Traditional Chinese medicine composition with effects of tonifying kidney, dispelling cold and dredging collaterals as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition with effects of tonifying kidney, dispelling cold and dredging collaterals as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 20 to 40 parts of rhizoma cibotii, 5 to 15 parts of fructus psoraleae, 10 to 20 parts of cortex eucommiae, 10 to 20 parts of caulis sinomenii, 20 to 40 parts of caulis spatholobi, 1 to 10 parts of scorpio, 10 to 20 parts of honeycomb and 10 to 20 parts of rhizoma drynariae. The preparation method comprises the following steps: adding a solvent into the rhizoma cibotii, the fructus psoraleae, the cortex eucommiae, the caulis sinomenii, the caulis spatholobi, the scorpio, the honeycomb and the rhizoma drynariae, extracting, and filtering to obtain an extracting solution; and concentrating the extracting solution to obtain thick paste. The traditional Chinese medicine composition disclosed by the invention is mainly used for tonifying kidney and strengthening governor meridian, is not forgotten to activate blood and remove stasis, and is combined with insect medicines for dispelling wind and dredging collaterals, warming kidney and tonifying deficiency to play a synergistic effect, so that the treatment effect of the ankylosing spondylitis can be remarkably enhanced.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition with the effects of tonifying kidney, dispelling cold and dredging collaterals, and a preparation method and application thereof. BACKGROUND

[0002] Ankylosing spondylitis (AS) is a kind of serum-negative spondyloarthritis, which is a systemic inflammatory disease characterized by involvement of the spine and sacroiliac joints. Inflammation involves synovial joints and cartilage joints, as well as muscle tendon, ligament attachment to bone (tendon end), often causing fibrous and bony ankylosis. In clinical practice, most of them show inflammatory low back pain, stiffness and limited activity, and some patients may have peripheral arthritis, enthesiopathy, eye inflammation and other extra-articular manifestations.

[0003] The etiology of ankylosing spondylitis is not clear, and it is currently believed to be a polygenic genetic disease caused by the combined action of genetic, environmental, infection, immune and other factors. Environmental cold, humidity, cold water stimulation, etc. can induce ankylosing spondylitis. Long-term sitting, inactivity of the spine, fixed posture can affect joint mobility, which is easy to cause spinal injury. Increased stress on the spine and joints can increase tendon attachment point pressure, thereby exacerbating inflammatory reactions.

[0004] However, if AS patients can be diagnosed and treated reasonably in time, symptoms can be controlled and prognosis can be improved. Non-drug, drug and surgical comprehensive treatment should be used to relieve pain and stiffness, control or reduce inflammation, maintain good posture, prevent spinal or joint deformation, and correct deformed joints if necessary, in order to improve and improve the quality of life of patients.

[0005] Drugs for treating AS can be divided into the following categories: ① non-steroidal anti-inflammatory drugs (NSAIDs), suitable for patients with severe pain and stiffness at night; ② disease-modifying antirheumatic drugs (DMARDs), drugs that affect disease progression; ③ glucocorticoids; and ④ biological agents.

[0006] Since there is no radical treatment for AS, the above western medicines or biological agents are used for long-term use, which only improves temporary pain, but cannot change the course of the disease, such as non-steroidal anti-inflammatory drugs (NSAIDs), and some drugs can produce obvious side effects, such as glucocorticoids.

[0007] Traditional Chinese medicine (TCM) treatments, with their advantages of multiple components, multiple targets, and fewer side effects, are gaining increasing recognition from patients. The first description of "great hunchback" in ancient Chinese medical texts appears in the *Huangdi Neijing* (Yellow Emperor's Inner Classic). The *Suwen* (Plain Questions) chapter "On the Circulation of Vital Energy" states, "Yang energy, when refined, nourishes the spirit; when supple, it nourishes the tendons. If the opening and closing of the pores are disordered, cold pathogens can invade, leading to great hunchback." This means that the body's Yang energy, when nourishing the spirit, becomes refined; when nourishing the tendons, it becomes supple. If the opening and closing of the pores are disordered, cold pathogens can invade, resulting in great hunchback. While "great hunchback" here may not necessarily refer to ankylosing spondylitis, this passage is the first to propose that after external pathogens invade the body, the stagnation of cold pathogens in the meridians can cause a pathological state of impaired spinal flexion and extension.

[0008] Chinese invention patent application CN2024117896477 discloses a traditional Chinese medicine composition for treating lumbar spine disorders and its preparation method. It is made from the following raw materials in the indicated weight ratios: 70-80g of Psoralea corylifolia, 70-80g of Corydalis yanhusuo, 70-80g of Drynaria fortunei, 70-80g of Cibotium barometz, 85-95g of Rehmannia glutinosa, 70-80g of Dipsacus asper, 85-95g of Eucommia ulmoides, 45-55g of deer antler, 70-80g of Chaenomeles speciosa, 85-95g of Angelica pubescens, 70-80g of Notopterygium incisum, 70-80g of Gentiana macrophylla, 85-95g of Achyranthes bidentata, 85-95g of Taxillus chinensis, 115-125g of Clematis chinensis, 70-80g of Angelica sinensis, 70-80g of Ligusticum chuanxiong, and 55g of Eupolyphaga sinensis. ~65g, earthworm 55~65g, black ant 45~55g, *Dioscorea nipponica* 70~80g, *Lycopodium clavatum* 85~95g, cinnamon 25~35g, *Clematis chinensis* 85~95g, frankincense 45~55g, myrrh 45~55g, *Epimedium 85~95g*, *Spatholobus suberectus* 115~125g, licorice 55~65g, *Aconitum carmichaelii* 70~80g, scorpion 25~35g, centipede 15~25g, *Zaocys dhumnades* 25~35g, *Bungarus tiglium* 10~15g, *Piper kadsura* 85~95g, *Trachelospermum jasminoides* 85~95g. This invention's prescription is precise and effective, safe and reliable, with significant therapeutic effects, and convenient to take. It is an excellent remedy for treatment, recovery, and prevention of relapse.

[0009] Chinese invention patent application CN201710899849.0 discloses a traditional Chinese medicine composition for treating joint pain. The components and their weight percentages of the composition are as follows: 60-300g of Rehmannia glutinosa (processed), 100-250g of Drynaria fortunei, 60-150g of Angelica sinensis, 60-100g of Psoralea corylifolia, 50-160g of Cynanchum paniculatum, 50-160g of Eupolyphaga sinensis, 30-160g of Bombyx mori (stir-fried with wheat bran), 60-150g of Cibotium barometz, 20-50g of Scolopendra subspinipes, 20-50g of Buthus martensii, and 30g of Vespa nidus (stir-fried). ~60g, Dipsacus asper 90-160g, Pheretima aspergillum (processed with wine) 50-100g, Zaocys dhumnades (processed with wine) 50-150g, Corydalis yanhusuo 80-160g, Pyrola rotundifolia 150-350g, Eucommia ulmoides 60-120g, Epimedium brevicornu 30-100g, Clematis chinensis 100-250g, Geranium wilfordii 90-350g, Taxillus chinensis 90-160g, Spatholobus suberectus 100-160g, Humulus scandens 100-160g, Rehmannia glutinosa 100-160g, Polygonum cuspidatum 100-160g, Ligustrum lucidum 60-150g.

[0010] Existing technologies have been studied and have achieved some results in the treatment of arthritis and its symptoms. However, there are still many shortcomings in the treatment of ankylosing spondylitis, such as complicated medications, poor patient compliance, and the need to improve their efficacy.

[0011] Therefore, current TCM treatments still need to include TCM compositions that can improve treatment from multiple angles to achieve more significant and efficient therapeutic effects. Summary of the Invention

[0012] The purpose of this invention is to provide a traditional Chinese medicine composition with the effects of tonifying the kidney, dispelling cold, and unblocking the meridians, as well as its preparation method and application. Through the refinement of the prescription, a simplified prescription with strict compatibility and synergistic effect is achieved, which can significantly improve the therapeutic effect on ankylosing spondylitis.

[0013] To achieve the above-mentioned objectives, the technical solution of this invention is as follows: A traditional Chinese medicine composition with the effects of tonifying the kidney, dispelling cold, and unblocking the meridians, comprising the following ingredients by weight: Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Sinomenium acutum, Spatholobus suberectus, Buthus martensii, Vespa nidus, and Drynaria fortunei.

[0014] Preferably, the raw materials, by weight, include the following components: 20-40 parts of Cibotium barometz, 5-15 parts of Psoralea corylifolia, 10-20 parts of Eucommia ulmoides, 10-20 parts of Sinomenium acutum, 20-40 parts of Spatholobus suberectus, 1-10 parts of Buthus martensii, 10-20 parts of Vespa nidus, and 10-20 parts of Drynaria fortunei.

[0015] Preferably, the raw materials, by weight, include the following components: 30-40 parts of Cibotium barometz, 10-15 parts of Psoralea corylifolia, 15-20 parts of Eucommia ulmoides, 15-20 parts of Sinomenium acutum, 30-40 parts of Spatholobus suberectus, 6-10 parts of Buthus martensii, 15-20 parts of Vespa nidus, and 15-20 parts of Drynaria fortunei.

[0016] Preferably, the raw materials, by weight, include the following components: 30 parts of Cibotium barometz, 10 parts of Psoralea corylifolia, 15 parts of Eucommia ulmoides, 15 parts of Sinomenium acutum, 30 parts of Spatholobus suberectus, 6 parts of Buthus martensii, 15 parts of Vespa nidus, and 15 parts of Drynaria fortunei.

[0017] The second objective of this invention is a pharmaceutical preparation comprising the aforementioned traditional Chinese medicine composition having the effects of tonifying the kidney, dispelling cold, and unblocking the meridians, as well as pharmaceutically acceptable excipients.

[0018] Preferably, the dosage form of the pharmaceutical preparation is selected from pills, capsules, granules, oral liquids, powders, or tablets.

[0019] For different dosage forms, appropriate drug carriers can be selected in this field.

[0020] The pharmaceutical excipients used serve as carriers, which can be solid, liquid, or gaseous. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate, and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil, and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0021] When preparing compositions into oral dosage forms, any convenient pharmaceutical medium can be used. For example, water, ethanol, oils, alcohols, flavoring agents, preservatives, coloring agents, etc., can be used to form oral liquid dosage forms, such as suspensions and solutions; while carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulators, emulsifiers, lubricants, binders, and disintegrants, can be used to form oral solid dosage forms, such as powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or non-aqueous techniques.

[0022] Tablets containing the traditional Chinese medicine composition of the present invention can be prepared by compression or molding, and one or more excipients or adjuvants may be used. The active ingredient can be compressed in a free-flowing form (e.g., powder or granules) in a suitable machine, optionally mixed with binders, lubricants, inert diluents, surfactants, or dispersants. Molded tablets can be molded in a suitable machine, i.e., a powdery mixture moistened with an inert liquid diluent, each tablet preferably containing about 0.05 mg to about 5 g of active ingredient, and each sachet or capsule preferably containing about 0.05 mg to about 5 g of active ingredient. For example, a formulation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active drug, mixed with a suitable and convenient carrier material, which may comprise about 5% to 95% of the total composition. Unit dosage forms typically contain about 1 mg to about 2 g of active ingredient, typically in doses of 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg, or 1000 mg.

[0023] The pharmaceutical compositions of this invention suitable for parenteral administration can be prepared as aqueous solutions or suspensions of the active compound and may include suitable surfactants, such as hydroxypropyl cellulose. Dispersions can also be prepared in mixtures of glycerol, liquid polyethylene glycol, and their oils. Furthermore, preservatives may be added to prevent harmful microbial growth.

[0024] The medicaments of the present invention can be in forms suitable for topical use, such as aerosols, creams, ointments, lotions, powders, or the like. Furthermore, the compositions can be in suitable forms for transdermal drug delivery devices. These formulations can be prepared using the traditional Chinese medicine compositions of the present invention through conventional processing methods. For example, a cream or ointment with a desired consistency can be prepared by mixing a hydrophilic material and water, and about 5 wt% to about 10 wt% of the compound.

[0025] The medicament of the present invention can be in a form suitable for rectal administration, wherein the carrier is solid. It is preferable to formulate the mixture into a single-dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories can be made by first forming a mixture containing a softened or melted carrier, followed by cooling and shaping in a mold.

[0026] In addition to the carrier components described above, the pharmaceutical formulations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. Furthermore, other excipients may be added, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, colorants, and flavoring agents, and the components containing the traditional Chinese medicine composition of this invention can also be prepared in powder or concentrated form.

[0027] The third objective of this invention is to provide a method for preparing the aforementioned traditional Chinese medicine composition with the effects of tonifying the kidney, dispelling cold, and unblocking the meridians, comprising the following steps: (1) Extract the following herbs by adding solvent: Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Sinomenium acutum, Spatholobus suberectus, Buthus martensii, Vespa nidus, and Drynaria fortunei; filter the extract to obtain the extract. (2) The extract is concentrated to obtain a thick paste.

[0028] Preferably, in step (1), the amount of solvent added is 8-12 times the total mass of the raw materials, and the solvent is water or a 10-50% aqueous ethanol solution.

[0029] Preferably, in step (1), the extraction is performed 1-3 times, and the extraction time is 1-3 hours each time.

[0030] Preferably, step (2) further includes drying the paste.

[0031] Another object of the present invention is to provide the application of the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method described above in the preparation of a drug for treating ankylosing spondylitis of the kidney deficiency and cold type.

[0032] The *Neijing* (Inner Canon of Medicine) contains numerous passages suggesting that kidney deficiency is the root cause of lower back pain. The *Suwen* (Plain Questions) chapter on Bi syndrome states, "Kidney Bi syndrome is characterized by distension, with the buttocks replacing the heels and the spine replacing the head," describing a state of extreme difficulty in movement due to a hunched back, contracture of the lower limbs, and general malaise. It attributes this condition to kidney deficiency. The *Suwen* chapter on the essential principles of pulse diagnosis states, "The waist is the residence of the kidneys; if it cannot turn or move, the residence is exhausted." This means that the kidneys are located beside the lumbar vertebrae, hence the waist is considered the residence of the kidneys. If kidney qi is sufficient, the waist can move and turn freely. If kidney qi is deficient, it can lead to a condition where the waist cannot turn or move. The *Neijing* also first demonstrates the role of the Du meridian in the pathogenesis of lower back pain. The Du meridian originates in the lower abdomen, emerges at the perineum, ascends along the interior of the spine, passes through the top of the head and forehead, and terminates at the frenulum of the upper lip. The Du meridian is known as the "Sea of ​​Yang Meridians," governing the yang qi of the entire body. Running along the spine, it plays a vital role in maintaining the health of the spine.

[0033] The *Neijing* (Inner Canon of Medicine), in its chapter on bone cavities, states, "When the Du meridian is diseased, the spine becomes stiff and twisted." This suggests that diseases of the Du meridian can cause spinal stiffness and even twisting. The *Maijing* (Pulse Classic), in its chapter on the eight extraordinary meridians, states, "This is the Du meridian; there is stiffness and pain in the lower back, and the inability to bend forward or backward." The Du meridian runs along the midline of the spine. Asthenia gravis (AS) presents with lower back pain, stiffness, and in severe cases, an inability to bend forward or backward, clinical manifestations consistent with the descriptions of symptoms caused by Du meridian diseases in the *Neijing* and *Maijing*. (*Zhengzhi Zhunsheng*). The *Lingshu* (Spiritual Pivot), in its chapter on *Yingqi*, also explicitly states that the Du meridian is actually a branch of the Foot Shaoyin Kidney meridian. Subsequently, many ancient texts have proposed a close connection between kidney deficiency, Du meridian deficiency, and lower back pain. The *Yixue Zhongzhong Canxi Lu* (Records of Integrating Chinese and Western Medicine) states, "All lower back pain in people originates in the spine, which is mainly caused by the Du meridian… Those with kidney deficiency will inevitably have a weak Du meridian, hence the lower back pain." This clearly indicates that pain in multiple areas of the spine is a result of Du meridian disease. It is suggested that kidney deficiency can be combined with deficiency of the Du meridian, which together lead to the onset of lower back pain.

[0034] The fundamental pathogenesis of kyphosis (dilatational kyphosis) is a deficiency of the root and an excess of the branch, namely, deficiency of the kidney and the Du meridian as the root, and pathogenic factors as the branch. When wind, cold, dampness, and heat invade the body, they linger in the tendons, muscles, and joints, obstructing the flow of qi and blood, leading to spinal stiffness and kyphosis. Internal accumulation of wind, cold, dampness, and heat can generate phlegm and blood stasis, further aggravating the condition. Among these, kidney deficiency and depletion of the Du meridian are the basic pathogenesis and prerequisites of kyphosis, while various external pathogenic factors are driving factors that promote the evolution and deterioration of the condition. Therefore, tonifying the kidney and strengthening the Du meridian is the fundamental principle for treating kyphosis. Based on this, treatment methods such as dispelling cold and warming yang, eliminating dampness, and clearing heat are used according to the strength of the pathogenic factors in the patient. Phlegm and blood stasis are important pathological factors leading to the persistence and aggravation of the condition, a consensus among most physicians. Activating blood circulation, removing blood stasis, resolving phlegm, and unblocking the meridians should be a consistent and recognized key point in treatment. Some medical practitioners advocate the appropriate use of insect-based medicines. On the one hand, they believe that insect-based medicines can be used to treat stubborn diseases by leveraging their properties of dispelling wind, clearing the meridians, and relieving pain. On the other hand, their effects of warming the kidneys, strengthening yang, and tonifying the body should not be overlooked.

[0035] This invention presents a systematic study on the TCM syndrome classification of ankylosing spondylitis (AS). By including 278 AS patients and collecting clinical diagnostic information, factor analysis and systemic cluster analysis were used to establish four core TCM syndrome groups for AS: Kidney Deficiency with Cold in the Governing Vessel, Kidney Yin Deficiency, Damp-Heat Obstruction, and Blood Stasis Obstruction. Further large-sample meta-analysis (including 18,541 AS patients) showed that there are 29 common AS syndromes, with Liver and Kidney Deficiency (46.64%), Damp-Heat Obstruction, Blood Stasis Obstruction, and Cold-Dampness Obstruction being the top four syndrome types, confirming the key role of "Kidney Deficiency" in the TCM pathogenesis of AS. Clinical observations indicate that patients with Cold syndrome have more severe spinal structural damage than those with Heat syndrome. Their mSASSS scores are positively correlated with age, disease duration, sacroiliac joint X-ray grading, BASFI index, and spinal mobility indicators, but negatively correlated with flexibility indicators such as thoracic mobility. This study focuses on the differentiation and treatment of Cold syndrome based on Kidney Deficiency with Governing Vessel Emptiness.

[0036] The beneficial effects of this invention are as follows: (1) The Chinese medicine composition of the present invention is based on the basic principle of "tonifying the kidney" in Dalou Chinese medicine. It takes tonifying the kidney and strengthening the Du meridian as the foundation, while also promoting blood circulation and removing blood stasis. It combines insect medicine to dispel wind and unblock the meridians, warm the kidney and replenish deficiency.

[0037] The formula uses Cibotium barometz, which is warm in nature and enters the liver and kidney meridians. It strengthens the lower back and knees, dispels wind and dampness, and is particularly effective in tonifying the liver and kidneys and strengthening the Du meridian. It is the chief herb in the formula, directly entering the kidney and Du meridians to consolidate the foundation. Eucommia ulmoides and Psoralea corylifolia are the assistant herbs. Psoralea corylifolia is pungent and warm, tonifying kidney yang, consolidating essence and reducing urination, warming the fire of the gate of life, and assisting Cibotium barometz in strengthening the yang qi of the kidney and Du meridians. Eucommia ulmoides is an essential herb for tonifying the liver and kidneys and strengthening tendons and bones. It is sweet and warm in nature and works with Cibotium barometz to enhance the support of the spine and improve cold pain in the lower back. The three herbs work together to tonify the kidneys and strengthen yang, strengthen the Du meridian, consolidate the innate foundation, nourish tendons and bones, and replenish yang qi to resist the invasion of external pathogens.

[0038] Drynaria fortunei has the effects of promoting blood circulation, healing injuries, tonifying the kidneys and strengthening bones, and dispelling wind and dampness, which can enhance the kidney-tonifying and bone-strengthening effects of Psoralea corylifolia. Sinomenium acutum is bitter, pungent, and neutral in nature, dispelling wind and dampness, clearing the meridians, and effectively removing cold and dampness from the muscles and bones, relieving joint stiffness and pain. Scorpion is pungent and neutral in nature, dispelling wind and clearing the meridians, relieving pain and numbness, and has strong penetrating power, able to penetrate deep into the joints to dispel latent cold and dampness. Beehive is sweet and neutral in nature, dispelling wind and attacking toxins, dispersing nodules and relieving pain, assisting scorpion in clearing the meridians, and also dispersing the accumulation of cold and dampness; its sweet nature is mild, tonifying deficiency and relieving pain. The three herbs work synergistically to dispel cold and dampness externally and clear the meridians internally, breaking through the stagnation of pathogenic factors, especially effective in relieving stiffness and pain caused by cold and dampness obstruction. Spatholobus suberectus is bitter, sweet, and warm in nature, excelling at promoting blood circulation, nourishing blood, and relaxing muscles and tendons, both clearing stagnation and nourishing the meridians, preventing the harm of prolonged illness entering the meridians. The combination of *Sinomenium acutum* and *Spatholobus suberectus* dispels wind and unblocks the meridians, enhancing the effects of the principal herb in tonifying the liver and kidneys, strengthening the waist and knees, dispelling wind and dampness, and facilitating bending and stretching. *Drynaria fortunei* also enhances the effect of promoting blood circulation and unblocking the meridians. The entire formula uses *Cibotium barometz* and *Psoralea corylifolia* to tonify the kidneys and strengthen the *Du* meridian, thus consolidating the root cause; *Sinomenium acutum* and *Scorpio* to dispel cold and unblock the meridians, addressing the symptoms; and *Spatholobus suberectus* to invigorate blood and prevent further complications, achieving a comprehensive approach that addresses both the root cause and the symptoms. The formula uses both tonifying and expelling herbs, tonifying without retaining pathogens and expelling without harming the body's vital energy, achieving a balance of tonification and attack. *Scorpio* and *Vessel* utilize the insect's ability to search and eliminate pathogens, directly targeting deeply hidden pathogens and enhancing the effect of relieving pain and numbness.

[0039] (2) The present invention achieves synergistic effect by combining specific medicinal ingredients in a specific ratio. The formula is concise and effective. Research results show that the refined formula of the present invention has a significant therapeutic effect on ankylosing spondylitis.

[0040] (3) The traditional Chinese medicine composition of the present invention is based on tonifying the kidney and strengthening the Du meridian, while also promoting blood circulation and removing blood stasis. Combined with insect medicine to dispel wind and unblock the meridians, warm the kidney and replenish deficiency, it plays a synergistic and enhanced role, which can significantly enhance the therapeutic effect of ankylosing spondylitis. Detailed Implementation

[0041] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of protection claimed in this application.

[0042] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention were obtained through conventional commercial means. Unless otherwise specified, all contents mentioned below are mass contents. Unless otherwise specified, it is understood that the process was carried out at room temperature.

[0043] Example 1 The formula consists of 20 parts Cibotium barometz, 5 parts Psoralea corylifolia, 10 parts Eucommia ulmoides, 10 parts Sinomenium acutum, 20 parts Spatholobus suberectus, 1 part Buthus martensii, 10 parts Vespa nidus, and 10 parts Drynaria fortunei.

[0044] The preparation method is as follows: (1) Add 12 times the amount of water to Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Sinomenium acutum, Spatholobus suberectus, Buthus martensii, Vespa nidus and Drynaria fortunei, heat and reflux for 1.5 h, filter, and obtain the extract; (2) The extract is concentrated and dried to obtain the final product.

[0045] Example 2 The formula consists of 30 parts Cibotium barometz, 10 parts Psoralea corylifolia, 15 parts Eucommia ulmoides, 15 parts Sinomenium acutum, 30 parts Spatholobus suberectus, 6 parts Buthus martensii, 15 parts Vespa nidus, and 15 parts Drynaria fortunei.

[0046] The preparation method is as follows: (1) Add 6 times the amount of water to Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Sinomenium acutum, Spatholobus suberectus, Buthus martensii, Vespa nidus and Drynaria fortunei, heat and reflux for 0.5 h, extract three times, filter, combine the filtrates to obtain the extract; (2) The extract is concentrated and dried to obtain the final product.

[0047] Example 3 The formula consists of 40 parts Cibotium barometz, 15 parts Psoralea corylifolia, 20 parts Eucommia ulmoides, 20 parts Sinomenium acutum, 40 parts Spatholobus suberectus, 10 parts Buthus martensii, 20 parts Vespa nidus, and 20 parts Drynaria fortunei.

[0048] The preparation method is as follows: (1) Add 8 times the amount of water to Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Sinomenium acutum, Spatholobus suberectus, Buthus martensii, Vespa nidus and Drynaria fortunei, heat and reflux for 1 hour, extract twice, filter, combine the filtrates to obtain the extract; (2) The extract is concentrated and dried to obtain the final product.

[0049] Comparative Example 1 The formula for this comparative proportion by weight is as follows: 30 parts of Cibotium barometz, 10 parts of Astragalus complanatus, 15 parts of Dipsacus asper, 15 parts of Sinomenium acutum, 30 parts of Spatholobus suberectus, 6 parts of Buthus martensii, 15 parts of Vespa nidus, and 15 parts of Drynaria fortunei.

[0050] The preparation method is as follows: (1) Add 6 times the amount of water to Cibotium barometz, Astragalus complanatus, Dipsacus asper, Sinomenium acutum, Spatholobus suberectus, Buthus martensii, Vespa nidus and Drynaria fortunei, heat and reflux for 0.5 h, extract three times, filter, and obtain the extract; (2) The extract is concentrated and dried to obtain the final product.

[0051] The difference between this and Example 2 is that it does not contain Eucommia ulmoides, but contains an equal amount of Dipsacus asper, and replaces Psoralea corylifolia with Astragalus complanatus.

[0052] Comparative Example 2 The formula for this comparative proportion by weight is as follows: 30 parts Cibotium barometz, 10 parts Psoralea corylifolia, 15 parts Eucommia ulmoides, 15 parts Trachelospermum jasminoides, 30 parts Spatholobus suberectus, 6 parts Buthus martensii, 15 parts Vespa nidus, and 15 parts Taxillus chinensis.

[0053] The preparation method is as follows: (1) Add 6 times the amount of water to Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Trachelospermum jasminoides, Spatholobus suberectus, Buthus martensii, Vespa nidus and Taxillus chinensis and heat under reflux for 0.5 h. Extract three times, filter, and combine the filtrates to obtain the extract. (2) The extract is concentrated and dried to obtain the final product.

[0054] The difference from Example 2 is that it does not contain Drynaria fortunei, but instead uses Loranthus parasiticus, which has similar effects, and replaces Sinomenium acutum with Trachelospermum jasminoides.

[0055] Comparative Example 3 The formula for this comparative proportion, by weight, is as follows: 30 parts Cibotium barometz, 10 parts Epimedium, 15 parts Eucommia ulmoides, 15 parts Clematis chinensis, 30 parts Spatholobus suberectus, 6 parts Buthus martensii, 15 parts Vespa nidus, and 15 parts Drynaria fortunei.

[0056] The preparation method is as follows: (1) Add 6 times the amount of water to Cibotium barometz, Epimedium, Eucommia ulmoides, Clematis chinensis, Spatholobus suberectus, Buthus martensii, Vespa nidus and Drynaria fortunei, heat and reflux for 0.5 h, extract three times, filter, and combine the filtrates to obtain the extract; (2) The extract is concentrated and dried to obtain the final product.

[0057] The difference from Example 2 is that it does not contain Psoralea corylifolia, but contains Epimedium, which has similar effects; it does not contain Sinomenium acutum, but contains Clematis chinensis, which has similar effects.

[0058] Comparative Example 4 The formula for this comparative proportion by weight is as follows: 30 parts Cibotium barometz, 10 parts Psoralea corylifolia, 15 parts Eucommia ulmoides, 15 parts Sinomenium acutum, 15 parts Angelica sinensis, 15 parts Ligusticum chuanxiong, 3 parts stir-fried Bombyx mori, 3 parts Scolopendra subspinipes, 7.5 parts Angelica pubescens, 7.5 parts Cynanchum paniculatum, and 15 parts Drynaria fortunei.

[0059] The preparation method is as follows: (1) Add 6 times the amount of water to Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Sinomenium acutum, Angelica sinensis, Ligusticum chuanxiong, stir-fried Bombyx mori, Scolopendra subspinipes, Angelica pubescens, Cynanchum paniculatum and Drynaria fortunei, heat and reflux for 0.5 h, extract three times, filter, and combine the filtrates to obtain the extract; (2) The extract is concentrated and dried to obtain the final product.

[0060] The difference from Example 2 is that the whole scorpion is replaced with bran-fried silkworm and centipede, the honeycomb is replaced with Angelica pubescens and Cynanchum paniculatum, and the chicken blood vine is replaced with Angelica sinensis and Ligusticum chuanxiong.

[0061] I. Animal efficacy experiments 1. Materials and Methods 1.1 Laboratory Animals SPF-grade female SD rats, 6 weeks old, were acclimatized for 1 week, and SD rats with good mental state and normal joint mobility were selected for model construction.

[0062] 1.2 Experimental Drugs Blank group: distilled water; Experimental group: Traditional Chinese medicine compositions prepared in Examples 1-3 and Comparative Examples 1-4; Positive control drug: Celecoxib capsules (Celebrex) (specification: 100mg, manufactured by Pfizer Pharmaceuticals Ltd.), the specific dosage was 13mg / kg / day by gavage.

[0063] Modeling drugs: bovine type II collagen, incomplete Freund's adjuvant. Take 2 mg / mL. -1 Freund's incomplete adjuvant with 2 mg / mL -1 Equal volumes of bovine type II collagen were mixed and thoroughly stirred to emulsify the mixture. When the emulsifier clumped and agglomerated in water without dispersing, a successfully prepared bovine type II collagen-French adjuvant emulsifier was obtained. The entire preparation process was performed on ice. Arthritis was induced in rats by intradermal injection of the emulsifier at the base of the tail. The initial immunization dose was 200 μL per rat, followed by a booster immunization of 100 μL per rat one week later. After the booster immunization, the rats were periodically assessed for arthritis scores and their ankle joint circumference was measured to confirm the successful establishment of the arthritis model.

[0064] 2. Experimental Methods 2.1 Animal grouping and modeling Except for the 10 rats in the blank group, the remaining rats were injected into the tail root with the above-mentioned bovine type II collagen-complete Freund's adjuvant on days 0, 7 and 14 to establish the model. After successful modeling, the SD rats were randomly divided into model group, Example 1-3 group, Comparative Example 1-4 group and positive group, with 10 rats in each group.

[0065] Treatment began the day after the final tail root injection. The control group and model group were administered an equal volume of distilled water by gavage; the positive control group was administered celecoxib tablet solution by gavage.

[0066] Examples 1-3: 40g crude drug / kg of the traditional Chinese medicine composition prepared in Examples 1-3 was administered by gavage. Comparative Examples 1-4: 40g crude drug / kg of the traditional Chinese medicine composition prepared in Comparative Examples 1-4 was administered by gavage. Once daily for a total of 28 days.

[0067] After the experiment, rats were fasted for 12 hours. The circumference of the ankle joints of both feet was measured with a soft measuring tape, and the average value was calculated, retaining two decimal places. The swelling of the joints was observed. Rats were anesthetized with 10% chloral hydrate, and blood was collected by enucleation. After centrifugation (centrifugation radius: 15cm, 3000r / min, centrifugation for 10min), serum was extracted and stored at 80℃. The concentrations of TNF-α, IL-1β, IL-6, IL-17, IL-23, and IFN-γ in the serum were measured using enzyme-linked immunosorbent assay (ELISA).

[0068] The handling of animals during the experiment complied with the animal ethics requirements stipulated in the "Regulations on the Management of Experimental Animals" issued by the State Science and Technology Commission.

[0069] Results (1) The average circumference of the ankle joints of both feet of SD rats is shown in Table 1.

[0070] Table 1

[0071] Note: # Compared with the blank group: P < 0.05; * Compared with the model group: P < 0.05; & Compared with Example 2 group: P < 0.05.

[0072] (2) Changes in serum concentrations of TNF-α, IL-1β, IL-6, IL-17, IL-23 and IFN-γ in SD rats The results are shown in Table 2.

[0073] Table 2

[0074] Note: # Compared with the blank group: P < 0.05; * Compared with the model group: P < 0.05; & Compared with Example 2 group: P < 0.05.

[0075] II. Clinical Research (I) Research Methods 1. Research Subjects 1.1 Source of cases All cases in this study were patients with ankylosing spondylitis admitted to the outpatient and inpatient departments of the Department of Rheumatology and Immunology at Guanghua Hospital affiliated with Shanghai University of Traditional Chinese Medicine between March 2023 and December 2024. This study was approved by the Ethics Committee of Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine.

[0076] 1.2 Number of cases The subjects were divided into two groups: a treatment group and a control group, with 40 cases in each group, for a total of 80 cases in both groups.

[0077] 2 Diagnostic criteria 2.1 Western Medicine Diagnostic Criteria 1) The AS New York Standard, revised in 1984; 2) The axial SpA classification standard published by the International SpA Evaluation Working Group (ASAS) in 2010.

[0078] 2.2 Traditional Chinese Medicine Diagnostic Criteria It meets the diagnostic criteria for "Dalou" (kidney deficiency and cold syndrome) in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine (Trial)" and the "Traditional Chinese Medicine Diagnosis and Treatment Plan for 95 Diseases in 22 Specialties (Combined Edition)"; Main symptoms: ① Lumbosacral pain, back pain; ② Limited lumbar spine mobility; ③ Sensitivity to cold and preference for warmth, relief upon exposure to heat, or cold and painful joints; ④ Morning stiffness Secondary symptoms: ① Soreness and weakness in the lower back and knees; ② Fatigue and weakness; ③ No thirst or dry mouth with no desire to drink; ④ Cold scrotum in men or cold and slippery vaginal discharge in women; ⑤ Loose stools or frequent urination with clear urine at night; Tongue and pulse: The tongue is dark red with a thin white or thick white coating, and the pulse is deep and wiry or deep and wiry and thin.

[0079] A diagnosis can be made if all the primary symptoms are present, or at least 3 secondary symptoms are present, and the tongue coating and pulse are basically consistent with the diagnosis.

[0080] 2.3 Case Selection Criteria 2.3.1 Inclusion Criteria 1) Meets the Western medical diagnostic criteria for ankylosing spondylitis; 2) Meets the diagnostic criteria and syndrome differentiation criteria of "severe hunchback, kidney deficiency and cold in the Du meridian" in traditional Chinese medicine; 3) Age ≥ 18 years; 4) Ankylosing spondylitis disease activity score (ASDAS-CRP) ≥1.3; 5) At the time of screening, patients had been taking a stable dose of NSAIDs for ≥2 weeks, or had stopped taking NSAIDs for ≥2 weeks; 6) Willing to take medication as required by the plan and attend follow-up examinations on time; 7) Understand and voluntarily sign the informed consent form.

[0081] 2.3.2 Exclusion Criteria 1) Has or has had rheumatoid arthritis, intervertebral disc herniation, diffuse idiopathic hypertrophic osteomyelitis syndrome, osteitis condensans of the iliac bone, psoriasis, inflammatory bowel disease, etc.; 2) Individuals with internal fixation of the spine who have undergone spinal surgery within the past 3 months or who plan to undergo spinal surgery within the next 3 months; 3) Those who received biological disease-modifying drugs, including TNFi, IL-17i, and JAKi, within the previous 8 weeks; 4) Individuals who have used disease-modifying antirheumatic drugs such as sulfasalazine, thalidomide, or methotrexate within the previous 4 weeks, or have used leflunomide within the previous 8 weeks; 5) Peripheral blood leukocyte or neutrophil count is below the lower limit of normal, i.e., the total white blood cell count is below 3.0 × 10⁹ / L; 6) Individuals with severe liver or kidney dysfunction, ALT or AST levels exceeding 1.5 times the upper limit of normal, or serum Cr levels exceeding normal. 7) Positive pregnancy test, breastfeeding, planning to conceive, or unwilling to use effective contraception; 8) Patients with a history of severe drug abuse, alcoholism, or mental illness with clinical symptoms; 9) Individuals allergic to any component of the investigational drug (including excipients); 10) Researchers believe there are other reasons why it is not appropriate to include it.

[0082] 2.3.3 Shedding Criteria 1) Subjects who experience adverse events during the trial and are unable to tolerate the trial, and are deemed unsuitable to continue the trial by the researchers; 2) Subjects with poor compliance who fail to attend hospital visits on time, do not take medication as required by the protocol, or arbitrarily use drugs prohibited by the protocol, thus affecting the determination of efficacy; 3) The patient withdrew from the study voluntarily for personal reasons.

[0083] 3. Research Methods 3.1 Research Groups and Cycle Treatment group: The herbal composition of Example 2 of this invention, which tonifies the kidney, strengthens the spleen and dispels cold, is 1 bag / time, once a day, orally; Control group: Oral NSAIDs, administered according to the instructions; The study duration of medication was 8 weeks.

[0084] 3.2 Research Drugs Example 2 of the present invention: The herbal composition of the present invention consists of 30g of Cibotium barometz, 10g of Psoralea corylifolia, 15g of Eucommia ulmoides, 15g of Sinomenium acutum, 30g of Spatholobus suberectus, 6g of Buthus martensii, 15g of Vespa nidus, and 15g of Drynaria fortunei. Dissolve in boiling water and drink, once daily, one packet each time.

[0085] 3.3 Combined medication 1) During the entire study period, patients are prohibited from taking disease-modifying antirheumatic drugs such as sulfasalazine tablets, methotrexate, thalidomide, etc., and are prohibited from using glucocorticoids and biological targeted drugs. 3) The use of any drugs or external treatments that may affect the evaluation of efficacy is prohibited, such as Chinese herbal medicine slices, Chinese herbal medicine mixtures, surgical treatments, etc.

[0086] 3.4 Treatment course and follow-up visits The screening period was 1 week, and the treatment period was 8 weeks. There were 3 visits in total: V1 (-7 to 0 days), V2 (end of the 4th week after medication), and V3 (end of the 8th week after medication).

[0087] 4 Observation Indicators 4.1 Main Observation Indicators 1) Disease activity assessment The ASDAS-CRP score was adopted: proposed by the Ankylosing Spondylitis Assessment Task Force (ASAS) in 2009: ASDAS-CRP = 0.12 × BASDAI2 + 0.06 × BASDAI6 + 0.11 × VAS + 0.07 × BASDAI3 + 0.58 × In(CRP+1), where VAS is the visual analog scale score for overall patient assessment.

[0088] The grading of AS disease activity is based on the ASDAS score, which is divided into four levels: inactive disease (ASDAS < 1.3), low disease activity (1.3 ≤ ASDAS-CRP < 2.1), high disease activity (2.1 ≤ ASDAS-CRP < 3.5), and very high disease activity (ASDAS ≥ 3.5).

[0089] 2) Traditional Chinese Medicine Syndrome Scoring The TCM syndrome score grading and quantification table for kidney deficiency and cold syndrome is set with reference to the "Guiding Principles for Clinical Research of New Chinese Medicines (Trial)" and the "Diagnosis and Treatment Plan for Ankylosing Spondylitis (Ankylosing Spondylitis) - TCM Diagnosis and Treatment Plan for 22 Specialties and 95 Diseases (Combined Edition)", as shown in Table 3.

[0090] Table 3. Quantitative Indicators for TCM Syndrome Grading (Kidney Deficiency and Cold in the Governing Vessel)

[0091] 4.2 Secondary observation indicators The patient's spinal pain visual analog scale score, patient global assessment (PGA), Bathylosing spondylitis disease activity index (BASDAI), Bathylosing spondylitis functional index (BASFI, Appendix B), C-reactive protein, erythrocyte sedimentation rate (ESR), ASDAS-ESR, Bathylosing spondylitis functional index (BASMI), and chest wall mobility (cm) were measured.

[0092] 4.3 Safety Indicators Before treatment, at 4 weeks of treatment, and at 8 weeks of treatment follow-up visits, all patients underwent routine blood and urine tests, as well as liver and kidney function tests. During the treatment period, the occurrence of adverse reactions such as nausea, vomiting, diarrhea, rash, fever, and sweating was recorded in both groups of patients.

[0093] 4.4 Efficacy Target Achievement 1) Based on the scoring system developed by the International Spondyloarthritis Assessment Team (ASAS), the following items were statistically analyzed: ASAS20, ASAS40, ASAS5 / 6, and BASDAI50.

[0094] 2) Improvement in ASDAS-CRP: A difference of ≥1.1 in ASDAS-CRP before and after the test is defined as a clinically significant improvement.

[0095] 4.5 Criteria for Evaluating the Efficacy of Traditional Chinese Medicine Referring to the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine", the disease is divided into four levels: clinical cure, significant effect, effective and ineffective, as shown in Table 4 below. The effectiveness rate is calculated according to the TCM syndrome scoring formula.

[0096] Table 4

[0097] 5. Statistical Analysis Statistical analysis was performed using SPSS 26.0. All data were described as mean ± standard deviation (x ± s), and count data were described as number of cases and percentages. For continuous data, paired-samples t-tests were used to compare within-group data before and after treatment, and independent-samples t-tests were used to compare between-group data. For non-normally distributed data, independent-samples Mann-Whitney U tests were used to compare between-group data, and Wilcoxon signed-rank tests were used to compare before and after treatment. Count data were expressed as number of cases and percentages, and the chi-square test was used. 2 For ordinal data, the rank-sum test was used. P<0.05 indicates a statistically significant difference.

[0098] (II) Research Results 1. Test completion status This study included 80 eligible cases in two groups, with 40 in the experimental group and 40 in the control group. A total of 11 patients dropped out across both groups. In the treatment group, 35 patients ultimately completed the trial; 1 withdrew due to adverse events, 1 voluntarily withdrew their informed consent, and 3 were lost to follow-up. In the control group, 34 patients ultimately completed the trial; 2 withdrew due to adverse events, 1 voluntarily withdrew their informed consent, and 3 were lost to follow-up.

[0099] 2 Baseline data A total of 69 patients completed the study, including 35 in the treatment group and 34 in the control group. There were no significant differences between the two groups in basic information such as gender, age, disease duration, and baseline clinical indicators, making them comparable (see Table 5). There were no significant differences in disease activity grading at baseline between the two groups (see Table 6). Patients in the control group received NSAIDs during the study period, as detailed in Table 7.

[0100] Table 5 shows the two sets of basic information.

[0101] Table 6. Baseline disease activity grading for the two groups (cases)

[0102] Table 7. NSAID use in the control group.

[0103] 3. Evaluation of clinical efficacy 3.1 Efficacy Target Achievement At 4 weeks of treatment, there was no statistically significant difference in the number of patients achieving ASAS20, ASAS40, ASAS5 / 6, and BASDAI50 between the two groups. P >0.05); at 8 weeks of treatment, there was a statistically significant difference in the number of patients in the two groups who achieved ASAS20, ASAS40, ASAS5 / 6, and BASDAI50 (χ²). 2 The values ​​are 7.832, 7.568, 8.603, and 12.699 respectively. P <0.01), see Table 8.

[0104] Table 8 Comparison of therapeutic efficacy outcomes between the two groups [n(%)]

[0105] Note: Compared with the control group at the same time point. ** P <0.01; n is the number of cases.

[0106] Comparison of ASDAS-CRP clinical improvement After 4 weeks of treatment, 7 cases in the treatment group showed clinical improvement, and 28 cases showed no improvement, with a total improvement rate of 20%; in the control group, 1 case showed clinical improvement, and 33 cases showed no improvement, with a total effective rate of 2.94%. After 8 weeks of treatment, 13 cases in the treatment group showed clinical improvement, and 22 cases showed no improvement, with a total improvement rate of 37.14%; in the control group, 3 cases showed clinical improvement, and 31 cases showed no improvement, with a total effective rate of 8.82%. The chi-square test showed a statistically significant difference in clinical improvement between the two groups of ASDAS-CRP (χ² test). 2 =7.765, P =0.009), see Table 9.

[0107] Table 9 Comparison of clinical improvement rates of ASDAS-CRP between the two groups [n(%)]

[0108] Note: Compared with the control group at the same time point. * P <0.05; n is the number of cases.

[0109] 3.2 Comparison of therapeutic effects between the two groups of TCM syndromes At 4 weeks of treatment, there was no statistically significant difference in the total effective rate between the treatment groups in the TCM syndrome efficacy evaluation. P >0.05); at 8 weeks of treatment, the total effective rate in the treatment group was better than that in the control group, and the difference between the two groups was statistically significant (χ²). 2 =11.11, P =0.001), see Table 10.

[0110] Table 10. Therapeutic effects of TCM syndromes in two groups [cases (%)]

[0111] 3.3 Comparison of disease activity indicators between the two groups There were no statistically significant differences in CRP, ESR, ASDAS-CRP, and ASDAS-ESR levels between the two groups at baseline. P >0.05), at 4 weeks of treatment, the CRP level in the treatment group decreased compared with that before treatment, and the difference was statistically significant (P<0.05); at 8 weeks of treatment, the ESR and CRP levels in the treatment group decreased significantly compared with those before treatment (P<0.05). P <0.01); at 4 and 8 weeks of treatment, both groups showed improvements in ASDAS-CRP and ASDAS-ESR compared to pre-treatment levels ( P <0.05, P <0.01), but the ASDAS-ESR in the treatment group improved more significantly than before treatment. Intergroup comparison showed that the ASDAS-CRP in the treatment group was lower than that in the control group ( P<0.05), see Table 11.

[0112] Table 11 Comparison of disease activity indicators between the two groups ( ±S)

[0113] Note: Compared with the pre-treatment level in this group. * P <0.05, ** P <0.01, compared with the control group at the same period, # P <0.05, where n is the number of cases.

[0114] 3.4 Comparison of key clinical indicators between the two groups At 4 weeks of treatment, spinal pain scores, PGA, and BASDI in both groups improved compared to before treatment. P <0.05, P <0.01, intergroup comparison showed that the BASDAI in the treatment group was lower than that in the control group ( P <0.01); at 8 weeks of treatment, the spinal pain scores and BASDAI scores in both groups improved compared to before treatment ( P <0.01, BASFI in the treatment group improved compared to before treatment ( P <0.01, the spinal pain score, PGA, and BASDAI of the treatment group were all lower than those of the control group ( P <0.01, P <0.05); Regarding the improvement of TCM syndrome scores, both groups showed significant improvement at 4 and 8 weeks of treatment compared to before treatment ( P <0.01), intergroup comparison showed that the TCM syndrome score of the treatment group was lower than that of the control group at 8 weeks, and the difference was statistically significant. P <0.5), see Table 12.

[0115] Table 12 Comparison of major clinical indicators between the two groups ( ±S)

[0116] Note: Compared with the pre-treatment level in this group. * P <0.05, ** P <0.01, compared with the control group at the same period, # P <0.05, ## P <0.01, where n is the number of cases.

[0117] 3.5 Comparison of physical activity function indicators between the two groups At baseline, there were no significant differences in any physical activity function indicators or BASMI between the two groups. At 4 weeks of treatment, none of the indicators in either group showed significant changes compared to baseline; at 8 weeks of treatment, the treatment group showed improvements in Schober, chest wall mobility, ankle-to-ankle distance, and BASMI compared to pre-treatment levels. P <0.05, P <0.01), see Table 13.

[0118] Table 13 Comparison of Physical Activity Function Indicators ( ±S)

[0119] Note: Compared with the pre-treatment level in this group. * P <0.05, ** P <0.01.

[0120] III. Analysis and Discussion The composition of this invention not only significantly improves clinical symptoms and functional indices such as lower back pain and morning stiffness in patients with ankylosing spondylitis (AS), but also significantly improves hip joint mobility, suggesting a certain therapeutic advantage for hip joint diseases. Furthermore, it has good long-term safety with no toxic side effects.

[0121] The results of this study showed that, according to the efficacy evaluation criteria of the ASAS working group, the treatment group achieved significantly better efficacy targets at 8 weeks than the control group. At 8 weeks, the number of patients in the treatment group who achieved ASAS20, ASAS40, ASAS5 / 6, and BASDAI50 was higher than that in the control group. P <0.01) Spinal pain scores, PGA, BASDI, and ASDAS-CRP all improved in both groups after 4 weeks of treatment. P <0.05, P <0.01, the treatment group showed more significant improvement in BASDAI ( P <0.01; while at 8 weeks, the spinal pain scores, BASDAI, and ASDAS-CRP in both groups were significantly improved compared to before treatment ( P <0.01, although intragroup comparisons showed that at 8 weeks, spinal pain scores, BASDAI, and ASDAS-CRP in both groups improved compared to before treatment ( P <0.05, but intergroup comparisons showed that the above scores in the treatment group were all lower than those in the control group ( P <0.05, and the efficacy evaluation results showed that the treatment group was more effective than the control group ( P <0.05).

[0122] The above results indicate that the composition of the present invention is superior in improving TCM syndromes, clinical symptoms and physical functions, and its effect increases with the duration of medication.

[0123] The ASAS20 / 40 standard is commonly used in clinical trials of bDMARDs as a primary endpoint for determining the efficacy of AS. However, in recent years, the ASAS standard has also been increasingly used to evaluate the efficacy of traditional Chinese medicine (TCM) compound treatments for AS. The results of this study show that at 8 weeks, the proportion of patients achieving ASAS20 and ASAS40 in the TCM group was higher than that in the control group, fully demonstrating the definite efficacy of the composition of this invention for AS patients.

[0124] Over the past decade, the Ankylosing Spondylitis Disease Activity Score (ASDAS) has become the most suitable tool for assessing disease activity in ankylosing spondylitis (axSpA) and is widely recommended for monitoring axSpA patients. ASDAS is the first validated disease activity index for AS, combining patient-reported assessments and acute-phase reactants. As a comprehensive and reliable assessment tool, ASDAS has significant value in the clinical management and research of AS. With further research and validation, ASDAS is expected to become the gold standard for ankylosing spondylitis assessment in the future.

[0125] The BathAS metrology index (BASMI) is a standardized tool for assessing spinal mobility in patients with ankylosing spondylitis (AS). It objectively reflects clinical changes in spinal motor function by quantifying parameters such as tragus-to-wall distance, lateral flexion, cervical rotation, modified Schober index, and interankular distance. Currently, BASMI 10 has become a core indicator of spinal mobility recommended by the Association for the Assessment of Spondylarthritis International (ASAS) and is widely used in clinical trials of anti-tumor necrosis factor drugs. Spinal mobility is dually regulated by inflammatory response and structural damage: in the early stages, reversible inflammation plays a dominant role, while in the later stages, irreversible structural damage is the primary driver. This study, using BASMI 10 assessment, found that after 8 weeks of treatment with the composition of this invention, the treatment group showed improvements in total BASMI score, chest wall mobility, and interankular distance compared to baseline; scoliosis amplitude showed an increasing trend. It is noteworthy that the patients included in this study had a relatively long average disease duration, and spinal structural damage may have become a major factor in mobility impairment, which may be an important reason for the lack of significant treatment response.

[0126] During this study, the ASDAS-CRP level in the treatment group gradually decreased, reaching a significantly lower level than that in the control group by week 8, and the overall improvement rate of ASDAS-CRP was significantly higher in the treatment group than in the control group. This suggests that the composition of this invention can improve disease activity in AS patients. The results showed that after 8 weeks of treatment, the treatment group achieved significant improvements in disease activity (ASDAS-CRP), clinical symptoms, and physical function, indicating that the composition of this invention has clear clinical value for patients with low to moderate active AS. Current international guidelines mainly develop stepwise biologic therapy regimens for patients with high disease activity, while this study shows that traditional Chinese medicine can provide a safe and effective alternative or complementary treatment option for patients with low to moderate active AS, such as those who do not respond well to NSAIDs but do not meet the criteria for biologic therapy, or those who have concerns about the cost or safety of biologics.

[0127] The TCM syndrome scoring and grading scale for Kidney Deficiency and Du Meridian Cold Syndrome used in this study was designed with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine (Trial)" and the "Treatment Plan for Ankylosing Spondylitis (22 Specialties and 95 Diseases) (Combined Edition)". The scoring scale includes 10 main symptoms: pain in the lower back, buttocks, and hips; morning stiffness; limited lumbar and spinal mobility; coldness in peripheral joints; aversion to cold and preference for warmth; soreness and weakness in the lower back and knees; fatigue; bland taste and lack of thirst; loose stools; and frequent urination at night. A semi-quantitative score was set. Kidney and Du Meridian deficiency, insufficient Yang Qi, allows wind and cold to deeply invade the Kidney and Du Meridians. When the Du Meridian is affected by pathogenic factors, the opening and closing of Yang Qi is impaired, and its distribution is disrupted. Since the Kidney governs the bones, pain in the lower back, buttocks, and hips occurs. Cold congeals and obstructs the meridians, leading to muscle spasms and spinal stiffness, thus limiting lumbar and spinal mobility. Over time, blood stasis is generated internally, obstructing the meridians and spine, and in severe cases, lumbar and spinal rigidity or kyphosis may occur, making walking, sitting, and lying down impossible. When cold pathogens invade internally, the Yang Qi is suppressed, leading to symptoms such as aversion to cold and preference for warmth, cold peripheral joints, and cold hands and feet. Insufficient Yang Qi prevents the clear Yang from ascending, resulting in fatigue and weakness; deficiency of Kidney Yang, along with Spleen Yang deficiency and dampness, leads to impaired digestion and loose stools; and Kidney deficiency and bladder dysfunction result in frequent urination at night. This study shows that in terms of TCM syndrome efficacy evaluation, the overall effective rate in the treatment group was significantly higher than that in the control group at 4 and 8 weeks, while the TCM syndrome score in the treatment group was lower than that in the control group (…). P <0.05, and the difference was more significant at 8 weeks ( P <0.05). This suggests that the composition of the present invention can effectively improve TCM syndromes.

[0128] This article uses specific examples to illustrate the inventive concept in detail. The description of the above embodiments is only for the purpose of helping to understand the core idea of ​​the present invention. It should be noted that any obvious modifications, equivalent substitutions or other improvements made by those skilled in the art without departing from the inventive concept should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition with the effects of tonifying the kidney, dispelling cold, and unblocking the meridians, characterized in that, The raw materials, by weight, include the following components: 20-40 parts of Cibotium barometz, 5-15 parts of Psoralea corylifolia, 10-20 parts of Eucommia ulmoides, 10-20 parts of Sinomenium acutum, 20-40 parts of Spatholobus suberectus, 1-10 parts of Buthus martensii, 10-20 parts of Vespa nidus, and 10-20 parts of Drynaria fortunei.

2. The traditional Chinese medicine composition with kidney-tonifying, cold-dispelling, and meridian-clearing effects according to claim 1, characterized in that, The raw materials, by weight, include the following components: 30-40 parts of Cibotium barometz, 10-15 parts of Psoralea corylifolia, 15-20 parts of Eucommia ulmoides, 15-20 parts of Sinomenium acutum, 30-40 parts of Spatholobus suberectus, 6-10 parts of Buthus martensii, 15-20 parts of Vespa nidus, and 15-20 parts of Drynaria fortunei.

3. The traditional Chinese medicine composition with kidney-tonifying, cold-dispelling, and meridian-clearing effects according to claim 1, characterized in that, The raw materials, by weight, include the following components: 30 parts of Cibotium barometz, 10 parts of Psoralea corylifolia, 15 parts of Eucommia ulmoides, 15 parts of Sinomenium acutum, 30 parts of Spatholobus suberectus, 6 parts of Buthus martensii, 15 parts of Vespa nidus, and 15 parts of Drynaria fortunei.

4. A pharmaceutical preparation, characterized in that, Its pharmaceutical preparations include the traditional Chinese medicine composition with the effects of tonifying the kidney, dispelling cold, and unblocking the meridians as described in any one of claims 1-3, as well as pharmaceutically acceptable excipients.

5. The pharmaceutical preparation according to claim 4, characterized in that, The dosage form of the pharmaceutical preparation is selected from pills, capsules, granules, oral liquids, powders, or tablets.

6. A method for preparing a traditional Chinese medicine composition with kidney-tonifying, cold-dispelling, and meridian-clearing effects as described in any one of claims 1-3, characterized in that, Includes the following steps: (1) Extract the following herbs by adding solvent: Cibotium barometz, Psoralea corylifolia, Eucommia ulmoides, Sinomenium acutum, Spatholobus suberectus, Buthus martensii, Vespa nidus, and Drynaria fortunei; filter the extract to obtain the extract. (2) The extract is concentrated to obtain a thick paste.

7. The preparation method according to claim 6, characterized in that, In step (1), the amount of solvent added is 8-12 times the total mass of the raw materials, and the solvent is water or a 10-50% ethanol aqueous solution.

8. The preparation method according to claim 6, characterized in that, In step (1), the extraction is performed 1-3 times, and the extraction time is 1-3 hours each time.

9. The method for preparing the traditional Chinese medicine composition according to claim 6, characterized in that, Step (2) also includes drying the paste.

10. The use of a traditional Chinese medicine composition according to any one of claims 1-3 or a traditional Chinese medicine composition prepared by any one of claims 6-9 in the preparation of a medicament for treating ankylosing spondylitis of the kidney deficiency and cold type.

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