A traditional Chinese medicine composition for treating frozen shoulder, its preparation method and application

Abstract

This invention relates to a traditional Chinese medicine composition, its preparation method, and its application. The traditional Chinese medicine composition of this invention comprises two components: Achyranthes bidentata and Glycyrrhiza uralensis. By taking the traditional Chinese medicine composition of this invention, the overall effective rate in treating frozen shoulder reaches 90%, and the cure rate exceeds 60%.

Description

A traditional Chinese medicine composition for treating scapulohumeral periarthritis and its preparation method and application

[0001] Cross-reference to related applications

[0002] This application claims priority to Chinese patent application number CN202311304080.5, filed on October 9, 2023, which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating scapulohumeral periarthritis, and a preparation method and application thereof. Background Art

[0004] Frozen shoulder, also known as periarthritis of the shoulder or adhesive capsulitis, is commonly known as frozen shoulder or frozen shoulder, and is characterized by stiffness and pain in the shoulder joint. Signs and symptoms usually develop slowly and then worsen. The main manifestations are aseptic inflammation of the soft tissues surrounding the shoulder joint, such as the muscles, tendons, ligaments, synovium, and joint capsule, with changes such as congestion, exudation, edema, and adhesions, leading to shoulder pain and functional impairment. The cause of frozen shoulder is unknown, but certain factors such as age, gender, fractures, and surgical procedures may increase the risk of developing the disease. Clinically, pricaine and prednisone are commonly used for pain point blocking, or oral administration of anti-inflammatory and analgesic drugs. Acupuncture, moxibustion, and massage are also used. Although these therapies have some efficacy, the results are often not obvious, and they mainly focus on relieving pain and waiting for spontaneous recovery.

[0005] At present, Chinese medicine is often applied externally and combined with oral analgesics. The use of Chinese medicine is relatively complicated. For example, CN103920118A discloses a Chinese herbal medicine for external use, which is indicated in the specification as being used to treat periarthritis of the shoulder. It is made of the following raw materials in parts by weight: 18-20 parts of melon seeds, 16-18 parts of wild celery, 10-12 parts of notoginseng, 10-12 parts of millettia reticulata, 13-15 parts of clematis root, 15-16 parts of verbena, 15-16 parts of scutellaria baicalensis, 13-14 parts of liquorice, 10-12 parts of earthworm, 5-7 parts of pearl grass, 10-12 parts of saffron, 9-11 parts of peach kernel, 10-12 parts of angelica sinensis, 13-15 grams of cinnamon twig, 16-18 grams of mulberry twig, 16-18 grams of jujube twig, 15-17 grams of elm twig, 17-18 grams of locust twig, 10-12 grams of pine flower, 8-10 grams of fennel, 10-12 grams of dried ginger, 7-8 grams of pepper, 15-18 grams of Chuanxiong, 13-15 grams of Notopterygium wilfordii, 15-16 grams of Achyranthes bidentata, 15-18 grams of Acanthopanax cortex, 10-12 grams of raw Chuanwu, and 8-10 grams of raw Caowu. No therapeutic effect was shown. Therefore, it is necessary to develop a traditional Chinese medicine composition that is simple to operate and has good therapeutic effects.

[0006] Summary of the Invention

[0007] Aiming at the lack of an ideal treatment method for scapulohumeral periarthritis in the prior art, the present invention provides a traditional Chinese medicine composition, a preparation method and an application thereof.

[0008] On the one hand, the present invention provides a traditional Chinese medicine composition for treating periarthritis of the shoulder, comprising: Achyranthes bidentata and licorice, characterized in that, by mass percentage, the Achyranthes bidentata accounts for 60%-80% and the licorice accounts for 20%-40%.

[0009] In some embodiments, the composition is characterized in that, by mass percentage, the Radix Achyranthis Bidentatae accounts for 70%-80%, and the Radix Glycyrrhizae accounts for 20%-30%.

[0010] In some embodiments, the composition comprises, by mass percentage, 70% of the Radix Achyranthis Bidentatae and 30% of the Radix Glycyrrhizae.

[0011] In some embodiments, the Achyranthes bidentata is produced in Guangzhou.

[0012] In some embodiments, the composition is a liquid preparation, a paste preparation, a powder preparation, or a granular preparation.

[0013] In some embodiments, the present invention provides that the composition is prepared by the following method:

[0014] Step 1: Grind the Radix Achyranthis Bidentatae and Radix Glycyrrhizae into powder respectively, and soak and dissolve them in ethanol for later use;

[0015] Step 2: heating and refluxing the solution obtained in step 1;

[0016] Step 3: Filter the solution obtained in step 2 to obtain filtrate 1.

[0017] In some embodiments, the amount of ethanol used in the preparation method is 300 mL of ethanol per 100 grams of drug powder.

[0018] In some embodiments, the concentration of ethanol used for soaking Achyranthes bidentata in the preparation method is above 75%, and the soaking time in ethanol is at least 20 minutes.

[0019] In some embodiments, the time of heating and reflux in the preparation method is at least one hour.

[0020] In some embodiments, the preparation method further comprises: dissolving the filter residue obtained after filtering in step 3 by adding ethanol, further heating and refluxing, adding water at a ratio of 500 mL of water per 100 g of medicinal powder, refluxing and filtering for a second time to obtain filtrate 2.

[0021] In some embodiments, the preparation method further comprises: dissolving the filter residue obtained from the second filtration in ethanol, further heating and refluxing, adding water at a ratio of 500 mL of water per 100 g of medicinal powder, refluxing and filtering for a third time to obtain filtrate 3.

[0022] In some embodiments, the preparation method further comprises a concentration step after filtration to obtain an extract, wherein the concentration step comprises concentrating the filtrate obtained in the previous step under reduced pressure, wherein the temperature of the reduced pressure concentration does not exceed 60°C, and the specific gravity of the extract is 1.30-1.35.

[0023] In some embodiments, the preparation method further comprises, after concentration, adding dextrin and soluble starch to the extract, mixing with alcohol, granulating, and drying to obtain a granular preparation.

[0024] In another aspect, the present invention provides use of the composition in preparing a medicament for treating scapulohumeral periarthritis.

[0025] In some embodiments, the frozen shoulder is ankylosing frozen shoulder.

[0026] In some embodiments, the drug is an oral granule formulation.

[0027] In some embodiments, the granular formulation is orally administered to a subject at 15-35 g / day for at least 7 days.

[0028] In some embodiments, the granular formulation is orally administered to a subject 9 times a day, for a total of 30 g, for 7-15 days.

[0029] In another aspect, the present invention provides a method for preparing a Chinese medicine composition, comprising:

[0030] Step 1: Grind the Radix Achyranthis Bidentatae and Radix Glycyrrhizae into powder respectively, and soak and dissolve them in ethanol for later use;

[0031] Step 2: heating and refluxing the solution obtained in step 1;

[0032] Step 3: Filter the solution obtained in step 2 to obtain filtrate 1.

[0033] In some embodiments, the mass percentages of the Radix Achyranthis Bidens and Radix Glycyrrhizae are 60%-80% and 20%-40%, respectively.

[0034] In some embodiments, the mass percentages of the Radix Achyranthis Bidens and Radix Glycyrrhizae are 70%-80% and 20%-30%, respectively.

[0035] In some embodiments, the mass percentages of the Radix Achyranthis Bidentatae and Radix Glycyrrhizae are 70% and 30%, respectively.

[0036] In some embodiments, the amount of ethanol used is 300 mL of ethanol per 100 grams of medicinal powder.

[0037] In some embodiments, the concentration of ethanol used for soaking Achyranthes bidentata is greater than 75%, and the soaking time is at least 20 minutes.

[0038] In some embodiments, the time of heating and refluxing is at least one hour.

[0039] In some embodiments, the preparation method further comprises dissolving the filter residue obtained after filtering in step 3 in ethanol, further heating and refluxing, adding water at a ratio of 500 mL of water per 100 g of medicinal powder, refluxing and filtering for a second time to obtain filtrate 2.

[0040] In some embodiments, the preparation method further comprises: dissolving the filter residue obtained from the second filtration in ethanol, further heating and refluxing, adding water at a ratio of 500 mL of water per 100 g of medicinal powder, refluxing and filtering for a third time to obtain filtrate 3.

[0041] In some embodiments, the preparation method further comprises a concentration step after filtration to obtain an extract, wherein the concentration step comprises concentrating the filtrate obtained in the previous step under reduced pressure, wherein the temperature of the reduced pressure concentration does not exceed 60°C, and the specific gravity of the extract is 1.30-1.35.

[0042] In some embodiments, the preparation method further comprises, after concentration, adding dextrin and soluble starch to the extract, mixing with alcohol, granulating, and drying to obtain a granular preparation.

[0043] In some embodiments, the composition is used to treat frozen shoulder.

[0044] In another aspect, the present invention provides a method for using the composition to treat periarthritis of shoulder.

[0045] In some embodiments, the frozen shoulder is ankylosing frozen shoulder.

[0046] In some embodiments, the method of treatment is administering an oral granular formulation to the subject.

[0047] In some embodiments, the method of treatment comprises administering 15-35 g / day of the granular formulation orally to the subject for at least 7 days.

[0048] In some embodiments, the treatment method is to administer the granule formulation to the subject 9 times a day, for a total of 30 g, for 7-15 days. Beneficial effects:

[0049] The ratio of Chinese medicine composition of the present invention is different from prior art, and the present invention has found first that the Chinese medicine formula of this proportioning has extraordinary therapeutic effect in scapulohumeral periarthritis treatment, the effective rate to scapulohumeral periarthritis patient is 90%, cure rate is 60%, pain reduction is greater than 5 grade ratios and is 80%, and after treatment, pain is below 3 grades and is 90%, and shoulder joint range of motion improvement ratio is 80%.And 77% effective patients are effective after taking for 7 days (one course of treatment) continuously, have outstanding advantages compared with commercially available product and method.Compared to the common Chinese medicine of this area, only can treat or improve early stage (painful phase or claim coagulation phase) scapulohumeral periarthritis symptom, composition of the present invention has good therapeutic effect for the scapulohumeral periarthritis treatment of middle and late stages (stiff phase or claim freezing phase).In addition, the component of Chinese medicine of the present invention is simple, and medication is convenient, and usage is simple, and effective is fast, and cost is low, and treatment time is short, and patient suffering is few, and has no toxic and side effect. DETAILED DESCRIPTION

[0050] Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0051] The term "frozen shoulder" was first used by Codman in 1934. Neviaser later pointed out that the pathology of this condition is actually located within the shoulder capsule and therefore named it "adhesive capsulitis" (Codman E. Rupture of the supraspinatus tendon and other lesions in or about the subacromial bursa. In: The shoulder. Boston: Thomas Todd, 1934; Neviaser J. Adhesive capsulitis of the shoulder: a study of the pathological findings in periarthritis of the shoulder. J Bone Joint Surg, 1945). Frozen shoulder is a common shoulder disease with a prevalence of 2%-5% in the population. It is mainly caused by degenerative changes in the joint and surrounding soft tissues, and its pathogenesis has not yet been clearly elucidated. There are many known influencing factors. Any factor that reduces shoulder muscle activity can cause frozen shoulder, including the influence of underlying diseases such as diabetes, hyperthyroidism, hypothyroidism, cardiopulmonary disease, rotator cuff injury, biceps tendinitis, adrenal insufficiency, Parkinson's disease, calcific tendinitis, and humeral fracture (P.H. Laubscher et al. Frozen shoulder: A review, SA ORTHOPAEDIC JOURNAL, Spring 2009). The occurrence of frozen shoulder is also related to age and gender. For example, it is more common in people over 40 years old and is more common in women (Robinson PM et al. Randomized controlled trial of supervised physiotherapy versus a home exercise program after hydrodilatation for the management of primary frozen shoulder. J Shoulder Elbow Surg. 2017).

[0052] Frozen shoulder is characterized by gradually increasing spontaneous pain and limited range of motion in the glenohumeral joint. Clinically, it presents as shoulder pain with progressively limited active and passive range of motion, with normal glenohumeral arthrography (Dimitris Challoumas et al. Comparison of Treatments for Frozen Shoulder: A Systematic Review and Meta-analysis. JAMA Network Open. 2020.). According to the Traditional Chinese Medicine Diagnosis and Treatment Criteria, the diagnosis of frozen shoulder includes:

[0053] 1) Shoulder pain gradually worsens;

[0054] 2) Limited shoulder movement, especially in arm elevation, abduction, internal rotation, extension, and external rotation;

[0055] 3) Tenderness in the anterior and posterior shoulder joint, coracoid process, subacromial process, and long head of biceps tendon, or typical "shoulder resistance" phenomenon;

[0056] 4) If the disease persists for a long time, the patient may suffer from muscle atrophy;

[0057] 5) No special findings are found in X-ray examination. Osteoporosis is common in patients with long-term illness or elderly patients.

[0058] Typically, frozen shoulder progresses through three phases: the first, the pain phase, also known as the freezing phase, during which pain gradually worsens and may last two to nine months. The second, the stiffness phase, also known as the frozen phase, during which shoulder pain is slightly lessened, but shoulder joint motion is limited and stiffness gradually begins to develop, which may last four to twelve months. The third, the recovery phase, also known as the thawing phase, during which stiffness gradually decreases and shoulder function gradually returns, may take five to 24 months (Reeves B, The natural history of the frozen shoulder syndrome, Scand J Rheumatol, 1975). However, this timeframe is only theoretical; some patients have reported persistent pain symptoms for up to six years (Hand C et al., Long-term outcome of frozen shoulder, J Shoulder Elbow Surg, 2008).

[0059] Currently, there is no effective treatment for frozen shoulder. Treatment options typically aim to relieve pain and improve joint range of motion, and are divided into surgical and non-surgical conservative therapies. When shoulder pain is significantly relieved but joint stiffness persists, surgical release under general anesthesia can be performed to restore range of motion. However, due to the greater risks of surgery, conservative treatment remains the primary treatment for frozen shoulder.

[0060] Traditional Chinese Medicine (TCM) treatments for frozen shoulder often rely on massage and acupuncture. The China Rehabilitation Research Center recommends a combination of oral anti-inflammatory and analgesic medications, physical therapy, local blockade of pain points, massage, and self-massage. Acupuncture, massage, and patient-guided joint movements are effective, often combined with oral analgesics and Chinese herbal fumigation. Commonly used analgesics include nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids. Both oral and injected steroids are effective only in the early stages of frozen shoulder, such as the coagulation and early freezing phases, to control inflammation and relieve pain. They are not suitable for use in the late stages of frozen shoulder, when fibrosis has developed but no severe inflammation has occurred. Furthermore, the side effects of steroid injections have been widely reported (Vivek Pandey et al., Clinical Guidelines in the Management of Frozen Shoulder: An Update!, Indian Journal of Orthopaedics, 2021). Traditional Chinese medicine treatments also focus on dispelling wind and cold, unblocking meridians, and promoting blood circulation and removing blood stasis. Traditional Chinese medicine often incorporates herbs such as Notopterygium wilfordii, Saposhnikovia divaricata, and Cinnamon twig for internal and external application to dispel wind and promote blood circulation. For example, Professor Zhu Hui uses a formula for external application: 25g each of Herba Lycopodii, Herba Tougucao, Morus alba, Notopterygium wilfordii, Saposhnikovia divaricata, Herba Millettiae, Radix Aconiti Kusnezoffii, and Radix Aconiti Kusnezoffii, along with 20g each of Carthamus Tinctorius, Frankincense, Myrrh, Corydalis yanhusuo, Cinnamon twig, and Artemisia argyi. The herbs are soaked in vinegar, then, after the vinegar is absorbed, bagged, steamed, and then applied to the affected area (Zhu Hui et al., 98 Cases of Early Periarthritis of the Shoulder Treated with Traditional Chinese Medicine Hot Compress, Journal of External Therapy in Traditional Chinese Medicine, 2000).

[0061] Compared to commonly used analgesics in clinical practice, the composition provided by the present invention utilizes traditional Chinese medicine ingredients, has no side effects, and exhibits excellent therapeutic effects. In some embodiments of the present invention, the composition is used to prepare a medicament for treating frozen shoulder. In some embodiments, the frozen shoulder is in the pain stage, also known as the coagulation stage; in other embodiments, the frozen shoulder is in the stiff stage, also known as the freezing stage; and in yet other embodiments, the frozen shoulder is in the recovery stage, also known as the thawing stage.

[0062] "Achyranthes bidentata" is rich in oleanolic acid and ursolic acid saponins. Meng et al. reported that the pharmacological activities of ursolic acid saponins include uterine smooth muscle stimulation and anti-fertility effects (Meng DL et al., The research development of Achyranthes identata Bl, [J]. Chin J Med Chem, 2001); Liu et al. reported that oleanolic acid has multiple biological activities such as anti-inflammatory, hepatoprotective, anti-HIV, and anti-tumor (Liu D et al., Recent advance in the study on derivatives of oleanolic acid and ursolic acid [J], Chemistry, 2007); Li et al.'s research showed that five new oleanolic acid glycosides from A. bidentata can inhibit osteoclast formation (Li JX et al., Five new oleanolic acid glycosides from Achyranthes bidentata with inhibitory activity on osteoclast formation, Planta Med, 2005).

[0063] Through rigorous experimental design and careful data comparison, the present invention found that the best effect was obtained from the Achyranthes bidentata produced in Guangzhou. In some preferred embodiments, the Achyranthes bidentata is produced in Guangzhou. At the same time, the present invention found that the root of the wild Achyranthes bidentata has the best effect through comparison of the effects. In some embodiments, the Achyranthes bidentata contained in the traditional Chinese medicine composition of the present invention is a wild species.

[0064] Licorice (Radix Glycyrrhizae) refers to the roots and rhizomes of the dicotyledonous plant Leguminosae, including Glycyrrhiza uralensis Fisch, Glycyrrhiza inflata Batal, or Glycyrrhiza glabra L. It is harvested in spring and autumn, the fibrous roots removed, and sun-dried. Remove impurities, wash, soak thoroughly, cut into thick slices, and dry. Licorice grows primarily in arid and semi-arid desert steppes, desert margins, and loess hilly areas. It is primarily distributed in Asia, Europe, North America, and South America, with eight species found throughout China (Editorial Committee of Flora of China. Flora of China; Science Press: Beijing, China, 2010). Commercial licorice is generally divided into two types, eastern and western, depending on its origin. Eastern licorice, also known as Dongcao, is produced in Northeast China, Hebei, and Shanxi. Western licorice, also known as Xicao, is produced in Gansu, Inner Mongolia, Qinghai, Shaanxi, and Xinjiang. Other names for licorice include Guolao, honey grass, honey sweet, beautiful grass, stick grass, sweet licorice, sweet grass, sweet grass root, sweet root, red licorice, powdered licorice, powdered grass, rubbing grass, Lingtong, master, big cry, and stealing honey coral meat.

[0065] Licorice root is neutral in nature and sweet in taste. Traditional Chinese medicine believes it nourishes the spleen and replenishes qi, soothes coughs and moistens the lungs, relieves urgency and detoxifies, and harmonizes various other medicines. Ancient Chinese texts record the benefits of licorice, with the earliest reference dating back to the Han Dynasty. Volume 1 of Shennong's Herbal Classic states: "Licorice root, sweet in taste, neutral. It treats cold and heat in the five internal organs, strengthens tendons and bones, increases muscle strength, heals wounds, and detoxifies."

[0066] "Compendium of Materia Medica" states: "Hu Qia used licorice to treat phlegm and phlegm, and added licorice to Shizao Decoction; Dongyuan used it with seaweed to treat tuberculosis; Danxi used Lianxin Decoction with Daphne daphne to treat tuberculosis; Zhongjing created Gancao Decoction, Gancao Shaoyao Decoction, Gancao Fuling Decoction, Zhigancao Decoction, as well as decoctions such as Guizhi, Mahuang, Pueraria, Qinglong, Lizhong, Sini, Tiaowei, Jianzhong, Chaihu, and Baihu, all of which heavily utilized licorice and contributed to its success." Similarly, later generations of qi-invigorating, tonifying, fire-purging, and detoxifying prescriptions all relied on licorice as the main ingredient, requiring its heavy use for effectiveness. This is an ancient method. However, Master Shi used only two or three parts of licorice. I don't know where this practice originated, but it has become a practice that is unbreakable. I note this here to correct this error.

[0067] "New Compendium of Materia Medica": Licorice root, sweet in taste, mild in nature, warm in nature, can both ascend and descend, and is the yang of yang. It is non-toxic and enters the Taiyin, Shaoyin, and Jueyin meridians.

[0068] "Yaoyao Huayi" states: "Licorice, when used raw, cools and purges heat. It dispels external pathogens, eliminates carbuncles and swellings, relieves sore throats, detoxifies various drugs, removes stomach heat, and relieves urinary tract pain. This is due to its sweet and cooling properties that dispel heat. Roasted, it warms and tonifies the middle, treating spleen deficiency, diarrhea, stomach deficiency, thirst, coughs caused by cold or heat, shortness of breath, fatigue, and exhaustion from labor. This is due to its sweet and warm properties that support the spleen." However, its strong and sweet flavor makes it unsuitable for excessive use in tonics, as it may cause irritation and loss of appetite.

[0069] Compendium of Materia Medica: In prescriptions, roasted licorice root should be moistened with running water and roasted, and the red skin should be scraped off when cooked. Alternatively, it can be roasted with starch water.

[0070] "Bielu": Warms the middle and lowers the qi, relieves irritability and shortness of breath, relieves cough caused by damaged internal organs, quenches thirst, dredges the meridians, promotes blood circulation and qi, and detoxifies all kinds of medicines.

[0071] For over 2,000 years, licorice has been one of the most commonly used herbs in traditional Chinese medicine. Southern Dynasty physician Tao Hongjing revered licorice as the "National Elder," stating, "This herb is the king of all medicines, and few classical prescriptions do not use it." Li Shizhen also noted in his Compendium of Materia Medica, "Among all herbs, licorice is the king. It treats 72 types of lactic acid poisons, detoxifies 1,200 plant poisons, and effectively harmonizes all other herbs, earning it the title 'National Elder.'"

[0072] The clinical application of licorice is divided into "raw" and "honey-roasted." Honey-roasted, also known as roasted licorice, is a processed product made by frying raw licorice until it reaches a yellow to dark yellow color. Traditional Chinese medicine theory suggests that the pharmacodynamics of licorice vary before and after honey-roasting, with honey-roasted licorice significantly enhancing its tonic properties. As early as the Han Dynasty, Zhang Zhongjing's Treatise on Febrile Diseases distinguished two types of licorice and recorded a famous prescription using roasted licorice: "For colds with irregular pulses and palpitations, roasted licorice soup is the main treatment." Zhang Zhongjing also noted that raw licorice was commonly used to treat sore throats and heat invading the blood chambers, while roasted licorice was also commonly used to treat insufficient heart qi and spleen and stomach deficiency. The "Compendium of Chinese Materia Medica" records the main functions and indications of licorice as follows: "It harmonizes the stomach, relieves urgency, moistens the lungs, detoxifies, and harmonizes various herbs. Roasted licorice is used to treat spleen and stomach weakness, fatigue, poor appetite, abdominal pain and loose stools, cramps and pain in the limbs, irritability, and lung atrophy and cough; raw licorice is used to treat sore throat, carbuncles, swellings, fetal toxicity in children, and drug and food poisoning." Research on the effects of processed licorice also indicates differences in the functions of raw and roasted licorice. For example, Sun et al. showed that roasted licorice is superior to raw licorice in improving immune function and stress resistance (Sun Fujun et al., Comparison of Pharmacodynamics of Licorice Before and After Processing, Chinese Journal of Experimental Traditional Chinese Medicine, 2010). This shows that since ancient times, the functions of raw licorice and honey-roasted licorice have differed.

[0073] Modern pharmacological studies have further demonstrated that licorice has multiple pharmacological effects, including anti-inflammation, oxidative stress, immunomodulation, viral infection, and cancer. Using modern medical and pharmaceutical techniques, Wang et al. identified the chemical components contained in licorice and showed that the main bioactive secondary metabolites of licorice include triterpenoid saponins, various flavonoids, coumarins, polysaccharides, and other phenolic substances (Wang, CC et al., Comprehensive review for phytochemical, pharmacological, and biosynthesis studies on Glycyrrhiza spp. Am. J. Chin. Med, 2020; Rozi, P et al., Isolations, characterizations, and bioactivities of polysaccharides from the seeds of three species of Glycyrrhiza. Int. J. Biol. Macromol, 2020). Licorice contains approximately seventy triterpenoid saponins (Feifei Li et al., Review of Constituents and Biological Activities of Triterpene Saponins from Glycyrrhizae Radix et Rhizoma and Its Solubilization Characteristics, Molecules, 2020), which are the main chemical components of licorice. Glycyrrhizic acid is the most abundant saponin in licorice, exceeding 2% and even reaching 7% in high-quality wild licorice. Glycyrrhizic acid preparations have anti-allergic and anti-inflammatory effects (Gao Xueyan et al., Research Progress on the Pharmacological Activities of Licorice and Its Active Ingredients, China Journal of Traditional Chinese Medicine, 2009).

[0074] In addition to licorice, there are many other traditional Chinese medicines that can harmonize other herbs and provide anti-inflammatory effects. Different drug ratios, such as the combination and selection of monarch and ministerial herbs, significantly impact the medicinal properties and stability. In some embodiments, the traditional Chinese medicine composition described herein comprises Radix Achyranthis Bidentatae and Radix Glycyrrhizae, with Radix Achyranthis Bidentatae comprising 20%-90% and Radix Glycyrrhizae comprising 10%-80%. In some embodiments, Radix Achyranthis Bidentatae comprises 30%-90% and Radix Glycyrrhizae comprises 10%-70%. In some embodiments, Radix Achyranthis Bidentatae comprises 40%-90% and Radix Glycyrrhizae comprises 10%-60%. In some embodiments, Radix Achyranthis Bidentatae comprises 50%-90% and Radix Glycyrrhizae comprises 10%-50%. In some embodiments, Radix Achyranthis Bidentatae comprises 30%-80% and Radix Glycyrrhizae comprises 20%-70%. In some embodiments, Radix Achyranthis Bidentatae comprises 40%-80% and Radix Glycyrrhizae comprises 20%-60%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 50%-80% and the Radix Glycyrrhizae Root accounts for 20%-50%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 60%-80% and the Radix Glycyrrhizae Root accounts for 20%-40%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 10% and the Radix Glycyrrhizae Root accounts for 90%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 20% and the Radix Glycyrrhizae Root accounts for 80%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 30% and the Radix Glycyrrhizae Root accounts for 70%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 40% and the Radix Glycyrrhizae Root accounts for 60%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 50% and the Radix Glycyrrhizae Root accounts for 50%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 60% and the Radix Glycyrrhizae Root accounts for 40%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 70% and the Radix Glycyrrhizae Root accounts for 30%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 80% and the Radix Glycyrrhizae Root accounts for 20%. In some embodiments, the Radix Achyranthis Bidentatae accounts for 90% and the Radix Glycyrrhizae Root accounts for 10%. After experimenting with hundreds of drug combinations and different ratios, the present invention ultimately discovered the most suitable drug combination and the drug ratio with the best therapeutic effect. In some embodiments, the composition comprises 60%-80% of Radix Achyranthis Bidentatae and 20%-40% of Radix Glycyrrhizae Root. In some embodiments, the composition comprises 70% of Radix Achyranthis Bidentatae and 30% of Radix Glycyrrhizae Root.

[0075] A "composition" refers to a mixture containing one or more of the components described herein and other traditional Chinese medicine components or chemical components, such as physiologically / pharmaceutically acceptable carriers and excipients or other commonly used analgesic and anti-inflammatory traditional Chinese herbal ingredients. The purpose of a pharmaceutical composition is to maintain the stability of the active ingredients, promote administration to an organism, facilitate absorption of the active ingredients, and thus exert their biological activity. In some embodiments, the composition comprises Achyranthes bidentata and Licorice root. In some embodiments, the composition is obtained by a specific preparation method. In some embodiments, the preparation method comprises Achyranthes bidentata soaked in 75% or greater alcohol. In some embodiments, the preparation method comprises Achyranthes bidentata soaked in 80%, 85%, 90%, 95%, or 98% alcohol. In some embodiments, the preparation method comprises Achyranthes bidentata soaked in 95% or greater alcohol. In some embodiments, the preparation method comprises Licorice root soaked in alcohol. In some embodiments, the preparation method comprises Licorice root soaked in 50% or greater alcohol. In some embodiments, the preparation method uses 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 98% alcohol to soak the licorice. In some embodiments, the preparation method uses 95% alcohol to soak the licorice.

[0076] As used herein, "pharmaceutical composition" and "preparation" are not mutually exclusive. The "preparation" described herein includes various forms of pharmaceutical preparations. In some embodiments, the preparation is a liquid preparation, a paste preparation, a powder preparation, or a granular preparation. In some embodiments, the preparation is a granular preparation. In some embodiments, the granular preparation is obtained by drying. In some embodiments, the drying temperature is above 50°C, for example, 60°C, 70°C, or 80°C. In some embodiments, the granular preparation is sieved and packaged as a finished product after drying. In some embodiments, the sieving is performed through a 60-mesh sieve.

[0077] The term "administration" refers to delivering a bioactive composition or formulation to a subject by a route of administration, including but not limited to oral, intravenous, intraarterial, intramuscular, intraperitoneal, subcutaneous, intramuscular, topical, or a combination thereof. In certain embodiments, the subject's route of administration is oral. In some embodiments, the administration method is oral administration of 15-35g granular formulation / day to a subject for 7-15 days. In some embodiments, the administration method is oral administration of 15-30g granular formulation / day to a subject for 7-15 days. In some embodiments, the administration method is oral administration of 15g, 20g, 25g, or 30g granular formulation / day to a subject for 7-15 days. In some embodiments, the administration method is oral administration of 15g, 20g, 25g, or 30g granular formulation / day to a subject for 7 days.

[0078] The term "subject" means a human being.

[0079] The technical solutions of the present invention will be further described in detail below by way of examples and in conjunction with the accompanying drawings. Unless otherwise stated, the methods and materials of the embodiments described below are all conventional products that can be purchased on the market. Those skilled in the art will appreciate that the methods and materials described below are merely exemplary and should not be construed as limiting the scope of the present invention.

[0080] Example 1:

[0081] The method for preparing the Chinese medicine granule granules of the present invention comprises the following steps:

[0082] 1. Accurately weigh 70 grams of Radix Achyranthis Bidens (from Guangzhou) and 30 grams of Radix Licorice, grind the ingredients to obtain 100 grams of medicinal powder.

[0083] 2.100 g of the powder was added to 300 ml of 95% ethanol (1:3) and soaked for 0.5 h, then heated and refluxed for 1 h, and filtered to obtain the filtrate (1).

[0084] 3. Add 500 ml of water (1:5) to the residue in step 2 and reflux for 1 hour, filter, and filter to obtain the filtrate ⑵.

[0085] 4. Add 300 ml of water (1:3) to the residue in step 3 and reflux for 0.5 hours. Filter to obtain the filtrate (3) and discard the residue.

[0086] 5. Combine the filtrates (1), (2) and (3), and concentrate under reduced pressure using a rotary evaporator (below 60°C) to obtain an extract with a specific gravity of 1.30 to 1.35.

[0087] 6. Add one times the amount of dextrin and one times the amount of soluble starch to the extract, add appropriate amount of alcohol and mix well, granulate, dry at 80℃, pass through a 60-mesh sieve after drying, and package to obtain the finished product.

[0088] Example 2:

[0089] 1. Accurately weigh 60 g of Radix Achyranthis Bidens (from Sichuan) and 40 g of Radix Licorice, grind the ingredients to obtain 100 g of medicinal powder.

[0090] 2.100 g of the powder was added to 300 ml of 95% ethanol (1:3) and soaked for 0.5 h, then heated and refluxed for 1 h, and filtered to obtain the filtrate (1).

[0091] 3. Add 500 ml of water (1:5) to the residue in step 2 and reflux for 1 hour, filter, and filter to obtain the filtrate ⑵.

[0092] 4. Add 300 ml of water (1:3) to the residue in step 3 and reflux for 0.5 hours. Filter to obtain the filtrate (3) and discard the residue.

[0093] 5. Combine the filtrates (1), (2) and (3), and concentrate under reduced pressure using a rotary evaporator (below 60°C) to obtain an extract with a specific gravity of 1.30 to 1.35.

[0094] 6. Add one times the amount of dextrin and one times the amount of soluble starch to the extract, add appropriate amount of alcohol and mix well, granulate, dry at 80℃, pass through a 60-mesh sieve after drying, and package to obtain the finished product.

[0095] Example 3

[0096] 1. Accurately weigh 80 grams of Radix Achyranthis Bidens (from Henan Province) and 20 grams of Radix Licorice, grind the ingredients to obtain 100 grams of medicinal powder.

[0097] 2.100 g of the powder was added to 300 ml of 95% ethanol (1:3) and soaked for 0.5 h, then heated and refluxed for 1 h, and filtered to obtain the filtrate (1).

[0098] 3. Add 500 ml of water (1:5) to the residue in step 2 and reflux for 1 hour, filter, and filter to obtain the filtrate ⑵.

[0099] 4. Add 300 ml of water (1:3) to the residue in step 3 and reflux for 0.5 hours. Filter to obtain the filtrate (3) and discard the residue.

[0100] 5. Combine the filtrates (1), (2) and (3), and concentrate under reduced pressure using a rotary evaporator (below 60°C) to obtain an extract with a specific gravity of 1.30 to 1.35.

[0101] 6. Add one times the amount of dextrin and one times the amount of soluble starch to the extract, add appropriate amount of alcohol and mix well, granulate, dry at 80℃, pass through a 60-mesh sieve after drying, and package to obtain the finished product.

[0102] Example 4:

[0103] The present invention is a clinical overall therapeutic effect experimental study.

[0104] 1. Subjects: There were 10 patients with periarthritis of shoulder, including 4 males and 6 females, aged 35-69 years.

[0105] 2. Diagnostic criteria: According to the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine" for the diagnosis of periarthritis of shoulder.

[0106] 3. Inclusion criteria:

[0107] a. Patients aged 35-70 years old can be included if they meet the diagnostic criteria for frozen shoulder in the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine".

[0108] 4. Exclusion criteria:

[0109] a. Reflex shoulder pain caused by heart and biliary tract diseases.

[0110] b. Radiating pain in the cervical spine.

[0111] c. Tumors, tuberculosis and other diseases.

[0112] d. Rheumatoid arthritis, etc.

[0113] The basic information of the enrolled patients is shown in Table 1.

[0114] Table 1: Basic information of enrolled patients

[0115] 5. Treatment methods:

[0116] Take the Chinese medicine granule granule of the present invention, 9 packets (30g in total) a day, and take it continuously for 7 days, which is a course of treatment.

[0117] 6. Efficacy evaluation:

[0118] Clinically cured: Shoulder pain symptoms disappear, and the patient is free to move. Upper arm elevation ≥150°, extension ≥75°, and abduction ≥75° are possible. Shoulder joint function has essentially returned to normal, and muscle atrophy has improved.

[0119] Effective: Shoulder pain symptoms are alleviated. Upper arm elevation ≥110°, extension ≥60°, and abduction ≥60°. Shoulder joint range of motion is increased.

[0120] Ineffective: There was no significant improvement in shoulder pain symptoms, and the sum of the improvements in upper arm raising, extension, and abduction movements was ≤30°.

[0121] The treatment effects and data statistics are shown in Tables 2 to 5.

[0122] Table 2: Statistical results of clinical efficacy

[0123] Table 3: Clinical pain improvement evaluation results

[0124] The clinical results of improvement in shoulder joint range of motion are shown in Table 4.

[0125] Table 4: Clinical statistics of improvement results of shoulder joint range of motion

[0126] The summary statistics of clinical results are shown in Table 5 .

[0127] Table 5: Summary statistics of clinical outcomes

[0128] Results showed that the effective rate of the Chinese medicine composition of the present invention for patients with periarthritis of shoulder was 90%, the cure rate was 60%, the pain reduction was greater than 5 levels in 80%, the pain after treatment was below 3 levels in 90%, and the improvement ratio of shoulder joint range of motion was 80%. Moreover, 77% of the effective patients were effective after taking the medicine for 7 consecutive days (one course of treatment), which is superior to commercially available products and methods. This shows that the Chinese medicine composition of the present invention is scientifically compatible and has a reasonable ratio, and has a quick effect and remarkable efficacy in the treatment of periarthritis of shoulder.

[0129] The embodiments of the present invention are not limited to the above embodiments. Without departing from the spirit and scope of the present invention, ordinary technicians in this field can make various changes and improvements to the present invention in form and details, and these are all considered to fall within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating scapulohumeral periarthritis, comprising: Radix Achyranthis Bidentatae and Radix Glycyrrhizae, characterized in that: Calculated by mass percentage, the Radix Achyranthis Bidentatae accounts for 60%-80%, and the Radix Glycyrrhizae accounts for 20%-40%.

2. The composition according to claim 1, characterized in that Calculated by mass percentage: the Radix Achyranthis Bidentatae accounts for 70%-80%, and the Radix Glycyrrhizae accounts for 20%-30%.

3. The composition according to claim 2, characterized in that Calculated by mass percentage: the Radix Achyranthis Bidentatae accounts for 70%, and the Radix Glycyrrhizae accounts for 30%.

4. The composition according to claim 1, wherein the Achyranthes bidentata is produced in Guangzhou.

5. The composition according to any one of claims 1 to 4, which is a liquid preparation, a paste preparation, a powder preparation or a granular preparation.

6. The composition according to claim 5, characterized in that The composition is prepared by the following method: Step 1: Grind the Radix Achyranthis Bidentatae and Radix Glycyrrhizae into powder respectively, and soak and dissolve them in ethanol for later use; Step 2: heating and reflux the solution obtained in step 1; Step 3: Filter the solution obtained in step 2 to obtain filtrate 1.

7. The composition according to claim 6, characterized in that The amount of ethanol used in the preparation method is 300 mL of ethanol for soaking every 100 grams of medicinal powder.

8. The composition according to claim 6, characterized in that In the preparation method, the concentration of ethanol used for soaking the Radix Achyranthis Bidentatae is above 75%, and the soaking time of the ethanol is at least 20 minutes.

9. The composition according to claim 6, characterized in that The time of heating and reflux in the preparation method is at least one hour.

10. The composition according to claim 6, characterized in that The preparation method further comprises: adding ethanol to dissolve the filter residue obtained after filtering in step 3, further heating and refluxing, adding water at a ratio of 500 mL of water per 100 g of medicinal powder, refluxing and filtering for a second time, and obtaining filtrate 2.

11. The composition according to claim 10, characterized in that The preparation method further comprises: adding ethanol to dissolve the filter residue obtained by the second filtration as claimed in claim 10, further heating and refluxing, adding water at a ratio of 500 mL of water per 100 g of medicinal powder, refluxing and filtering for a third time to obtain filtrate 3.

12. The composition according to any one of claims 6 to 11, characterized in that The preparation method further comprises a concentration step after filtration to obtain an extract, wherein the concentration step comprises concentrating the filtrate obtained in the above step under reduced pressure, wherein the temperature of the reduced pressure concentration does not exceed 60° C., and the specific gravity of the extract is 1.30-1.

35.

13. The composition according to claim 12, characterized in that The preparation method further comprises, after concentration, adding dextrin and soluble starch to the extract, mixing with alcohol, granulating, and drying to obtain a granular preparation.

14. Use of the composition according to any one of claims 1 to 13 in the preparation of a medicament for treating scapulohumeral periarthritis.

15. The use according to claim 14, wherein the scapulohumeral periarthritis is scapulohumeral periarthritis in the stiff stage.

16. The use according to claim 14 or 15, wherein the drug is an oral granule preparation.

17. The use according to claim 16, wherein the granular preparation is orally administered to a subject at 15-35 g / day for at least 7 days.

18. The use according to claim 17, wherein the granular preparation is orally administered to a subject 9 times a day, with a total of 30 g, for 7-15 days.

19. A method for preparing a Chinese medicine composition, comprising: Step 1: Grind the Radix Achyranthis Bidentatae and Radix Glycyrrhizae into powder respectively, and soak and dissolve them in ethanol for later use; Step 2: heating and reflux the solution obtained in step 1; Step 3: Filter the solution obtained in step 2 to obtain filtrate 1; The mass percentages of Radix Achyranthis Bidentatae and Radix Glycyrrhizae are 60%-80% and 20%-40% respectively; preferably, the mass percentages are 70%-80% and 20%-30% respectively; more preferably, the mass percentages are 70% and 30% respectively.

20. The method according to claim 19, characterized in that The usage amount of the ethanol is 300 mL of ethanol per 100 g of medicinal powder.

21. The method according to claim 19, characterized in that The concentration of ethanol used for soaking Achyranthes bidentata is above 75%, and the soaking time of ethanol is at least 20 minutes.

22. The method according to claim 19, characterized in that The time for the temperature rise reflux is at least one hour.

23. The method according to claim 19, characterized in that Further including: The filter residue obtained after filtering in step 3 is dissolved in ethanol, and the temperature is further raised to reflux, and water is added at a ratio of 500 mL of water per 100 g of medicinal powder, and the mixture is refluxed for a second filtration to obtain filtrate 2.

24. The method according to claim 23, characterized in that Further including: The filter residue obtained by the second filtration as described in claim 23 is dissolved in ethanol, further heated and refluxed, water is added at a ratio of 500 mL of water per 100 g of medicinal powder, and refluxed for a third filtration to obtain filtrate 3.

25. The method according to any one of claims 19 to 24, characterized in that: After filtration, a concentration step is further included to obtain an extract, wherein the concentration step includes concentrating the filtrate obtained in the above step under reduced pressure, wherein the temperature of the reduced pressure concentration does not exceed 60° C., and the specific gravity of the extract is 1.30-1.

35.

26. The method according to claim 25, characterized in that After concentration, the extract is added with dextrin and soluble starch, mixed with alcohol, granulated, and dried to obtain a granular preparation.