Tablet containing loxoprofen sodium and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and relates to loxoprofen sodium-containing tablets and a preparation method thereof. The loxoprofen sodium tablet is prepared from the following components in parts by weight: 100 parts of loxoprofen, 15 to 45 parts of soy isoflavone, 10 to 30 parts of brasenia schreberi polysaccharide, 2 to 5 parts of lacrotitol, 150 to 242 parts of microcrystalline cellulose, 12 to 50 parts of low-substituted hydroxypropyl cellulose, 3 to 20 parts of colloidal silicon dioxide and 3 to 8 parts of magnesium stearate. The preparation process is simple, the dissolution curve of the obtained tablet is consistent with that of a commercially available product, and an acceleration test shows that the loxoprofen sodium tablet prepared by the preparation method disclosed by the invention is relatively low in content of related substances and relatively stable in active substances, is suitable for clinical use, and has a development value.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a tablet containing loxoprofen sodium and a preparation method thereof. Background Art

[0002] Lornoxicam sodium was developed by Sankyo Co., Ltd. of Japan and was approved for marketing in 1986 under the trade name Loxonin. Its structure is shown in Formula I below:

[0003]

[0004] Loxoprofen sodium is a nonsteroidal anti-inflammatory drug (NSAIDs) belonging to the pyrrolidone class of drugs, which is widely used to relieve pain, reduce inflammation and reduce fever. Its main mechanism of action is to inhibit the activity of cyclooxygenase (COX) and reduce the synthesis of prostaglandins, thereby achieving anti-inflammatory, analgesic and antipyretic effects.

[0005] Compared with similar drugs in clinical practice, the main characteristics of loxoprofen sodium are: good clinical effect and few side effects. Another characteristic is its wide range of indications. It can be widely used in clinical practice for anti-inflammatory and analgesic treatment of rheumatoid arthritis, low back pain, frozen shoulder, cervical shoulder and wrist syndrome, analgesia and anti-inflammatory treatment after surgery, trauma and tooth extraction, and antipyretic and analgesia for acute upper respiratory tract inflammation.

[0006] Chinese patent 201210123938.3 discloses a loxoprofen sodium dispersion composition, containing loxoprofen sodium and silicon dioxide, characterized in that the silicon dioxide is added by internal addition. Generally, silicon dioxide is added as a glidant by external addition, that is, added after granulation to increase the fluidity of the particles and reduce the resistance of tableting. The technical solution adopted by the invention is internal addition, and the amount of silicon dioxide used accounts for 3-5% (weight percentage) of the total amount of the prescription.

[0007] Chinese Patent 202010581439.3 discloses a loxoprofen sodium tablet and a preparation process thereof, wherein the loxoprofen sodium tablet is composed of the following components in parts by weight: 100-120 parts of loxoprofen sodium, 200-250 parts of microcrystalline cellulose, 8-20 parts of sophorolipids, 10-20 parts of konjac glucomannan, 15-20 parts of cross-linked polyvinylpyrrolidone and 1-5 parts of magnesium stearate; the weight ratio of the sophorolipids to konjac glucomannan is 6:7.5, and sophorolipids and konjac glucomannan are easily denatured during hot melt extrusion.

[0008] In the current prior art, loxoprofen sodium tablets do not contain a combination of Brasenia schrenkiana polysaccharide and loxoprofen sodium, and there is no related report. Summary of the invention

[0009] In order to overcome the shortcomings of the prior art, the present invention provides a tablet containing loxoprofen sodium and a preparation method thereof. The dissolution curves of the tablet prepared by the present invention in three solutions are consistent with those of commercially available products. After accelerated tests, the tablet prepared by the present invention has a low content of related substances and relatively stable active substances, thereby solving the problem of high content of related substances in loxoprofen sodium tablets in the prior art.

[0010] Specifically, the technical solution of the present invention is achieved as follows:

[0011] A loxoprofen sodium tablet comprises the following components by weight: 100 parts of loxoprofen, 15-45 parts of soy isoflavones, 10-30 parts of Brasenia schrenkiana polysaccharide, 2-5 parts of lactitol, 150-242 parts of microcrystalline cellulose, 12-50 parts of low-substituted hydroxypropyl cellulose, 3-20 parts of colloidal silicon dioxide and 3-8 parts of magnesium stearate.

[0012] Furthermore, in a preferred embodiment of the present invention, the loxoprofen sodium tablets are composed of the following components by weight: 100 parts of loxoprofen, 20 parts of soy isoflavones, 15 parts of water shield polysaccharide, 3 parts of lactitol, 200 parts of microcrystalline cellulose, 17 parts of low-substituted hydroxypropyl cellulose, 8 parts of colloidal silicon dioxide and 5 parts of magnesium stearate.

[0013] Furthermore, in a preferred embodiment of the present invention, the loxoprofen sodium tablets are composed of the following components by weight: 100 parts of loxoprofen, 15 parts of soy isoflavones, 10 parts of water shield polysaccharide, 2 parts of lactitol, 150 parts of microcrystalline cellulose, 12 parts of low-substituted hydroxypropyl cellulose, 3 parts of colloidal silicon dioxide and 3 parts of magnesium stearate.

[0014] Furthermore, the preparation process of loxoprofen sodium tablets comprises the following steps:

[0015] (1) Weighing ingredients: weigh microcrystalline cellulose, low-substituted hydroxypropyl cellulose, soy isoflavones, bran polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside;

[0016] (2) Granulation 1: Loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, and microcrystalline cellulose M112 were sequentially added to a dry granulator for granulation to obtain mixed powder 1;

[0017] (3) Granulation 2: Add mixed powder 1, water shield polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soybean isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence for granulation to obtain mixed powder 2;

[0018] (4) Tableting: Add magnesium stearate to mixed powder 2, set the mixing speed to 10 rpm, mix for 5 minutes, and then press into tablets.

[0019] Furthermore, the screen size in the granulator in step (3) and step (4) is 0.8 mm and the rotation speed is 900±100 rpm.

[0020] Furthermore, the loxoprofen sodium tablet has a tablet hardness of 80-100N.

[0021] Furthermore, for the loxoprofen sodium tablets, the screen size in the granulator in step (3) and step (4) is 0.8 mm, and the rotation speed is 900 rpm; the tablet hardness is 90N.

[0022] The loxoprofen sodium tablets comprise the following steps:

[0023] (1) Weighing ingredients: Weigh microcrystalline cellulose, low-substituted hydroxypropyl cellulose, soy isoflavones, bran polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside;

[0024] (2) Granulation 1: Loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, and microcrystalline cellulose M112 were added to a dry granulator in sequence, with a screen size of 0.8 mm and a rotation speed of 900 ± 100 rpm. After granulation, mixed powder 1 was obtained.

[0025] (3) Granulation 2: Add mixed powder 1, Brasenia schrenkiana polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soybean isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence, with a rotation speed of 900±100 rpm and a screen size of 0.8 mm. After granulation, mixed powder 2 is obtained;

[0026] (4) Tableting: Add magnesium stearate to mixed powder 2, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet press to control the tablet hardness to 80N-100N.

[0027] The microcrystalline cellulose of the present invention is microcrystalline cellulose M112 and microcrystalline cellulose V101, and the weight ratio of the two is 0.5-1.5. Furthermore, the weight ratio of the microcrystalline cellulose M112 and microcrystalline cellulose V101 is 1:1.

[0028] Furthermore, the loxoprofen sodium tablets prepared by the present invention are used in preparing drugs for treating acute arthritis.

[0029] Compared with the prior art, the present invention has the following advantages:

[0030] In the pharmacodynamic experiment, the tablets prepared by the present invention significantly reduced the IL-1β content and the NF-κB protein expression, which was better than loxoprofen sodium alone and had a significant difference (P<0.05 or P<0.01), indicating that the tablets prepared by the present invention can inhibit the progression of severe bone destruction and have a significant improvement effect on acute gouty arthritis.

[0031] The loxoprofen sodium compound of the present invention has low hygroscopicity, a small content of related substances, is stable in properties after accelerated testing, and has better safety; the dissolution curve is highly consistent with that of commercially available products, is suitable for use in clinical practice, and has greater development value. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 : Single impurity content (%) in the relevant examples of the present invention. The single impurity content of Examples 1-3 is below 0.1%, while the control example does not contain Brasenia polysaccharide or soybean isoflavone components, and the impurity content exceeds 0.1% in the second month. The use of different dosages or preparation processes also has a relatively large impact on the content of related substances, resulting in a significantly higher final impurity content than the examples.

[0033] Figure 2 : Total impurity content (%) in the examples of the present invention. The impurity content of Examples 1-3 was below 0.2%, while the impurity content of the comparative example, which did not contain Brasenia schrenkiana polysaccharide or soybean isoflavone components, exceeded 0.4% in the third month.

[0034] Figure 3 : The dissolution rate (%) in the hydrochloric acid solution of pH 1.2 in the relevant examples of the present invention, the comparison of the dissolution rate at 0, 1, 2, 3, and 6 months. It can be seen that the dissolution rate of Examples 1-3 is significantly higher than that of Comparative Examples 1-7.

[0035] Figure 4 : Dissolution rate (%) in pH 1.2 hydrochloric acid solution in the relevant embodiments of the present invention. The cumulative dissolution rates of the commercially available product, Example 1, and Comparative Examples 5-6 in pH 1.2 hydrochloric acid solution at 2, 5, 10, 15, 20, and 30 minutes show that the dissolution of the commercially available product is basically consistent with that of Example 1, and they have similar dissolution rates.

[0036] Figure 5 : Dissolution rate (%) in pH 4.2 hydrochloric acid solution in the relevant embodiments of the present invention. The cumulative dissolution rate of the commercially available product, Example 1, and Comparative Examples 5-6 in pH 4.2 hydrochloric acid solution at 2, 5, 10, 15, 20, and 30 minutes shows that the dissolution of the commercially available product is basically consistent with that of Example 1, and has similar dissolution rates.

[0037] Figure 6: Dissolution in water in the relevant embodiments of the present invention (%). The cumulative dissolution of the commercial product and Example 1 and Comparative Examples 5-6 in aqueous solution at 2, 5, 10, 15, 20, and 30 minutes shows that the dissolution of the commercial product is basically consistent with that of Example 1 and has similar dissolution.

[0038] Figure 7 :Detection of IL-1β content in pharmacodynamic experiments.

[0039] Figure 8 :Detection of NF-κB protein expression in pharmacodynamic experiments.

[0040] Fig. 9 : The largest single hetero compound structural formula in loxoprofen sodium.

[0041] Fig.10 : Structural formulas of several main impurity compounds in loxoprofen sodium. DETAILED DESCRIPTION

[0042] In order to make the purpose and technical solution of the present invention clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited to these embodiments, and the embodiments are only used to explain the present invention. It should be understood by those skilled in the art that any changes or equivalent substitutions that do not deviate from the concept of the present invention are included in the protection scope of the present invention.

[0043] Example 1: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0044]

[0045] Preparation process:

[0046] (1) Weighing ingredients: Weigh microcrystalline cellulose (microcrystalline cellulose M112 and microcrystalline cellulose V101 in a ratio of 1:1), low-substituted hydroxypropyl cellulose, soy isoflavones, branvin polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside;

[0047] (2) Granulation 1: Loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, and microcrystalline cellulose M112 were added to a dry granulator in sequence, with a screen size of 0.8 mm and a rotation speed of 900 ± 100 rpm. After granulation, mixed powder 1 was obtained.

[0048] (3) Granulation 2: Add mixed powder 1, Brasenia schrenkiana polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soy isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence, with a rotation speed of 900 rpm and a screen size of 0.8 mm. After granulation, mixed powder 2 is obtained;

[0049] (4) Tabletting: Add magnesium stearate, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet.

[0050] Control tablet hardness: 80N-100N.

[0051] Example 2: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0052]

[0053] The type and dosage ratio of microcrystalline cellulose are microcrystalline cellulose M112 and microcrystalline cellulose V101, respectively, at a ratio of 1:0.5. The preparation process is as follows:

[0054] (1) Weighing ingredients: Weigh microcrystalline cellulose (microcrystalline cellulose M112, microcrystalline cellulose V101 in an amount of 1:0.5), low-substituted hydroxypropyl cellulose, soy isoflavones, branvin polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside;

[0055] (2) Granulation 1: Loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, and microcrystalline cellulose M112 were added to a dry granulator in sequence, with a screen size of 0.8 mm and a rotation speed of 800 rpm. After granulation, mixed powder 1 was obtained.

[0056] (3) Granulation 2: Add mixed powder 1, Brasenia schrenkiana polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soy isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence, with a rotation speed of 800 rpm and a screen size of 0.8 mm. After granulation, mixed powder 2 is obtained;

[0057] (4) Tabletting: Add magnesium stearate, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet press. Control the tablet hardness to 80N.

[0058] Example 3: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0059]

[0060]

[0061] The type and dosage ratio of microcrystalline cellulose are microcrystalline cellulose M112 and microcrystalline cellulose V101, respectively, at a ratio of 1:1.5. The preparation process is as follows:

[0062] Preparation process:

[0063] (1) Weighing ingredients: Weigh microcrystalline cellulose (microcrystalline cellulose M112, microcrystalline cellulose V101 in an amount of 1:1.5), low-substituted hydroxypropyl cellulose, soy isoflavones, branvin polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside;

[0064] (2) Granulation 1: Loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, and microcrystalline cellulose M112 were added to a dry granulator in sequence, with a screen size of 0.8 mm and a rotation speed of 1000 rpm. After granulation, mixed powder 1 was obtained.

[0065] (3) Granulation 2: Add mixed powder 1, Brasenia schrenkiana polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soy isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence, with a rotation speed of 1000 rpm and a screen size of 0.8 mm. After granulation, mixed powder 2 is obtained;

[0066] (4) Tabletting: Add magnesium stearate, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet.

[0067] Control tablet hardness: 100N.

[0068] Comparative Example 1: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0069]

[0070]

[0071] The type and dosage ratio of microcrystalline cellulose are 1:1 of microcrystalline cellulose M112 and microcrystalline cellulose V101. The preparation process is the same as that of Example 1.

[0072] Comparative Example 2: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0073]

[0074] The type and dosage ratio of microcrystalline cellulose are 1:1 of microcrystalline cellulose M112 and microcrystalline cellulose V101. The preparation process is the same as that of Example 1.

[0075] Comparative Example 3: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0076]

[0077] The type and dosage ratio of microcrystalline cellulose are 1:1 of microcrystalline cellulose M112 and microcrystalline cellulose V101. The preparation process is the same as that of Example 1.

[0078] Comparative Example 4: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0079]

[0080] The type and dosage ratio of microcrystalline cellulose are 1:1 of microcrystalline cellulose M112 and microcrystalline cellulose V101. The preparation process is the same as that of Example 1.

[0081] Comparative Example 5: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0082]

[0083] The type and amount ratio of microcrystalline cellulose are microcrystalline cellulose M112. The preparation process is the same as that of Example 1.

[0084] Comparative Example 6: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0085]

[0086]

[0087] Among them, the types and dosage ratios of microcrystalline cellulose are microcrystalline cellulose M112, microcrystalline cellulose V101

[0088] The dosage is 1:1. The preparation process is the same as in Example 1.

[0089] Comparative Example 7: A tablet containing loxoprofen sodium, the content and preparation process of which are as follows

[0090]

[0091] Preparation process:

[0092] (1) Weighing ingredients: Weigh microcrystalline cellulose (microcrystalline cellulose M112 and microcrystalline cellulose V101 in a ratio of 1:1), low-substituted hydroxypropyl cellulose, soy isoflavones, branvin polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside;

[0093] (2) Granulation 1: loxoprofen sodium, low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, microcrystalline cellulose M112, water shield polysaccharide, soybean isoflavones, and microcrystalline cellulose V101 are added to a dry granulator in sequence, and the sieve size is 0.8 mm; the rotation speed is 900 rpm. After granulation, mixed powder 1 is obtained;

[0094] (3) Tablet pressing: Add magnesium stearate, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet press. Control tablet hardness: Target value: 90.0N, range 60.0N-120.0N

[0095] 1. Physical performance testing

[0096] 1.1 Accelerated test conditions: The impurity content and dissolution effect data of the 0th, 1st, 2nd, 3rd and 6th months were tested under accelerated conditions (temperature: 40±2°C, humidity 75±5%).

[0097] Chromatographic conditions: octadecylsilane bonded silica gel was used as the filler; mobile phase A was a phosphoric acid aqueous solution adjusted to pH 2.5 with phosphoric acid, and mobile phase B was acetonitrile, and gradient elution was performed. The gradient elution program was:

[0098]

[0099] 1) Preparation of test solution: Take an appropriate amount of loxoprofen sodium, dissolve it in acetonitrile water and quantitatively dilute it to make a solution containing about 0.5 mg per 1 ml;

[0100] 2) Preparation of reference solution: Accurately measure an appropriate amount of the test solution and quantitatively dilute it with acetonitrile water to make a solution containing about 0.5 μg per 1 ml;

[0101] 3) Preparation of system suitability solution: Take appropriate amounts of impurity A, impurity B, impurity D and loxoprofen sodium, add solvent acetonitrile water to dissolve and dilute to prepare a mixed solution containing about 0.75 μg of impurity A, 0.75 μg of impurity B, 0.5 μg of impurity D and 0.5 mg of loxoprofen sodium per 1 ml;

[0102] 4) Determination: Accurately measure 20 μl of each of the above solutions, inject into the liquid chromatograph, run the gradient program, and record the chromatogram. The detection wavelength is 220-224 nm; the detection column temperature is 35-45°C; the detection flow rate is 0.8-1.2 ml / min. 2. Dissolution comparison experiment

[0103] The dissolution test was carried out at a speed of 50 r / min using the second method of General Rules 0931 of the 2020 edition of the Chinese Pharmacopoeia, with different pH 1.2 hydrochloric acid solutions, pH 4.5 acetate buffer and water as dissolution media. Test objects: Tablets of Example 1, Comparative Example 5 and Comparative Example 6 of the present invention, and commercially available loxoprofen sodium tablets (approval number: National Medicine Standard H20050437; production unit: Disha Pharmaceutical Group Co., Ltd.; drug code: 86903944000214).

[0104] 1.2 Test results

[0105] 1.2.1 Content of related substances

[0106] Figure 1 :from Figure 1 It can be seen that the single impurity content of Examples 1-3 is below 0.1%, while the control example does not contain Brasenia polysaccharide or soybean isoflavones, and the impurity content exceeds

[0107] 0.1%, and using different dosages or preparation processes also has a relatively large impact on the content of related substances, resulting in a final impurity content that is significantly higher than that in the examples.

[0108] Figure 2 :from Figure 2 It can be seen that the impurity content of Examples 1-3 is below 0.2%, while the impurity content of the control example, which does not contain Brasenia schrenkiana polysaccharide or soy isoflavone components, exceeds 0.4% in the third month.

[0109] Figure 3 : Comparison of the dissolution rates of the embodiments of the present invention in pH 1.2 hydrochloric acid solution at 0, 1, 2, 3, and 6 months. It can be seen that the dissolution rates of embodiments 1-3 are significantly higher than those of comparative examples 1-7.

[0110] Figure 4 : The commercially available product and Example 1, Comparative Examples 5-6 were in a pH 1.2 hydrochloric acid solution, the 2nd, 5th,

[0111] From the cumulative dissolution at 10, 15, 20, and 30 min, it can be seen that the dissolution of the commercially available product is basically consistent with that of Example 1 and has a similar dissolution rate.

[0112] The commercially available product and Example 1, Comparative Examples 5-6 were in a pH 4.2 hydrochloric acid solution, and the 2nd, 5th, 10th,

[0113] From the cumulative dissolution at 15, 20, and 30 min, it can be seen that the dissolution of the commercially available product is basically consistent with that of Example 1 and has similar dissolution.

[0114] From the cumulative dissolution of the commercially available product, Example 1, and Comparative Examples 5-6 in aqueous solution at 2, 5, 10, 15, 20, and 30 minutes, it can be seen that the dissolution of the commercially available product is basically consistent with that of Example 1 and has similar solubility.

[0115] 2. Pharmacodynamics Experiment

[0116] 2.1 Animals and groups

[0117] 32 male 6-8 week old SPF grade SD rats, weighing 220±30 g, license number: SYXK(Lu)2023 0031, produced by: Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The rats were divided into: normal group (n=8), model group (n=8), Example 1 group (n=8), and Comparative Example 2 group (n=8).

[0118] Growth conditions: Raise in a quiet space with a room temperature of 25-27°C and a humidity of 45%, drink sterilized water, and ensure that the rats are healthy and free from malnutrition and other diseases.

[0119] 2.2 Model group establishment

[0120] Acute gouty arthritis models were established in all groups except the normal group: rats were supine and the fur of the knee joints was cleaned. Sodium urate was injected into the knee joint to induce acute arthritis. 0.2 mL of sodium urate suspension was injected into each joint of the model group, Example 1 group, and Comparative Example 2 group of rats, and the normal group was injected with an equal amount of normal saline. Subsequently, 0.3 mg / kg of loxoprofen sodium was administered to the rats in Example 1 group and Comparative Example 2 group, and both were mixed with 10 mL of warm water for gavage, and the other two groups were administered with normal saline. The gavage time was 8:00 a.m., once a day, for 7 consecutive days.

[0121] 2.3 Detection indicators

[0122] 2.3.1. Detection of IL-1β levels

[0123] The experiment was carried out 24 hours after modeling. The experimental animals were anesthetized with chloral hydrate. The rats were placed in supine position, the limbs were fixed, and the abdomen was fully exposed. The abdomen was cut open, the abdominal aorta was found, punctured, and blood samples were obtained. The samples were left to stand at room temperature for 1 hour. The samples were centrifuged at 3000r / min for 15 minutes, the supernatant was aspirated, and the ELISA kit was used for detection.

[0124] 2.3.2 Detection of NF-κB protein expression in synovial tissue by Western blot

[0125] The experimental animals were killed, and the synovial tissue of the knee joint was separated and placed in a clean grinder on ice. After grinding with RIPA lysis buffer, the homogenate was obtained and the total protein was extracted. 50 μg of protein was loaded into each well. Before loading, an equal volume of 2×Loading buffer was added and boiled for 5 min. The voltage of electrophoresis was set to 90 V in the stacking gel and 120 V in the separation gel for 2.5 h. The protein was transferred to the PVDF membrane under 200 mA constant current conditions. After blocking with 5% bovine serum albumin at room temperature for 120 min, the primary antibody diluted 1:600 ​​was added and incubated at 4 ° C for 10 h, and the secondary antibody diluted 1:2000 was added and incubated at room temperature for about 2 h. The ECL luminescence kit was used for luminescence and development. The gray value of NF-κB and β-actin bands was analyzed by QuantityOne software. The expression level of NF-κB protein = gray value of NF-κB band / gray value of β-actin band.

[0126] 2.4 Statistical analysis

[0127] Graphad Prism 9.0 was used for statistical analysis, and the data were expressed as mean ± standard deviation. The data of each group were tested for normal distribution and homogeneity of variance, which met the requirements of Pearson's test, and one-way analysis of variance was used for comparison between groups. P < 0.05 was considered statistically significant.

[0128] 2.5 Results Analysis

[0129] 2.5.1 Detection of IL-1β levels

[0130] Figure 7 The IL-1β content in the serum of the model group was increased, and the IL-1β content in the normal group was lower than that in the model group, and there was a significant difference (P<0.001), indicating that the modeling was successful. Compared with the comparative example 2 group, the embodiment 1 group had a significant difference (P<0.05). Brasenia schrenkiana polysaccharide and loxoprofen sodium had a synergistic effect, and the effect was better than that of the comparative example 2 group alone, indicating that embodiment 1 had a significant improvement effect on acute gouty arthritis in rats.

[0131] Figure 8 The expression of NF-κB protein in the synovial tissue of the model group was increased, and the normal group was significantly lower than the model group, with a significant difference (P<0.001). The Example 1 group was compared with the Comparative Example 2 group, with a significant difference (P<0.01), suggesting that the vegetable polysaccharide and loxoprofen sodium have a synergistic effect and can inhibit the progression of severe bone destruction.

Claims

1. A loxoprofen sodium tablet, characterized in that The loxoprofen sodium tablets are composed of the following components by weight: 100 parts of loxoprofen, 15-45 parts of soy isoflavones, 10-30 parts of Brasenia schrenkiana polysaccharide, 2-5 parts of lactitol, 150-242 parts of microcrystalline cellulose, 12-50 parts of low-substituted hydroxypropyl cellulose, 3-20 parts of colloidal silicon dioxide and 3-8 parts of magnesium stearate. The preparation process of the loxoprofen sodium tablets comprises the following steps: (1) Weighing ingredients: weigh microcrystalline cellulose, low-substituted hydroxypropyl cellulose, soy isoflavones, bran polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside; (2) Granulation 1: Loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, and microcrystalline cellulose M112 were sequentially added to a dry granulator for granulation to obtain mixed powder 1; (3) Granulation 2: Add mixed powder 1, water shield polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soybean isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence for granulation to obtain mixed powder 2; (4) Tableting: Add magnesium stearate to mixed powder 2, set the mixing speed to 10 rpm, mix for 5 minutes, and then press into tablets.

2. The loxoprofen sodium tablet according to claim 1, characterized in that The loxoprofen sodium tablets are composed of the following components by weight: 100 parts of loxoprofen, 20 parts of soy isoflavones, 15 parts of water shield polysaccharide, 3 parts of lactitol, 200 parts of microcrystalline cellulose, 17 parts of low-substituted hydroxypropyl cellulose, 8 parts of colloidal silicon dioxide and 5 parts of magnesium stearate.

3. The loxoprofen sodium tablet according to claim 1, characterized in that The loxoprofen sodium tablets are composed of the following components by weight: 100 parts of loxoprofen, 15 parts of soy isoflavones, 10 parts of water shield polysaccharide, 2 parts of lactitol, 150 parts of microcrystalline cellulose, 12 parts of low-substituted hydroxypropyl cellulose, 3 parts of colloidal silicon dioxide and 3 parts of magnesium stearate.

4. The loxoprofen sodium tablet according to claim 1, characterized in that The screen size in the granulator in step (3) and step (4) is 0.8 mm, and the rotation speed is 900±100 rpm.

5. The loxoprofen sodium tablet according to claim 1, characterized in that The hardness of the tablet is 80-100N.

6. The loxoprofen sodium tablet according to claim 1, characterized in that The sieve size in the granulator in step (3) and step (4) is 0.8 mm, and the rotation speed is 900 rpm; the tablet hardness is 90N.

7. The loxoprofen sodium tablet according to claim 1, characterized in that The preparation process comprises the following steps: (1) Weighing ingredients: Weigh microcrystalline cellulose, low-substituted hydroxypropyl cellulose, soy isoflavones, bran polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, and loxoprofen sodium respectively and set aside; (2) Granulation 1: Loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, and microcrystalline cellulose M112 were added to a dry granulator in sequence, with a screen size of 0.8 mm and a rotation speed of 900 ± 100 rpm. After granulation, mixed powder 1 was obtained. (3) Granulation 2: Add mixed powder 1, Brasenia schrenkiana polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soybean isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence, with a rotation speed of 900±100 rpm and a screen size of 0.8 mm. After granulation, mixed powder 2 is obtained; (4) Tableting: Add magnesium stearate to mixed powder 2, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet press to control the tablet hardness to 90N.

8. The loxoprofen sodium tablet according to any one of claims 1 to 7, characterized in that The microcrystalline cellulose is microcrystalline cellulose M112 and microcrystalline cellulose V101, and the weight ratio of the two is 0.5-1.

5.

9. The loxoprofen sodium tablet according to claim 8, characterized in that The microcrystalline cellulose is microcrystalline cellulose M112 and microcrystalline cellulose V101 in a weight ratio of 1:

1.

10. Use of the loxoprofen sodium tablets according to any one of claims 1 to 7 in the preparation of a drug for treating acute arthritis.

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