Carbon medicine with effects of resisting gouty arthritis and reducing uric acid

Abstract

The invention discloses a charcoal medicine with gouty arthritis resisting and uric acid reducing effects, belongs to the technical field of medicines, and particularly relates to a novel application of monkshood charcoal in preparation of a medicine for resisting gouty arthritis or reducing uric acid. Animal pharmacological experiments show that monkshood charcoal has a definite improvement effect on gouty arthritis symptoms, has anti-inflammatory and analgesic effects, and can effectively reduce the serum uric acid level.

Description

Technical Field

[0001] The invention relates to the medical field, and in particular to a new use of aconite charcoal in the medical field. Background Art

[0002] Gouty arthritis is a disease caused by elevated blood uric acid, with clinical manifestations of redness, swelling, heat and pain in the joints of the limbs. The incidence rate is increasing year by year, and the quality of life of patients is seriously reduced after the onset of the disease. Hyperuricemia is an important prerequisite for gouty arthritis. Modern medicine cannot cure gouty arthritis. Commonly used drugs in the acute phase are colchicine, nonsteroidal anti-inflammatory drugs and glucocorticoids; uric acid-lowering treatment is often used in the chronic phase. The current treatment plans all have the disadvantage of large side effects. Therefore, the demand for more effective and safe drugs in clinical practice is very urgent.

[0003] Aconite is a processed product of the root of Aconitum carmichaelii Debx, a plant of the Ranunculaceae family. Aconite is pungent in taste and warm in nature. It has the effects of restoring yang and rescuing adverse conditions, dispelling cold and relieving pain. It can break up tumors, disperse blood stasis, and eliminate accumulation. It is widely used in the treatment of various diseases. According to literature records, the processed Aconite has the effects of dispelling cold and relieving pain, warming yang, and can be used to treat body pain caused by cold evil.

[0004] Whether Aconite Carbonate has the effect of anti-gouty arthritis has not been reported in modern research. Summary of the invention

[0005] In view of this, the object of the present invention is to provide a safe and efficient Chinese herbal charcoal medicine for anti-gouty arthritis, so that it can be used alone or in combination with aconite charcoal as the main component in clinical practice.

[0006] Specifically, the present invention is achieved by using aconite carbon in the preparation of a drug for anti-gouty arthritis or uric acid lowering, and the preparation of aconite carbon comprises the following steps:

[0007] Put the aconite raw medicine slices into a crucible, wrap and seal the crucible mouth with tin foil, cover the crucible with a lid, put it into a muffle furnace and set a certain temperature for firing.

[0008] The invention provides a new use of aconite charcoal with effective therapeutic effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 .Effect of Aconite Carbonate on the clinical symptoms of gouty arthritis in rats. Figure 1 A. Arthritis index; Figure 1 B. Appearance of ankle joint 48 hours after modeling; Figure 1 C. Ankle joint swelling

[0010] Figure 2. Pathological damage sections of ankle joint tissues of rats with gouty arthritis treated with Aconite charcoal. Representative images of H&E-stained ankle synovial tissue sections (scale bar = 100 μm).

[0011] Figure 3 .Effect of Aconite Carbonate on the levels of serum inflammatory factors in rats with gouty arthritis. Figure 3 A: tumor necrosis factor α (TNF-α); Figure 3 B: interleukin-1β (IL-1β); Figure 3 C: interleukin-6 (IL-6); Figure 3 D: interleukin-8 (IL-8); Figure 3 E: C-reactive protein (CRP); Figure 3 F: Prostaglandin E2 (PGE2).

[0012] Figure 4 Effect of Fuzi carbonized on the expression of TLR2 / 4-NF-κB protein pathway in ankle synovial tissue of rats with gouty arthritis. The distribution and expression of TLR2, TLR4, MyD88 and NF-κB proteins were determined. DETAILED DESCRIPTION

[0013] The technical solution of the present invention will be clearly and completely described below in conjunction with specific embodiments, but the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0014] Embodiment 1: a method for preparing aconite charcoal (calcination method), comprising the following steps:

[0015] Put the aconite pieces into a crucible, cover the crucible mouth with aluminum foil, cover the lid tightly, and put it in a muffle furnace for carbonization (calcination temperature 400℃, time 1h). The obtained aconite charcoal is black inside and outside and has a uniform texture.

[0016] Example 2: Study on the effect of Aconite Carbon in treating gouty arthritis

[0017] 1. Experimental Animals

[0018] In this experiment, SPF male SD rats weighing (200.0±10.0) g were used as experimental subjects and were adaptively raised at a temperature of (24.0±1.0)°C and a relative humidity of 55-65% for 7 days. During this period, the animals were guaranteed to have free access to water and food.

[0019] 2. Drug administration, modeling and sampling of experimental animals

[0020] The experimental animals were divided into control group, model group, positive drug (loxoprofen sodium tablets) group, and aconite charcoal treatment group (high, medium, and low doses) according to the random number table, with a total of 6 groups, 6 in each group. Each group was given equal volumes of normal saline and aconite charcoal decoction on the first day of the experiment, and the administration method was oral administration. The administration was continued for 3 days. One hour after the administration on the third day, the control group was injected with 0.2ml of normal saline into the right ankle joint, and the rats in the other groups were injected with 0.2ml of 2.5% sodium urate suspension (2.5g / 100ml) into the right ankle joint for modeling. The mental state, hair state, activity, body weight, diet, and bowel movements of the rats in each group before and after modeling were recorded, and a preliminary comparative study was conducted. The arthritis index of the rats was evaluated at 1h, 6h, 12h, and 24h after the modeling injection.

[0021] The diameter of the test joints was measured with a vernier caliper before modeling and 1h, 6h, 12h, and 24h after injection, and the joint swelling index was calculated. The changes in the appearance and diameter of the joints of the test rats before and after modeling and after treatment were observed. 48h after modeling, the rats were anesthetized and blood was collected from the abdominal aorta. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP), and prostaglandin E2 (PGE2) in the serum were detected by ELISA. The pathological morphology of the ankle joints of rats was observed by H&E sections. The expression of TLR2 / 4-NF-κB protein pathway in the synovial tissue of the ankle joints of rats was detected by immunohistochemistry.

[0022] 3. Evaluation of the therapeutic effect of Aconite Carbonate on rats with gouty arthritis

[0023] Figure 1 A shows the evaluation of the arthritis swelling index of the right ankle joint of the rat after MSU ankle joint injection. Compared with the model group, the arthritis index of the positive drug group and the different doses of Fuzi carbon treatment groups were reduced. The ankle swelling level of the Fuzi carbon high-dose group was significantly lower than that of the model group at 1h, 6h, 12h, 24h, and 48h after modeling, and the ankle swelling level of the Fuzi carbon medium-dose group was also significantly lower than that of the model group at 6h, 12h, 24h, and 48h after modeling. Figure 1 B shows the appearance of the ankle joint of rats 48 hours after modeling. 48 hours after modeling, compared with the model group, the swelling of the ankle joints in the positive drug group and the different doses of Fuzi carbon treatment groups were alleviated. Among them, the positive drug and Fuzi carbon high and medium dose groups had a more obvious effect on the alleviation of ankle swelling. Figure 1C shows the degree of ankle swelling in rats with gouty arthritis. After MSU ankle joint injection modeling, the ankle swelling of each dose group of Fuzi carbon was reduced to the lowest after 48 hours, and the high-dose group showed a therapeutic effect similar to that of the positive drug. The ankle swelling level of the high-dose group was significantly lower than that of the model group at 1h, 6h, 12h, 24h, and 48h after modeling, and the ankle swelling level of the medium-dose group was also significantly lower than that of the model group at 1h, 6h, 12h, 24h, and 48h after modeling.

[0024] In order to quantify the extent of gouty arthritis-induced synovial pathological damage in the ankle joints of each group of rats, we observed the H&E-stained sections ( Figure 2 ). The synovial surface of the ankle joint of the rats in the control group was smooth and flat, with a single layer of synovial cells with good morphology and neat arrangement. There was no inflammatory cell infiltration, and it was in a normal state. After MSU injection modeling, the synovial surface of the ankle joint of the model group was rough and uneven, and obvious swelling, congestion and hypertrophy were observed. The synovial cells changed from a single layer to a multilayer, and the proliferation was active. A large number of inflammatory cell infiltrations were observed. Compared with the model group, the degree of inflammatory cell infiltration and synovial swelling and hyperplasia in the positive drug group and the high, medium and low dose groups of Aconite Carbon were all reduced. The use of Aconite Carbon can reduce the pathological damage of the ankle synovium caused by MSU-induced gouty arthritis.

[0025] 4. Effect of Aconite Carbonate on Serum Inflammatory Factors in Rats with Gouty Arthritis

[0026] Studies have shown that inflammatory factors play a very important role in the occurrence and development of gouty arthritis. In view of the inflammatory cell infiltration in pathological sections, the infiltration of inflammatory cells in serum was further evaluated by the level of inflammatory factors. Combined with previous related studies, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), C-reactive protein (CRP), and prostaglandin E2 (PGE2) were selected for detection. Figure 3 The results showed that after MSU ankle joint injection, the levels of TNF-α, IL-1β, IL-6, IL-8, CRP, and PGE2 in the serum of the model group were significantly higher than those of the control group. Based on the above findings, we believe that Fuzi carbon has a protective effect on gouty arthritis in reducing inflammatory infiltration.

[0027] 5. Effect of Aconite Carbon on the Expression of TLR2 / 4-NF-κB Protein Pathway in Ankle Synovial Tissue of Rats with Gouty Arthritis

[0028] To determine whether there is a difference in the expression of the TLR2 / 4-NF-κB protein pathway in the gouty arthritis rat model, this section performed immunohistochemical analysis to detect several key pathway proteins in the extracted ankle synovial tissue ( Figure 4). The results showed that compared with the model group, the levels of TLR2, TLR4 and MyD88NF-κB proteins in the positive drug group and the high and medium dose groups of Fuzi carbon were significantly downregulated. Fuzi carbon can significantly inhibit the expression of TLR2 and TLR4 proteins in the synovium of rats with acute gout, and can also significantly antagonize the expression of NF-κB in the synovium. This indicates that Fuzi carbon can inhibit the activation of NF-κB by weakening the recognition and internalization of TLR4 in the inflammatory response and blocking the intracellular transduction of MyD88 connection.

Claims

1. Use of aconite charcoal in the preparation of anti-gouty arthritis or uric acid-lowering drugs.

2. The use according to claim 1, characterized in that The aconite charcoal is used alone.

3. The use according to claim 1, characterized in that It is used mainly with aconite charcoal.

4. The use according to claim 1, characterized in that The aconite charcoal and pharmaceutically acceptable auxiliary materials are prepared into a clinical preparation.

5. The use according to claim 4, characterized in that The clinical preparations include, but are not limited to, injections, oral preparations, external preparations, and various dosage forms for intracavitary administration.

6. A method for preparing the aconite charcoal according to any one of claims 1 to 5, characterized in that: The aconite root is prepared by charcoal calcination method.

7. The preparation method according to claim 6, characterized in that: The preparation method comprises the following steps: taking the aconite root medicinal pieces, sealing them, adopting a calcination method, and setting a certain temperature for firing.

8. The preparation method according to claim 6, characterized in that: The preparation method comprises the following steps: sealing the aconite raw medicinal slices and placing them in a muffle furnace for carbonization (calcination temperature is 400° C. and time is 1 hour).

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