Lipoic acid pharmaceutical composition and preparation method thereof

Abstract

The invention discloses a lipoic acid pharmaceutical composition and a preparation method thereof, the form of the pharmaceutical composition is wet particles, and the pharmaceutical composition comprises lipoic acid, hydroxy propyl cellulose and an ethanol aqueous solution; the preparation method comprises the following steps: adding an ethanol aqueous solution of hydroxy propyl cellulose into a lipoic acid-containing mixed material, carrying out wet granulation, and controlling the concentration of the ethanol aqueous solution to be 20-60%, the problems of sticking and cracking in the tabletting process are avoided, and process feasibility is achieved; moreover, the dosage of the ethanol aqueous solution of the hydroxy propyl cellulose is only 15-30% of the mass of the lipoic acid, so that the problem of difficult particle drying caused by excessive wetting is avoided, and industrial production is facilitated.

Description

Technical Field

[0001] The present invention belongs to the technical field of lipoic acid preparations, and particularly relates to a lipoic acid pharmaceutical composition and a preparation method thereof. Background Art

[0002] Lipoic acid, also known as α-lipoic acid, is an eight-carbon fatty acid with dual characteristics of water solubility and fat solubility. Lipoic acid can effectively eliminate oxygen free radicals, chelate metal ions and regenerate other antioxidants in the body, and is a potent multifunctional oxidative stress inhibitor. The American Diabetes Association (ADA) guidelines and the European Association for the Study of Diabetes (EASD) guidelines in Europe unanimously regard lipoic acid as a first-line drug for the prevention and treatment of diabetic neuropathy; the "Expert Consensus on Diabetic Peripheral Neuropathy" of the Chinese Medical Doctor Association recommends lipoic acid for the etiological and symptomatic treatment of diabetic neuropathy. Based on abundant evidence-based medical evidence, the antioxidant stress treatment of diabetic neuropathy with lipoic acid has gradually become the mainstream clinical treatment plan.

[0003] Currently, lipoic acid preparations marketed globally include tablets, injections, soft capsules, etc. The original research manufacturer of lipoic acid tablets is MEDA Pharmaceuticals in Germany, with the trade name Thioctacid, and the specifications are 0.2g and 0.6g. The drug instruction manual discloses that its excipient composition is hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate and coating materials (hydroxypropyl methylcellulose, polyethylene glycol 6000, talc powder, titanium dioxide, quinoline yellow, aluminum lake, indigo carmine, aluminum salt).

[0004] However, the development of lipoic acid tablets has its technical difficulties: the melting point of lipoic acid is about 60°C. When the lipoic acid content in the tableting material is greater than 45%, problems such as sticking to the punch and capping are likely to occur during the tableting process; increasing the amount of excipients to dilute the main drug content can overcome the tableting problems, but it will lead to an increase in tablet weight and tablet diameter, making it difficult for patients to swallow. Therefore, it is necessary to develop a lipoic acid tablet and its preparation method to overcome the tableting problems while increasing the main drug content.

[0005] The original research formulation patent US5376382A solves the above-mentioned main drug content and tableting problems by a method of wet granulation with the addition of a large amount of water or binder solution (more than 30% of the main drug mass). Examples 3 and 4 disclose a preparation method of a lipoic acid tablet: a mixture of lipoic acid and hydroxypropyl cellulose is wet granulated with water accounting for 60% of the mass of lipoic acid. After the granules are dried, they are mixed with magnesium stearate and then tableted to obtain tablets with a lipoic acid content of 300mg / 331mg tablet weight and smooth and crack-free tablet surfaces. However, this preparation method of lipoic acid tablets has the problem of difficult drying of over-wetted granules, which is not conducive to industrial production.

[0006] Reference 1 (Ni Huali. Experimental Study on Thioctic Acid Tablets [D]. Shandong University, 2013.) solved the above-mentioned problems of the main drug content and tableting by optimizing the type and dosage of lubricants. "2.5 Verification of the Optimal Prescription and Process" discloses a thioctic acid tablet: 300 g / tablet of thioctic acid, 100 g / tablet of microcrystalline cellulose, 50 g / tablet of sodium carboxymethyl starch, 140 - 160 g / tablet of 3% PVP ethanol solution, 15 g / tablet of colloidal silicon dioxide, and 5 g / tablet of magnesium stearate. However, the improvement of the type and dosage of lubricants on the tableting problem is limited, and a large amount of excipients such as diluents are still required, resulting in the thioctic acid content in the obtained tablets being less than 60%, and the main drug content not being significantly increased.

[0007] Patent CN 113181129 A solved the above-mentioned problems of the main drug content and tableting through a secondary granulation process combining wet granulation and dry granulation. Example 3 discloses a preparation method of a thioctic acid tablet: a mixture of thioctic acid, low-substituted hydroxypropyl cellulose and hydroxypropyl cellulose is wet granulated with an appropriate amount of 50% ethanol solution. After the granules are dried, they are mixed with low-substituted hydroxypropyl cellulose and magnesium stearate and dry granulated, and magnesium stearate is added for total mixing and tableting to obtain a tablet with a thioctic acid content of 600 mg / 800 mg tablet weight and no sticking during tableting. However, this preparation method of the thioctic acid tablet has the disadvantage of a complex granulation process, which is not conducive to industrial production.

[0008] In summary, providing a thioctic acid pharmaceutical composition and its preparation method, which can solve the problems of the main drug content and tableting at the same time, avoid the problems of multiple granulations and difficult particle drying to be suitable for industrial production, and improve the preparation quality stability of the composition product, is a technical problem that has not been solved in this field. Summary of the Invention

[0009] The first technical problem to be solved by the present invention is to provide a thioctic acid pharmaceutical composition and its preparation method, which can improve the main drug content while overcoming the tableting problem by wet granulation with an aqueous ethanol solution of hydroxypropyl cellulose as a binder, and avoid the problems of multiple granulations and difficult particle drying, which is conducive to industrial production.

[0010] Due to the particularity of the thioctic acid material, when wet granulation is carried out using a binder, although the influence of a specific type of binder on solving the sticking problem during tableting is investigated; the inventor further studies and finds that after solving the sticking problem during tableting, due to the difference in the selection of the binder type, it will also have a different impact on the dissolution stability of the preparation (especially the long-term stability of the preparation), which is not conducive to the quality control of the preparation during industrial production.

[0011] Therefore, the second technical problem to be solved by the present invention is: on the basis of solving problems such as sticking or capping of tablets, by optimizing the selection of a specific type of hydroxypropyl cellulose and an appropriate dosage, to ensure the dissolution stability after 6 months of acceleration, which is beneficial to the long-term stability of the preparation quality of the lipoic acid pharmaceutical composition.

[0012] The technical problem of the present invention is solved by the following technical solutions:

[0013] On the one hand, the present invention provides a lipoic acid pharmaceutical composition, and the form of the pharmaceutical composition is wet granules, which includes lipoic acid, hydroxypropyl cellulose, and an aqueous ethanol solution.

[0014] Preferably, the ratio of hydroxypropyl cellulose and aqueous ethanol solution to lipoic acid is (0.15 - 0.3):1 (w / w).

[0015] Preferably, the concentration of the aqueous ethanol solution is 20 - 60 wt%.

[0016] More preferably, the concentration of the aqueous ethanol solution is 30 - 45 wt%.

[0017] Preferably, the hydroxypropyl cellulose is low-viscosity hydroxypropyl cellulose, including but not limited to one or more of hydroxypropyl cellulose ELF, hydroxypropyl cellulose EXF, and hydroxypropyl cellulose LXF.

[0018] More preferably, the hydroxypropyl cellulose is hydroxypropyl cellulose ELF.

[0019] Preferably, the ratio of hydroxypropyl cellulose to lipoic acid is (0.01 - 0.1):1 (w / w).

[0020] More preferably, the ratio of hydroxypropyl cellulose to lipoic acid is (0.015 - 0.05):1 (w / w).

[0021] More preferably, the mass ratio of hydroxypropyl cellulose to lipoic acid is 1.5%, or 3.33%, or 5%.

[0022] Preferably, it further includes pharmaceutically acceptable excipients added internally, including but not limited to diluents and disintegrants.

[0023] More preferably, the diluents include but not limited to one or more of microcrystalline cellulose, starch, lactose, and calcium phosphate.

[0024] More preferably, the disintegrants include but not limited to one or more of low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, and polyvinylpyrrolidone.

[0025] More preferably, the ratio of other pharmaceutically acceptable excipients to lipoic acid is (0 - 0.25):1 (w / w).

[0026] The types and dosages of pharmaceutically acceptable excipients added internally do not have a significant impact on the tableting problem of lipoic acid. Appropriate addition of excipients can improve the color difference problem of lipoic acid. However, increasing the dosage of excipients is not suitable for solving the lipoic acid content problem. Those skilled in the art can know that on the basis of solving the technical problem, the dosage of excipients should be minimized as much as possible. Therefore, the types and dosages of pharmaceutically acceptable excipients added internally can be appropriately adjusted.

[0027] Preferably, calculated by weight, it comprises the following components:

[0028] Lipoic acid 600 parts by weight

[0029] Hydroxypropyl cellulose 6 - 30 parts by weight

[0030] Ethanol aqueous solution 90 - 150 parts by mass.

[0031] More preferably, calculated by weight, it comprises the following components:

[0032]

[0033] Most preferably, calculated by weight, it comprises the following components:

[0034]

[0035] A preparation method of a lipoic acid pharmaceutical composition, comprising adding an ethanol aqueous solution of hydroxypropyl cellulose to a mixed material containing lipoic acid for wet granulation.

[0036] A preparation method of a lipoic acid pharmaceutical composition, comprising the following steps:

[0037] a) Mix lipoic acid or lipoic acid and pharmaceutically acceptable excipients added internally evenly;

[0038] b) Add an ethanol aqueous solution of hydroxypropyl cellulose for wet granulation;

[0039] c) Wet screening.

[0040] Preferably, in step a), wet granulation is carried out using a wet granulator.

[0041] More preferably, in step a), the stirring speed of the wet granulator is 150 - 300 rpm, and the cutter speed is 900 - 1500 rpm.

[0042] Preferably, in step b), wet granulation is carried out using a wet granulator.

[0043] More preferably, in step b), the stirring speed of the wet granulator is 150 - 300 rpm, and the cutter speed is 900 - 1500 rpm.

[0044] Preferably, the aqueous ethanol solution of hydroxypropyl cellulose in step b) is added in a reverse slurry manner or a spraying slurry manner.

[0045] Preferably, in step b), the liquid addition time for wet granulation is 2 - 5 min, and the granulation time is 2 - 5 min.

[0046] Preferably, in step c), a swing granulator is used for wet screening and sizing.

[0047] More preferably, in step c), the mesh number of the wet screening and sizing sieve is 16 - 24 meshes.

[0048] Those skilled in the art can appropriately adjust the process equipment and process parameter ranges according to the phenomena during the wet granulation process to achieve the purpose of preparing wet granules.

[0049] On the other hand, the present invention provides a lipoic acid pharmaceutical composition in the form of tablets, which includes the above-mentioned wet granules and externally added pharmaceutically acceptable excipients. Among them, the aqueous ethanol solution is removed during the production process.

[0050] Preferably, the externally added pharmaceutically acceptable excipients include, but are not limited to, one or more of diluents, disintegrants, lubricants, and film coating premixes.

[0051] More preferably, the diluents include, but are not limited to, one or more of microcrystalline cellulose, starch, lactose, and calcium phosphate.

[0052] More preferably, the disintegrants include, but are not limited to, one or more of low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, and polyvinylpyrrolidone.

[0053] More preferably, the lubricants include, but are not limited to, one or more of magnesium stearate, colloidal silica, and talc powder.

[0054] More preferably, for other pharmaceutically acceptable excipients: the ratio of lipoic acid is (0.05 - 0.25):1 (w / w).

[0055] The types and dosages of the externally added pharmaceutically acceptable excipients do not have a significant impact on the tableting problem of lipoic acid. Appropriate addition of excipients such as lubricants is common knowledge in the art. However, increasing the dosage of excipients is not suitable for solving the problem of lipoic acid content. Those skilled in the art can know that on the basis of solving the technical problem, the dosage of excipients should be minimized as much as possible. Therefore, the types and dosages of the externally added pharmaceutically acceptable excipients can be appropriately adjusted.

[0056] Preferably, calculated by weight, it includes the following components:

[0057]

[0058] Among them, the aqueous ethanol solution is removed during the production process.

[0059] More preferably, by weight, it comprises the following components:

[0060]

[0061] Most preferably, by weight, it comprises the following components:

[0062]

[0063] Among them, the aqueous ethanol solution is removed during the production process.

[0064] More preferably, by weight, it further comprises the following components:

[0065] Film coating premix 24 parts by weight

[0066] Water 135 parts by weight

[0067] Among them, water is removed during the production process.

[0068] A preparation method of a lipoic acid pharmaceutical composition, the pharmaceutical composition is in the form of tablets, comprising the following steps:

[0069] Dry and size the wet granules obtained by wet granulation, mix them evenly with externally added pharmaceutically acceptable excipients, tableting, and coating.

[0070] Preferably, fluidized bed drying is used for drying.

[0071] More preferably, the inlet air temperature for drying is controlled at 40 - 45 °C.

[0072] Preferably, a swing granulator is used for sizing.

[0073] More preferably, the mesh number of the sizing screen is 14 - 24 meshes.

[0074] Preferably, the material temperature is controlled below 45 °C during the coating process.

[0075] Those skilled in the art can appropriately adjust the process equipment and process parameter ranges according to the phenomena during the drying, tableting, and coating processes to achieve the purpose of preparing lipoic acid tablets.

[0076] Compared with the prior art, the beneficial effects of the lipoic acid pharmaceutical composition of the present invention are as follows:

[0077] 1. The lipoic acid pharmaceutical composition of the present invention uses an aqueous ethanol solution of hydroxypropyl cellulose as a binder for wet granulation, and controls the concentration of the aqueous ethanol solution to be 20-60%, preferably 30-45%, so as to avoid sticking and capping problems during the tabletting process, and has process feasibility; moreover, the amount of the aqueous ethanol solution of hydroxypropyl cellulose is only 15-30% of the mass of lipoic acid, avoiding the problem of difficult particle drying caused by excessive wetting in US5376382A, which is beneficial to industrial production.

[0078] 2. The preferred binder hydroxypropyl cellulose of the lipoic acid pharmaceutical composition of the present invention has the model ELF, and the preferred amount is 1.5%-5% of the mass of lipoic acid, and has excellent dissolution stability effect. After being placed at accelerated conditions (40°C, 75% RH) for 6 months, the dissolution degree at 45 minutes > 75%, meeting the internal control requirements of the product quality of the enterprise; while other hydroxypropyl celluloses with low viscosity, such as hydroxypropyl cellulose EXF and hydroxypropyl cellulose LXF, do not have dissolution stability, and the dissolution degree decreases significantly during the placement at accelerated conditions. Detailed implementation mode

[0079] The following are specific examples of the present invention to further describe the technical solutions of the present invention, but the protection scope of the present invention is not limited to these examples. Any changes or equivalent substitutions that do not deviate from the concept of the present invention are protected within the protection scope of the present invention.

[0080] The reagents and instruments used in the examples are all conventional reagents and instruments in the art, and can be obtained through conventional channels. The following is only for illustration.

[0081] Reagents:

[0082] Lipoic acid (model: pharmaceutical grade, manufacturer: Suzhou Fushilai)

[0083] Hydroxypropyl cellulose (model: ELF, manufacturer: Ashland)

[0084] Hydroxypropyl cellulose (model: LXF, manufacturer: Ashland)

[0085] Low-substituted hydroxypropyl cellulose (model: SH-LH22, manufacturer: Anhui Shanhe)

[0086] Magnesium stearate (model: SH-YM-M, manufacturer: Anhui Shanhe)

[0087] Film coating premix (model: gastric-soluble type, Shanghai Colorcon)

[0088] Instruments:

[0089] Wet granulator (model: GM-150E, manufacturer: Zhejiang Xiaolun)

[0090] Fluidized Bed Dryer Granulator (Model: FBG-150E, Manufacturer: Zhejiang Xiaolun)

[0091] High-Efficiency Tablet Press (Model: GZP-26, Manufacturer: Beijing Xinlongli)

[0092] High-Efficiency Coating Machine (Model: BGB-75FD, Manufacturer: Zhejiang Xiaolun)

[0093] Example 1

[0094] A thioctic acid tablet, the prescription composition is as shown in the following table:

[0095]

[0096] A preparation method of a thioctic acid tablet, comprising the following steps:

[0097] (1) Granulation: Add the prescribed amount of thioctic acid and low-substituted hydroxypropyl cellulose (added internally) to a wet granulator, set the stirring speed to 150 - 300 rpm, the cutter speed to 900 - 1500 rpm, and mix evenly; add the ethanol aqueous solution of hydroxypropyl cellulose in the prescribed amount in the pouring slurry manner, control the liquid addition time to 2 - 3 min, and continue granulation for 2 - 3 min; perform wet screening with a rocking granulator (20-mesh sieve).

[0098] (2) Drying: Fluidized bed drying, control the inlet air temperature to 40 - 45 °C, so that the material loss on drying ≤ 1.5%; perform dry screening with a rocking granulator (16-mesh sieve).

[0099] (3) Total mixing: Add the prescribed amount of low-substituted hydroxypropyl cellulose (added externally) and magnesium stearate, and mix at 12 rpm for 5 min.

[0100] (4) Tableting: Control the weight variation within ±5%, the average weight within ±3%, and the average main pressure at 10 - 23 KN.

[0101] (5) Coating: Prepare a coating solution with a solid content of 15% for coating, control the inlet air temperature at 40 - 60 °C, the inlet air volume at 1200 - 2000 m 3 / h, the atomizing air pressure at 0.2 - 0.4 MPa, the fan pressure at 0.2 - 0.4 MPa, the peristaltic pump speed at 10 - 40 rpm, and keep the product temperature at 33 - 38 °C during the coating process.

[0102] Examples 2 - 5

[0103] On the basis of Example 1, investigate the effects of the dosage of the binder hydroxypropyl cellulose (Examples 2 and 3) and the proportion of the mixed solvent of the binder (Examples 4 and 5) on the feasibility of the tableting process and the dissolution stability.

[0104] A thioctic acid tablet, the prescription composition is as shown in the following table:

[0105]

[0106] The preparation method of a lipoic acid tablet is the same as that in Example 1.

[0107] Example 6

[0108] On the basis of Example 1, investigate the types of the binder hydroxypropyl cellulose: ELF (Example 1), LXF (Example 6), and their effects on the feasibility of the tableting process and dissolution stability.

[0109] A lipoic acid tablet, the difference in the prescription composition from Example 1 is that: the type of hydroxypropyl cellulose is replaced with LXF.

[0110] The preparation method of a lipoic acid tablet is the same as that in Example 1.

[0111] Example 7

[0112] On the basis of Example 1, investigate the addition method of the binder hydroxypropyl cellulose during the granulation process: added in the form of a solution (Example 1) or in the form of dry powder (Example 7), and their effects on the feasibility of the tableting process and dissolution stability.

[0113] The difference from Example 1 is that: for the preparation method of a lipoic acid tablet, (1) Granulation: Add the prescribed amount of lipoic acid, low-substituted hydroxypropyl cellulose (added internally), and hydroxypropyl cellulose into a wet granulator, set the stirring speed at 150 - 300 rpm, the cutter speed at 900 - 1500 rpm, and mix evenly; Add the prescribed amount of ethanol aqueous solution in the pouring slurry mode, control the liquid addition time at 2 - 3 min, and continue granulating for 2 - 3 min; Perform wet screening with a swing granulator (20-mesh sieve).

[0114] Detection of the properties of the lipoic acid tablet and its intermediates in Example 8

[0115] Detect the properties of the lipoic acid tablets and their intermediates in Examples 1 - 7 above. The detection items include the properties of dry granules, particle size distribution, tableting phenomenon, and tablet dissolution curve.

[0116] The detection process is as follows:

[0117] Properties of powder: Determined with reference to the method for determining bulk density and tapped density (General Chapter 0993, Volume IV, Chinese Pharmacopoeia 2020 Edition).

[0118] Particle size distribution: Determined with reference to the method for determining particle size and particle size distribution (General Chapter 0982, Volume IV, Chinese Pharmacopoeia 2020 Edition).

[0119] Tablet pressing phenomenon: Observe the phenomenon during tablet pressing, referring to the method for determination of weight variation (General Chapter 0101, Volume IV, Chinese Pharmacopoeia 2020) and the method for examination of friability (General Chapter 0923, Volume IV, Chinese Pharmacopoeia 2020).

[0120] Dissolution of tablets: Refer to the method for determination of dissolution (Second Method, General Chapter 0931, Volume IV, Chinese Pharmacopoeia 2020). Use 900 ml of water as the dissolution medium and the rotation speed is 75 revolutions per minute.

[0121] The test results are as follows:

[0122]

[0123] The investigation results show that:

[0124] ① The addition method of the binder hydroxypropyl cellulose in wet granulation affects tablet pressing: When hydroxypropyl cellulose is added in dry powder form (Example 7), sticking to the punch occurs during the subsequent tablet pressing process; when added in solution form (Example 1), the problem of sticking to the punch during tablet pressing can be avoided.

[0125] ② The concentration of the ethanol aqueous solution of the binder hydroxypropyl cellulose affects tablet pressing: When the concentration of the ethanol aqueous solution is 11 wt% (Example 4), sticking to the punch occurs during the subsequent tablet pressing process; when the concentration is 20 - 60%, especially 34 (Example 5) - 45% (Example 2), the problem of sticking to the punch during tablet pressing can be avoided; when the concentration is higher than 60%, chipping is likely to occur.

[0126] ③ The type of the binder hydroxypropyl cellulose affects dissolution stability: When the type of hydroxypropyl cellulose is LXF (Example 6), the dissolution at 6 months of accelerated test significantly decreases, and the dissolution at 45 min < 75% (the dissolution at 45 min is 66.2% at 3 months of accelerated test); when the type is ELF (Example 2), the dissolution at 6 months of accelerated test has no significant change, and still maintains the dissolution at 45 min > 75%, showing excellent dissolution stability.

[0127] ④ The dosage of the binder hydroxypropyl cellulose affects dissolution stability: When the dosage of hydroxypropyl cellulose is 9 parts by weight (i.e., 1.5% of the mass of lipoic acid, Example 2) - 30 parts by weight (i.e., 5% of the mass of lipoic acid, Example 3), the dissolution at 6 months of accelerated test has no significant change, and still maintains the dissolution at 45 min > 75%, showing excellent dissolution stability.

[0128] In addition, the inventors found through research that: when the dosage ratio of hydroxypropyl cellulose further increases, for example, from 5% of the mass of lipoic acid to 10%, the dissolution is likely to decrease to less than 75%, affecting the dissolution stability, and cannot meet the internal control requirements of product quality of the enterprise.

[0129] In summary, the present invention uses an aqueous ethanol solution of hydroxypropyl cellulose as a binder solution for wet granulation, and controls the concentration of the aqueous ethanol solution to be 20-60%, which can avoid the problems of sticking to the punch and capping during the subsequent tabletting process, and has process feasibility.

[0130] Furthermore, the present invention preferably uses ELF as the type of hydroxypropyl cellulose, and preferably uses 1.5-5% of the mass of lipoic acid as the dosage of hydroxypropyl cellulose, which can achieve the effect of dissolution stability with a dissolution rate > 75% at 45 minutes in 6 months of acceleration.

Claims

1. A lipoic acid pharmaceutical composition, the pharmaceutical composition is in the form of wet granules, characterized in that: It includes lipoic acid, hydroxypropyl cellulose and ethanol in water.

2. The lipoic acid pharmaceutical composition according to claim 1, characterized in that The ratio of the hydroxypropyl cellulose and the ethanol aqueous solution to the lipoic acid is (0.15-0.3):1 (w / w).

3. The lipoic acid pharmaceutical composition according to claim 1, characterized in that The concentration of the ethanol aqueous solution is 20-60 wt %; more preferably, the concentration of the ethanol aqueous solution is 30-45 wt %.

4. The lipoic acid pharmaceutical composition according to claim 1, characterized in that The hydroxypropyl cellulose is a low-viscosity hydroxypropyl cellulose, including but not limited to one or more of hydroxypropyl cellulose ELF, hydroxypropyl cellulose EXF, and hydroxypropyl cellulose LXF; more preferably, the hydroxypropyl cellulose is hydroxypropyl cellulose ELF.

5. The lipoic acid pharmaceutical composition according to claim 1, characterized in that The ratio of hydroxypropyl cellulose to lipoic acid is (0.01-0.1):1 (w / w); more preferably, the ratio of hydroxypropyl cellulose to lipoic acid is (0.015-0.05):1 (w / w).

6. The lipoic acid pharmaceutical composition according to claim 1, characterized in that The pharmaceutical composition further comprises pharmaceutically acceptable excipients, including but not limited to diluents and disintegrants.

7. The method for preparing the lipoic acid pharmaceutical composition according to any one of claims 1 to 6, characterized in that: The method comprises adding ethanol aqueous solution of hydroxypropyl cellulose into a mixture containing lipoic acid for wet granulation.

8. The lipoic acid pharmaceutical composition according to claim 1, characterized in that The following steps are involved: a) mixing lipoic acid or lipoic acid and pharmaceutically acceptable excipients uniformly; b) adding ethanol aqueous solution of hydroxypropyl cellulose for wet granulation; c) Wet granulation.

9. A lipoic acid pharmaceutical composition in the form of a tablet, characterized in that: The wet granules according to any one of claims 1 to 6 and pharmaceutically acceptable excipients are added, wherein the ethanol aqueous solution is removed during the production process.

10. The method for preparing the lipoic acid pharmaceutical composition according to claim 9, characterized in that: The following steps are involved: The wet granules obtained by wet granulation are dried and sized, mixed evenly with external pharmaceutically acceptable excipients, tableted, and coated.

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