Composition for relaxing muscles and stimulating blood circulation, extract for relaxing muscles and stimulating blood circulation, preparation as well as preparation method and application thereof

Abstract

The invention provides a tendon-relaxing and blood-activating composition, a tendon-relaxing and blood-activating extract, a preparation and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The composition for relaxing the muscles and stimulating the blood circulation comprises gentiana macrophylla, speranskia tuberculata, cassia twig, eucommia ulmoides, rhizoma atractylodis, radix aconiti, myrrh, salvia miltiorrhiza, divaricate saposhnikovia root, the root of kudzu vine, safflower carthamus, the root of bidentate achyranthes, notopterygium root, rhizoma drynariae, fermented rheum officinale and fermented hiraute shiny bugleweed herb. The pharmaceutical composition can effectively relieve, treat and prevent joint diseases, and is good in stability and convenient to store for a long time.

Description

TECHNICAL FIELD

[0001] The application provides a tendon-softening and blood-activating composition, a tendon-softening and blood-activating extract, a preparation and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. BACKGROUND

[0002] Pain in the shoulder, neck, waist and back belongs to a chronic disease, and needs long-term drug taking. At present, western medicines for treating the disease include celecoxib capsules, nimesulide, diclofenac sodium and the like. However, the western medicines have large side effects, can cause drug dependence of patients, and can also cause adverse reactions such as headache, dizziness, nausea, fatigue and the like. There are many traditional Chinese medicine varieties, such as Wangbi tablets, Duhuo Jisheng pills and Shufeng Dingtong pills. However, the oral efficacy of the traditional Chinese medicines is slow, and long-term application has certain influence on the gastrointestinal tract.

[0003] In the treatment of traditional Chinese medicine, the disease is derived from the theory of "three pathogenic factors of wind, cold and dampness" described in Huangdi Neijing, which clearly points out that the exogenous "wind, cold and dampness" evil is the external condition for the formation of the arthralgia disease. At the same time, the basic pathogenesis theories of traditional Chinese medicine of "stagnation of Qi and blood" and "stagnation of blood in the collaterals" are followed. When the wind, cold and dampness evil blocks the meridians, the circulation of Qi and blood is not smooth, which leads to the internal generation of "stagnation of blood", forming the complex pathogenesis of "wind, cold and dampness arthralgia and stagnation of blood in the collaterals". This not only explains the pain, but also explains the local stiffness, numbness, limited activity and the like.

[0004] The acupoint sticking therapy of traditional Chinese medicine is one of the treatment methods for the disease in the current clinical medicine, that is, the drug is absorbed through the skin after sticking, and then the meridian Qi of the body is stimulated to achieve the effect of regulating the human body, that is, the pain of surgical treatment of western medicine is avoided, and the trouble of oral traditional Chinese medicine is reduced. The internal disease is treated externally through the absorption of drugs by the skin acupoints to achieve the treatment purpose.

[0005] The journal "Inner Mongolia Ancient Chinese Medicine" discloses: "Observation on the Curative Effect of Ex-Bi Tongluo Decoction External Use Combined with Meridian Massage in the Treatment of Neck, Shoulder, Waist and Leg Pain", which is treated by Ex-Bi Tongluo Decoction external use combined with meridian massage. The Ex-Bi Tongluo Decoction is composed of 20g of Qinjiao, 6g of Gancao, 10g of Tougucao, 10g of Guizhi, 8g of Sumu, 10g of Shenjincao, 10g of Qianghuo, 30g of Yiyiren, 10g of Hongteng, 10g of Danshen, 10g of Weilingxian, 10g of Fangfeng and 10g of Luoshiteng. However, it needs Ex-Bi Tongluo Decoction external use combined with meridian massage treatment, and the treatment method is complex, and the patient compliance is poor.

[0006] Chinese patent CN105664092A discloses a topical medicinal wine for treating orthopedic diseases, formulated with 41 medicinal herbs: white peony root, red peony root, astragalus root, kudzu root, eucommia bark, frankincense, myrrh, chicken blood vine, Sichuan teasel root, dried ginger, cibotium barometz, clematis root, peach kernel, clematis root, angelica root, angelica pubescens root, angelica sinensis root, angelica dahurica root, lycopus lucidus root, turmeric, notopterygium root, achyranthes root, chuanxiong rhizome, natural copper, psoralea corylifolia root, cinnamon bark, corydalis rhizome, safflower, cistanche deserticola root, cinnamon twig, *Homalomena occulta* root, salvia miltiorrhiza root, *Trachelospermum jasminoides* vine, eleutherococcus root, ephedra, *Lycopodium clavatum* root, *Piper kadsura* vine, mulberry mistletoe root, asarum root, prepared rehmannia root, *Ligusticum striatum* root, and *Drynaria fortunei* root. It can treat intervertebral disc bulging, bone hyperplasia, cervical / lumbar spondylosis, etc. However, the application steps of the medicinal wine are cumbersome, resulting in poor patient compliance. Even when formulated as a plaster, it suffers from slow therapeutic effects and poor formulation stability. Summary of the Invention

[0007] This invention provides: a muscle-relaxing and blood-activating composition, a muscle-relaxing and blood-activating extract, a preparation, a method for preparing the same, and applications thereof. The muscle-relaxing and blood-activating composition can effectively relieve, treat, and prevent joint diseases, and the preparation has good stability and is easy to store for a long time.

[0008] Terminology Explanation: Unless otherwise defined, all technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter pertains. Unless otherwise stated, all patents, patent inventions, and publications cited throughout this document are incorporated herein by reference in their entirety. Where multiple definitions exist for terms, the definitions provided in this chapter shall prevail.

[0009] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0010] Definitions of standard chemical terms can be found in the references “Chinese Pharmacopoeia, 2020 Edition” and “Chinese Journal of Fermentation and Processing, 2013, Qiao Yanjiang”.

[0011] Unless otherwise specified, conventional methods within the scope of the art, such as microbial detection and HPLC chromatography, shall be used.

[0012] Unless specific definitions are provided, the use of each of the various terms herein is intended to be consistent with the definitions set forth in the Handbook of Pharmaceutical Excipients, Sixth Edition, Rowe et al., Eds., American Pharmaceutical Association and Pharmaceutical Press (2009), which is incorporated herein by reference. Unless otherwise indicated, the techniques utilized in the present application are those that are well understood and commonly employed on a commercial scale, such as found in the literature or otherwise standard in the art. For example, standard techniques can be used for chemical synthesis, chemical analyses, pharmaceutical formulation, and the like. As examples of reference works of a standard nature that can be used for bench work are Techniques in Pharmaceutical Research, First Edition, Susten et al., Eds., Aslib (1979); and Pharmaceutical Analysis, Second Edition, Marsh et al., Eds., Churchill Livingstone (1984), which are incorporated by reference herein. Still further, various teachings set forth in the present specification can be used in connection with the various techniques described in the present application, and the application is intended to embrace all such techniques. The foregoing description and examples have been given by way of illustration. From this disclosure, those skilled in the art will not only understand the general principles of the application, but will also be able to devise various

[0013] In a first aspect, the present application provides: a Shujin Huoxue composition, comprising: Qinjiao, Zhenzhutonggucao, Guizhi, Duzhong, Cangzhu, Chuanwu, Modya, Danshen, Fangfeng, Gegen, Honghua, Niuxi, Qianghuo, Gushugu, fermented Dahuang, fermented Zelan.

[0014] Further, the Cangzhu is fermented Cangzhu.

[0015] Further, the Chuanwu is prepared Chuanwu.

[0016] Further, the Modya is at least one of vinegar Modya, fried Modya.

[0017] Further, the mass ratio of the Qinjiao, Zhenzhutonggucao, Danshen, Gegen is (10-20):(10-15):(12-15):(10-15).

[0018] Preferably, the mass ratio of the Qinjiao, Zhenzhutonggucao, Danshen, Gegen is 10:15:12:15, 10:15:15:15, 12:14:13:14, 15:12:13:12, 18:11:15:10, 20:15:12:10, 20:10:12:10, or a range consisting of any two of them.

[0019] Further, the mass ratio of the Cangzhu, Chuanwu, Modya is (10-15):(1-5):(5-10).

[0020] Preferably, the mass ratio of the Cangzhu, Chuanwu, Modya is 13:4:7, 10:5:5, 15:1:10, 12:2:8, 13:4:9, or a range consisting of any two of them.

[0021] Further, the mass ratio of the Guizhi, Duzhong, Niuxi, Qianghuo is (5-10):(8-12):(10-15):(12-16).

[0022] Preferably, the mass ratio of the Guizhi, Duzhong, Niuxi, Qianghuo is 7:9:13:13, 5:12:5:12, 10:8:10:16, or a range consisting of any two of them.

[0023] Further, the mass ratio of the Honghua, fermented Dahuang, fermented Zelan is (5-10):(8-12):(11-15).

[0024] Preferably, the mass ratio of the safflower, fermented rhubarb, and fermented lamiophlomis is 7:9:12, 5:8:15, 10:12:11, 8:10:14, or a range consisting of any two thereof.

[0025] Further, the Shujin Huoxue composition comprises, by weight fraction: 10-20 parts of Gentiana, 10-15 parts of Pearl Bone-Transmitting Herb, 5-10 parts of Cinnamon Twig, 8-12 parts of Eucommia, 10-15 parts of Atractylodes, 1-5 parts of Radix et Rhizoma Aconiti, 5-10 parts of Myrrh, 12-15 parts of Salvia, 11-16 parts of Saposhnikovia, 10-15 parts of Pueraria, 5-10 parts of Safflower, 10-15 parts of Radix Hedysari, 12-16 parts of Notopterygium, 5-10 parts of Drynaria, 8-12 parts of Fermented Rhubarb, and 11-15 parts of Fermented Lamiophlomis.

[0026] Preferably, the Gentiana can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, or a range consisting of any two thereof.

[0027] Preferably, the Pearl Bone-Transmitting Herb can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, or a range consisting of any two thereof.

[0028] Preferably, the Cinnamon Twig can be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, or a range consisting of any two thereof.

[0029] Preferably, the Eucommia can be 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, or a range consisting of any two thereof.

[0030] Preferably, the Atractylodes can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, or a range consisting of any two thereof.

[0031] Preferably, the Radix et Rhizoma Aconiti can be 1 part, 2 parts, 3 parts, 4 parts, 5 parts, or a range consisting of any two thereof.

[0032] Preferably, the Myrrh can be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, or a range consisting of any two thereof.

[0033] Preferably, the Salvia can be 12 parts, 13 parts, 14 parts, 15 parts, or a range consisting of any two thereof.

[0034] Preferably, the Saposhnikovia can be 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, or a range consisting of any two thereof.

[0035] Preferably, the Pueraria can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, or a range consisting of any two thereof.

[0036] Preferably, the safflower can be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts or any two ranges thereof.

[0037] Preferably, the Cyathula officinalis can be 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts or any two ranges thereof.

[0038] Preferably, the Notopterygium can be 12 parts, 13 parts, 14 parts, 15 parts, 16 parts or any two ranges thereof.

[0039] Preferably, the Drynaria can be 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts or any two ranges thereof.

[0040] Preferably, the fermented rhubarb can be 8 parts, 9 parts, 10 parts, 11 parts, 12 parts or any two ranges thereof.

[0041] Preferably, the fermented Lantana can be 11 parts, 12 parts, 13 parts, 14 parts, 15 parts or any two ranges thereof.

[0042] Further, the preparation method of the fermented rhubarb and the fermented Lantana is as follows: soaking the rhubarb and the Lantana to a water content of 50-60wt%, and using yeast to ferment at 25-35℃ for 2-10 days.

[0043] Preferably, the fermentation condition further includes a normal oxygen environment.

[0044] Further preferably, the normal oxygen environment is a normal atmospheric oxygen environment.

[0045] Preferably, the yeast is Saccharomyces cerevisiae.

[0046] Preferably, the addition amount of the yeast is 0.3-0.8% of the dry weight of the rhubarb and the Lantana.

[0047] In a second aspect, the present application provides: a Shujinhuoxue extract prepared from the Shujinhuoxue composition, and the preparation method comprises the following steps: (1) crushing and sieving Commiphora molmol to obtain Commiphora molmol powder; (2) extracting the other medicinal materials to obtain an extract; (3) mixing the Commiphora molmol powder and the extract.

[0048] Further, the particle size of the Commiphora molmol powder is 150-180μm.

[0049] Preferably, the extraction is: frying the medicinal materials in the Shujin Huoxue composition except for Myrrha in a pharmaceutically acceptable oil at 120-180℃ for 3-10 minutes, and refining the filtered liquid at 200-300℃ for 3-10 minutes.

[0050] Further preferably, the mass ratio of the Shujin Huoxue composition and the pharmaceutically acceptable oil is 1: (4-6).

[0051] Further preferably, the pharmaceutically acceptable oil comprises: at least one of sesame oil, tea oil, and peanut oil.

[0052] In a third aspect, the present application provides: a Shujin Huoxue preparation comprising a Shujin Huoxue extract and a pharmaceutically acceptable excipient.

[0053] Further, the pharmaceutically acceptable excipient is: red lead.

[0054] Preferably, the preparation method of the Shujin Huoxue preparation comprises the following steps: stirring the Shujin Huoxue extract and the red lead uniformly to obtain a plaster, and soaking the plaster in water for 20-30 minutes and then taking it out.

[0055] Preferably, the red lead and the Shujin Huoxue extract are (1-1.5):(2-4).

[0056] Further, the preparation is an external preparation.

[0057] Preferably, the external preparation comprises: an ointment, a cream, a gel, a patch, a wine, a lotion a liniment, a coating agent, a film coating agent, a plaster, a plaster.

[0058] In a fourth aspect, the present application provides: an application of the Shujin Huoxue composition in the preparation of a medicine for treating joint diseases.

[0059] Further, the joint diseases comprise: at least one of rheumatoid arthritis, hyperosteogeny, ankylosing spondylitis, waist / back / shoulder neck / leg pain, and joint stiffness.

[0060] The beneficial effects of the present application are: The present application releases the medicinal properties of Rhubarb and Lantana through the microbial fermentation of Rhubarb and Lantana, and has good therapeutic effect on diseases such as rheumatoid arthritis, hyperosteogeny, ankylosing spondylitis, waist / back / shoulder neck / leg pain, and joint stiffness. And long-term sticking, no adverse reactions on the skin.

[0061] Compatibility of monarch and minister: Qinjiao is the monarch herb, and its main function is to dispel wind-dampness, relax muscles and tendons, and clear heat. It is cold in nature and bitter in taste, and belongs to the liver and gallbladder channels. It can effectively relieve symptoms such as wind-dampness arthralgia, muscle and tendon contracture, etc. Qinjiao can clear heat and cool blood, and improve local redness, heat and pain caused by heat and toxic accumulation. It is the main herb for treating rheumatic arthralgia. Zhenzhutonggucao and Qinjiao complement each other and have the effect of penetrating bones and dispelling wind, relaxing muscles and tendons. It is cold in nature and bitter in taste, and belongs to the liver and kidney channels. It is good at treating bone pain, rheumatic arthralgia, etc. Zhenzhutonggucao has strong bone-penetrating properties and can relieve deep arthralgia. Guizhi is warm in nature and pungent in taste, and belongs to the heart, lung and bladder channels. It has the effect of warming the meridians, dispelling cold, and relieving pain. It can enhance the effect of the monarch herb in dispelling wind and dampness, and relieve joint cold pain caused by cold and dampness. The warmth of Guizhi can also promote local blood circulation and improve numbness. Duzhong is warm in nature and sweet in taste, and belongs to the liver and kidney channels. It can supplement the liver and kidney, strengthen the muscles and bones, and relieve symptoms such as soreness of the waist and knees, weakness of the muscles and bones, etc. Duzhong can supplement the liver and kidney, strengthen the muscles and bones, and improve joint mobility. Cangzhu is warm in nature, bitter and pungent in taste, and belongs to the spleen and stomach channels. After being roasted with bran, it can strengthen the spleen and dry dampness, enhance the function of the spleen and stomach, and help dispel dampness, relieve symptoms such as heaviness of the limbs, fatigue, etc. Shuchuanwu is hot in nature, pungent and bitter in taste, and belongs to the heart, liver and spleen channels. After being processed, its toxicity is reduced, and it can warm the meridians and relieve pain. It is good at treating cold and damp arthralgia. It can warm and unblock the meridians, dispel cold and dampness, and relieve joint cold pain, but the dosage should be strictly controlled to avoid poisoning. Muyan is neutral in nature and bitter in taste, and belongs to the heart and liver channels. After being pickled, it can activate blood and relieve pain, and dissipate swelling and promote tissue regeneration. It can dissipate blood stasis, relieve symptoms such as contusion, swelling and pain, etc. Danshen is cold in nature and bitter in taste, and belongs to the heart and liver channels. It has the effect of activating blood and dissipating stasis, and can relieve pain and swelling caused by blood stasis blocking the collaterals. It can enhance the overall effect of activating blood and dissipating stasis. Fangfeng is slightly warm in nature, pungent and sweet in taste, and belongs to the bladder, liver and spleen channels. It has the effect of dispelling wind and relieving the exterior, and relieving pain. It can enhance the effect of the monarch herb in dispelling wind, and relieve rheumatic arthralgia caused by excessive wind. Gegen is cool in nature and sweet in taste, and belongs to the spleen and stomach channels. It has the effect of relieving the exterior, relieving fever, and promoting fluid production. It can relieve symptoms such as fever, sweating, etc. Honghua is warm in nature and pungent in taste, and belongs to the heart and liver channels. It has the effect of activating blood and unblocking the collaterals, and dissipating stasis and relieving pain. It can relieve pain and swelling caused by blood stasis blocking the collaterals, and enhance the overall effect of activating blood and dissipating stasis. Niuxi is neutral in nature and sweet and sour in taste, and belongs to the liver and kidney channels. It has the effect of supplementing the liver and kidney, and strengthening the muscles and bones. It can enhance the effect of the monarch herb on the muscles and bones, and relieve symptoms such as soreness of the waist and knees, weakness of the muscles and bones, etc. Qianghuo is warm in nature, bitter and pungent in taste, and belongs to the bladder and kidney channels. It has the effect of dispelling wind and relieving the exterior, and overcoming dampness and relieving pain. It can enhance the effect of the monarch herb in dispelling wind and dampness, and relieve joint cold pain caused by wind, cold and dampness. Gushu is warm in nature, bitter and pungent in taste, and belongs to the liver and kidney channels. It has the effect of connecting muscles and bones, and activating blood and relieving pain. It can treat contusion, fracture and swelling, and help repair damaged muscles and bones.Although rhubarb has the effect of clearing heat and purging fire, it mainly plays a role of regulating various drugs in this prescription, helping to balance the cold and hot properties and ensuring the coordination of the overall therapeutic effect. The effects of promoting blood circulation and removing blood stasis and diuresis and detumescence of zelan not only directly treat symptoms but also help to regulate drugs and ensure the balanced exertion of drug efficacy. Through drugs such as qinjiao, zhenaotuoguo, fangfeng, and qianghuo, wind-dampness can be effectively removed, and the muscles and joints can be relaxed and activated, relieving rheumatic pain and joint swelling and pain. Drugs such as danshen, vinegar myrrh, safflower, and zelan can promote blood circulation and remove blood stasis, and are suitable for symptoms such as contusion and swelling pain. Drugs such as guizhi and duzhong can warm the meridians and dispel cold, strengthen the bones and joints, and improve joint cold pain and muscle weakness caused by cold and dampness. Drugs such as gushu bu and rhubarb have the effects of detumescence and analgesia, and can relieve local swelling and pain. The combined use of various drugs can achieve the effects of expelling wind and dampness, promoting blood circulation and removing blood stasis, and dredging collaterals and relieving pain. DETAILED DESCRIPTION

[0062] The advantages and effects of the present application can be easily understood by those skilled in the art from the disclosure of the present specification. The present application can also be implemented or applied by different specific embodiments, and various modifications or changes can be made to the details in the specification without departing from the spirit of the present application.

[0063] Before further describing the specific embodiments of the present application, it should be understood that the protection scope of the present application is not limited to the following specific embodiments; and it should also be understood that the terms used in the embodiments of the present application are for describing the specific embodiments, but not for limiting the protection scope of the present application.

[0064] When the embodiments give numerical ranges, it should be understood that, unless otherwise specified by the present application, both ends of each numerical range and any number between the two ends can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art to which the present application belongs.

[0065] I. Source of raw materials The standard source of the medicinal ingredient zhenaotuoguo in the prescription is derived from the "Anhui Province Chinese Herbal Pieces Processing Specification" 2019 edition, and the standards of other medicinal ingredients are derived from the "Chinese Pharmacopoeia" 2020 edition Part I, as follows: (1) Qinjiao The product is the dried root of Gentiana rigescentis Gentiana macrophylla Pall. It is commonly known as "Qinjiao" according to its appearance. It is harvested in spring and autumn, and the mud and sand are removed. The qinjiao is dried until the surface is red and yellow or grayish yellow, or it is directly dried without "sweating". The production place is Sichuan.

[0066] This product should comply with the relevant provisions of the Gentiana macrophylla entry on page 282 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0067] (2) Pearl-like herb This product is the leaf of *Broussonetia papyrifera*, a plant in the Euphorbiaceae family. Speranskia tuberculata (Bunge)Baill's dried whole herb. Harvested in summer and autumn, impurities removed, and dried. Origin: Henan, China.

[0068] This product should comply with the relevant provisions under the Pearl and Bone-Penetrating Herb section on page 201 of the 2019 edition of the "Anhui Province Standards for Processing Traditional Chinese Medicine Pieces".

[0069] (3) Cinnamon twig This product is cinnamon, a plant belonging to the Lauraceae family. Cinnamomum cassia Dried young shoots of Presl. Harvested in spring and summer, leaves removed, then sun-dried, or sliced ​​and sun-dried. Origin: Guangxi.

[0070] This product should comply with the relevant provisions under the Guizhi (Cinnamon Twig) section on page 288 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0071] (4) Eucommia ulmoides This product is Eucommia ulmoides, a plant belonging to the Eucommiaceae family. Eucommia ulmoides Dried bark of Oliv. Harvested from April to June, the outer bark is scraped off, and the bark is piled up to "sweat" until the inner bark turns purplish-brown, then sun-dried. Origin: Sichuan.

[0072] This product should comply with the relevant provisions under the Eucommia ulmoides entry on page 172 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0073] (5) Stir-fried Atractylodes lancea This product is Atractylodes lancea, a plant belonging to the Asteraceae family. Atractylodes lancea Dried rhizome of (Thunb.) DC. Harvested in spring and autumn, cleaned of mud and sand, sun-dried, and the fibrous roots removed. Take slices of Atractylodes lancea and stir-fry according to the wheat bran stir-frying method (General Rule 0213) until the surface turns deep yellow. Origin: Inner Mongolia.

[0074] This product should comply with the relevant provisions of the Atractylodes lancea entry on page 168 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0075] (6) Prepared Aconitum carmichaelii This product is a processed form of Aconitum carmichaelii. Origin: Sichuan.

[0076] This product should comply with the relevant provisions under the section on processed Aconitum carmichaelii on page 41 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0077] (7) Vinegar and myrrh This product is from the plant *Viola yedoensis*, belonging to the Burseraceae family. Commiphora myrrha Myrrh is the dried resin of Engl. It is divided into natural myrrh and gum myrrh. Take clean myrrh and stir-fry it according to the vinegar-processing method (General Rule 0213) until the surface is glossy. Origin: Yunnan.

[0078] This product should comply with the relevant provisions of the Myrrh section on page 193 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0079] (8) Salvia miltiorrhiza This product is *Salvia miltiorrhiza*, a plant belonging to the Lamiaceae family. Salvia miltiorrhiza Dried roots and rhizomes of Bge. Harvested in spring and autumn, cleaned of mud and sand, and dried. Origin: Shandong.

[0080] This product should comply with the relevant provisions of the Danshen (Salvia miltiorrhiza) entry on page 77 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0081] (9) Windproof This product is made from the plant Saposhnikovia divaricata, belonging to the Apiaceae family. Saposhnikovia divaricata The dried root of (Turcz.) Schishk. The roots of plants that have not yet produced flower stalks are harvested in spring and autumn, the fibrous roots and soil are removed, and then the roots are dried. Origin: Inner Mongolia.

[0082] This product should comply with the relevant provisions of the "Fangfeng" section on page 156 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0083] (10) Kudzu root This product is wild kudzu, a plant belonging to the legume family. Pueraria lobata Dried root of (Willd.) Ohwi. Commonly known as wild kudzu. Harvested in autumn and winter, cut into thick slices or small pieces while fresh; then dried. Origin: Guangxi.

[0084] This product should comply with the relevant provisions under the entry for Pueraria lobata on page 347 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0085] (11) Safflower This product is made from safflower, a plant belonging to the Asteraceae family. Carthamus tinctorius Dried flowers of L. Harvested in summer when the flowers turn from yellow to red, then air-dried or sun-dried. Origin: Xinjiang.

[0086] This product should comply with the relevant provisions under the Safflower entry on page 157 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0087] (12) Achyranthes bidentata This product is Achyranthes bidentata, a plant belonging to the Amaranthaceae family. Achyranthes bidentata Dried roots of Bl. Harvested in winter when stems and leaves wither, remove fibrous roots and soil, bundle into small bunches, sun-dry until wrinkled, then trim the top and sun-dry again. Origin: Hebei Province.

[0088] This product should comply with the relevant provisions of the Achyranthes bidentata section on page 74 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0089] (13) Notopterygium incisum This product is notopterygium root (Notopterygium incisum), a plant belonging to the Apiaceae family. Notopterygium incisumDried rhizomes and roots of *Ting ex HT Chang*. Harvested in spring and autumn, fibrous roots and soil are removed, and then dried. Origin: Sichuan.

[0090] This product should comply with the relevant provisions of the "Notopterygium incisum" entry on page 190 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0091] (14) Drynaria fortunei This product is *Polygonum cuspidatum*, a plant belonging to the Polypodiaceae family. Drynaria fortunei Dried rhizomes of (Kunze) J. Sm. Harvesting can be done year-round. Remove dirt and sand, dry, or singe off the hairs (scales). Origin: Zhejiang.

[0092] This product should comply with the relevant provisions of the Drynaria fortunei section on page 267 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0093] (15) Rhubarb This product is Rheum palmatum, a plant belonging to the Polygonaceae family. Rheum palmatum Dried roots and rhizomes of L. Harvested in late autumn when the stems and leaves wither or before sprouting in the following spring. Fine roots are removed, the outer skin is scraped off, and the roots are cut into segments or sections and strung together for drying, or dried directly. Origin: Sichuan.

[0094] This product should comply with the relevant provisions of the Rhubarb entry on page 24 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0095] (16) Ze Lan This product is the seedling of *Sweet Potato Leafy Green*, a plant belonging to the Lamiaceae family. Lycopus lucidus Turcz. var. hirtus The dried aerial parts of Regel. Harvested in summer and autumn when the stems and leaves are lush, and then sun-dried. Origin: Henan Province.

[0096] This product should comply with the relevant provisions under the entry for Ze Lan on page 239 of Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0097] (17) Lead oxide manufacturer: Hebei Renxin Pharmaceutical Co., Ltd.; Sesame oil manufacturer: Anhui Yinglu Sesame Oil Co., Ltd.

[0098] II. A muscle-relaxing and blood-activating composition Examples 1-4 are a composition for relieving muscle tension and promoting blood circulation. The prescriptions for Examples 1-3 are shown in Table 1.

[0099] Comparative Examples 1-6 are comparative examples, and the formulations of Comparative Examples 1-4 are shown in Table 2.

[0100] Table 1 (Unit: parts by weight)

[0101] Note: In Examples 1-3 of this invention, Atractylodes lancea is stir-fried with wheat bran, Aconitum carmichaelii is processed Aconitum carmichaelii, and Commiphora myrrha is vinegar-processed.

[0102] Example 4 The prescription amount of Example 4 is the same as Example 1, except that the myrrh is fried myrrh.

[0103] The preparation method of fermented rhubarb and fermented lantana is as follows: the rhubarb and lantana are soaked with water to have a water content of 55wt%, sterilized before fermentation, and 0.5% of a wine yeast suspension (1×10 9 CFU·mL -1 ) of dry weight of the rhubarb and lantana is added, and dried after aerobic fermentation at 30℃ for 5 days to obtain fermented rhubarb and fermented lantana, respectively.

[0104] The aerobic condition is a normal atmospheric oxygen condition.

[0105] The wine yeast used in the present application is: Angel low-sugar high-activity dry yeast.

[0106] Table 2 (unit: weight parts)

[0107] The preparation method of Comparative Examples 1-4 is the same as Example 1.

[0108] Comparative Example 5 The prescription is the same as Example of Chinese patent CN105664092A.

[0109] Preparation method: the myrrh is crushed, sieved, and 180μm myrrh powder is obtained.

[0110] Comparative Example 6 The difference from Example 1 is that the rhubarb and lantana are fermented by lactic acid bacteria, and the specific method is as follows: The rhubarb and lantana are soaked with water to have a water content of 55wt%, sterilized before fermentation, and 0.5% of a Lactobacillus plantarum suspension (1×10 9 CFU·mL -1 ) of dry weight of the rhubarb and lantana is added, and dried after anaerobic fermentation at 30℃ for 5 days to obtain fermented rhubarb and fermented lantana, respectively.

[0111] Three, an extract and plaster for relaxing muscles and promoting blood circulation The preparation method of the extract for relaxing muscles and promoting blood circulation is as follows: (1) The myrrh is crushed, sieved, and 180μm myrrh powder is obtained.

[0112] (2) The medicinal materials in the muscle-relaxing and blood-circulation-promoting composition except myrrh are fried in sesame oil at 150℃ for 5min, the filtered liquid is heated to 260℃ for 5min to obtain medicinal oil, and medicinal oil beads are formed by dripping water.

[0113] (3) The medicinal oil and myrrh powder are mixed.

[0114] The mass ratio of the Shujinhuoxue composition to the sesame oil is 1:5.

[0115] A preparation method of the Shujinhuoxue plaster: (1) The Shujinhuoxue extract and red lead are stirred uniformly to obtain the plaster, and the plaster is soaked in water for 20 min and then taken out.

[0116] (2) The plaster is heated and melted at 60°C, stirred for 10 min, and then distributed on the medicinal polyester fiber cloth to obtain the Shujinhuoxue plaster.

[0117] The mass ratio of the red lead to the Shujinhuoxue extract is 1:2.5.

[0118] The Shujinhuoxue composition is respectively Example 1-4 and Comparative Example 1-6, and the prepared plasters are respectively Application Example 1-4 and Application Comparative Example 1-6.

[0119] IV. Effect Example 1. Animal experiment Healthy female ICR mice are taken, the abdomen is depilated (to ensure that the skin is not damaged), and the mice are rested for 24 h. Then, the hot plate instrument is preheated to 50-55°C, the mice are placed in the hot plate, and the timing is started. When the mice lick their feet, the timing is stopped, and the time of the process is calculated as the initial pain threshold of the mice. Mice with a pain threshold exceeding 30 s (hypoalgesia) or less than 5 s (hyperalgesia) are eliminated, and the average value of two times of the remaining mice is taken as the initial pain threshold of the mice.

[0120] The qualified mice are randomly divided into a negative control group, Application Example 1-4 groups, and Application Comparative Example 1-6 group. The negative control group is applied with the plaster without medicine on the feet, and the remaining feet are applied with the plaster of the corresponding group. The dose of the plaster is 0.1 g of the plaster / Kg of the mice. One hour after 2 h, 7 h, 24 h, 3 d, and 7 d of administration, the pain threshold of each mouse is measured, and the measurement results are shown in Table 3.

[0121] Table 3 (n=8)

[0122] Note: Different letters (a-c) in the same column represent significant differences (p<0.05).

[0123] As shown in Table 3, the negative control group recovers to the initial pain threshold after 3 days of hot plate stimulation.

[0124] The Application Example 1-4 groups of the present application have taken effect after 2 h of administration, have recovered to the initial pain threshold after 7 h, and have a higher pain threshold than the initial pain threshold after continuous administration.

[0125] The application of comparative example 1-6 group, after 2h, no effect was observed, and after 24h, the pain threshold was restored to the initial value, and the mice's pain threshold increased slowly.

[0126] 2. Clinical test Yingji City Hospital recruited 93 volunteers to participate in the treatment.

[0127] (1) The enrolled population: ① Shoulder and neck, back pain caused by wind, cold and dampness, blood stasis and obstruction of collaterals, local stiffness, numbness, joint cold pain, flexion and extension difficulty, limited activity, heavy limbs; rheumatoid arthritis, osteoarthritis, ankylosing spondylitis with the above symptoms. And no surgical indications.

[0128] Among them, 34 cases of osteoarthritis, 31 cases of rheumatoid arthritis, and 28 cases of ankylosing spondylitis.

[0129] ② Age 25-80 years old.

[0130] ③ No related treatment and oral medication in the past 2 weeks.

[0131] ④ Voluntarily participate, actively cooperate with treatment and evaluation.

[0132] (2) The administration method: the plaster of example 1 is applied, one plaster per day, each plaster weighs 6g, and is applied to the affected area for 12h.

[0133] (3) After treatment, the volunteers evaluate the treatment effect and treatment time, and the evaluation criteria are: Marked effect: local mild tenderness, and the pain site activity is basically normal.

[0134] Improvement: symptoms are relieved, and signs are not obvious.

[0135] No effect: compared with before treatment, the symptoms are basically unchanged.

[0136] After 30 days of treatment, all volunteers were improved, and the average experimental results of the effective time and the improved time are shown in table 4.

[0137] Table 4 (unit: day)

[0138] During the use of all volunteers, the skin had no adverse reactions.

[0139] The Shujin Huoxue composition of the application has good treatment effect on shoulder and neck, back pain caused by cold and dampness, blood stasis and obstruction of collaterals, local stiffness, numbness, joint cold pain, flexion and extension difficulty, limited activity, heavy limbs; rheumatoid arthritis, osteoarthritis, ankylosing spondylitis with the above symptoms.

[0140] 3. Stability experiment The application examples 1-4 and 1-6 are subjected to accelerated stability test and long-term stability test.

[0141] Stability test content and qualified standard: Appearance: The product is black plaster spread on cloth, the plaster body is black, oily and delicate, bright, no red spot, and uniform spreading.

[0142] Weight difference: ± 7%.

[0143] Acetic myrrh identification: In the test sample chromatogram, at the corresponding position of the control medicinal material chromatogram, the same colored spots are shown.

[0144] Double ester type alkaloid: In the test sample chromatogram, at the corresponding positions of the control extract chromatogram of new aconitine, aconitine and hypaconitine, no spots should appear.

[0145] Total number of aerobic bacteria: ≤10 4 cfu / g.

[0146] Total number of mold and yeast: ≤10 2 cfu / g.

[0147] Staphylococcus aureus: not detected per 1 g.

[0148] Pseudomonas aeruginosa: not detected per 1 g.

[0149] (1) Accelerated stability The simulation of on-market packaging (polyester aluminum-plated composite film packaging for medicine packaging) is placed in an accelerated stability box, the relative humidity is controlled at 65% ± 5%, the temperature is controlled at 30℃ ± 2℃, and the constant is maintained, and the sample is taken and detected at 0 months, 1 month, 2 months, 3 months, 6 months, and the detection data are compared with the 0-month detection data.

[0150] (2) Long-term stability The product uses simulation of on-market packaging (polyester aluminum-plated composite film packaging for medicine packaging), and is stored at a humidity of 60% ± 5% and a temperature of 25℃ ± 2℃, and the sample is taken and detected at 0 months, 1 month, 2 months, 3 months, 6 months, and the detection data are compared with the 0-month detection data.

[0151] (3) Experimental results ① Accelerated stability In the accelerated stability experiment of the application example 1-4, the detection indexes are qualified and the stability is good compared with 0 months.

[0152] The application comparative examples 1-3 and 5 have oil droplets seeping out of the plaster surface at 6 months, and the rest of the indexes are qualified.

[0153] The application of comparative example 4, at 6 months, the paste is dark and gray, and the rest of the indicators are qualified.

[0154] The application of comparative example 6, at 6 months, the paste is too sticky, and pseudomonas aeruginosa is detected, and the rest of the indicators are qualified.

[0155] ②Long-term stability In the long-term stability experiment, the application examples 1-4, 1-6 months compared with 0 months, the detection indexes are qualified, and the stability is good.

[0156] The application of comparative examples 1-3 and comparative example 5, at 6 months, the paste surface exudes oil droplets, and the rest of the indicators are qualified.

[0157] The application of comparative example 4, at 6 months, the paste is dark and gray, and the rest of the indicators are qualified.

[0158] The application of comparative example 6, at 6 months, the paste is too sticky, and pseudomonas aeruginosa is detected, and the rest of the indicators are qualified.

[0159] Finally, it should be noted that the above content is only used to explain the technical solutions of the present application, and is not a limitation on the protection scope of the present application. The ordinary skilled in the art makes simple modifications or equivalent replacements to the technical solutions of the present application, without departing from the essence and scope of the present application.

Claims

1. A composition for relaxing muscles and promoting blood circulation, characterized by comprising, comprising: Rhizoma Gentianae Macrophyllae, Radix et Rhizoma Bistortae, Ramulus Cinnamomi, Radix Eucommiae, Radix Atractylodis, Radix et Rhizoma Aconiti, Myrrha, Radix Salviae Miltiorrhizae, Radix Saposhnikoviae, Radix Puerariae, Flos Carthami, Radix et Rhizoma Millettiae, Radix et Rhizoma Notopterygii, Radix et Rhizoma Drynariae, fermented Radix et Rhizoma Rhei, and fermented Lamiophlomis rotata.

2. The muscle relaxing and blood activating composition according to claim 1, characterized in that, The mass ratio of the Rhizoma Gentianae Macrophyllae, Radix et Rhizoma Bistortae, Radix Salviae Miltiorrhizae, and Radix Puerariae is (10-20):(10-15):(12-15):(10-15) and / or The mass ratio of the Radix Atractylodis, Radix et Rhizoma Aconiti, and Myrrha is (10-15):(1-5):(5-10).

3. The muscle relaxing and blood activating composition according to claim 1, characterized in that, The mass ratio of the Ramulus Cinnamomi, Radix Eucommiae, Radix et Rhizoma Millettiae, and Radix et Rhizoma Notopterygii is (5-10):(8-12):(10-15):(12-16).

4. The mass ratio of the Flos Carthami, fermented Radix et Rhizoma Rhei, and fermented Lamiophlomis rotata is (5-10):(8-12):(11-15).

5. The tendon relaxing and blood activating composition according to any one of claims 1-4, characterized in that, The Shujinhuoxue composition comprises, by weight fraction, 10-20 parts of Rhizoma Gentianae Macrophyllae, 10-15 parts of Radix et Rhizoma Bistortae, 5-10 parts of Ramulus Cinnamomi, 8-12 parts of Radix Eucommiae, 10-15 parts of Radix Atractylodis, 1-5 parts of Radix et Rhizoma Aconiti, 5-10 parts of Myrrha, 12-15 parts of Radix Salviae Miltiorrhizae, 11-16 parts of Radix Saposhnikoviae, 10-15 parts of Radix Puerariae, 5-10 parts of Flos Carthami, 10-15 parts of Radix et Rhizoma Millettiae, 12-16 parts of Radix et Rhizoma Notopterygii, 5-10 parts of Radix et Rhizoma Drynariae, 8-12 parts of fermented Radix et Rhizoma Rhei, and 11-15 parts of fermented Lamiophlomis rotata.

6. The tendon relaxing and blood activating composition according to any one of claims 1-4, characterized in that, The preparation method of the fermented Radix et Rhizoma Rhei and the fermented Lamiophlomis rotata is as follows: soaking Radix et Rhizoma Rhei and Lamiophlomis rotata to a water content of 50-60 wt%, and then fermenting them at 25-35℃ for 2-10 days using yeast.

7. A muscle relaxing and blood circulation promoting extract, characterized by, The Shujinhuoxue composition prepared by the method of any one of claims 1-6, wherein the preparation method comprises the following steps: (1) crushing Myrrha, sieving, and obtaining Myrrha powder; (2) extracting the medicinal materials in the Shujinhuoxue composition except Myrrha to obtain an extract; (3) mixing the extract and the Myrrha powder.

8. A tendon relaxing and blood activating preparation, characterized in that, The Shujinhuoxue composition of any one of claims 1-6 or the Shujinhuoxue extract of claim 7 and a pharmaceutically acceptable excipient.

9. The tendon relaxing and blood activating preparation according to claim 8, characterized in that, The preparation is an external preparation.

10. Use of the Shujinhuoxue composition of any one of claims 1-6 or the Shujinhuoxue extract of claim 7 in the preparation of a medicament for treating joint diseases.

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