Traditional Chinese medicine composition for raising yang, replenishing qi and nourishing blood, and preparation method and application thereof

Abstract

The invention discloses a Chinese medicine composition for raising yang, replenishing qi and nourishing blood, and a preparation method and application thereof, and belongs to the field of medical technology. The Chinese medicine composition for raising yang, replenishing qi and nourishing blood comprises astragalus, angelica, bupleurum, scutellaria slices, dried orange peel, pinellia tuber, dried ginger slices, cinnamon bark, roasted licorice, codonopsis slices and jujube. The Chinese medicine composition is composed of astragalus as the monarch drug, codonopsis tuber, cinnamon bark, dried ginger, angelica and jujube as the minister drug, pinellia tuber, dried orange peel and scutellaria tuber as the adjuvant drug, bupleurum as the adjuvant and messenger drug, and roasted licorice as the messenger drug, which conforms to the "monarch, minister, assistant and messenger" compatibility treatment principle, and all drugs are compatible, cold and hot are used together, qi is replenished and qi is adjusted, and the rise and fall are adjusted in unison, so as to achieve the effects of replenishing qi, raising clearness, warming yang and nourishing blood. The invention also prepares the drug into granules by improving the drug preparation process, which is conducive to long-term use by patients, and meets the needs of clinical drug use and preparation production at the same time, and has high social and clinical value. The invention provides a practical new drug for the efficient treatment of patients with neck arthralgia of qi and blood deficiency syndrome.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a Chinese medicine composition for promoting yang, replenishing qi and nourishing blood, and a preparation method and application thereof. Background Art

[0002] Neck arthralgia, also known as cervical spondylosis, is a disease with degeneration of the cervical intervertebral disc as the main lesion, causing cervical spinal stenosis and nerve root compression. It is a general term for cervical radiculopathy, cervical disc herniation, and hyperplastic cervical spondylosis. It belongs to the categories of "arthralgia", "spasm", "paralysis", and "vertigo" in traditional Chinese medicine. At present, there are many methods to choose from in the clinical treatment of cervical spondylosis, but the actual efficacy reports vary, and there is a lack of radical treatment measures. The main methods are cervical traction, oral non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy to relieve pain symptoms and promote cervical rehabilitation. NSAIDs are the first-line medication for relieving pain in cervical spondylosis, but long-term use significantly increases the risk of gastrointestinal bleeding, and fails to fundamentally cure cervical spondylosis, and the recurrence rate after treatment is high.

[0003] According to different causes of neck arthralgia, TCM divides this disease into wind-cold-dampness obstruction type, qi stagnation and blood stasis type, phlegm-dampness obstruction type, liver-kidney deficiency type, qi-blood deficiency type, qi-deficiency and blood stasis type, and qi-deficiency and dampness excess type according to syndrome differentiation and treatment based on clinical practice. However, there are few reports on the research of Chinese medicine auxiliary therapy for qi-blood deficiency type neck arthralgia. Summary of the invention

[0004] The purpose of the present invention is to provide a Chinese medicine composition for raising yang, invigorating qi and nourishing blood, and a preparation method and application thereof, so as to solve the problems existing in the above-mentioned prior art. The Chinese medicine composition for raising yang, invigorating qi and nourishing blood prepared by the present invention can significantly improve the neck arthralgia of qi and blood deficiency syndrome, and provide a practical new drug for the efficient treatment of patients with neck arthralgia of qi and blood deficiency syndrome.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] The present invention provides a Chinese medicine composition for promoting yang, replenishing qi and nourishing blood, comprising the following components in parts by weight:

[0007] 400-600 parts of astragalus, 200-300 parts of angelica, 100-200 parts of bupleurum, 100-200 parts of scutellaria slices, 100-200 parts of tangerine peel, 100-200 parts of pinellia, 200-300 parts of dried ginger slices, 100-300 parts of cinnamon, 100-200 parts of roasted liquorice, 200-500 parts of codonopsis slices and 200-500 parts of jujube.

[0008] Further, it comprises the following components in parts by weight:

[0009] 400 parts of Astragalus, 200 parts of Angelica, 200 parts of Bupleurum, 133 parts of Scutellaria slices, 200 parts of Tangerine peel, 100 parts of Pinellia, 200 parts of Dry ginger slices, 100 parts of Cinnamon, 100 parts of Roasted Licorice, 200 parts of Codonopsis slices and 200 parts of Jujube.

[0010] The present invention also provides a method for preparing the Chinese medicine composition, comprising the following steps:

[0011] Take the prescribed amount of components and boil them, collect the filtrate and concentrate it under reduced pressure to obtain a clear paste;

[0012] Add auxiliary materials to the clear paste, spray dry, collect the extract powder, add auxiliary materials to the extract powder, mix well, granulate and package.

[0013] Furthermore, the decoction condition is to decoct twice, adding 8 times the volume of water to the prescribed amount of components each time, and decoct for 1 hour.

[0014] Furthermore, the reduced pressure concentration is performed to a clear paste with a relative density of 1.08-1.12.

[0015] Furthermore, the auxiliary material is maltodextrin; the mass ratio of the total amount of maltodextrin added to the amount of clear paste used is 1:2.29.

[0016] The present invention also provides application of the traditional Chinese medicine composition in preparing medicine for treating neck arthritis.

[0017] Furthermore, the neck arthralgia is neck arthralgia of qi and blood deficiency syndrome.

[0018] The present invention also provides a medicine for auxiliary treatment of neck arthralgia of qi and blood deficiency syndrome, comprising the traditional Chinese medicine composition.

[0019] Furthermore, the dosage form of the drug comprises granules.

[0020] The present invention discloses the following technical effects:

[0021] The invention prepares a Chinese medicinal composition for promoting yang, invigorating qi and nourishing blood for qi and blood deficiency syndrome of neck arthralgia and arthralgia. The prescription comprises eleven Chinese medicinal materials, namely, astragalus, angelica, bupleurum, scutellaria slices, tangerine peel, pinellia tuber, dried ginger slices, cinnamon bark, roasted liquorice, codonopsis pilosula slices and jujube. Through reasonable compatibility, the whole prescription uses astragalus as the monarch medicine, codonopsis pilosula, cinnamon bark, dried ginger, angelica and jujube as minister medicines, pinellia tuber, tangerine peel and scutellaria tuber as adjuvant medicines, bupleurum as adjuvant and messenger medicine, and roasted liquorice as messenger medicine. The prescription complies with the treatment principle of "monarch, minister, assistant and messenger" compatibility, uses cold and heat together, invigorates qi and regulates qi, and regulates ascending and descending in unison, so as to achieve the effects of invigorating qi, raising clearness, warming yang and nourishing blood. The present invention also improves the drug preparation process to prepare the drug into granules. The granules have the advantages of large drug loading capacity, good stability, and convenient taking and carrying. Without reducing the efficacy or changing the medicinal properties, they better adapt to the requirements of modern fast-paced life and are conducive to long-term use by patients. At the same time, they meet the needs of clinical drug use and preparation production, and have high social and clinical value.

[0022] The Shengyang Yiqi Yangxue granule medicine prepared by the invention can obviously improve the neck arthralgia of qi and blood deficiency syndrome, and provides a practical new medicine for the efficient treatment of the neck arthralgia patients of qi and blood deficiency syndrome. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 This is a process flow chart for preparing Shengyang Yiqi Yangxue Granules;

[0025] Figure 2-Figure 4 This is the HPLC spectrum of the specificity test of the astragaloside IV content determination method; Figure 2 Astragaloside IV is the reference substance; Figure 3 For the test product; Figure 4 is the negative control sample;

[0026] Figure 5 This is a statistical chart of the moisture absorption rate of particles under different humidity fields. DETAILED DESCRIPTION

[0027] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0028] It should be understood that the terms described in the present invention are only for describing a particular embodiment and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. The intermediate value in any stated value or stated range, and each smaller range between any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0029] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0030] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0031] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0032] The sources and quality requirements of the decoction pieces of each component of the Shengyang Yiqi Yangxue granules of the present invention are as follows:

[0033] Astragalus: This product is a processed product of the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, a plant of the Leguminosae family. The quality meets the identification description under Astragalus in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0034] Angelica sinensis: This product is a processed product of the dried root of Angelica sinensis (Oliv.) Diels, a plant of the Umbelliferae family. The quality meets the identification description under Angelica sinensis in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0035] Bupleurum: This product is a processed product of the dried root of Bupleurum chinense DC., a plant of the Umbelliferae family. The quality meets the identification description under Bupleurum in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0036] Huangqin Tablets: This product is a processed product of the dried root of Scutellaria baicalensis Georgi, a plant of the Lamiaceae family. The quality meets the identification description under Scutellaria baicalensis in Volume 1 of the 2020 edition of the Chinese Pharmacopoeia.

[0037] Tangerine peel: The product is the processed dried mature peel of the Rutaceae plant Citrus reticulata Blanco and its cultivars. The quality meets the identification description under Tangerine peel in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0038] French Pinellia: This product is a processed product of the dried tuber of Pinellia ternata (Thunb.) Breit., a plant of the Araceae family. The quality meets the identification description under the Pinellia item in Volume 1 of the 2020 edition of the Chinese Pharmacopoeia.

[0039] Dried ginger slices: This product is a processed product of the dried rhizome of Zingiber officinal Rosc., a plant of the ginger family. The quality meets the identification description under the dried ginger item in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0040] Cinnamon: This product is a processed product of the dried bark of Cinnamomum cassia Presl, a plant of the Lauraceae family. The quality meets the identification description under Cinnamon in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0041] Roasted Licorice: This product is a processed product of the dried roots and rhizomes of Glycyrrhiza uralensis Fisch., a plant of the Leguminosae family. The quality meets the identification description under Licorice in Volume 1 of the 2020 edition of the Chinese Pharmacopoeia.

[0042] Codonopsis pilosula tablets: This product is a processed product of the dried root of Codonopsis pilosula (Franch.) Nannf., a plant of the Campanulaceae family. The quality meets the identification description under Codonopsis pilosula in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0043] Jujube: This product is a processed product of the dried mature fruit of the Rhamnaceae plant Ziziphusjujuba Mill. The quality meets the identification description under the jujube item in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0044] The above-mentioned components of the decoction pieces were purchased from Guangzhou Zhixin Chinese Medicine Decoction Pieces Co., Ltd.; the auxiliary material maltodextrin was purchased from Hunan Jiudian Hongyang Pharmaceutical Co., Ltd.

[0045] The root cause of neck pain in the syndrome of qi and blood deficiency is that the clear yang does not rise, the yang qi is insufficient, and the yin blood does not grow. The "Inner Canon" states: "The essence of the five internal organs and six bowels is all injected into the eyes... It goes up to the brain and then comes out of the neck." "If the upper qi is insufficient, the brain will be dissatisfied, the ears will ring, the head will tilt, and the eyes will be dizzy." The neck is a bridge connecting the internal organs and the brain. Due to congenital weakness, or acquired chronic strain, or exogenous wind, cold and dampness that deplete yang qi and block the qi mechanism, the clear yang does not rise, and the upper part of the body is deficient. Qi and blood are mutually dependent, and if one is damaged, all are damaged, and if one is deficient, all are deficient. Qi deficiency cannot be warmed into tangible essence and blood, resulting in the obstruction of qi and blood in the neck meridians, which cannot nourish the brain, the head, and the five senses, resulting in dizziness and other manifestations of qi and blood deficiency syndrome.

[0046] The spleen is the foundation of the acquired constitution, so this method starts with the spleen and stomach. It is believed that due to damage to the spleen and stomach, the production of qi and blood is weak, resulting in poor qi movement and loss of nourishment to the tendons and veins, which leads to qi and blood deficiency. The spleen and stomach qi deficiency leads to blood deficiency and blood stasis, which causes dizziness and pain. Therefore, Buzhong Yiqi Decoction should be used to replenish qi, strengthen the spleen, and raise yang. The astragalus, codonopsis, roasted licorice, tangerine peel, and bupleurum in this prescription meet this purpose, and the ginger is replaced with dried ginger to add more yang-warming power.

[0047] Based on the above pathogenesis, the "Inner Canon of Medicine" says: "If the body is deficient, warm it with qi; if the essence is deficient, supplement it with flavor. In terms of treatment, it is necessary to raise the clear and lower the turbid, warm the yang and nourish the blood first. The present invention has created the "Qi-invigorating, Yang-invigorating and Blood-nourishing Method" in clinical practice, and the specific prescription is explained as follows:

[0048] In the formula, Astragalus is the main ingredient, which can both replenish qi and raise yang. It can replenish the middle qi, raise yang and consolidate the exterior, and help yang to produce blood, so it is used as the main ingredient. Codonopsis is sweet and neutral in nature. It enters the spleen and lung meridians, helping Astragalus to replenish the middle qi; Cinnamon is pungent and sweet in nature, and has the effect of warming and replenishing the heart yang and warming and promoting yang qi. Dried ginger is pungent in nature and hot in nature, which can warm and replenish the spleen yang and help the heart to promote yang. Angelica is pungent in nature and active in nature, and is a product that replenishes both qi and blood. When paired with Astragalus, it can further increase the effect of replenishing qi and nourishing blood; Jujube has the function of replenishing the middle qi and nourishing blood, and relieving the medicinal properties; the above five medicines are combined as the ministerial medicine, which can not only replenish the spleen and stomach, the source of qi and blood biochemical transformation, but also warm the heart yang and help blood production. French Pinellia is pungent and slightly bitter in taste. The pungent taste can help the clear yang rise, and the bitter taste can help the turbid yin descend and discharge, and is mainly used to reduce qi. Tangerine peel is bitter and pungent in taste and warm in nature. Bitterness can dry out dampness and reduce turbid yin, while pungentness can help yang qi rise. It also has the function of regulating the spleen and stomach qi to prevent sweet and warm tonic products from blocking the middle jiao. Scutellaria baicalensis is bitter and cold in nature. It is used to control the sweet and warm nature of the main and ministerial drugs and prevent pungent, hot, warm and dry. The three are used together to achieve the effect of raising the clear yang and reducing turbid yin, and are collectively adjuvant drugs. Bupleurum is an adjuvant, carrying the drugs upward, leading the clear to remove the turbid, and raising the clear yang. Roasted licorice harmonizes the drugs and is a guiding drug. The drugs are combined, cold and hot, invigorating qi and regulating qi, and ascending and descending in unison, so as to achieve the effect of invigorating qi and raising the clear, warming yang and nourishing blood.

[0049] The preliminary study of the present invention adjusted the compatibility principle of monarch, minister, assistant and envoy of each prescription, and optimized the above compatibility ratio. The prescription drugs according to this compatibility principle have the most significant effect on patients with neck arthralgia of qi and blood deficiency syndrome.

[0050] Example 1

[0051] 1. Shengyang Yiqi Yangxue Granules Decoction Piece Prescription

[0052] It contains 400g of Astragalus, 200g of Angelica, 200g of Bupleurum, 133g of Scutellaria baicalensis slices, 200g of Tangerine Peel, 100g of Pinellia ternata, 200g of Dry Ginger Slices, 100g of Cinnamon Bark, 100g of Roasted Licorice, 200g of Codonopsis pilosula slices and 200g of Jujube.

[0053] 2 Preferred preparation process

[0054] (1) Decoction: Decoction the above 11 ingredients twice, adding 8 times the volume of water each time, and decoct for 1 hour. Combine the decoctions, filter (through a 200-mesh sieve) to obtain the extract, and set aside.

[0055] (2) Concentration: The extract is concentrated under reduced pressure (-0.06 to -0.08 MPa, 60 to 80°C) until the relative density of the clear paste is 1.08 to 1.12 (60°C). Filter and check the appearance, charred matter, insoluble matter and relative density (60°C) of the clear paste. If qualified, weigh it and set aside.

[0056] (3) Drying: Take qualified clear paste, add 150 g of maltodextrin, mix well, spray dry, control the inlet air temperature at 175 ± 5 °C, the outlet air temperature at 90 ± 5 °C, and collect the dry extract powder.

[0057] (4) Mixing: Take the above dry extract powder, add appropriate amount of maltodextrin to make the total amount of material 1 kg, mix well and set aside.

[0058] (5) Granulation: Take the mixed dry paste powder obtained in step (4), dry granulate it, and collect qualified granules.

[0059] (6) Take qualified granules, use polyester / aluminum / polyethylene medicinal composite film and bags, and heat-seal them into bags with 5 g each, which are Shengyang Yiqi Yangxue Granules.

[0060] Figure 1 This is a flow chart of the preparation process of Shengyang Yiqi Yangxue Granules.

[0061] 3 Preparation process optimization study

[0062] 3.1 Specificity test of astragaloside IV content determination method

[0063] Determined by high performance liquid chromatography (General Rules 0512 of Part IV of the 2020 edition of the Chinese Pharmacopoeia).

[0064] ①Chromatographic conditions: Chromatographic column: Kromasil C18 column (4.6×250 mm, 5 μm); Mobile phase: acetonitrile-water (32:68); Evaporative light scattering detector; Flow rate: 1 mL·min -1 ; Column temperature: 25℃.

[0065] ② Preparation of reference solution: Take an appropriate amount of astragaloside IV reference substance (batch number: 110781-201616), accurately weigh it, and add 80% methanol to make a solution containing 319.9 μg of astragaloside IV per 1 mL.

[0066] ③ Preparation of test solution: Weigh 183g of 11 pieces of decoction including astragalus, angelica, bupleurum, etc. (36g of astragalus, 18g of angelica, 18g of bupleurum, 12g of scutellaria, 18g of tangerine peel, 9g of pinellia, 18g of dried ginger, 9g of cinnamon, 9g of licorice, 18g of codonopsis and 18g of jujube) according to the prescription ratio, add 8 times the amount of water, decoct twice, each time for 2h, combine the decoction, filter, concentrate the filtrate and make up to 250mL, accurately pipette 5mL of the concentrate into a 50mL stoppered conical flask , accurately add 50mL of 80% methanol solution containing 4% concentrated ammonia test solution (take 4mL of concentrated ammonia test solution, add 80% methanol to 100mL, shake well), weigh the weight, heat under reflux for 1 hour, cool, weigh again, make up the lost weight with 80% methanol solution containing 4% concentrated ammonia test solution, shake well, filter, accurately measure 25mL of the filtrate, evaporate to dryness, dissolve the residue with 80% methanol, transfer to a 5mL volumetric flask, add 80% methanol to the scale, shake well, filter, and take the filtrate.

[0067] ④ Preparation of negative sample solution: Weigh the slices except Astragalus according to the prescription ratio, add 8 times the amount of water, decoct twice, 2 hours each time, combine the decoctions, filter, concentrate the filtrate and make up to 250mL, and prepare the negative sample solution according to the preparation method of the test sample.

[0068] ⑤ Judgment of negative interference: Pipette the above-mentioned reference substance, test substance and negative control solution, inject them into liquid chromatograph respectively, record the chromatogram, and the results show that there is no other peak interference in the retention time corresponding to astragaloside I in the negative control spectrum and the reference substance and test sample spectrum, indicating good selectivity and no negative interference. Figure 2-Figure 4 This is the HPLC spectrum of the specificity test for the determination method of astragaloside IV.

[0069] 3.2 Orthogonal test optimization process

[0070] The factor level design is shown in Table 1

[0071] Table 1 Factor level table

[0072]

[0073] 3.3 Preparation of orthogonal samples

[0074] According to the prescription ratio, 183 g of 11 medicinal pieces including Astragalus, Angelica, and Bupleurum were weighed, extracted according to the orthogonal experimental arrangement in Table 2, the decoctions were combined, filtered, and the filtrate was concentrated and fixed to 250 mL.

[0075] 3.4 Determination of solid matter content

[0076] Accurately pipette 25 mL of each sample concentrate into an evaporating dish at a constant weight, evaporate to dryness in a water bath, and determine the solid mass according to the drying loss determination method (Chinese Pharmacopoeia 2020 Edition Part IV 2201). The formula is as follows:

[0077] Solid mass (g) = (W × V) / 25;

[0078] W is the mass of dry solids in 25 mL of concentrate, and V is the constant volume.

[0079] 3.5 Determination of Astragaloside IV

[0080] Determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, 0521).

[0081] 3.6 Data processing and process optimization

[0082] The comprehensive weighted scoring method was used, with the maximum value of 9 tests of solid quality and astragaloside IV content as 100 points. The total amount of each index component was converted into a scoring value, the weighting coefficient of astragaloside IV content was determined to be 0.6, and the weighting coefficient of solid quality was 0.4. The score values ​​of each index component in each test were multiplied by the corresponding weighting coefficients and then summed to obtain a comprehensive score value. The orthogonal test results were calculated using the comprehensive score value, and variance analysis was performed. The results are shown in Tables 2 and 3.

[0083] Table 2 Orthogonal test arrangement and results

[0084]

[0085] Comprehensive score = (total amount of astragaloside IV / maximum total amount of astragaloside IV) × 60 + (yield of ointment / maximum yield of ointment) × 40

[0086] Table 3 ANOVA results

[0087]

[0088] F 0.05 (2, 2)) = 19.00

[0089] From the intuitive analysis, we can see that the order of factors affecting the extraction effect is: decoction times > water addition > decoction time, and the best process combination is A3B2C3. From the variance analysis, we can see that the decoction times (A) have a significant impact on the results. Considering that the level range of factors A 2 and 3 is small, the final optimal extraction process is A2B1C2, that is, decoction twice, each time adding 8 times the amount of water, and extraction for 1h.

[0090] 3.7 Verification of optimal extraction process conditions

[0091] According to the prescription ratio, 3 portions of the decoction pieces were weighed, each portion was 183 g, and the extraction was carried out according to the optimized process, and the total content of astragaloside IV and the solid mass were determined. The results are shown in Table 4.

[0092] Table 4 Process verification test results

[0093]

[0094] The results show that the verification test results are basically consistent with the orthogonal test optimization results, indicating that the process conditions selected by the orthogonal test are reasonable, stable and feasible.

[0095] 3.8 Investigation of concentration and drying process

[0096] In combination with actual production conditions, the extract is concentrated by reduced pressure and the paste is dried by spray drying.

[0097] Since the relative density of the concentrate has a great influence on the spray drying effect, the test investigated the spray drying effect of the concentrate with relative density of 1.05, 1.10, and 1.15 (60°C), and determined the content of astragaloside IV in the dry paste. The test weighed 3 portions of the slices according to the prescription ratio, each 187g, and after the preferred extraction process, the concentrates were concentrated under reduced pressure to relative density of 1.05, 1.10, and 1.15 (60°C), and then spray dried to obtain dry paste powder. The results are shown in Table 5.

[0098] 3.8.1 Preparation of extract samples

[0099] Accurately measure 10mL of the extract and place it in a 50mL volumetric flask, accurately add 50mL of 80% methanol solution containing 4% concentrated ammonia test solution (take 4mL of concentrated ammonia test solution, add 80% methanol to 100mL, shake well), weigh the weight, heat under reflux for 1 hour, cool, weigh again, make up the lost weight with 80% methanol solution containing 4% concentrated ammonia test solution, shake well, filter, accurately measure 40mL of the filtrate, evaporate to dryness, dissolve the residue with 80% methanol, transfer to a 2mL volumetric flask, add 80% methanol to the scale, shake well, filter, and take the filtrate.

[0100] 3.8.2 Preparation of concentrated test samples

[0101] Accurately measure 5 mL of the concentrate and place it in a 50 mL volumetric flask, accurately add 50 mL of 80% methanol solution containing 4% concentrated ammonia test solution (take 4 mL of concentrated ammonia test solution, add 80% methanol to 100 mL, and shake well), weigh the weight, heat under reflux for 1 hour, cool, weigh again, make up the lost weight with 80% methanol solution containing 4% concentrated ammonia test solution, shake well, filter, accurately measure 25 mL of the filtrate, evaporate to dryness, dissolve the residue with 80% methanol, transfer to a 5 mL volumetric flask, add 80% methanol to the scale, shake well, filter, and take the filtrate.

[0102] 3.8.3 Preparation of dry paste powder test sample

[0103] Accurately measure 1 g of dry powder and place it in a 50 mL volumetric flask, accurately add 50 mL of 80% methanol solution containing 4% concentrated ammonia test solution (take 4 mL of concentrated ammonia test solution, add 80% methanol to 100 mL, and shake well), weigh the weight, heat and reflux for 1 hour, cool, weigh again, make up the lost weight with 80% methanol solution containing 4% concentrated ammonia test solution, shake well, filter, accurately measure 25 mL of the filtrate, evaporate to dryness, dissolve the residue with 80% methanol, transfer to a 5 mL volumetric flask, add 80% methanol to the scale, shake well, filter, and take the filtrate.

[0104] 3.8.4 Determination method

[0105] Accurately pipette each test sample solution into a sample, record the chromatogram, and determine the content of astragaloside IV in the sample.

[0106] Table 5 Concentration and drying test results

[0107]

[0108] The results showed that when the extract was concentrated under reduced pressure to a relative density of 1.05-1.15, there was no significant difference in the retention rate of astragaloside IV. When the concentrate was spray-dried, there was also no significant difference in the retention rate of astragaloside IV in the dry paste powder. However, during the spray drying process, the wall sticking phenomenon was serious when the relative density was 1.15, and the powder was dark brown. There was less wall sticking when the relative densities were 1.05 and 1.10. Combined with production experience, when the relative density was 1.08-1.12, the dry paste powder was in a more ideal state and less time-consuming. Therefore, the relative density of the concentrate was determined to be 1.08-1.12.

[0109] Considering that the wall sticking phenomenon will be more serious during pilot scale-up production, in order to minimize the loss of dry paste, an appropriate amount of anti-adhesive agent is planned to be added to the concentrate. Maltodextrin has good solubility and good formability in dry granulation. Based on preliminary experiments and production experience, maltodextrin is selected as the anti-adhesive agent for spray drying. Since the daily dosage of this prescription is 61g, the average paste yield is 34.26%, that is, the dry extract is about 20.90g, so the daily dosage of the preparation is planned to be 30g. In the experiment, 3 portions of the clear paste prepared according to the aforementioned preferred process were taken, each portion was equivalent to 610g of the decoction piece (intended to be made into 300g), and the relative density was 1.08-1.12 (60°C). After adding 10%, 15%, and 20% of the preparation amount of maltodextrin, respectively, they were placed in a DC-1500 experimental spray dryer for spray drying (the inlet air temperature was controlled at 180±5°C and the outlet air temperature was 90±5°C). After drying, the weight of the dry extract adhering to the drying tower was weighed respectively. The results are shown in Table 6.

[0110] Table 6 Effect of maltodextrin addition on spray drying effect

[0111]

[0112] The results showed that when 15% of maltodextrin was added, the sticking phenomenon of the extract during spray drying could be effectively improved. Therefore, it was determined that 15% of maltodextrin was added to the extract of this product during spray drying.

[0113] 3.9 Molding process research

[0114] 3.9.1 Determination of the ratio of extract powder to excipients in the prescription

[0115] The daily dosage of the raw medicinal slices in this prescription is 61g, calculated based on an average solid yield of 34.23%, that is, 20.88g of dry extract powder without loss, 30g of which is planned to be made into granules, and 9.12g of auxiliary materials are added. Calculated based on 3 times a day, 2 bags at a time, the planned dosage specification is 5g per bag, and the ratio of extract to auxiliary materials is approximately 2.29:1.

[0116] 3.9.2 Determination of diluent type

[0117] According to the current production equipment conditions, this preparation uses dry granulation. Common fillers for Chinese patent medicine granules include dextrin, soluble starch, maltodextrin, etc. Among them, maltodextrin has the characteristics of stability, good filling effect, excellent solubility, low moisture absorption, and no odor, and is suitable as a filler for dry granulation. Therefore, this product chooses maltodextrin as a filler.

[0118] 3.9.3 Determination of moisture content of materials

[0119] For dry granulation, the moisture content of the material is one of the main factors affecting the granulation effect. The moisture content has a significant impact on the granule forming rate and moisture absorption rate. Therefore, the test uses the granule yield and granule appearance of one dry pressing as indicators to examine the most suitable material moisture content in the dry pressing granulation process.

[0120] Weigh the dry extract powder and maltodextrin, mix them, dry them or add appropriate amount of water, adjust the moisture content to 3%, 4%, 5%, 6%, mix them, use METTLER MJ33 infrared moisture meter to measure the moisture content of the materials, granulate them with GLZ2-25 dry granulator, control the pressure of the pressing wheel to 0.3-0.6Mpa, granulate them with 18 mesh galvanized screen, take the particles with particle size between No. 1 sieve and No. 5 sieve obtained in a dry granulation test as qualified particles, and the rest as unqualified particles, weigh them respectively, calculate the forming rate, and observe the appearance of the particles. The results are shown in Table 7.

[0121] Table 7 Results of one-step dry granulation of materials with different moisture contents

[0122]

[0123] The results show that when the moisture content of the material is 3-6%, the granule forming rate is equivalent. When the moisture content exceeds 6%, a small amount of mottled phenomenon appears in the granules. Therefore, the moisture content of the dry granulation material is controlled between 3 and 5%.

[0124] 3.9.4 Determination of critical relative humidity

[0125] Prepare a series of saturated salt solutions, place them in glass desiccators, and keep them at a constant temperature of 25°C for 48 hours to balance the internal humidity and form an environment with different relative humidity (RH). Put about 2g of Shengyang Yiqi Yangxue Granules in a weighing bottle that has been dried to constant weight, spread it on the bottom of the bottle with a thickness of about 2mm, weigh it, and dry it to constant weight. Weigh it accurately, open the weighing bottle cap, place it in the above-mentioned desiccators with different RH, absorb moisture to constant weight, and calculate the moisture absorption rate by accurate weighing to determine its CRH. Plot the moisture absorption percentage data as the vertical axis and the relative humidity data as the horizontal axis to calculate the critical relative humidity. The results are shown in Table 8. Figure 5 .

[0126] Table 8 Determination results of critical relative humidity of particles

[0127]

[0128] The results show that the critical relative humidity of the granules is about 65%. Therefore, when producing this preparation, the relative humidity of the environment should be controlled below 65%. At the same time, corresponding requirements are also put forward for packaging materials and storage conditions.

[0129] 3.9.5 Selection of packaging materials

[0130] Take 6 bags of PET / AL / PE structure, weigh each bag accurately, put 5g of granules in each bag, seal tightly, weigh the packaged granule sample accurately, and put the sample in a dryer with saturated sodium chloride solution (RH is 75±1% at constant temperature of 15.5~60℃) at the bottom, observe at 40±2℃ for 10 days, take samples on the 5th and 10th day to measure the weight of the sample after moisture absorption, calculate the moisture absorption weight gain of the granules, and observe the appearance of the 10-day sample. The results are shown in Table 9.

[0131]

[0132] Table 9 Investigation results of medicinal composite films (n=3)

[0133]

[0134] The results showed that the moisture content and appearance of the particles packaged with polyester / aluminum / polyethylene medicinal composite film did not change significantly after 10 days. Therefore, polyester / aluminum / polyethylene medicinal composite film can be used as a packaging material that directly contacts drugs.

[0135] 3.9.6 Stability test of Shengyang Yiqi Yangxue granules

[0136] Under the sample packaging conditions, Shengyang Yiqi Yangxue Granules were inspected at a constant temperature and humidity for 6 months. There was no change in appearance and the identification showed positive reactions. The particle size, moisture, solubility, filling volume difference, and microbial limit tests showed that the extract met the requirements, indicating that the sample was basically stable within 6 months (Table 10).

[0137] Table 10 Shengyang Yiqi Yangxue Granule Stability Test Results

[0138]

[0139] Effect example

[0140] 1 Clinical Data

[0141] 1.1 General Information

[0142] This experiment was divided into an experimental group and a control group, with 60 cases in each group, for a total of 120 cases. Among them, the experimental group had 60 cases, including 31 males and 29 females, with an average age of 54.90±2.97 years old; the control group had 60 cases, including 30 males and 30 females, with an average age of 55.60±2.55 years old. The statistical tests of gender and age between the two groups were comparable (P>0.05).

[0143] 1.2. TCM diagnostic criteria

[0144] According to the 2002 edition of the "Guidelines for Clinical Research of New Chinese Medicines" formulated by the Ministry of Health of the People's Republic of China, regarding the "Clinical Guidelines for the Treatment of Cervical Spondylosis with New Chinese Medicines", the diagnostic criteria for Qi and Blood Deficiency are as follows:

[0145] Main symptoms: dizziness, headache, limb numbness, limb paralysis. Secondary symptoms: palpitations, insomnia, tinnitus, chills, dry mouth, constipation.

[0146] 1.3 Inclusion criteria

[0147] Meet the criteria of 1.2 TCM diagnosis form; be between 18 and 60 years old; have good compliance with medical treatment and can take medicine and acupuncture treatment as directed; have not received other treatment methods in the past month; agree to participate in this study and sign the informed consent form.

[0148] 1.4. Exclusion criteria

[0149] Patients who do not meet the inclusion criteria; those with a history of allergy to the ingredients in Shengyang Yiqi Yangxue Granules and methylcobalamin; those with a history of cervical trauma such as cervical fracture, cervical spinal cord injury, or cervical surgery; those with tuberculosis or tumors; those with cognitive impairment; those with severe cardiopulmonary insufficiency, liver and kidney insufficiency, abnormal coagulation function, those in the acute infectious period of infectious diseases, those in the acute and severe onset period of infectious diseases; pregnant or lactating women.

[0150] 1.5. Shedding standard:

[0151] Those who are unable to complete the trial due to any of the following reasons may be considered as dropouts.

[0152] Those who have poor compliance, use other treatment methods without authorization, etc., which violate the research protocol; those who voluntarily request to withdraw from the clinical research; those who have serious adverse reactions or progressive aggravation of other diseases during the treatment process and are not suitable for continuing treatment; those who are lost to follow-up later.

[0153] 1.6. Cervical spondylosis symptom grading and quantitative table

[0154] A quantitative table was developed based on the symptoms and signs of cervical spondylosis in the "Principles for Clinical Guidance Research of New Chinese Medicines (Trial)" issued in 2002, and 10 items were used to evaluate the cervical function.

[0155] Table 11 Quantitative table of symptoms and signs of cervical spondylosis

[0156]

[0157]

[0158] 2 Treatment and observation methods

[0159] 2.1. Treatment

[0160] Treatment group: On the basis of conventional acupuncture treatment, the patients orally took Shengyang Yiqi Yangxue Granules prepared by the above preferred preparation method, washed down with boiled water, 3 times a day, 2 bags each time (5 g / bag).

[0161] Control group: In addition to conventional acupuncture treatment, patients took 1 tablet of methylcobalamin orally 3 times a day.

[0162] Acupuncture conventional treatment group acupoints:

[0163] Fengchi (double), cervical Jiaji (double), Tianzhu (double), Jianjing (double), Houxi (double), Hegu (double), Waiguan (double).

[0164] Acupuncture technique: Use a 0.3mm diameter acupuncture needle. After the needle is inserted and qi is obtained, the method of equal supplementation and equal drainage is applied. Electricity is applied, continuous wave stimulation is used, and the needle is retained for 30 minutes.

[0165] 2.2. Observation items and treatment course

[0166] One week is one course of treatment. Before and after treatment, the patient's TCM symptoms, tongue, pulse and concomitant symptoms were observed.

[0167] 2.3. Clinical efficacy evaluation criteria

[0168] 2.3.1. Evaluation of TCM cervical syndrome: A quantitative table was developed based on the symptoms and signs of cervical spondylosis in the “Principles for Clinical Guidance Research of New TCM Drugs (Trial)” issued in 2002. Ten items were used to evaluate cervical function, and each item was evaluated at a four-level level, namely, asymptomatic, mild, moderate, and severe, corresponding to 0 points, 2 points, 4 points, and 6 points, respectively.

[0169] 2.3.2. The score of the cervical spondylosis symptom grading quantitative table combined with the reduction rate of the "Principles of Clinical Guidance Research on New Chinese Medicines (Trial)" is used as the evaluation index:

[0170] Score reduction rate (nimodipine method) = (score before treatment - score after treatment) / score before treatment × 100%.

[0171] Clinical cure: pain, numbness, or dizziness and other clinical symptoms and signs score reduction ≥ 95%. Significant effect: 70% < pain, numbness, or dizziness and other symptoms and signs score reduction < 95%. Effective: 30% ≤ pain, numbness, or dizziness and other symptoms and signs score reduction ≤ 70%. Ineffective: pain, numbness, or dizziness and other symptoms and signs score reduction rate < 30%.

[0172] Statistical analysis

[0173] SPSS13.0 statistical software was used, and the data were expressed as x±s. The measurement data were tested by t test, and the count data were tested by X test. 2 test.

[0174] 3. Treatment Outcomes

[0175] 3.1. Comparison of baseline data between the two groups of patients

[0176] There were 31 males and 29 females in the treatment group, with an average age of 50 years (54.90±2.97) years; there were 30 males and 30 females in the control group, with an average age of (55.60±2.55) years. There was no significant difference in the age, TCM syndrome score before treatment and other data between the two groups (P>0.05), see Table 12.

[0177] Table 12 Comparison of baseline data

[0178]

[0179] 3.2. Covariance analysis of TCM syndrome scores between the two groups

[0180] Covariance analysis was used to perform statistical analysis on the changes in the two groups compared with the baseline, with the scores before treatment as the covariate. The results showed that there was a significant difference in the changes in the TCM syndrome scores between the two groups (P<0.05), indicating that the treatment group had better improvement in TCM syndrome than the control group (see Table 13).

[0181] Table 13 Covariance analysis of TCM syndrome scores

[0182]

[0183] 3.3 Comparison of the effective rates between the two groups

[0184] The total effective rates of intervention in the treatment group and the control group were 96.67% and 88.33%, respectively. There was a significant difference in the total effective rate between the treatment group and the control group (P<0.05), as shown in Table 14.

[0185] Table 14 Comparative analysis of effective rate

[0186]

[0187] 4. Security

[0188] There was no clear feedback on drug safety issues in the application of Shengyang Yiqi Yangxue Granules in this clinical trial. No drug-induced adverse reactions were found in this clinical control experiment. The whole prescription is harmonious and has no contraindications of "18 anti-indications and 19 fears". Looking at this prescription, the medication is excellent and the safety is relatively high.

[0189] 5 Results Analysis

[0190] Neck pain is a disease caused by overwork, lack of nourishment to tendons and veins, or blocking of meridians by pathogenic factors such as wind, cold, dampness and heat, which affect the circulation of qi and blood. It is characterized by frequent pain and numbness in the neck, which may extend to the head, shoulders and upper limbs, and may be accompanied by dizziness. The occurrence of this disease is mainly related to overwork, exposure to external pathogens, weak vital energy, insufficient qi and blood, lack of nourishment to tendons and veins, so pain occurs when the tendons and veins are not nourished; long-term work at the desk, excessive overwork, injury to tendons and veins, stagnation of qi and blood in the neck, or exposure to external pathogens such as wind, cold and dampness, obstruction of meridians, and stagnation of qi and blood, so pain occurs when the qi and blood are not flowing.

[0191] The main contradiction of the neck arthralgia of the deficiency of qi and blood syndrome is the deficiency of qi and blood, which leads to pain if it is not nourished. Through the principle of raising yang and replenishing qi, the effect of nourishing blood and relieving arthralgia can be achieved. Starting from the spleen, replenishing the "acquired foundation" is based on the Buzhong Yiqi Decoction, which is supplemented by the function of "warming yang" to build an important bridge connecting "replenishing qi" and "nourishing blood" in the treatment of the deficiency of qi and blood. In the prescription, astragalus is the monarch, which can both replenish qi and raise yang, replenish the middle and replenish qi, raise yang and consolidate the surface, and help yang to produce blood, so it is used as the monarch. Codonopsis is sweet and flat in nature, enters the spleen and lung meridians, and helps astragalus to replenish the middle and replenish qi; cinnamon is spicy and sweet, and has a hot nature. It has the effect of warming and replenishing the heart yang and warming and promoting yang qi. Dried ginger is spicy and hot in nature, which can warm and replenish the spleen yang and help the heart promote yang. Angelica sinensis is spicy and active in nature, and is a product that can replenish both qi and blood. When paired with astragalus, it can further increase qi and nourish blood. Jujube can nourish the middle and nourish blood, and moderate the medicinal properties. The above five medicines are combined as ministerial medicines, which can not only replenish the spleen and stomach, the source of qi and blood production, but also warm the heart yang and help blood production. Fructus aconitifolia is spicy and slightly bitter in taste. The spiciness can help the clear yang rise, and the bitterness can help the turbid yin descend and discharge, and it is mainly used to lower qi. Tangerine peel is bitter and spicy in taste and warm in nature. The bitterness can dry dampness and lower turbid yin. The spiciness can help the yang rise, and it has the function of regulating the qi of the spleen and stomach to prevent the sweet and warm tonic products from stagnating the middle jiao. Scutellaria baicalensis is bitter in taste and cold in nature. It is used to control the sweet and warm nature of the monarch and ministerial medicines, and prevent spiciness, heat, warmness and dryness. The three are used together to achieve the effect of raising the clear yang and lowering the turbid yin, and are collectively adjuvants. Bupleurum is an adjuvant, carrying the medicine upward, leading the clear to remove the turbid, and raising the clear yang. Roasted licorice harmonizes the various medicines and is an adjuvant. The combination of various medicines can have both cold and hot effects, invigorate Qi and regulate Qi, and rise and fall in unison, so as to achieve the effects of invigorating Qi, raising clearness, warming Yang and nourishing blood.

[0192] The patients in the treatment group were given Shengyang Yiqi Yangxue Granules on the basis of acupuncture, while the patients in the control group were given acupuncture plus methylcobalamin. The results showed that the total clinical effective rate of clinical symptoms in the treatment group was significantly higher than that in the control group, and the covariance of TCM symptom scores in the treatment group after treatment was better than that in the control group, indicating that Shengyang Yiqi Yangxue Granules has a definite therapeutic effect on patients with neck arthralgia due to qi and blood deficiency syndrome.

[0193] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. Use of a Chinese medicine composition for raising yang, replenishing qi and nourishing blood in the preparation of a medicine for treating neck arthralgia due to qi and blood deficiency syndrome, characterized in that: The Chinese medicine composition is composed of the following components in parts by weight: 400 parts of Astragalus, 200 parts of Angelica, 200 parts of Bupleurum, 133 parts of Scutellaria slices, 200 parts of Tangerine peel, 100 parts of Pinellia, 200 parts of Dry ginger slices, 100 parts of Cinnamon, 100 parts of Roasted Licorice, 200 parts of Codonopsis slices and 200 parts of Jujube.

2. The method for preparing the drug according to claim 1, characterized in that: The steps include: Take the prescribed amount of components and boil them, collect the filtrate and concentrate it under reduced pressure to obtain a clear paste; Add auxiliary materials to the clear paste, spray dry, collect the extract powder, add auxiliary materials to the extract powder, mix well, granulate and package.

3. The preparation method according to claim 2, characterized in that: The decoction condition is to decoct twice, adding 8 times the volume of water to the prescribed amount of components each time, and decoct for 1 hour.

4. The preparation method according to claim 2, characterized in that: The reduced pressure concentration is performed to a clear paste with a relative density of 1.08-1.

12.

5. The preparation method according to claim 2, characterized in that: The auxiliary material is maltodextrin; the mass ratio of the total amount of maltodextrin added to the amount of clear paste used is 1:2.

29.

6. A drug for assisting the treatment of neck arthralgia due to deficiency of qi and blood, characterized in that: Contains the Chinese medicine composition as claimed in claim 1.

7. The drug according to claim 6, characterized in that The dosage form of the drug comprises granules.

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