CN114306332B - Application of talassamidine in preparation of medicines for treating arthritis - Google Patents

Abstract

The invention discloses the application of Tara salsa in preparing the medicine for treating arthritis, and it can also be applied in preparing the medicine for treating arthritis and its anti-inflammatory, analgesic and antipyretic activity, the invention verifies that Tara salsa has obvious therapeutic effect to rheumatoid arthritis through rat experiment, it can obviously reduce MMP3 concentration in serum, and its therapeutic effect is better than indomethacin, and has no side effect; experiments prove that the medicine has the characteristics of obvious anti-inflammatory and analgesic activities, and the like, has the advantages of high permeability, good absorption, high oral bioavailability and the like, has good pharmaceutical prospect, and can enrich the treatment means for rheumatoid arthritis.

Description

Application of talassamidine in preparation of medicines for treating arthritis

Technical Field

The invention relates to the technical field of medical biology, in particular to application of traditional Chinese medicine active ingredients, namely application of talassamidine in preparation of medicines for treating arthritis.

Background

Rheumatoid arthritis (Rheumatoid arthritis, RA) is a chronic, inflammatory, systemic autoimmune disease. The clinical characteristics are that the joints are symmetrical swelling, morning stiffness, local joint pain, dysfunction, systemic light or moderate fever and the like. The RA disability rate is high, and the erosion of multi-joint cartilage and bone can occur in time when the treatment is not performed, so that the life quality of patients is seriously affected.

The pathogenesis of RA is still under investigation, and current treatment of RA is mainly to control symptoms and delay disease. In Western medicine, non-steroidal anti-inflammatory drugs, glucocorticoids, immune response inhibitors and the like are mostly adopted for treating RA, but the adverse reactions of the drugs are more, so that the adverse reactions are not ignored while the illness state is delayed.

Talazamine (TE) is a C-19 type amino alcohol aconite alkaloid, and TE has remarkable pharmacological effects and good clinical application prospects, and has remarkable anti-inflammatory, antihypertensive, antitumor, neuroprotection and other effects. And it has been found that TE can relieve cytotoxicity caused by beta-amyloid oligomer by blocking potassium ion channels, and is a potential lead compound in the development of novel medicines for treating neurodegenerative diseases. In addition, TE has also been found to be useful in the treatment of swine dysentery. However, studies on TE for treating rheumatoid arthritis have not been reported yet.

Disclosure of Invention

Therefore, based on the background, the invention provides the application of the talassamidine (CAS number: 20501-56-8) in preparing the medicine for treating the arthritis, and the new application research of the talassamidine can enrich the treatment means for the rheumatoid arthritis.

The technical scheme of the invention is as follows:

one of the invention is that:

use of TE in the manufacture of a medicament for the treatment of arthritis, said TE having the structural formula:

further, the arthritis is rheumatoid arthritis.

Further, the dosage form of the medicine is a conventional dosage form for clinically treating arthritis.

Further, the dosage form of the medicine can be an oral preparation or an injection preparation or an external preparation.

The invention also provides an anti-rheumatoid arthritis medicament, which comprises an effective amount of TE and pharmaceutically acceptable auxiliary agents.

The anti-rheumatoid arthritis medicament is an oral preparation or an injection preparation or an external preparation, wherein the oral preparation comprises but is not limited to tablets, capsules, granules and the like.

The invention also provides application of TE in preparing medicines with anti-inflammatory, analgesic and antipyretic activities.

By adopting the technical scheme, the beneficial effects are as follows:

the invention verifies through rat experiments that TE has obvious curative effect on rheumatoid arthritis, can obviously reduce the concentration of arthritis marker matrix metalloproteinase-3 (Matrix metalloproteinase, MMP 3) in serum, and has obvious curative effect superior to indometacin; experiments prove that the medicine has the characteristics of obvious anti-inflammatory, analgesic and pyrolytic activities, and the like, has the advantages of high permeability, good absorption, high oral bioavailability and the like, has good pharmaceutical prospect, and can enrich the treatment means for rheumatoid arthritis.

Drawings

In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a photograph of a right hind paw lesion of a rat in a treatment experiment with TE versus RA in example 1 of the present invention;

wherein Normal (FIG. 1A), model (FIG. 1B), positive (FIG. 1C), high (4 mg/kg TE) (FIG. 1D) and low (2 mg/kg TE) (FIG. 1E);

FIG. 2 shows the foot swelling rates measured on days 9, 12, 15, 18 and 21 for rats in the middle normal, model, positive, high and low TE groups of the TE versus RA treatment experiment of example 1 of the present invention;

FIG. 3 shows joint swelling numbers on days 9, 12, 15, 18 and 21 in rats in the normal, model, positive, high and low TE groups of the TE versus RA treatment experiment of example 1 according to the present invention;

FIG. 4 shows the arthritis scores on days 9, 12, 15, 18 and 21 in rats in the normal, model, positive, high and low TE groups of the TE versus RA treatment experiment of example 1 of the present invention;

FIG. 5 shows the systemic scores on days 9, 12, 15, 18 and 21 for rats in the normal, model, positive, high and low TE groups of the treatment experiment with RA for TE of example 1 of the present invention;

FIG. 6 shows the weight changes on days 9, 12, 15, 18 and 21 of rats in the normal, model, positive, high and low TE groups of the TE versus RA treatment experiment of example 1 of the present invention;

FIG. 7 shows the concentration of matrix metalloproteinase 3 (MMP 3) in the serum of rats in the normal, model, positive, high and low TE groups of example 1 of the present invention;

FIG. 8 shows the foot swelling rate of the mice according to example 2 of the present invention after 6h injection of lambda carrageenan into the right hind feet of the mice after 30min of gastric lavage Saline (Saline), 50mg/kg diclofenac sodium (Positive) and 15, 7.5 and 3.75mg/kg TE, respectively;

FIG. 9 shows the number of pain twists after intraperitoneal injection of 1% acetic acid after 30min of mice according to example 2 of the present invention, respectively, with gastric physiological Saline (Saline), 50mg/kg diclofenac sodium (Positive), and 15, 7.5 and 3.75mg/kg TE;

FIG. 10 shows the thermal threshold of mice in example 2 of the present invention, which were recorded on a liquid crystal display after the mice had developed behaviors such as leg lifting, flapping, licking, etc., by administering IR heat radiation with an intensity of IR55 to the hind legs after the mice had been respectively perfused with physiological Saline (Saline), 50mg/kg diclofenac sodium (Positive), and 15, 7.5, and 3.75mg/kg TE for 30 min.

FIG. 11 is a graph showing the blood concentration versus time after oral administration of 10mg/kg TE (FIG. 11A) and intravenous injection of 1mg/kg TE (FIG. 11B) in mice of example 3 of the present invention, respectively;

FIG. 12 shows pharmacokinetic parameters of mice of example 3 of the present invention after oral administration of 10mg/kg TE and intravenous injection of 1mg/kg TE, respectively:

wherein FIG. 12A is the area under the blood concentration versus time curve (AUC _0-t )；

FIG. 12B is an average residence time (MRT) _0-t )；

FIG. 12C is half-life (T _1/2 )；

FIG. 12D is an apparent distribution volume (V _d )；

Fig. 12E is Clearance (CL).

FIG. 13 is an absorption transport profile of TE of example 3 of the present invention on Caco-2 monolayer cell model;

FIG. 13A is the effect of efflux transporters P-gp inhibitor (Verapeil), BCRP inhibitor (KO 143) and MRP2 inhibitor (MK 571) on BL-side transport when TE is transported from the AP-BL side:

FIG. 13B is an effect of 3 efflux transporter inhibitors on AP side transport capacity upon TE transport from BL-AP side;

FIG. 13C is the apparent permeability coefficient (P) of 3 efflux transporter inhibitors to TE _app ) Is a function of (1);

FIG. 13D is the effect of 3 efflux transporter inhibitors on TE efflux rate.

Detailed Description

Reference now will be made in detail to embodiments of the invention, one or more examples of which are described below. Each example is provided by way of explanation, not limitation, of the invention. Indeed, it will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one embodiment can be used on another embodiment to yield still a further embodiment.

Accordingly, it is intended that the present invention cover such modifications and variations as fall within the scope of the appended claims and their equivalents. Other objects, features and aspects of the present invention will be disclosed in or be apparent from the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention. The invention is further illustrated below with reference to examples. The invention is further described below with reference to the accompanying drawings.

Example 1: TE-to-RA therapeutic experiments

In this example, treatment experiments of rat adjuvant arthritis with Tamassamiable (TE) were conducted to examine the therapeutic effect of TE on rheumatoid arthritis.

60 male SD rats of 120+ -20 g were used, and 6 were randomly divided into 5 groups, namely, a normal group, a model group, an indomethacin group (positive drug group), a high-dose TE group (4 mg/kg TE) and a low-dose TE group (2 mg/kg TE).

After the rats were fixed, the hairs near the tail root were shaved off, and the rats were sterilized by wiping with 75% alcohol, and 0.1mL of physiological saline was subcutaneously injected at about 1cm of the tail root of the normal group of rats, and the other group of rats was injected with the same volume of Freund's complete adjuvant. Rats started to develop disease on day 9 after injection of Freund's complete adjuvant. From day 9, rats in the normal group, model group, indomethacin group (positive drug group), high-dose TE group and low-dose TE group were perfused with 20% beta-cyclodextrin, 2mg/kg indomethacin, 4mg/kg TE and 2mg/kg TE, respectively, at a volume of 10mL/kg daily for 14 days. In the experiment, 2mg/kg of indomethacin, 4mg/kg of TE and 2mg/kg of TE were prepared by using 20% beta-cyclodextrin. During the experiment, the foot volume of the rats was measured every 3 days and the number of joint swelling, arthritis score and whole body score were calculated.

(1) The foot swelling rate of the rats was calculated from the foot volume values:

joint swelling number 1 ankle joint (or wrist joint) and 5 finger (toe) joints per paw, up to 24 joints per rat.

(2) The arthritis index scoring criteria were:

normally, marking 0 point;

erythema and slight swelling of the ankle joint were noted for 1 minute;

erythema and slight swelling of ankle to toe or metacarpal joints, recorded 2 minutes;

erythema and moderate swelling of ankle to toe or metacarpal joints, recorded 3 minutes;

erythema and severe swelling occurred from ankle to toe, recorded 4 minutes.

(3) The whole body scoring criteria were:

the ears have no nodule and redness symptoms, and record 0 points;

one ear nodule and redness symptoms, recorded 1 minute;

two ear nodules and redness symptoms, recorded 2 points;

the nose has no connective tissue swelling, and the score is 0;

obvious connective tissue swelling, recorded 1 minute;

the tail has no nodule, and the score is 0;

if there are nodules, record 1 minute;

the full paw has no swelling, and the score is 0;

one forefoot paw is swollen, 1 minute;

swelling of the two forefoot paws, recorded 2 minutes;

hind paw is free from swelling, and the score is 0;

one hind paw is swollen, 1 minute;

swelling of the two hind paws, recorded 2 minutes; each rat was rated at most 8 points.

After the experiment is finished, fixing the rats, and taking right hind foot pictures of all groups of rats; rats were then anesthetized, collected by abdominal aorta, and after the blood sample was allowed to stand at room temperature for 2 hours, serum was isolated by centrifugation at 3000rpm for 10 minutes, and the concentration of arthritis marker matrix metalloproteinase-3 (Matrix metalloproteinase-3, MMP 3) in serum of each rat was measured according to the operating instructions of the Elisa kit. The results obtained in this experiment are shown in fig. 1 to 7. The results of fig. 2-7 are expressed in terms of mean ± standard deviation, the data were analyzed using a Shapiro-Wilk test for normal distribution, an independent sample t-test for normal distribution and variance alignment for the two sets of mean-compared data, and a Satterthwaite corrected t-test for normal distribution and variance alignment. In addition, the data were analyzed using a non-parametric Wilcoxon rank sum test when the data did not fit the normal distribution. P <0.05 indicates a statistical difference. In the figure "#" indicates a statistical difference between the model group and the normal group, and "×" indicates a statistical difference between the drug-treated group and the model group (n=6).

From the analysis of the results of fig. 1 to 7, rats began to develop disease on day 9 of modeling. Compared with the normal group of rats (figure 1A), the ankle joint of the model group of rats is obviously swollen (figure 1B); from day 9, the rate of foot swelling (fig. 2) and the number of joint swelling (fig. 3) for the model group rats, both the arthritis score (fig. 4) and the systemic score (fig. 5) increased over the normal group; and from day 12 on the model group rats had a significant increase in foot swelling rate (fig. 2), joint swelling number (fig. 3), arthritis score (fig. 4) and whole body score (fig. 5) over the normal group (P < 0.05). Meanwhile, from day 9, the body weight of the model group rats began to decrease (fig. 6), and from day 12, the body weight of the model group rats was significantly lower than that of the normal group rats (P < 0.05). In addition, MMP3 (arthritis marker) concentration in the serum of rats in the model group was also significantly increased over that in the normal group (fig. 7, p < 0.05). The results show that the rat adjuvant arthritis model is successfully established.

And as is evident from fig. 1 to 7, TE has a remarkable effect of treating rat adjuvant arthritis. Compared with the model group, the joint swelling, deformation and redness of rats are obviously improved after TE treatment of the high-dose TE group and the low-dose TE group, and the improvement degree is equivalent to that of indomethacin (figure 1); both TE and indomethacin treatments reduced the rate of foot swelling in rats compared to the model group (fig. 2), and high dose (4 mg/kg) TE treatments significantly reduced the rate of foot swelling in rats (P < 0.05) at days 12, 15 and 21, and low dose (2 mg/kg) TE treatments significantly reduced the rate of foot swelling in rats (P < 0.05) at days 15 and 21; both TE and indomethacin treatments reduced the number of joint swelling in rats compared to the model group (fig. 3), and both TE and indomethacin treatments significantly reduced the number of joint swelling in rats from day 12 (P < 0.05); both TE and indomethacin treatments reduced the arthritis score in rats compared to the model group (fig. 4), and from day 15, the high dose (4 mg/kg) TE treatment significantly reduced the arthritis score in rats (P < 0.05); both TE and indomethacin treatment at high/low doses significantly reduced the systemic score of rats compared to the model group (fig. 5, p < 0.05) and to a greater extent than indomethacin; compared with the model group, both TE and indomethacin treatments at high/low doses significantly restored the body weight of rats (fig. 6, p < 0.05), and the degree of restoration was superior to that of indomethacin; both TE and indomethacin treatments at high/low doses significantly reduced the concentration of MMP3 in rat serum compared to the model group (fig. 7, p < 0.05). In conclusion, the TE has remarkable effect of treating RA, can improve joint swelling, redness and deformation of the rat with adjuvant arthritis, can remarkably reduce foot swelling rate, joint swelling number, arthritis score and whole body score of the rat, can remarkably recover body weight of the rat, and remarkably reduce MMP3 concentration in serum of the rat with arthritis, and can be seen to have better effect of treating RA by FE than that of indomethacin which is a non-steroidal anti-inflammatory drug based on experimental results of the examples.

Example 2: pharmacological and pharmacodynamic related experiments for treating RA by TE

RA is clinically characterized by joint inflammation and swelling, localized joint pain, and associated systemic mild or moderate fever. Thus, anti-inflammatory, analgesic and antipyretic are key to alleviating RA symptoms, effectively eliminating joint swelling, alleviating pain and restoring body temperature. The example shows the pharmacological activity of TE in resisting inflammation, relieving pain and relieving fever through experiments.

(1) Anti-inflammatory Activity of TE

Male 8-week-old C57 mice were selected 24, randomly divided into 4 groups of 6, and the right foot thickness of each mouse was measured with a vernier caliper. After the 4 groups of mice were perfused with physiological saline, 50mg/kg of diclofenac sodium (positive drug), 15mg/kg of TE, 7.5mg/kg of TE and 3.75mg/kg of TE for 30min, respectively, 20. Mu.L of lambda. Carrageenan was subcutaneously injected into the right foot plantar of each group of mice to cause inflammation. After 6h of inflammation, the right foot thickness of each mouse was measured with a vernier caliper. The foot swelling rate of each mouse was calculated using the following formula:

the anti-inflammatory test results of TE are shown in fig. 8, the results are expressed as mean ± standard deviation, the data are analyzed using independent sample t-test, and the symbol "×" indicates P <0.05, i.e. there is a significant difference between the drug-treated group and the physiological saline group (n=6). As shown in FIG. 8, 50mg/kg of diclofenac sodium and 15mg/kg of TE, 7.5mg/kg of TE and 3.75mg/kg of TE significantly reduced the rate of foot swelling in mice by 37.36%, 46.76%, 39.01% and 37.90%, respectively, compared to the physiological saline group (P <0.05, FIG. 3). The lambda carrageenan inflammatory model is a classical anti-inflammatory drug screening model, and experiments of the lambda carrageenan inflammatory model show that TE has remarkable anti-inflammatory activity, and the anti-inflammatory activity of high-dose TE in vivo is stronger than that of non-steroidal anti-inflammatory drug diclofenac sodium. The obvious anti-inflammatory activity of TE is probably one of the pharmacodynamic bases of RA treatment, and can obviously inhibit the arthritis of patients with RA.

(2) Analgesic effect of TE

Male 8-week-old C57 mice were randomized into 4 groups of 6. The 4 groups of mice are respectively infused with gastric physiological saline, 50mg/kg of diclofenac sodium (positive medicine), 15mg/kg of TE, 7.5mg/kg of TE and 3.75mg/kg of TE for 30min according to the volume of 10mL/kg, then 1% acetic acid solution is injected intraperitoneally according to the volume of 10mL/kg, the times of pain and torsion of the mice are started to be observed and recorded after 5min, and the total observation is 15min. The pain inhibition rate of each group of medicines is calculated by the number of times of twisting the body, and the calculation formula is as follows:

the analgesic test results of TE are shown in fig. 9, the results are expressed as mean ± standard deviation, the data are analyzed using independent sample t-test, and the symbol "×" indicates P <0.05, i.e. there is a significant difference between the drug-treated group and the physiological saline group (n=6). As shown in FIG. 9, 50mg/kg of diclofenac sodium, 15mg/kg of TE, 7.5mg/kg of TE and 3.75mg/kg of TE each significantly reduced the pain torsion times (P < 0.05) of mice, and the pain suppression rates were 52.08%, 71.88%, 41.66% and 55.21%, respectively, compared to the physiological saline group. The acetic acid induced mouse pain torsion model is a classical analgesic screening model, and experimental results show that TE has remarkable analgesic effect, and the high-dose TE analgesic activity is stronger than that of a non-steroidal anti-inflammatory drug, namely diclofenac sodium. Thus, analgesic activity may be one of the pharmacodynamic bases of TE treatment of RA, significantly alleviating pain in RA patients.

(3) Antipyretic Activity of TE

Male 8-week-old C57 mice were randomized into 4 groups of 6. After the 4 groups of mice were respectively perfused with gastric physiological saline, 50mg/kg of diclofenac sodium (positive drug), 15mg/kg of TE, 7.5mg/kg of TE and 3.75mg/kg of TE for 30min in a volume of 10mL/kg, infrared heat radiation was given to the right hind legs of the mice, and the infrared light intensity was IR55. And recording the thermosensitive threshold of the mouse displayed by the liquid crystal display after the behaviors of leg lifting, flapping, foot adding and the like of the mouse occur. To avoid scalding the mice, the mice without leg lifting reaction still have the detection stopped after 25s, and the threshold value is calculated according to 25 s.

The results of the TE antipyretic experiments are shown in fig. 10, and the results are expressed as mean ± standard deviation, the data are analyzed using independent sample t-test, and the symbol "×" indicates P <0.05, i.e. there is a significant difference between the drug-treated group and the physiological saline group (n=6). Compared with the physiological saline group, 50mg/kg of diclofenac sodium, 15mg/kg of TE, 7.5mg/kg of TE and 3.75mg/kg of TE can significantly increase the thermosensitive threshold of mice by 173.53%, 127.94%, 100.49% and 50% (P < 0.05), respectively. The infrared thermosensitive experiment is a common antipyretic screening model, and the result shows that TE has obvious antipyretic effect. Thus, the antipyretic activity is probably one of the pharmacodynamic bases of TE for treating RA, and can remarkably restore the body temperature of RA patients.

Example 3: TE oral availability and absorption transport experiments

(1) Oral bioavailability of TE

Male 8-week-old C57 mice were randomized into 2 groups of 5. Groups 2 mice were perfused with 10mg/kg TE and 1mg/kg TE were intravenously injected, and blood was collected from the tail vein at time points 0, 3, 7, 10, 15, 20, 30, 50, 80, 120, 240, 360, and 480 min. After blood samples are centrifugally separated to obtain plasma, the plasma is treated by organic solvent to precipitate protein, 2 mu L of the plasma is taken to enter a UHPLC-MS/MS system for analysis and detection of TE concentration in the plasma, a blood concentration-time curve is drawn, pharmacokinetic parameters are calculated, and the oral bioavailability is calculated according to the following formula:

oral bioavailability (%) = (AUC) _P，O ×Dose _i，v )/(AUC _i，v ×Dose _p，o )×100%

(2) Absorption transport characteristics of TE

Taking Caco-2 cells in logarithmic growth phase, diluting with DMEM complete medium containing 10% fetal calf serum, 1% diabody and 1% nonessential amino acids, inoculating into 6-well Transwell plate to obtain cell density of 5×10 ⁵ The cells/wells were subjected to 5% CO at 37 ℃ ₂ Is cultured in the incubator for 21 days. Changing the cell culture liquid once a day, after 21 days of cells grow into stable and compact cell tissue, washing with 37 deg.C HBSS buffer solution for 3 times, and measuring transepithelial cell resistance when the resistance is greater than 420 Ω/cm ² When a tight and intact monolayer of cells has been formed, it is indicated that it can be used to conduct transmembrane transport experiments. After the resistance measurement is completed, 2mL of HBSS buffer solution is added to two sides of each hole, and the mixture is placed on a shaking table at 37 ℃ for incubation for 30min, so that the cells release nutrient substances absorbed in the culture process. Drug transport process from AP side to BL side: 2mL of HBSS solution containing 2. Mu.M TE was added from the AP side, and an equal volume of blank HBSS solution was added to the BL side. Samples of 0.5mL were taken on both sides at 30, 60, 90 and 120min after dosing, while 0.5mL of HBSS solution containing 2. Mu.M TE was added on the AP side and an equal volume of blank HBSS solution was added on the BL side, each group of samples was in parallel 3. The drug transfer from BL side to AP side was identical to the AP side to BL side transfer experiment operation, i.e., drug was added to BL side and blank HBSS solution was added to AP side.

Inhibitor experiments: when the drug is transported from the AP-BL, adding a mixed HBSS solution containing 2 mu M TE and inhibitor from the AP side, and simultaneously adding a blank HBSS solution from the B side; when the drug is transported from BL-AP, the drug is added to BL side, and the HBSS solution containing the inhibitor is added to A side, and the rest steps are the same. 100 mu L of acetonitrile solution containing an internal standard is added into a sample, and after uniform mixing and centrifugation, 2 mu L of supernatant is taken and subjected to UHPLC-MS/MS analysis to detect the concentration of TE.

The results are shown in figures 11 to 13, wherein the results of figure 13 are expressed as mean ± standard deviation, the data are analyzed using the independent sample t-test, and the symbol "x" indicates P <0.05, i.e. there is a significant difference between the different inhibitor groups and the control group (n=3).

As can be seen from FIGS. 11 to 13, TE was rapidly absorbed in mice with a high absorption degree, and the blood concentration reached a peak (FIG. 11A) for 14min, and the oral bioavailability was calculated to be 86.27%. In vitro cell transport experiments showed apparent permeability coefficient (P) _app ) Mainly at 0.79 x 10 ^-5 cm/s to 2.60 x 10 ^-5 In the cm/s range (FIG. 13C), indicating good uptake of TE on cells, possibly into and out of cells mainly by passive diffusion; in addition, TE excretion rate is low (Effect ratio)<3.5 When inhibitors of efflux transporters P-gp, BCRP and MRP2 were added, the efflux rate of TE on Caco-2 cells was significantly reduced (FIG. 13D, P)<0.05 It was shown that efflux transporters P-gp, BCRP and MRP2 are all involved in TE efflux. Experiments prove that TE is rapidly absorbed by oral administration, has high bioavailability, better permeability, low excretion rate and better patentability, and can be applied to preparing medicines for treating RA.

From the experiments of examples 1 to 3, it is evident that TE can significantly treat and improve symptoms of the adjuvant arthritic rats, and that the therapeutic effect of TE is superior to that of the non-steroidal anti-inflammatory drug indomethacin; through a pharmacodynamic basic experiment, the TE has very excellent anti-inflammatory activity, analgesic activity and antipyretic activity, and the excellent anti-inflammatory, analgesic and antipyretic activity can be used for purposefully relieving and improving the symptoms of arthritis; through an oral bioavailability experiment and an in vitro absorption and transport experiment, the TE is proved to have good oral absorption, high bioavailability and better drug property.

The invention and its embodiments have been described above with no limitation, and the actual construction is not limited to the embodiments of the invention as shown in the drawings. In summary, if one of ordinary skill in the art is informed by this disclosure, a structural manner and an embodiment similar to the technical solution should not be creatively devised without departing from the gist of the present invention.

Claims (4)

1. The application of the talassamidine in preparing the medicine for treating the rheumatoid arthritis is characterized in that the structural formula of the talassamidine is as follows:

（Ⅰ）

the only active component of the medicine is taraxamamine.

2. The use of talassamidine according to claim 1 in the preparation of a medicament for the treatment of rheumatoid arthritis, wherein the dosage form of said medicament is a conventional dosage form for the clinical treatment of arthritis.

3. The use of talassamidine according to claim 2 in the preparation of a medicament for the treatment of rheumatoid arthritis, wherein the medicament is in the form of an oral formulation or an injectable formulation or an external formulation.

4. Use of talassamidine according to claim 2 in the preparation of a medicament for the treatment of rheumatoid arthritis, wherein said medicament further comprises a pharmaceutically acceptable adjuvant.

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