Muscle and bone tablets with reduced toxic and side effects as well as preparation method and application thereof
Processed Chuanwu and Caowu are extracted with organic solvents and made into enteric-coated microspheres, which solves the toxicity problem of Wantong Jingu Tablets, improves safety and efficacy, and is suitable for dispelling wind, dispersing cold, unblocking meridians and relieving pain.
Patent Information
- Application Number
- CN202410394232.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-04-02
- Publication Date
- 2025-10-14
AI Technical Summary
In the existing Wantong Muscle and Bone Tablets, the toxicity problem caused by the diterpenoid alkaloids in processed Chuanwu and processed Caowu causes strong side effects during long-term use and has low safety. They must be used strictly according to the usage and dosage.
Prepared Chuanwu and Caowu are extracted with organic solvents to make enteric-coated microspheres, which are then used together with other Chinese medicinal materials to prepare tendon and bone tablets, thereby reducing toxicity and improving efficacy.
It significantly improves the safety of tendon and bone tablets, reduces acute toxicity, and enhances the effects of dispelling wind and cold, unblocking meridians and relieving pain, and is superior to traditional Wantong tendon and bone tablets.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of Chinese patent medicine preparations, and particularly relates to a tendon and bone tablet with reduced toxic and side effects, and a preparation method and use thereof. Background Art
[0002] The main ingredients of "Wantong Jingu Tablets" are 25 Chinese herbal medicines such as Chuanwu, Caowu, and Strychnos nux vomica. It has the effects of dispelling wind and cold, unblocking meridians and relieving pain, strengthening tendons and bones, nourishing the liver and kidneys, etc. It is suitable for the treatment of limb pain and flexion and extension problems caused by rheumatoid arthritis, rheumatoid arthritis, cervical spondylosis, and periarthritis of the shoulder.
[0003] However, both the processed Chuanwu and processed Caowu in Wantong Jingu Tablets contain a large amount of diterpenoid alkaloids. Diterpenoid alkaloids can be divided into three types: diester type, monoester type or alcoholamine type alkaloids. Diester type alkaloids (for example, aconitine) are the most toxic components, while the toxicity of monoester type alkaloids is only 1 / 200 of that of diester type alkaloids. Aconitine is a potent neurotoxin that can inhibit nerve conduction and respiratory centers, leading to respiratory failure and death. In view of the toxicity of diester type alkaloids, the content of aconitine is strictly limited in the current standards for Wantong Jingu Tablets. However, since processed Chuanwu and processed Caowu are used as raw materials in Wantong Jingu Tablets and are used in large quantities, although the toxicity-reducing effects of medicinal materials such as licorice and ginseng on diester type alkaloids are taken into account in the formulation, in clinical applications, the diseases treated by Wantong Jingu Tablets require long-term medication, which leads to frequent side effects in patients during the course of taking the medicine.
[0004] Therefore, when taking Wantong Muscle and Bone Tablets, you must strictly follow your doctor's instructions and the instructions for use and dosage. Do not take excessive doses or take them for long periods of time. If you experience symptoms of poisoning such as nausea, vomiting, dizziness, palpitations, or difficulty breathing, you should stop taking the medicine immediately and seek medical attention.
[0005] In recent years, to improve the safety of Wantong Jingu Tablets, the inventors have conducted in-depth research on how to reduce the toxicity of processed Chuanwu and Kusnezoffii by improving the processing and formulation of the Chinese medicinal materials. Through extensive experiments, they have discovered a method that can reduce the toxicity of processed Chuanwu and Kusnezoffii while simultaneously improving the efficacy of the Jingu Tablets. Currently, no relevant reports exist. Summary of the Invention
[0006] In order to further reduce the potential risks of Wantong Muscle and Bone Tablets currently used in clinical practice and to further improve the safety of medication, the present invention conducts secondary development of this traditional Chinese patent medicine and provides a muscle and bone tablet with reduced toxic and side effects, as well as a preparation method and use thereof.
[0007] Specifically, the present invention is achieved through the following technical solutions:
[0008] In a first aspect, the present invention provides a tendon and bone tablet with reduced toxic and side effects, wherein the tendon and bone tablet is prepared from the following Chinese medicinal raw materials: processed Chuanwu, Epimedium, Guanzhong, Deer Antler, Asarum, Carthami, Earthworm, Drynaria fortunei, Red Ginseng, processed Kusnezoffii, Achyranthes bidentata, Phellodendron chinense, Dipsacus asper, Ephedra, Acanthopanax senticosus, Morus alba, Radix Aconiti Lateralis Preparata, processed Strychnos nux vomica, Notopterygium wilfordii, Snakehead aconite, Plum, Cinnamomum cassia, Honeysuckle, Licorice and prepared Myrrh. In the preparation method of the tendon and bone tablet, the two Chinese medicinal raw materials, processed Chuanwu and processed Kusnezoffii, are first extracted with an organic solvent, the extract is dried and crushed to form enteric-coated microspheres, and then the microspheres are prepared together with other raw materials to prepare the tendon and bone tablet.
[0009] As an option, the organic solvent is methanol, ethanol, n-propanol, isopropanol, n-butanol or isobutanol.
[0010] Preferably, the organic solvent is ethanol with a volume concentration of 85%.
[0011] As an optional manner, in the above-mentioned tendon and bone tablets, the tendon and bone tablets are made of the following Chinese medicinal raw materials in parts by weight: processed Chuanwu, Epimedium, Guanzhong, Deer Antler, Asarum, Safflower, Earthworm, Boiled Drynaria, and Red Ginseng are 1-6 parts, 1-10 parts, 1-10 parts, 1-4 parts, 1-3 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, and 1-6 parts respectively; processed Kusnezoffius, Achyranthes, Phellodendron, Dipsacus, Ephedra, Acanthopanax, Morus alba, and Radix Glycyrrhizae are 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, and 1-6 parts respectively; processed Strychnos nux vomica, Notopterygium wilfordii, Snakehead snake, Plum, Cassia twig, Honeysuckle, Licorice, and processed Myrrh are 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, and 1-6 parts respectively.
[0012] As an optional manner, in the above-mentioned tendon and bone tablets, the tendon and bone tablets are made of the following Chinese medicinal raw materials in parts by weight: 4-6 parts, 5-9 parts, 5-9 parts, 2-4 parts, 1-3 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, and 4-6 parts of processed Chuanwu, Epimedium, Guanhuangbai, Dipsacus asper, Ephedra, Acanthopanax, Morus alba, and Radix Glycyrrhizae are respectively 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, and 4-6 parts of processed Kusnezoffii, Achyranthes bidentata, Phellodendron chinense, Dipsacus asper, Ephedra, Acanthopanax senticosus, Morus alba, and Radix Glycyrrhizae are respectively 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, and 4-6 parts of processed Strychnos nux vomica, Notopterygium wilfordii, Snakehead amurense, Plum, Cassia twig, Honeysuckle, Licorice, and processed Myrrh are respectively 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, and 4-6 parts.
[0013] Preferably, the tendon and bone tablets are made of the following Chinese medicinal raw materials in parts by weight: processed Chuanwu, Epimedium, Cyperus, Deer Antler, Asarum, Safflower, Earthworm, Drynaria fortunei, and red ginseng are 6 parts, 8 parts, 8 parts, 4 parts, 3 parts, 6 parts, 6 parts, 6 parts, and 6 parts respectively; processed Kusnezoffii, Achyranthes bidentata, Phellodendron chinense, Dipsacus asper, Ephedra, Acanthopanax senticosus, Morus alba, and Radix Glycyrrhizae are 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, and 6 parts respectively; processed Strychnos nux vomica, Notopterygium wilfordii, Snakehead amurense, Plum, Cassia twig, Honeysuckle, Licorice, and processed Myrrh are 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, and 6 parts respectively.
[0014] In a second aspect, the present invention provides a preparation method for the tendon and bone tablets described in the first aspect, which comprises the following steps: taking the above 25 medicinal materials, first extracting the two Chinese medicinal raw materials, processed Chuanwu and processed Caowu, with an organic solvent, drying and crushing the extract to make enteric-coated microspheres for later use; decocting mistletoe, ephedra, epimedium, dipsacus, licorice, Acanthopanax, Phellodendron chinense, Drynaria fortunei, earthworm, Achyranthes bidentata, Radix Glehniae, Cyperus rotundus and Prunus mume with water for three times, combining the decoctions, filtering, and concentrating the filtrate to 50°C to obtain a clear paste with a relative density of 1.25-1.30, for later use; crushing the remaining medicinal ingredients into fine powder, mixing them with the above-mentioned enteric-coated microspheres and clear paste, drying them below 60°C, crushing them into granules, pressing them into tablets, and coating them with sugar or film.
[0015] Preferably, the water is decocted three times, the first time for 2 hours, and the second and third times for 1 hour each.
[0016] In the preparation method, the extraction method of processed Chuanwu and processed Caowu is to add an organic solvent to the processed Chuanwu and processed Caowu, reflux extraction for 1-3 hours, collect the extract, then add the organic solvent to the filter residue, reflux extraction for 1-3 hours, combine the two extracts, recover the organic solvent, and concentrate the extract until the relative density measured at 60-80°C is 1.20-1.30 to obtain an extract concentrate, and then dry and crush the extract concentrate.
[0017] As an option, the organic solvent is methanol, ethanol, n-propanol, isopropanol, n-butanol or isobutanol.
[0018] Preferably, the organic solvent is ethanol with a volume concentration of 85%.
[0019] Preferably, the reflux extraction time is 2 hours.
[0020] As an optional method, in the above preparation method, the preparation method of enteric-coated microspheres containing processed Chuanwu and processed Caowu is as follows: the extract concentrate prepared above is dried and crushed into 80-mesh fine powder, then mixed with an appropriate amount of microcrystalline cellulose and lauryl magnesium sulfate, extruded and dried to obtain a sphere core, an appropriate amount of cross-linked polyvinylpyrrolidone and chitosan are mixed to prepare a coating liquid, the coating liquid is evenly sprayed on the sphere core in a coating pan, and granules are obtained after drying, an acrylic resin is prepared into a coating liquid, the coating liquid is sprayed on the granules in a coating pan, and the enteric-coated microspheres are obtained after drying.
[0021] Preferably, the weight ratio of the processed Chuanwu and processed Caowu extract concentrate powders, microcrystalline cellulose, and lauryl magnesium sulfate is 2:3:1. The weight ratio of cross-linked polyvinylpyrrolidone to chitosan is 1:7.
[0022] In a third aspect, the present invention provides use of the tendon and bone tablets described in the first aspect or the tendon and bone tablets prepared by the preparation method described in the second aspect in preparing a medicine having the effects of dispelling wind, dispersing cold, unblocking meridians and relieving pain.
[0023] As an optional mode, in the above-mentioned use, the medicine is used for arthritis, low back pain, muscle and joint pain, flexion and extension problems, as well as frozen shoulder, cervical spondylosis, rheumatoid arthritis, and rheumatoid arthritis with the above symptoms.
[0024] Compared with the prior art, the present invention has the following beneficial effects:
[0025] The Jingu Tablet of the present invention is an upgraded product produced by improving the preparation method of Wantong Jingu Tablet. It has a good detoxifying effect on processed Chuanwu and Caowu, while also enhancing the Jingu Tablet's efficacy in dispelling wind and cold, unblocking meridians, and alleviating pain. This effectively addresses the potential for strong side effects and low safety associated with long-term use of Wantong Jingu Tablet in clinical practice. DETAILED DESCRIPTION
[0026] The present invention will be further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to illustrate the present invention and are not intended to limit the scope of the present invention.
[0027] The application and research progress of the main ingredients in Wantong Muscle and Bone Tablets are as follows:
[0028] Chuanwu: The dried root of the Aconitum plant, a member of the Ranunculaceae family, is pungent, bitter, and warm in nature. It has the effects of dispelling wind and dampness, warming the meridians, and relieving pain. It is commonly used to treat wind-cold-dampness arthritis, cold joint pain, and as an anesthetic. Chuanwu has anti-inflammatory and analgesic effects and plays a key role in the clinical treatment of rheumatic diseases. Its main chemical components are alkaloids, including aconitine, mesaconitine, and mesaconitine.
[0029] Epimedium, also known as Xianlingpi, is a common Chinese medicinal herb. It originates from the dried leaves of the Berberidaceae plants Epimedium, Epimedium sagittatum, Epimedium pubescens, or Epimedium koreana. It has the effects of tonifying the kidneys and strengthening yang, dispelling wind and dampness, and is one of the main ingredients in Wantong Jingu Tablets. It is commonly used clinically to treat conditions such as osteoporosis, femoral head necrosis, and sexual dysfunction. The main chemical components of epimedium are flavonoids, represented by icariin, epimedin, epimedin A, epimedin B, and epimedin C. Traditional Chinese Medicine believes that epimedium has the effects of "tonifying kidney yang and strengthening tendons and bones." Epimedium or herbal formulas containing epimedium are often used to treat osteoarthritis, with definite therapeutic effects.
[0030] Nux vomica: It has the effects of dredging meridians, relieving pain, dispersing nodules and reducing swelling. It is used to treat rheumatic arthritis, numbness and paralysis, rheumatoid arthritis and other symptoms.
[0031] "Processed Caowu": Belongs to the Ranunculaceae family, along with Chuanwu, it has clinical benefits such as improving blood circulation, resisting cold, anti-inflammatory and analgesic, myocardial protection, cardiotonic, anti-shock, and anti-tumor. It is commonly used for wind-cold-dampness arthralgia, joint pain, heart and abdominal pain, and cold hernia pain.
[0032] Guan Huangbai (Phellodendron amurense) is the dried bark of the Rutaceae plant Phellodendron amurense (Phellodendron amurense). It clears away heat and dampness, relieves internal heat and dampness, detoxifies and eliminates decay, and has anti-tumor and immune-enhancing properties.
[0033] "Black-banded snake": dispels wind, dredges meridians, and stops spasms. It can treat polio.
[0034] Deer antler: nourishes the kidneys and strengthens yang, produces essence and blood, and strengthens the marrow and bones. Studies have reported that deer antler extract can increase SOD activity in ischemic myocardial tissue and has a good anti-arrhythmic effect.
[0035] "Dipsacus": The dried root of the plant Dipsacus asper of the Dipsacus family is named after its ability to "set bones". It has the effect of nourishing the body and strengthening the tendons and bones. It is often used to treat tendon injuries, fractures, and soreness of the waist and knees.
[0036] "Wumei": It has the effects of astringing the lungs, astringing the intestines, promoting the production of body fluids and calming ascaris. It is used for long-term cough due to lung deficiency, long-term diarrhea and dysentery, deficiency heat and thirst, ascariasis and vomiting and abdominal pain.
[0037] "Asarum": has the effects of dispelling wind, dispersing cold, promoting water circulation and opening the orifices.
[0038] Ephedra: Pungent and warm in nature, it has the effects of inducing sweating and dispelling cold, promoting lung function and relieving asthma, warming and promoting yang energy, and promoting diuresis and reducing swelling. It is mainly used to treat typhoid fever. Modern pharmacological experiments have shown that pseudoephedrine has a significant diuretic effect.
[0039] Acanthopanax: Tonifies the middle and replenishes Qi, strengthens the bones and muscles, and strengthens the will. Studies have shown that Acanthopanax contains superoxide dismutase, which can enhance immunity. Acanthopanax glycosides inhibit mitosis and deoxyribonucleic acid synthesis, thereby reducing cancer cell proliferation and promoting apoptosis.
[0040] Honeysuckle: It has the effect of clearing away heat and detoxifying. Its main ingredient is chlorogenic acid, which studies have shown to have strong antiviral, anti-inflammatory and antibacterial effects.
[0041] "Mistletoe": dispels rheumatism, benefits the liver and kidneys, and strengthens the bones and muscles. It is reported that the quercetin and quercetin components in mistletoe are important medicinal substances for dispelling rheumatism.
[0042] "Tang Gu Sui Bu": nourishes the kidneys and strengthens bones, heals injuries and relieves pain.
[0043] Ground maple bark, processed myrrh, red ginseng, licorice, earthworm, cinnamon twig, safflower, etc. are mostly adjuvant drugs, which play the role of strengthening the body, warming and nourishing, warming the interior to treat cold, and cooperating with other ingredients to achieve better therapeutic effects.
[0044] If no specific techniques or conditions are specified in the examples, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product instructions. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.
[0045] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.
[0046] Preparation Example:
[0047] Example:
[0048] The bone and tendon tablets with reduced toxic and side effects are prepared from the following Chinese medicinal raw materials in parts by weight: 6 parts, 8 parts, 8 parts, 4 parts, 3 parts, 6 parts, 6 parts, 6 parts and 6 parts of processed Chuanwu, epimedium, cyperus rotundus, pilose antler, asarum, safflower, earthworm, scalded drynaria rhizome and red ginseng respectively; 6 parts, 6 parts, 6 parts, 6 parts, 6 parts and 6 parts of processed kusnezoffii, cyperus rotundus, coptis chinensis, dipsaccharin, ephedra, acanthopanax senticosus, mistletoe and ground maple bark respectively; 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts, 6 parts and 6 parts of processed strychnos nux vomica, notopterygium wilfordii, serpentine snake, black plum, cassia twig, honeysuckle, liquorice and processed myrrh respectively.
[0049] The preparation method comprises the following steps: taking the above 25 medicinal materials, first extracting the two traditional Chinese medicine raw materials of prepared monkshood and prepared radix aconiti using 85% ethanol by volume, drying and pulverizing the extract to prepare enteric microspheres for standby; decocting the following 13 medicinal materials: taxillus, ephedra, herba epimedii, rhizoma discontinu, licorice, acanthopanax, phellodendron amurense, drynaria, earthworm, radix astragali, cortex periplocae, and prunus mume three times, 2 hours for the first time, and 1 hour for each of the second and third times, combining the decoction, filtering, concentrating the filtrate to a clear extract with a relative density of 1.25-1.30 at 50°C, and standby; pulverizing the remaining medicinal materials into fine powder, mixing with the above enteric microspheres and clear extract, drying below 60°C, pulverizing, preparing granules, tabletting, sugar coating or film coating, and obtaining the product.
[0050] The extraction method of prepared monkshood and prepared radix aconiti is as follows: adding 85% ethanol by volume to prepared monkshood and prepared radix aconiti, refluxing and extracting for 2 hours, collecting the extract, adding 85% ethanol by volume to the residue, refluxing and extracting for 2 hours, combining the two extracts, recovering 85% ethanol by volume, concentrating the extract to a relative density of 1.20-1.30 at 60-80°C, obtaining an extract concentrate, and then drying and pulverizing the extract concentrate.
[0051] The preparation method of the enteric microspheres containing prepared monkshood and prepared radix aconiti is as follows: drying and pulverizing the prepared monkshood and prepared radix aconiti extract concentrate into 80-mesh fine powder, mixing with appropriate amounts of microcrystalline cellulose and lauryl sulfate magnesium, extruding and molding, drying, obtaining the core, mixing appropriate amounts of cross-linked povidone and chitosan to prepare a coating liquid, uniformly spraying the coating liquid to the core in a coating pan, drying, obtaining the granules, preparing an acrylic resin coating liquid, spraying the coating liquid to the granules in a coating pan, drying, and obtaining the enteric microspheres. The weight ratio of the prepared monkshood and prepared radix aconiti extract concentrate fine powder, lauryl sulfate magnesium, cross-linked povidone, and chitosan is 2:3:1:1:7.
[0052] Comparative example (commercial Wantoongujin Gu tablet formula):
[0053] The Wantoongujin Gu tablet is prepared from the following weight parts of traditional Chinese medicine raw materials: prepared monkshood, herba epimedii, radices discontinu, pilose antler, asarum, safflower, earthworm, drynaria, red ginseng, each 6 parts; prepared radix aconiti, radix astragali, phellodendron amurense, rhizoma discontinu, ephedra, acanthopanax, taxillus, cortex periplocae, each 6 parts; prepared strychnos nux-vomica, notopterygium, amphiesma, prunus mume, ramulus cinnamomi, honeysuckle, licorice, prepared myrrh, each 6 parts.
[0054] The bone and muscle tablets are prepared by the following method: taking the above 25 medicinal materials, adding mistletoe, ephedra, epimedium, dipsacus, liquorice, acanthopanax, phellodendron, drynaria, earthworm, cyperus, radix achyranthis Bidentatae, rhizoma dioscoreae, cyperus rotundus and black plum into water and boiling for three times, the first time for 2 hours; the second and third times for 1 hour each, combining the decoctions, filtering, and concentrating the filtrate to 50°C to obtain a clear paste with a relative density of 1.25-1.30, which is set aside; the remaining 12 medicinal materials are crushed into fine powder, mixed with the above clear paste, dried below 80°C, crushed, made into granules, pressed into tablets, and coated with sugar or film.
[0055] Effect embodiment:
[0056] Effect Example 1: Comparison of acute toxicity of the tendon and bone tablets of the present invention (Example) and Wantong tendon and bone tablets (Comparative Example)
[0057] 240 SPF-grade SD male rats, weighing 180 ± 220 g, were purchased from Changchun Yisi Experimental Animal Technology Co., Ltd. After 7 days of adaptive feeding, the rats were randomly divided into two large groups: the example group (Group S) and the comparative example group (Group D). Each large group was further divided into 6 small groups (Groups G1, G2, G3, G4, G5, and G6), with 20 rats in each group.
[0058] The experimental animals were fasted for 12 hours before administration, but had free access to water. On the first day, each group of rats was administered once according to the experimental protocol, and then the mortality of the rats was observed and recorded every day for 14 consecutive days, and the LD50 of the examples and comparative examples was calculated using the modified Coulter method.
[0059] Modified Kouts method calculation formula: LogLD 50 =x K-i ×(∑p-0.5), where X k : maximum dose logarithm value, i: difference between two adjacent dose logarithm values.
[0060] The experimental results of the comparative example group and the embodiment group are shown in Table 1 and Table 2, respectively.
[0061] Table 1: Acute toxicity test of rats in the comparative group (Wantong Jingu Tablets) (14 days)
[0062]
[0063] The LogLD of the comparative group (Wantong Jingu Tablets) was calculated to be 50 =1.5-0.3×(2.85-0.5)=0.795
[0064] Table 2: Acute toxicity test (14 days) of rats in the Example group (Jingu tablets of the present invention)
[0065]
[0066] The LogLD of the Example Group (Skeletons and Bones Tablets of the Present Invention) was calculated to be50 = 1.5 - 0.3 x (1.55 - 0.5) = 1.185
[0067] It can be seen that under the same experimental conditions, the mortality of the rats in the example group is significantly lower than that of the rats in the comparative example group, and the LogLD 50 of the rats in the example group is significantly higher than that of the rats in the comparative example group. The above results show that the safety of the Jingu Tablet of the present application is significantly higher than that of the Wantong Jingu Tablet.
[0068] Effect Example 2: Effect of the Tendon and Bone Tablets of the Present Invention (Example) and the Wantong Tendon and Bone Tablets (Comparative Example) on Type II Collagen-Induced Arthritis Comparison of therapeutic effects in rats
[0069] 2.1 Experimental drugs:
[0070] The example (Jingu Tablet of the present application) and the comparative example (Wantong Jingu Tablet) prepared in the preparation example part above.
[0071] The bovine type II collagen was dissolved in 0.1 mol / L acetic acid to a concentration of 10 mg / mL, stirred at 4°C to fully dissolve, and placed at 4°C overnight. The high-pressure sterilized liquid paraffin was heated to 70°C, and the inactivated attenuated BCG was added to the liquid paraffin to a concentration of 10 mg / mL, and fully ground to completely dissolve, as a complete adjuvant.
[0072] 2.2 Experimental animals:
[0073] 40 SPF male SD rats weighing 180±220 g were purchased from Changchun Yisi Experimental Animal Technology Co., Ltd. After the rats were adaptively fed for 7 days, they were randomly divided into a blank group, a model group, an example group, and a comparative example group.
[0074] The joint volume of the right hind foot of all rats was determined by the water volume method, and recorded as the volume before inflammation. The bovine type II collagen acetic acid solution with a concentration of 10 mg / mL was mixed with the complete adjuvant in equal volume to emulsify, to obtain a suspension, which was intradermally injected into the metatarsal pad of the right hind foot of the rats in the model group, the example group, and the comparative example group, with an injection amount of 0.1 mL. After 7 days, the rats were reinforcedly injected once at the tail root, wherein the blank group was injected with 0.1 mL of high-pressure sterilized liquid paraffin.
[0075] Four hours after the injection of bovine type II collagen, rats were gavaged with a suspension obtained by crushing the corresponding tablets and adding purified water. The gavage volume was 1 mL / 100 g body weight, and the gavage volume was 3.0 g of crude drug / kg body weight. The model group was gavaged with 1 mL / 100 g body weight of purified water. The blank group was raised normally. The gavage was continued for 5 weeks, twice a day. On the 7th, 21st, and 35th day, the right hind paw joint volume of the rats was measured using the water volumetric method. The rat right hind paw joint swelling rate (%) and the rat paw joint swelling inhibition rate were calculated. Rats in the model group, the example group, and the comparative example group whose right hind paw joint swelling rate (%) was less than that of the blank group were eliminated during the experiment. The specific experimental results are shown in Tables 4-5, where:
[0076] Swelling rate of rat right hind paw joint (%) = (joint volume after inflammation - joint volume before inflammation) / joint volume before inflammation × 100%;
[0077] The inhibition rate of rat foot joint swelling (%) = (foot joint volume of model group - foot joint volume of experimental group) / foot joint volume of model group × 100%.
[0078] 2.3 Experimental results:
[0079] The data were analyzed using the multivariate analysis of variance module of the statistical software SPSS, and P < 0.05 indicated that the difference was statistically significant.
[0080] Table 3: Effects of the Example Group (Tendon Tablets of the Present Invention) and the Comparative Example Group (Wantong Tendon Tablets) on the Foot Joint Volume of Rats with Type II Collagen-Induced Arthritis
[0081] Group Sample size Day 7 Day 21 Day 35 Blank group 10 1.08±0.05 1.13±0.12 1.17±0.13 Model Group 10 1.78±0.35 2.74±0.51 3.62±0.48 Example Group 10 <![CDATA[1.15±0.11 ** ]]> <![CDATA[1.24±0.16 ** ]]> 1.29 ± 0.15 **,# ]] Comparative group 10 <![CDATA[1.25±0.28 ** ]]> <![CDATA[1.43±0.24 ** ]]> <![CDATA[1.57±0.31 ** ]]>
[0082] Note: Compared with the model group: ** p<0.01; compared with the control group: # p<0.05.
[0083] Table 4: Inhibition rate of the embodiment group (muscle and bone tablets of the present invention) and the comparative example group (Wantong muscle and bone tablets) on foot joint swelling in rats with arthritis induced by type II collagen
[0084] Group Sample size Day 7 Day 21 Day 35 Example Group 10 35.39％ 54.74％ 92.34％ Comparative group 10 29.77％ 47.81％ 56.63％
[0085] The experimental results in Tables 3 and 4 show that the foot joint volume of the rats in the model group that received intradermal injection of bovine type II collagen into the plantar pad of the right hind foot of rats was significantly increased compared with the blank group, proving that the method of intradermal injection of bovine type II collagen into the plantar pad of the right hind foot of rats can be used to model rheumatoid arthritis rats.
[0086] The experimental results showed that the right foot joint volume of rats in the embodiment group and the comparative example group was significantly reduced compared with that in the model group ( **p<0.01), and the rat foot joint volume in the Example group was smaller than that in the Comparative Example group (the experimental results on the 35th day in Table 3 showed a significant difference between the two groups. # This indicates that the effect of the embodiment of the present invention (the tendon and bone tablet of the present invention) in treating rheumatoid arthritis is significantly better than that of the comparative example (Wantong tendon and bone tablet).
[0087] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.
Claims
1. A bone and tendon tablet with reduced toxic and side effects, characterized in that: The tendon and bone tablets are prepared from the following Chinese medicinal raw materials: processed Chuanwu, Epimedium, Guanzhong, Deer Antler, Asarum, Safflower, Earthworm, Drynaria fortunei, Red Ginseng, processed Kusnezoffii, Achyranthes bidentata, Phellodendron chinense, Dipsacus asper, Ephedra, Acanthopanax senticosus, Morus alba, Radix Aconiti Lateralis Preparata, processed Strychnos nux vomica, Notopterygium wilfordii, Snakehead aconite, Prunus mume, Cinnamomum cassia, Honeysuckle, Licorice and prepared Myrrh. In the preparation method of the tendon and bone tablets, the two Chinese medicinal raw materials, processed Chuanwu and processed Kusnezoffii, are first extracted with an organic solvent, the extracts are dried and crushed to prepare enteric-coated microspheres, and then the extracts are prepared together with other raw materials to prepare the tendon and bone tablets.
2. The tendon and bone piece according to claim 1, wherein: The bone and tendon tablets are prepared from the following Chinese medicinal raw materials in parts by weight: 1-6 parts, 1-10 parts, 1-10 parts, 1-4 parts, 1-3 parts, 1-6 parts, 1-6 parts, 1-6 parts, and 1-6 parts of processed Chuanwu, Epimedium, Cyperus, Deer Antler, Asarum, Safflower, Earthworm, Drynaria fortunei, and red ginseng respectively; 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, and 1-6 parts of processed Kusnezoffii, Achyranthes bidentata, Phellodendron chinense, Dipsacus asper, Ephedra, Acanthopanax senticosus, Morus alba, and Radix Glehniae are respectively; 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, 1-6 parts, and 1-6 parts of processed Nux vomica, Notopterygium wilfordii, Snakehead serpentis, Plum, Cassia twig, Honeysuckle, Licorice, and processed Myrrh are respectively.
3. The tendon-bone piece according to claim 2, characterized in that: The bone and tendon tablets are prepared from the following Chinese medicinal raw materials in parts by weight: 4-6 parts, 5-9 parts, 5-9 parts, 2-4 parts, 1-3 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, and 4-6 parts of processed Chuanwu, Epimedium, Cyperus, Deer Antler, Asarum, Safflower, Earthworm, Drynaria fortunei, and red ginseng respectively; 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, and 4-6 parts of processed Kusnezoffii, Achyranthes bidentata, Phellodendron chinense, Dipsacus asper, Ephedra, Acanthopanax senticosus, Morus alba, and Radix Glehniae are respectively; 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, 4-6 parts, and 4-6 parts of processed Nux vomica, Notopterygium wilfordii, Snakehead serpentis, Plum, Cassia twig, Honeysuckle, Licorice, and processed Myrrh are respectively.
4. The method for preparing the tendon and bone tablet according to any one of claims 1 to 3, characterized in that: The preparation method comprises the following steps: taking the above 25 medicinal materials, first extracting the two Chinese medicinal raw materials of Chuanwu and Caowu with an organic solvent, drying and crushing the extract to prepare enteric-coated microspheres for later use; decocting mistletoe, ephedra, epimedium, dipsacus root, liquorice, acanthopanax, phellodendron chinense, drynaria root, earthworm, cyperus rotundus, radix achyranthis Bidentatae, rhizoma dioscoreae, cyperus rotundus and plum blossoms with water for three times, combining the decoctions, filtering, and concentrating the filtrate to 50° C. to obtain a clear paste with a relative density of 1.25-1.30, for later use; crushing the remaining medicinal ingredients into fine powder, mixing the powder with the enteric-coated microspheres and the clear paste, drying below 60° C., crushing the powder into granules, pressing the granules into tablets, and coating the tablets with sugar or film.
5. The preparation method according to claim 4, characterized in that: In the preparation method, the extraction method of processed Chuanwu and processed Caowu is to add an organic solvent to the processed Chuanwu and processed Caowu, reflux extraction for 1-3 hours, collect the extract, then add the organic solvent to the filter residue, reflux extraction for 1-3 hours, combine the two extracts, recover the organic solvent, and concentrate the extract until the relative density measured at 60-80°C is 1.20-1.30 to obtain an extract concentrate, and then dry and crush the extract concentrate.
6. The preparation method according to claim 4 or claim 5, characterized in that: The organic solvent is methanol, ethanol, n-propanol, isopropanol, n-butanol or isobutanol.
7. The preparation method according to claim 5, characterized in that: The preparation method of enteric-coated microspheres containing processed Chuanwu and processed Caowu is as follows: the extract concentrate prepared in claim 5 is dried and crushed into 80-mesh fine powder, which is then mixed with an appropriate amount of microcrystalline cellulose and lauryl magnesium sulfate, extruded and dried to obtain a spherical core, an appropriate amount of cross-linked polyvinylpyrrolidone and chitosan are mixed to prepare a coating liquid, the coating liquid is evenly sprayed onto the spherical core in a coating pan, and granules are obtained after drying, an acrylic resin is prepared into a coating liquid, the coating liquid is sprayed onto the granules in a coating pan, and the enteric-coated microspheres are obtained after drying.
8. Use of the Jingu tablet according to any one of claims 1 to 3 or the Jingu tablet prepared by the preparation method according to any one of claims 4 to 7 in the preparation of a medicine having the effects of dispelling wind, dispersing cold, unblocking meridians and relieving pain.
9. The use according to claim 8, characterized in that: The medicine is used for arthritis, low back pain, muscle and joint pain, flexion and extension problems, as well as frozen shoulder, cervical spondylosis, rheumatoid arthritis and rheumatoid arthritis with the above symptoms.