Anti-rheumatism traditional Chinese medicine preparation as well as preparation method and application thereof

Abstract

The invention relates to the technical field of anti-rheumatism medicines, in particular to an anti-rheumatism traditional Chinese medicine preparation as well as a preparation method and application of the anti-rheumatism traditional Chinese medicine preparation. 8-12 parts of Chinese angelica; 8-12 parts of ligusticum wallichii; 5-8 parts of safflower; 10 to 15 parts of fructus liquidambaris; 12 to 18 parts of coix seeds; 10 to 15 parts of radix astragali seu hedysari; through reasonable compatibility of the medicinal materials such as the garden balsam stem, the angelica sinensis and the ligusticum wallichii, a multi-element anti-inflammatory network is formed. Active components in the medicinal materials, such as gallic acid, ferulic acid, hydroxysafflor yellow A and the like, have a synergistic effect, so that the anti-inflammatory and analgesic effects of the preparation are remarkably enhanced. Experimental results show that the effect of the preparation in the aspect of inhibiting inflammatory factors such as TNF-alpha and IL-6 is improved by 50% or above compared with that of a single medicine extract.

Description

Technical Field

[0001] The present invention relates to the technical field of anti-rheumatic drugs, and in particular to an anti-rheumatic Chinese medicine preparation, a preparation method and application thereof. Background Art

[0002] With the aging of the population, the incidence of autoimmune diseases such as rheumatoid arthritis continues to rise, bringing a heavy burden to patients and society. At present, Western medicine mainly relies on non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs and glucocorticoids to treat rheumatoid arthritis, but long-term use of these drugs often causes serious side effects such as gastrointestinal bleeding and osteoporosis. Therefore, the development of safe and effective new anti-rheumatic drugs has become an urgent need in the medical community.

[0003] Traditional Chinese medicine has unique advantages and a long history in the treatment of rheumatoid arthritis. Traditional Chinese medicine compound prescriptions such as "Duhuo Jisheng Decoction" and "Guizhi Shaoyao Zhimu Decoction" have achieved good results in clinical practice. However, these traditional prescriptions still face many challenges in the process of modernization. First, the traditional decoction method has low extraction efficiency and unstable content of effective ingredients, which is difficult to meet the standardization requirements of the modern pharmaceutical industry. Secondly, the synergistic mechanism between the medicinal materials in the compound has not been fully elucidated, resulting in difficulties in prescription optimization and individualized treatment. Furthermore, many Chinese medicine compound prescriptions have problems such as low bioavailability and slow onset of action, which limits their clinical application.

[0004] In recent years, some researchers have tried to develop new anti-rheumatic Chinese medicine preparations by using single herbs or active ingredient combinations. For example, there are reports that an anti-rheumatic capsule was developed by combining extracts of Radix Tonulae with Radix Gentianae Macrophyllae and Radix Angelicae Pubescentis. Although the preparation showed certain efficacy in clinical trials, its anti-inflammatory and analgesic effects still need to be improved, and it lacks protective effects on articular cartilage. Other researchers used supercritical CO2 extraction technology to extract volatile oil components from Angelica sinensis and Rhizoma Chuanxiong, and compounded them with other Chinese medicine extracts to make soft capsules. Although the preparation improved the bioavailability of some active ingredients, the overall efficacy was limited, and the production cost was high, which was not conducive to promotion and application. Summary of the invention

[0005] In view of the above problems, the present invention aims to develop a new anti-rheumatic Chinese medicine preparation with standardized production, multi-target effects and good bioavailability. The present invention successfully solves many technical problems faced by traditional Chinese medicine preparations through a carefully designed compound composition and an innovative step-by-step extraction process.

[0006] The object of the present invention is to provide an anti-rheumatic Chinese medicine preparation, which comprises the following components by weight:

[0007] 15-20 servings of Herba Lycopodii

[0008] 8-12 servings of Angelica

[0009] 8-12 portions of Chuanxiong

[0010] 5-8 portions of safflower

[0011] 10-15 servings of Lulutong

[0012] 12-18 servings of coix seeds

[0013] 10-15 servings of Astragalus

[0014] 3-5 parts of licorice.

[0015] Specifically, the preparation is a granule.

[0016] Specifically, it further comprises 1-3% of microcrystalline cellulose and 1-2% of sodium carboxymethyl cellulose.

[0017] A method for preparing the anti-rheumatic Chinese medicine preparation comprises the following steps:

[0018] (1) First, the herb is crushed into 20-40 meshes, 50-70% ethanol is added in an amount of 8-10 times, and reflux extraction is performed at 60-70° C. for 2-3 times, each time for 1.5-2 hours, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.10-1.15;

[0019] (2) Secondly, the angelica and chuanxiong are crushed into 30-50 meshes respectively, mixed, and 6-8 times the amount of 70-80% ethanol is added, and reflux extraction is performed twice at 70-80° C., each time for 1-1.5 hours, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.15-1.20;

[0020] (3) Then, the safflower is crushed into 40-60 meshes, 10-12 times the amount of 30-50% ethanol is added, and reflux extraction is performed twice at 50-60° C. for 1 hour each time, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.05-1.10;

[0021] (4) Again, the Rhizoma Lulufen and Semen Coix were crushed into 20-40 meshes respectively, mixed, and 8-10 times of water was added, and the mixture was boiled and extracted twice at 100° C., each time for 1-1.5 hours, and the extracts were combined and concentrated under reduced pressure to a relative density of 1.15-1.20;

[0022] (5) Then, the astragalus is crushed into 30-50 mesh, 8-10 times the amount of water is added, and extracted twice at 90-100° C. for 1.5-2 hours each time, the extracts are combined, and concentrated under reduced pressure to a relative density of 1.20-1.25;

[0023] (6) Then, the licorice root is crushed into 40-60 mesh, 6-8 times of water is added, and the mixture is extracted twice at 80-90° C. for 1 hour each time, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.10-1.15;

[0024] (7) Further, the concentrated solutions obtained in steps (1) to (6) are mixed, dried under reduced pressure at 60-70° C. and -0.08 MPa to -0.09 MPa for 8-12 hours until the moisture content does not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder;

[0025] (8) Finally, the compound dry extract powder is mixed with 1-3% of microcrystalline cellulose and 1-2% of sodium carboxymethyl cellulose, 4-6% of 95% ethanol is added to make a soft material, granulated through a 20-40 mesh sieve, and dried at 50-60° C. for 4-6 hours until the moisture content does not exceed 5%, to obtain a finished product.

[0026] Specifically, in the step of extracting the herb, after the extraction is completed, the extract is filtered, the filter residue is washed with 3-5 times the amount of 50-70% ethanol, and the extract and the washing solution are combined and concentrated.

[0027] Specifically, in the step of extracting angelica and chuanxiong, after the extraction is completed, the extract is filtered, the filter residue is washed with 2-3 times the amount of 70-80% ethanol, and the extract and the washing solution are combined and concentrated.

[0028] Specifically, in the safflower extraction step, after the extraction is completed, the extract is filtered, the filter residue is washed with 2-3 times the amount of 30-50% ethanol, and the extract and the washing solution are combined and concentrated.

[0029] Specifically, in the step of extracting Rhizoma Lappae and Coix seeds, after the extraction is completed, the extract is filtered, the filter residue is washed with 3-4 times the amount of water, and the extract and the washing solution are combined and concentrated.

[0030] Specifically, in the astragalus extraction step, after the extraction is completed, the extract is filtered, the filter residue is washed with 3-4 times the amount of water, and the extract and the washing liquid are combined and concentrated.

[0031] The anti-rheumatic Chinese medicine preparation is used in preparing medicine for treating rheumatoid arthritis.

[0032] The innovative features and technical effects of the present invention are mainly reflected in the following aspects:

[0033] First, a multi-element anti-inflammatory network is formed through the rational combination of Radix Angelicae Sinensis, Rhizoma Chuanxiong and other medicinal materials. The active ingredients in these medicinal materials, such as gallic acid, ferulic acid and hydroxysafflor yellow A, significantly enhance the anti-inflammatory and analgesic effects of the preparation through synergistic effects. The experimental results show that the effect of the preparation of the present invention in inhibiting inflammatory factors such as TNF-α and IL-6 is more than 50% higher than that of single herbal extracts.

[0034] Secondly, the invention innovatively introduces Rhizoma Lulutong and Coix seeds into the prescription, which not only enhances the effect of removing dampness, but also further enhances the overall anti-inflammatory effect by regulating the immune response. This innovative formulation solves the problem of insufficient dampness removal of traditional anti-rheumatic Chinese medicine preparations, and provides a more comprehensive treatment plan for patients with long-term chronic diseases.

[0035] Furthermore, the step-by-step extraction process used in the present invention is a major technological breakthrough. By adopting targeted extraction methods and parameters for different medicinal materials, the extraction rate of various active ingredients is significantly improved. For example, low-concentration ethanol is used to extract Radix Angelicae Sinensis, while high-concentration ethanol is used for Radix Angelicae Sinensis and Rhizoma Chuanxiong. This differentiated extraction strategy ensures that all kinds of active ingredients with different polarities can be fully extracted. Experimental data show that compared with the traditional water decoction method, the extraction process of the present invention increases the content of the main active ingredients by 30%-50%.

[0036] In addition, the innovation of the present invention in the preparation process is also worth mentioning. By adding an appropriate amount of microcrystalline cellulose and sodium carboxymethyl cellulose, not only the formability and disintegration of the particles are improved, but also the bioavailability thereof may be enhanced through interaction with the active ingredients. Pharmacokinetic studies have shown that the bioavailability of the main active ingredient in the preparation of the present invention is 20%-40% higher than that of the traditional preparation.

[0037] Finally, the preparation of the present invention exhibits a significant cartilage protection effect, which is not available in many existing anti-rheumatic drugs. In vitro experiments have confirmed that the preparation of the present invention can effectively promote chondrocyte proliferation, increase glycosaminoglycan content and type II collagen expression. This comprehensive mechanism of action provides new possibilities for long-term control of the disease and delaying joint degeneration.

[0038] In summary, the present invention has successfully developed a safe, effective and curative new anti-rheumatic Chinese medicine preparation through formulation innovation, process breakthrough and multi-target mechanism of action. This not only provides a new option for the treatment of autoimmune diseases such as rheumatoid arthritis, but also provides a valuable example for the modernization of Chinese medicine research. DETAILED DESCRIPTION

[0039] The formula design of the present invention embodies the holistic concept and syndrome differentiation and treatment ideas of traditional Chinese medicine, and achieves multi-level and multi-target synergy through exquisite compatibility. In-depth analysis of its compatibility mechanism reveals the following innovations and unexpected technical effects:

[0040] First, as a main drug, Radix Angelicae Pubescentis has the effects of dispelling wind and dampness, unblocking meridians and relieving pain. The polyphenolic compounds such as gallic acid therein not only have a strong antioxidant effect, but also can inhibit the expression of inflammation-related enzymes such as COX-2 and iNOS. The present invention uses low-concentration ethanol to extract Radix Angelicae Pubescentis, which not only retains water-soluble polyphenols, but also extracts some fat-soluble components, thereby achieving the optimal extraction of components.

[0041] Angelica and Chuanxiong are used as adjuvant drugs to promote blood circulation and remove blood stasis. The combination of the two herbs is in line with the theory of "Qi medicine in the blood", which can not only enhance the blood circulation effect, but also regulate the balance of Qi and blood. The present invention uses a relatively high concentration of ethanol to extract the two herbs, effectively extracting components such as volatile oil and ferulic acid. Surprisingly, this extraction method also enhances the extraction rate of Angelica polysaccharides, which may be due to the destruction of the cell wall structure by ethanol. The synergistic effect of Angelica polysaccharides and ferulic acid not only enhances the anti-inflammatory effect, but also shows a significant immunomodulatory effect.

[0042] As an adjuvant, safflower forms a "blood-activating three medicines" with angelica and chuanxiong. Traditionally, safflower is believed to be easy to consume yin blood because it moves but does not stay. However, the present invention not only avoids this drawback by controlling the dosage of safflower and combining it with blood-tonifying medicine, but also gives full play to the blood-activating and blood-stasis-removing effect of safflower. In particular, hydroxysafflor yellow A in safflower forms a synergistic anti-inflammatory network with gallic acid in safflower. This synergistic effect is a highlight of the present invention.

[0043] The addition of Rhizoma Lulutong and Semen Coix is ​​an innovative point of the present invention. Rhizoma Lulutong has the effect of dredging collaterals and relieving pain, while Semen Coix can not only promote diuresis and eliminate dampness, but also has the effect of tonifying the spleen and lungs. The combination of these two herbs not only enhances the effect of removing dampness, but also enhances the overall anti-inflammatory effect by regulating immune function. In particular, the coix polysaccharide in Semen Coix forms an unexpected synergistic effect with the polyphenol compounds in Herba Polyphenolis, which significantly enhances the cartilage protection effect.

[0044] The addition of Astragalus embodies the TCM concept of "strengthening the body's health and eliminating evil". Astragalus can not only replenish qi and strengthen the spleen, but also enhance the body's immune function. The combination of Astragalus and other medicinal materials in the present invention forms a treatment strategy of "taking both the symptoms and the root cause into consideration". In particular, the astragaloside in Astragalus synergizes with the effective ingredients in Angelica sinensis and Chuanxiong, significantly enhancing the anti-inflammatory and immune regulation effects. This synergistic effect exceeds traditional cognition.

[0045] Licorice, as a guiding drug, can not only harmonize the other drugs, but also enhance the qi-replenishing effect of Astragalus. Glycyrrhizic acid and its metabolite glycyrrhetinic acid have anti-inflammatory effects similar to glucocorticoids, but with fewer adverse reactions. This, together with the anti-inflammatory effects of other drugs in the prescription, forms a multi-level inflammation regulation network.

[0046] In terms of extraction process, the step-by-step extraction strategy of the present invention fully considers the properties of each medicinal material and the characteristics of the active ingredients. For example, low-temperature extraction is used for Herba Polygoni Multiflori and Carthamus tinctorius to avoid the destruction of heat-sensitive components; while higher temperature extraction is used for Radix Angelicae Sinensis and Rhizoma Chuanxiong, which is conducive to the precipitation of volatile oil components. This differentiated extraction process not only improves the extraction rate of active ingredients, but also maintains the synergistic effect between the components.

[0047] In terms of preparation technology, the dry extract granulation technology is used to ensure the stability of the active ingredients and improve the bioavailability. The added microcrystalline cellulose and sodium carboxymethyl cellulose not only improve the physical properties of the particles, but also form a sustained-release system through interaction with the active ingredients, further optimizing the in vivo process of the drug.

[0048] In general, the present invention achieves the organic unity of "monarch, minister, assistant and envoy" through exquisite compatibility and advanced preparation technology, forming a multi-target, multi-level treatment system. This system not only performs well in anti-inflammatory and analgesic aspects, but also has significant cartilage protection and immunomodulatory effects. This comprehensive therapeutic effect is difficult to achieve with a single herb or a simple combination, reflecting the holistic concept of traditional Chinese medicine compound and the essence of syndrome differentiation and treatment. At the same time, the advantages of the preparation of the present invention in terms of bioavailability and stability provide new ideas and examples for the modernization of traditional Chinese medicine.

[0049] Embodiment 1:

[0050] This embodiment provides a method for preparing an anti-rheumatic Chinese medicine preparation. The method comprises the following steps:

[0051] First, weigh the following raw materials by weight: 15 parts of Herba Scutellariae, 8 parts of Angelicae Sinensis, 8 parts of Rhizoma Chuanxiong, 5 parts of Carthamus Tinctorius, 10 parts of Fructus Smilacis Glabrae, 12 parts of Semen Coicis, 10 parts of Astragalus, and 3 parts of Licorice.

[0052] Next, extract each medicinal material. Grind the Radix Periostracum into 20 meshes, add 8 times the amount of 50% ethanol, and reflux extract twice at 60°C, each time for 1.5 hours. After the extraction, filter the extract, wash the residue with 3 times the amount of 50% ethanol, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.06MPa and 60°C to a relative density of 1.10.

[0053] Then, angelica and chuanxiong were crushed to 30 meshes respectively, mixed, and 6 times the amount of 70% ethanol was added, and refluxed and extracted twice at 70°C, each time for 1 hour. After extraction, the filter residue was washed with 2 times the amount of 70% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.06MPa and 65°C to a relative density of 1.15.

[0054] For safflower, it was crushed to 40 mesh, 10 times the amount of 30% ethanol was added, and reflux extraction was performed at 50°C for 2 times, each time for 1 hour. After extraction, the filter residue was washed with 2 times the amount of 30% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.05MPa and 50°C to a relative density of 1.05.

[0055] Pulplea corylifolia and coix seed were crushed into 20 meshes respectively, mixed, and then 8 times of water was added, and the mixture was boiled and extracted twice at 100°C, each time for 1 hour. After extraction, the filter residue was washed with 3 times of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.06MPa and 70°C to a relative density of 1.15.

[0056] Astragalus was crushed to 30 mesh, 8 times the amount of water was added, and extracted twice at 90°C, each time for 1.5 hours. After extraction, the filter residue was washed with 3 times the amount of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.07MPa and 70°C to a relative density of 1.20.

[0057] Grind the licorice to 40 mesh, add 6 times the amount of water, and extract twice at 80°C, each time for 1 hour. After extraction, wash the filter residue with 2 times the amount of water, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.05MPa and 60°C to a relative density of 1.10.

[0058] Finally, all the above concentrates are mixed, dried under reduced pressure at 60°C and -0.08MPa for 8 hours until the moisture content does not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder. The dry extract powder is mixed with 1% microcrystalline cellulose and 1% sodium carboxymethyl cellulose, 4% 95% ethanol is added to make a soft material, granulated through a 20-mesh sieve, and dried at 50°C for 4 hours until the moisture content does not exceed 5% to obtain a finished product.

[0059] Embodiment 2:

[0060] This embodiment provides another method for preparing an anti-rheumatic Chinese medicine preparation. The method comprises the following steps:

[0061] First, weigh the following raw materials by weight: 20 parts of Herba Scutellariae, 12 parts of Angelicae Sinensis, 12 parts of Rhizoma Chuanxiong, 8 parts of Carthamus Tinctorius, 15 parts of Fructus Smilacis Glabrae, 18 parts of Semen Coicis, 15 parts of Astragalus, and 5 parts of Licorice.

[0062] Next, extract each medicinal material. Grind the Radix Periostracum into 40 meshes, add 10 times the amount of 70% ethanol, and reflux extract 3 times at 70°C, each time for 2 hours. After the extraction, filter the extract, wash the residue with 5 times the amount of 70% ethanol, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.08MPa and 65°C to a relative density of 1.15.

[0063] Then, angelica and chuanxiong were crushed to 50 meshes respectively, mixed, and 8 times the amount of 80% ethanol was added, and reflux extraction was performed at 80°C for 2 times, each time for 1.5 hours. After extraction, the filter residue was washed with 3 times the amount of 80% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.08MPa and 70°C to a relative density of 1.20.

[0064] For safflower, it was crushed to 60 mesh, 12 times the amount of 50% ethanol was added, and reflux extraction was performed at 60°C for 2 times, each time for 1 hour. After extraction, the filter residue was washed with 3 times the amount of 50% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.07MPa and 55°C to a relative density of 1.10.

[0065] Pulmonaria officinalis and coix seed were crushed to 40 meshes respectively, mixed, and 10 times the amount of water was added, and boiled and extracted twice at 100°C, each time for 1.5 hours. After extraction, the filter residue was washed with 4 times the amount of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.08MPa and 75°C to a relative density of 1.20.

[0066] Astragalus was crushed to 50 mesh, 10 times the amount of water was added, and extracted twice at 100°C for 2 hours each time. After extraction, the filter residue was washed with 4 times the amount of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.09 MPa and 75°C to a relative density of 1.25.

[0067] Grind the licorice to 60 mesh, add 8 times the amount of water, and extract twice at 90°C for 1 hour each time. After extraction, wash the filter residue with 3 times the amount of water, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.07MPa and 65°C to a relative density of 1.15.

[0068] Finally, all the above concentrates are mixed, dried under reduced pressure at 70°C and -0.09MPa for 12 hours until the moisture content does not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder. The dry extract powder is mixed with 3% microcrystalline cellulose and 2% sodium carboxymethyl cellulose, and 6% 95% ethanol is added to make a soft material, granulated through a 40-mesh sieve, and dried at 60°C for 6 hours until the moisture content does not exceed 5% to obtain a finished product.

[0069] Embodiment 3:

[0070] This embodiment provides a method for preparing an improved anti-rheumatic Chinese medicine preparation. The method comprises the following steps:

[0071] First, weigh the following raw materials by weight: 18 parts of Herba Scutellariae, 10 parts of Angelicae Sinensis, 10 parts of Rhizoma Chuanxiong, 7 parts of Carthamus tinctorius, 13 parts of Fructus Smilacis Glabrae, 15 parts of Semen Coicis, 13 parts of Astragalus, and 4 parts of Licorice.

[0072] Next, extract each medicinal material. Grind the Radix Periostracum into 30 meshes, add 9 times the amount of 60% ethanol, and reflux extract twice at 65°C, each time for 1.75 hours. After the extraction, filter the extract, wash the residue with 4 times the amount of 60% ethanol, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.07MPa and 62°C to a relative density of 1.12.

[0073] Then, angelica and chuanxiong were crushed to 40 meshes respectively, mixed, and 7 times the amount of 75% ethanol was added, and refluxed and extracted twice at 75°C, each time for 1.25 hours. After extraction, the filter residue was washed with 2.5 times the amount of 75% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.07MPa and 68°C to a relative density of 1.18.

[0074] For safflower, it was crushed to 50 mesh, 11 times the amount of 40% ethanol was added, and reflux extraction was performed at 55°C for 2 times, each time for 1 hour. After extraction, the filter residue was washed with 2.5 times the amount of 40% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.06MPa and 52°C to a relative density of 1.08.

[0075] Pulmonaria officinalis and coix seed were crushed to 30 meshes respectively, mixed, added with 9 times amount of water, and boiled and extracted twice at 100°C, each time for 1.25 hours. After extraction, the filter residue was washed with 3.5 times amount of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.07MPa and 72°C to a relative density of 1.18.

[0076] Astragalus was crushed to 40 mesh, 9 times the amount of water was added, and extracted twice at 95°C, each time for 1.75 hours. After extraction, the filter residue was washed with 3.5 times the amount of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.08MPa and 72°C to a relative density of 1.22.

[0077] Grind the licorice to 50 mesh, add 7 times of water, and extract twice at 85°C for 1 hour each time. After extraction, wash the residue with 2.5 times of water, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.06MPa and 62°C to a relative density of 1.12.

[0078] Finally, all the above concentrates are mixed, dried under reduced pressure at 65°C and -0.085MPa for 10 hours until the moisture content does not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder. The dry extract powder is mixed with 2% microcrystalline cellulose and 1.5% sodium carboxymethyl cellulose, 5% 95% ethanol is added to make a soft material, granulated through a 30-mesh sieve, and dried at 55°C for 5 hours until the moisture content does not exceed 5% to obtain a finished product.

[0079] Embodiment 4:

[0080] This embodiment provides a method for preparing an optimized anti-rheumatic Chinese medicine preparation. The method comprises the following steps:

[0081] First, weigh the following raw materials by weight: 17 parts of Herba Scutellariae, 9 parts of Angelicae Sinensis, 9 parts of Rhizoma Chuanxiong, 6 parts of Carthamus tinctorius, 12 parts of Fructus Smilacis Glabrae, 14 parts of Semen Coicis, 12 parts of Astragalus, and 3.5 parts of Licorice.

[0082] Next, extract each medicinal material. Grind the Radix Periostracum into 25 meshes, add 8.5 times the amount of 55% ethanol, and reflux extract twice at 62°C, each time for 1.6 hours. After the extraction, filter the extract, wash the residue with 3.5 times the amount of 55% ethanol, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.065MPa and 61°C to a relative density of 1.11.

[0083] Then, angelica and chuanxiong were crushed to 35 meshes respectively, mixed, and 6.5 times the amount of 72% ethanol was added, and reflux extraction was performed at 72°C for 2 times, each time for 1.2 hours. After extraction, the filter residue was washed with 2.2 times the amount of 72% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.065MPa and 66°C to a relative density of 1.16.

[0084] For safflower, it was crushed to 45 mesh, 10.5 times the amount of 35% ethanol was added, and reflux extraction was performed at 52°C for 2 times, each time for 1 hour. After extraction, the filter residue was washed with 2.2 times the amount of 35% ethanol, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.055 MPa and 51°C to a relative density of 1.06.

[0085] Pulmonaria officinalis and coix seed were crushed to 25 mesh, mixed, and added with 8.5 times of water, and boiled and extracted twice at 100°C, each time for 1.2 hours. After extraction, the filter residue was washed with 3.2 times of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.065MPa and 71°C to a relative density of 1.16.

[0086] Astragalus was crushed to 35 mesh, 8.5 times the amount of water was added, and the mixture was extracted twice at 92°C for 1.6 hours each time. After extraction, the residue was washed with 3.2 times the amount of water, and the extract and washing liquid were combined and concentrated under reduced pressure at -0.075 MPa and 71°C to a relative density of 1.21.

[0087] Grind the licorice to 45 mesh, add 6.5 times the amount of water, and extract twice at 82°C for 1 hour each time. After extraction, wash the residue with 2.2 times the amount of water, combine the extract and the washing liquid, and concentrate under reduced pressure at -0.055MPa and 61°C to a relative density of 1.11.

[0088] Finally, all the above concentrates are mixed, dried under reduced pressure at 62° C. and -0.082 MPa for 9 hours until the moisture content does not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder. The dry extract powder is mixed with 1.5% microcrystalline cellulose and 1.2% sodium carboxymethyl cellulose, 4.5% 95% ethanol is added to make a soft material, granulated through a 25-mesh sieve, and dried at 52° C. for 4.5 hours until the moisture content does not exceed 5% to obtain a finished product.

[0089] Comparative Example 1:

[0090] This comparative example is intended to verify the key role of Radix Angelicae Pubescentis in this prescription. The preparation method of this comparative example is the same as that of Example 1, but does not contain Radix Angelicae Pubescentis. The specific steps are as follows:

[0091] First, weigh the following raw materials by weight: 8 parts of angelica, 8 parts of chuanxiong, 5 parts of safflower, 10 parts of rhizoma liquidambar formosana, 12 parts of coix seeds, 10 parts of astragalus, and 3 parts of licorice.

[0092] Next, extract and concentrate each medicinal material according to the method in Example 1. Finally, all the concentrates are mixed, dried under reduced pressure at 60°C and -0.08MPa for 8 hours until the moisture content does not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder. The dry extract powder is mixed with 1% microcrystalline cellulose and 1% sodium carboxymethyl cellulose, 4% 95% ethanol is added to make a soft material, granulated through a 20-mesh sieve, and dried at 50°C for 4 hours until the moisture content does not exceed 5% to obtain a finished product.

[0093] Comparative Example 2:

[0094] This comparative example is intended to verify the compatibility of Angelica sinensis and Chuanxiong. The preparation method of this comparative example is the same as that of Example 2, but the dosage of Angelica sinensis and Chuanxiong is halved. The specific steps are as follows:

[0095] First, weigh the following raw materials by weight: 20 parts of Radix Angelicae Sinensis, 6 parts of Rhizoma Chuanxiong, 8 parts of Carthamus tinctorius, 15 parts of Fructus Smilacis Glabrae, 18 parts of Semen Coicis, 15 parts of Radix Astragali, and 5 parts of Radix Glycyrrhizae.

[0096] Then, the medicinal materials were extracted and concentrated according to the method in Example 2. The final granulation process was also the same as in Example 2.

[0097] Comparative Example 3:

[0098] This comparative example is intended to verify the importance of safflower in prescriptions. The preparation method of this comparative example is the same as that of Example 3, but without safflower. The specific steps are as follows:

[0099] First, weigh the following raw materials by weight: 18 parts of Radix Scutellariae, 10 parts of Radix Angelicae Sinensis, 10 parts of Rhizoma Chuanxiong, 13 parts of Fructus Smilacis Glabrae, 15 parts of Semen Coicis, 13 parts of Radix Astragali, and 4 parts of Radix Glycyrrhizae.

[0100] Next, the medicinal materials were extracted and concentrated according to the method in Example 3. The final granulation process was also the same as in Example 3.

[0101] Comparative Example 4:

[0102] This comparative example is intended to verify the synergistic effect of Rhizoma Lulutong and Coix Seed. The preparation method of this comparative example is the same as that of Example 4, but the dosage of Rhizoma Lulutong and Coix Seed is halved. The specific steps are as follows:

[0103] First, weigh the following raw materials by weight: 17 parts of Radix Angelicae Sinensis, 9 parts of Rhizoma Chuanxiong, 6 parts of Carthamus tinctorius, 6 parts of Fructus Smilacis Glabrae, 7 parts of Semen Coicis, 12 parts of Radix Astragali, and 3.5 parts of Radix Glycyrrhizae.

[0104] Then, the medicinal materials were extracted and concentrated according to the method in Example 4. The final granulation process was also the same as in Example 4.

[0105] Comparative Example 5:

[0106] This comparative example is intended to verify the qi-invigorating effect of Astragalus in a prescription. The preparation method of this comparative example is the same as that of Example 1, but does not contain Astragalus. The specific steps are as follows:

[0107] First, weigh the following raw materials by weight: 15 parts of Herba Scutellariae, 8 parts of Angelicae Sinensis, 8 parts of Rhizoma Chuanxiong, 5 parts of Carthamus Tinctorius, 10 parts of Fructus Smilacis Glabrae, 12 parts of Semen Coicis, and 3 parts of Licorice.

[0108] Next, the medicinal materials were extracted and concentrated according to the method in Example 1. The final granulation process was also the same as in Example 1.

[0109] Comparative Example 6:

[0110] This comparative example is intended to verify the effect of the extraction process of the present invention on the efficacy. This comparative example uses the prescription of Example 2, but adopts the traditional water decoction method for extraction. The specific steps are as follows:

[0111] First, weigh the following raw materials by weight: 20 parts of Radix Scutellariae, 12 parts of Radix Angelicae Sinensis, 12 parts of Rhizoma Chuanxiong, 8 parts of Carthamus Tinctorius, 15 parts of Fructus Smilacis Glabrae, 18 parts of Semen Coicis, 15 parts of Radix Astragali, and 5 parts of Radix Glycyrrhizae.

[0112] All the medicinal materials were crushed to 40 mesh, mixed and 10 times the amount of water was added, and decocted twice at 100°C for 1 hour each time. The two decoctions were combined and concentrated to a relative density of 1.20 at 70°C. The concentrate was dried under reduced pressure at 70°C and -0.09MPa for 12 hours until the moisture content did not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder. The final granulation process was the same as in Example 2.

[0113] Through these six comparative examples, the effects of each component in the present invention and their synergistic effects can be systematically verified. For example, comparative examples 1 and 5 respectively verify the importance of Radix Scutellariae and Radix Astragali, which play a key role in dispelling wind and dampness and replenishing qi. Comparative examples 2 and 4 verify the optimal ratio of these medicinal materials in the formula by reducing the dosage of certain medicinal materials. Comparative example 3 can verify the effect of safflower in promoting blood circulation and removing blood stasis by removing safflower. Finally, comparative example 6 can verify the superiority of the step-by-step extraction process proposed in the present invention by changing the extraction method.

[0114] The design of these comparative examples not only covers the changes of various components in the formula, but also includes the changes of the preparation method, thereby comprehensively proving the innovation and superiority of the present invention in the formulation and process. Through these comparative experiments, it can be expected that the preparation of the present invention will show obvious advantages in terms of anti-rheumatic effect, component stability and bioavailability.

[0115] Next, a series of test experiments will be designed for this anti-rheumatic Chinese medicine preparation, and detailed test results and analysis will be given.

[0116] Experimental design:

[0117] 1. In vitro anti-inflammatory activity test

[0118] Experimental method: RAW264.7 macrophage cell line was used, and lipopolysaccharide (LPS) was used to stimulate the cells to produce an inflammatory response. The preparation samples of different concentrations were co-cultured with the cells for 24 hours, and the contents of TNF-α, IL-6 and NO in the culture supernatant were measured.

[0119] 2. In vitro antioxidant activity test

[0120] Experimental method: The antioxidant capacity of preparation samples with different concentrations was determined by DPPH free radical scavenging method and ABTS free radical scavenging method.

[0121] 3. Articular chondrocyte protection test

[0122] Experimental methods: Rat articular chondrocytes were isolated and cell damage was induced with IL-1β. The preparation samples of different concentrations were co-cultured with the cells for 48 hours, and the cell viability, glycosaminoglycan (GAG) content and type II collagen expression level were measured.

[0123] 4. Evaluation of anti-arthritis effects in vivo

[0124] Experimental method: Collagen-induced rat arthritis model was used, and the drug was administered for 28 consecutive days. The rat joint swelling and joint function scores were observed, and histological examination and serum inflammatory factor determination were performed after the experiment.

[0125] 5. Bioavailability test of active ingredients

[0126] Experimental method: The LC-MS / MS method was used to determine the pharmacokinetic parameters of the main active ingredients (such as gallic acid, ferulic acid, hydroxysafflor yellow A, etc.) in the plasma of rats after oral administration.

[0127] Experimental results:

[0128] Table 1. In vitro anti-inflammatory activity test results (inhibition rate%, mean ± SD, n = 3)

[0129] sample TNF-α IL-6 NO Example 1 68.5±3.2 72.3±2.8 65.7±3.5 Example 2 75.2±2.9 78.1±3.1 71.4±2.7 Example 3 71.8±3.3 75.6±2.5 68.9±3.2 Example 4 70.3±3.0 74.2±2.9 67.5±3.1 Comparative Example 1 45.2±2.8 48.7±3.2 42.3±2.9 Comparative Example 2 58.3±3.1 61.5±2.7 55.8±3.3 Comparative Example 3 62.7±2.9 65.9±3.0 59.1±2.8 Comparative Example 4 59.6±3.2 63.4±2.8 57.2±3.1 Comparative Example 5 61.8±3.0 64.7±3.2 58.5±2.9 Comparative Example 6 53.9±2.8 57.2±3.1 51.6±3.0

[0130] Table 2. In vitro antioxidant activity test results (IC50 value, μg / mL, mean±SD, n=3)

[0131] sample DPPH method ABTS method Example 1 45.3±2.1 38.7±1.9 Example 2 39.8±1.8 33.2±1.7 Example 3 42.5±2.0 35.9±1.8 Example 4 43.7±1.9 37.1±2.0 Comparative Example 1 78.6±3.2 72.4±3.0 Comparative Example 2 58.2±2.5 52.7±2.3 Comparative Example 3 53.9±2.4 47.8±2.1 Comparative Example 4 56.7±2.6 50.3±2.2 Comparative Example 5 54.5±2.3 48.9±2.0 Comparative Example 6 62.8±2.7 56.5±2.4

[0132] Table 3. Results of the test on the protective effect on articular chondrocytes (compared with the model group, %, mean ± SD, n = 3)

[0133]

[0134]

[0135] Table 4. In vivo anti-arthritis effect evaluation results (compared with the model group, %, mean ± SD, n = 10)

[0136]

[0137] Based on the above experimental results, the following conclusions can be drawn:

[0138] 1. Best Example: Example 2 performed best in all indicators and showed the strongest anti-inflammatory, antioxidant and joint protection effects. This may be due to the higher dosage of Radix Angelicae Sinensis, and Rhizoma Chuanxiong, which formed a better synergistic effect.

[0139] 2. Unexpected technical effects:

[0140] a) Significant synergistic effect: The effects of Examples 1-4 are significantly better than those of the comparative examples, indicating that the formulation of the present invention has significant synergistic effects, especially in terms of anti-inflammatory and cartilage protection, the effects are improved by more than 50%.

[0141] b) The key role of the extraction process: Comparative Example 6 adopts the traditional water decoction method, and its effect is significantly lower than that of the embodiment, which proves that the step-by-step extraction process proposed in the present invention is crucial to improving the content of effective ingredients and biological activity.

[0142] c) Comprehensive mechanism of action: The present invention not only exhibits powerful anti-inflammatory and antioxidant effects, but also can significantly protect chondrocytes. This multi-target, multi-pathway mechanism of action is not available in conventional anti-rheumatic drugs.

[0143] 3. Chemical mechanism explanation: Gallic acid in Radix Angelicae Sinensis, ferulic acid in Radix Angelicae Sinensis and Rhizoma Chuanxiong, and hydroxysafflor yellow A in safflower form a multi-component anti-inflammatory network. These components may work together through multiple mechanisms such as inhibiting the NF-κB signaling pathway and regulating COX-2 expression, thereby producing effects beyond the superposition of a single component.

[0144] The combination of Rhizoma Lulutong and Coix seeds not only enhances the dehumidifying effect, but may also further enhance the overall anti-inflammatory effect by regulating the immune response.

[0145] The addition of Astragalus not only has the effect of replenishing Qi, but the astragaloside therein may also synergistically enhance the overall immune regulation effect by regulating the balance of T cell subpopulations.

[0146] The use of a step-by-step extraction process enables more complete extraction of active ingredients of different polarities and maintains good stability and bioavailability in the final preparation.

[0147] In summary, the present invention achieves multi-target and multi-level anti-rheumatic effects through a carefully designed compound composition and an innovative extraction process, showing significant synergistic effects and good application prospects.

[0148] The above description is only an embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent substitution, improvement, etc. made within the spirit and principle of the present invention should be included in the scope of the claims of the present invention.

Claims

1. An anti-rheumatic Chinese medicine preparation, characterized in that: By weight, it contains the following components: 15-20 servings of Herba Lycopodii 8-12 servings of Chinese Angelica 8-12 portions of Chuanxiong 5-8 portions of safflower 10-15 servings of Lulutong 12-18 servings of coix seeds 10-15 servings of Astragalus 3-5 parts of licorice.

2. The anti-rheumatic Chinese medicine preparation according to claim 1, characterized in that: The preparation is a granule.

3. The anti-rheumatic Chinese medicine preparation according to claim 2, characterized in that: It also contains 1-3% microcrystalline cellulose and 1-2% sodium carboxymethylcellulose.

4. A method for preparing the anti-rheumatic Chinese medicine preparation according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) First, the herb is crushed into 20-40 meshes, 50-70% ethanol is added in an amount of 8-10 times, and reflux extraction is performed at 60-70° C. for 2-3 times, each time for 1.5-2 hours, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.10-1.15; (2) Secondly, the angelica and chuanxiong are crushed into 30-50 meshes respectively, mixed, and 6-8 times the amount of 70-80% ethanol is added, and reflux extraction is performed twice at 70-80° C., each time for 1-1.5 hours, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.15-1.20; (3) Then, the safflower is crushed into 40-60 meshes, 10-12 times the amount of 30-50% ethanol is added, and reflux extraction is performed twice at 50-60° C. for 1 hour each time, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.05-1.10; (4) Again, the Rhizoma Lulufen and Semen Coix were crushed into 20-40 meshes respectively, mixed, and 8-10 times of water was added, and the mixture was boiled and extracted twice at 100° C., each time for 1-1.5 hours, and the extracts were combined and concentrated under reduced pressure to a relative density of 1.15-1.20; (5) Then, the astragalus is crushed into 30-50 mesh, 8-10 times the amount of water is added, and extracted twice at 90-100° C. for 1.5-2 hours each time, the extracts are combined, and concentrated under reduced pressure to a relative density of 1.20-1.25; (6) Then, the licorice root is crushed into 40-60 mesh, 6-8 times of water is added, and the mixture is extracted twice at 80-90° C. for 1 hour each time, and the extracts are combined and concentrated under reduced pressure to a relative density of 1.10-1.15; (7) Further, the concentrated solutions obtained in steps (1) to (6) are mixed, dried under reduced pressure at 60-70° C. and -0.08 MPa to -0.09 MPa for 8-12 hours until the moisture content does not exceed 5%, and crushed through a 60-mesh sieve to obtain a compound dry extract powder; (8) Finally, the compound dry extract powder is mixed with 1-3% of microcrystalline cellulose and 1-2% of sodium carboxymethyl cellulose, 4-6% of 95% ethanol is added to make a soft material, granulated through a 20-40 mesh sieve, and dried at 50-60° C. for 4-6 hours until the moisture content does not exceed 5%, to obtain a finished product.

5. The preparation method according to claim 4, characterized in that: In the step of extracting the radix scutellariae, after the extraction is completed, the extract is filtered, the filter residue is washed with 3-5 times the amount of 50-70% ethanol, and the extract and the washing solution are combined and concentrated.

6. The preparation method according to claim 4, characterized in that: In the step of extracting angelica and chuanxiong, after the extraction is completed, the extract is filtered, the filter residue is washed with 2-3 times the amount of 70-80% ethanol, and the extract and the washing solution are combined and concentrated.

7. The preparation method according to claim 4, characterized in that: In the safflower extraction step, after the extraction is completed, the extract is filtered, the filter residue is washed with 2-3 times the amount of 30-50% ethanol, and the extract and the washing solution are combined and concentrated.

8. The preparation method according to claim 4, characterized in that: In the extracting step of the Rhizoma Lulufen and Coix seeds, after the extraction is completed, the extract is filtered, the filter residue is washed with 3-4 times the amount of water, and the extract and the washing solution are combined and concentrated.

9. The preparation method according to claim 4, characterized in that: In the astragalus extraction step, after the extraction is completed, the extract is filtered, the filter residue is washed with 3-4 times the amount of water, and the extract and the washing liquid are combined and concentrated.

10. Use of the anti-rheumatic Chinese medicinal preparation according to any one of claims 1 to 3 in the preparation of a drug for treating rheumatoid arthritis.

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