperature water bath stirrer (model: HH-S) and stir at 45℃ for 1.5 hours (stirring speed 400r / min). Then, it was placed in a refrigerator at 4℃ and allowed to stand for 18 hours. It was then filtered (using a 0.45μm microporous membrane) to collect the inclusion complex. It was then dried at 65℃ for 3 hours to obtain 10.8g of volatile oil inclusion complex (moisture content 4.5%, inclusion rate 92.3%) for later use.

[0022] 5. Granulation: Take 89.5g of the extract powder, 10.8g of the volatile oil inclusion complex, add 9.0g of microcrystalline cellulose (10% of the extract powder mass) and 4.5g of crospovidone (5% of the extract powder mass), place them in a three-dimensional mixer (model: SYH-10), mix at 200r / min for 18min to obtain 113.8g of mixed powder; Add 17.1g of 80% ethanol solution (15% of the mass of the mixed powder) to prepare a soft material (which can be formed into a ball by hand and crumbles easily when pressed lightly). The soft material was granulated through an 18-mesh sieve to obtain wet granules; the wet granules were placed in a hot air circulating oven and dried at 60°C for 2 hours, and the moisture content was measured to be 3.8%; the granules were then sized through a 16-mesh sieve to obtain 110.2g of dry granules (93.5% of which were 18-40 mesh granules).

[0023] 6. Filler capsules: The dry granules were placed in a fully automatic capsule filling machine (model: NJP-400) and filled into No. 0 hydroxypropyl methylcellulose capsule shells. The amount per capsule was set to 0.3g, and a total of 367 capsules were prepared.

[0024] 1.3 Quality Inspection 1. Appearance: The capsules are clean in appearance, without spots or deformation, and have a uniform color (light yellow). 2. Content weight variation: 20 capsules were randomly selected and the content weight was measured. The average value was 0.302g, and the content weight variation range was -4.2% to +3.8%, which meets the requirements of the Capsule section of the 2020 edition of the Chinese Pharmacopoeia, Part IV (within ±7.5%). 3. Disintegration time limit: The disintegration time was tested using a disintegration time limit tester (model: BJ-1), and the disintegration time was 22 minutes, which meets the requirements (≤30 minutes). 4. Content of active ingredients: HPLC analysis showed that each capsule contained 8.2 mg of puerarin, 0.22 mg of imperatorin, 0.55 mg of tetramethylpyrazine, 0.18 mg of forsythoside, and 0.042 mg / g of xanthin (based on dry powder). 5. Microbial limits: Total bacterial count ≤1000 cfu / g, total mold and yeast count ≤100 cfu / g, free of Escherichia coli and Salmonella, meeting pharmaceutical requirements.

[0025] 1.4 Stability Test 1. Accelerated testing: The capsules were placed in a constant temperature and humidity chamber at 40℃±2℃ and relative humidity (RH) 75%±5% for 6 months, with monthly samples taken for testing. Appearance: No obvious changes; Disintegration time limit: 22-25 minutes; Content of active ingredients: The content change rate of puerarin, tetramethylpyrazine, etc., is ≤3%; Microbial limits: Meets requirements.

[0026] 2. Long-term test: The capsules were placed in an environment of 25℃±2℃ and RH60%±5% for 12 months, with samples taken and tested every 3 months. No significant changes were observed in any of the indicators, and the change rate of the effective ingredient content was ≤5%, indicating good stability.

[0027] 1.5 Clinical efficacy trial 1. Subjects: 200 patients diagnosed with tension headache were selected, including 86 males and 114 females, aged 18-65 years, with a disease duration of 3 months to 5 years. They were randomly divided into a treatment group (100 cases) and a control group (100 cases).

[0028] 2. Medication regimen: Treatment group: Take 2 headache capsules each time, 3 times a day, prepared in Example 1, for 4 weeks; Control group: Take 3 capsules of a commercially available headache capsule each time, 3 times a day, for 4 weeks.

[0029] 3. Criteria for evaluating therapeutic efficacy: Cure: Headache symptoms completely disappeared, with no recurrence within 3 months; Significant effect: headache symptoms are significantly reduced, the frequency of attacks is reduced by ≥70%, and the visual analog scale (VAS) score for pain is reduced from 8-10 points to 2-3 points; Effective: Headache symptoms are reduced, frequency of attacks is reduced by 30%-69%, and VAS score drops to 4-5; Ineffective: Headache symptoms do not improve or worsen, and the frequency of attacks decreases by <30%.

[0030] 4. Experimental Results: Group Example Recovery (example) Effective (example) Effective (example) Ineffective (example) Total effective rate (%) Side effect incidence (%) Treatment group 100 38 42 12 8 92 1 (mild abdominal distension) Control group 100 22 33 20 25 75 8 (gastrointestinal discomfort) Example 2: Preparation of headache capsules (steam distillation extraction of Ligusticum chuanxiong volatile oil + alcohol extraction) 2.1 Raw material preparation Same as Example 1, except that the excipients were changed to lactose, sodium carboxymethyl starch, and 5% hydroxypropyl methylcellulose solution (homemade).

[0031] 2.2 Preparation steps 1. Raw material pretreatment: Same as in Example 1, the moisture content of the medicinal slices is 7.2%.

[0032] 2. Extraction of active ingredients: Extraction of volatile oil from Ligusticum chuanxiong: Take 250g of Ligusticum chuanxiong slices, place them in a steam distillation apparatus, add 10 times the amount (2500mL) of purified water, heat and distill for 3 hours, and collect 1.7mL of volatile oil (1.564g) for later use; Extraction of mixed medicinal materials: Take 110g of Angelica dahurica, 250g of Pueraria lobata, 150g of Forsythia suspensa, 150g of Xanthium sibiricum, and 70g of Bupleurum chinense, mix them evenly, add 8 times (6640mL) of 70% ethanol, place in a reflux extraction tank, and heat and reflux twice, the first time for 2 hours and the second time for 1.5 hours; combine the reflux liquids, filter with a 100-mesh filter cloth, and collect about 5200mL of filtrate; place the filtrate in a rotary evaporator (model: RE-52AA), and recover the ethanol at -0.08MPa and 60℃ until there is no alcohol odor, to obtain about 380mL of concentrated alcohol extract for later use.

[0033] 3. Concentration and Drying: The alcohol extract concentrate was placed in a vacuum concentration tank and concentrated at -0.085 MPa and 55°C to a clear extract with a relative density of 1.22 (measured at 60°C) of approximately 390 g; then dried in a vacuum drying oven (model: DZF-6050) at -0.09 MPa and 60°C for 8 h, and pulverized to obtain 86.3 g of dry extract powder (moisture content 4.8%) for later use.

[0034] 4. Inclusion of volatile oil: Take 1.564g of volatile oil from Ligusticum chuanxiong, add 10.948g of β-cyclodextrin (mass ratio 1:7), add 4 times the amount of purified water, stir and include at 42℃ for 1.8h, refrigerate and stand for 20h, filter and dry to obtain 10.5g of volatile oil inclusion complex (inclusion rate 90.8%), for later use.

[0035] 5. Granulation: Take 86.3g of extract dry powder and 10.5g of volatile oil inclusion complex, add 6.9g of lactose (8% of the mass of extract dry powder) and 5.2g of sodium carboxymethyl starch (6% of the mass of extract dry powder), and mix in a three-dimensional mixer for 15min; add 12.4g of 5% hydroxypropyl methylcellulose solution (12% of the mass of mixed powder) to prepare soft material; granulate through a 16-mesh sieve, dry at 60℃ for 2.5h (moisture content 4.1%), and granulate through a 14-mesh sieve to obtain 108.9g of dry granules.

[0036] 6. Filling capsules: Fill the No. 0 capsule shells with 0.32g per capsule, and prepare a total of 340 capsules.

[0037] 2.3 Quality Inspection Appearance: Neat, light yellow; Filling volume variation: -3.9% to +4.1%, which meets the requirements; Disintegration time limit: 26 minutes; Active ingredient content: Each capsule contains 7.9mg of puerarin, 0.52mg of tetramethylpyrazine, and 0.045mg / g of xanthin (based on dry powder). Microbial limits: Meets requirements.

[0038] 2.4 Clinical efficacy trials 1. Subjects: 150 patients with vascular headache were selected, including 62 males and 88 females, aged 20-68 years, with a disease duration of 6 months to 8 years. They were randomly divided into a treatment group (100 cases) and a control group (50 cases).

[0039] 2. Medication regimen: Treatment group: Take 2 headache capsules each time, 3 times a day, for 4 weeks; Control group: Ibuprofen sustained-release capsules (0.3g / capsule), 1 capsule each time, twice a day, with an additional capsule taken when pain occurs, for a course of 4 weeks.

[0040] 3. Treatment Results: Group Example Recovery (example) Effective (example) Effective (example) Ineffective (example) Total effective rate (%) Side effect incidence (%) Treatment group 100 35 40 15 10 90 2 (abdominal distension, dry mouth) Control group 50 8 16 12 14 72 18 (gastrointestinal discomfort, dizziness) The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit the scope of protection of the invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on these embodiments, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art can still combine, add, delete, or otherwise adjust the features of the various embodiments of the present invention according to the circumstances without conflict or creative effort, thereby obtaining different technical solutions that do not fundamentally depart from the concept of the present invention. These technical solutions also fall within the scope of protection of the present invention.

Claims

1. A headache capsule, characterized in that, It is prepared from the following raw medicinal materials and excipients in parts by weight: The raw medicinal materials include: 11 parts Angelica dahurica, 25 parts Pueraria lobata, 25 parts Ligusticum chuanxiong, 15 parts Forsythia suspensa, 15 parts Xanthium sibiricum, and 7 parts Bupleurum chinense. The excipients include: fillers, disintegrants, and binders. The fillers are selected from one or more of microcrystalline cellulose, lactose, and starch. The disintegrants are selected from one or more of crospovidone, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose. The binders are selected from one or more of 80% ethanol solution and 5% hydroxypropyl methylcellulose solution.

2. The headache capsule according to claim 1, characterized in that, The dosage range of the excipients is as follows: the amount of filler is 5%-15% of the mass of the raw material extract powder, the amount of disintegrant is 3%-8% of the mass of the raw material extract powder, and the amount of binder is 10%-20% of the total mass of the raw material extract powder, volatile oil inclusion complex and excipients; the capsule shell of the headache capsule is hydroxypropyl methylcellulose capsule shell, with specifications of No. 0 or No. 1, the content of each capsule is 0.25-0.35g, the content difference is within ±7.5%, and the disintegration time is ≤30 minutes.

3. A method for preparing a headache capsule, characterized in that, The method is used to prepare the headache capsule as described in any one of claims 1-2, and the method includes the following steps: S1. Pretreatment of raw medicinal materials: Take Angelica dahurica, Pueraria lobata, Ligusticum chuanxiong, Forsythia suspensa, Xanthium sibiricum, and Bupleurum chinense, select and remove impurities, rinse quickly with purified water 2-3 times, then cut Angelica dahurica, Pueraria lobata, Ligusticum chuanxiong, Xanthium sibiricum, and Bupleurum chinense into slices with a thickness of 2-4 mm, place them in a 60-70℃ hot air circulating oven and dry until the moisture content is ≤8%, for later use; S2. Extraction of active ingredients: a. Extraction of volatile oil from Ligusticum chuanxiong: Take the pretreated Ligusticum chuanxiong slices from step S1 and extract the volatile oil using supercritical CO2 extraction or steam distillation. If using supercritical CO2 extraction, the extraction conditions are: extraction pressure 25-35 MPa, extraction temperature 35-45℃, CO2 flow rate 20-30 L / h, and extraction time 1.5-2.5 h. If using steam distillation, the extraction conditions are: add 8-12 times the amount of purified water, and distill for 2-4 h. Collect the volatile oil and store it at 5-10℃ away from light for later use. b. Extraction of mixed medicinal materials: Take the pretreated Angelica dahurica, Pueraria lobata, Forsythia suspensa, Xanthium sibiricum, and Bupleurum chinense slices from step S1, mix them evenly, and add 6-10 times the amount of purified water or 60%-80% ethanol. If water extraction is used, soak for 0.5-1.5 hours and then heat to boiling, and simmer for 1-2 times. If ethanol extraction is used, heat and reflux for 1-2 times. Combine the extracts, filter with a 100-120 mesh filter cloth, collect the filtrate, and set aside. S3. Concentration and Drying: The filtrate collected in step S2b is placed in a vacuum concentration tank and concentrated under reduced pressure at a vacuum degree of -0.08 to -0.09 MPa and a temperature of 50-60℃ to obtain a clear extract with a relative density of 1.20-1.

25. The clear extract is dried using either spray drying or vacuum drying. If spray drying is used, the conditions are: inlet air temperature 170-190℃, outlet air temperature 75-85℃, and feed rate 10-15 mL / min. If vacuum drying is used, the conditions are: vacuum degree -0.09 MPa and temperature 55-65℃. After drying, a dry powder of the raw material medicinal extract is obtained for later use. S4. Volatile oil inclusion: Take the volatile oil collected in step S2a, add β-cyclodextrin, the mass ratio of volatile oil to β-cyclodextrin is 1:5-1:8, then add 3-5 times the amount of purified water, stir and include at 300-500 r / min for 1-2 h at 40-50℃, then place in a refrigerator at 4℃ and let stand for 12-24 h, filter, collect the inclusion complex, dry at 60-70℃ until the moisture content is ≤5%, and obtain the volatile oil inclusion complex for later use; S5. Granulation: The raw material extract powder obtained in step S3, the volatile oil inclusion complex obtained in step S4, and the excipients are mixed evenly, and a binder is added to prepare a soft material; the soft material is granulated through a 16-20 mesh sieve to obtain wet granules; the wet granules are placed in a 55-65℃ hot air circulating oven and dried to a moisture content of 3%-5%, and then granulated through a 14-18 mesh sieve to obtain dry granules; S6. Filling capsules: Fill the capsule shells with the dry granules obtained in step S5, with each capsule containing 0.25-0.35g, to obtain headache capsules.

4. The method for preparing the headache capsule according to claim 3, characterized in that, In step S2a, when extracting the volatile oil of Ligusticum chuanxiong using supercritical CO2 extraction, the extraction pressure is 30 MPa, the extraction temperature is 40℃, the CO2 flow rate is 25 L / h, and the extraction time is 2 h; when extracting using steam distillation, 10 times the amount of purified water is added, and the distillation time is 3 h.

5. The method for preparing the headache capsule according to claim 3, characterized in that, In step S2b, when water extraction is used, add 8 times the amount of purified water, soak for 1 hour, and decoct twice, the first decoction for 1.5 hours and the second decoction for 1 hour; when alcohol extraction is used, add 8 times the amount of 70% ethanol, reflux extract twice, the first reflux for 2 hours and the second reflux for 1.5 hours.

6. The method for preparing the headache capsule according to claim 3, characterized in that, In step S4, the mass ratio of volatile oil to β-cyclodextrin is 1:

6. Four times the amount of purified water is added, and the mixture is stirred at 400 r / min for 1.5 h at 45°C and then refrigerated and allowed to stand for 18 h. In step S5, the excipients are microcrystalline cellulose and crospovidone. The amount of microcrystalline cellulose is 10% of the mass of the raw material extract dry powder, and the amount of crospovidone is 5% of the mass of the raw material extract dry powder. The binder is an 80% ethanol solution, and the amount is 15% of the total mass of the raw material extract dry powder, volatile oil inclusion complex, and excipients.

7. The method for preparing the headache capsule according to claim 3, characterized in that, In step S5, granulation is performed using an 18-mesh sieve, followed by drying and granulation using a 16-mesh sieve. In step S6, a fully automatic capsule filling machine is used to fill the capsules at a speed of 400 capsules / minute. After filling, the capsules are visually inspected, and deformed or leaking capsules are removed. The final product must meet the following microbial limits: total bacterial count ≤1000 cfu / g, total mold and yeast count ≤100 cfu / g, and no Escherichia coli or Salmonella.

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