A traditional Chinese medicine fumigation and washing compound preparation for treating rheumatoid arthritis of the wind-cold obstruction type.

Abstract

This is a traditional Chinese medicine fumigation and washing compound preparation for treating rheumatoid arthritis of the wind-cold obstruction type, belonging to the field of traditional Chinese medicine preparations for the treatment of rheumatoid arthritis. It is made from 10-25 parts of Morinda officinalis, 5-15 parts of Angelica sinensis (tail), 8-12 parts of raw licorice root, 5-12 parts of Schizonepeta tenuifolia, 5-15 parts of Atractylodes macrocephala, 8-15 parts of Clerodendrum trichotomum, 10-20 parts of Tripterygium wilfordii, 5-12 parts of Agkistrodon halys, 5-12 parts of Curcuma longa, 8-15 parts of Eucommia ulmoides powder, 8-15 parts of processed Strychnos nux-vomica, 8-15 parts of Caesalpinia sappan, and 5-15 parts of Cnidium monnieri. The traditional Chinese medicine fumigation and washing compound preparation proposed in this invention for treating rheumatoid arthritis of the wind-cold obstruction type is composed of Morinda officinalis, Angelica sinensis tail, raw licorice, Schizonepeta tenuifolia, Atractylodes macrocephala, Clerodendrum trichotomum, Tripterygium wilfordii, Agkistrodon halys, Curcuma longa, Eucommia ulmoides powder, processed Strychnos nux-vomica, Caesalpinia sappan, and Cnidium monnieri. Through heating, the effective components of the traditional Chinese medicine are extracted to achieve the effects of dispelling cold and dampness, and promoting blood circulation.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparations for the treatment of rheumatoid arthritis, specifically relating to a traditional Chinese medicine fumigation and washing compound preparation for treating rheumatoid arthritis of the wind-cold obstruction type. Background Technology

[0002] In traditional Chinese medicine, rheumatoid arthritis falls under the category of "Bi syndrome." The "Suwen·Bi Lun" states, "When wind, cold, and dampness invade the body, they combine to form Bi syndrome." Traditional Chinese medicine believes that Bi syndrome is caused by the invasion of pathogenic factors such as wind, cold, dampness, and heat into the body, obstructing the meridians and flowing into the joints, resulting in symptoms such as joint pain and limited mobility.

[0003] Wind-cold obstruction syndrome is caused by cold pathogens combined with wind, which stagnate in the meridians and obstruct the flow of qi and blood, resulting in joint pain, and symptoms such as pain, heaviness, soreness, and numbness in the muscles and bones. Therefore, the treatment of wind-cold obstruction type rheumatoid arthritis should focus on warming and unblocking the meridians, promoting blood circulation, and relieving pain. In view of this, this invention proposes a traditional Chinese medicine fumigation and washing compound preparation that can treat wind-cold obstruction type rheumatoid arthritis. Summary of the Invention

[0004] The purpose of this invention is to provide a traditional Chinese medicine fumigation and washing compound preparation for effectively treating rheumatoid arthritis of the wind-cold obstruction type, with good therapeutic effect.

[0005] The technical solution adopted in this invention is as follows:

[0006] A traditional Chinese medicine fumigation and washing compound preparation for treating rheumatoid arthritis of the wind-cold obstruction type, wherein the effective components of the traditional Chinese medicine fumigation and washing compound preparation are obtained from the following traditional Chinese medicine raw materials in parts by weight:

[0007]

[0008] The efficacy of each raw material in the above-mentioned traditional Chinese medicine fumigation and washing compound preparation is as follows:

[0009] Morinda officinalis, Angelica sinensis (tail), and Cnidium monnieri are all warm-natured herbs, playing a role in warming the meridians and promoting blood circulation in prescriptions. Modern pharmacological studies have found that Morinda officinalis contains iridoids, which have analgesic, anti-inflammatory, and osteoprotective effects. Morinda officinalis and its processed products also have pharmacological effects such as enhancing immunity and dispelling wind and dampness. Studies have shown that extracts from different parts of Morinda officinalis and different processed products all have wind-dampness-dispelling effects. Salt-processed Morinda officinalis, the n-butanol fraction of Morinda officinalis, and the ethyl acetate fraction of Morinda officinalis have significant effects on improving various indicators in mice with rheumatoid arthritis, which may be related to Morinda officinalis inhibiting NO production, thereby exerting an anti-inflammatory effect. Regarding the tail of Angelica sinensis, Chen Jiamo summarized its effects in *Ben Cao Meng Quan* as follows: "The head stops bleeding, the body nourishes blood, the tail invigorates blood, and the tail harmonizes blood." Modern pharmacology has found that the tail of Angelica sinensis has anti-inflammatory, liver-protective, kidney-protective, immune-enhancing, and asthma-relieving effects, mainly related to its ability to weaken or eliminate free radicals. The ferulic acid content in the tail of Angelica sinensis is significantly higher than other components, which can increase PGI2 biological activity and reduce TXA2 biological activity, thereby eliminating free radicals and achieving an antioxidant effect. Licorice polysaccharides can induce Th1 cell proliferation, secrete IL-2 and TNF-α, activate T lymphocytes, and thus enhance immune activity. Osthol, contained in Cnidium monnieri, can exert anti-inflammatory effects by blocking nuclear factor κB and MAPK / p38 signaling pathways, inhibiting lipopolysaccharide-induced p38 protein kinase, and inhibiting the release of tumor necrosis factor-α and interleukin-6.

[0010] Turmeric, Eucommia ulmoides powder, and Sappanwood primarily function to promote blood circulation and unblock meridians in traditional Chinese medicine fumigation formulas. Modern research has also confirmed their important roles in anti-inflammation and immunosuppression. Curcumin in turmeric exerts its anti-inflammatory effect by inhibiting the expression levels of IL-6, CRP, and TNF-α. Eucommia ulmoides powder mainly contains various effective components such as iridoids, flavonoids, and Eucommia polysaccharides. Flavonoids in Eucommia ulmoides, such as quercetin, have good anti-inflammatory, anti-oxidative stress, and chondrocyte apoptosis-inhibiting effects. Quercetin can inhibit inflammatory responses by increasing the expression of superoxide dismutase and TIMP-1 in synovial tissue, inhibiting MMP-13 expression, and regulating the JNK / p38 MAPK pathway. Sappanwood contains hematoxylin A, which has anti-inflammatory effects. Some researchers have used hematoxylin A to intervene in a rat model of rheumatoid arthritis and found that it can inhibit the expression of inflammatory mediators IL-6 and TNF-α in the synovial tissue of the ankle joint.

[0011] Strychnos nux-vomica, Clerodendrum trichotomum, Tripterygium wilfordii, and Agkistrodon halys all have the effect of clearing the meridians and relieving pain, while raw licorice plays a role in reducing toxicity and enhancing efficacy. Strychnos nux-vomica alkaloids can effectively reduce the proliferation of immune T cells, exert an immunosuppressive effect, reduce inflammatory response, and effectively reduce the degree of ear swelling in model mice. Terpenoids contained in Strychnos nux-vomica leaves can regulate macrophage-mediated inflammatory processes, thereby exerting anti-inflammatory and analgesic effects. Furthermore, the combination of Strychnos nux-vomica and Sappanwood at a ratio of 1:18 can significantly reduce the degree of paw edema in adjuvant arthritis rats. The combination of the two can effectively reduce the content of strychnos nux-vomica alkaloids and strychnine, and can synergistically enhance the anti-inflammatory and analgesic effects. Clerodendrum trichotomum has the effect of dispelling wind and dampness and can be used to treat rheumatoid arthritis. The petroleum ether and ethyl acetate fractions of Clerodendrum trichotomum leaves can significantly inhibit the release of NO from mononuclear macrophages in rheumatoid arthritis model mice in a dose-dependent manner. Tripterygium wilfordii glycosides possess various pharmacological activities, including anti-inflammatory and immunomodulatory effects. They can reduce joint tenderness and swelling index in rheumatoid arthritis patients and improve immune function. Tripterygium oleoresin, a member of the Tripterygium wilfordii glycoside family, can induce osteoclast precursor cell apoptosis, inhibit inflammatory cell infiltration, and reduce bone erosion and destruction in rheumatoid arthritis mice. Furthermore, it exerts anti-inflammatory effects by increasing Treg levels and decreasing Th17 levels. The combination of raw licorice root and Tripterygium wilfordii can improve liver damage and arthritis symptoms in rheumatoid arthritis patients through cytokine regulation, thus reducing toxicity and enhancing efficacy. Agkistrodon halys, whose main active components are nucleosides and phospholipids, contains extracts from different effective parts that can reduce synovial cell degeneration, proliferation, and inflammatory cell infiltration in the ankle joint of rats. It can also exert anti-inflammatory effects by downregulating serum levels of inflammatory cytokines TNF-α, IL-1β, and IL-17.

[0012] Patients with rheumatoid arthritis have different constitutions, and those with sensitive skin may experience allergic reactions to traditional Chinese medicine fumigation. In contrast, this invention adds Schizonepeta and Atractylodes macrocephala to the formula primarily for their anti-allergic effects. Modern pharmacological studies have found that Schizonepeta volatile oil has good anti-allergic effects. Whole Schizonepeta volatile oil can significantly reduce the secretion of dermal fibroblast monocyte chemoattractant protein-1 (MCP-1), thus alleviating skin allergies. Schizonepeta volatile oil can also inhibit the production of IL-1, IL-2, and TNF in synovitis-induced mice, exerting an anti-inflammatory effect. Atractylodes macrocephala polysaccharide, the effective component of Atractylodes macrocephala, can effectively promote the transformation of splenic lymphocytes, enhance the body's immunity, and reduce the levels of inflammatory mediators such as IL-1β, IL-6, and TNF-α, thus improving rheumatoid arthritis and reducing the body's inflammatory response.

[0013] This traditional Chinese medicine fumigation compound preparation for treating rheumatoid arthritis of wind-cold obstruction type proposed by the present invention. In this fumigation prescription, Morinda officinalis has a sweet, pungent taste and a slightly warm nature, and has the effects of tonifying kidney yang, strengthening muscles and bones, and dispelling wind-dampness. Its nature is warm but not dry, and it is tonifying without being greasy, mainly playing the role of warming yang and removing dampness in the prescription; Strychnos nux-vomica has a bitter taste and a warm nature, and has the functions of reducing swelling and dissipating nodules, promoting blood circulation and dredging collaterals. The two together play the role of warming meridians and dredging collaterals. Tripterygium wilfordii Hook. f. is highly poisonous, cold in nature, with a bitter and pungent taste, and plays the role of dispelling wind-dampness and dredging collaterals to stop pain in the prescription. When combined with Angelica tail, it nourishes muscles and bones and promotes blood circulation to stop pain. Agkistrodon acutus has a warm nature, a sweet and salty taste, and is poisonous, and has the function of searching wind, dredging collaterals and stopping convulsions. As recorded in "Compendium of Materia Medica", "It can penetrate bones to search wind, stop convulsions and seizures, and is an important medicine for wind-bi, convulsions, scabies and ulcers. It can enter the internal organs and penetrate the skin, reaching everywhere." Agkistrodon acutus helps Tripterygium wilfordii Hook. f. dredge meridians and collaterals in the prescription. Sappanwood has a sweet taste, promotes blood circulation to dredge menstruation, dispels stasis and stops pain. Its mild nature can relieve the toxicity of Strychnos nux-vomica, complementing each other. Turmeric has a warm nature, helps Angelica and Sappanwood promote qi circulation by activating blood circulation, and helps Tripterygium wilfordii Hook. f. dredge collaterals to stop pain. Cnidium monnieri warms the kidney and invigorates yang, dries dampness and dispels wind; Clerodendrum trichotomum Thunb. dispels wind-dampness and dredges collaterals; Schizonepeta tenuifolia Briq. dispels wind and relieves the exterior; Atractylodes macrocephala Koidz. has a sweet and warm nature, invigorates qi and strengthens the spleen, and together assist Morinda officinalis to play the role of dispelling wind-dampness. Eucommia ulmoides Oliv. powder has a sweet and warm nature, nourishes the liver and kidney, strengthens muscles and bones; Licorice root relieves spasm and pain, harmonizes various medicines, and relieves the toxicity of Tripterygium wilfordii Hook. f., Strychnos nux-vomica, Agkistrodon acutus and Cnidium monnieri. Collaterals are dredged for use, and pain is due to qi stagnation. When these medicines are combined, they together play the roles of warming meridians and dredging collaterals, dispelling wind and cold, and removing dampness and stopping pain.

[0014] This traditional Chinese medicine fumigation compound preparation for treating rheumatoid arthritis of wind-cold obstruction type proposed by the present invention is composed of Morinda officinalis, Angelica tail, raw licorice root, Schizonepeta tenuifolia Briq., Atractylodes macrocephala Koidz., Clerodendrum trichotomum Thunb., Tripterygium wilfordii Hook. f., Agkistrodon acutus, Turmeric, Eucommia ulmoides Oliv. powder, processed Strychnos nux-vomica, Sappanwood, and Cnidium monnieri. Through the heating effect, the effective components of traditional Chinese medicines are extracted, achieving the effects of dispelling cold and dampness, and dredging meridians and collaterals.

[0015] As a preferred technical solution of this traditional Chinese medicine fumigation compound preparation for treating rheumatoid arthritis of wind-cold obstruction type in the present invention, its effective components are prepared from the following traditional Chinese medicine raw materials in parts by weight:

[0016]

[0017] The present invention also proposes a preparation method of this traditional Chinese medicine fumigation compound preparation, and the steps are as follows: <000004The comparison of arthritis indices before and after treatment in two groups of rats showed that the arthritis index in the study group decreased significantly after treatment.

[0021] Figure 3 The study compared the levels of serum IL-1, IL-6, and TNF-α in the two groups of rats before and after treatment, suggesting that the inflammatory factors decreased more in the study group after treatment. Detailed Implementation

[0022] The following detailed description, in conjunction with the accompanying drawings and embodiments, provides a traditional Chinese medicine fumigation and washing compound preparation for treating rheumatoid arthritis of the wind-cold obstruction type according to the present invention.

[0023] Example 1

[0024] The herbal fumigation and washing formula consists of: Morinda officinalis 15g, Angelica sinensis (tail) 10g, Glycyrrhiza uralensis (raw) 10g, Schizonepeta tenuifolia 10g, Atractylodes macrocephala 10g, Clerodendrum trichotomum 10g, Tripterygium wilfordii 15g, Agkistrodon halys 10g, Curcuma longa 10g, Eucommia ulmoides powder 10g, Strychnos nux-vomica (processed) 10g, Sappanwood 10g, and Cnidium monnieri 10g. All the herbs were provided by the pharmacy of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. The Eucommia ulmoides powder needs to be decocted in a bag. All the herbs are placed in a non-woven fabric bag, sealed, and then placed in a container. Water is added and the mixture is boiled to obtain the fumigation and washing solution.

[0025] Animal experiments:

[0026] This experiment established a rat model of collagen-induced arthritis by using type II collagen emulsion for immune induction, and studied the effects of traditional Chinese medicine fumigation on the level of arthritis, the degree of toe swelling, and the level of inflammatory factors in the model rats.

[0027] 1. Materials and Methods

[0028] 1.1 Animals

[0029] Twenty male SD rats, clean grade, weighing 180-200 grams, were purchased from Shanghai Xipu-Bikai Experimental Animal Co., Ltd.

[0030] 1.2 Main Reagents and Instruments

[0031] Bovine type II collagen (Chondrex); chloral hydrate; IL-1, IL-6, TNF-α (Wuhan Genemei Co., Ltd., catalog numbers: JYM0419Ra, JYM0651Ra, JYM0636Ra); sample homogenizer (Dragonlab, USA); benchtop high-speed refrigerated centrifuge (Eppendorf, Germany).

[0032] 1.3 Methods

[0033] 1.3.1 Modeling

[0034] A rat model of collagen-induced arthritis was established in SD rats by administering bovine type II collagen emulsion twice. Rats were anesthetized with chloral hydrate and then initially immunized with bovine type II collagen emulsion via intradermal injection (0.2 mL / rat) into the tail base and back. Two weeks later, booster immunizations were administered via intradermal injection of bovine type II collagen emulsion into the tail base and back (0.3 mL / rat). Rats were then housed for two weeks in an environment with a constant temperature of 10°C, forced ventilation, and 12 hours of light exposure to establish a rat model of collagen-induced arthritis due to wind-cold syndrome.

[0035] 1.3.2 Administration

[0036] Twenty rats were randomly divided into two groups. The control group was given methotrexate tablets (Shanghai Shangyao Xinyi Pharmaceutical Co., Ltd., National Drug Approval Number H31020644), 10 mg / time, once every Wednesday by gavage; and folic acid tablets (Fuzhou Haiwang Fuyao Pharmaceutical Co., Ltd., batch number 21030120), 10 mg / time, once every Friday by gavage. The study group received the same treatment as the control group, plus fumigation with a high-concentration traditional Chinese medicine fumigation formula (prepared according to the method in Example 1), once a day for 30 minutes at a temperature of 41℃, for 4 weeks. Various indicators of the rats in both groups were observed daily during the four weeks.

[0037] 1.3.3 Statistical Methods

[0038] SPSS 27.0 and GraphPad Prism 9.0 statistical software were used for analysis. Numerical data were analyzed using... The data before and after treatment in the study group and the control group were analyzed using a paired-samples t-test, and P < 0.05 indicated that the difference was statistically significant.

[0039] 1.4 Observation Indicators and Detection Methods

[0040] 1.4.1 Degree of swelling in the toes

[0041] The degree of swelling was determined by the volume of the toes after modeling, and the changes in toe volume were recorded before and after 4 weeks of herbal fumigation. The volume of the toes in each group of rats was measured by the water displacement method. The rats' hind limbs were immersed in a graduated glass container filled with water, just above the rat's ankle joint. The measurement was repeated 3 times, and the water displacement was recorded and the average value was taken.

[0042] 1.4.2 Arthritis Index

[0043] Arthritis indices were recorded before and 4 weeks after the herbal fumigation treatment, and scored using a point system: 0 points for normal, no arthritis; 1 point for redness or slight swelling; 2 points for moderate swelling; 3 points for severe swelling; and 4 points for severe swelling and inability to bear weight. The total score for each rat's limbs was calculated.

[0044] 1.4.3 Blood IL-1, IL-6, TNF-α

[0045] The expression of cytokines IL-1, IL-6, and TNF-α in rat serum was detected using ELISA. Blood was collected from the heart, centrifuged, and the supernatant was collected. IL-1, IL-6, and TNF-α were detected according to the ELISA kit instructions. Standard curves for IL-1, IL-6, and TNF-α were plotted, and the concentrations of IL-1, IL-6, and TNF-α in rat serum were calculated. All instrument parameters were kept constant during the assay, and all procedures were strictly performed according to the instructions with quality control monitoring.

[0046] 2. Experimental Results

[0047] 2.1 Degree of swelling in the toes

[0048] Changes in paw volume were measured in rats before and after 4 weeks of herbal fumigation. The paw volume in the study group was significantly lower than that in the control group after treatment (p<0.05), indicating a statistically significant difference. Figure 1 (As shown).

[0049] 2.2 Joint Inflammation Index

[0050] The changes in joint inflammation index of rats in each group after 4 weeks of traditional Chinese medicine fumigation were measured. Compared with the control group, the joint inflammation index of the study group was significantly lower after treatment (p<0.05), and the difference was statistically significant. Figure 2 (As shown).

[0051] 2.3 Serum IL-1, IL-6, and TNF-α

[0052] The expression levels of serum IL-1, IL-6, and TNF-α in rats of each group were measured after 4 weeks of fumigation. The expression levels of IL-1, IL-6, and TNF-α in the treatment group were significantly decreased after treatment (p<0.05), and the difference was statistically significant. Figure 3 (As shown).

[0053] This invention has shown through experiments that traditional Chinese medicine fumigation therapy can significantly improve the arthritis index and toe swelling symptoms in rats with collagen-induced arthritis, and can reduce the expression levels of inflammatory factors such as IL-1, IL-6, and TNF-α, indicating that this traditional Chinese medicine fumigation formula can improve inflammation in rats with collagen-induced arthritis by reducing inflammatory factors.

[0054] The above description is merely an example and illustration of the concept of the present invention. Those skilled in the art can make various modifications or additions to the specific embodiments described or use similar methods to replace them, as long as they do not deviate from the concept of the invention or exceed the scope defined in the claims, they should all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine fumigation and washing compound preparation for treating rheumatoid arthritis of the wind-cold obstruction type, characterized in that, The effective components of the traditional Chinese medicine fumigation and washing compound preparation are obtained from the following parts by weight of traditional Chinese medicine raw materials: Morinda officinalis 15 parts; Angelica sinensis tail 10 parts; Raw licorice root 10 parts; Schizonepeta tenuifolia 10 parts; 10 parts of Atractylodes macrocephala; 10 parts of Clerodendrum trichotomum; 15 portions of Tripterygium wilfordii; 10 portions of Agkistrodon halys; 10 parts turmeric; 10 parts of Eucommia ulmoides powder; 10 parts of processed strychnine; 10 parts of sappanwood; 10 portions of Cnidium monnieri; The Eucommia ulmoides powder packet and other Chinese medicines are placed in a non-woven fabric and sealed. Then, the mixture is placed in a container, water is added, and the mixture is boiled to obtain a fumigation solution.

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