A tablet containing sodium loxoprofen and a method for preparing the same

Abstract

The application belongs to the technical field of pharmaceutical preparations and relates to a loxoprofen sodium-containing tablet and a preparation method thereof. The loxoprofen sodium tablet is composed of the following components in parts by weight: loxoprofen 100 parts, soybean isoflavone 15-45 parts, potamogeton crispus polysaccharide 10-30 parts, lactitol 2-5 parts, microcrystalline cellulose 150-242 parts, low-substitution hydroxypropyl cellulose 12-50 parts, colloidal silicon dioxide 3-20 parts and magnesium stearate 3-8 parts. The preparation process is simple, the dissolution curve of the obtained tablet is consistent with that of a commercial product, the tablet prepared by the application has a low content of related substances, the active substance is stable, the tablet is suitable for clinical use and has high development value.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pharmaceutical preparations, and specifically relates to a lornoxicam sodium-containing tablet and a preparation method thereof. BACKGROUND

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

[0003]

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

[0005] Compared with the same drugs in clinical practice, lornoxicam sodium has the following characteristics: good clinical effect and small side effects. Another characteristic is wide indications, which can be widely used in clinical practice for anti-inflammatory analgesia of rheumatoid arthritis, low back pain, shoulder periarthritis, cervical shoulder wrist syndrome, etc., analgesic and anti-inflammatory after surgery, trauma and tooth extraction, and antipyretic analgesia for acute upper respiratory inflammation.

[0006] Chinese patent 201210123938.3 discloses a lornoxicam sodium dispersion composition containing lornoxicam sodium and silicon dioxide, characterized in that the silicon dioxide is added by internal addition method. Generally, silicon dioxide is used as a flow aid and is added by external addition method, i.e. added after granulation to increase the flowability of the granules and reduce the resistance of tabletting. The technical solution adopted by the present application is internal addition, and the amount of silicon dioxide accounts for 3-5% (wt%) of the total prescription.

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

[0008] At present, lornoxicam sodium tablets do not contain a combination of lornoxicam sodium and naiad polysaccharide, and there is no related report. SUMMARY

[0009] To overcome the deficiencies 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. Accelerated tests show that the loxoprofen sodium 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] Disclosed are loxoprofen sodium tablets, which are composed of the following components in parts by weight: 100 parts of loxoprofen, 15-45 parts of soy isoflavones, 10-30 parts of water shield 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, water shield 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 powder mix 1, water shield polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soy isoflavones, and microcrystalline cellulose V101 to a dry granulator in sequence and granulate to obtain powder mix 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, water shield 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, a mixed powder 1 was obtained.

[0025] (3) Granulation 2: Add mixed powder 1, water shield 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 ± 100 rpm and a screen size of 0.8 mm. After granulation, mixed powder 2 is obtained;

[0026] (4) Tabletting: Add magnesium stearate to mixed powder 2, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet. 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 medicines for treating acute arthritis.

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

[0030] In the pharmacodynamics experiment, the tablets prepared by the present invention significantly reduced the IL-1β content and the NF-κB protein expression, which was superior to the use of 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 low 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 was below 0.1%, while the control example, which did not contain water shield polysaccharide or soy isoflavones, had an impurity content exceeding 0.1% in the second month. The use of different dosages or preparation processes also had a significant impact on the content of the relevant substances, resulting in a final impurity content significantly higher than that of 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 water shield polysaccharide or soy isoflavones, exceeded 0.4% in the third month.

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

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

[0036] Figure 5 : Dissolution rate (%) in pH 4.2 hydrochloric acid solution of the relevant embodiments of the present invention. The cumulative dissolution rate of the commercial 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 rate of the commercial product is basically consistent with that of Example 1, and has similar dissolution rates.

[0037] Figure 6Dissolution in water (%) in the related embodiments of the present application. The cumulative dissolution of the commercial product and Example 1, Comparative Examples 5-6 in aqueous solution at 2, 5, 10, 15, 20, 30 min can be seen to be basically consistent with the dissolution of the commercial product and Example 1, and to have similar dissolution rates.

[0038] Figure 7 Detection of IL-1β content in the pharmacodynamics experiment.

[0039] Figure 8 Detection of NF-κB protein expression in the pharmacodynamics experiment.

[0040] Figure 9 Structure of the largest single impurity compound in sodium loxoprofen.

[0041] Figure 10 Structure of several main impurity compounds in sodium loxoprofen. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical solutions of the present application more clear, the following embodiments, the present application is further explained, but the protection scope of the present application is not limited to these embodiments, the embodiments are only used to explain the present application. Those skilled in the art should understand that any change or equivalent replacement without departing from the concept of the present application is included in the protection scope of the present application.

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

[0044]

[0045] Preparation process:

[0046] (1) weighing ingredients: respectively weighing microcrystalline cellulose (microcrystalline cellulose M112, the dosage of microcrystalline cellulose V101 is 1:1), low-substituted hydroxypropyl cellulose, soy isoflavone, potenace polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, sodium loxoprofen, standby;

[0047] (2) granulation 1: sodium loxoprofen, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, microcrystalline cellulose M112 are added to the dry granulator in turn, screen size: 0.8 mm; speed: 900±100 rpm, the granulation is finished, and the mixed powder 1 is obtained;

[0048] (3) granulation 2: mixed powder 1, potenace polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soy isoflavone, microcrystalline cellulose V101 are added to the dry granulator in turn, speed: 900 rpm, screen size: 0.8 mm, the granulation is finished, and the 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 a ratio of 1:0.5), low-substituted hydroxypropyl cellulose, soy isoflavones, water shield 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 powder mix 1, water shield 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, powder mix 2 is obtained.

[0057] (4) Tabletting: Add magnesium stearate, set the mixing speed to 10 rpm, mix for 5 minutes, and tablet. 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: respectively weigh microcrystalline cellulose (the use amount of microcrystalline cellulose M112, microcrystalline cellulose V101 is 1:1.5), low-substituted hydroxypropyl cellulose, soy isoflavone, potenacean polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, loxoprofen sodium, standby;

[0064] (2) Granulation 1: add loxoprofen sodium, 1 / 2 amount of low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, microcrystalline cellulose M112 into a dry granulator in turn, screen size: 0.8 mm; rotation speed: 1000 rpm, granulation is completed, and mixed powder 1 is obtained;

[0065] (3) Granulation 2: add mixed powder 1, potenacean polysaccharide, 1 / 2 amount of low-substituted hydroxypropyl cellulose, soy isoflavone, microcrystalline cellulose V101 into the dry granulator in turn, rotation speed: 1000 rpm, screen size: 0.8 mm, granulation is completed, and mixed powder 2 is obtained;

[0066] (4) Tabletting: add magnesium stearate, set the mixing rotation speed to 10 revolutions / minute, mix for 5 minutes, and tablet.

[0067] Control the tablet hardness: 100 N.

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

[0069]

[0070]

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

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

[0079]

[0080] The types and amounts of microcrystalline cellulose are microcrystalline cellulose M112 and microcrystalline cellulose V101, and the amount ratio is 1:1. The preparation process is the same as that of Example 1.

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

[0082]

[0083] The types and amounts 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 sodium loxoprofen, the content and preparation process of which are as follows

[0085]

[0086]

[0087] The types and amounts of microcrystalline cellulose are microcrystalline cellulose M112 and microcrystalline cellulose V101, and the amount ratio is 1:1. The preparation process is the same as that of Example 1.

[0088] Comparative Example 7: A tablet containing sodium loxoprofen, the content and preparation process of which are as follows

[0089]

[0090] Preparation process:

[0091] (1) Weigh the ingredients: weigh microcrystalline cellulose (the amount ratio of microcrystalline cellulose M112 and microcrystalline cellulose V101 is 1:1), low-substituted hydroxypropyl cellulose, soy isoflavones, potenacean polysaccharide, lactitol, colloidal silicon dioxide, magnesium stearate, sodium loxoprofen, and reserve;

[0092] (2) Granulation 1: sequentially add sodium loxoprofen, low-substituted hydroxypropyl cellulose, colloidal silicon dioxide, lactitol, microcrystalline cellulose M112, potenacean polysaccharide, soy isoflavones, microcrystalline cellulose V101 into the dry granulator, and add into the dry granulator. The screen size is 0.8 mm, and the rotation speed is 900 rpm. After granulation, mixed powder 1 is obtained;

[0093]

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

[0095] 1. Physical performance testing

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

[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, with gradient elution. The gradient elution program was as follows:

[0098]

[0099] 1) Preparation of test solution: Take an appropriate amount of loxoprofen sodium, dissolve it in acetonitrile and water, and quantitatively dilute it to a solution containing approximately 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 solvent to produce a solution containing approximately 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, dissolve in acetonitrile-water solvent, and dilute to produce a mixed solution containing approximately 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] Dissolution tests were conducted using the second method of General Chapter 0931 of the 2020 edition of the Chinese Pharmacopoeia, using different pH 1.2 hydrochloric acid solutions, pH 4.5 acetate buffer, and water as dissolution media at a speed of 50 r / min. Test subjects: 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; Manufacturer: 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 water shield polysaccharide or soy isoflavone components, and the impurity content exceeds

[0107] 0.1%, and the use of 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 control example does not contain water shield polysaccharide or soy isoflavone components, and the impurity content exceeds 0.4% in the third month.

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

[0110] Figure 4 : Commercially available products and Example 1, Comparative Examples 5-6 in pH 1.2 hydrochloric acid solution, No. 2, 5,

[0111] From the cumulative dissolution rates 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 similar dissolution rates.

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

[0113] From the cumulative dissolution rates 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 rates.

[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 dissolution rates.

[0115] 2. Pharmacodynamics Experiment

[0116] 2.1 Animals and groups

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

[0118] Growth conditions: Rats were raised in a quiet space with room temperature of 25-27℃ and humidity of 45%, and were given sterilized water to ensure their health and prevent malnutrition and other diseases.

[0119] 2.2 Model group establishment

[0120] Except for the normal group, an acute gouty arthritis model was established: the rats were placed on their backs and the skin around the knee joint was cleaned. Uric acid sodium was injected into the knee joint to induce acute arthritis. The model group, Example 1 group, and Comparative Example 2 group of rats were each injected with 0.2 mL of a uric acid sodium suspension into each joint, and the normal group was injected with an equal amount of normal saline. Subsequently, the rats in the Example 1 group and the Comparative Example 2 group were given 0.3 mg / kg of loxoprofen sodium, which was mixed with 10 mL of warm water and administered orally, and the other two groups were given normal saline. The administration time was 8:00 every day, 1 time / d, for 7 consecutive days.

[0121] 2.3 Detection index

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

[0123] This was performed 24 h after modeling. The experimental animals were anesthetized with chloral hydrate. The rats were placed on their backs, their limbs were fixed, and their abdomens were fully exposed. The abdomen was cut open, the abdominal aorta was found, and blood samples were obtained by puncture. The samples were allowed to stand at room temperature for 1 h. Centrifugation was performed at 3000 r / min for 15 min, the supernatant was aspirated, and an ELISA kit was used for detection.

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

[0125] The experimental animals were sacrificed, the synovial tissue of the knee joint was isolated, and the tissue was placed in a clean grinder and operated on ice. After grinding with RIPA lysis buffer, the homogenate was obtained, and total protein was extracted. 50 μg of protein was loaded per well, and an equal volume of 2xLoading buffer was added before boiling for 5 min. The voltage was set to 90 V for electrophoresis in the stacking gel, and 120 V for electrophoresis in the separation gel, and the electrophoresis was performed for 2.5 h. The protein was transferred to a PVDF membrane at a constant current of 200 mA, and after blocking with 5% bovine serum albumin at room temperature for 120 min, an antibody diluted 1:600 was added and incubated at 4°C for 10 h. A secondary antibody diluted 1:2000 was added and incubated at room temperature for about 2 h. After luminescence with an ECL luminescence kit, the film was developed. The gray values of the NF-κB and β-actin bands were analyzed using QuantityOne software, and the protein expression level of NF-κB = gray value of NF-κB band / gray value of β-actin band.

[0126] 2.4 Statistical analysis

[0127] Data statistics was performed by Graphad Prism 9.0, and the obtained data was expressed as mean ± standard deviation It was shown that normal distribution test and variance homogeneity test of each group of data were in line with the requirements of Pearson test, and single factor variance analysis was used for comparison between groups. P<0.05 was considered to have statistically significant difference.

[0128] 2.5 Result analysis

[0129] 2.5.1 Level detection of IL-1β

[0130] Figure 7 The IL-1β content in the serum of the model group was increased, the IL-1β content of the normal group was reduced compared with the model group, and there was a significant difference (P<0.001), which indicated that the modeling was successful. There was a significant difference (P<0.05) between the example 1 group and the comparative example 2 group, and the polysaccharide of Potamogeton crispus and sodium loxoprofen had a synergistic effect, which was better than the single use of the comparative example 2 group. It was shown that the example 1 had a significant improvement effect on the acute gouty arthritis of 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 reduced compared with the model group, and there was a significant difference (P<0.001). There was a significant difference (P<0.01) between the example 1 group and the comparative example 2 group, which indicated that the polysaccharide of Potamogeton crispus and sodium loxoprofen had a synergistic effect, and could inhibit the progress 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 water shield 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, water shield 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, soy 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; Wherein, the microcrystalline cellulose is microcrystalline cellulose M112 and microcrystalline cellulose V101, and the weight ratio of the two is 0.5-1.

5.

2. Loxoprofen sodium tablets 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. Loxoprofen sodium tablets 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. Loxoprofen sodium tablets according to claim 1, characterized in that, The screen size in the granulator in step (2) and step (3) is 0.8 mm, and the rotation speed is 900±100 rpm.

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

6. The loxoprofen sodium tablet according to claim 1, wherein The screen size in the granulator in step (2) and step (3) is 0.8 mm, and the rotation speed is 900 rpm; the hardness of the loxoprofen sodium tablets is 90N.

7. The loxoprofen sodium tablet according to claim 1, wherein The preparation process comprises the following steps: (1) Weighing ingredients: Weigh microcrystalline cellulose, low-substituted hydroxypropyl cellulose, soy isoflavones, water shield 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. The screen size was 0.8 mm and the rotation speed was 900 ± 100 rpm. After granulation, mixed powder 1 was obtained. (3) Granulation 2: Add mixed powder 1, water shield 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 ± 100 rpm and a screen size of 0.8 mm. After granulation, mixed powder 2 is obtained; (4) Tablet pressing: Add magnesium stearate to mixed powder 2, set the mixing speed to 10 rpm, mix for 5 minutes, and press the tablets to control the tablet hardness to 90N.

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

1.

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

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