Traditional Chinese medicine micro-powder capsule for promoting blood circulation to remove blood stasis, dispelling wind and eliminating dampness and activating meridians to stop pain

Abstract

The invention relates to the technical field of traditional Chinese medicine pharmacy, and discloses a traditional Chinese medicine micro-powder capsule based on functions of promoting blood circulation to remove blood stasis, dispelling wind and eliminating dampness and activating meridians to stop pain. 0.8%-1.2% of scorpion; 0.8%-1.2% of Chinese polyphaga; 0.8%-1.2% of safflower carthamus; 0.8%-1.2% of peach kernels; 0.8%-1.2% of zaocys dhumnade; 0.8% to 1.2% of frankincense; 0.8%-1.2% of ligusticum wallichii; 0.8%-1.2% of cortex moutan; 0.8% to 1.2% of myrrh; 0.8%-1.2% of notopterygium root; 0.8%-1.2% of radix angelicae pubescentis; 0.8%-1.2% of fructus lycii; 0.8%-1.2% of centipede; 15%-25% of a functional auxiliary material: 3%-5% of a nano dispersion carrier; and 3%-5% of an inclusion compound. By adopting a beta-cyclodextrin inclusion technology, volatile oil and a humid and hot environment can be effectively isolated, the stability of the volatile oil can be enhanced, by taking ligustrazine as an example, under an accelerated test condition, the retention rate of the ligustrazine in 6 months is up to 89.5%, and compared with a non-inclusion condition, the retention rate is improved, the degradation rate is reduced by 3.1 times, and the stability of the core component for promoting blood circulation to remove blood stasis in the storage and use process is ensured.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine pharmaceutical manufacturing, in particular to a traditional Chinese medicine micropowder capsule capable of promoting blood circulation, removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain. Background Art

[0002] In the field of Traditional Chinese Medicine, Chinese medicines that promote blood circulation and remove blood stasis, dispel wind and dampness play an important role in the treatment of traumatic injuries, rheumatoid arthritis, cardiovascular and cerebrovascular diseases, etc. With the development of pharmaceutical technology, Chinese medicine micropowder capsules have emerged. However, the existing Chinese medicine micropowder capsules have shortcomings in the preparation process. In the extraction process, traditional decoction methods, reflux extraction methods, etc., not only have low extraction efficiency, but also easily introduce impurities, affecting the purity and efficacy of the drug. In the drying process, commonly used methods such as oven drying are difficult to accurately control the temperature, which easily leads to the decomposition and denaturation of heat-sensitive active ingredients, reducing the activity of the drug. In the micronization process, how to ensure the uniformity and stability of the particle size of the micropowder and avoid micropowder agglomeration are also challenges faced by the existing technology.

[0003] In terms of formulation, traditional Chinese medicine formulas often rely on empirically determined ratios of medicinal ingredients, lacking in-depth research and precise control of the active ingredients within the herbs. For example, in classic formulas for promoting blood circulation and removing blood stasis, and dispelling wind and dampness, the proportions of herbs such as Chuanxiong, peach kernel, and Angelica dahurica often lack scientific basis and fail to fully consider the synergistic mechanisms between the active ingredients of each herb, resulting in the formula being unable to maximize its efficacy. Furthermore, existing formulas rarely consider the addition of adjuvants to improve the solubility and stability of the drug, resulting in suboptimal dissolution and absorption of the drug within the body. Summary of the Invention

[0004] In response to the shortcomings of the existing technology, the present invention provides a Chinese medicine micropowder capsule based on the effects of promoting blood circulation and removing blood stasis, dispelling wind and dampness, and unblocking meridians and relieving pain, which solves the many defects of existing Chinese medicine preparations for promoting blood circulation and removing blood stasis, dispelling wind and dampness, and unblocking meridians and relieving pain in dosage form, preparation process and formula, resulting in low drug dissolution rate, unstable efficacy and inconvenience in use.

[0005] To achieve the above objectives, the present invention is implemented by the following technical solution: a Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and unblocking meridians and relieving pain, comprising the following raw materials in percentage by mass:

[0006] Original medicinal material components (70% to 80%):

[0007] 2.1% to 2.5% earthworms;

[0008] 0.8% to 1.2% of scorpions;

[0009] 0.8%~1.2% ground beetle;

[0010] 0.8% to 1.2% safflower;

[0011] 0.8% to 1.2% peach kernel;

[0012] 0.8%~1.2% black snake;

[0013] 0.8% to 1.2% frankincense;

[0014] 0.8%-1.2% Chuanxiong;

[0015] 0.8%~1.2% Cortex Moutan;

[0016] 0.8% to 1.2% myrrh;

[0017] 0.8%~1.2% Notopterygium wilfordii;

[0018] 0.8%~1.2% Angelica dahurica;

[0019] 0.8% to 1.2% wolfberry;

[0020] 0.8% to 1.2% centipede;

[0021] Functional excipients (15% to 25%):

[0022] 3% to 5% nano-dispersed carrier;

[0023] 3% to 5% inclusion compound;

[0024] 5% to 8% water activity regulator;

[0025] 1% to 3% silicon dioxide;

[0026] 5% to 10% volatile oil phase of frankincense, frankincense and myrrh.

[0027] Preferably, the nanodispersion carrier is PVP K30.

[0028] Preferably, the inclusion compound is β-cyclodextrin.

[0029] Preferably, the water activity regulator is microcrystalline cellulose.

[0030] In addition, the present invention also provides a method for preparing a Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and unblocking meridians and relieving pain, comprising the following steps:

[0031] S1. Directed extraction of animal medicines including earthworms, scorpions, and centipedes, and low-temperature enzymatic hydrolysis to form enzymatic hydrolyzates;

[0032] S2, targeted extraction of botanicals including safflower, peach kernel, and wolfberry, and supercritical CO2 extraction;

[0033] S3, adding volatile oil and β-cyclodextrin in a molar ratio of 1:3, and performing molecular inclusion by ultrasound assistance;

[0034] S4, mixing the enzymatic hydrolysate with PVP K30, and nano-dispersing the mixture by high-pressure homogenization to form nanopowder;

[0035] S5, spray drying the nanopowder;

[0036] S6, mixing the inclusion compound, nanopowder and medicinal material ultrafine powder in equal amounts by self-increase to form a micropowder composite;

[0037] S7. Fill the micro powder into capsules under nitrogen protection environment.

[0038] Preferably, the low-temperature enzymatic hydrolysis enzyme is trypsin, the enzymatic hydrolysis pH is 6.5-8.0, and the temperature is 30°C-45°C.

[0039] Preferably, the supercritical CO2 extraction environment has a pressure of 10 MPa to 59 MPa, and the mass of the entrainer ethanol is 5% to 20%.

[0040] Preferably, the high-pressure homogenization environment is 500 bar to 1500 bar, and the homogenization times are 2 to 5 times.

[0041] Preferably, during the equal-incremental mixing process, the particle size distribution has a D90 difference of no more than 10 μm to 15 μm.

[0042] Preferably, the nitrogen filling protection pressure environment is 0.1MPa to 0.3MPa, and the nitrogen filling flow rate is 5L / min to 15L / min.

[0043] The present invention provides a Chinese medicine micropowder capsule that promotes blood circulation, dispels wind and dampness, and relieves pain. It has the following beneficial effects:

[0044] 1. The present invention adopts β-cyclodextrin inclusion technology to effectively isolate volatile oils from hot and humid environments, greatly enhancing their stability. Taking ligustrazine as an example, under accelerated test conditions (40°C / RH75%), the 6-month retention rate is as high as 89.5%. Compared with the case without inclusion, the retention rate is improved, the degradation rate is reduced by 3.1 times, and the peroxide value is only about a quarter of that without inclusion (8.6meq / kg vs. 32.7meq / kg), ensuring the stability of the core component of promoting blood circulation and removing blood stasis during storage and use, providing a solid guarantee for the long-term effectiveness of the drug.

[0045] 2. This invention successfully solves the dissolution barrier problem of peptide components in animal medicines due to their large molecular weight and strong hydrophobicity through PVP K30 nanodispersion and high-pressure homogenization technology. Taking centipede peptide as an example, the dissolution rate reached 73.6% in 15 minutes, which is 2.36 times higher than the traditional process (31.9%). This enables the drug to release active ingredients faster, significantly improving the speed of the drug's effect of dispelling wind and dampness, allowing patients to feel the therapeutic effect of the drug more quickly, and improving the timeliness and effectiveness of treatment.

[0046] 3. This invention utilizes gradient inclusion and low-temperature nanocrystallization processes to precisely protect active ingredients of varying polarity. The retention rate of boswellic acid under strong light increased from 44.1% in conventional processes to 82.3%, fully demonstrating the protective effect of this process on the active ingredient. This process avoids significant loss of active ingredients during processing, effectively extending the shelf life of the drug and ensuring consistent, effective medication for patients.

[0047] 4. The present invention utilizes multiple medicinal materials to work together to relax the tendons and dredge the meridians, as well as relieve pain. Centipede, frankincense, myrrh, etc. can dredge the meridians, allowing the smooth flow of qi and blood. This can effectively relieve numbness, pain, and other discomforts in the limbs, providing a good conditioning and therapeutic effect, helping patients restore normal limb function. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 Flow chart of the preparation method of the present invention. DETAILED DESCRIPTION

[0049] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0050] Please see the attached Figure 1 The embodiment of the present invention provides a Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredge meridians and relieve pain, comprising the following raw materials in percentage by mass:

[0051] Original medicinal material components (70% to 80%):

[0052] 2.1% to 2.5% earthworms;

[0053] 0.8% to 1.2% of scorpions;

[0054] 0.8%~1.2% ground beetle;

[0055] 0.8% to 1.2% safflower;

[0056] 0.8% to 1.2% peach kernel;

[0057] 0.8%~1.2% black snake;

[0058] 0.8% to 1.2% frankincense;

[0059] 0.8%-1.2% Chuanxiong;

[0060] 0.8%~1.2% Cortex Moutan;

[0061] 0.8% to 1.2% myrrh;

[0062] 0.8%~1.2% Notopterygium wilfordii;

[0063] 0.8%~1.2% Angelica dahurica;

[0064] 0.8% to 1.2% wolfberry;

[0065] 0.8% to 1.2% centipede;

[0066] Functional excipients (15% to 25%):

[0067] 3% to 5% nano-dispersed carrier;

[0068] 3% to 5% inclusion compound;

[0069] 5% to 8% water activity regulator;

[0070] 1% to 3% silicon dioxide;

[0071] 5% to 10% volatile oil phase of frankincense, frankincense and myrrh.

[0072] The nanodispersion carrier is PVP K30.

[0073] The inclusion compound is β-cyclodextrin.

[0074] The water activity regulator is microcrystalline cellulose.

[0075] In addition, the present invention also provides a method for preparing a Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and unblocking meridians and relieving pain, comprising the following steps:

[0076] S1. Directed extraction of animal medicines including earthworms, scorpions, and centipedes, and low-temperature enzymatic hydrolysis to form an enzymatic hydrolyzate, wherein the enzyme used for low-temperature enzymatic hydrolysis is trypsin, the enzymatic hydrolysis pH is 6.5-8.0, and the temperature is 30°C-45°C;

[0077] S2. Directed extraction of botanicals including safflower, peach kernel, and wolfberry, and supercritical CO2 extraction, the supercritical CO2 extraction environment is at a pressure of 10 MPa to 59 MPa, and the entrainer ethanol mass is 5% to 20%;

[0078] S3, adding volatile oil and β-cyclodextrin in a molar ratio of 1:3, and performing molecular inclusion by ultrasound assistance;

[0079] S4. Mix the enzymatic hydrolysate with PVP K30, and nano-disperse the mixture by high-pressure homogenization to form nanopowder. The high-pressure homogenization environment is 500 bar to 1500 bar, and the homogenization times are 2 to 5 times.

[0080] S5, spray drying the nanopowder;

[0081] S6. The inclusion compound, the nanopowder and the medicinal material ultrafine powder are mixed in equal amounts by self-incremental mixing to form a micropowder compound, wherein the difference in the particle size distribution at D90 does not exceed 10 μm to 15 μm during the equal-amount incremental mixing process;

[0082] S7. Fill the micro powder into capsules under a nitrogen protection environment. The nitrogen protection pressure environment is 0.1MPa~0.3MPa and the nitrogen flow rate is 5L / min~15L / min.

[0083] Example:

[0084] Example 1: High inclusion rate optimized type

[0085] The composition ratio (total amount 1000g) is as follows:

[0086] Table 1:

[0087]

[0088]

[0089] Preparation steps:

[0090] S1. Extract the volatile oil phase: put Chuanxiong, frankincense, and myrrh into a supercritical CO2 extraction kettle (35 MPa, 45°C) with 12% ethanol as the entrainer. Extract for 2 hours to obtain 55 g of volatile oil (purity>92% as determined by GC);

[0091] S2, molecular inclusion, volatile oil and β-cyclodextrin were mixed in a molar ratio of 1:3.5, sonicated at 40 kHz for 45 min (50°C), and the precipitate was collected by centrifugation (inclusion efficiency 96.3%);

[0092] S3, nano-dispersion, earthworm, scorpion, centipede enzymatic hydrolysate (trypsin pH 8.0, 50 ° C × 4h) and PVP K30 were mixed at a ratio of 1:2.7, high-pressure homogenization at 1800 bar for 4 cycles, and spray drying (inlet air 185 ° C, outlet air 85 ° C) to obtain nano powder (D50 = 163 nm);

[0093] S4, micro powder compounding, inclusion compound, nano powder, other medicinal material ultrafine powder (D90 = 13 μm) and auxiliary materials are mixed in equal amounts and gradually increased, and then filled with nitrogen.

[0094] Example 2: Fast dissolution optimized

[0095] The composition ratio (total amount 1000g) is as follows:

[0096] Table 2:

[0097]

[0098] Preparation steps:

[0099] S1, nano-dispersion enhancement, PVP K30 dosage increased to 7.5%, homogenization pressure increased to 2000 bar, cycled 5 times, obtained D50 = 128 nm nanoparticles (PDI = 0.18);

[0100] S2, inclusion process was improved, 0.1% Tween 80 was added as a solubilizer when the volatile oil was included with β-cyclodextrin, and the inclusion time was shortened to 25 minutes (inclusion rate 94.8%);

[0101] S3, water activity control: microcrystalline cellulose was added three times during the mixing phase, with an interval of 10 minutes between each addition, and the final Aw = 0.31.

[0102] Example 3: Stability-bioavailability balance

[0103] The composition ratio (total amount 1000g) is as follows:

[0104] Table 3:

[0105]

[0106]

[0107] Preparation steps:

[0108] S1, gradient inclusion technology, including two-stage inclusion: first, β-cyclodextrin was used to include Chuanxiong volatile oil (1:3), and the remaining cyclodextrin was used to include boswellic acid (1:2.5), with an inclusion rate of 95.1%;

[0109] S2, low-temperature nanocrystallization, maintaining the liquid temperature <15°C (ice-water jacket) during homogenization to prevent polypeptide denaturation, obtaining D50 = 145 nm particles (activity retention rate 98.7%);

[0110] S3, dynamic mixing process, using a three-dimensional motion mixer (speed 25rpm, inclination angle 30°), the mixing time is shortened by 40%, and the powder uniformity RSD is <3%.

[0111] Comparative Example:

[0112] Comparative Example 1: Degradation of the inclusion process (corresponding to Example 1)

[0113] Adjustment of component ratio: the dosage of β-cyclodextrin was reduced to 1% (originally 5%).

[0114] Preparation steps: According to the method of Example 1, a Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and unblocking meridians and relieving pain was prepared, wherein the β-cyclodextrin inclusion step was omitted, the volatile oil and the medicinal material powder were directly mixed, and the ultrasonic time was shortened to 15 minutes (originally 45 minutes).

[0115] Comparative Example 2: Weakened Dispersion Technology (Corresponding to Example 2)

[0116] Adjustment of the composition ratio: the dosage of PVP K30 was reduced to 3% (originally 7.5%).

[0117] Preparation steps: According to the method of Example 2, Chinese medicine micropowder capsules based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and unblocking meridians and relieving pain were prepared, wherein the high-pressure homogenization step was eliminated and ordinary stirring mixing was used instead of the nano-dispersion process. The volatile oil inclusion ratio remained the same, but the nano-carrier was not combined for synergistic enhancement.

[0118] Comparative Example 3: Process Reverse Adjustment (Corresponding to Example 3)

[0119] Preparation steps: cancel the gradient inclusion, mix Chuanxiong and frankincense oil and then uniformly include them (molar ratio 1:2), raise the temperature of the nano-process to 25°C (originally <15°C low temperature control), and change the mixing process to conventional two-dimensional stirring (originally three-dimensional dynamic mixing).

[0120] Comparative experiment:

[0121] Experiment 1: Comparison of volatile oil stability

[0122] Test Subject:

[0123] Example 1 (High inclusion rate optimized type)

[0124] Comparative Example 1 (no inclusion process)

[0125] Comparison variables:

[0126] Single variable: β-cyclodextrin inclusion process (present / absent)

[0127] Fixation conditions: volatile oil source, storage conditions (40°C / RH75%), detection time point

[0128] Experimental methods:

[0129] 1. Sample preparation:

[0130] Example 1: Preparation of capsule contents (containing β-cyclodextrin inclusion volatile oil) according to the process of Example 1

[0131] Comparative Example 1: The inclusion process was eliminated and the non-inclusion volatile oil was directly adsorbed on microcrystalline cellulose

[0132] 2. Accelerated test conditions: temperature 40°C, relative humidity 75%, aluminum-plastic blister packaging, sampling time points: 0 / 3 / 6 months

[0133] 3. Detection method:

[0134] Ligustrazine retention rate (HPLC detection, mobile phase acetonitrile-0.1% phosphoric acid water 35:65, flow rate 1.0 mL / min, detection wavelength 280 nm)

[0135] Sampling at 0 / 3 / 6 months, calculation of degradation rate constant (k)

[0136] Peroxide value (GB 5009.227-2016)

[0137] Assessing the degree of oil oxidation

[0138] Experimental data:

[0139] Table 4:

[0140]

[0141] Experimental summary:

[0142] In Example 1 using β-cyclodextrin inclusion technology, in an accelerated test (40°C / RH75%), the 6-month retention rate of ligustrazine reached 89.5%, which was significantly higher than that of the unincluded comparative example 1 (47.8%), and the degradation rate was reduced by 3.1 times. The comparison of peroxide values showed that the degree of oxidation of comparative example 1 was 3.8 times that of Example 1 (32.7 vs 8.6 meq / kg), verifying the antioxidant mechanism of molecular inclusion technology that isolates oxygen free radicals through hydrophobic cavities, solving the problem of rapid oxidative inactivation of volatile oils due to exposure to a humid and hot environment in traditional processes, and ensuring the long-term stability of the core ingredients for promoting blood circulation and removing blood stasis (such as ligustrazine).

[0143] Experiment 2: Comparison of dissolution rates of poorly soluble components

[0144] Test Subject:

[0145] Example 2 (fast dissolution optimized type)

[0146] Comparative Example 2 (without nanodispersion technology)

[0147] Comparison variables:

[0148] Single variable: PVP K30 + high pressure homogenization process (present / cancel)

[0149] Fixed conditions: same dissolution medium (pH 6.8 PBS), rotation speed (50 rpm)

[0150] Experimental methods:

[0151] 1. Dissolution conditions: dissolution apparatus (SOTAXAT7smart), medium: pH 6.8 PBS 900 mL, temperature 37 ± 0.5 ° C, paddle method 50 rpm

[0152] 2. Sampling and analysis:

[0153] Sampling time: 5 / 10 / 15 / 30 / 45 minutes, filtered with 0.45 μm filter membrane

[0154] Centipede polypeptide dissolution (UV method, λ = 280nm, standard curve y = 0.0215x + 0.003, R 2 =0.999)

[0155] Sampling is done at 5 / 15 / 30 minutes and T50 (time required for 50% dissolution) is calculated.

[0156] Experimental data:

[0157] Table 5:

[0158]

[0159] Experimental summary:

[0160] In Example 2, the 15-minute solubility of the centipede polypeptide reached 73.6% through PVPK30 nano-dispersion and high-pressure homogenization technology, while the traditional process (Comparative Example 2) was only 31.9%, and the dissolution rate was increased by 2.36 times. Particle size analysis showed that the D50 of the nanoparticles in Example 2 was 128nm (PDI=0.18), which was much better than the micron-sized aggregates in Comparative Example 2 (D50>2000nm), which was in line with the dissolution enhancement theory of the Noyes-Whitney equation. It overcomes the dissolution barrier caused by the large molecular weight and strong hydrophobicity of the polypeptide components in animal drugs, and provides key technical support for improving the onset speed of the wind-removing and dampness-removing efficacy.

[0161] Experiment 3: Comparison of bioavailability of active ingredients

[0162] Test Subject:

[0163] Example 3 (Stability-bioavailability balance type)

[0164] Comparative Example 3 (High Temperature Mixing + Non-Gradient Inclusion)

[0165] Comparison variables:

[0166] Single variable: gradient inclusion + low-temperature nanocrystallization (presence / cancellation)

[0167] Fixed conditions: dosage (based on body surface area), animal model (SD rat)

[0168] Experimental methods:

[0169] 1. Animal experiments:

[0170] SD rats (200±20g, n=8 / group), oral administration (equivalent human dose 50mg / kg)

[0171] Blood collection time: 0.5 / 1 / 2 / 4 / 8 / 12 / 24 hours, heparin anticoagulation, centrifugation to obtain plasma

[0172] 2. Active ingredient detection:

[0173] Earthworm plasmin: ELISA kit (Cusabio, CSB-E17066r), detection limit 0.1 ng / mL

[0174] Photodegradation of boswellic acid: light box (4500 Lux, 25 ° C × 10 days), HPLC detection of retention rate

[0175] Detection indicators:

[0176] 1. Concentration of earthworm plasmin in plasma (ELISA method, standard curve range 0.1-100 ng / mL)

[0177] Calculate AUC0-24h (area under the drug-time curve)

[0178] 2. Photodegradation rate of boswellic acid (HPLC detection, 4500 Lux light irradiation for 10 days)

[0179] Experimental data:

[0180] Table 6:

[0181]

[0182] Experimental summary: The gradient inclusion and low-temperature nano-process of Example 3 increased the in vivo bioavailability (AUC) of earthworm fibrinolytic enzyme to 2.1 times that of Comparative Example 3 (286.4 vs 136.2 ng·h / mL), confirming that low-temperature treatment can reduce polypeptide denaturation. The retention rate of boswellic acid under strong light increased from 44.1% in Comparative Example 3 to 82.3%, indicating that the gradient inclusion technology can specifically protect active ingredients of different polarities. Through the refined regulation of process parameters, the dual goals of stabilization and high efficiency are achieved, avoiding the loss of active ingredients in the processing link in traditional processes.

[0183] The present invention provides a Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredge meridians to relieve pain. By adopting β-cyclodextrin inclusion technology, it can effectively isolate volatile oils from the hot and humid environment, greatly enhancing its stability. Taking ligustrazine as an example, under the conditions of accelerated test (40°C / RH75%), the 6-month retention rate is as high as 89.5%, which is significantly improved compared to the case without inclusion. The degradation rate is reduced by 3.1 times, and the peroxide value is only about one-fourth of that without inclusion (8.6meq / kg vs. 32.7meq / kg), ensuring the stability of the core component of promoting blood circulation and removing blood stasis during storage and use, providing a solid guarantee for the long-term effectiveness of the drug. Through PVP K30 nano-dispersion and high-pressure homogenization technology, the dissolution barrier problem caused by the large molecular weight and strong hydrophobicity of the polypeptide components in animal medicines is successfully solved. Taking centipede polypeptide as an example, the 15-minute dissolution rate reaches 73.6%, which is 2.36 times higher than the traditional process (31.9%). This allows the drug to release its active ingredients more quickly, significantly increasing the speed of its wind-dispelling and dampness-removing effects, allowing patients to experience the drug's therapeutic effects more quickly, improving the timeliness and effectiveness of treatment. The synergistic effects of various medicinal ingredients dispel wind and dampness, activate blood circulation, remove blood stasis, and dredge meridians to relieve pain. Centipede is particularly effective in activating blood circulation, removing blood stasis, and dredge meridians to relieve pain. The "Medical Records of Chinese and Western Medicine" states: "Centipedes are the fastest-moving, opening up internal organs and external meridians, wherever qi and blood are concentrated." The scorpion and earthworm in the formula activate blood circulation and dissipate stagnation. The black-banded snake enters the liver meridian, dispelling wind, dredge meridians, and relieving pain. Chuanxiong rhizome relaxes tendons, activates meridians, dispels wind, and relieves pain. In the formula, it enters both the qi and blood components, activating blood circulation and promoting qi, making it a "qi-inducing medicine within the blood." Notopterygium wilfordii and Angelica dahurica pubescens unclog the meridians. Frankincense and myrrh in this formula demonstrate blood circulation, stasis, and pain-relieving effects. Therefore, the combination of the above-mentioned medicines can relieve the symptoms of back pain, numbness of hands and feet, morning stiffness, and difficulty walking caused by wind, cold and dampness, and have the effects of dispelling wind and dampness, promoting blood circulation and removing blood stasis, and dredging meridians to relieve pain.

[0184] The gradient inclusion and low-temperature nano-process of Example 3 increased the in vivo bioavailability (AUC) of earthworm fibrinolytic enzyme to 2.1 times that of the traditional process (286.4 ng·h / mL vs. 136.2 ng·h / mL). This means that the drug can be more fully absorbed and utilized by the human body, reducing drug waste, and can exert a stronger therapeutic effect at the same dose, improving the therapeutic effect of the drug. It is also possible to reduce the patient's medication dosage and reduce potential adverse drug reactions. Low-temperature treatment effectively reduces polypeptide denaturation, ensures the integrity of the active ingredient of the drug, enables the drug to better function in the body, further improves the therapeutic effect of the drug, and provides a more effective treatment plan for patients.

[0185] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain, characterized in that: Including the following raw materials in percentage by mass: Original medicinal material components (70% to 80%): 2.1% to 2.5% earthworms; 0.8% to 1.2% of scorpions; 0.8%~1.2% ground beetle; 0.8% to 1.2% safflower; 0.8% to 1.2% peach kernel; 0.8%~1.2% black snake; 0.8% to 1.2% frankincense; 0.8%-1.2% Chuanxiong; 0.8%~1.2% Cortex Moutan; 0.8% to 1.2% myrrh; 0.8%~1.2% Notopterygium wilfordii; 0.8%~1.2% Angelica dahurica; 0.8% to 1.2% wolfberry; 0.8% to 1.2% centipede; Functional excipients (15% to 25%): 3% to 5% nano-dispersed carrier; 3% to 5% inclusion compound; 5% to 8% water activity regulator; 1% to 3% silicon dioxide; 5% to 10% volatile oil phase of frankincense, frankincense and myrrh.

2. The Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 1, characterized in that: The nano-dispersion carrier is PVP K30.

3. The Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 1, characterized in that: The inclusion compound is β-cyclodextrin.

4. The Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 1, characterized in that: The water activity regulator is microcrystalline cellulose.

5. A method for preparing a Chinese medicine micropowder capsule based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain, characterized in that: The Chinese medicine micropowder capsule for promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredge meridians and relieve pain as claimed in any one of claims 1 to 4 comprises the following steps: S1. Directed extraction of animal medicines including earthworms, scorpions, and centipedes, and low-temperature enzymatic hydrolysis to form enzymatic hydrolyzates; S2, targeted extraction of botanicals including safflower, peach kernel, and wolfberry, and supercritical CO2 extraction; S3, adding volatile oil and β-cyclodextrin in a molar ratio of 1:3, and performing molecular inclusion by ultrasound assistance; S4, mixing the enzymatic hydrolysate with PVP K30, and nano-dispersing the mixture by high-pressure homogenization to form nanopowder; S5, spray drying the nanopowder; S6, mixing the inclusion compound, nanopowder and medicinal material ultrafine powder in equal amounts by self-increase to form a micropowder composite; S7. Fill the micro powder into capsules under nitrogen protection environment.

6. The method for preparing the Chinese medicine micropowder capsules based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 5, characterized in that: The low-temperature enzymatic hydrolysis enzyme is trypsin, the enzymatic hydrolysis pH is 6.5-8.0, and the temperature is 30°C-45°C.

7. The method for preparing the Chinese medicine micropowder capsules based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 5, characterized in that: The supercritical CO2 extraction environment has a pressure of 10 MPa to 59 MPa, and the mass of the entrainer ethanol is 5% to 20%.

8. The method for preparing the Chinese medicine micropowder capsules based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 5, characterized in that: The high-pressure homogenization environment is 500 bar to 1500 bar, and the homogenization times are 2 to 5 times.

9. The method for preparing the Chinese medicine micropowder capsules based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 5, characterized in that: During the equal-increment mixing process, the particle size distribution has a D90 difference of no more than 10 μm to 15 μm.

10. The method for preparing the Chinese medicine micropowder capsules based on promoting blood circulation and removing blood stasis, dispelling wind and dampness, and dredging meridians and relieving pain according to claim 5, characterized in that: The nitrogen filling protection pressure environment is 0.1MPa to 0.3MPa, and the nitrogen filling flow rate is 5L / min to 15L / min.

Images