Application of tripterygium glycosides tablets in improving central sensitization pain

Abstract

The invention relates to application of tripterygium glycosides tablets to improvement of central sensitization pain. The invention provides application of a tripterygium glycoside tablet in preparation of a product. The product is used for preventing or treating central sensitization pain. Based on animal experiment verification, the inventor of the invention finds that the tripterygium glycoside tablet can be used for treating the central sensitization type pain, and a new treatment means is provided for the central sensitization type pain.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and more specifically, to the use of Tripterygium glycosides tablets in improving central sensitization pain. Background Art

[0002] Central sensitization refers to the situation where, under long-term or repeated pain stimuli, the nervous system in the spinal cord and brain becomes more sensitive, resulting in even a slight stimulus being misinterpreted as a pain signal. Simply put, it means that the pain perception threshold is reduced, and the same stimulus may trigger a stronger pain sensation. Central sensitization pain (CSP) is a pain state caused by abnormal processing of pain signals by the central nervous system. It usually manifests as an enhanced perception of pain and may not have obvious external injuries or primary lesions. This phenomenon can occur in various pain symptoms, especially in patients with chronic pain.

[0003] Therefore, there is an urgent need for a new means of treating or preventing central sensitization pain. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art to some extent. For this reason, an object of the present invention is to provide a means that can be effectively used for treating or preventing central sensitization pain.

[0005] Therefore, in the first aspect of the present invention, there is provided the use of Tripterygium glycosides tablets in the preparation of a product for preventing or treating central sensitization pain. The inventors of the present invention have proven through a large number of experiments that central sensitization pain is induced using a chronic inflammation model, and based on animal experiments, the effectiveness of the candidate drug Tripterygium glycosides tablets is evaluated, and it is found that it can effectively improve central sensitization pain.

[0006] According to the embodiments of the present invention, the use may further include at least one of the following additional technical features:

[0007] According to the embodiments of the present invention, the product is a drug or a pharmaceutical preparation.

[0008] According to the embodiments of the present invention, the central sensitization pain is induced by central inflammation or chronic inflammatory pain.

[0009] According to the embodiments of the present invention, the drug or the pharmaceutical preparation is an oral preparation.

[0010] According to the embodiments of the present invention, the oral preparation is a tablet, a capsule, a pill, a granule, a decoction, an oral liquid, a dropping pill or a syrup.

[0011] According to an embodiment of the present invention, the therapeutically effective amount of Tripterygium glycosides tablets is 1 mg / kg - 1.5 mg / kg.

[0012] In a second aspect of the present invention, the present invention provides a pharmaceutical composition. According to an embodiment of the present invention, the pharmaceutical composition comprises: Tripterygium glycosides tablets. The inventors of the present invention have verified through a large number of experiments that Tripterygium glycosides tablets can effectively treat central sensitization-like pain. Thus, the pharmaceutical composition of the present invention can also effectively treat central sensitization-like pain.

[0013] According to an embodiment of the present invention, the pharmaceutical composition may further comprise at least one of the following additional technical features:

[0014] According to an embodiment of the present invention, it further comprises a pharmaceutically acceptable excipient or carrier.

[0015] According to an embodiment of the present invention, the pharmaceutical composition is an oral preparation.

[0016] According to an embodiment of the present invention, the oral preparation is a tablet, capsule, pill, granule, decoction, oral liquid, dripping pill or syrup.

[0017] In a third aspect of the present invention, the present invention provides the use of the pharmaceutical composition described in the second aspect in the preparation of a drug for preventing or treating central sensitization-like pain. The inventors of the present invention have verified through a large number of experiments that Tripterygium glycosides tablets can effectively treat central sensitization-like pain. Thus, the pharmaceutical composition of the present invention can also effectively treat central sensitization-like pain.

[0018] According to an embodiment of the present invention, the central sensitization-like pain is induced by central inflammation or chronic inflammatory pain.

[0019] Additional aspects and advantages of the present invention will be given in part in the following description, become apparent in part from the following description, or be learned through the practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The above and / or additional aspects and advantages of the present invention will become apparent and be readily understood from the following description of the embodiments in conjunction with the accompanying drawings, wherein:

[0021] Figure 1 shows the changes in various indicators of mice eight weeks after injection of CFA according to an embodiment of the present invention, wherein:

[0022] A shows the change in mechanical pain threshold of mice eight weeks after plantar injection of CFA. At the eighth week, the mechanical pain threshold was still lower than that before injection, with a significant difference (*p < 0.05, n = 10);

[0023] B shows the change in thermal pain threshold of mice at 8 weeks after plantar injection of CFA. At the 8th week, the thermal pain threshold was still lower than that before injection, with significant difference (***p<0.001, n = 10);

[0024] C shows the change in plantar thickness of mice at 8 weeks after plantar injection of CFA. At the 8th week, the plantar thickness recovered to the thickness before injection (***p<0.001, n = 10);

[0025] Figure 2 is the change in plantar thickness of mice on the first day and the 56th day after plantar injection of CFA according to the embodiments of the present invention;

[0026] Figure 3 is the result of qPCR detection of inflammatory factors IL-1β, IL-6 and TNF-α in the paw tissues of control group mice, mice on the first day after plantar injection of CFA and mice on the 56th day after plantar injection of CFA according to the embodiments of the present invention. There were significant differences between the first day group and the control group and the 56th day group (***p<0.001);

[0027] Figure 4 is the result of qPCR detection of inflammatory factors IL-1β, IL-6 and TNF-α in the sera of control group mice and mice on the 56th day after plantar injection of CFA according to the embodiments of the present invention, and there were no significant differences;

[0028] Figure 5 is the change in each index of mice treated with tripterygium glycosides tablets (TG) according to the embodiments of the present invention, where:

[0029] A is the mechanical pain threshold of each group before treatment, and there were significant differences between the other four groups and the control group (***p<0.001);

[0030] B is that after one week of treatment, the mechanical pain thresholds of the three treatment groups with different doses were significantly different from those of the CSP group (***p<0.001);

[0031] C is that after two weeks of treatment, the mechanical pain thresholds of the three treatment groups with different doses were significantly different from those of the CSP group (***p<0.001);

[0032] D is the change in mechanical pain threshold of each mouse in the TG 6.0mg / kg dose group before drug administration, one week after drug administration and two weeks after drug administration (***p<0.001);

[0033] E is the change in mechanical pain threshold of each mouse in the TG 12.0mg / kg dose group before drug administration, one week after drug administration and two weeks after drug administration (***p<0.001);

[0034] Group F shows the changes in mechanical pain thresholds of each mouse before drug administration, one week after drug administration, and two weeks after drug administration at a dose of 24.0 mg / kg of TG (***p < 0.001);

[0035] Group G shows the thermal thresholds of each group before treatment, and there are significant differences between the other four groups and the control group (***p < 0.001);

[0036] Group H shows that after one week of treatment, the thermal thresholds of the three treatment groups with different doses are significantly different from those of the CSP group (**p < 0.01, ***p < 0.001);

[0037] Group I shows that after two weeks of treatment, the thermal thresholds of the three treatment groups with different doses are significantly different from those of the CSP group (**p < 0.01, ***p < 0.001);

[0038] Group J shows the changes in thermal pain thresholds of each mouse before drug administration, one week after drug administration, and two weeks after drug administration at a dose of 6.0 mg / kg of TG (**p < 0.01);

[0039] Group K shows the changes in thermal pain thresholds of each mouse before drug administration, one week after drug administration, and two weeks after drug administration at a dose of 12.0 mg / kg of TG (***p < 0.001);

[0040] Group L shows the changes in thermal pain thresholds of each mouse before drug administration, one week after drug administration, and two weeks after drug administration at a dose of 24.0 mg / kg of TG (**p < 0.01, ***p < 0.001). Detailed implementation manners

[0041] Unless otherwise specified or there is an obvious conflict in the context, the articles "a", "an", and "the" used in this article are intended to include "at least one" or "one or more". Therefore, these articles used in this article refer to articles for one or more (i.e., at least one) objects. For example, "a component" refers to one or more components, that is, there may be more than one component considered to be adopted or used in the implementation manners of the described embodiments.

[0042] In this article, the term "comprising" or "including" is an open expression, that is, it includes the content specified by the present invention, but does not exclude other aspects of the content.

[0043] In this article, the terms "optionally", "optional", or "option" generally mean that the subsequent events or conditions may but do not necessarily occur, and this description includes the cases where the events or conditions occur, as well as the cases where the events or conditions do not occur.

[0044] As used herein, the term "prevention" means not causing the worsening of a disease, disorder, symptom or manifestation or severity. Thus, the presently disclosed Tripterygium glycosides tablets can be administered prophylactically to prevent or reduce the occurrence or recurrence of the disease or disorder.

[0045] As used herein, the term "treatment" of any disease or disorder means all that can slow down, interrupt, stop, control or halt the progression of the disease or disorder, but does not necessarily mean that all symptoms of the disease or disorder disappear. It also includes prophylactic treatment of the symptoms, especially in patients prone to such diseases or disorders. In some of these embodiments, it refers to improving the disease or disorder (i.e., slowing down or stopping or alleviating the development of the disease or at least one of its clinical symptoms). In other embodiments, "treatment" refers to alleviating or improving at least one physical parameter, including physical parameters that may not be perceptible to the patient. In other embodiments, "treatment" refers to modulating the disease or disorder physically (e.g., stabilizing perceptible symptoms) or physiologically (e.g., stabilizing physical parameters) or both. In other embodiments, "treatment" refers to preventing or delaying the onset, occurrence or worsening of the disease or disorder.

[0046] The clinical manifestations of central sensitization-like pain are as follows:

[0047] 1. Excessive pain response: Patients with central sensitization usually have a stronger pain response to mild touch, temperature changes or non-painful stimuli (such as pressure).

[0048] 2. Pain spread: The local pain area may spread to the surrounding area, forming "radiating" pain.

[0049] 3. Pain mismatch: In some cases, the intensity of pain may not be proportional to the actual degree of tissue damage. That is to say, the patient may feel extremely strong pain, but after imaging examination, no obvious physical damage or lesion is found.

[0050] 4. Chronic pain: Central sensitization is often associated with chronic pain (such as fibromyalgia, chronic headache, etc.), and patients are in a state of persistent or intermittent pain for a long time.

[0051] The goal of treating central sensitization-like pain is to relieve pain, restore the normal function of the nervous system, and improve the quality of life of patients. Currently, the treatment methods for central sensitization-like pain include: 1) Pharmacological treatment: antidepressants (such as tricyclic antidepressants or SSRIs), antiepileptic drugs (such as gabapentin or pregabalin), non-steroidal anti-inflammatory drugs (NSAIDs), and analgesics; 2) Physical therapy: including physiotherapy, massage, traction, etc., to relax muscles, improve joint mobility, and reduce muscle hypertonicity; 3) Cognitive behavioral therapy (CBT): to help patients change their cognitive and emotional responses to pain, reduce anxiety and depression caused by pain, and relieve symptoms; 4) Neuromodulation techniques: such as transcutaneous electrical nerve stimulation (TENS) or spinal cord stimulation (SCS), which regulate pain signals by electrically stimulating the nervous system.

[0052] However, the above-mentioned drugs have one or more of the following side effects: such as drowsiness, tremors, inattention, mood depression, thinking disorders, confusion, anxiety, hallucinations and delusions, rashes, urticaria, anaphylactic shock, etc. Therefore, there is an urgent need for a new drug to improve central sensitization-like pain.

[0053] The present invention proposes a new use of Tripterygium glycosides tablets, a pharmaceutical composition and its use, which will be described in detail below respectively.

[0054] New use of Tripterygium glycosides tablets

[0055] In one aspect of the present invention, the present invention proposes a new use of Tripterygium glycosides tablets, that is, the use of Tripterygium glycosides tablets in the preparation of a product for preventing or treating central sensitization-like pain. The inventors of the present invention have proven through a large number of experiments that central sensitization-like pain is induced using a chronic inflammation model, and based on animal experiments, the effectiveness of the candidate drug Tripterygium glycosides tablets is evaluated, and it is found that it can effectively improve central sensitization-like pain.

[0056] In some embodiments of the present invention, the product is a drug or a pharmaceutical preparation.

[0057] As used herein, the term "central sensitization-like pain" refers to symptoms caused by abnormal processing of pain signals by the central nervous system, usually manifested as abnormal sensitivity to pain, and may cause persistent pain without obvious external causes. According to the embodiments of the present invention, the central sensitization-like pain can be induced by central inflammation or chronic inflammatory pain.

[0058] In some embodiments of the present invention, the drug or pharmaceutical preparation is an oral preparation. The shape of the oral preparation is not particularly limited and can be any one of round, small capsules, doughnut, rectangular, etc.

[0059] In some embodiments of the present invention, the oral preparation can be a solid preparation or a liquid preparation.

[0060] In some embodiments of the present invention, the oral preparation is a tablet, a capsule, a pill, a granule, a decoction, an oral liquid, a dropping pill or a syrup.

[0061] For solid preparations, it can involve, for example, tablets, capsules, powders, granules, lozenges, etc.

[0062] Solid preparations can be coated with a coating agent and can have markings and letters for identification and further scoring for separation. Coating is carried out under the condition of adding conventional coating media and film-forming agents (generally collectively referred to as coating materials) familiar to those skilled in the art. Coating can be carried out using, for example, sugar coating matrices, water-soluble film coating matrices, enteric film coating matrices, sustained-release film coating matrices, etc. For sugar coating matrices, sucrose and a combination of one or more selected from the following substances can be used: talc, precipitated calcium carbonate, gelatin, gum arabic, amylopectin, carnauba wax, etc. For water-soluble film coating matrices, for example, cellulose polymers such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, methyl hydroxyethyl cellulose, etc.; synthetic polymers such as polyvinyl acetal diethylaminoethyl ester, aminoalkyl methacrylate copolymer E [Eudragit E (trade name)], polyvinylpyrrolidone, etc.; polysaccharides such as amylopectin, etc. can be used. For enteric film coating matrices, for example, cellulose polymers such as hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethyl ethyl cellulose, cellulose acetate phthalate, etc.; acrylic polymers such as methacrylic acid copolymer L [Eudragit L (trade name)], methacrylic acid copolymer LD [Eudragit L-30D55 (trade name)], methacrylic acid copolymer S [Eudragit S (trade name)], etc.; naturally occurring substances such as shellac, etc. can be used. For sustained-release film coating matrices, for example, cellulose polymers such as ethyl cellulose, cellulose acetate, etc.; acrylic polymers such as aminoalkyl methacrylate copolymer RS [Eudragit RS (trade name)], ethyl acrylate-methyl methacrylate copolymer suspension [Eudragit NE (trade name)], etc. can be used. Two or more of the above coating matrices can be mixed and used in a suitable ratio. Moreover, coating additives can also be used during coating. For coating additives, for example, light masking agents and / or coloring agents such as titanium oxide, talc, iron oxide, etc.; plasticizers such as polyethylene glycol, triethyl citrate, castor oil, polysorbate, etc.; organic acids such as citric acid, tartaric acid, malic acid, ascorbic acid, etc. can be used.

[0063] Solid dosage forms can be formulated for immediate release (i.e., rapid release) and / or modified release. Modified release formulations include delayed release, sustained release, pulsed release, controlled release, targeted release, and programmed release.

[0064] When the solid dosage form is a tablet, any pharmaceutically acceptable excipient commonly used in the preparation of solid dosage forms can be used. Tablets can be prepared by compression or molding, optionally using one or more physiologically acceptable / pharmaceutically acceptable excipients. Compressed tablets can also be prepared by compressing the active ingredient in a free-flowing form (such as powder or capsules) in a suitable machine, and the active ingredient is optionally mixed with binders, lubricants, fillers, solubilizers, or disintegrants. Molded tablets can be prepared by molding a mixture of a wetted powdery compound and an inert liquid dispersion medium in a suitable machine. Tablets can optionally be coated or scored and can be formulated to provide sustained release or controlled release of the active ingredient therein. The formulation of tablets is discussed in detail in "Pharmaceutical Dosage Forms: Tablets, Vol.1", by H. Lieberman and L. Lachman, Marcel Dekker, N.Y. 1980.

[0065] When the solid dosage form is a capsule, any conventional encapsulation is suitable, such as using the carriers mentioned above in hard gelatin capsules. When the composition is in the form of a soft gelatin capsule, any physiologically acceptable / pharmaceutically acceptable excipient commonly used in the preparation of dispersants or suspending agents can be considered, and the physiologically acceptable / pharmaceutically acceptable excipient is incorporated into the soft gelatin capsule.

[0066] For liquid dosage forms, it particularly refers to solutions, suspensions having solid particles dispersed in a liquid, emulsions having liquid droplets dispersed in a liquid, or syrups.

[0067] In some embodiments of the present invention, the therapeutically effective amount of the Tripterygium glycosides tablets is 1 mg / kg - 1.5 mg / kg. For example, it can be 1 mg / kg, 1.1 mg / kg, 1.2 mg / kg, 1.3 mg / kg, 1.4 mg / kg, 1.5 mg / kg, etc., or can be a range composed of any of the above arrays. Thus, the Tripterygium glycosides tablets can be effectively used for preventing or treating central sensitization-like pain.

[0068] It should be noted that the above "therapeutically effective amount" is related to the dosage. If each tablet contains 10 mg of Tripterygium glycosides, taking 1 mg / kg - 1.5 mg / kg per day according to body weight can achieve a therapeutic effect. For example, an adult weighing 60 kg needs to take 6 - 9 tablets per day to effectively prevent or treat central sensitization-like pain.

[0069] For a drug or a pharmacological active agent, the terms "effective dose", "effective amount" or "therapeutically effective amount" refer to a sufficient amount of the drug or agent that is non-toxic but can achieve the desired effect. For the oral dosage form in the present invention, the "effective amount" of the active substance in Tripterygium glycosides tablets is the amount required to achieve the desired effect. The determination of the effective amount varies from person to person, depending on the age and general condition of the recipient, and also depends on the specific active substance. In a specific case, the appropriate effective amount can be determined by those skilled in the art according to conventional tests.

[0070] Drug composition

[0071] In yet another aspect of the present invention, the present invention provides a drug composition. According to an embodiment of the present invention, the drug composition comprises: Tripterygium glycosides tablets. The inventors of the present invention have verified through a large number of experiments that Tripterygium glycosides tablets can effectively treat central sensitization-like pain. Thus, the drug composition of the present invention can also effectively treat central sensitization-like pain.

[0072] In some embodiments of the present invention, the drug composition further comprises a pharmaceutically acceptable excipient or carrier.

[0073] The term "pharmaceutically acceptable carrier" used in the present invention includes any solvent, dispersion medium, coating material, surfactant, antioxidant, preservative (such as antibacterial agent, antifungal agent), isotonic agent, salt, drug stabilizer, binder, excipient, dispersant, lubricant, sweetening agent, flavoring agent, coloring agent, or a combination thereof, which are known to those skilled in the art (as described in Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329). Except in cases where any conventional carrier is incompatible with the active ingredient, its use in a therapeutic or drug composition is covered.

[0074] The term "pharmaceutically acceptable excipient" used in the present invention can include any solvent, solid excipient, diluent or other liquid excipient, etc., suitable for a specific target dosage form. Except in the range where any conventional excipient is incompatible with the siRNA disclosed in the present application, such as any adverse biological effects produced or any interaction with any other component of the pharmaceutically acceptable composition in a harmful manner, their use is also within the scope contemplated by the present disclosure.

[0075] In some embodiments of the present invention, the drug composition is an oral preparation. The shape of the oral preparation is not particularly limited and can be any one of round, small capsule, doughnut, rectangular, etc.

[0076] In some embodiments of the present invention, the oral preparation can be a solid preparation or a liquid preparation.

[0077] In some embodiments of the present invention, the oral preparation is a tablet, a capsule, a pill, a granule, a decoction, an oral liquid, a dripping pill or a syrup.

[0078] In some embodiments of the present invention, the pharmaceutical composition can be conveniently presented in unit dosage form and can be prepared by any method known in the pharmaceutical field, so that a unit dosage can be administered to a subject. Preferably, the drug is in unit dosage form, such as a solid preparation in unit dosage form (such as a tablet, a powder, a dry suspension, a granule or a capsule). According to the embodiments of the present invention, each unit dosage contains 10-30 mg of the Tripterygium glycosides tablets. Thus, it is possible to effectively treat or prevent central sensitization-like pain after a single administration of the pharmaceutical composition.

[0079] Use

[0080] In another aspect of the present invention, the present invention provides the use of the aforementioned pharmaceutical composition in the preparation of a drug for preventing or treating central sensitization-like pain. The inventors of the present invention have verified through a large number of experiments that Tripterygium glycosides tablets can effectively treat central sensitization-like pain. Thus, the pharmaceutical composition of the present invention can also effectively treat central sensitization-like pain.

[0081] In some embodiments of the present invention, the central sensitization-like pain is induced by central inflammation or chronic inflammatory pain.

[0082] In another aspect of the present invention, the present invention provides a method for treating or preventing central sensitization-like pain. According to the embodiments of the present invention, the method includes: administering a therapeutically effective amount of Tripterygium glycosides tablets or the aforementioned pharmaceutical composition to a person suffering from or prone to central sensitization-like pain.

[0083] As used in the present invention, the term "therapeutically effective amount" or "therapeutically effective dose" refers to an amount that can elicit a biological or medical response in an individual (such as improving symptoms, alleviating the disease condition, slowing down or delaying the development of the disease, or preventing the disease, etc.).

[0084] The following will explain the solution of the present invention in combination with embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. For those not specified in the embodiments regarding specific techniques or conditions, they shall be carried out according to the techniques or conditions described in the literature in the art or according to the product specifications. For reagents or instruments not specified as to the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0085] Example 1: Construction of a central sensitization-like pain model

[0086] Common chronic inflammatory pain models include complete Freund's adjuvant (CFA), carrageenan, formalin model, etc. Among them, the CFA model is the most commonly used in the study of chronic inflammatory pain caused by arthritis. Therefore, in this example, C57BL / 6J mice were used to construct a CFA model, that is, an emulsion obtained by mixing 10 μL of CFA and normal saline at a ratio of 1:1 was subcutaneously injected into the plantar surface of the mice to establish a chronic inflammatory pain model. This model has a long disease cycle, a simple modeling protocol, and can exhibit abnormal thermal and mechanical pain for up to 8 weeks.

[0087] Example 2: Construction of a mouse model of central sensitization-like pain (CSP)

[0088] For the model mice 8 weeks after CFA injection, by measuring the mechanical pain threshold, hot plate pain threshold, changes in plantar thickness, as well as inflammatory factors in the paw tissue and inflammatory factors in the serum, to observe whether the model mice showed central sensitization-like pain. The experimental results are as Figure 1 shown. In the eighth week after CFA injection into the plantar surface of the mice, the mechanical pain threshold was still lower than that before injection ( Figure 1 A), and the hot pain threshold was still lower than that before injection ( Figure 1 B), but the plantar thickness recovered to the thickness before injection ( Figure 1 C and Figure 2 ). At the same time, qPCR was used to detect the expression levels of inflammatory factors IL-1β, IL-6, and TNF-α in the paw tissue, as well as inflammatory factors IL-1β, IL-6, and TNF-α in the serum. The results are as Figure 3 and Figure 4 shown. The inflammatory factors in the paw tissue and the inflammatory factors in the serum both returned to normal values. Therefore, these results indicate that the mice showed central sensitization-like pain, that is, a mouse model of central sensitization-like pain (CSP model) was successfully constructed.

[0089] Example 3: Improvement of central sensitization-like pain

[0090] After the model was successfully established, the model mice were divided into 4 groups, with 5 mice in each group. Each group of mice was intragastrically administered 0 mg / kg, 6 mg / kg, 12 mg / kg, and 24 mg / kg of tripterygium glycosides tablets respectively, and continuously intragastrically administered for 14 days for treatment. Behavioral experiments were used to detect whether tripterygium glycosides tablets had the effect of improving central sensitization-like pain. The experimental results are as Figure 5 shown. The mechanical pain threshold and thermal threshold of the mice in the CSP group and each dose group decreased, showing a significant difference from the control group, as Figure 5 A shown; after treatment with different concentrations of tripterygium glycosides tablets for 7 days, compared with the CSP group, the mechanical pain threshold and thermal threshold of the mice in each dose group were significantly increased, showing a significant difference from the CSP group, as shown in Figure 5as shown in Figures B and 5H; after treating with different concentrations of celastrol for 14 days, compared with the CSP group, the mechanical pain threshold and thermal threshold of mice in each dose group were significantly increased, showing significant differences from the CSP group, as shown in Figure 5 Figures C and 5I respectively. Therefore, it shows that tripterygium glycosides tablets can significantly increase the pain threshold of mice and improve the central sensitization-like pain behavior of mice.

[0091] In order to better observe the effects of different concentrations of tripterygium glycosides tablets on the mechanical pain threshold and thermal pain threshold of model mice after one week and two weeks of administration, the inventor statistically analyzed each data. The changes in the mechanical pain threshold and thermal pain threshold after administration with 6 mg / kg tripterygium glycosides tablets are shown in Figure 5 Figures D and 5J respectively. The mechanical pain threshold and thermal pain threshold of mice increased after 7 days of administration, and the therapeutic effect after 14 days of administration was not as good as that after 7 days; the changes in the mechanical pain threshold and thermal pain threshold after administration with 12 mg / kg tripterygium glycosides tablets are shown in Figure 5 Figures E and 5K respectively. The mechanical pain threshold and thermal pain threshold of mice increased after 7 days of administration, and increased more after 14 days of administration, indicating a better therapeutic effect; the changes in the mechanical pain threshold and thermal pain threshold after administration with 24 mg / kg tripterygium glycosides tablets are shown in Figure 5 Figures F and 5L respectively. The mechanical pain threshold and thermal pain threshold of mice increased after 7 days of administration, and the therapeutic effect after 14 days of administration was not as good as that after 7 days. Thus, the above results show that tripterygium glycosides tablets can be effectively used to treat central sensitization-like pain.

[0092] In the description of this specification, the description referring to terms such as "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0093] Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those of ordinary skill in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present invention.

Claims

1. Use of Tripterygium glycosides tablets in the preparation of a product for preventing or treating central sensitization-like pain.

2. The use according to claim 1, wherein The product is a drug or a pharmaceutical preparation.

3. The use according to claim 1, characterized in that, The central sensitization-like pain is induced by central inflammation or chronic inflammatory pain.

4. The use according to claim 2, characterized in that, The drug or pharmaceutical preparation is an oral preparation; Optionally, the oral preparation is a tablet, capsule, pill, granule, decoction, oral liquid, dripping pill or syrup.

5. The use according to any one of claims 1 to 4, characterized in that, The therapeutically effective amount of the Tripterygium glycosides tablets is 1 mg / kg - 1.5 mg / kg.

6. A pharmaceutical composition, characterized in that, Comprising: Tripterygium glycosides tablets.

7. The pharmaceutical composition according to claim 6, wherein Further comprising a pharmaceutically acceptable excipient or carrier.

8. The pharmaceutical composition according to claim 6, wherein The pharmaceutical composition is an oral preparation; Optionally, the oral preparation is a tablet, capsule, pill, granule, decoction, oral liquid, dripping pill or syrup.

9. Use of the pharmaceutical composition according to any one of claims 6 - 8 in the preparation of a drug for preventing or treating central sensitization-like pain.

10. The use according to claim 9, characterized in that, The central sensitization-like pain is induced by central inflammation or chronic inflammatory pain.

Images