Medicine for treating arthritis as well as preparation method and application thereof

Abstract

The invention relates to the technical field of biological medicines, and particularly discloses a medicine for treating arthritis as well as a preparation method and application of the medicine. The diclofenac diethylamine medicine carrying system is prepared from magnesium aluminum metasilicate, diclofenac diethylamine, hexadecyl trimethyl ammonium bromide, propylene glycol and deionized water according to the dosage ratio of (4 to 10) g: (1 to 5) g: (0.1 to 1) g: (40 to 60) mL: (90 to 110) mL. According to the diclofenac diethylamine drug-loading system provided by the invention, a stable drug-loading structure formed by magnesium aluminum metasilicate and hexadecyl trimethyl ammonium bromide has a synergistic effect, and the release rate of a drug on the skin surface is controlled, so that the irritation of the drug is reduced, and the action time of the drug is prolonged.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, in particular to a medicine for treating arthritis and a preparation method and application thereof. BACKGROUND

[0002] Diclofenac diethylamine emulsion as an external non-steroidal anti-inflammatory drug is widely used for the symptomatic relief of rheumatoid arthritis, rheumatoid arthritis and osteoarthritis and other diseases. However, the existing diclofenac diethylamine emulsion has the problems of too fast drug release and too short action time, and the patient needs to frequently apply the drug, which increases the treatment burden and reduces the persistence of the treatment effect. In addition, the existing emulsion has obvious skin irritation while relieving joint pain. Therefore, it is necessary to develop a new type of diclofenac diethylamine emulsion. SUMMARY

[0003] In order to develop a new type of diclofenac diethylamine emulsion with less skin irritation, the present application provides a medicine for treating arthritis and a preparation method and application thereof. The medicine for treating arthritis (diclofenac diethylamine emulsion) provided by the present application has excellent skin permeability, and the synergistic effect of the stable drug-loaded structure formed by magnesium metasilicate aluminum and cetyltrimethylammonium bromide controls the release rate of the drug on the skin surface, thereby reducing the irritation of the drug and prolonging the action time of the drug, and effectively reducing the skin irritation by reducing the instantaneous high concentration exposure of the drug.

[0004] The present application provides a diclofenac diethylamine emulsion, which comprises a diclofenac diethylamine drug-loaded system. The diclofenac diethylamine drug-loaded system comprises magnesium metasilicate aluminum, diclofenac diethylamine, cetyltrimethylammonium bromide, propylene glycol and deionized water in a weight ratio of 4 g-10 g: 1 g-5 g: 0.1 g-1 g: 40 mL-60 mL: 90 mL-110 mL.

[0005] The present application controls the release rate of the drug on the skin surface through the synergistic effect of the stable drug-loaded structure formed by magnesium metasilicate aluminum and cetyltrimethylammonium bromide, thereby reducing the irritation of the drug and prolonging the action time of the drug.

[0006] Further, the weight ratio of the magnesium metasilicate aluminum, diclofenac diethylamine, cetyltrimethylammonium bromide, propylene glycol and deionized water is 4 g-6 g: 1 g-3 g: 0.4 g-0.6 g: 45 mL-55 mL: 95 mL-100 mL.

[0007] Further, the use amount ratio of the magnesium metasilicate aluminum, diclofenac diethylamine, cetyltrimethylammonium bromide, propylene glycol and deionized water is 5g:2g:0.5g:50mL:100mL.

[0008] Further, the diclofenac diethylamine emulsion further comprises an aqueous phase and an oil phase.

[0009] Further, the aqueous phase is prepared by mixing sodium hyaluronate, disodium edetate, ethyl p-hydroxybenzoate and deionized water; The oil phase is prepared by mixing vaseline, stearic acid and polysorbate.

[0010] Further, the aqueous phase is prepared by mixing sodium hyaluronate, disodium edetate, ethyl p-hydroxybenzoate and deionized water in a use amount ratio of 0.5g-2.0g:0.1g-0.5g:0.2g-0.4g:190mL-210mL; The oil phase is prepared by mixing vaseline, stearic acid and polysorbate 80 in a use amount ratio of 8g-12g:4g-6g:3g-6g.

[0011] Further, the aqueous phase is prepared by mixing sodium hyaluronate, disodium edetate, ethyl p-hydroxybenzoate and deionized water in a use amount ratio of 1g:0.2g:0.3g:200mL; The oil phase is prepared by mixing vaseline, stearic acid and polysorbate 80 in a use amount ratio of 10g:5g:3g.

[0012] The application further provides a preparation method of the diclofenac diethylamine emulsion, comprising the following steps: Preparation of the diclofenac diethylamine drug delivery system: disperse the magnesium metasilicate aluminum into deionized water to form a magnesium metasilicate aluminum colloid solution after sufficient swelling; Dissolve the diclofenac diethylamine in propylene glycol to obtain a diclofenac diethylamine solution; Mix the diclofenac diethylamine solution and the magnesium metasilicate aluminum colloid solution and fully react to obtain a reaction system; add cetyltrimethylammonium bromide into the reaction system to fully react to obtain the diclofenac diethylamine drug delivery system; The diclofenac diethylamine drug delivery system comprises the magnesium metasilicate aluminum, the diclofenac diethylamine, the cetyltrimethylammonium bromide, the propylene glycol and the deionized water in a use amount ratio of 4g-10g:1g-5g:0.1g-1g:40mL-60mL:90mL-110mL; Then, add the diclofenac diethylamine drug delivery system into the oil phase to uniformly disperse to obtain an oil phase containing the diclofenac diethylamine, and add the oil phase containing the diclofenac diethylamine into the aqueous phase to uniformly disperse to obtain the diclofenac diethylamine emulsion.

[0013] The application also provides the use of the medicine for treating arthritis in the preparation of a medicine for treating arthritis.

[0014] Compared with the prior art, the application has the beneficial effects that: The diclofenac diethylamine emulsion provided by the application mainly comprises a diclofenac diethylamine drug carrier system, and the release rate of the drug on the skin surface is controlled through the synergistic effect of the stable drug carrier structure formed by magnesium metasilicate aluminum and cetyltrimethylammonium bromide, so as to reduce the irritation of the drug and prolong the action time of the drug. The magnesium metasilicate aluminum can effectively adsorb the diclofenac diethylamine molecules to form a stable complex, so as to reduce the direct contact of the drug with the skin and reduce the irritation of the skin; the cationic surfactant cetyltrimethylammonium bromide (CTAB) not only enhances the solubility of the drug, but also forms a stable complex structure through the interaction with the silicate mineral (magnesium metasilicate aluminum), so as to effectively control the sustained release of the drug. The cationic part of the CTAB interacts with the negative charge on the surface of the carrier to form a double sustained release mechanism, so as to effectively prolong the release time of the drug. The magnesium silicate aluminum can control the release rate of the drug molecules through its unique structure and hydrophilic surface, and ensure that the drug is slowly and uniformly released to the skin surface. The CTAB enhances the binding force between the drug and the carrier through electrostatic adsorption, so as to slow down the release rate of the drug from the carrier. The CTAB can further optimize the skin permeability of the drug through the interaction with the skin surface.

[0015] The diclofenac diethylamine emulsion prepared by the application has excellent skin permeability, can effectively deliver the drug to the required site, and in the drug release process, the structure of the emulsion ensures that the drug is slowly released on the skin surface, reduces the direct irritation of the drug, and thus improves the use comfort and long-term treatment effect of the patient. BRIEF DESCRIPTION OF DRAWINGS

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description only constitute some embodiments of the application, and for those skilled in the art, other drawings can also be obtained without creative labor on the basis of these drawings.

[0017] Figure 1 The in vitro release curve of the diclofenac diethylamine emulsion prepared for the embodiment 1 of the application. DETAILED DESCRIPTION

[0018] The specific embodiments of the present application are described in detail below, but it should be understood that the scope of the present application is not limited to the specific embodiments. Based on the examples in the present application, all other examples obtained by those of ordinary skill in the art without creative work are within the scope of the present application. The experimental methods described in the embodiments of the present application are conventional methods, and the materials and reagents used in the following examples are commercially available unless otherwise specified.

[0019] Example 1: A drug for treating arthritis (diclofenac diethylamine emulsion) and a preparation method thereof.

[0020] 1. Preparation of a diclofenac diethylamine drug delivery system Magnesium metasilicate aluminum 5g was dispersed in 100mL deionized water, and stirred at 2500rpm in a high-speed stirrer for 45 minutes to form a uniform magnesium metasilicate aluminum colloid solution.

[0021] Diclofenac diethylamine 2g was dissolved in 50mL propylene glycol to prepare a diclofenac diethylamine solution.

[0022] The diclofenac diethylamine solution was slowly added to the magnesium metasilicate aluminum colloid solution at a stirring speed of 600rpm, and the addition time was controlled at 30 minutes. After the addition was completed, the stirring was continued for 2 hours to allow the magnesium metasilicate aluminum to fully embed the diclofenac diethylamine, and a embedding system was obtained.

[0023] 0.5g of cetyltrimethylammonium bromide was added to the embedding system, and the stirring reaction was continued for 1 hour to make the drug delivery system more stable, and a diclofenac diethylamine drug delivery system was obtained.

[0024] The magnesium metasilicate aluminum and cetyltrimethylammonium bromide (CTAB) form a stable drug delivery structure through electrostatic interaction. Magnesium metasilicate aluminum, as a drug carrier, has strong surface adsorption and good biocompatibility. Magnesium metasilicate aluminum can effectively adsorb diclofenac diethylamine molecules to form a stable complex, reducing the direct contact of the drug with the skin and thus reducing the skin irritation.

[0025] The cationic surfactant cetyltrimethylammonium bromide (CTAB) not only enhances the solubility of the drug in this system, but also forms a stable complex structure through interaction with magnesium metasilicate aluminum, thereby effectively controlling the sustained release of the drug. The cationic part of CTAB interacts with the negatively charged surface of the carrier, forming a double sustained release mechanism that effectively prolongs the release time of the drug.

[0026] It was found through detection that the loading capacity of diclofenac diethylamine in the diclofenac diethylamine drug delivery system was 5mg / g. The specific detection method is as follows:

[0027] Separation of diclofenac diethylamine drug-loaded system: centrifugation to remove unabsorbed drugs. Determine the concentration of free drugs: use UV-Vis or HPLC to analyze the drug concentration remaining in the supernatant. Calculate the diclofenac diethylamine loading according to the following formula:

[0028] Actual loading (mg / g) = (initial drug mass - free drug mass) / carrier mass.

[0029] 2. Preparation of a drug (diclofenac diethylamine emulsion) for treating arthritis (1) Add 1 g of sodium hyaluronate, 0.2 g of disodium edetate, and 0.3 g of ethyl p-hydroxybenzoate to 200 mL of deionized water, stir to dissolve, heat to 65°C, and continue stirring until completely dissolved and uniform to obtain an aqueous phase.

[0030] The combination of sodium hyaluronate and disodium edetate synergistically reduces skin irritation and promotes drug penetration.

[0031] (2) Mix 10 g of vaseline, 5 g of stearic acid, and 3 g of polysorbate 80 in the appropriate proportions, heat to 85°C, and stir until completely melted and mixed evenly to obtain an oil phase.

[0032] (3) Slowly add the diclofenac diethylamine drug-loaded system to the oil phase and stir for 45 minutes to ensure uniform dispersion. Then, slowly add the diclofenac diethylamine-containing oil phase to the aqueous phase under stirring and homogenize at 13000 rpm for 30 minutes to obtain a uniform and stable diclofenac diethylamine emulsion, which is a drug for treating arthritis.

[0033] This step ensures the stability of the emulsion by combining stepwise loading with high-speed homogenization.

[0034] The diclofenac diethylamine emulsion obtained from Example 1 and the ordinary emulsion were subjected to performance and safety testing. The specific testing methods and results are as follows.

[0035] I. Test Methods 1. In vitro release test detection method Supplementary test design and detection method (1) Materials and equipment The ordinary emulsion was purchased from GSK Consumer Healthcare Schweiz AG, with the item number KK2F.

[0036] Dialysis bag (MWCO 8-14 kDa, Spectrum Labs, USA); pH 7.4 PBS buffer (containing 0.1% Tween 80, filter sterilization); constant temperature water bath oscillator (model THZ-98A, temperature fluctuation ±0.2℃); HPLC system (Agilent 1260, equipped with automatic sampler).

[0037] 2. Experimental procedure ① Sample preparation: Accurately weigh 1.000±0.005 g (n=6) of the diclofenac diethylamine emulsion prepared in Example 1, the common emulsion, and the blank control, respectively, into the pretreated dialysis bag (double tied at both ends), and place the dialysis bag in a container containing 500.0±1.0 mL of PBS (37.0±0.5℃).

[0038] Blank control: an equal amount of blank matrix (same composition and preparation method as the diclofenac diethylamine emulsion in Example 1, except that it does not contain diclofenac diethylamine, which is used to calculate the cumulative release amount by deducting the excipient peak).

[0039] ② Release conditions: Medium volume: 500.0±1.0 mL PBS (37.0±0.5℃); shaking frequency: 50±1 rpm; operate in the dark.

[0040] ③ Sampling time points: Burst phase: 0.5, 1, 1.5, 2, 3, 4, 6 h; sustained release phase: 8, 12, 24, 48, 72, 96 h.

[0041] ④ Detection method: Sampling volume: 5.00 mL (immediately replenish); filtration: 0.22 μm PVDF filter membrane; HPLC conditions: column: Agilent ZORBAX SB-C18 (4.6×250 mm, 5 μm) mobile phase: methanol-0.1% phosphoric acid water (65:35, v / v). Flow rate: 1.0 mL / min. Detection wavelength: 276 nm. Injection volume: 20 μL. Retention time: diclofenac diethylamine 6.8±0.2 min.

[0042] 3. Data analysis Cumulative release amount calculation formula: Qn = Cn × V +∑ i =1 n −1 Ci × Vs ​Vs For sampling volume); Wherein, Qn: cumulative release amount at the nth time point (%); Cn: concentration measured at the nth sampling (μg / mL); V: total volume of medium (500 mL); Ci: concentration measured at the ith sampling (μg / mL); Vs: sampling volume (5 mL).

[0043] 2. Skin irritation test method (1) Animals and grouping SPF New Zealand rabbits weighing 2.5-3.0 kg, half male and half female, were selected and divided into four groups: the test group, the ordinary latex agent group, the blank matrix group, and the positive control group (0.5% SDS solution), with 8 rabbits in each group.

[0044] (2) Operation process ① Skin preparation: back hair removal (electric shaver + hair removal cream, hair removal area 5x5 cm²); 24 h after hair removal, confirm skin integrity (no erythema / edema).

[0045] ② Dosing regimen: single dose: 0.5 g of drug evenly applied (coverage area 2x2 cm²); semi-closed patch (3M Tegaderm™ film covering). Different groups of drugs were selected according to experimental grouping.

[0046] ③ Observation and scoring: drug removal time: 4±0.5 h; scoring time points: 1, 24, 48, 72, 96, 120 h; see Table 1 for scoring criteria. Table 1 Scoring criteria 3. Transdermal absorption test method (1) Materials Skin model: excised pig ear skin (thickness 0.8±0.05 mm, stored at -80℃ for ≤3 months).

[0047] Receiving solution: pH 7.4 PBS + 30% ethanol (37℃ saturated solubility verification).

[0048] Diffusion cell parameters: effective area: 1.766 cm² (diameter 15 mm); receiving chamber volume: 7.0±0.1 mL; stirring speed: 600±10 rpm (polytetrafluoroethylene magnetic stirrer).

[0049] (2) Operation steps ① Skin treatment: after thawing, soak in normal saline (37℃, 30 min); fix the stratum corneum upwards on the diffusion cell, with the dermis layer contacting the receiving solution.

[0050] ② Administration and sampling: Administration: 50.0±0.5 mg of latex (invention group and conventional latex group, spread by microsyringe); Sampling time: 1, 2, 4, 6, 8, 12, 24 h; Sample processing: Receiving solution: Direct HPLC detection; Skin: Homogenization followed by methanol ultrasonic extraction (40 kHz, 30 min).

[0051] 4. Stability test method The stability test method is shown in Table 2. The group of the present invention and the conventional latex group were tested under accelerated conditions (40°C / RH75%) for 1, 2, 3, and 6 months, and under long-term conditions (25°C / RH60%) for 3, 6, 9, and 12 months, and the sample content, pH value, and viscosity were tested.

[0052] Table 2 Stability test 2. Test results Table 3 Performance test results of diclofenac diethylamine emulsion prepared in Example 1 Note: “ / ” means no data for this item.

[0053] 1. Sustained release performance In vitro release curves showed that ( Figure 1 ), the diclofenac diethylamine emulsion in Example 1 of the present invention has a cumulative release of 89.2% in 72 hours, and a stable release rate (24h / 72h release ratio≈2:1), indicating that the diclofenac diethylamine drug delivery system (magnesium aluminum metasilicate-CTAB system) in the present invention significantly prolongs the drug action time, while the conventional emulsion has a burst release mode (release amount>80% in 4 hours).

[0054] 2. Transdermal enhancement As shown in Table 3, the epidermal drug retention of the diclofenac diethylamine emulsion prepared in Example 1 of the present invention was 3.2 times higher than that of a conventional emulsion (32.5 vs. 10.1 μg / cm²), demonstrating that sodium hyaluronate synergistically enhances drug accumulation at target skin sites. The steady-state permeation rate (Jss) of the diclofenac diethylamine emulsion prepared in Example 1 was 80% higher than that of a conventional emulsion, demonstrating that the diclofenac diethylamine emulsion prepared in Example 1 can maintain an effective therapeutic concentration.

[0055] 3. Stability advantage In the accelerated test, the drug retention rate was >95%, and the viscosity change rate was <5%, indicating that the oil phase combination of vaseline-stearic acid-polysorbate 80 in Example 1 of the present invention has excellent compatibility with the drug delivery system, which is far superior to that of ordinary latexes (retention rate <80%, viscosity change >30%).

[0056] 4. Skin safety The skin erythema and edema scores of the diclofenac diethylamine emulsion prepared in Example 1 of the present application are significantly lower than those of the common emulsion (reduced by more than 60%), proving that the diclofenac diethylamine emulsion prepared in Example 1 of the present application effectively reduces irritation by reducing the instantaneous high-concentration exposure of the drug.

[0057] Example 2: A diclofenac diethylamine emulsion and a preparation method thereof.

[0058] 1. Preparation of a diclofenac diethylamine drug delivery system Magnesium metasilicate 4g was dispersed in 90mL of deionized water, and stirred at 2000rpm in a high-speed stirrer for 50 minutes to allow it to swell sufficiently to form a uniform magnesium metasilicate colloid solution.

[0059] Diclofenac diethylamine 1g was dissolved in 40mL of propylene glycol to prepare a diclofenac diethylamine solution.

[0060] The diclofenac diethylamine solution was slowly added to the magnesium metasilicate colloid solution under stirring at a speed of 500rpm, and the addition time was controlled to be 30 minutes. After the addition was completed, the reaction was continued to stir for 2 hours to obtain a reaction system.

[0061] 0.1g of cetyltrimethylammonium bromide was added to the reaction system, and the reaction was continued to stir for 1 hour to make the drug delivery system more stable, thereby obtaining a diclofenac diethylamine drug delivery system.

[0062] 2. Preparation of a diclofenac diethylamine emulsion Sodium hyaluronate 0.5g, disodium edetate 0.1g, and ethyl p-hydroxybenzoate 0.2g were added to 190mL of deionized water, stirred and dissolved, heated to 65°C, and continuously stirred until completely dissolved and uniform to obtain an aqueous phase.

[0063] Sodium hyaluronate and disodium edetate are combined to reduce skin irritation and promote drug penetration.

[0064] Vaseline 8g, stearic acid 4g, and 3.0g of polysorbate 80 were mixed in proportion, heated to 85°C, and stirred until completely melted and uniformly mixed to obtain an oil phase.

[0065] The diclofenac diethylamine drug delivery system was slowly added to the oil phase, and stirred for 45 minutes to uniformly disperse, thereby obtaining an oil phase containing diclofenac diethylamine. Then, the oil phase containing diclofenac diethylamine was slowly added to the aqueous phase under stirring, and homogenized at 15000rpm for 30 minutes to prepare a uniform and stable diclofenac diethylamine emulsion.

[0066] Example 3: A diclofenac diethylamine emulsion and a preparation method thereof.

[0067] 1. Preparation of diclofenac diethylamine drug delivery system Disperse 10 g of magnesium aluminum metasilicate in 110 mL of deionized water and stir at 2500 rpm in a high-speed stirrer for 50 minutes to fully swell the mixture and form a uniform magnesium aluminum metasilicate colloidal solution.

[0068] Dissolve 5 g of diclofenac diethylamine in 60 mL of propylene glycol to prepare diclofenac diethylamine solution.

[0069] The diclofenac diethylamine solution was slowly added dropwise to the magnesium aluminum metasilicate colloidal solution while stirring at 500 rpm. The addition time was controlled within 30 minutes. After the addition was completed, the mixture was stirred and reacted for 2 hours to obtain a reaction system.

[0070] 1 g of hexadecyltrimethylammonium bromide was added to the reaction system, and the reaction was continued with stirring for 1 hour to make the drug-loading system more stable, thereby obtaining a diclofenac diethylamine drug-loading system.

[0071] 2. Preparation of diclofenac diethylamine emulsion Add 2 g of sodium hyaluronate, 0.5 g of disodium edetate, and 0.4 g of ethyl parahydroxybenzoate to 210 mL of deionized water, stir to dissolve, heat to 65°C, and continue stirring until completely dissolved to obtain an aqueous phase.

[0072] Sodium hyaluronate is combined with disodium edetate to reduce skin irritation and promote drug penetration.

[0073] Mix 12 g of vaseline, 6 g of stearic acid, and 6 g of polysorbate 80 in proportion, heat to 85°C, and stir until completely melted and mixed uniformly to obtain an oil phase.

[0074] The diclofenac diethylamine drug-carrying system was slowly added to the oil phase and stirred for 45 minutes to uniformly disperse the system to obtain an oil phase containing diclofenac diethylamine. The oil phase containing diclofenac diethylamine was then slowly added to the aqueous phase under stirring and homogenized at 15,000 rpm for 30 minutes to prepare a uniform and stable diclofenac diethylamine emulsion.

[0075] Example 4: A diclofenac diethylamine emulsion and a preparation method thereof.

[0076] The experimental steps were basically the same as those in Example 1, except that montmorillonite was used instead of magnesium aluminum metasilicate, and the CTAB concentration was adjusted to 0.3%.

[0077] Example 5: A diclofenac diethylamine emulsion and a preparation method thereof.

[0078] The test procedure is basically the same as that of Example 1, except that sodium hyaluronate is replaced by sodium carboxymethyl cellulose, and 0.05% of sodium heparin by mass percentage of the water phase is additionally added during the preparation of the water phase to compensate for the loss of moisturizing property.

[0079] Comparative Example 1: A diclofenac diethylamine emulsion and a preparation method thereof.

[0080] The composition is basically the same as that of Example 1, except that no magnesium metasilicate aluminum is added. The specific process is as follows:

[0081] 1. Dissolve 5g of diclofenac diethylamine in 60mL of propylene glycol to prepare a diclofenac diethylamine propylene glycol solution.

[0082] 2. Preparation of a diclofenac diethylamine emulsion Add 1g of sodium hyaluronate, 0.2g of disodium edetate, and 0.3g of ethyl p-hydroxybenzoate to 200mL of deionized water, stir to dissolve, heat to 65°C, and continue stirring until completely dissolved and uniform to obtain a water phase.

[0083] Sodium hyaluronate and disodium edetate are combined to reduce skin irritation and promote drug penetration.

[0084] Mix 10g of vaseline, 5g of stearic acid, and 3g of polysorbate 80 in proportion, heat to 85°C, stir until completely melted and mixed uniformly to obtain an oil phase.

[0085] Slowly add the diclofenac diethylamine drug delivery system to the oil phase, stir for 45 minutes to uniformly disperse, and obtain an oil phase containing diclofenac diethylamine. Then, slowly add the oil phase containing diclofenac diethylamine to the water phase under stirring, and homogenize at 13000rpm for 30 minutes to prepare a uniform and stable diclofenac diethylamine emulsion.

[0086] Comparative Example 2: A diclofenac diethylamine emulsion and a preparation method thereof.

[0087] The composition is basically the same as that of Example 1, except that the amount of magnesium metasilicate aluminum is 1g.

[0088] The preparation method is the same as that of Comparative Example 1.

[0089] Comparative Example 3: A diclofenac diethylamine emulsion and a preparation method thereof.

[0090] The composition is basically the same as that of Example 1, except that the amount of magnesium metasilicate aluminum is 15g.

[0091] The preparation method is the same as that of Comparative Example 1.

[0092] The cumulative release amount of the diclofenac diethylamine emulsion prepared in Example 1 and Comparative Examples 1-3 was detected respectively. The specific detection method was the same as above, and the detection results are shown in Table 4.

[0093] Table 4 Cumulative release amount of the diclofenac diethylamine emulsion prepared in Example 1 and Comparative Examples 1-3 The in vitro release curve is shown in Figure 1 The cumulative release amount of the diclofenac diethylamine emulsion in Example 1 was 89.2% in 72 hours, and the release rate was stable (24h / 72h release ratio ≈ 2:1), indicating that the diclofenac diethylamine drug delivery system (magnesium metasilicate aluminum-CTAB system) in the application significantly prolonged the drug action time. Comparative Example 1 without adding magnesium metasilicate aluminum was close to the burst mode (4-hour release amount close to 80%); Comparative Example 2 had a small amount of magnesium metasilicate aluminum, and the sustained-release effect was not significant; Comparative Example 3 had too much magnesium metasilicate aluminum, and the release rate was too slow, with a release amount of less than 50% in 72 hours, which could not effectively relieve pain.

[0094] Although the preferred embodiments of the present application have been described, those skilled in the art can make further changes and modifications to these embodiments once they know the basic inventive concept.

[0095] Obviously, those skilled in the art can make various modifications and variations to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application belong to the scope of the claims of the present application and their equivalent technologies, the present application also intends to include these modifications and variations.

Claims

1. A drug for treating arthritis, characterized in that It includes a diclofenac diethylamine drug delivery system; The diclofenac diethylamine drug-carrying system comprises silicate mineral, diclofenac diethylamine, hexadecyltrimethylammonium bromide, propylene glycol and deionized water in a dosage ratio of 4 g to 10 g: 1 g to 5 g: 0.1 g to 1 g: 40 mL to 60 mL: 90 mL to 110 mL.

2. The drug for treating arthritis according to claim 1, characterized in that The usage ratio of the silicate mineral, diclofenac diethylamine, hexadecyltrimethylammonium bromide, propylene glycol and deionized water is 4 g to 6 g: 1 g to 3 g: 0.4 g to 0.6 g: 45 mL to 55 mL: 95 mL to 100 mL.

3. The drug for treating arthritis according to claim 2, characterized in that The usage ratio of the silicate mineral, diclofenac diethylamine, hexadecyltrimethylammonium bromide, propylene glycol and deionized water is 5g:2g:0.5g:50mL:100mL.

4. The drug for treating arthritis according to any one of claims 1 to 3, characterized in that The diclofenac diethylamine emulsion further comprises an aqueous phase and an oily phase.

5. The drug for treating arthritis according to claim 4, characterized in that The aqueous phase is prepared by mixing sodium hyaluronate, disodium edetate, ethyl hydroxybenzoate and deionized water; The oil phase is a mixture of petrolatum, stearic acid and polysorbate.

6. The drug for treating arthritis according to claim 5, characterized in that The aqueous phase is prepared from sodium hyaluronate, disodium edetate, ethyl parahydroxybenzoate and deionized water in a dosage ratio of 0.5 g to 2.0 g: 0.1 g to 0.5 g: 0.2 g to 0.4 g: 190 mL to 210 mL; The oil phase is prepared from vaseline, stearic acid and polysorbate 80 in a mass ratio of 8-12:4-6:3-6.

7. The drug for treating arthritis according to claim 6, characterized in that The aqueous phase is prepared from sodium hyaluronate, disodium edetate, ethyl hydroxybenzoate and deionized water in a ratio of 1 g: 0.2 g: 0.3 g: 200 mL; The oil phase is made of petrolatum, stearic acid and polysorbate 80 in a ratio of 10g:5g:3g.

8. A method for preparing the drug for treating arthritis according to any one of claims 1 to 7, characterized in that: The steps include: Preparation of diclofenac diethylamine drug delivery system: silicate mineral is dispersed in deionized water and fully swelled to form silicate mineral colloidal solution; Dissolving diclofenac diethylamine in propylene glycol to obtain a diclofenac diethylamine solution; The diclofenac diethylamine solution and the silicate mineral colloidal solution are mixed and reacted fully to obtain a reaction system; cetyltrimethylammonium bromide is added to the reaction system and reacted completely to obtain the diclofenac diethylamine drug-carrying system of claim 1; The diclofenac diethylamine drug-carrying system includes silicate mineral, diclofenac diethylamine, hexadecyltrimethylammonium bromide, propylene glycol and deionized water in a dosage ratio of 4 g to 10 g: 1 g to 5 g: 0.1 g to 1 g: 40 mL to 60 mL: 90 mL to 110 mL; Then, the diclofenac diethylamine drug-carrying system is added to the oil phase and uniformly dispersed to obtain an oil phase containing diclofenac diethylamine. The oil phase containing diclofenac diethylamine is added to the water phase and uniformly dispersed to obtain a diclofenac diethylamine emulsion.

9. The method for preparing a drug for treating arthritis according to claim 8, characterized in that: The silicate mineral is magnesium aluminum metasilicate, silicon dioxide, montmorillonite, talc, muscovite, kaolinite or serpentine.

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

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