Traditional Chinese medicine composition for promoting blood circulation to remove blood stasis as well as preparation method, quality control method and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for promoting blood circulation to remove blood stasis as well as a preparation method, a control method and application of the traditional Chinese medicine composition. The preparation method of the traditional Chinese medicine composition comprises the following steps: extracting angelica sinensis, ligusticum wallichii, cinnamon and moutan bark with water, and collecting volatile oil at the same time to obtain medicine residues, an extracting solution and the volatile oil; adding water into the medicine residue, white paeony root, ginseng and radix rehmanniae recen, decocting, filtering, merging the filtrate and the extracting solution, and concentrating to obtain clear paste; beta-cyclodextrin and volatile oil are subjected to clathration, and a clathrate compound is obtained; and preparing the excipient, the clear paste and the inclusion compound into the traditional Chinese medicine composition in the required dosage form. The traditional Chinese medicine composition disclosed by the invention has obvious effects of promoting blood circulation to remove blood stasis; meanwhile, the composition has the characteristics of stable quality, exact curative effect and good patient compliance.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for promoting blood circulation and removing blood stasis, its preparation method, quality control method and application. Background Technology

[0002] The method of promoting blood circulation and removing blood stasis is an important method in traditional Chinese medicine for treating a variety of diseases. Wang Qingren, a medical scientist in the Qing Dynasty, systematically expounded the core idea of ​​"blood stasis causing disease" in his book "Corrections of Errors in Medical Classics". He proposed that "the key to treating diseases lies in understanding qi and blood". He believed that both external and internal injuries can lead to qi and blood imbalance, and that blood stasis is the source of all diseases. He also created eight major blood-stasis-removing decoctions with the characteristic of "removing blood stasis in different parts", which became a milestone in the development of the method of promoting blood circulation and removing blood stasis.

[0003] Modern Traditional Chinese Medicine (TCM), building upon the theories of Wang Qingren and incorporating microscopic pathological research, has expanded the application of blood-activating and stasis-removing methods to multiple systemic diseases, deepening the system of syndrome differentiation and treatment. Currently, based on these theories, TCM compositions with blood-activating and stasis-removing effects have been developed, which can be used to treat various diseases such as cardiovascular diseases, traumatic injuries, and gynecological blood stasis syndromes. However, these TCM compositions suffer from poor homogeneity, stability, and efficacy of their components, and there is a lack of effective detection methods for the content of these components. Therefore, a TCM composition with high homogeneity, stability, and efficacy, along with its detection method, has become a research hotspot. Summary of the Invention

[0004] To address at least one of the aforementioned technical problems, the present invention provides a traditional Chinese medicine composition for promoting blood circulation and removing blood stasis, its preparation method, quality control method, and application.

[0005] In one aspect, the present invention provides a traditional Chinese medicine composition for promoting blood circulation and removing blood stasis. The raw materials of the traditional Chinese medicine composition include: Angelica sinensis, Ligusticum chuanxiong, Paeonia lactiflora, Cinnamomum cassia, Paeonia suffruticosa, Panax ginseng, and Rehmannia glutinosa.

[0006] The traditional Chinese medicine composition of this invention has significant efficacy in promoting blood circulation and removing blood stasis, and can be used to treat various diseases such as cardiovascular diseases, traumatic injuries, and gynecological blood stasis. This traditional Chinese medicine composition focuses on promoting blood circulation and removing blood stasis, integrating methods of warming, tonifying, and cooling the blood, embodying the wisdom of traditional Chinese medicine in "treating both qi and blood" and "using both warm and cold herbs," and is suitable for symptoms of qi and blood deficiency combined with cold-induced blood stasis or a mixture of deficiency and excess.

[0007] The compatibility mechanism of the traditional Chinese medicine composition provided by this invention is as follows: Angelica sinensis (sweet, pungent, and warm): It enters the liver, heart, and spleen meridians and is known as the "holy medicine of blood". It can not only nourish and invigorate blood, but also regulate menstruation and relieve pain. It is rich in volatile oil and ferulic acid, which can improve microcirculation and inhibit platelet aggregation.

[0008] Chuanxiong (pungent and warm): It enters the liver, gallbladder, and pericardium meridians. It is a "qi-regulating herb in the blood," which is good at reaching the head and eyes and the limbs, promoting both blood circulation and qi flow. Chuanxiongqin can dilate blood vessels and increase coronary blood flow. When combined with Danggui (Angelica sinensis), it enhances the effects of promoting blood circulation, qi flow, removing blood stasis, and clearing the meridians.

[0009] Moutan bark (bitter, pungent, and slightly cold) enters the heart, liver, and kidney meridians, cools the blood and disperses blood stasis, and is especially suitable for syndromes of blood heat and blood stasis. Paeonol can inhibit thrombus formation, and when combined with the warm and cool properties of cinnamon, it can prevent heat and dryness from damaging yin.

[0010] Cinnamon (pungent, sweet, and very hot) enters the kidney, spleen, heart, and liver meridians, tonifying fire and assisting yang, warming and unblocking the meridians. Its cinnamaldehyde can promote blood circulation. When combined with white peony root, one disperses and the other astringes, warming the meridians and dispelling cold, harmonizing the nutritive and defensive qi, and relieving cold pain in the limbs caused by cold stagnation and blood stasis.

[0011] White peony root (bitter, sour, and slightly cold) enters the liver and spleen meridians, nourishing blood and astringing yin, softening the liver and relieving pain. Paeoniflorin has antispasmodic and analgesic effects. When used with angelica and chuanxiong, it not only prevents excessive dispersion but also enhances the effects of nourishing blood and softening the liver.

[0012] Ginseng and Rehmannia glutinosa can invigorate qi and nourish yin, strengthen the body's foundation and cultivate vitality. Ginseng (sweet, slightly bitter, and warm) enters the spleen, lung, and heart meridians, greatly replenishing vital energy and promoting blood circulation. Ginsenosides can enhance myocardial contractility and improve ischemia and hypoxia, which aligns with the theory of "where qi flows, blood flows," providing impetus for blood-activating drugs.

[0013] Rehmannia glutinosa (sweet and cold in nature) enters the heart, liver, and kidney meridians, clearing heat and cooling the blood, nourishing yin and generating fluids. Its catalpol component can resist coagulation and inflammation, forming a "cooling-heat counteracting" effect with cinnamon, which not only prevents dryness and blood depletion but also restrains the cold nature of peony bark, maintaining the balance of yin and yang.

[0014] In some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Angelica sinensis 6-15 parts; Chuanxiong (Ligusticum striatum) 5-12 parts; 10-20 parts of white peony root; 3-8 parts cinnamon; 8-15 parts of peony bark; 5-10 portions of ginseng; 10-30 parts of raw Rehmannia glutinosa.

[0015] In some embodiments of the present invention, the weight parts of the raw material Angelica sinensis may be 6.2 parts, 6.9 parts, 7.3 parts, 8.1 parts, 8.9 parts, 9.3 parts, 10.6 parts, 10.6 parts, 11.2 parts, 11.9 parts, 12.3 parts, 13.6 parts, 13.9 parts, 14.1 parts, 14.6 parts, 14.9 parts, etc.

[0016] In some embodiments of the present invention, the weight parts of the raw material Ligusticum chuanxiong may be 5.2 parts, 5.9 parts, 6.3 parts, 7.1 parts, 7.9 parts, 8.3 parts, 8.6 parts, 9.5 parts, 10.2 parts, 10.9 parts, 11.3 parts, 11.6 parts, 11.9 parts, etc.

[0017] In some embodiments of the present invention, the weight parts of the raw material, white peony root, may be 10.2 parts, 10.9 parts, 11.3 parts, 11.9 parts, 12.3 parts, 12.6 parts, 13.6 parts, 14.2 parts, 15.9 parts, 16.3 parts, 17.6 parts, 18.9 parts, 19.1 parts, 19.8 parts, etc.

[0018] In some embodiments of the present invention, the weight parts of the raw material cinnamon may be 3.6 parts, 4.3 parts, 5.2 parts, 6.3 parts, 6.9 parts, 7.3 parts, 7.9 parts, etc.

[0019] In some embodiments of the present invention, the weight parts of the raw material peony bark may be 8.2 parts, 8.9 parts, 9.3 parts, 9.9 parts, 10.3 parts, 11.6 parts, 12.6 parts, 13.2 parts, 14.9 parts, etc.

[0020] In some embodiments of the present invention, the weight parts of the raw material ginseng may be 5.2 parts, 6.9 parts, 7.3 parts, 7.9 parts, 8.2 parts, 9.6 parts, 9.9 parts, etc.

[0021] In some embodiments of the present invention, the weight parts of the raw material Rehmannia glutinosa can be 10.2 parts, 12.9 parts, 13.3 parts, 14.9 parts, 16.3 parts, 18.6 parts, 21.6 parts, 25.2 parts, 28.9 parts, 29.8 parts, etc.

[0022] In some embodiments of the present invention, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 8-12 parts of Angelica sinensis; Chuanxiong (Ligusticum striatum) 6-10 parts; 12-18 parts of white peony root; 3-6 parts cinnamon; 8-12 parts of peony bark; 6-10 portions of ginseng; 10-15 parts of raw Rehmannia glutinosa.

[0023] In some embodiments of the present invention, preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10 parts Angelica sinensis, 8 parts Ligusticum chuanxiong, 15 parts Paeonia lactiflora, 3 parts Cinnamomum cassia, 10 parts Paeonia suffruticosa, 6 parts Panax ginseng, and 20 parts Rehmannia glutinosa.

[0024] In another aspect, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition, the method comprising: decocting Angelica sinensis, Ligusticum chuanxiong, Cinnamomum cassia and Paeonia suffruticosa in water, while collecting volatile oil to obtain dregs, extract and volatile oil; decocting the dregs, Paeonia lactiflora, Panax ginseng and Rehmannia glutinosa in water, filtering, combining the filtrate and the above extract, concentrating to obtain a clear extract; incorporating β-cyclodextrin and volatile oil in water at 50-80°C, refrigerating, filtering to obtain an inclusion complex; and preparing the excipient, the clear extract and the inclusion complex into a traditional Chinese medicine composition of the desired dosage form.

[0025] In some embodiments of the present invention, the decoction method is as follows: each decoction is performed for 0.5 to 4 hours, and the decoction is performed 2 to 5 times; and / or, the relative density of the extract at 50 to 80°C is 1.10 to 1.20.

[0026] In some embodiments of the present invention, the mass ratio of volatile oil to β-cyclodextrin is 1:(5~15); and / or, the excipient includes at least one of soluble starch, maltodextrin, and sucrose powder; and / or, the dosage form is any one of granules, tablets, or capsules.

[0027] In another aspect, the present invention provides a quality control method for the above-mentioned traditional Chinese medicine composition. The quality control method includes: qualitatively identifying ginseng and rehmannia in the traditional Chinese medicine composition using thin-layer chromatography; establishing a fingerprint spectrum of the traditional Chinese medicine composition using high-performance liquid chromatography; and determining the contents of ferulic acid, ligustilide, paeoniflorin, paeonol, and cinnamaldehyde in the traditional Chinese medicine composition using high-performance liquid chromatography.

[0028] In some embodiments of the present invention, the determination conditions for high-performance liquid chromatography are as follows: chromatographic column: C 18 Chromatographic column; and / or mobile phase: mobile phase A is acetonitrile, mobile phase B is 0.1% ~ 0.5% phosphoric acid solution; and / or detection wavelength: 230 nm ~ 321 nm; and / or flow rate: 0.5 ~ 1.2 mL / min; and / or column temperature: 25 ~ 30 °C; and / or gradient elution program: 0–5 min, mobile phase A (%): 15→17, mobile phase B (%): 85→83; 5–8 min, mobile phase A (%): 17→26, mobile phase B (%): 83→74; 8–15 min, mobile phase A (%): 26→38, mobile phase B (%): 74→62; 15–54 min, mobile phase A (%): 38 → 65, mobile phase B (%): 62 → 35; 54–60 min, mobile phase A (%): 65→90, mobile phase B (%): 35→10; 60–74 min, mobile phase A (%): 90→15, mobile phase B (%): 10→85; 75 min, mobile phase A (%): 15, mobile phase B (%): 85.

[0029] In another aspect, the present invention provides the application of the above-mentioned traditional Chinese medicine composition or the traditional Chinese medicine composition obtained by the above-mentioned preparation method in the preparation of a drug for promoting blood circulation and removing blood stasis.

[0030] In some embodiments of the present invention, the drugs for promoting blood circulation and removing blood stasis include any one of the following: drugs for treating coronary heart disease, drugs for treating traumatic blood stasis, and drugs for treating menopausal blood stasis.

[0031] The technical solution provided by the embodiments of the present invention has the following advantages: This invention provides a traditional Chinese medicine composition that invigorates Qi and nourishes Yin, warms and unblocks the meridians, and promotes blood circulation and removes blood stasis. The compatibility mechanism of the composition is "invigorating Qi and promoting blood circulation + warming and unblocking to remove blood stasis". Specifically, the traditional Chinese medicine composition of this invention is based on Angelica sinensis, Ligusticum chuanxiong, and Paeonia lactiflora to nourish and invigorate blood, with Cinnamomum cassia to warm Yang and unblock the meridians as the key, Paeonia suffruticosa to clear heat and remove blood stasis, and Ginseng and Rehmannia glutinosa to invigorate Qi and nourish Yin, forming a compatibility system that "invigorates blood without harming the body's vital energy, warms and unblocks without promoting fire, and tonifies without leaving blood stasis". It is suitable for symptoms of Qi and blood deficiency and mixed cold and heat, such as dysmenorrhea of ​​deficiency-cold type (dark menstrual blood with clots, lower abdominal cold pain), chronic angina pectoris (chest tightness and stabbing pain accompanied by shortness of breath and fatigue), and postoperative blood stasis (slow wound healing accompanied by cold limbs). This traditional Chinese medicine composition achieves the therapeutic goal of "removing blood stasis and generating new blood" through three-dimensional intervention: blood-activating drugs to unblock blood stasis, warming drugs to dispel cold stagnation, and tonifying drugs to strengthen the body's vital energy.

[0032] In the preparation method of the traditional Chinese medicine composition of the present invention, the extraction rate of effective components in the medicinal materials is improved by the efficient synergistic extraction of volatile and non-volatile components in the traditional Chinese medicine composition, thus ensuring the efficacy of the traditional Chinese medicine composition.

[0033] The quality control method for the traditional Chinese medicine composition of this invention can cover aspects such as properties, identification, inspection, characteristic chromatograms and content determination. The detection method is scientific and feasible, and can comprehensively control the quality of the traditional Chinese medicine composition, ensuring stable and uniform product quality, and providing a reliable guarantee for the industrial production and clinical application of the traditional Chinese medicine composition. Attached Figure Description

[0034] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0035] 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.

[0036] Figure 1 These are thin-layer chromatography images of ginseng from Examples 1-3 of this invention. Figure 2 These are thin-layer colorimetric images of Rehmannia glutinosa from Examples 1-3 of this invention. Figure 3 The fingerprint spectrum of Example 4 of the present invention is prepared from the sample characteristic spectrum of Example 1. Detailed Implementation

[0037] To better understand the above-mentioned objectives, features, and advantages of the present invention, the solutions of the present invention will be further described below. It should be noted that, unless otherwise specified, the embodiments of the present invention and the features thereof can be combined with each other.

[0038] Many specific details are set forth in the following description in order to provide a full understanding of the invention, but the invention may also be practiced in other ways different from those described herein; obviously, the embodiments in the specification are only some embodiments of the invention, and not all embodiments.

[0039] According to an embodiment of the present invention, a traditional Chinese medicine composition for promoting blood circulation and removing blood stasis is provided. The raw materials of the traditional Chinese medicine composition include: Angelica sinensis, Ligusticum chuanxiong, Paeonia lactiflora, Cinnamomum cassia, Paeonia suffruticosa, Panax ginseng, and Rehmannia glutinosa.

[0040] According to an embodiment of the present invention, a method for preparing the above-mentioned traditional Chinese medicine composition is provided, the method comprising the following steps: (1) Pretreatment: Remove impurities from Angelica sinensis, Ligusticum chuanxiong, Paeonia lactiflora, Cinnamomum cassia, Paeonia suffruticosa, Panax ginseng, and Rehmannia glutinosa, wash them, dry them, and crush them into coarse particles; (2) Extraction of volatile oil: The pretreated raw medicinal materials Angelica sinensis, Ligusticum chuanxiong, Cinnamomum cassia and Paeonia suffruticosa obtained in step (1) are mixed and 6 to 20 times (e.g., 7 times, 9 times, 11 times, 13 times, 15 times, 17 times, 19 times, etc., preferably 8 times) of water are added to extract the volatile oil, and the residue, extract and volatile oil are obtained. (3) Preparation of the extract: The dregs obtained in step (2), the white peony root, ginseng, and rehmannia root obtained in step (1) are decocted with water 2 to 5 times (for example, 3, 4, or 5 times, preferably 2 times). Each decoction uses 9 to 20 times (for example, 10, 12, 14, 16, or 19 times, preferably 10 times) of water, and each decoction lasts for 0.5 to 4 hours (for example, 0.9 hours, 2.1 hours, or 3.2 hours). The boiling time is 1 hour, 3.9 hours, preferably 1 hour. Preferably, 10 times the amount of water is used for each boiling, and the boiling time is 1 hour. All the filtrates after multiple boilings are combined, and the combined filtrates are concentrated at 50~80℃ (e.g., 56℃, 60℃, 63℃, 72℃, etc., preferably 60℃) to a relative density of 1.10~1.20 (e.g., 1.12, 1.14, 1.16, 1.18, 1.19, etc.) to obtain a clear extract. (4) Preparation of inclusion complex: The volatile oil obtained in step (2) is added to β-cyclodextrin (wherein the mass ratio of volatile oil to β-cyclodextrin is 1:(5~15), for example, it can be 1:5, 1:6, 1:7, 1:8.5, 1:9, 1:9.5, 1:10, 1:10.5, 1:11, 1:12, 1:13, 1:14, 1:15 (w / w), preferably 1:10), and inclusion is carried out in water at 50~80℃ (for example, it can be 56℃, 60℃, 63℃, 72℃, 80℃, etc.), refrigerated, filtered, and the inclusion complex is obtained; (5) Drying: The inclusion complex obtained in step (4) and the aqueous extract obtained in step (3) are dried, pulverized and mixed evenly to prepare extract powder; (6) Preparation: The dry extract obtained in step (5) is mixed with an appropriate amount of soluble starch, maltodextrin or sucrose powder to make granules; or further compressed into tablets; or filled into capsules to make capsules. Further, in the traditional Chinese medicine composition obtained in step (6), the granules are brownish-yellow to brownish-brown granules with a slightly fragrant odor and a slightly bitter and sweet taste; the tablets are brownish-brown tablets with a slightly fragrant odor and a slightly bitter and pungent taste; the contents of the capsules are brownish-yellow to brownish-brown powder with a slightly fragrant odor and a slightly bitter and sweet taste.

[0041] According to an embodiment of the present invention, a quality control method for the above-mentioned traditional Chinese medicine composition is provided, the quality control method specifically including the following steps: (I) Thin-layer chromatography was used to detect ginseng and rehmannia in the traditional Chinese medicine composition. (1) The thin-layer chromatography identification steps for ginseng are as follows: ① Take 1g of the Chinese herbal medicine composition granules to be tested, dissolve it in 30mL of water, add it to a D101 macroporous adsorption resin column (inner diameter 1.5cm, column height 15cm), elute with 80mL of water, discard the aqueous solution, then elute with 80mL of 30% ethanol, discard the eluent, continue to elute with 80mL of 80% ethanol, collect the eluent, evaporate to dryness, dissolve the residue in 1mL of methanol, and use it as the test solution.

[0042] ② Take another batch of ginseng-deficient Chinese herbal medicine granules and prepare a ginseng negative sample solution using the same method.

[0043] ③ Take ginsenosides Rg1 and Rb1 reference standards, add methanol to prepare a mixed solution containing 2 mg of each per 1 mL, and use it as the ginseng reference solution.

[0044] ④ Perform the thin-layer chromatography test (General Rule 0502). Take 3 μL of the negative sample, 4 μL of the reference solution, and 4 μL of the test solution sequentially and spot them onto a silica gel G thin-layer plate. Develop with chloroform-ethyl acetate-methanol-water (15:40:22:10) as the developing solvent. Remove the plate, air dry, spray with 2% vanillin-sulfuric acid ethanol solution, and heat at 105°C for 2 min. The test sample and the reference solution will show pale purple spots at the corresponding positions, while the negative sample will not show spots at the same positions.

[0045] (2) The thin-layer chromatography identification steps for raw Rehmannia glutinosa are as follows: ① Take 1g of the Chinese herbal composition granules to be tested, add 3mL of methanol, sonicate for 15min, filter, and take the filtrate as the test solution.

[0046] ② Take another 0.5g of raw Rehmannia glutinosa, grind it into powder, and prepare a raw Rehmannia glutinosa solution using the same method.

[0047] ③ Take another batch of Rehmannia glutinosa-containing Chinese herbal medicine granules and prepare a Rehmannia glutinosa negative sample solution using the same method.

[0048] ④ Take another ziziphus alcohol reference standard and add methanol to prepare a solution containing approximately 0.50 mg per 1 mL, which will be used as the reference solution.

[0049] ⑤ Perform the thin-layer chromatography test (Chinese Pharmacopoeia 2015 Edition, Part IV, General Chapter 0502, Thin-layer Chromatography). Take 3 μL of each of the above two solutions and spot them separately on the same silica gel G thin-layer plate. Use chloroform-methanol-water (14:6:1) as the developing solvent, develop, remove, air dry, spray with 10% concentrated sulfuric acid ethanol solution, and heat at 105℃ until the spots are clear. In the chromatogram of the test sample, spots of the same color appear at the corresponding positions as in the chromatogram of the reference standard and the solution of Rehmannia glutinosa.

[0050] (II) The contents of ferulic acid, ligustilide, paeoniflorin, paeonol and cinnamaldehyde in the traditional Chinese medicine composition were determined by high performance liquid chromatography. (1) The steps for determining fingerprint spectra are as follows: High-performance liquid chromatography (HPLC) conditions: chromatographic column: Dikma Diamonsil C10 ... 18 The column temperature was 30℃; the mobile phase was acetonitrile (A)-0.1% phosphoric acid (B); elution was performed according to the gradient elution program in Table 1; the volumetric flow rate was 1.0 mL / min; and the detection wavelength was 230 nm.

[0051] Table 1 Gradient elution program ① Preparation of reference solution Accurately weigh cinnamaldehyde (the active ingredient of cinnamon), ferulic acid (the active ingredient of Angelica sinensis and Ligusticum chuanxiong), ligustilide (the active ingredient of Angelica sinensis and Ligusticum chuanxiong), paeonol (the active ingredient of Paeonia suffruticosa), and paeoniflorin (the active ingredient of Paeonia lactiflora) reference standards, and add methanol to prepare a mixed solution containing 85 μg of paeoniflorin, 2.5 μg of cinnamaldehyde, 10 μg of paeonol, 5 μg of ferulic acid, and 5 μg of ligustilide per mL. Shake well to obtain the final product.

[0052] ② Preparation of the test solution Take 1g of the granules of the Chinese herbal medicine composition to be tested, dissolve it in 50% ethanol, make up to volume, and filter it through a 0.45μm microporous membrane to obtain the final product.

[0053] ③ Determination method Accurately pipette 10 µL each of the reference solution and the test solution into the liquid chromatograph, measure and record the chromatograms to obtain the solution.

[0054] The chromatogram of the test sample should show 13 common characteristic peaks, of which 5 peaks should have the same retention time as the corresponding reference peak. The peak corresponding to the paeoniflorin reference peak is the S peak. The relative retention time of each characteristic peak should be calculated and should be within ±10% of the specified value, which is 0.75 (peak 1), 0.86 (peak 2), 1.00 (peak 3 [S]), 1.46 (peak 4), 1.53 (peak 5), 1.73 (peak 6), 2.02 (peak 7), 2.88 (peak 8), 3.42 (peak 9), 4.28 (peak 10), 4.51 (peak 11), 5.10 (peak 12), and 5.74 (peak 13). Among them, in the HPLC chromatogram analysis results, peak 3 is paeoniflorin; peak 5 is ferulic acid; peak 9 is paeonol; peak 11 is cinnamaldehyde; and peak 13 is ligustilide.

[0055] (2) Determination of multiple index contents The contents of paeoniflorin, ferulic acid, paeonol, cinnamaldehyde and ligustilide were determined by high performance liquid chromatography.

[0056] Octadecylsilane-bonded silica gel was used as the packing material; acetonitrile was used as mobile phase A and 0.1% phosphoric acid solution was used as mobile phase B, and gradient elution was performed according to the specifications in Table 1; the detection wavelengths were 230 nm, 274 nm, 290 nm and 321 nm; the flow rate was 1.0 mL per minute; and the column temperature was 30 °C.

[0057] ① Preparation of the reference solution: Take appropriate amounts of paeoniflorin reference standard, glycyrrhizin reference standard, paeonol reference standard, cinnamaldehyde reference standard, ammonium glycyrrhizate reference standard, ferulic acid reference standard, and ligustilide reference standard, accurately weigh them, add methanol to prepare a mixed solution containing 70 μg paeoniflorin, 60 μg cinnamaldehyde, 20 μg paeonol, 4 μg ferulic acid, and 8 μg ligustilide per mL, shake well, and the solution is obtained.

[0058] ② Preparation of the test solution: Take the Chinese herbal composition granules, grind them into a fine powder, weigh about 0.5g accurately, place them in a volumetric flask, add 50% ethanol to dissolve, make up to volume, filter through a membrane, and the product is obtained.

[0059] ③ Determination method: Accurately pipette 10 μL each of the reference solution and the test solution into the liquid chromatograph and determine the result.

[0060] In some embodiments of the present invention, the quality control method of the traditional Chinese medicine composition further includes the properties, specifically, the granules are brownish-yellow to brownish-brown granules with a slightly fragrant odor and a slightly bitter and sweet taste; the tablets are brownish-brown tablets with a slightly fragrant odor and a slightly bitter and pungent taste; the contents of the capsules are brownish-yellow to brownish-brown powder with a slightly fragrant odor and a slightly bitter and sweet taste.

[0061] In some embodiments of the present invention, each g of the traditional Chinese medicine composition contains 2.5-7.0 mg of paeoniflorin, 1.0-3.0 mg of ferulic acid, 0.75-2.5 mg of paeonol, 0.1-0.5 mg of cinnamaldehyde, and 0.2-0.8 mg of ligustilide.

[0062] The technical solution of the present invention will be further explained and illustrated below through specific embodiments.

[0063] All reagents used in the following examples are commercially available.

[0064] Example 1 This embodiment provides a traditional Chinese medicine composition comprising the following raw materials in parts by weight: 10 parts of Angelica sinensis; Chuanxiong (Ligusticum striatum) 8 parts; 15 parts of white peony root; 3 parts cinnamon; 10 parts of peony bark; 6 portions of ginseng; 20 parts of raw Rehmannia glutinosa.

[0065] This embodiment also provides a traditional Chinese medicine composition in granule form: (1) Pretreatment: Weigh out 10g of Angelica sinensis, 8g of Ligusticum chuanxiong, 15g of Paeonia lactiflora, 3g of Cinnamomum cassia, 10g of Paeonia suffruticosa, 6g of Panax ginseng, and 20g of Rehmannia glutinosa. Remove impurities from each of them, wash them, dry them, and crush them into coarse particles. (2) Extraction of volatile oil: The pretreated raw medicinal materials Angelica sinensis, Ligusticum chuanxiong, Cinnamomum cassia and Paeonia suffruticosa obtained in step (1) are mixed and extracted with 8 times the amount of water. The volatile oil is collected at the same time to obtain the residue, extract and volatile oil. (3) Preparation of clear paste: The dregs obtained in step (2), the white peony root, ginseng and rehmannia root obtained in step (1) are decocted twice with water (10 times the amount of water, 1 hour each time). The filtrate after the two decoctions and the extract obtained in step (2) are combined. The combined filtrate is concentrated at 60°C to a relative density of 1.10 to 1.20 to obtain clear paste. (4) Preparation of inclusion complex: At 60°C, β-cyclodextrin was added to the volatile oil obtained in step (2), dissolved in water, and then included. The mixture was refrigerated and filtered to obtain the inclusion complex. The mass ratio of volatile oil to β-cyclodextrin was 1:8 (w / w). (5) Drying: The inclusion complex obtained in step (4) is dried at 50°C, and the aqueous extract obtained in step (3) is dried, pulverized, and mixed evenly at 70°C to prepare extract powder; (6) Formulation: Mix the dry extract powder obtained in step (5) with 10g of maltodextrin to make granules.

[0066] Example 2 This embodiment provides a traditional Chinese medicine composition comprising the following raw materials in parts by weight: 15 portions of Angelica sinensis; 12 parts of Ligusticum chuanxiong; 18 portions of white peony root; 6 parts cinnamon; 12 parts of peony bark; 10 portions of ginseng; 15 parts of raw Rehmannia glutinosa.

[0067] This embodiment also provides a traditional Chinese medicine composition in tablet form: (1) Pretreatment: Weigh out 15g of Angelica sinensis, 12g of Ligusticum chuanxiong, 18g of Paeonia lactiflora, 6g of Cinnamomum cassia, 12g of Paeonia suffruticosa, 10g of Panax ginseng and 15g of Rehmannia glutinosa, remove impurities, wash and dry them, and crush them into coarse particles; (2) Extraction of volatile oil: The pretreated raw medicinal materials Angelica sinensis, Ligusticum chuanxiong, Cinnamomum cassia and Paeonia suffruticosa obtained in step (1) are mixed and extracted with 8 times the amount of water. At the same time, the volatile oil is collected to obtain the residue, extract and volatile oil. (3) Preparation of clear paste: The dregs obtained in step (2), the white peony root, ginseng and rehmannia root obtained in step (1) are decocted twice with water (10 times the amount of water, 1 hour each time). The filtrate after the two decoctions and the extract obtained in step (2) are combined. The combined filtrate is concentrated at 60°C to a relative density of 1.10 to 1.20 to obtain clear paste. (4) Preparation of inclusion complex: At 60°C, β-cyclodextrin was added to the volatile oil obtained in step (2), dissolved in water, and then included. The mixture was refrigerated and filtered to obtain the inclusion complex. The mass ratio of volatile oil to β-cyclodextrin was 1:8 (w / w). (5) Drying: The inclusion complex obtained in step (4) is dried at 40°C, and the aqueous extract obtained in step (3) is dried, pulverized, and mixed evenly at 80°C to prepare extract powder; (6) Formulation: The dry extract powder obtained in step (5) is mixed with 20g of maltodextrin to form granules, which are then further compressed into tablets.

[0068] Example 3 This embodiment provides a traditional Chinese medicine composition comprising the following raw materials in parts by weight: 8 parts of Angelica sinensis; Chuanxiong (Ligusticum striatum) 8 parts; 12 parts of white peony root; 3 parts cinnamon; 8 parts of peony bark; 6 portions of ginseng; 10 parts of raw Rehmannia glutinosa.

[0069] This embodiment also provides a traditional Chinese medicine composition in capsule form: (1) Pretreatment: Weigh out 8g of Angelica sinensis, 8g of Ligusticum chuanxiong, 12g of Paeonia lactiflora, 3g of Cinnamomum cassia, 8g of Paeonia suffruticosa, 6g of Panax ginseng and 10g of Rehmannia glutinosa, remove impurities from them, wash them, dry them and crush them into coarse particles; (2) Extraction of volatile oil: The pretreated raw medicinal materials Angelica sinensis, Ligusticum chuanxiong, Cinnamomum cassia and Paeonia suffruticosa obtained in step (1) are mixed and extracted with 8 times the amount of water to obtain the residue, extract and volatile oil; (3) Preparation of clear paste: The dregs obtained in step (2), the white peony root, ginseng and rehmannia root obtained in step (1) are decocted twice with water (10 times the amount of water, 1 hour each time). The filtrate after the two decoctions and the extract obtained in step (2) are combined. The combined filtrate is concentrated at 60°C to a relative density of 1.10 to 1.20 to obtain clear paste. (4) Preparation of inclusion complex: At 60°C, β-cyclodextrin was added to the volatile oil obtained in step (2), dissolved in water, and then included. The mixture was refrigerated and filtered to obtain the inclusion complex. The mass ratio of volatile oil to β-cyclodextrin was 1:12 (w / w). (5) Drying: The inclusion complex obtained in step (4) is dried at 45°C, and the aqueous extract obtained in step (3) is dried, pulverized, and mixed evenly at 60°C to prepare extract powder; (6) Preparation: Mix the dry extract powder obtained in step (5) with 15g of maltodextrin to make granules, fill them into capsules, and make capsules.

[0070] Example 4 Quality control methods for traditional Chinese medicine compositions: The quality control method for the traditional Chinese medicine compositions prepared in Examples 1-3 specifically includes the following steps: (1) The thin-layer chromatography identification steps for ginseng are as follows: ① Take 1g of the traditional Chinese medicine composition prepared in Examples 1-3, dissolve it in 30mL of water, add it to a D101 macroporous adsorption resin column (inner diameter 1.5cm, column height 15cm), elute with 80mL of water, discard the aqueous solution, elute with 80mL of 30% ethanol, discard the eluent, continue to elute with 80mL of 80% ethanol, collect the eluent, evaporate to dryness, dissolve the residue in 1mL of methanol, and use it as the test solution.

[0071] ② Take another batch of ginseng-deficient Chinese herbal medicine granules and prepare a ginseng negative sample solution using the same method.

[0072] ③ Take ginsenosides Rg1 and Rb1 reference standards, add methanol to prepare a mixed solution containing 2 mg of each per 1 mL, and use it as the ginseng reference solution.

[0073] ④ Perform the thin-layer chromatography (General Rule 0502) test. Take 3 μL of the negative sample, 4 μL of the reference solution, and 4 μL of the test solution sequentially and spot them onto a silica gel G thin-layer plate. Develop with chloroform-ethyl acetate-methanol-water (15:40:22:10) as the developing solvent. Remove the plate, air dry, spray with 2% vanillin-sulfuric acid ethanol solution, and heat at 105℃ for 2 min. The test sample and reference solution will show pale purple spots at the corresponding positions, while the negative sample will not show spots at the same positions. The results of the thin-layer chromatography analysis are shown in the figure. Figure 1 .exist Figure 1 In the middle, from left to right, are: negative control, ginsenoside control, and three batches of samples.

[0074] (2) The thin-layer chromatography identification steps for raw Rehmannia glutinosa are as follows: ① Take 1g of the traditional Chinese medicine composition prepared in Examples 1-3, add 3mL of methanol, sonicate for 15min, filter, and take the filtrate as the test solution.

[0075] ② Take another 0.5g of raw Rehmannia glutinosa, grind it into powder, and prepare a raw Rehmannia glutinosa solution using the same method.

[0076] ③ Take another batch of Rehmannia glutinosa-containing Chinese herbal medicine granules and prepare a Rehmannia glutinosa negative sample solution using the same method.

[0077] ④ Take another ziziphus alcohol reference standard and add methanol to prepare a solution containing approximately 0.50 mg per 1 mL, which will be used as the reference solution.

[0078] ⑤ Perform the thin-layer chromatography test (Chinese Pharmacopoeia 2015 Edition, Part IV, General Chapter 0502, Thin-layer Chromatography). Apply 3 μL of each of the two solutions mentioned above to the same silica gel G thin-layer plate. Develop the plate using chloroform-methanol-water (14:6:1) as the developing solvent. Remove the plate, air dry, spray with 10% concentrated sulfuric acid in ethanol, and heat at 105℃ until the spots are clear. The test sample chromatogram should show spots of the same color at the corresponding positions as the reference standard chromatogram and the Rehmannia glutinosa herb solution. The results of the thin-layer chromatography analysis are shown below. Figure 2 .exist Figure 2 In the middle, from left to right: ziziphus jujuba var. spinosa reference standard; raw Rehmannia glutinosa medicinal material; negative control standard; three batches of samples.

[0079] (3) Establish fingerprint chromatogram using high performance liquid chromatography. The liquid chromatography conditions for determining fingerprint chromatograms are as follows: The chromatographic column was a Dikma Diamonsil C10 column. 18 The column temperature was 30℃; the mobile phase was acetonitrile (A) - 0.1% phosphoric acid (B); gradient elution was performed according to the procedure in Table 1, with a flow rate of 1.0 mL / min; the detection wavelength was 230 nm. Specifically, the gradient elution procedure was as follows: 0–5 min, mobile phase A (%): 15→17, mobile phase B (%): 85→83; 5–8 min, mobile phase A (%): 17→26, mobile phase B (%): 83→74; 8–15 min, mobile phase A (%): 26→38, mobile phase B (%): 74→62; 15–54 min, mobile phase A (%): 38 → 65, mobile phase B (%): 62 → 35; 54–60 min, mobile phase A (%): 65→90, mobile phase B (%): 35→10; 60–74 min, mobile phase A (%): 90→15, mobile phase B (%): 10→85; 75 min, mobile phase A (%): 15, mobile phase B (%): 85.

[0080] ① Preparation of reference solution Accurately weigh cinnamaldehyde (the active ingredient of cinnamon), ferulic acid (the active ingredient of angelica and chuanxiong), ligustilide (the active ingredient of angelica and chuanxiong), paeonol (the active ingredient of peony bark), and paeoniflorin (the active ingredient of white peony root) reference standards, and add methanol to prepare a mixed solution containing 85 μg of paeoniflorin, 2.5 μg of cinnamaldehyde, 10 μg of paeonol, 5 μg of ferulic acid, and 5 μg of ligustilide per mL. Shake well to obtain the reference solution.

[0081] ② Preparation of the test solution Take 1g of the traditional Chinese medicine composition prepared in Examples 1-3, dissolve it in 50% ethanol, make up the volume, and filter it through a 0.45μm microporous membrane to obtain the test solution.

[0082] ③ Determination method Accurately pipette 10 µL each of the reference solution prepared in step ① and the test solution prepared in step ②, inject them into the liquid chromatograph, measure and record the chromatograms to obtain the final product.

[0083] The characteristic chromatogram of the test sample prepared in step ② should show 13 common characteristic peaks, of which 5 peaks should have the same retention time as the corresponding reference peak; the peak corresponding to the paeoniflorin reference peak is the S peak. Calculate the relative retention time of each characteristic peak, and its relative retention time should be within ±10% of the specified value. The specified values ​​are 0.75 (peak 1), 0.86 (peak 2), 1.00 (peak 3 [S]), 1.46 (peak 4), 1.53 (peak 5), 1.73 (peak 6), 2.02 (peak 7), 2.88 (peak 8), 3.42 (peak 9), 4.28 (peak 10), 4.51 (peak 11), 5.10 (peak 12), and 5.74 (peak 13).

[0084] The chromatographic analysis results of HPLC are as follows: Figure 3 As shown. In Figure 3 In the sample, peak 3 is paeoniflorin; peak 5 is ferulic acid; peak 9 is paeonol; peak 11 is cinnamaldehyde; and peak 13 is ligustilide.

[0085] (4) The contents of ferulic acid, ligustilide, paeoniflorin, paeonol and cinnamaldehyde in the traditional Chinese medicine composition were determined by high performance liquid chromatography. Octadecylsilane-bonded silica gel was used as the packing material; acetonitrile was used as mobile phase A and 0.1% phosphoric acid solution was used as mobile phase B, and gradient elution was performed according to the specifications in Table 1; the detection wavelengths were 230 nm, 274 nm, 290 nm and 321 nm; the flow rate was 1.0 mL per minute; and the column temperature was 30 °C.

[0086] ① Preparation of reference solution: Take appropriate amounts of paeoniflorin reference standard, glycyrrhizin reference standard, paeonol reference standard, cinnamaldehyde reference standard, ammonium glycyrrhizate reference standard, ferulic acid reference standard, and ligustilide reference standard, accurately weigh them, add methanol to prepare a mixed solution containing 70 μg paeoniflorin, 60 μg cinnamaldehyde, 20 μg paeonol, 4 μg ferulic acid, and 8 μg ligustilide per 1 mL, shake well, and the solution is ready.

[0087] ② Preparation of test solution: Take the traditional Chinese medicine composition prepared in Examples 1 to 3, grind it into a fine powder, take about 0.5g, weigh it accurately, put it in a volumetric flask, add 50% ethanol to dissolve it, make up to volume, filter through a membrane, and the solution is obtained.

[0088] ③ Determination method: Accurately pipette 10 μL each of the reference solution and the test solution into the liquid chromatograph and determine the result.

[0089] The traditional Chinese medicine composition of this invention contains 2.5-7.0 mg of paeoniflorin, 1.0-3.0 mg of ferulic acid, 0.75-2.5 mg of paeonol, 0.1-0.5 mg of cinnamaldehyde, and 0.2-0.8 mg of ligustilide per gram of the traditional Chinese medicine composition.

[0090] Example 5 Clinical case of the traditional Chinese medicine composition of this invention for myocardial ischemia in elderly men Mr. Zhang, an 86-year-old male patient with myocardial ischemia (Qi deficiency and blood stasis syndrome), first visited on September 15, 2023.

[0091] Chief complaint: Recurrent chest tightness and dull pain for 3 years, worsening in the past week, accompanied by shortness of breath and fatigue. Medical history: 20-year history of hypertension; coronary angiography showed 60% stenosis of the left anterior descending artery; long-term use of aspirin and isosorbide dinitrate; increased frequency of chest pain attacks in the past week, especially after activity. Tongue: purplish-dark with ecchymosis on the edges, thin white coating; pulse: deep, thready, and hesitant.

[0092] Diagnostic analysis: The patient is elderly and suffers from deficiency of vital energy (ginseng, rehmannia root), weakness of heart yang (cinnamon), and insufficient qi to propel blood, leading to blood stasis in the heart vessels (angelica root, chuanxiong rhizome), compounded by cold stagnation and blood stasis (white peony root, moutan bark as a counteracting agent). This condition belongs to the category of "chest pain" characterized by deficiency of the root and excess of the branch, with the disease location in the heart and involving the spleen and kidneys.

[0093] Treatment: Tonify Qi and promote blood circulation, warm Yang and unblock the meridians, supplemented with methods to resolve blood stasis and relieve pain.

[0094] Prescription: Angelica sinensis 10g, Ligusticum chuanxiong 9g, Paeonia lactiflora 15g, Cinnamomum cassia 5g, Paeonia suffruticosa 9g, Panax ginseng 6g, Rehmannia glutinosa 18g. 7 doses, decocted in water and taken orally, 1 dose per day, divided into 2 warm doses.

[0095] Second visit (September 23): Chest pain attacks decreased by 50%, limbs warmed up, and pulse was stronger than before. Continue taking 14 doses.

[0096] Example 6 Clinical case of the traditional Chinese medicine composition of this invention treating insomnia due to blood stasis after a fall in elderly women. Grandma Li, 80 years old, visited the hospital in December 2024.

[0097] Chief complaint: Insomnia has persisted for over half a month since an accidental fall and lower back injury. Current symptoms include difficulty falling asleep, vivid dreams and easy awakening, sharp, localized lower back pain that worsens with pressure, accompanied by a sallow complexion, fatigue, a purplish-dark tongue with ecchymosis, a thin white coating, and a thready, hesitant pulse. Western medical examination ruled out fractures; the diagnosis was soft tissue contusion with localized hematoma.

[0098] Diagnosis: Blood stasis obstructs the flow of Qi and blood, leading to malnourishment of the heart vessels and deficiency of Qi and blood. The fall caused local blood stasis, which stagnated internally, affecting the circulation of Qi and blood, resulting in malnourishment of the heart and spirit, thus causing insomnia.

[0099] Treatment principle: Promote blood circulation and remove blood stasis, nourish blood and calm the mind, and also replenish qi.

[0100] Prescription: Angelica sinensis 12g, Ligusticum chuanxiong 10g, Paeonia lactiflora 15g, Cinnamomum cassia 6g, Paeonia suffruticosa 10g, Panax ginseng 10g, Rehmannia glutinosa 12g, Polygonum multiflorum 30g, Albizia julibrissin 15g. 7 doses, decocted in water and taken orally, one dose per day, divided into two warm doses in the morning and evening.

[0101] Second visit: After taking the medication, the lower back pain was relieved, and the patient could sleep for 3-4 hours at night. The prescription was continued with adjustments for 2 weeks, and the lower back pain significantly decreased, and sleep returned to normal.

[0102] Example 7 Clinical cases of the traditional Chinese medicine composition of this invention treating menopausal headaches Patient: Ms. Zhang, 50 years old, visited the hospital in January 2025.

[0103] Chief complaint: Recurrent headaches for over six months, worsening in the past week. The patient is currently going through menopause and has experienced stabbing headaches for the past six months, most severe on both sides and the vertex, with a fixed location of pain, accompanied by hot flashes, sweating, irritability, insomnia, and vivid dreams. Her menstrual cycle is irregular, with dark purple menstrual blood containing clots. Her tongue is dark red with ecchymosis on the edges, a thin yellow coating, and her pulse is wiry and hesitant. Western medicine diagnosed it as menopausal syndrome. Traditional Chinese medicine, based on the four diagnostic methods, identified it as qi stagnation and blood stasis, and malnourishment of the liver and kidneys.

[0104] Diagnosis: Blood stasis obstructing the collaterals, liver and kidney yin deficiency, and deficiency fire disturbing the clear orifices. During menopause, the liver and kidneys gradually become deficient, qi and blood become disharmonious, blood stasis is generated internally, and the brain collaterals are obstructed, causing headaches.

[0105] Treatment principle: Promote blood circulation and remove blood stasis, nourish the liver and kidneys, and clear deficiency heat.

[0106] Prescription: Angelica sinensis 10g, Ligusticum chuanxiong 8g, Paeonia lactiflora 15g, Cinnamomum cassia 3g (added later), Paeonia suffruticosa 10g, Panax ginseng 6g, Rehmannia glutinosa 15g. 7 doses, decocted in water and taken orally, 1 dose per day, divided into morning and evening warm doses.

[0107] Second visit: After taking the medication, the headache lessened, and the hot flashes and sweating decreased. The prescription was adjusted according to the symptoms, and after continuing to take it for 2 weeks, the headache basically disappeared, the mood and sleep improved significantly, and the menstrual situation also improved.

[0108] Example 8 Clinical cases of the effects of the traditional Chinese medicine composition of this invention on hypertension Patient: Zhao, male, 55 years old, visited the hospital in February 2025.

[0109] Chief complaint: Elevated blood pressure for 5 years, currently fluctuating between 150-160 / 95-100 mmHg. Although taking antihypertensive medication regularly, blood pressure control is poor. Symptoms include stabbing headache with a fixed location, intermittent dizziness, chest tightness and palpitations, restless sleep, sallow complexion, purplish-dark tongue with ecchymosis, thin yellow coating, and wiry, hesitant pulse. Western medicine diagnosis: Grade 3 primary hypertension. Traditional Chinese medicine diagnosis, based on the four diagnostic methods, is blood stasis obstructing the collaterals and liver yang hyperactivity.

[0110] Diagnosis: Blood stasis obstructs the meridians, hindering the flow of qi and blood. Combined with hyperactivity of liver yang, which disturbs the sensory orifices, this results in headache and dizziness. Treatment principle: Activate blood circulation, remove blood stasis, calm the liver, and subdue yang.

[0111] Prescription: Angelica sinensis 10g, Ligusticum chuanxiong 8g, Paeonia lactiflora 15g, Cinnamomum cassia 3g, Paeonia suffruticosa 10g, Panax ginseng 6g, Rehmannia glutinosa 12g, Gastrodia elata 10g, Uncaria rhynchophylla 15g. 7 doses, decocted in water and taken orally, one dose daily, divided into morning and evening warm doses.

[0112] Second visit: After taking the medication, the headache and dizziness lessened, and the blood pressure dropped to around 140 / 90 mmHg. The prescription was adjusted according to the symptoms, and after continuing to take it for 2 weeks, the blood pressure stabilized, and the discomfort symptoms were significantly relieved. Later, pills were used to consolidate the therapeutic effect.

[0113] Example 9 The main pharmacodynamic experiments of the traditional Chinese medicine composition of this invention related to its blood-activating and stasis-removing effects The traditional Chinese medicine compositions used in the following experiments include those prepared in Example 2.

[0114] (1) Effects on acute myocardial ischemia in rats Seventy healthy Wistar rats, weighing (250-280) g, were selected and randomly divided into seven groups according to body weight: sham-operated group, model group, traditional Chinese medicine combination groups (2.25, 4.5, and 9.0 g / kg), compound Danshen dripping pills group (0.22 mg / kg), and Sichuan pepper heart-saving spray group (4.5 g / kg), with 10 rats in each group, half male and half female. Except for the Sichuan pepper spray group, which was administered orally, the other test drug groups were administered by gavage. The sham-operated group and the model group were given 0.05% Tween by gavage, with a gavage volume of 10 mL / kg, once daily for 5 consecutive days. One hour after the last administration (15 minutes after administration of the Sichuan pepper spray), rats were anesthetized with an intraperitoneal injection of urethane / kg. A standard lead II electrocardiogram (ECG) was recorded before ligation. The chest cavity was then opened, and the left anterior descending coronary artery was ligated. Standard lead II ECGs were recorded at 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, and 4 hours after ligation. Changes in the ST segment value were observed, and the degree of myocardial ischemia was represented by the ST elevation (mv). At the end of the experiment (4 hours after ligation), the rats were sacrificed, and the hearts were removed. The ventricular myocardium was cut into 5 slices below the ligation site and placed in 0.5% TTC staining solution. After shaking and staining for 15 minutes, the slices were removed. Normal myocardium stained red, while infarcted myocardium did not stain. The slices were carefully dissected, and the weights of normal and infarcted myocardium were weighed separately. The percentage of infarcted myocardium weight was calculated as (infarcted myocardial weight / infarcted myocardial weight + normal myocardial weight × 100%) to observe the effects of the traditional Chinese medicine composition.

[0115] The results showed that, compared with the model control group, after 5 days of continuous gavage administration to rats, the 4.5 and 9.0 g / kg dose groups of the traditional Chinese medicine composition significantly inhibited the ST segment elevation after ligation of the left anterior descending coronary artery and significantly reduced the percentage of myocardial infarction in rats. This indicates that the traditional Chinese medicine composition of the present invention has a significant protective effect on acute myocardial ischemia in rats. The positive control drug, Compound Danshen Dripping Pills, also had a significant effect. Compared with the same dose of spray, the effect intensity was increased, but there was no significant difference. The results are shown in Tables 2 and 3.

[0116] Table 2. Effects of the herbal composition of this invention on the percentage of myocardial infarction in rats with acute myocardial ischemia ( ) (2) Effects on platelet aggregation in rats with blood stasis Healthy male Wistar rats, weighing (220-250) g, were randomly divided into 8 groups: normal group, model group, groups treated with the herbal composition of this invention at 2.25, 4.5, and 9.0 g / kg, a group treated with compound Danshen dripping pills at 218.7 mg / kg, a group treated with aspirin at 200 mg / kg, and a group treated with Sichuan pepper spray at 4.5 g / kg, with 10 rats in each group. Except for the Sichuan pepper spray group, which was administered orally, all other test drug groups were administered by gavage. The sham-operated group and the model group were administered 0.05% Tween by gavage at a volume of 10 mL / kg, once daily for 5 consecutive days. All rats except the normal group were subcutaneously injected with 0.1% epinephrine hydrochloride at 0.8 mL / kg twice, 6 hours apart, one day before the experiment. During this time (approximately 3 hours), the rats were immersed in ice water for 5 minutes and then fasted overnight. One hour after gavage administration the following day (15 minutes after inhaled administration), anesthesia was achieved via intraperitoneal injection of 40 mg / kg sodium pentobarbital. Blood was drawn from the abdominal aorta and anticoagulated with 3.8% sodium citrate (anticoagulant to whole blood ratio 1:9). After centrifugation, platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared. PRP was adjusted with PPP (platelet count approximately 300,000 / mm³). 3 The platelet aggregation experiment was conducted using a turbidimetric method with ADP, AA, and collagen as inducing agents in a PAM-3 dual-channel platelet aggregator. The maximum platelet aggregation percentage was calculated, and the effect of the traditional Chinese medicine composition of the present invention was observed. The results are shown in Table 4.

[0117] Table 4. Effects of the herbal composition of the present invention on platelet aggregation function in rats with blood stasis ( (N=10) The results showed that, compared with the normal control group, the percentage of maximum platelet aggregation in the model control group was significantly increased, indicating that a blood stasis model had been established. Compared with the model control group, the herbal composition of this invention had varying degrees of anti-platelet aggregation effects against different inducers. The 4.5 and 9.0 g / kg dose groups significantly inhibited ADP-induced platelet aggregation; the 2.25, 4.5, and 9.0 g / kg dose groups significantly inhibited AA-induced platelet aggregation; and the 9.0 g / kg dose group significantly inhibited collagen-induced platelet aggregation. The positive control also showed significant effects. The effects were comparable to those of the equal-dose spray.

[0118] (3) Effect on the time of carotid artery thrombosis in rats Healthy Wistar rats, weighing (220-250) g, were randomly divided into 6 groups: a normal group, groups receiving the herbal composition of this invention at 2.25, 4.5, and 9.0 g / kg, a group receiving Compound Danshen Dripping Pills at 218.7 mg / kg, and a group receiving Sichuan Perilla Heart-Saving Spray at 4.5 g / kg. Each group consisted of 10 rats, half male and half female. Except for the Sichuan Perilla Spray group, which received the drug orally, all other groups received the drug via gavage. The sham-operated group and the model group received 0.05% Tween via gavage, with a gavage volume of 10 mL / kg. The administration was once daily for 5 consecutive days. One hour after the last administration (15 minutes after the spray administration), rats in each dosage group were anesthetized by intraperitoneal injection of 40 mg / kg sodium pentobarbital. One carotid artery was isolated, and a BT87-3 thrombosis instrument with stimulation electrodes and a temperature sensor was attached to the carotid artery. The vessel wall was continuously stimulated with a current of 1.5 mA for 7 minutes, and then stimulation was stopped. At the same time, the temperature sensor monitored the change in the surface temperature of the vessel. After 3 minutes, the temperature sensor pointer was zeroed. When thrombus formation occurred and blocked the blood flow, the temperature at the distal end of the vessel suddenly dropped, and the instrument alarmed. The time from the start of stimulation to the alarm was recorded as the thrombus formation time. The effect of the traditional Chinese medicine composition was observed, and the results are shown in Table 5.

[0119] Table 5. Effects of the herbal composition of the present invention on the time of carotid artery thrombosis in rats ( ) Note: Compared with the normal control group, * P<0.05 The results showed that, compared with the model group, the 9.0 g / kg dose of the traditional Chinese medicine composition significantly prolonged the thrombus formation time, indicating that it had a significant antithrombotic effect.

[0120] (4) Effects on whole blood viscosity in rats with hyperviscosity syndrome Healthy Wistar rats, weighing (220-260) g, were randomly divided into 7 groups according to sex and weight: normal group, model group, traditional Chinese medicine combination groups (2.25, 4.5, and 9.0 g / kg), compound Danshen dripping pills group (218.7 mg / kg), and Sichuan pepper heart-saving spray group (4.5 g / kg). Each group consisted of 10 rats, half male and half female. Except for the Sichuan pepper spray group, which received oral administration, all other drug groups were administered via gavage. The sham-operated group and model group received 0.05% Tween via gavage. The gavage volume was 10 mL / kg, once daily for 5 consecutive days. One hour after the last administration (15 minutes after the spray administration), rats in each dosage group were anesthetized by intraperitoneal injection of 40 mg / kg sodium pentobarbital. Except for the normal control group, all other groups were injected with 1 mL / kg of 10% high molecular weight dextran (molecular weight 300,000) via tail vein. Ten minutes after the injection, 4 mL of blood was collected from the abdominal aorta and anticoagulated with 3.8% sodium citrate (the ratio of anticoagulant to whole blood was 1:9). The whole blood viscosity at different shear rates was measured using an LG-R-80C blood viscometer to observe the effect of the traditional Chinese medicine composition of this invention. The results are shown in Table 6.

[0121] Table 6. Effects of the traditional Chinese medicine composition of the present invention on whole blood viscosity in rats with hyperviscosity syndrome. (N=10) The results showed that, compared with the normal group, intravenous injection of high molecular weight dextran significantly increased the whole blood viscosity of rats in the model group, indicating that a rat model of hyperviscosity syndrome had been established. Compared with the model group, the 2.25, 4.5, and 9.0 g / kg doses of the traditional Chinese medicine composition significantly inhibited the increase in whole blood viscosity in rats with hyperviscosity syndrome, showing a significant anti-hyperviscosity syndrome effect. Compared with the same dose of Chuansu Jiuxin spray, the effect intensity was increased, but there was no significant difference.

[0122] Experiment Summary When rats were administered the herbal composition of this invention (4.5 or 9.0 g / kg) by gavage once a day for 5 consecutive days, it significantly antagonized ST segment elevation in standard lead II electrocardiogram and reduced the percentage of myocardial infarction, showing a significant anti-myocardial ischemia effect.

[0123] In rats with blood stasis syndrome, oral administration of the herbal composition of this invention (2.25, 4.5, and 9.0 g / kg) once daily for 5 consecutive days significantly inhibited the maximum platelet aggregation percentage induced by ADP, AA, and collagen. This demonstrates a significant antiplatelet aggregation effect.

[0124] When rats were administered the herbal composition of this invention (9.0 g / kg) by gavage once a day for 5 consecutive days, it significantly prolonged the time of carotid artery thrombosis, showing a significant antithrombotic effect.

[0125] In rats, oral administration of the herbal composition of this invention (2.25, 4.5, and 9.0 g / kg) once daily for 5 consecutive days significantly inhibited the increase in whole blood viscosity caused by high molecular weight dextran, demonstrating a significant anti-hyperviscosity syndrome effect.

[0126] Therefore, it can be seen that the traditional Chinese medicine composition of the present invention has a significant effect of promoting blood circulation and removing blood stasis.

[0127] In summary, the traditional Chinese medicine composition of the present invention, with Angelica sinensis, Ligusticum chuanxiong, Paeonia lactiflora, Cinnamomum cassia, Paeonia suffruticosa, Panax ginseng, and Rehmannia glutinosa as its main components, is suitable for cardiovascular and cerebrovascular diseases, traumatic injuries, external blood stasis, and gynecological blood stasis syndrome. The production process of the blood-activating and stasis-removing traditional Chinese medicine composition of the present invention is controllable, and the prepared traditional Chinese medicine composition has the characteristics of stable quality, definite efficacy, and good patient compliance.

[0128] It should be noted that, in this document, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0129] 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. Therefore, the present invention is not to be limited to the embodiments described herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A traditional Chinese medicine composition for promoting blood circulation and removing blood stasis, characterized in that, The raw materials of the traditional Chinese medicine composition include: Angelica sinensis, Ligusticum chuanxiong, Paeonia lactiflora, Cinnamomum cassia, Paeonia suffruticosa, Panax ginseng, and Rehmannia glutinosa.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition comprises the following raw materials in parts by weight: Angelica sinensis 6-15 parts; Chuanxiong (Ligusticum striatum) 5-12 parts; 10-20 parts of white peony root; 3-8 parts cinnamon; 8-15 parts of peony bark; 5-10 portions of ginseng; 10-30 parts of raw Rehmannia glutinosa.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 8-12 parts of Angelica sinensis; Chuanxiong (Ligusticum striatum) 6-10 parts; 12-18 parts of white peony root; 3-6 parts cinnamon; 8-12 parts of peony bark; 6-10 portions of ginseng; 10-15 parts of raw Rehmannia glutinosa.

4. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The preparation method includes: Angelica sinensis, Ligusticum chuanxiong, cinnamon and peony bark are decocted in water, and the volatile oil is collected at the same time to obtain the dregs, extract and volatile oil; The dregs, white peony root, ginseng, and rehmannia root were decocted in water, filtered, and the filtrate and the extract were combined and concentrated to obtain a clear extract. β-cyclodextrin and volatile oil were encapsulated in water at 50-80℃, refrigerated, and filtered to obtain the inclusion complex. The excipients, the extract, and the inclusion complex are prepared into a traditional Chinese medicine composition of the desired dosage form.

5. The method for preparing the traditional Chinese medicine composition according to claim 4, characterized in that, The decoction method is as follows: decoct for 0.5 to 4 hours each time, and decoct 2 to 5 times; And / or, the relative density of the ointment at 50~80°C is 1.10~1.

20.

6. The preparation method according to claim 4 or 5, characterized in that, The mass ratio of the volatile oil to β-cyclodextrin is 1:(5~15). And / or, the excipients include at least one of soluble starch, maltodextrin, and sucrose powder; And / or, the dosage form is any one of granules, tablets or capsules.

7. A method for quality control of the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The quality control method includes: Thin-layer chromatography was used to qualitatively identify ginseng and rehmannia in traditional Chinese medicine compositions. Fingerprint chromatograms of traditional Chinese medicine compositions were established using high performance liquid chromatography. The contents of ferulic acid, ligustilide, paeoniflorin, paeonol and cinnamaldehyde in the traditional Chinese medicine composition were determined by high performance liquid chromatography.

8. The quality control method according to claim 7, characterized in that, The determination conditions for the high performance liquid chromatography method are as follows: Column: C 18 Chromatographic column; And / or, mobile phase: mobile phase A is acetonitrile, mobile phase B is 0.1%~0.5% phosphoric acid solution; And / or, detection wavelength: 230nm~321nm; And / or, flow rate: 0.5~1.2 mL / min; And / or, column temperature: 25~30℃; And / or, the gradient elution procedure is as follows: 0–5 min, mobile phase A (%): 15→17, mobile phase B (%): 85→83; 5–8 min, mobile phase A (%): 17→26, mobile phase B (%): 83→74; 8–15 min, mobile phase A (%): 26→38, mobile phase B (%): 74→62; 15–54 min, mobile phase A (%): 38 → 65, mobile phase B (%): 62 → 35; 54–60 min, mobile phase A (%): 65→90, mobile phase B (%): 35→10; 60–74 min, mobile phase A (%): 90→15, mobile phase B (%): 10→85; 75 min, mobile phase A (%): 15, mobile phase B (%):

85.

9. The use of a traditional Chinese medicine composition according to any one of claims 1 to 3 or a traditional Chinese medicine composition obtained by the preparation method according to any one of claims 4 to 8 in the preparation of a drug for promoting blood circulation and removing blood stasis.

10. The application according to claim 9, characterized in that, The drugs for promoting blood circulation and removing blood stasis include any one of the following: drugs for treating coronary heart disease, drugs for treating traumatic blood stasis, and drugs for treating menopausal blood stasis.

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