A tablet of silybum marianum and salvia miltiorrhiza and a preparation method thereof

Abstract

The application discloses a kind of shuifei dan sheng sanpil and preparation method thereof, belong to the technical field of health food.The tablet is according to 1000 pieces, by salvia miltiorrhiza extract 400g, sanpil extract 150g, shuifei extract 80g, microcrystalline cellulose 150g, crosslinked polyvinylpyrrolidone 55g, crosslinked sodium carboxymethylcellulose 60g, magnesium stearate 5g and film coating premix 27g composition;Its preparation method uses the step granulation process of inner disintegrant+outer disintegrant, first, raw materials are mixed with inner disintegrant granulation, drying whole particle is added to outer disintegrant and lubricant total mix again, finally, film coating is carried out.The application is compounded by three kinds of plant extracts, and the effects of antioxidation, anti-inflammation and liver cell membrane protection are synergistically exerted.

Description

Technical Field

[0001] This invention belongs to the field of health food technology, specifically relating to a milk thistle, salvia miltiorrhiza and notoginseng tablet and its preparation method. Background Technology

[0002] Chemical liver injury, caused by hepatotoxic substances such as alcohol, drugs, and environmental pollutants, has become a global public health problem. Long-term chemical liver injury can lead to hepatocyte necrosis, fibrosis, and even cirrhosis and liver cancer. Currently, most health supplements on the market designed to help protect against chemical liver injury use milk thistle extract as their main ingredient, resulting in limited efficacy and poor synergistic effects.

[0003] Tablets are a common dosage form for health foods. However, plant extracts generally have strong hygroscopicity and high viscosity. In the tablet production process, improper selection of the type and amount of fillers and disintegrants can lead to poor particle flowability and poor compressibility. This can cause problems such as tablet cracking, loose tablets, and sticking during compression. In addition, excessively long disintegration time can affect product absorption. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a milk thistle, salvia miltiorrhiza and notoginseng tablet and its preparation method, thereby solving the technical problems of poor efficacy of single ingredients, easy moisture absorption, slow disintegration and unstable quality of plant extract tablets in the prior art.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A milk thistle, salvia miltiorrhiza, and notoginseng tablet, per 1000 tablets, is composed of the following raw and excipient materials: Raw materials: 350-400g salvia miltiorrhiza extract, 120-150g notoginseng extract, 80-90g milk thistle extract; Excipients: 150-170g microcrystalline cellulose, 50-55g crospovidone, 50-60g crospovidone sodium carboxymethyl cellulose, 3-5g magnesium stearate; Coating material: 25-27g film coating premix; The salvia miltiorrhiza extract contains ≥1% tanshinone IIA, with an extraction ratio of 7:1; The notoginseng extract contains ≥20% total saponins, with an extraction ratio of 6.7:1; The milk thistle extract contains ≥20% silybin, with an extraction ratio of 25:1.

[0006] As an improvement, based on 1000 tablets, it is composed of the following raw and excipient materials: Raw materials: 400g of Salvia miltiorrhiza extract, 150g of Panax notoginseng extract, and 80g of milk thistle extract; Excipients: 150g of microcrystalline cellulose, 55g of crospovidone, 60g of crospovidone sodium carboxymethyl cellulose, and 5g of magnesium stearate; Coating material: 27g of film coating premix.

[0007] As an improvement, the tablets are film-coated tablets, with the uncoated tablets weighing 0.9g-1.0g / tablet and the coated tablets weighing 0.927g-1.0g / tablet, resulting in a weight gain of approximately 1-3% after coating.

[0008] Furthermore, the content of tanshinone IIA in the tanshinone extract is ≥1%, the content of total saponins in the Panax notoginseng extract is ≥20%, and the content of silybin in the milk thistle extract is ≥20%.

[0009] This invention also provides a method for preparing the above-mentioned milk thistle, salvia miltiorrhiza, and notoginseng tablets, comprising the following steps: S1. Raw material pretreatment: Pass all raw materials through an 80-100 mesh sieve and use them after passing the inspection. S2. Premixing: Weigh out the Salvia miltiorrhiza extract, Panax notoginseng extract, milk thistle extract, microcrystalline cellulose and crospovidone according to the formula, and mix them in a three-dimensional motion mixer for 6-10 minutes to obtain a mixed powder. S3. Preparation of soft material and granulation: Add an appropriate amount of ethanol to the mixed powder, stir to make a soft material of moderate hardness, granulate through a sieve to obtain wet granules. S4. Drying: Place the wet granules in a hot air circulating oven and dry at 45-55℃ for 20-30 minutes until the granule moisture content is ≤5%; S5. Granulation: The dried granules are granulated by passing them through a mesh sieve to obtain granulated granules; S6. Total Mixing: Place the whole granules in a mixer, add cross-linked sodium carboxymethyl cellulose and magnesium stearate, and mix to obtain total mixed granules; S7. Tableting: The total mixture of granules is compressed into tablets using a rotary tablet press; S8. Coating: Prepare a 5-10% coating solution using purified water with the film coating premix, and then coat the uncoated tablets with a film. The coating weight gain is approximately 1-3%. S9. Inner and outer packaging: The coated sheets are bottled, then the outer packaging is carried out, and the product is put into storage after passing inspection.

[0010] As an improvement, in the S1 raw material pretreatment, all raw materials are passed through an 80-mesh sieve.

[0011] As an improvement, the S2 premixing was carried out in a Class 100,000 clean area at a temperature of 22°C and a relative humidity of 55%.

[0012] As an improvement, S3 produces soft material and granules: an appropriate amount of 80% ethanol is slowly added to the mixed powder while stirring, to produce a soft material that can be formed into a ball when squeezed but crumbles when touched.

[0013] As an improvement, the soft material is granulated by passing it through a 16-mesh sieve to obtain wet granules.

[0014] As an improvement, the dried particles are granulated through a 14-mesh sieve during the S5 granulation process.

[0015] As an improvement, the tableting parameters in the S7 tableting process were adjusted to produce unprocessed tablets of 0.9g / tablet, with a tablet weight difference controlled within ±5%, a hardness ≥100N, and a brittleness ≤0.3%.

[0016] As an improvement, in the S8 coating process, the uncoated tablets are placed in a high-efficiency coating pan with a pan rotation speed of 8 r / min, an inlet air temperature of 78℃, an outlet air temperature of 43℃, and a tablet bed temperature of 42℃ for spray coating until the coating weight gain is about 3%. As an improvement, in the S9 packaging and outer packaging, the coated tablets are packaged in high-density polyethylene bottles for oral solid medicine at a rate of 60 tablets / bottle and sealed; then the outer packaging is carried out, and a full range of tests are conducted according to the enterprise standards. After passing the tests, the tablets are stored in the warehouse.

[0017] Beneficial effects Compared with the prior art, the present invention has the following beneficial effects: (1) This invention determined the optimal compound ratio of 40:15:8 for tanshinone extract, notoginseng extract, and milk thistle extract. Among them, silybin can stabilize hepatocyte membranes, scavenge free radicals, and promote hepatocyte repair; tanshinone IIA has antioxidant, anti-inflammatory, and hepatic microcirculation-improving effects; and total saponins of notoginseng can inhibit hepatocyte apoptosis and reduce inflammatory response. The three components work synergistically to exert auxiliary protective effects against chemically induced liver injury from multiple targets, with significantly better effects than single-component products.

[0018] (2) Through systematic screening experiments, this invention has determined the optimal excipient formulation using microcrystalline cellulose as a filler, crospovidone as an internal disintegrant, crospovidone sodium carboxymethyl cellulose as an external disintegrant, and magnesium stearate as a lubricant. The internal disintegrant causes rapid disintegration within the granules, while the external disintegrant promotes overall tablet disintegration. The combination of the two results in a product disintegration time of ≤25 minutes, far superior to the 40-60 minutes of conventional tablets. At the same time, the good compressibility of microcrystalline cellulose makes the tablet hardness ≥100N and the friability ≤0.3%, completely solving the problems of cracked and loose tablets.

[0019] (3) The present invention optimizes the process parameters of the whole process: the mixing time is 10 minutes to ensure uniform distribution of active ingredients and the RSD of tanshinone IIA content is ≤4.38%; 80% ethanol is used as a wetting agent, which has a good granulation effect and a particle yield ≥95%; the drying temperature is controlled at 45-55℃, which not only ensures the drying efficiency but also avoids the degradation of active ingredients; the film coating process effectively isolates moisture and oxygen in the air and improves product stability.

[0020] (4) This invention determines the critical relative humidity of the product to be 74% through hygroscopicity studies, and formulates a production environment humidity control standard (≤74%) accordingly, which effectively reduces the hygroscopicity of the product. Accelerated test results show that the product meets the standard requirements after being placed at 40℃ and 75% relative humidity for 6 months, and the shelf life can reach 24 months.

[0021] (5) The preparation process of this invention does not require special equipment, is easy to operate, and the yield of three batches of pilot products is ≥98%. The process has good reproducibility and is suitable for large-scale industrial production. Detailed Implementation

[0022] The present invention will be further described in detail below with reference to specific embodiments and comparative examples.

[0023] Example 1 This embodiment provides a milk thistle, salvia miltiorrhiza, and notoginseng tablet. The formula for 1000 tablets is as follows: 400g of salvia miltiorrhiza extract (tanshinone IIA 1.2%), 150g of notoginseng extract (total saponins 21.5%), 80g of milk thistle extract (silymarin 22.3%), 150g of microcrystalline cellulose, 55g of crospovidone, 60g of crospovidone sodium carboxymethyl cellulose, 5g of magnesium stearate, and 27g of film coating premix.

[0024] The preparation method is as follows: S1. Raw material pretreatment: All raw materials are passed through an 80-mesh sieve and used after passing inspection; S2. Premixing: Weigh the above raw and auxiliary materials (except for cross-linked sodium carboxymethyl cellulose, magnesium stearate and coating premixing agent) and mix them in a three-dimensional motion mixer for 10 minutes; S3. Preparation of soft material and granulation: Add an appropriate amount of 80% ethanol to prepare soft material, and granulate it through a 16-mesh sieve. S4. Drying: Dry at 50℃ for 30 minutes until the moisture content is ≤5%; S5. Granulation: Granulate through a 14-mesh sieve; S6. General Mixing: Add croscarmellose sodium cellulose and magnesium stearate, and mix for 10 minutes; S7. Tableting: Compressed into plain tablets of 0.9g / tablet; S8. Coating: Film coating with 10% coating solution results in a weight gain of approximately 3%; S9. Inner packaging, outer packaging, inspection and warehousing.

[0025] Comparative Example 1 The single internal disintegrant process was adopted, with 115g of crosslinked polyvinylpyrrolidone added internally, and the rest of the formulation and preparation method were the same as in Example 1.

[0026] Comparative Example 2 Corn starch was used as a filler, with a dosage of 150g. The rest of the formula and preparation method were the same as in Example 1.

[0027] Comparative Example 3 70% ethanol was used as the wetting agent, and the rest of the formulation and preparation method were the same as in Example 1.

[0028] Example 2: Comparative Test of Excipient Formulations The tablets prepared in Example 1, Comparative Example 1, and Comparative Example 2 were subjected to quality testing, and the results are shown in the table below:

[0029] The experimental results show that the internal and external disintegrant processes and microcrystalline cellulose fillers used in this invention enable the tablets to simultaneously possess good hardness, brittleness, and disintegration time, which are significantly better than those of the comparative example.

[0030] Example 3: Comparative Test of Wetting Agents The particles prepared in Example 1 and Comparative Example 3 were subjected to quality testing, and the results are shown in the table below:

[0031] The experimental results show that using 80% ethanol as a wetting agent results in better granulation, more uniform particles, and a higher yield.

[0032] Example 4: Three batches of pilot tests Following the formulation and process of Example 1, three batches of pilot production were conducted, with each batch containing 100,000 tablets. The production results are shown in the table below:

[0033] All three batches of pilot products met the standard requirements, with a yield of ≥98%, indicating that the process of this invention is stable and reliable and suitable for large-scale industrial production.

[0034] Example 5: Functional Evaluation Test for Assisted Protection Against Chemical Liver Injury In accordance with the requirements of the "Technical Specifications for Inspection and Evaluation of Health Foods" (2003 edition), the product of this invention was subjected to a mouse acute alcoholic liver injury model test.

[0035] 1. Experimental animals: 60 male SPF-grade Kunming mice, weighing 18-22g.

[0036] 2. Experimental grouping: Mice were randomly divided into 6 groups of 10 each: blank control group, model control group, positive control group (biphenyl diester, 150 mg / kg), low-dose group of the present invention (0.927 g / kg), medium-dose group (1.854 g / kg), and high-dose group (3.708 g / kg).

[0037] 3. Experimental Methods: Mice in each treatment group were administered the corresponding test substance by gavage daily, while the blank control group and model control group were administered an equal volume of physiological saline by gavage for 30 consecutive days. One hour after the last administration, except for the blank control group, mice in the other groups were administered 50% ethanol (12 ml / kg) by gavage to establish an acute alcoholic liver injury model. Sixteen hours later, blood was collected from the eyeballs of mice, serum was separated, and the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Mice were sacrificed, and livers were harvested to measure the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in liver tissue.

[0038] 4. Experimental Results:

[0039] Note: Compared with the model control group, *P<0.05, **P<0.01.

[0040] The experimental results show that the product of this invention can significantly reduce the serum ALT and AST activities and liver tissue MDA content in mice with acute alcoholic liver injury, and increase liver tissue SOD activity, thus having a significant auxiliary protective function against chemical liver injury.

[0041] Example 6 Accelerated Stability Test The product prepared in Example 1 was subjected to an accelerated stability test for 6 months at a temperature of 40℃±2℃ and a relative humidity of 75%±5%. Samples were taken and tested at 0, 1, 2, 3, and 6 months, and the results are shown in the table below: sheet

[0042] Accelerated testing results show that the product of this invention, after being placed under accelerated conditions for 6 months, meets all standard requirements and exhibits stable quality.

[0043] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A type of milk thistle, salvia miltiorrhiza, and notoginseng tablets, characterized in that, Based on 1000 tablets, the product is composed of the following raw and excipient materials: Raw materials: 350-400g of Salvia miltiorrhiza extract, 120-150g of Panax notoginseng extract, and 80-90g of milk thistle extract; Excipients: 150-170g of microcrystalline cellulose, 50-55g of crospovidone, 50-60g of crospovidone sodium carboxymethyl cellulose, and 3-5g of magnesium stearate; Coating material: 25-27g of film coating premix; The content of tanshinone IIA in the Salvia miltiorrhiza extract is ≥1%, and the extraction ratio is 7:1; The content of total saponins in the Panax notoginseng extract is ≥20%, and the extraction ratio is 6.7:1; The content of silybin in the milk thistle extract is ≥20%, and the extraction ratio is 25:

1.

2. The milk thistle and salvia miltiorrhiza tablets according to claim 1, characterized in that, The tablets are film-coated tablets, with a raw tablet weight of 0.9g-1.0g / tablet and a coated tablet weight of 0.927g-1.0g / tablet, resulting in a weight gain of approximately 1-3% after coating.

3. The milk thistle, salvia miltiorrhiza, and notoginseng tablets according to claim 1, characterized in that, The tablets have a disintegration time of ≤25 minutes, a hardness of ≥100N, a friability of ≤0.3%, and a moisture content of ≤5%.

4. A method for preparing milk thistle, salvia miltiorrhiza, and notoginseng tablets as described in any one of claims 1-3, characterized in that, Includes the following steps: S1. Raw material pretreatment: Pass all raw materials through an 80-100 mesh sieve and use them after passing the inspection. S2. Premixing: Weigh out the Salvia miltiorrhiza extract, Panax notoginseng extract, milk thistle extract, microcrystalline cellulose and crospovidone according to the formula, and mix them in a three-dimensional motion mixer for 6-10 minutes to obtain a mixed powder. S3. Preparation of soft material and granulation: Add an appropriate amount of ethanol to the mixed powder, stir to make a soft material of moderate hardness, granulate through a sieve to obtain wet granules. S4. Drying: Place the wet granules in a hot air circulating oven and dry at 45-55℃ for 20-30 minutes until the granule moisture content is ≤5%; S5. Granulation: The dried granules are granulated by passing them through a mesh sieve to obtain granulated granules; S6. Total Mixing: Place the whole granules in a mixer, add cross-linked sodium carboxymethyl cellulose and magnesium stearate, and mix to obtain total mixed granules; S7. Tableting: The total mixture of granules is compressed into tablets using a rotary tablet press; S8. Coating: Prepare a 5-10% coating solution using purified water with the film coating premix, and then coat the uncoated tablets with a film. The coating weight gain is approximately 1-3%. S9. Inner and outer packaging: The coated sheets are bottled, then the outer packaging is carried out, and the product is put into storage after passing inspection.

5. The preparation method according to claim 4, characterized in that, In steps S2 and S6, the mixing process is carried out in a Class 100,000 clean area, with the ambient temperature controlled at 18-26℃ and the relative humidity controlled below 74%.

6. The preparation method according to claim 4, characterized in that, In step S4, the granules are turned over every 10 minutes during the drying process to ensure uniform drying.

7. The preparation method according to claim 4, characterized in that, In step S8, the coating process parameters are: coating pan rotation speed 5-10 r / min, inlet air temperature 75-80℃, outlet air temperature 40-45℃, and tablet bed temperature controlled at 40-45℃.

Images