A method for preparing lipoic acid enteric capsules

Abstract

The application provides a preparation method of lipoic acid enteric-soluble capsules and relates to the technical field of medicines.The raw materials of the capsule include lipoic acid, and the preparation steps are as follows: lipoic acid is mixed with a disintegrating agent and stirred, a wetting agent is added for granulation, the granulation is discharged to obtain wet granules; the obtained wet granules are dried, sieved and coated to obtain coated granules, the coating liquid includes a binder, an opacifier and a plasticizer; the coated granules are filled with a lubricant into capsules to prepare lipoic acid capsules.The bulk density of the prepared lipoic acid coated granules can reach 0.5-0.7g / mL, which can meet the filling requirements of large-size capsules (such as 600mg capsules), and the lipoic acid coated granules have excellent dissolution performance and high stability.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a method for preparing thioctic acid enteric-coated capsules. Background Technology

[0002] Thioctanoic acid (CLA), chemically known as (±)-5-[3-(1,2-dithiacyclopentane)]-valeric acid, acts as a coenzyme in acyl transfer during metabolism, eliminating free radicals that accelerate aging and cause disease. It can be used for the treatment and therapeutic maintenance of acute and chronic hepatitis, cirrhosis, hepatic coma, fatty liver, diabetes, and other diseases. Thioctanoic acid preparations were marketed in Germany as early as the 1980s for the treatment of diabetic neurological symptoms; the original marketed dosage forms were tablets, small-volume injections, and sterile powder for injection. Thioctanoic acid is a B vitamin and a coenzyme for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase systems. In vitro studies show that lipoic acid can reduce lipid oxidation in nerve tissue, inhibit protein glycosylation, and inhibit aldose reductase. In vivo, lipoic acid has antioxidant effects and participates in the recycling of antioxidants such as glutathione and coenzyme Q10. However, thioctic acid has a low melting point, and it begins to soften and become viscous at 60°C. The heat generated in the production equipment has a significant impact on the drug, making large-scale production infeasible.

[0003] Patent document CN101670111B discloses a method for preparing a lipoic acid-dextran conjugate to achieve long-lasting sustained release; however, the in vivo absorption of the active ingredient after oral administration of this formulation is not ideal. Lipoic acid, as a poorly soluble compound, has limited solubility in the body after being formulated into an oral solid dosage form, affecting its absorption and utilization. In other words, the active ingredient of this formulation is not effectively absorbed by the human body. Patent CN102579395A relates to a lipoic acid capsule containing a solid dispersion composed of lipoic acid and a carrier material selected from poloxamer, ultimately yielding a lipoic acid formulation. Currently prepared lipoic acid formulations generally suffer from poor stability.

[0004] Therefore, it is particularly urgent to develop a thioctic acid capsule that dissolves quickly, has good stability, and is easily absorbed. Summary of the Invention

[0005] This invention addresses the problems existing in the prior art by providing a method for preparing thioctic acid enteric-coated capsules, which can ensure that the particle size range is between 20-80 mesh, and that the coated particles do not stick or degrade during the filling process, ultimately resulting in a thioctic acid enteric-coated capsule with good stability and good dissolution.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] This invention provides a method for preparing thioctic acid enteric-coated capsules, comprising the following steps:

[0008] (1) Mix thioctic acid with a disintegrant, add a wetting agent, and extrude to granulate to obtain wet granules;

[0009] (2) The wet granules obtained in step (1) are sieved, dried, and coated;

[0010] (3) The coated granules and lubricant were filled with enteric-coated capsules to obtain thioctic acid enteric-coated capsules.

[0011] Furthermore, in the above technical solution, step (1) specifically involves putting dried thioctic acid and disintegrant into a wet mixing granulator, turning on the stirring paddle and shear blade to mix, spraying in a wetting agent to granulate, discharging the granules, and feeding them into an extrusion granulator to extrude and granulate them to obtain wet granules.

[0012] Furthermore, in the above technical solution, after extrusion granulation in step (1), the wet granules are fed into a swing granulator for sieving.

[0013] Furthermore, in the above technical solution, the mixing time of the thioctic acid and the disintegrant does not exceed 1 minute to prevent the material from generating heat due to mechanical friction, causing adhesion and degradation.

[0014] Furthermore, in the above technical solution, the wetting agent in step (1) is water and / or ethanol.

[0015] Furthermore, in the above technical solution, the disintegrant in step (1) is selected from one or more of croscarmellose sodium, croscarmellose polyvinyl chloride, sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose.

[0016] Furthermore, in the above technical solution, the weight percentage of the disintegrant in step (1) in the capsule is 1.0%-5.0%, and the weight percentage of thioctic acid in the capsule is 80%-95%.

[0017] Furthermore, in the above technical solution, the sieving in step (2) is to pass through a 20-mesh sieve to remove large, agglomerated particles. Particles smaller than 20 mesh are fed into a fluidized bed granulation coating machine for spray coating, resulting in a coating weight gain of 3%-5%.

[0018] Furthermore, in the above technical solution, the drying temperature in step (2) is 20-30℃.

[0019] Furthermore, in the above technical solution, the coating temperature in step (2) is 30-40℃.

[0020] Furthermore, in the above technical solution, the coating liquid used for coating in step (2) is an aqueous solution or ethanol solution with a solid content of 8%-20% containing adhesive, opacifier and plasticizer.

[0021] Further, the adhesive is hydroxypropyl methylcellulose and / or hydroxypropyl cellulose, and the adhesive has a mass fraction of 6%-20% in the coating solution; the opacifier is titanium dioxide and / or talc, and the opacifier has a mass fraction of 0.1%-1% in the coating solution; the plasticizer is one or more of glycerol, propylene glycol, and polyethylene glycol, and the plasticizer has a mass fraction of 0.1%-1% in the coating solution.

[0022] Furthermore, the coating material is Calcare coating premix powder, such as Nufit or Opadry.

[0023] Furthermore, in the above technical solution, the lubricant in step (3) is selected from one or more of silica, magnesium stearate, and talc, and the amount used is 0.5%-1.0% of the total mass of the capsule.

[0024] Furthermore, in the above technical solution, the main components of the enteric-coated capsule in step (3) are gelatin and / or hydroxypropyl methylcellulose.

[0025] The present invention also provides thioctic acid enteric-coated capsules prepared by the above method.

[0026] The technical effects achieved by this invention are:

[0027] 1. The bulk density of the lipoic acid coated particles prepared by this invention can reach 0.5-0.7 g / mL, which can meet the filling requirements of large-sized capsules (such as 600 mg capsules);

[0028] 2. The thioctic acid enteric-coated capsules prepared by this invention can avoid mechanical friction-induced thermal degradation and photodegradation during the production process, thereby improving stability and enhancing dissolution performance. Detailed Implementation

[0029] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0030] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention.

[0031] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0032] It is worth noting that the raw materials used in this invention are all commercially available products, and therefore their sources are not specifically limited.

[0033] Example 1

[0034] Preparation of lipoic acid enteric-coated capsules:

[0035] The components of the lipoic acid enteric-coated capsules are shown in Table 1.

[0036] Table 1

[0037]

[0038] 1. Wet granulation: After the thioctic acid and cross-linked carboxymethyl cellulose sodium are mixed evenly, they are put into a wet granulator. The stirring speed is 200 rpm ± 10 rpm. 50% ethanol aqueous solution is added to form a soft material. The shearing speed is 1000 rpm ± 100 rpm to granulate. The wet granules of thioctic acid are discharged.

[0039] 2. Extrusion granulation: The above wet granules are fed into a planetary extruder with an extruder orifice diameter of 0.4 mm and an extrusion speed of 15 rpm. The output material is lipoic acid fine granules.

[0040] 3. Granulation: The above-mentioned thioctic acid fine strip granules are fed into a gyratory pellet mill and passed through an 18-mesh sieve to obtain uniform short granules.

[0041] 4. Drying and Coating: Pass the above wet granules through a 20-mesh sieve to remove large, agglomerated particles. Particles smaller than 20 mesh are fed into a fluidized bed spray coating pan. Inlet air temperature: 40°C; material temperature: 30°C. Dry until the particle moisture content is <3%. Then, spray coating with a 20% coating solution, adding hydroxypropyl methylcellulose, titanium dioxide, and polyethylene glycol. Maintain the rotary table speed at 200 rpm and the atomization pressure at 0.22 MPa. Stop coating when the coating weight gain is approximately 4%. Discharge the material after drying for 20 minutes.

[0042] 5. Mix the dried coated granules evenly with the prescribed amount of magnesium stearate;

[0043] 6. Filling: Fill the above total mixed granules into No. 00 enteric-coated capsules.

[0044] The final thioctic acid-coated granules have a bulk density of 0.5-0.7 g / mL, which can meet the filling requirements of large-sized capsules such as 600 mg.

[0045] Comparative Example 1

[0046] Preparation of lipoic acid enteric-coated capsules:

[0047] The components of the lipoic acid enteric-coated capsules are shown in Table 2.

[0048] Table 2

[0049] Raw material name mg / particle Alpha-lipoic acid 600 Cross-linked carboxymethyl cellulose sodium 24 magnesium stearate 3 total 627

[0050] 1. Wet granulation: After the thioctic acid and cross-linked carboxymethyl cellulose sodium are mixed evenly, they are put into a wet granulator. The stirring speed is 200 rpm ± 10 rpm. 50% ethanol aqueous solution is added to form a soft material. The shearing speed is 1000 rpm ± 100 rpm to granulate. The wet granules of thioctic acid are discharged.

[0051] 2. Drying: The above wet granules are put into a fluidized bed dryer with an air inlet temperature of 40°C and a material temperature of 30°C. The granules are dried until the moisture content is less than 3% and then discharged. The dried granules are sized using a 18-mesh oscillating pellet mill to obtain dried granules with a bulk density of 0.3 g / mL.

[0052] 3. Mixing: Mix the above dried granules with the prescribed amount of magnesium stearate until homogeneous;

[0053] 4. Filling: Fill the above total mixed granules into No. 00 enteric-coated capsules.

[0054] Comparative Example 1 did not undergo extrusion granulation and coating. Since the wet granulation particles are relatively loose with a bulk density of 0.3 g / mL, when filling 600 mg capsules, pressure needs to be applied to the powder for filling. During the production process, due to the mechanical force of the punch, the powder is prone to heat polymerization and sticking to the punch. The lower punch needs to be cleaned every 15 minutes, resulting in insufficient production convenience.

[0055] Comparative Example 2

[0056] Preparation of lipoic acid gastric-soluble capsules:

[0057] Prepared according to the method of Example 1, except that it is finally filled into No. 00 gastric-soluble capsules.

[0058] Comparative Example 3

[0059] Preparation of lipoic acid gastric-soluble capsules:

[0060] Prepared according to the method of Comparative Example 1, the difference being that it is finally filled into No. 00 gastric-soluble capsules.

[0061] Comparative Example 4

[0062] Preparation of enteric-coated thioctic acid capsules (without particle coating):

[0063] The components of the lipoic acid enteric-coated capsules are shown in Table 3.

[0064] Table 3

[0065] Raw material name mg / particle Alpha-lipoic acid 600 Cross-linked carboxymethyl cellulose sodium 24 magnesium stearate 3 total 627

[0066] 1. Wet granulation: After the thioctic acid and cross-linked carboxymethyl cellulose sodium are mixed evenly, they are put into a wet granulator. The stirring speed is 200 rpm ± 10 rpm. 50% ethanol aqueous solution is added to form a soft material. The shearing speed is 1000 rpm ± 100 rpm to granulate. The wet granules of thioctic acid are discharged.

[0067] 2. Extrusion granulation: The above wet granules are fed into a planetary extruder with an extruder orifice diameter of 0.4 mm and an extrusion speed of 15 rpm. The output material is lipoic acid fine granules.

[0068] 3. Granulation: The above-mentioned thioctic acid fine strip granules are fed into a gyratory pellet mill and passed through an 18-mesh sieve to obtain uniform short granules.

[0069] 4. Drying: Put the above wet granules into a fluidized bed dryer, with an inlet air temperature of 40°C and a material temperature of 30°C, and dry until the granule moisture content is <3% before discharge.

[0070] 5. Mix the dried granules evenly with the prescribed amount of magnesium stearate;

[0071] 6. Filling: Fill the above total mixed granules into No. 00 enteric-coated capsules.

[0072] Test Example 1

[0073] Drug dissolution test

[0074] The specific method for dissolution testing is as follows:

[0075] Dissolution method: rotating basket method, 100 rpm;

[0076] Dissolution medium and volume: 900 ml of 0.1 M hydrochloric acid solution and 900 ml of pH 6.8 phosphate buffer solution;

[0077] Sampling time points: 5, 10, 15, 30, 60, 120 minutes;

[0078] Sampling volume: 2 ml for each point of fully automated dissolution sampling, 0.5 ml of which is discarded after filtration through a 0.45 μm filter membrane, and the remaining sample is injected by HPLC to accumulate dissolution rate.

[0079] The reference formulation information is as follows: Thioctacid tablets, trade name: Thioctacid, strength: 600mg.

[0080] The test results are shown in Table 4:

[0081] Table 4

[0082]

[0083] Example 1, Comparative Example 1, and Comparative Example 4 are enteric-coated capsules, and the dissolution medium used is a pH 6.8 buffer solution; Comparative Example 2, Comparative Example 3, and the reference preparation are gastric-coated preparations, and the dissolution medium used is a 0.1M hydrochloric acid solution.

[0084] In 0.1M hydrochloric acid solution, comparative examples 2, 3, and the reference formulation did not completely dissolve until 2 hours due to the instability of thioctic acid in acid, and the raw materials and excipients remained in a viscous state in the dissolution medium. The difference between Example 1 and Comparative Example 1 lies in the granulation process; Example 1 showed significantly better dissolution than Comparative Example 1, and its stability was also better after 6 months. The difference between Example 1 and Comparative Example 2 is that Example 1 used enteric-coated capsules, protecting thioctic acid from degradation by gastric juices. This reduces the dosage for patients; commercially available 600mg tablets are large and difficult to swallow. Using enteric-coated capsules can reduce the dosage by 30%, greatly improving patient compliance. Compared to Comparative Example 4, the dissolution curves of Example 1 show that, because the granules in Comparative Example 4 were uncoated, the thermal and photodegradation during the production process may have slightly reduced the product content, with only about 95% of the total dissolved within 2 hours. Therefore, it is believed that the granule coating in this process improves both the dissolution and stability of the product.

[0085] Test Example 2

[0086] Drug stability assessment (impurities and content)

[0087] To demonstrate the advantages of this invention, the stability of the thioctic acid capsules was further investigated. Referring to the European Pharmacopoeia formulations and the raw material standards recorded in the USP, quality standards were established to test for impurity A and other single impurities. Impurity A is EP Pharmacopoeia impurity A; impurity B is EP Pharmacopoeia impurity B, which is the main degradation impurity. The test results are shown in Table 5:

[0088] Table 5

[0089]

[0090] Accelerated conditions were maintained at 30°C and 65% RH for 6 months. Comparative Examples 2 and 3 differed from Examples 1 and 1 only in the shell material; therefore, no stability comparison study was conducted.

[0091] The stability results show that the thioctic acid enteric-coated capsules produced using the preparation process of the present invention have significantly better stability than the reference preparation and also significantly better stability than Comparative Example 1. The difference between Example 1 and Comparative Example 4 is that Example 1 coated the particles, which effectively reduced the probability of thermal degradation caused by friction on the particle surface during the production process, thereby improving the process stability of the product and also improving the stability of long-term storage.

[0092] Comparative Example 5

[0093] Preparation of lipoic acid enteric-coated capsules:

[0094] The components of the lipoic acid enteric-coated capsules are shown in Table 6.

[0095] Table 6:

[0096]

[0097] 1. Wet granulation: After the thioctic acid and cross-linked carboxymethyl cellulose sodium are mixed evenly, they are put into a wet granulator. The stirring speed is 200 rpm ± 10 rpm. 50% ethanol aqueous solution is added to form a soft material. The shearing speed is 1000 rpm ± 100 rpm to granulate. The wet granules of thioctic acid are discharged.

[0098] 2. Extrusion granulation: The above wet granules are fed into a planetary extruder with an extruder orifice diameter of 0.4 mm and an extrusion speed of 15 rpm. The output material is lipoic acid fine granules.

[0099] 3. Granulation: The above-mentioned thioctic acid fine strip granules are fed into a gyratory pellet mill and passed through an 18-mesh sieve to obtain uniform short granules.

[0100] 4. Drying and Coating: Put the above wet granules into the fluidized bed test spray coating pan. The inlet air temperature is 40°C and the material temperature is 30°C. Dry until the granule moisture content is <3%. Then, use 20% coating solution for test spray coating. Keep the turntable speed at 200 rpm and the atomization pressure at 0.22 MPa. Stop coating when the coating weight gain is about 4%. After drying for 20 minutes, discharge the material.

[0101] 5. Mix the dried coated granules with the prescribed amount of magnesium stearate until homogeneous.

[0102] 6. Filling: Fill the above total mixed granules into No. 00 enteric-coated capsules.

[0103] Comparative Example 6

[0104] Preparation of lipoic acid enteric-coated capsules:

[0105] The components of the lipoic acid enteric-coated capsules are shown in Table 7.

[0106] Table 7:

[0107]

[0108] 1. Wet granulation: After the thioctic acid and cross-linked carboxymethyl cellulose sodium are mixed evenly, they are put into a wet granulator. The stirring speed is 200 rpm ± 10 rpm. 50% ethanol aqueous solution is added to form a soft material. The shearing speed is 1000 rpm ± 100 rpm to granulate. The wet granules of thioctic acid are discharged.

[0109] 2. Extrusion granulation: The above wet granules are fed into a planetary extruder with an extruder orifice diameter of 0.4 mm and an extrusion speed of 15 rpm. The output material is lipoic acid fine granules.

[0110] 3. Granulation: The above-mentioned thioctic acid fine strip granules are fed into a gyratory pellet mill and passed through an 18-mesh sieve to obtain uniform short granules.

[0111] 4. Drying and Coating: Put the above wet granules into the fluidized bed test spray coating pan. The inlet air temperature is 40°C and the material temperature is 30°C. Dry until the granule moisture content is <3%. Then, use 20% coating solution for test spray coating. Keep the turntable speed at 200 rpm and the atomization pressure at 0.22 MPa. Stop coating when the coating weight gain is about 4%. After drying for 20 minutes, discharge the material.

[0112] 5. Mix the dried coated granules with the prescribed amount of magnesium stearate until homogeneous.

[0113] 6. Filling: Fill the above total mixed granules into No. 00 enteric-coated capsules.

[0114] Test Example 3-4

[0115] Following the methods of Test Examples 1-2, the dissolution and stability of the thioctic acid enteric-coated capsules obtained in Comparative Examples 5 and 6 were tested and compared with those in Example 1. The test results are shown in Tables 8 and 9.

[0116] Table 8

[0117]

[0118] Table 9

[0119]

[0120] Impurity B is a thioctic acid polymer, which is the main degradation impurity and a thermal degradation product.

[0121] The difference between Comparative Examples 5 and 6 and Example 1 lies in the fact that the coating materials do not contain the light-blocking agent and plasticizer described in the examples. Comparative Example 5, which does not contain the light-blocking agent, experienced incomplete dissolution due to the degradation of thioctic acid upon exposure to light during the production process, resulting in significant degradation during the stability period. Comparative Example 6, which does not contain the plasticizer, showed slightly slower dissolution compared to Example 1, and also exhibited significant degradation during the stability period. This may be due to insufficient toughness of the coating film, leading to incomplete film coverage.

[0122] Comparative Example 7

[0123] Thioctanoic acid capsules were prepared according to the method in Example 1 of CN102579395A:

[0124] 1. Take 100g of lipoic acid, micronize it, and pass it through a 200-mesh sieve to obtain fine lipoic acid powder.

[0125] 2. Take 50g of poloxamer 237 and place it in a suitable container. Heat it in a 50°C water bath until it becomes a molten liquid. Add 100g of fine thioctic acid powder and stir quickly and thoroughly at 50°C until the mixture is homogeneous. Let it stand to remove air bubbles. Spread the mixture into a thin layer and place it in a -5°C refrigerator to cool rapidly. After the mixture has completely solidified, take it out and pulverize it. Place it in a vacuum desiccator and dry it at 35°C for 24 hours. Pulverize it through a 100-mesh sieve to obtain the thioctic acid solid dispersion.

[0126] 3. Add 82g of microcrystalline cellulose, 10g of lactose, 8g of sodium carboxymethyl starch, and 4g of magnesium stearate to the lipoic acid solid dispersion from step 2. All fillers, disintegrants, and lubricants are passed through a 100-mesh sieve. Use a 2% hydroxypropyl methylcellulose aqueous solution as a binder to prepare granules, which are then filled into capsules to obtain 1000 lipoic acid capsules, each containing approximately 0.1g of lipoic acid. The stability of the prepared lipoic acid capsules was determined, and the results are shown in Table 10.

[0127] Table 10

[0128]

[0129] The above results indicate that the thioctic acid enteric-coated capsules produced using the preparation process of this invention have significantly better stability than existing technologies.

[0130] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing an enteric-coated thioctic acid capsule, comprising the following steps: (1) Mix thioctic acid with a disintegrant, add a wetting agent, and extrude to granulate to obtain wet granules; (2) The wet granules obtained in step (1) are sieved, dried, and coated; (3) The coated granules and lubricant were filled with enteric-coated capsules to obtain thioctic acid enteric-coated capsules; The coating solution used for coating in step (2) is an aqueous solution or ethanol solution with a solid content of 8%-20% containing adhesive, opacifier, and plasticizer; The adhesive is hydroxypropyl methylcellulose and / or hydroxypropyl cellulose, and the mass fraction of the adhesive in the coating solution is 6%-20%. The opacifier is titanium dioxide and / or talc, and the mass fraction of the opacifier in the coating solution is 0.1%-1%. The plasticizer is one or more of glycerol, propylene glycol, and polyethylene glycol, and the mass fraction of the plasticizer in the coating solution is 0.1%-1%.

2. The preparation method according to claim 1, characterized in that, Step (1) specifically involves putting dried thioctic acid and disintegrant into a wet mixing granulator, adding a wetting agent to granulate, discharging the granules, and then feeding them into an extrusion granulator to extrude and granulate them to obtain wet granules.

3. The preparation method according to claim 2, characterized in that, Step (1) After extrusion granulation, the wet granules are sieved.

4. The preparation method according to claim 1, characterized in that, The mixing time of the lipoic acid and the disintegrant in step (1) shall not exceed 1 minute; And / or the wetting agent described in step (1) is water and / or ethanol; And / or the disintegrant mentioned in step (1) is selected from one or more of croscarmellose sodium, croscarmellose, sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose; And / or the disintegrant described in step (1) has a weight percentage of 1.0%-5.0% in the capsule and the thioctic acid has a weight percentage of 80%-95% in the capsule.

5. The preparation method according to claim 1, characterized in that, The weight gain during the coating process in step (2) is 3%-5%; And / or the drying temperature in step (2) is 20-30°C, and the coating temperature is 30-40°C.

6. The preparation method according to claim 1, characterized in that, The lubricant used in step (3) is selected from one or more of silica, magnesium stearate, and talc, and the amount used is 0.5%-1.0% of the total mass of the capsule.

7. The preparation method according to claim 1, characterized in that, The main components of the enteric-coated capsules in step (3) are gelatin and / or hydroxypropyl methylcellulose.

8. A lipoic acid enteric-coated capsule, characterized in that, Prepared by the preparation method according to any one of claims 1-7.

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