CN113197877B

CN113197877B - Pharmaceutical composition comprising silymarin

Info

Publication number: CN113197877B
Application number: CN202110358751.0A
Authority: CN
Inventors: 范敏华; 朱逸凡
Original assignee: Zhejiang Poly Pharmaceutical Co ltd; Hainan Poly Pharm Co ltd
Current assignee: Zhejiang Poly Pharmaceutical Co ltd; Hainan Poly Pharm Co ltd
Priority date: 2021-04-02
Filing date: 2021-04-02
Publication date: 2022-11-11
Anticipated expiration: 2041-04-02
Also published as: CN113197877A

Abstract

The application relates to a pharmaceutical composition containing silymarin, in particular to a silymarin liquid capsule, which comprises 1-20% of silymarin, 1-10% of sodium alginate, 1-10% of sorbitol, 1-10% of beeswax, 1-60% of soybean oil and 1-20% of lecithin.

Description

Pharmaceutical composition comprising silymarin

Technical Field

The application relates to a pharmaceutical composition containing silymarin, in particular to a silymarin liquid capsule which comprises silymarin, sodium alginate, sorbitol, beeswax, soybean oil and lecithin.

Background

Silymarin is a flavonoid compound extracted from fruit of Silybum marianum of Silybum of Compositae, and can be used for treating liver diseases. Silymarin has been shown to neutralize poisoning caused by muscarinic, α -amanita (a toxic substance found in amanita phalloidea), carbon tetrachloride, galactosamine, thioacetamide in various pathologic models of toxic liver damage. Silymarin has anti-peroxidation activity. Silymarin inhibits the pathophysiological processes of lipid peroxidation (causing damage to the cell membrane) and, in hepatocytes which have suffered damage, it stimulates the synthesis of proteins and normalizes phospholipid metabolism. Silymarin has a stabilizing effect on the liver cell membrane, which prevents or avoids the loss of dissolved cellular components (e.g., transaminase). Silymarin limits the penetration of certain hepatotoxic substances (e.g.. Alpha. -amanitin) into the interior of cells. Silymarin stimulates the activity of RNA polymerase I in the nucleus, thus aiding the synthesis of ribosomal RNA in hepatocytes, leading to the synthesis of structural and functional proteins (enzymes) in large quantities. Thus, silymarin can enhance the repair and regeneration ability of damaged hepatocytes.

Silymarin can relieve the liver cell damage and liver tissue inflammation mediated by the silymarin by removing free radicals, and can inhibit the triggering of hepatic fibrosis; in addition, inhibition of the fibroproliferative mechanism by down-regulation of type I collagen mRNA; by down-regulating mRNA of the tissue inhibitory factor-1 of the metalloprotease, the synthesis of the tissue inhibitory factor-1 of the metalloprotease is inhibited, and a mechanism of collagen decline is promoted. Thus, silymarin has both indirect and direct anti-fibrotic effects. The clinical application reports that the product has the curative effects of improving symptoms of hepatitis patients and promoting the recovery of liver functions. Acute and chronic hepatitis, liver cirrhosis, fatty liver, alcoholic liver injury, toxic liver injury, and cholelithiasis. The developed preparation of the medicine can be tablets, capsules, dripping pills and the like.

From the physical property, silymarin is almost insoluble in water and has poor fat solubility, so that the existing oral preparations such as tablets, liquid capsules and the like have the defects of poor stability and low bioavailability to different degrees, which has become a main factor for restricting the drug effect of the medicines.

Therefore, there is an urgent need to develop a silymarin oral preparation with high bioavailability and stability.

Disclosure of Invention

The application aims to provide a novel silymarin liquid capsule, which can overcome the defects of the silymarin, improve the bioavailability of the silymarin, and has the advantages of quick absorption and quick effect.

The applicant unexpectedly finds that the combined application of sodium alginate and sorbitol can greatly improve the bioavailability, stability and dissolution rate of silymarin, and further completes the invention.

One aspect of the invention provides a silymarin oral preparation, which comprises silymarin and pharmaceutically acceptable auxiliary materials.

One aspect of the invention provides a silymarin liquid capsule, which comprises silymarin and pharmaceutically acceptable auxiliary materials.

One aspect of the invention provides a silymarin liquid capsule, which comprises silymarin, sodium alginate, sorbitol, beeswax, soybean oil and lecithin.

In another aspect of the invention, a silymarin liquid capsule is provided, which comprises 1-20% of silymarin, 1-10% of sodium alginate, 1-10% of sorbitol, 1-10% of beeswax, 1-60% of soybean oil, and 1-20% of lecithin.

In another aspect of the invention, a silymarin liquid capsule is provided, which comprises 125g of silymarin, 20g of sodium alginate, 30g of sorbitol, 35g of beeswax, 360g of soybean oil and 30g of lecithin.

In another aspect of the invention, a method for preparing a silymarin liquid capsule is provided, which comprises the following steps:

(1) Pulverizing silymarin, and sieving with 100 mesh sieve;

(2) Adding sodium alginate, sorbitol, cera flava, and lecithin into soybean oil, heating to 50-60 deg.C, and stirring;

(3) Slowly adding silymarin into the solution obtained in the step (2), and uniformly stirring;

(4) Filling into capsule shell with 550mg per capsule, and sealing.

The silymarin liquid capsule prepared by the invention has the following beneficial effects:

1. the stability is good. The liquid capsule is stored for 2 years without the problems of silymarin precipitation, structural change, degradation and the like.

2. Sodium alginate and sorbitol which are selected in the liquid capsule can improve the solubility of silymarin.

3. The liquid capsule can more quickly and uniformly transfer the medicine to an absorption part, and improves the bioavailability.

Detailed Description

Example 1:

silymarin liquid capsule ingredients: 125g of silymarin, 20g of sodium alginate, 30g of sorbitol, 35g of beeswax, 360g of soybean oil and 30g of lecithin.

The preparation method comprises the following steps:

(1) Pulverizing silymarin, and sieving with 100 mesh sieve;

(4) Filling into capsule shell with 550mg each capsule, and sealing.

Example 2:

comparative example 1	Comparative example 2	Comparative example 3	Comparative example 4
				125g of silymarin	100g of silymarin	125g of silymarin	125g of silymarin
-	10g sodium alginate	20g of mannitol	20g microcrystalline cellulose
				-	10g sorbitol	30g of hydroxypropyl methylcellulose	30g xylitol
35g beeswax	70g beeswax	35g beeswax	35g of Arabic gum
				360g Soybean oil	200g of soybean oil	360g Soybean oil	360g Soybean oil
30g lecithin	100g lecithin	30g lecithin	30g of phospholipid

The preparation method is the same as example 1.

Example 3: stability control test

Example 1 and comparative examples 1-4 samples were bottled, left for 6 months at (40. + -. 2 ℃ C.) and relative humidity (75. + -.5)% and monitored for humidity, samples were taken at the end of 1, 2, 3, 6 months and the stability of silymarin in liquid capsules was checked to investigate the accelerated stability of the formulation. Similarly, the sample bottles are placed under the conditions of (25 +/-2 ℃) and relative humidity (60 +/-10)% for 24 months, the humidity is monitored, samples are taken at the end of 0, 3, 6, 9, 12 and 24 months, and the stability of the silymarin in the liquid capsules is tested to examine the long-term stability of the preparation. The results are shown in Table 1 and Table 2.

TABLE 1 accelerated test results

TABLE 2 Long term stability test

Compared with the components in the example 1, the components in the comparative example 1 are not sodium alginate and sorbitol, the components in the comparative example 2 are not changed but the dosage is changed, mannitol and hydroxypropyl methylcellulose are used in the comparative example 3 to replace sodium alginate and sorbitol, and the auxiliary material components in the comparative example 4 are changed. According to the stability test data in tables 1 and 2, sodium alginate and sorbitol have a decisive role in improving the stability of the silymarin liquid capsule, and in addition, the silymarin liquid capsule adopts specific auxiliary material components and specific dosage, so that the stability is reduced no matter the auxiliary material components are changed or the dosage is changed.

Example 4: dissolution test

The silymarin liquid capsules of example 1 and comparative examples 1 to 4 of the present invention were subjected to a comparative test of dissolution rate.

1. Instruments and reagents

Japanese Shimadzu LC-6A high performance liquid chromatograph, SPD-6AV ultraviolet detector; ZRS-8 Intelligent dissolution tester (Tianjin university Wireless Power plant). Example 1 and comparative examples 1-4 silymarin liquid capsule sample, acetonitrile (chromatographically pure), other reagents were analytically pure.

Preparation of reference solution and test solution

Preparation of control solutions: precisely weighing 25mg of silymarin liquid capsule samples of example 1 and comparative examples 1-4, which are dried at 100 deg.C for 5h, placing in a 250mL volumetric flask, adding appropriate amount of water, dissolving by ultrasonic treatment for 15min, cooling, adding purified water to scale, and shaking.

2. Measuring dissolution time and cumulative dissolution amount

Taking the silymarin liquid capsule samples of example 1 and comparative examples 1-4, according to the first dissolution test method, using 1000mL of water as solvent, and rotating at 120r min ^-1 According to the method, sampling 5mL (simultaneously replenishing 5mL solvent) at 30, 60, 90 and 120min respectively, filtering, taking 2mL filtrate, diluting to 5mL with mobile phase, testing according to the above chromatographic conditions, calculating cumulative dissolutionAmount (percentage) as shown in Table 3.

TABLE 3

Group of	30min	60min	90min	120min
					Comparative example 1	10.2	26.6	42.9	57.1
Comparative example 2	15.3	44.8	70.3	79.7
					Comparative example 3	12.5	33.5	44.3	63.8
Comparative example 4	8.8	35.2	63.6	71.1
					Example 1	22.3	56.3	90.6	98.7

Experimental results show that the silymarin liquid capsule combined by the sodium alginate and the sorbitol in the embodiment 1 of the invention has high dissolution speed and high bioavailability compared with the silymarin liquid capsules in the comparative examples 1-4, and has unexpected technical effects.

Claims

1. A silymarin soft capsule comprises silymarin 125g, sodium alginate 20g, sorbitol 30g, beeswax 35g, soybean oil 360g, and lecithin 30 g; the soft capsule is prepared by the following method:

(1) Pulverizing silymarin, and sieving with 100 mesh sieve;

(4) Filling into capsule shell with 550mg each capsule, and sealing.