A formulation composition of arylpropionic acid non-steroidal anti-inflammatory drugs and a preparation method thereof

Abstract

The application discloses an arylpropionic acid non-steroidal anti-inflammatory drug preparation composition and a preparation method thereof. The composition is a solution preparation or a gel paste preparation containing arylpropionic acid non-steroidal anti-inflammatory drugs, and is characterized by containing arylpropionic acid non-steroidal anti-inflammatory drugs or isomers thereof and pharmaceutically acceptable solvents and adjuvants such as propylene glycol; wherein the mass / volume percentage of the arylpropionic acid non-steroidal anti-inflammatory drugs in the solution preparation ranges from 1 mg / ml to 40 mg / ml, and the volume percentage of the propylene glycol ranges from 50% to 100%; the mass percentage of the arylpropionic acid non-steroidal anti-inflammatory drugs in the gel paste preparation ranges from 1% to 10%, and the mass percentage of the propylene glycol ranges from 5% to 12%. The arylpropionic acid non-steroidal anti-inflammatory drugs in the prescription are in RS-configuration or derivatives, R-configuration or derivatives, S-configuration or derivatives, or a combination of the R-configuration or derivatives and the S-configuration or derivatives in any ratio; and the pH regulator is one or more of lysine, arginine, tromethamine, meglumine and the like.

Description

Technical Field

[0001] This invention relates to the technical field of pharmaceutical preparations, specifically to arylpropionic acid nonsteroidal anti-inflammatory drug preparations, gel patch preparations, and their preparation methods. Background Technology

[0002] Arylpropionic acid nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of anti-inflammatory drugs that do not contain a steroidal structure. They are obtained by introducing a methyl group onto the α-carbon atom of arylacetic acid. Representative drugs include flurbiprofen, loxoprofen, pranoprofen, and ibuprofen. The introduction of the methyl group restricts the free rotation of the carboxyl group, maintaining a conformation suitable for receptors or enzyme structures, thereby improving anti-inflammatory effects and reducing toxic side effects. Simultaneously, the introduction of the methyl group makes the α-carbon atom of the carboxyl group a chiral carbon atom. Due to the unique structure of arylpropionic acid NSAIDs, problems such as crystallization and instability often occur when developing solution formulations and gel / patch formulations.

[0003] For example, flurbiprofen solution formulations were first developed and marketed by Japan's Kenshin Pharmaceutical Co., Ltd. in 1992. Later, domestic companies began to conduct formulation, process, and stability studies on flurbiprofen and flurbiprofen salt-containing formulations. However, due to flurbiprofen's near-insoluble nature in water, the tendency for visible foreign matter in the formulations to lead to non-compliance, and the ease with which impurities exceed standards, no flurbiprofen injectable formulations have been successfully marketed to date. Similarly, in research on flurbiprofen gel patch formulations, crystallization of the active pharmaceutical ingredient often occurs, leading to non-compliance in properties.

[0004]

[0005] Flurbiprofen structural formula

[0006] Patent CN103301101A discloses a novel pharmaceutical composition of 2-(2-fluoro-4-biphenyl)-propionic acid, which combines flurbiprofen with the basic amino acid arginine or lysine to form a pharmaceutical composition solution. The composition is simple, but its stability is relatively poor, especially its long-term stability. After 6 months, the content of related substances is high, and turbidity and other phenomena occur, which pose a significant risk to the safety of medication.

[0007] Patent CN111494308A discloses a flurbiprofen injection composition, which combines flurbiprofen with amino polyols, such as tromethamine and meglumine, to form a drug solution. The formulation prepared according to this prescription also exhibits poor long-term stability, showing significant turbidity after being stored under long-term conditions (30℃±2℃ / RH65%±5%) for 6 months.

[0008] Patent CN111494307A discloses a flurbiprofen injection composition, which combines flurbiprofen with a phosphate, such as disodium hydrogen phosphate, to form a drug solution. The formulation prepared according to this prescription also exhibits poor long-term stability (30℃±2℃ / RH65%±5%), showing significant turbidity after 6 months. This poses a significant risk to clinical drug safety. Summary of the Invention

[0009] To overcome the shortcomings of existing technologies and improve the problems of turbidity, crystallization, unqualified appearance, visible foreign matter, insoluble particulate matter, and high content of related substances in aryl propionic acid nonsteroidal anti-inflammatory drug solutions and gel patches during actual storage, the inventors, through long-term formulation process screening and literature review, have obtained a key excipient that ensures that all key indicators of aryl propionic acid nonsteroidal anti-inflammatory drug solutions, including appearance, visible foreign matter, insoluble particulate matter, and related substances, meet the standards under various influencing factors, accelerated conditions, and long-term conditions.

[0010] The specific technical solution of this invention is as follows:

[0011] A pharmaceutically acceptable solvent and excipients comprising an aryl propionic acid nonsteroidal anti-inflammatory drug or its isomers, lower fatty alcohols such as propylene glycol and butylene glycol, etc. The composition is characterized in that the solution composition contains an aryl propionic acid nonsteroidal anti-inflammatory drug at a mass-volume percentage ranging from 1 mg / ml to 40 mg / ml, and a lower fatty alcohol at a volume percentage ranging from 50% to 100%; the gel / patch dosage form composition contains an aryl propionic acid nonsteroidal anti-inflammatory drug at a mass percentage ranging from 1% to 10%, and a lower fatty alcohol at a mass percentage ranging from 5% to 12%.

[0012] The aryl propionic acid nonsteroidal anti-inflammatory drug in the composition is an RS-configuration or a derivative thereof, an R-configuration or a derivative thereof, an S-configuration or a derivative thereof, or any combination of an R-configuration or a derivative thereof and an S-configuration or a derivative thereof in any proportion.

[0013] The composition also contains a pH adjuster, which is one or more of lysine, arginine, tromethamine, meglumine, etc., and the pH value of the adjusting preparation is between 5.0 and 9.5.

[0014] The aryl propionic acid nonsteroidal anti-inflammatory drug in the composition is selected from one or more of the following: flurbiprofen, loxoprofen, pranoprofen, ketoprofen, ibuprofen, and naproxen.

[0015] The beneficial effects of adopting the technical solution of this invention are:

[0016] The aryl propionic acid nonsteroidal anti-inflammatory drug solution formulation of the present invention, by adding specific excipients, lower fatty alcohols, can significantly improve the turbidity problem of the corresponding solution formulation compared with formulations without lower fatty alcohols, and solve problems such as easy turbidity, visible foreign matter, failure to pass the detection of insoluble particles, and excessive impurity content in the solution formulation; it also improves the crystallization problem of gel patches and solves problems such as unqualified properties. Detailed Implementation

[0017] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. This should not be construed as limiting the scope of this patent application. Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing specific embodiments only and are not intended to limit the scope of protection of this invention. Unless otherwise specified, all reagents and raw materials used in this invention are commercially available products or products that can be prepared by known methods.

[0018] To better illustrate the present invention, further examples are provided below.

[0019] Example 1

[0020]

[0021] Preparation process:

[0022] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add 0.4 g of lysine and 0.6 g of S-flurbiprofen. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 7.1. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials and sterilize at 121 °C for 15 min to obtain the finished product.

[0023] Example 2

[0024]

[0025] Preparation process:

[0026] Add an appropriate amount of propylene glycol to the prepared solution system, then add 0.4 g of lysine and 0.6 g of R-flurbiprofen. After stirring and dissolving evenly, add propylene glycol to bring the volume to 100 ml and measure the pH value to 7.4. Filter the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials, and sterilize at 121℃ for 15 min to obtain the finished product.

[0027] Example 3

[0028]

[0029] Preparation process:

[0030] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add 0.06 g of tromethorphan and 0.1 g of S-flurbiprofen. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 5.3. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials and sterilize at 121 °C for 15 min to obtain the finished product.

[0031] Example 4

[0032]

[0033] Preparation process:

[0034] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add 3.6 g of meglumine and 4.0 g of R-flurbiprofen. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 7.7. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials and sterilize at 121 °C for 15 min to obtain the finished product.

[0035] Example 5

[0036]

[0037] Preparation process:

[0038] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add S-flurbiprofen lysine. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 7.6. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials and sterilize at 121°C for 15 min to obtain the finished product.

[0039] Example 6

[0040]

[0041] Preparation process:

[0042] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add R-flurbiprofen arginine. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 7.6. After filtering the above solution through one 0.45 μm and two 0.22 μm polytetrafluoroethylene membranes, it is filled into 5 ml vials to obtain the finished product.

[0043] Example 7

[0044]

[0045] Preparation process:

[0046] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add S-flurbiprofen tromethamine. After stirring and dissolving evenly, adjust the pH to 9.5 using sodium hydroxide solution, and add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 8.9. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials, and sterilize at 121°C for 15 min to obtain the finished product.

[0047] Example 8

[0048]

[0049] Preparation process:

[0050] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add S-praprofen lysine. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 7.5. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials and sterilize at 121°C for 15 min to obtain the finished product.

[0051] Example 9

[0052]

[0053] Preparation process:

[0054] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add arginine and S-loxoprofen. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 7.8. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials and sterilize at 121°C for 15 min to obtain the finished product.

[0055] Example 10

[0056]

[0057] Preparation process:

[0058] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, lysine, butylated hydroxytoluene, and silica are added and stirred evenly. S-flurbiprofen is then added and stirred evenly to obtain the ointment. The pH value of the ointment is 8.4.

[0059] The ointment is evenly applied to the protective layer, then bonded to the backing layer, and finally cut to a size of 5cm×5cm to obtain the flurbiprofen patch.

[0060] Example 11

[0061]

[0062] Preparation process:

[0063] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, arginine, butylated hydroxytoluene, and silica are added and stirred evenly. Then R-flurbiprofen is added and stirred evenly to obtain the ointment. The pH value of the ointment is 8.5.

[0064] The ointment is evenly applied to the protective layer, then bonded to the backing layer, and finally cut to a size of 5cm×5cm to obtain the flurbiprofen patch.

[0065] Example 12

[0066]

[0067] Preparation process:

[0068] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, tromethamine, butylated hydroxytoluene, and silica are added and stirred evenly. Then, S-flurbiprofen lysine is added and stirred evenly to obtain the ointment. The pH value of the ointment is 5.2.

[0069] The ointment is evenly applied to the protective layer, then bonded to the backing layer, and finally cut to a size of 5cm×5cm to obtain the flurbiprofen patch.

[0070] Example 13

[0071]

[0072] Preparation process:

[0073] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, meglumine, butylated hydroxytoluene, and silica are added and stirred evenly. Then, R-flurbiprofen lysine is added and stirred evenly to obtain the ointment. The pH value of the ointment is 8.7.

[0074] The ointment is evenly applied to the protective layer, then bonded to the backing layer, and finally cut to a size of 5cm×5cm to obtain the flurbiprofen patch.

[0075] Example 14

[0076]

[0077] Preparation process:

[0078] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, arginine, butylated hydroxytoluene, and silica are added and stirred evenly. Then, S-pranoprofen lysine is added and stirred evenly to obtain the ointment. The pH value of the ointment is 7.3.

[0079] The ointment is evenly applied to the protective layer, then attached to the backing layer, and finally cut to a size of 5cm×5cm to obtain the Pranoprofen patch.

[0080] Example 15

[0081]

[0082] Preparation process:

[0083] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Butylene glycol, lysine, butylated hydroxytoluene, and silica are added and stirred evenly. Then, S-loxoprofen is added and stirred evenly to obtain the ointment. The pH value of the ointment is 8.1.

[0084] The ointment is evenly applied to the protective layer, then attached to the backing layer, and finally cut to a size of 5cm×5cm to obtain the loxoprofen patch.

[0085] Comparative Example 1

[0086]

[0087] Preparation process:

[0088] Add an appropriate amount of water for injection to the solution preparation system, then add 0.3g of lysine and 0.6g of S-flurbiprofen. After stirring and dissolving evenly, add water for injection to bring the volume to 100ml. The pH of the solution is measured to be 4.8. After passing the above solution through a 0.22μm polytetrafluoroethylene filter membrane, fill into 5ml vials and sterilize at 121℃ for 15min to obtain the finished product.

[0089] Comparative Example 2

[0090]

[0091] Preparation process:

[0092] Add an appropriate amount of water for injection to the solution preparation system, then add 0.3g of tromethorphan and 0.6g of D-flurbiprofen. After stirring and dissolving evenly, add water for injection to bring the volume to 100ml. The pH of the solution is measured to be 6.6. After passing the above solution through a 0.22μm polytetrafluoroethylene filter membrane, fill into 5ml vials and sterilize at 121℃ for 15min to obtain the finished product.

[0093] Comparative Example 3

[0094]

[0095] Preparation process:

[0096] Add the prescribed amount of propylene glycol and an appropriate amount of water for injection to the solution preparation system, then add 1.2 g of S-flurbiprofen lysine. After stirring and dissolving evenly, add water for injection to bring the volume to 100 ml. The pH of the solution is measured to be 7.6. After passing the above solution through a 0.22 μm polytetrafluoroethylene filter membrane, fill into 5 ml vials and sterilize at 121 °C for 15 min to obtain the finished product.

[0097] Comparative Example 4

[0098]

[0099] Preparation process:

[0100] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, lysine, butylated hydroxytoluene, and silica are added and stirred evenly. S-flurbiprofen is then added and stirred evenly to obtain the ointment. The pH value of the ointment is 8.2.

[0101] The ointment is evenly applied to the protective layer, then bonded to the backing layer, and finally cut to a size of 5cm×5cm to obtain the flurbiprofen patch.

[0102] Comparative Example 5

[0103]

[0104] Preparation process:

[0105] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, lysine, butylated hydroxytoluene, and silica are added and stirred evenly. S-flurbiprofen is then added and stirred evenly to obtain the ointment. The pH value of the ointment is 7.5.

[0106] The ointment is evenly applied to the protective layer, then bonded to the backing layer, and finally cut to a size of 5cm×5cm to obtain the flurbiprofen patch.

[0107] Comparative Example 6

[0108]

[0109] Preparation process:

[0110] According to the formula composition ratio, styrene / isoprene / styrene copolymer, polyisobutylene, hydrogenated rosin glycerol ester, and liquid paraffin are heated until melted. Propylene glycol, lysine, butylated hydroxytoluene, and silica are added and stirred evenly. S-flurbiprofen is then added and stirred evenly to obtain the ointment. The pH value of the ointment is 4.7.

[0111] The ointment is evenly applied to the protective layer, then bonded to the backing layer, and finally cut to a size of 5cm×5cm to obtain the flurbiprofen patch.

[0112] The inventors conducted a systematic stability study on each formulation sample in the above embodiments and comparative examples. For liquid formulations, the study included changes in appearance, visible foreign matter, insoluble particles, and related substances. For semi-solid formulations, the study mainly examined appearance to confirm whether there was any precipitation of the active pharmaceutical ingredient.

[0113] Experimental Example 1

[0114] Appearance: Liquid preparations were assessed by visual inspection; gel patches were assessed by a combination of visual inspection and polarized light microscopy.

[0115] Experimental Example 2

[0116] Visible foreign matter: Tested according to the first method (lamp inspection method) in the 0904 Visible Foreign Matter Inspection Method of the Chinese Pharmacopoeia, Volume IV, 2020.

[0117] Experimental Example 3

[0118] Insoluble microparticles: According to the 0903 Insoluble Microparticle Test Method in Part IV of the 2020 Chinese Pharmacopoeia.

[0119] The first method (optical obscuration method) is used for detection.

[0120] Experiment Example 4

[0121] Related substances method (high performance liquid chromatography) (flurbiprofen solution preparation):

[0122] Chromatographic conditions:

[0123] Chromatographic column: octadecylsilane-bonded silica gel is used as the packing material (Kromasil 100-5-C18 4.6mm × 250mm or a column with equivalent performance).

[0124] Mobile phase: 1.26 g / L ammonium formate solution (pH adjusted to 3.0 with formic acid) was used as mobile phase A; methanol-acetonitrile (50:50) was used as mobile phase B; the flow rate was 1.0 mL / min; the column temperature was 30 °C; the detection wavelength was 254 nm; the injection volume was 10 μL, and the gradient was as follows:

[0125]

[0126] Test solution: Take an appropriate amount of this product, accurately weigh it, dissolve it in 45% acetonitrile solution and dilute it quantitatively to prepare a solution containing about 1 mg of flurbiprofen per 1 ml.

[0127] Reference solution: Weigh appropriate amounts of flurbiprofen reference standard and impurity I reference standard accurately, dissolve them in 45% acetonitrile solution to prepare a solution containing 1 μg each of flurbiprofen and impurity I per 1 ml.

[0128] Sensitivity solution: Take an appropriate amount of flurbiprofen reference standard, dissolve it in 45% acetonitrile solution, and prepare a solution containing 0.5 μg per 1 ml.

[0129] System suitability solution: Take appropriate amounts of flurbiprofen reference standard and impurity I reference standard, dissolve them in 45% acetonitrile solution to prepare a solution containing 1 mg of flurbiprofen and 5 μg of impurity I per 1 ml.

[0130] Limits: If there is a chromatographic peak in the chromatogram of the test solution that has the same retention time as impurity I, the peak area calculated by the external standard method shall not exceed 0.5%. Other impurities shall be calculated by the external standard method of the main component, and the peak area of ​​a single impurity shall not exceed 0.1%, and the sum of all impurities shall not exceed 1.0%.

[0131]

[0132] Impurity I structural formula

[0133] The test results are summarized below:

[0134]

[0135]

[0136]

[0137]

[0138]

[0139] The test results show that:

[0140] After 6 months of accelerated and long-term condition testing, the liquid formulation samples of Examples 1, 2, 3, 4, 5, 6, 7, 8, and 9 all showed that their properties, visible foreign matter, insoluble microparticles, and (related substances) were within acceptable limits.

[0141] After 6 months of accelerated and long-term condition testing, the liquid formulation samples of Comparative Examples 1, 2, and 3 showed varying degrees of abnormalities in appearance, visible foreign matter, and insoluble microparticles, and a significant increase in related substances.

[0142] After 6 months of accelerated and long-term condition testing, the gel patch samples of Examples 10, 11, 12, 13, 14, and 15 showed no significant changes in properties and no crystallization.

[0143] After 6 months of accelerated and long-term testing, the gel patch samples of Comparative Examples 4, 5, and 6 showed phenomena such as crystallization and colloidal exudation, and their properties were unqualified.

[0144] Acceptable standards for liquid dosage forms:

[0145] (1) Properties: Clear and transparent solution.

[0146] (2) Visible foreign matter: The test sample shall not contain metal shavings, glass shavings, fibers longer than 2 mm, lumps with a maximum particle size of 2 mm, smoke-like particulate deposits visible to the naked eye when gently rotated after standing for a certain period of time, uncountable particle clusters, or sediments that cannot be dispersed by shaking.

[0147] (3) Insoluble microparticles: The number of microparticles with a diameter of 10 μm or larger in each sample container shall not exceed 6,000, and the number of microparticles with a diameter of 25 μm or larger shall not exceed 600.

[0148] (4) Related substances (flurbiprofen): Impurity I shall not exceed 0.5%, a single impurity shall not exceed 0.1%, and the sum of all impurities shall not exceed 1.0%.

[0149] The test results show that Comparative Example 1, which did not contain lower fatty alcohols and had a lower pH value, and Comparative Example 2, which did not contain lower fatty alcohols, failed the tests for appearance, visible foreign matter, and insoluble particles under accelerated and long-term conditions of 6 months and 6 months, respectively, and related substances increased significantly. Comparative Example 3, which contained 45% propylene glycol, failed the tests for appearance, visible foreign matter, and insoluble particles, and related substances increased slightly.

[0150] Acceptable standards for the properties of gel patch formulations:

[0151] It has uniform properties, no obvious color change, no colloidal exudation, and no crystallization.

[0152] The test results show that Comparative Example 4 (with 4% propylene glycol), Comparative Example 5 (with 15% propylene glycol), and Comparative Example 6 (with pH 4.7) exhibited changes in properties and failed to meet the standards under accelerated and long-term conditions of 6 months and 6 months, respectively.

Claims

1. A composition containing an aryl propionic acid nonsteroidal anti-inflammatory drug, characterized in that... The composition contains aryl propionic acid nonsteroidal anti-inflammatory drugs or their isomers, lower fatty alcohols such as propylene glycol and butylene glycol, pharmaceutically acceptable solvents, and excipients; The solution composition contains aryl propionic acid nonsteroidal anti-inflammatory drugs in a mass-volume percentage range of 1 mg / ml to 40 mg / ml and lower fatty alcohols in a volume-volume percentage range of 50% to 100%; the semi-solid compositions such as gel patches contain aryl propionic acid nonsteroidal anti-inflammatory drugs in a mass-volume percentage range of 1% to 10% and lower fatty alcohols in a mass-volume percentage range of 5% to 12%.

2. The composition according to claim 1, characterized in that... It also contains a pH adjuster.

3. A solution formulation of an aryl propionic acid-containing nonsteroidal anti-inflammatory drug according to claims 1-2, characterized in that, Arylpropionic acid nonsteroidal anti-inflammatory drugs are RS-configuration or derivatives thereof, R-configuration or derivatives thereof, S-configuration or derivatives thereof, or any combination of R-configuration or derivatives thereof and S-configuration or derivatives thereof in any proportion.

4. The composition according to claims 1-3, characterized in that, pH adjusters are one or more of the following: lysine, arginine, tromethamine, meglumine, etc.

5. The composition according to claim 1, wherein the pH value ranges from 5.0 to 9.5, preferably from 7.0 to 9.

0.

6. The aryl propionic acid nonsteroidal anti-inflammatory drug according to claims 1-3 is selected from one or more combinations of flurbiprofen, loxoprofen, pranoprofen, ketoprofen, ibuprofen and naproxen.

7. The lower fatty alcohol according to claim 1 is one or a combination of several of propylene glycol, ethanol, phenoxyethanol, diethylene glycol monoethyl ether, and butanediol.

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