CN104523974A - A traditional Chinese medicine preparation for preventing and treating liver fibrosis, soft capsule and preparation process thereof - Google Patents

Abstract

The invention relates to the technical field of traditional Chinese medicine pharmacy, in particular to a traditional Chinese medicine preparation and a soft capsule for preventing and treating hepatic fibrosis and a preparation process thereof; the traditional Chinese medicine preparation comprises the following medicinal materials in parts by weight: 500-1000 parts of pseudo-ginseng, 150-350 parts of astragalus root, 100-300 parts of salvia miltiorrhiza and 150-350 parts of figwort root. The traditional Chinese medicine preparation provided by the invention adopts a multi-component traditional Chinese medicine compound, has a multi-link, multi-level and multi-target pharmacological effect, and has an obvious advantage in preventing and treating hepatic fibrosis. The soft capsule of the invention has the advantages of accurate content, good stability, good dissolution, quick absorption, small side effect, convenient carrying, safe and convenient taking, small dosage, high bioavailability, quick curative effect, good effect and the like.

Description

A traditional Chinese medicine preparation for preventing and treating liver fibrosis, soft capsule and preparation process thereof

technical field

The invention relates to the technical field of traditional Chinese medicine pharmacy, in particular to a traditional Chinese medicine preparation for preventing and treating liver fibrosis, a soft capsule and a preparation process thereof.

Background technique

Liver fibrosis refers to the abnormal proliferation of connective tissue in the liver caused by various pathogenic factors, leading to the pathological process of excessive precipitation of diffuse extracellular matrix in the liver. It is not an independent disease, and many chronic liver diseases can cause liver fibrosis. change. Liver fibrosis caused by accumulation of extracellular matrix (ECM) in the process of chronic liver injury can be reversed by effective treatment, but once cirrhosis is formed, it is difficult to reverse. Effective treatment of liver fibrosis mainly includes etiological treatment targeting the primary disease, anti-inflammatory treatment, inhibition of ECM generation in the liver, and promotion of ECM degradation. At the same time, the development of new drugs and treatment methods, and the new use of old drugs are also among them.

In recent years, some progress has been made in anti-hepatic fibrosis therapy, such as polyunsaturated lecithin and prostaglandins have been clinically evaluated; γ-interferon can inhibit the progress of fibrosis in the treatment of chronic liver disease, but the curative effect is not ideal . Judging from the results of modern biomedical research, so far there has been no breakthrough in the clinical treatment of liver fibrosis, and new drugs or new treatment methods that act on different stages of liver fibrosis have only made some progress in animal experiments. Almost all reports on the treatment of liver fibrosis are in the stage of experimental exploration, and none of them have been successfully applied in clinical practice.

In view of the fact that the treatment of liver fibrosis is difficult to break through for a while, the focus of research will be on basic research, in order to find a breakthrough from the gradually understood formation mechanism of liver fibrosis and develop new drugs and treatments.

Modern biomedicine only focuses on a certain point in the pathogenesis link in the research thinking of anti-hepatic fibrosis treatment, so this point can be regarded as one of the main reasons affecting the curative effect.

The formation and development of liver fibrosis is an extremely complicated process. In the past 10 years, the research on the anti-hepatic fibrosis treatment of traditional Chinese medicine has made some progress, but there is no breakthrough progress, and there are few studies under the guidance of the theory of traditional Chinese medicine. There are many researches on ingredients and few researches on compound recipes, and the effect is not good enough.

Contents of the invention

The object of the present invention is to provide a traditional Chinese medicine preparation with effective compound prescription for preventing and treating liver fibrosis aiming at the deficiencies of the prior art.

The object of the present invention is to aim at the deficiencies of the prior art, and provide a soft capsule with high bioavailability and good effect for preventing and treating liver fibrosis.

The object of the present invention is to aim at the deficiencies of the prior art, and provide a kind of preparation technology of the soft capsule with high production efficiency, high extraction purity, good effect of preventing and treating liver fibrosis.

A traditional Chinese medicine preparation for preventing and treating liver fibrosis, which comprises the following medicinal materials in parts by weight: 500-1000 parts of notoginseng, 150-350 parts of astragalus, 100-300 parts of salvia miltiorrhiza, and 150-350 parts of scrophulariae.

According to the pathology of hepatic fibrosis, compared with the relevant discussions in traditional Chinese medicine, combined with the research results in recent years, it can be considered that hepatic fibrosis has certain similarities with the "disease accumulation" in traditional Chinese medicine. Similarly, traditional Chinese medicine has many understandings of the pathogenesis of accumulated symptoms, but in terms of its essence, it is mainly based on blood stasis and phlegm. basic rule of thumb. According to modern medical theory, liver parenchymal cell damage and changes in the body's immune function play an important role in the occurrence and development of liver fibrosis. Affects the metabolism of connective tissue to a certain extent, and it can be used together with promoting blood circulation and removing blood stasis to achieve a complementary effect.

According to modern medicine, free radical damage can cause liver fibrosis, and the fibrosis process produces toxic free radical malondialdehyde (MAD). SOD), glutathione is a free radical scavenger. Effective against free radicals such as malondialdehyde.

Notoginseng, sweet and slightly bitter in taste, warm in nature, returns to liver and stomach meridian. It has the effects of dissipating blood stasis and hemostasis, reducing swelling and relieving pain. The notoginseng total saponins contained in the notoginseng of the present invention can reduce malondialdehyde and increase the amount of superoxide dismutase SOD and glutathione. Pharmacological experiments have shown that Panax notoginseng has a certain protective effect on liver cell damage, and can significantly inhibit the proliferation of fibroblasts and collagen fibers in liver tissue. It is an ideal drug for preventing and treating liver fibrosis.

Astragalus can enhance the resistance of patients, improve their immune function, and effectively fight against liver fibrosis.

The tanshinone possessed by Danshen has anti-fibrosis effect; studies have shown that Danshen has obvious protective effect on liver ischemia-reperfusion injury, has obvious protective effect on acute liver injury in rats, and salvianolic acid B-magnesium salt has anti-fibrosis. The role of D-galactosamine liver injury in rats, Danshen injection has a certain effect on isolated perfused liver and portal vein blood vessels in rats, and has a protective effect on isolated perfused liver in rats with CCl ₄ injury, which can effectively delay and alleviate Irreversible liver damage caused by ischemia reperfusion can promote liver regeneration; it can significantly promote liver DNA synthesis and cell division and proliferation after partial hepatectomy in rats; it can promote liver fiber reabsorption, Good anti-hepatic fibrosis effect.

The phenylpropanoid glycoside in Scrophulariaceae has liver protection effect. Studies have found that phenylpropanoid glycoside XS-10 has a significant protective effect on liver cell damage caused by D-galactosamine and can inhibit liver cell apoptosis. At the same time, Scrophulariaceae is a medicine for clearing heat, nourishing yin and cooling blood, which is beneficial to patients with chronic liver disease due to yin deficiency.

The traditional Chinese medicine preparation for preventing and treating liver fibrosis of the present invention mainly uses notoginseng and salvia miltiorrhiza for promoting blood circulation and removing blood stasis, and also uses astragalus and crocodile for nourishing qi and nourishing yin.

Preferably, a traditional Chinese medicine preparation for preventing and treating liver fibrosis includes the following medicinal materials in parts by weight: 500-750 parts of Panax notoginseng, 200-350 parts of Radix Astragali, 100-200 parts of Danshen, and 250-350 parts of Scrophulariae.

Preferably, a traditional Chinese medicine preparation for preventing and treating liver fibrosis includes the following medicinal materials in parts by weight: 750-1000 parts of Panax notoginseng, 150-200 parts of Radix Astragali, 200-300 parts of Salvia miltiorrhiza, and 150-250 parts of Scrophulariaceae.

Preferably, a traditional Chinese medicine preparation for preventing and treating liver fibrosis includes the following medicinal materials in parts by weight: 600-800 parts of Panax notoginseng, 200-300 parts of Radix Astragali, 100-200 parts of Danshen, and 200-300 parts of Scrophulariae.

Preferably, a traditional Chinese medicine preparation for preventing and treating liver fibrosis includes the following medicinal materials in parts by weight: 700-800 parts of Panax notoginseng, 200-250 parts of Radix Astragali, 140-200 parts of Salvia miltiorrhiza, and 260-300 parts of Scrophulariaceae.

Preferably, a traditional Chinese medicine preparation for preventing and treating liver fibrosis includes the following medicinal materials in parts by weight: 600-700 parts of Panax notoginseng, 250-300 parts of Radix Astragali, 100-140 parts of Danshen, and 200-260 parts of Scrophulariae.

Preferably, it includes the following medicinal materials in parts by weight: 750 parts of notoginseng, 240 parts of astragalus, 150 parts of salvia miltiorrhiza, and 240 parts of crocodile.

Preferably, 10-20 parts of Rhizoma Chuanxiong, 5-15 parts of Shengdi, 1-5 parts of Saffron, 20-30 parts of Eupatorium, 8-12 parts of Curcuma, and 8-12 parts of Wang Buliuxing.

More preferably, 5-10 parts of Bupleurum, 13-22 parts of Caulis Spatholobus, 18-29 parts of Radix Paeoniae Alba, 3-6 parts of Turtle Shell, 5-10 parts of Radix Paeoniae Rubra, and 20-30 parts of Licorice Root.

Ligusticum chuanxiong, commonly used for promoting blood circulation and promoting qi, dispelling wind and relieving pain. Ligusticum chuanxiong is pungent, warm, fragrant and dry. Blood stasis stagnates various diseases.

Habitat has the effects of clearing away heat and cooling blood, benefiting yin and promoting body fluid. It is used for febrile diseases, heat entering the camp and blood, strong heat, dizziness, dry mouth and tongue, such as Qingying Decoction.

Saffron has the effects of dredging meridian and activating collaterals, dredging meridians and dissolving silt, dispelling silt and unblocking knots, reducing swelling, relieving pain, cooling blood and detoxifying, and worrying and stagnant. Taking it for a long time can comprehensively improve the body's immunity.

Zeilan has the effects of promoting blood circulation and removing blood stasis; promoting water and reducing swelling; detoxifying and eliminating carbuncle.

Curcuma, pungent in taste, bitter, cold in nature, returns to the liver, heart, and lung meridian, has the functions of promoting qi and removing blood stasis, clearing away heart-fire and relieving stagnation, promoting gallbladder and relieving jaundice, promoting blood circulation and relieving pain, promoting qi and relieving depression, clearing heart and cooling blood.

Bupleurum, bitter and cool in nature, has the functions of dispersing and reducing fever, soothing the liver and relieving stagnation, restoring the normal metabolism and blood supply of liver cells, promoting the repair of damage and promoting the yang of liver cells. Clinically, in addition to the traditional treatment of liver depression and qi stagnation. It is also used in modern times to treat various liver diseases. From the perspective of modern pharmacology, acetylcholine has the function of regulating the functions of the digestive system and nervous system, and acetylcholine can be hydrolyzed by cholinesterase. Saikosaponin can inhibit cholinesterase, play a cholinergic effect, and then play a regulatory role on the digestive system and nervous system, thereby treating liver depression syndrome, and playing the role of soothing the liver and relieving depression. Bupleurum chinensis can inhibit the apoptosis of mouse liver cells, and has significant repairing and protecting effects on chronic liver injury in mice induced by CCl ₄ , D-galactosamine, lipopolysaccharide and BCG.

Spatholobus has good effects on hematopoietic system, blood coagulation, fibrinolysis, heart suppression, lowering blood pressure, anti-cancer, and regulation of lipid metabolism. Radix Paeoniae Alba, cool in nature, bitter and sour in taste, slightly cold, has the effects of nourishing blood and nourishing blood, calming liver yang, softening liver and relieving pain, astringing yin and stopping sweating.

Turtle shell has the functions of nourishing yin and suppressing yang, softening and resolving hard masses. Studies have shown that turtle shell has obvious protective effect on experimental liver fibrosis in rats, and early application can prevent or delay the formation and development of liver fibrosis.

Radix Paeoniae Rubra, bitter, slightly cold, returns to Liver Meridian. It has the effects of clearing away heat and cooling blood, dissipating blood stasis and relieving pain. Modern studies have shown that Radix Paeoniae Rubra has a strong direct inhibitory effect on DNAP of hepatitis B virus, can reduce red blood cell aggregation, improve liver microcirculation, restore normal metabolism and blood supply of liver cells, and promote damage repair and liver cell regeneration.

Licorice has glycyrrhizin, glycyrrhetinate, etc., which have anti-inflammatory, anti-allergic, and anti-liver damage effects.

A soft capsule for preventing and treating liver fibrosis, comprising a capsule shell and contents, wherein the contents of the soft capsule are composed of the effective dry paste powder of the extract of the above-mentioned traditional Chinese medicine preparation, soybean oil and beeswax; the effective dry paste powder and The weight ratio of soybean oil is 3-5:7-5, the addition ratio of beeswax is 4%-6% of soybean oil; 0.8-1.2 servings are made.

Preferably, the weight ratio of the effective dry paste powder to soybean oil is 4:6.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of traditional Chinese medicine preparation medicinal material dry cream powder:

A1. Preparation of Radix Notoginseng Dry Paste Powder: Grind Radix Notoginseng into 40-60 mesh fine powder in parts by weight, add 70%-80% ethanol 3-6 times the weight of Notoginseng powder, and percolate to high-efficiency liquid phase If the chromatographic determination is up to the standard, the percolation liquid that reaches the standard is heated under reduced pressure under the condition of -35KPa to -70KPa to recover ethanol, and concentrated to a relative density of 1.15-1.25, and the concentrated solution is dried in a vacuum continuous low-temperature belt dryer to obtain three Qigan paste powder is up to standard through high performance liquid chromatography, and the up-to-standard Radix Notoginseng paste powder is taken for subsequent use;

B1. Preparation of Salvia Miltiorrhiza Dry Paste Powder: Put Salvia Miltiorrhiza into the percolation extraction device in parts by weight. The percolation liquid extracted by the filter is qualitatively tested for tanshinone. The standard percolation liquid is heated under reduced pressure from -35KPa to -70KPa to recover ethanol and concentrated to a relative density of 1.15-1.25. The Danshen concentrated liquid is passed through a vacuum continuous low-temperature belt dryer Dried to prepare the dried salvia miltiorrhiza powder for subsequent use;

C1. Preparation of remaining medicinal material dry paste powder: add the remaining medicinal material to pure water and decoct for extraction 2 times in parts by weight: add pure water 3-4 times the weight of the remaining medicinal material for the first time, boil for 2-3 hours, and extract Liquid filtration, add 2-3.5 times the amount of pure water to the second extraction, boil for 1-2.5 hours, filter to remove the medicinal residue, combine the two extraction filtrates, and heat under reduced pressure at -35KPa to -70KPa to recover ethanol Concentrate to a relative density of 1.20-1.35, add 95% ethanol to make the ethanol content of the filtrate reach no less than 70%, refrigerate at 4-14°C, stand still for no less than 24 hours, filter, and the filtrate is under the condition of -35KPa to -70KPa Ethanol is recovered under reduced pressure and concentrated until the relative density of the filtrate is 1.20-1.35; the concentrated solution is dried by a vacuum belt-type low-temperature continuous dryer, and the remaining medicinal material dry cream powder is prepared for use;

(2) Preparation of soft capsule contents:

Mix the notoginseng dry paste powder, salvia miltiorrhiza dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1 evenly, add beeswax and soybean oil in parts by weight, heat and stir evenly, and all enter the colloid mill for grinding for 40- 120 minutes, pulverize and mix uniformly, make soft capsule content;

(3) Preparation of capsule shell

A2, by weight, put gelatin, water, glycerin into the gelatin tank and mix it into gelatin solution, stir, and heat water at 80-90°C in the sandwich pot to keep the temperature of the gelatin solution at 70-80°C, so that the gelatin is completely dissolved. -35KPa to -70KPa under reduced pressure and heat the gelatin solution until there are no bubbles, and the gelatin solution is ready for use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a spherical capsule that meets the specifications to make a soft capsule.

Wherein, in the step (1) preparation of dry cream powder of traditional Chinese medicine preparations, a percolation extraction device is used for percolation extraction; the inlet temperature of the belt drying system is 150°C, and the outlet temperature is 70°C.

The percolation extraction device used in the present invention is the structure described in the patent number "201320540307.1" and the title "A Soxhlet Extractor with Improved Structure".

Use high-performance liquid chromatography to measure the content of total saponins of Panax notoginseng. If the content reaches the standard, the ethanol is recovered, and if the content does not meet the standard, it will be used mechanically (reuse).

The soft capsules for preventing and treating liver fibrosis are washed with 75% ethanol and dried under the conditions of 35°C and 30% relative humidity. Each soft capsule for preventing and treating liver fibrosis contains not less than 36.0mg of total saponins of Panax notoginseng .

The content of chromium element in gelatin, which is the material for making capsule shells, must not exceed the national standard of 2mg/kg. Advanced atomic absorption spectrometer is used to measure the content of chromium element in the soft capsule rubber to be less than 1.5mg/kg. All standards met and 25% lower than specified.

The beneficial effects of the present invention are:

The traditional Chinese medicine preparation for preventing and treating liver fibrosis of the present invention comprises the following medicinal materials in parts by weight: 600-800 parts of notoginseng, 200-300 parts of astragalus, 100-200 parts of salvia miltiorrhiza and 200-300 parts of scrophulariae. The traditional Chinese medicine preparation for preventing and treating liver fibrosis of the present invention adopts the pharmacological effects of multi-components, multi-links, multi-levels and multi-target points of the traditional Chinese medicine compound, and has obvious advantages in preventing and treating liver fibrosis.

The soft capsule for preventing and treating liver fibrosis of the present invention has the advantages of accurate content, good stability, good dissolution, fast absorption, less side effects, convenient carrying, less dosage, high bioavailability, rapid curative effect, good effect and the like.

The preparation process of the soft capsule for preventing and treating liver fibrosis of the present invention has the following advantages:

(1) In step A1, extract Panax notoginseng by percolation extraction at room temperature (30°C±5°C), and optimize the concentration of ethanol to increase the extraction rate of active ingredients such as Panax notoginseng saponin, so that the active ingredients of Panax notoginseng will not be destroyed, By shortening the extraction time by more than 40%, the influence of oxidative degradation and other changes on the quality of the product is avoided, and the quantitative determination of high-performance liquid chromatography is used to ensure that the total saponin content of each capsule of notoginseng is not less than 36.0mg.

(2) In the step B1 of the present invention, the extraction of Salvia miltiorrhiza dry cream powder adopts the heat preservation and continuous percolation extraction method, which reduces the extraction time by more than 15%; the extraction temperature is lowered by more than 8% compared with the decoction method, and the belt drying method is better than the spray method. The drying temperature has been reduced by more than 10%. The method improves quality, increases efficiency and reduces costs.

(3) In step C1 of the present invention, the water extraction and alcohol precipitation extraction method can increase the removal of impurities such as ineffective components by more than 5%, which is beneficial to control the proportion of fat-soluble excipients in the soft capsule and improve the stability of the preparation.

(4) In the preparation process of the present invention, the dry paste powders made respectively are dried through a vacuum belt drying system, and the dry extract powders contain 95% of the active ingredients of the medicine, the extraction purity of the medicinal materials, and the bioavailability of the contents of the soft capsule High degree; and then made into soft capsules through various processes, the extraction efficiency is greatly improved, energy is saved by 20%, the extraction efficiency is increased by more than 25%, and the cost is reduced by more than 10%.

(5) The preparation process has high production efficiency, high extraction purity and good effect; using continuous percolation, the contents of the prepared soft capsule have accurate content, good stability, good dissolution, fast absorption, small side effects, easy to carry, and easy to take. Small amount, high bioavailability, rapid curative effect and so on.

Detailed ways

The present invention will be further described below in conjunction with embodiment.

Example 1.

A traditional Chinese medicine preparation for preventing and treating liver fibrosis, which comprises the following medicinal materials in parts by weight: 500 parts of Panax notoginseng, 300 parts of Radix Astragali, 100 parts of Danshen and 300 parts of Scrophulariae.

A soft capsule for preventing and treating liver fibrosis, the content of the soft capsule is composed of effective dry cream powder, soybean oil, and beeswax of the extracts of the above-mentioned traditional Chinese medicine preparation; the weight ratio of the effective dry cream powder to soybean oil is 3 : 7, the addition ratio of beeswax is 4% of soybean oil; the capsule shell is made of 0.95 part of gelatin, 0.5 part of glycerin and 0.8 part of water by weight.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of dry paste powder of traditional Chinese medicine preparations:

A1, the preparation of Radix Notoginseng dry paste powder: by weight, Radix Notoginseng is pulverized into 40 mesh fine powder, adds 70% ethanol of 3 times of Radix Notoginseng powder weight, infiltrates until high performance liquid chromatography is measured and reaches the standard, will reach the standard The percolation liquid is heated under reduced pressure at -35KPa to recover ethanol and concentrated to a relative density of 1.20. The concentrated liquid is dried in a vacuum continuous low-temperature belt dryer to obtain a dry paste of Sanqi, which is up to standard through high performance liquid chromatography. Get the standard notoginseng dry cream powder for later use;

B1. Preparation of Salvia Miltiorrhiza Dry Paste Powder: Put Salvia Miltiorrhiza into the percolation extraction device in parts by weight. Under the condition of 60° C., interlayer heat preservation is carried out for continuous percolation extraction, and a condensation device is provided to prevent ethanol volatilization; through continuous percolation extraction The percolation liquid was qualitatively tested for tanshinone, and the qualified percolation liquid was heated under reduced pressure at -35KPa to recover ethanol and concentrated to a relative density of 1.15. The Danshen concentrated liquid was dried in a vacuum continuous low-temperature belt dryer to obtain Danshen dry cream powder spare;

C1. Preparation of remaining medicinal material dry cream powder: by weight, add remaining medicinal material to pure water and decoct for extraction 2 times: add 3-4 times the amount of pure water of the weight of remaining medicinal material for the first time, boil for 2 hours, and filter the extract After the second extraction, add 2 times the amount of pure water, boil for 1 hour, filter to remove the medicinal residues, combine the two extraction filtrates, heat under reduced pressure at -35KPa to recover ethanol and concentrate to a relative density of 1.25, add 95 % ethanol to make the ethanol content of the filtrate reach no less than 70%, refrigerate at 4°C, stand still for no less than 24 hours, filter, and recover the ethanol from the filtrate under reduced pressure at -35KPa and concentrate until the relative density of the filtrate is 1.25; Dry in a belt-type low-temperature continuous dryer to prepare the remaining medicinal material dry cream powder for later use;

(2) Preparation of soft capsule contents:

Mix the Panax notoginseng dry paste powder, Danshen dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1 evenly, add beeswax and soybean oil in parts by weight, heat and stir evenly, and grind them all in a colloid mill for 40 minutes , ground and mixed evenly to obtain the contents of the soft capsule;

(3) Preparation of capsule shell

A2, by weight, gelatin, water, glycerin are put into the gelatin tank and mixed into gelatin liquid, stirred, jacketed pot is kept warm at 80 ℃, gelatin is completely dissolved, and the gelatin liquid is heated under reduced pressure under the condition of -35KPa until no bubbles are obtained. Gelatin solution for use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a streamlined capsule that meets the specifications and is made into a soft capsule.

Utilize high-performance liquid chromatography to measure the content of active ingredients in the extract. If the content is not up to the standard, it needs to be reused. The ethanol is about to reach the detection level range and the ethanol is directly recovered. If the content of the active ingredients does not reach the content, it is reused.

The step (1) uses a percolation extraction device for percolation extraction; the inlet temperature of the belt drying system is 150°C, and the outlet temperature is 70°C.

The soft capsules for preventing and treating liver fibrosis are washed with 75% ethanol and dried under the conditions of 35°C and 30% relative humidity. Each soft capsule for preventing and treating liver fibrosis contains not less than 36.0mg of total saponins of Panax notoginseng .

Example 2.

The difference between this example and Example 1 is: a traditional Chinese medicine preparation for preventing and treating liver fibrosis in this example, which includes the following medicinal materials in parts by weight: 650 parts of Panax notoginseng, 280 parts of Radix Astragali, 120 parts of Salvia miltiorrhiza, Scrophulariaceae 250 copies.

A soft capsule for preventing and treating liver fibrosis, the content of the soft capsule is composed of effective dry cream powder, soybean oil and beeswax of the extracts of the above-mentioned traditional Chinese medicine preparation; the weight ratio of the effective dry cream powder to soybean oil is 4 : 6, the addition ratio of beeswax is 4.5% of soybean oil; the capsule shell is made of 1 part of gelatin, 0.35 part of glycerin and 0.95 part of water in parts by weight.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of traditional Chinese medicine preparation medicinal material dry cream powder:

A1, the preparation of Radix Notoginseng dry paste powder: by weight, Radix Notoginseng is pulverized into 60 order fine powder, adds 80% ethanol of 6 times of Radix Notoginseng powder weight, infiltrates until high performance liquid chromatography is measured up to standard, and the up to standard The percolation liquid was heated under reduced pressure at -45KPa to recover ethanol and concentrated to a relative density of 1.25. The concentrated liquid was dried in a vacuum continuous low-temperature belt dryer to obtain a Sanqi dry cream powder, which was tested by high performance liquid chromatography and reached the standard. Get the standard notoginseng dry cream powder for later use;

B1. Preparation of Salvia Miltiorrhiza Dry Paste Powder: Put Salvia Miltiorrhiza into the percolation extraction device in parts by weight. Under the condition of 65° C., interlayer heat preservation is carried out for continuous percolation extraction, and a condensation device is provided to prevent ethanol volatilization; through continuous percolation extraction The percolation solution was qualitatively tested for tanshinone, and the percolation solution that reached the standard was heated under reduced pressure at -45KPa to recover ethanol and concentrated to a relative density of 1.21. The concentrated solution of Danshen was dried in a vacuum continuous low-temperature belt dryer to obtain dry paste powder of Danshen spare;

C1. Preparation of remaining medicinal material dry cream powder: by weight, add remaining medicinal material to pure water and decoct for extraction twice: add 2.5 times the amount of pure water of the remaining medicinal material for the first time, boil for 2.5 hours, and filter the extract , add 2 times the amount of pure water for the second extraction, boil for 1.5h, filter to remove the medicinal residues, combine the two extraction filtrates, heat under reduced pressure at -45KPa to recover ethanol and concentrate to a relative density of 1.25, add 95 % ethanol to make the ethanol content of the filtrate reach no less than 70%, refrigerate at 6°C, stand still for no less than 24 hours, filter, and recover the ethanol from the filtrate under reduced pressure at -45KPa and concentrate until the relative density of the filtrate is 1.25; Dry in a belt-type low-temperature continuous dryer to prepare the remaining medicinal material dry cream powder for later use;

(2) Preparation of soft capsule contents:

Mix the notoginseng dry paste powder, salvia miltiorrhiza dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1 evenly, add beeswax and soybean oil in parts by weight, heat and stir evenly, and grind them all in a colloid mill for 50 minutes , ground and mixed evenly to obtain the contents of the soft capsule;

(3) Preparation of capsule shell

A2, by weight, gelatin, water, glycerin are put into the gelatin tank and mixed into gelatin liquid, stirred, jacketed pot is kept warm at 72 ℃, gelatin is completely dissolved, and the gelatin liquid is heated under reduced pressure under the condition of -45KPa until there are no bubbles, to obtain Gelatin solution for use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a streamlined capsule that meets the specifications and is made into a soft capsule.

The step (1) uses a percolation extraction device for percolation extraction; the inlet temperature of the belt drying system is 150°C, and the outlet temperature is 70°C.

The soft capsules for preventing and treating liver fibrosis are washed with 75% ethanol and dried under the conditions of 35°C and 30% relative humidity. Each soft capsule for preventing and treating liver fibrosis contains not less than 36.0mg of total saponins of Panax notoginseng .

Example 3.

The difference between this example and Example 1 is: a Chinese medicine preparation for preventing and treating liver fibrosis in this example, which includes the following medicinal materials in parts by weight: 900 parts of Panax notoginseng, 180 parts of Astragalus membranaceus, 220 parts of Danshen, and Scrophulariaceae 220 copies.

A soft capsule for preventing and treating liver fibrosis, the content of the soft capsule is composed of effective dry cream powder, soybean oil and beeswax of the extracts of the above-mentioned traditional Chinese medicine preparation; the weight ratio of the effective dry cream powder to soybean oil is 5 : 7, the addition ratio of beeswax is 5% of soybean oil; the capsule shell is made of 0.98 part of gelatin, 0.45 part of glycerin and 0.9 part of water in parts by weight.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of traditional Chinese medicine preparation medicinal material dry cream powder:

A1. Preparation of Panax notoginseng dry cream powder: Grind notoginseng into 55 mesh fine powder in parts by weight, add an appropriate amount of 80% ethanol, percolate until the active ingredient total saponins of Panax notoginseng reaches the standard by high-performance liquid chromatography, and the standard notoginseng saponins The filtrate was heated under reduced pressure at -55KPa to recover ethanol, and concentrated to a relative density of 1.20. The concentrated solution was dried in a vacuum continuous low-temperature belt dryer to obtain a dry powder of Sanqi, which was tested by high performance liquid chromatography and reached the standard. Get the standard notoginseng dry cream powder for later use;

B1. Preparation of dry salvia miltiorrhiza powder: according to parts by weight, put salvia miltiorrhiza into the percolation extraction device, under the condition of 67°C, the interlayer is kept warm for continuous percolation extraction, and a condensation device is installed to prevent ethanol volatilization. The percolation liquid extracted by continuous percolation is qualitatively tested for tanshinone, and the percolation liquid that reaches the standard is heated under reduced pressure at -55KPa to recover ethanol and concentrated to a relative density of 1.22. The Danshen concentrate is dried in a vacuum continuous low-temperature belt dryer. The dry cream powder of salvia miltiorrhiza is prepared for subsequent use;

C1. Preparation of remaining medicinal material dry paste powder: by weight, add remaining medicinal material to pure water and decoct for extraction 2 times: add pure water of 3 times the weight of remaining medicinal material for the first time, boil for 3 hours, filter the extract, Add 2 times the amount of pure water for the second extraction, boil for 2 hours, filter to remove the medicinal residues, combine the two extraction filtrates, heat under reduced pressure at -55KPa to recover ethanol and concentrate to a relative density of 1.30, add 95% ethanol Make the ethanol content of the filtrate reach not less than 70%, refrigerate at 8°C, stand still for not less than 24 hours, filter, and recover the ethanol from the filtrate under reduced pressure at -55KPa and concentrate until the relative density of the filtrate is 1.30; pass the concentrated solution through a vacuum belt Drying in a low-temperature continuous dryer to obtain the remaining medicinal material dry paste powder for subsequent use;

(2) Preparation of soft capsule contents:

Mix the notoginseng dry paste powder, salvia miltiorrhiza dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1 evenly, add beeswax and soybean oil in parts by weight, heat and stir evenly, and grind them all in a colloid mill for 60 minutes , ground and mixed evenly to obtain the contents of the soft capsule;

(3) Preparation of capsule shell

A2, by weight, put gelatin, water, glycerin into the colloidal sol tank and mix it into gelatin liquid, stir, keep warm in the jacketed pot at 80°C to completely dissolve the gelatin, and heat under reduced pressure under the condition of -35KPa to -70KPa until the gelatin liquid is gone. until there are bubbles, get the gelatin solution for later use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a streamlined capsule that meets the specifications and is made into a soft capsule.

The step (1) uses a percolation extraction device for percolation extraction; the inlet temperature of the belt drying system is 150°C, and the outlet temperature is 70°C.

The soft capsules for preventing and treating liver fibrosis are washed with 75% ethanol and dried under the conditions of 35°C and 30% relative humidity. Each soft capsule for preventing and treating liver fibrosis contains not less than 36.0mg of total saponins of Panax notoginseng .

Example 4.

The difference between this example and Example 1 is that a traditional Chinese medicine preparation for preventing and treating liver fibrosis in this example includes the following medicinal materials in parts by weight: 750 parts of Panax notoginseng, 240 parts of Radix Astragali, 150 parts of Salvia miltiorrhiza, Scrophulariaceae 240 copies.

A soft capsule for preventing and treating liver fibrosis, the content of the soft capsule is composed of effective dry cream powder, soybean oil and beeswax of the extracts of the above-mentioned traditional Chinese medicine preparation; the weight ratio of the effective dry cream powder to soybean oil is 4 : 5, the addition ratio of beeswax is 5.5% of soybean oil; the capsule shell is made of 1.02 parts of gelatin, 0.5 parts of glycerin and 1.0 part of water in parts by weight.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of traditional Chinese medicine preparation medicinal material dry cream powder:

A1, the preparation of Radix Notoginseng dry paste powder: by weight, Radix Notoginseng is pulverized into 50 order fine powder, adds the 75% ethanol of 5 times of Radix Notoginseng powder weight, infiltrates until high-performance liquid chromatography is measured and reaches the standard, and the up-to-standard The percolation liquid was heated under reduced pressure at -65KPa to recover ethanol and concentrated to a relative density of 1.23. The concentrated liquid was dried in a vacuum continuous low-temperature belt dryer to obtain a dry cream powder of notoginseng, which was tested by high performance liquid chromatography and reached the standard. Get the standard notoginseng dry cream powder for later use;

B1. Preparation of dry salvia miltiorrhiza powder: according to parts by weight, put salvia miltiorrhiza into the percolation extraction device, under the condition of 70° C., the interlayer is kept warm for continuous percolation extraction, and a condensation device is installed to prevent ethanol volatilization. The percolation liquid extracted by continuous percolation is qualitatively tested for tanshinone, and the percolation liquid that reaches the standard is heated under reduced pressure at -65KPa to recover ethanol and concentrated to a relative density of 1.23. The dry cream powder of salvia miltiorrhiza is prepared for subsequent use;

C1. Preparation of remaining medicinal material dry cream powder: by weight, add remaining medicinal material to pure water and decoct for extraction 2 times: add pure water of 3 times the weight of remaining medicinal material for the first time, boil for 2 hours, filter the extract, Add 2 times the amount of pure water for the second extraction, boil for 2 hours, filter to remove the medicinal residues, combine the two extraction filtrates, heat under reduced pressure at -65KPa to recover ethanol and concentrate to a relative density of 1.25, add 95% ethanol Make the ethanol content of the filtrate reach no less than 70%, refrigerate at 10°C, stand still for no less than 24 hours, filter, and recover the ethanol from the filtrate under reduced pressure at -65KPa and concentrate until the relative density of the filtrate is 1.25; pass the concentrated solution through a vacuum belt Drying in a low-temperature continuous dryer to obtain the remaining medicinal material dry paste powder for subsequent use;

(2) Preparation of soft capsule contents:

Mix the notoginseng dry paste powder, Danshen dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1 evenly, add beeswax and soybean oil in parts by weight, heat and stir evenly, and put them into a colloid mill for grinding for 70 minutes , ground and mixed evenly to obtain the contents of the soft capsule;

(3) Preparation of capsule shell

A2, by weight, put gelatin, water, glycerin into a sol tank and mix to form a gelatin solution, stir, keep warm in a jacketed pot at 85°C to completely dissolve the gelatin, heat the gelatin solution under reduced pressure at -65KPa Until there are no bubbles, get the gelatin solution for later use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a streamlined capsule that meets the specifications and is made into a soft capsule.

Example 5.

The difference between this example and Example 1 is that a traditional Chinese medicine preparation for preventing and treating liver fibrosis in this example includes the following medicinal materials in parts by weight: 800 parts of Panax notoginseng, 200 parts of Astragalus membranaceus, 200 parts of Salvia miltiorrhiza, scrophulariaceae 200 parts, 15 parts of Chuanxiong, 10 parts of raw land, 5 parts of saffron, 25 parts of Eupatorium, 10 parts of turmeric, 10 parts of Wang Buliuxing.

A soft capsule for preventing and treating liver fibrosis, the content of the soft capsule is composed of effective dry cream powder, soybean oil and beeswax of the extracts of the above-mentioned traditional Chinese medicine preparation; the weight ratio of the effective dry cream powder to soybean oil is 5 : 5, the addition ratio of beeswax is 6% of soybean oil; the capsule shell is made of 1.05 parts of gelatin, 0.5 parts of glycerin and 1.1 parts of water by weight.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of traditional Chinese medicine preparation medicinal material dry cream powder:

A1, the preparation of Radix Notoginseng dry cream powder: by weight, Radix Notoginseng is pulverized into 45 order fine powder, adds 75% ethanol 5 times of Radix Notoginseng powder weight, infiltrates until high performance liquid chromatography is measured and reaches the standard, and the up-to-standard The percolation liquid is heated under reduced pressure at -70KPa to recover ethanol and concentrated to a relative density of 1.20. The concentrated liquid is dried in a vacuum continuous low-temperature belt dryer to obtain a dry cream powder of notoginseng, which is tested by high performance liquid chromatography. Get the standard notoginseng dry cream powder for later use;

B1. Preparation of Salvia miltiorrhiza dry cream powder: put Salvia miltiorrhiza into the percolation extraction device in parts by weight. Under the condition of 62°C, interlayer heat preservation is carried out for continuous percolation extraction. The percolation liquid extracted by continuous percolation is qualitatively tested for tanshinone and reaches the standard The percolation solution was heated under reduced pressure at -70 KPa to recover ethanol and concentrated to a relative density of 1.25. The Danshen concentrated solution was dried in a vacuum continuous low-temperature belt dryer to obtain the dried salvia miltiorrhiza powder for subsequent use;

C1. Preparation of remaining medicinal material dry paste powder: add remaining medicinal material to pure water and decoct for extraction 2 times according to parts by weight: add pure water of 3 times the weight of remaining medicinal material for the first time, boil for 2.5 hours, and filter the extract , add 2.5 times the amount of pure water to the second extraction, boil for 2 hours, filter to remove the medicinal residues, combine the two extraction filtrates, heat under reduced pressure at -70KPa to recover ethanol and concentrate to a relative density of 1.26, add 95% Ethanol to make the ethanol content of the filtrate reach no less than 70%, refrigerate at 10°C, stand still for no less than 24 hours, filter, and recover the ethanol from the filtrate under reduced pressure at -70KPa and concentrate until the relative density of the filtrate is 1.26; the concentrated solution is vacuum belt Drying in a low-temperature continuous dryer to obtain the remaining medicinal material dry cream powder for subsequent use;

(2) Preparation of soft capsule contents:

Mix the notoginseng dry paste powder, Danshen dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1 evenly, add beeswax and soybean oil in parts by weight, heat and stir evenly, and grind them all in a colloid mill for 90 minutes , ground and mixed evenly to obtain the contents of the soft capsule;

(3) Preparation of capsule shell

A2, by weight, put gelatin, water, glycerin into a sol tank and mix to form a gelatin solution, stir, keep warm in a jacketed pot at 73°C to completely dissolve the gelatin, heat the gelatin solution under reduced pressure at -70KPa Until there are no bubbles, get the gelatin solution for later use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a streamlined capsule that meets the specifications and is made into a soft capsule.

Utilize high-performance liquid chromatography to measure the content of active ingredients in the extract. If the content is not up to the standard, it needs to be reused. The ethanol is about to reach the detection level range and the ethanol is directly recovered. If the content of the active ingredients does not reach the content, it is reused.

The step (1) uses a percolation extraction device for percolation extraction; the inlet temperature of the belt drying system is 150°C, and the outlet temperature is 70°C.

The soft capsules for preventing and treating liver fibrosis are washed with 75% ethanol and dried under the conditions of 35°C and 30% relative humidity. Each soft capsule for preventing and treating liver fibrosis contains not less than 36.0mg of total saponins of Panax notoginseng .

Example 6.

The difference between this example and Example 1 is: a Chinese medicine preparation for preventing and treating liver fibrosis in this example, which includes the following medicinal materials in parts by weight: 1000 parts of Panax notoginseng, 300 parts of Astragalus membranaceus, 120 parts of Danshen, Scrophulariaceae 260 parts, 10 parts of Rhizoma Chuanxiong, 15 parts of Rehmannia, 1 part of Saffron, 30 parts of Eupatorium, 8 parts of Curcuma, 12 parts of Wangbuliuxing, 10 parts of Bupleurum, 13 parts of Milletanus, 22 parts, 18 parts of Paeoniae Alba , 6 parts of turtle shell, 5 parts of red peony root, 30 parts of licorice.

A soft capsule for preventing and treating liver fibrosis, the content of the soft capsule is composed of effective dry cream powder, soybean oil and beeswax of the extracts of the above-mentioned traditional Chinese medicine preparation; the weight ratio of the effective dry cream powder to soybean oil is 5 : 5, the addition ratio of beeswax is 4% of soybean oil; the capsule shell is made of 1.05 parts of gelatin, 0.3 parts of glycerin and 1.2 parts of water by weight.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of traditional Chinese medicine preparation medicinal material dry cream powder:

A1, the preparation of Radix Notoginseng dry cream powder: by weight, Radix Notoginseng is pulverized into 60 order fine powder, adds 80% ethanol of 5 times of Radix Notoginseng powder weight, infiltrates until high performance liquid chromatography is measured up to standard, and the up to standard The percolation liquid was heated under reduced pressure at -60KPa to recover ethanol and concentrated to a relative density of 1.21. The concentrated liquid was dried in a vacuum continuous low-temperature belt dryer to obtain a dry cream powder of Sanqi, which was tested by high performance liquid chromatography. Get the standard notoginseng dry cream powder for later use;

B1. Preparation of dry salvia miltiorrhiza powder: according to parts by weight, put salvia miltiorrhiza into the percolation extraction device, under the condition of 68° C., the interlayer is kept warm for continuous percolation extraction, and a condensation device is installed to prevent ethanol volatilization. The percolation liquid extracted by continuous percolation is qualitatively tested for tanshinone, and the percolation liquid that reaches the standard is heated under reduced pressure at -60KPa to recover ethanol and concentrated to a relative density of 1.25. The Danshen concentrated liquid is dried in a vacuum continuous low-temperature belt dryer. The dry cream powder of salvia miltiorrhiza is prepared for subsequent use;

C1. Preparation of remaining medicinal material dry cream powder: by weight, add remaining medicinal material to pure water and decoct for extraction 2 times: add pure water of 3 times the weight of remaining medicinal material for the first time, boil for 2 hours, filter the extract, Add 2 times the amount of pure water to the second extraction, boil for 1.5 hours, filter to remove the medicinal residues, combine the two extraction filtrates, heat under reduced pressure at -60KPa to recover ethanol and concentrate to a relative density of 1.22, add 95% Ethanol to make the ethanol content of the filtrate reach no less than 70%, refrigerate at 8°C, stand still for no less than 24 hours, filter, and recover the ethanol from the filtrate under reduced pressure at -60KPa and concentrate until the relative density of the filtrate is 1.22; the concentrated solution is vacuum belt Drying in a low-temperature continuous dryer to obtain the remaining medicinal material dry cream powder for subsequent use;

Specifically, in the step C1, the preparation of the dry cream powder of the remaining medicinal materials, the volatile oil obtained from the remaining medicinal materials is embedded by using the β-cyclodextrin embedding technology to prepare the volatile oil inclusions. β-cyclodextrin embedding technology is a preparation technology for a class of non-bonding compounds formed by encapsulating drug molecules in whole or in part with β-cyclodextrin (β-CD); it can increase the solubility and dissolution rate of drugs, and improve The stability of the drug, reducing the irritation of the drug and improving the bad smell; its preparation method is a saturated aqueous solution method: add the volatile oil extracted by percolation and decoction into a saturated aqueous solution of β-cyclodextrin, stir at a certain temperature for a certain period of time, and then cool Crystallize, filter, and dry to obtain volatile oil inclusions, and add the obtained volatile oil inclusions to the remaining medicinal material dry cream powder for later use;

(2) Preparation of soft capsule contents:

Mix the Panax notoginseng dry paste powder, Danshen dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1 evenly, add beeswax and soybean oil in parts by weight, heat and stir evenly, and grind them all in a colloid mill for 100 minutes , ground and mixed evenly to obtain the contents of the soft capsule;

(3) Preparation of capsule shell

A2, by weight, put gelatin, water, glycerin into the sol tank and mix into gelatin solution, stir, keep warm in the jacketed pot at 78°C to completely dissolve the gelatin, heat the gelatin solution under reduced pressure at -60KPa Until there are no bubbles, get the gelatin solution for later use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a streamlined capsule that meets the specifications and is made into a soft capsule.

Example 7.

The difference between this example and Example 1 is that a traditional Chinese medicine preparation for preventing and treating liver fibrosis in this example includes the following medicinal materials in parts by weight: 800 parts of Panax notoginseng, 220 parts of Radix Astragali, 180 parts of Salvia miltiorrhiza, Scrophulariaceae 290 parts, 20 parts of Rhizoma Chuanxiong, 5 parts of Rehmannia, 5 parts of Saffron, 20 parts of Eupatorium, 12 parts of Curcuma, 8 parts of Wangbuliuxing, 5 parts of Bupleurum, 22 parts of Millet, 13 parts, 29 parts of Paeoniae Alba , 3 parts of turtle shell, 10 parts of red peony root, 20 parts of licorice.

A soft capsule for preventing and treating liver fibrosis, the content of the soft capsule is composed of effective dry cream powder, soybean oil and beeswax of the extracts of the above-mentioned traditional Chinese medicine preparation; the weight ratio of the effective dry cream powder to soybean oil is 4.5 : 6.5, the addition ratio of beeswax is 6% of soybean oil; the capsule shell is made of 1.05 parts of gelatin, 0.4 parts of glycerin and 0.9 parts of water in parts by weight.

A preparation process of soft capsules for preventing and treating liver fibrosis, comprising the following steps:

(1) Preparation of traditional Chinese medicine preparation medicinal material dry cream powder:

A1, the preparation of Radix Notoginseng dry paste powder: by weight, Radix Notoginseng is pulverized into 60 order fine powder, adds 70% ethanol of 6 times of Radix Notoginseng powder weight, infiltrates until high-performance liquid chromatography is measured and reaches the standard, and the up-to-standard The percolation liquid is heated under reduced pressure at -50KPa to recover ethanol and concentrated to a relative density of 1.20, and the concentrated liquid is dried in a vacuum continuous low-temperature belt dryer to obtain a Sanqi dry cream powder, which is tested by high performance liquid chromatography and reaches the standard. Get the standard notoginseng dry cream powder for later use;

B1. Preparation of dry salvia miltiorrhiza powder: according to parts by weight, put salvia miltiorrhiza into the percolation extraction device, under the condition of 70° C., the interlayer is kept warm for continuous percolation extraction, and a condensation device is installed to prevent ethanol volatilization. The percolation liquid extracted by continuous percolation is qualitatively tested for tanshinone. The percolation liquid that meets the standard is heated under reduced pressure at -50KPa to recover ethanol and concentrated to a relative density of 1.18. The Danshen concentrated liquid is dried by a continuous low-temperature belt dryer in vacuum. The dry cream powder of salvia miltiorrhiza is prepared for subsequent use;

C1. Preparation of remaining medicinal material dry cream powder: by weight, add remaining medicinal material to pure water and decoct for extraction twice: add pure water of 3.5 times the weight of remaining medicinal material for the first time, boil for 2.5 hours, and filter the extract , add 2.5 times the amount of pure water to the second extraction, boil for 2 hours, filter to remove the medicinal residues, combine the two extraction filtrates, heat under reduced pressure at -50KPa to recover ethanol and concentrate to a relative density of 1.20, add 95% Ethanol to make the ethanol content of the filtrate reach no less than 70%, refrigerate at 10°C, stand still for no less than 24 hours, filter, and recover the ethanol from the filtrate under reduced pressure at -50KPa and concentrate until the relative density of the filtrate is 1.20; Drying in a continuous dryer to obtain the remaining medicinal material dry paste powder for subsequent use;

(2) Preparation of soft capsule contents:

Mix the Panax notoginseng dry paste powder, Danshen dry paste powder, and remaining medicinal material dry paste powder prepared in the above steps A1, B1, and C1, and add beeswax and soybean oil in parts by weight, heat and stir evenly, and grind them all in a colloid mill for 120 minutes , ground and mixed evenly to obtain the contents of the soft capsule;

(3) Preparation of capsule shell

A2. By weight, put gelatin, water, and glycerin into a sol tank and mix to form a gelatin solution, stir, keep warm in a jacketed pot at 75°C to completely dissolve the gelatin, and heat the gelatin solution under reduced pressure at -50KPa Until there are no bubbles, get the gelatin solution for later use;

B2. Preparation of soft capsules: It is produced by an automatic rotary capsule press machine, which runs continuously under the drive of the motor. The gelatin liquid flows into the rubber-making runner through the storage tank through the conduit, and the gelatin film is made and sent to both sides of the wedge-shaped body of the pressed pill; The contents of the capsule are quantitatively injected into the gap between the two wheel-shaped moulds, and the gelatin film and the contents of the soft capsule are pressed into the grooves of the two wheel-shaped molds due to the continuous rotation of the rotating wheel-shaped mould, so that the gelatin film is in the shape of two wheels. A hemispherical shape wraps the contents of the soft capsule to form a streamlined capsule that meets the specifications and is made into a soft capsule.

Utilize high-performance liquid chromatography to measure the content of active ingredients in the extract. If the content is not up to the standard, it needs to be reused. The ethanol is about to reach the detection level range and the ethanol is directly recovered. If the content of the active ingredients does not reach the content, it is reused.

Verification example

The beneficial effects of the soft capsules for preventing and treating liver fibrosis of the present invention are further illustrated by the following experiments.

(1) Toxicity test.

Acute toxicity test: Acute toxicity test shows that the maximum tolerated oral dose in mice is 60g/Kg/body weight, which is equivalent to 120 times of human administration without causing any obvious toxic reaction.

Long-term toxicity test: 6-month long-term toxicity test, three dosage groups (12.5g/Kg/body weight, 25 g/Kg/body weight, 50g/Kg/body weight) rats blood biochemical, pathological examination and behavioral activities etc. No abnormalities were found.

Pharmacodynamic research of the present invention shows:

1. Treatment of rat subacute CCl ₄ poisoning hepatitis liver fibrosis model: the present invention has a more comprehensive and consistent effect on alleviating subacute liver fibrosis and hepatitis lesions in rats caused by CCl ₄ , significantly reducing the proliferation of fibrous tissue, and liver cells The degeneration is significantly reduced, and the content of liver collagen is significantly reduced and close to the normal value;

2. Liver regeneration experiment in mice: the present invention has an obvious effect of promoting liver regeneration in mice with partial liver removed;

3. Anti-hepatitis B virus test: 8g/Kg has the most obvious inhibitory effect on duck hepatitis B virus infection serum HBV-DNA (P<0.01). Compared with the positive drug acyclovir, the difference is very significant.

(2) The therapeutic effect of the soft capsule for preventing and treating liver fibrosis of the present invention on rat liver fibrosis.

1, tested drug: the soft capsule (embodiment 4 and embodiment 6) of preventing and treating liver fibrosis of the present invention; Positive control drug: dexamethasone sodium phosphate; Other: carbon tetrachloride (analytically pure); Preparation method: Carbon tetrachloride was prepared into a 40% concentrated vegetable oil solution; animal: strain: SD rat; body weight: 180-220g; sex: male; number of animals in each group: 20.

2, experimental method: the present invention prevents and treats the soft capsule high dosage group (32g/kg), middle dosage group (20g/kg), low dosage group (10g/kg), modeling group, dexamethasone sodium phosphate group (0.6mg/g), and a normal control group.

Make carbon tetrachloride into a refined vegetable oil solution with a concentration of 40%. Except for the animals in the normal control group, other animals are subcutaneously injected twice a week at 1ml/g for 12 consecutive weeks. At the same time, they are fed with high-fat feed and 5% Alcoholic water. The treatment group was given the test drug or positive control drug at the same time. At the 4th and 12th week of administration, 8 rats were randomly selected from each group to take blood, weigh their body weight, and measure serum ALT, AST, ALP, TP, ALB, and T-BIL. The liver was weighed, and roughly the same piece of liver tissue from the same lobe of the liver was taken from each animal and fixed in 10% formalin for pathological examination.

3. Experimental results: ALT, AST, ALP, and T-BIL of the animals in the model group were significantly higher than those of normal rats, the liver shrank, became smaller, and turned yellow, and the model was successfully established. After 4 weeks of administration, the histopathological examination revealed severe diffuse fatty degeneration and moderate watery degeneration in the hepatocytes of the model group, especially the centrilobular lesion. Mild liver fibrosis, mainly manifested in the obvious increase of fibroblasts in the portal area, slightly increased collagen fibers around the liver lobules, and no obvious liver cell regeneration; the animals in the dexamethasone group had mild fatty degeneration of liver cells, and the central lobular lesions were more severe. Severe, no hepatic fibrosis formation; animal liver cells in the three dosage groups of the soft capsule for preventing and treating liver fibrosis of the present invention showed moderate to severe diffuse fatty degeneration, moderate watery degeneration, and no hepatic fibrosis formation. After 12 weeks of administration, the histopathological examination found that the watery degeneration of liver cells in the model group was obvious, with obvious necrosis of liver cells, liver fatty degeneration, and obvious liver fibrosis; the liver cells of animals in the dexamethasone group had obvious fatty degeneration and watery degeneration, only mild liver fibrosis: animal liver cells in the three dosage groups of soft capsules for preventing and treating liver fibrosis still have obvious fatty degeneration and watery degeneration, only mild liver fibrosis , the degree of fibrosis in the high and middle dose groups was similar to or slightly lighter than that of the dexamethasone group, and the degree of fibrosis in the low dose group was also lighter than that of the model group. The indicators of liver function test in the three dosage groups of soft capsules for preventing and treating liver fibrosis of the present invention are also lower than those in the model group.

5. Experimental conclusion: the soft capsule for preventing and treating liver fibrosis of the present invention has a definite anti-hepatic fibrosis effect on rats with liver fibrosis, reduces fatty degeneration and necrosis of liver cells, and promotes the proliferation and repair of liver cells.

(3), the clinical experiment of the soft capsule of preventing and treating liver fibrosis of the present invention.

Taking Example 4 and Example 6 as clinical trial drugs, the dosage is: adults take three times a day, 5g once.

1. Case selection: According to the diagnostic criteria established by the National Viral Hepatitis Conference in 1995, a total of 1,000 outpatients with liver fibrosis were collected from January 2009 to November 2013, aged 18-60 years, and the course of disease was 1-5 years . Randomly divided into: 400 cases in the treatment group of Example 4, 400 cases in the treatment group of Example 6, and 200 cases in the control group. Endocrine and other diseases were excluded in the two groups, and there was no significant difference in age, condition and other data, which were comparable.

2. Test method

2.1 The treatment group took orally the capsules prepared according to Embodiment 4 and Embodiment 6 of the present invention, once in the morning and evening, one capsule each time, and the course of treatment was three months.

2.2 The control group took compound Biejiaruangan tablets orally, once in the morning and evening, one tablet each time, and the course of treatment was three months.

3. Efficacy criteria and treatment results

3.1 Curative effect standard

Recovery from illness: all clinical symptoms disappeared, and the laboratory examination was normal. Significantly effective and effective: the clinical symptoms are relieved, the disease is under control, and the laboratory tests are improved or normal. Ineffective: no obvious improvement or aggravation of clinical symptoms.

Experimental results of embodiment 4: after treatment, the treatment group: 50 cases were cured, accounting for 12.50%; 301 cases were markedly effective and effective, accounting for 75.25%; 49 cases were ineffective, accounting for 12.25%; the total effective rate was 87.75%. Control group: 13 cases were cured, accounting for 6.50%; 134 cases were markedly effective and effective, accounting for 67%; 53 cases were ineffective, accounting for 26.5%, the total effective rate was 73.50%.

Experimental results of Example 6: After treatment, the treatment group: 57 cases were cured, accounting for 14.25%; 309 cases were markedly effective and effective, accounting for 77.25%; 34 cases were ineffective, accounting for 8.50%; the total effective rate was 91.50%. Control group: 13 cases were cured, accounting for 6.50%; 134 cases were markedly effective and effective, accounting for 67%; 53 cases were ineffective, accounting for 26.5%, the total effective rate was 73.50%.

Conclusion: From the above results, it can be seen that the present invention has the effects of protecting the liver, improving liver function and preventing liver fibrosis.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than limiting the protection scope of the present invention, although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand , the technical solution of the present invention may be modified or equivalently replaced without departing from the spirit and scope of the technical solution of the present invention.

Claims (10)

1. prevent and treat a Chinese medicine preparation for hepatic fibrosis, it is characterized in that: it comprises the medical material of following weight portion: Radix Notoginseng 500-1000 part, Radix Astragali 150-350 part, Radix Salviae Miltiorrhizae 100-300 part, Radix Scrophulariae 150-350 part.

2. a kind of Chinese medicine preparation preventing and treating hepatic fibrosis according to claim 1, is characterized in that: it comprises the medical material of following weight portion: Radix Notoginseng 600-800 part, Radix Astragali 200-300 part, Radix Salviae Miltiorrhizae 100-200 part, Radix Scrophulariae 200-300 part.

3. a kind of Chinese medicine preparation preventing and treating hepatic fibrosis according to claim 1, is characterized in that: it comprises the medical material of following weight portion: Radix Notoginseng 750 parts, the Radix Astragali 240 parts, Radix Salviae Miltiorrhizae 150 parts, Radix Scrophulariae 240 parts.

4. a kind of Chinese medicine preparation preventing and treating hepatic fibrosis according to claim 1, is characterized in that: it also comprises the medical material of following weight portion: Rhizoma Chuanxiong 10-20 part, Radix Rehmanniae 5-15 part, Stigma Croci 1-5 part, Herba Lycopi 20-30 part, Radix Curcumae 8-12 part, Semen Vaccariae 8-12 part.

5. a kind of Chinese medicine preparation preventing and treating hepatic fibrosis according to claim 1-4 any one, is characterized in that: it also comprises the medical material of following weight portion: Radix Bupleuri 5-10 part, Caulis Spatholobi 13-22 part, Radix Paeoniae Alba 18-29 part, Carapax Trionycis 3-6 part, Radix Paeoniae Rubra 5-10 part, Radix Glycyrrhizae 20-30 part.

6. prevent and treat the soft capsule of hepatic fibrosis for one kind, comprise softgel shell and content, it is characterized in that: described soft capsule content prevents and treats effective dried cream powder of the extract of each component medical material in the Chinese medicine preparation of hepatic fibrosis by a kind of described in claim 1-5 any one and soybean oil, Cera Flava form; The part by weight of described effective dried cream powder and soybean oil is 3-5: 7-5, and the additional proportion of Cera Flava is the 4%-6% of soybean oil; Described softgel shell is made up of gelatin 0.95-1.05 part by weight, glycerol 0.3-0.5 part, water 0.8-1.2 part.

7. a kind of soft capsule preventing and treating hepatic fibrosis according to claim 6, is characterized in that: the part by weight of described effective dried cream powder and soybean oil is 4: 6.

8. a kind of preparation technology preventing and treating the soft capsule of hepatic fibrosis described in claim 6 or 7, is characterized in that: it comprises the following steps:

(1) preparation of Chinese medicine preparation medical material dried cream powder:

The preparation of A1, Radix Notoginseng dried cream powder: by weight, Radix Notoginseng powder is broken into 40-60 order fine powder, add the 3-6 70%-80% ethanol doubly of Radix Notoginseng powder weight, percolation is up to standard to high-performance liquid chromatogram determination, and percolate up to standard is reclaimed ethanol at-35KPa to heating under reduced pressure under-70KPa condition, and to be concentrated into relative density be 1.15-1.25, concentrated solution is dry through vacuum continuous low temperature band drier, obtained Radix Notoginseng dried cream powder, detects up to standard through high performance liquid chromatography, gets Radix Notoginseng dried cream powder up to standard for subsequent use;

The preparation of B1, Radix Salviae Miltiorrhizae dried cream powder: by weight, drops into Radix Salviae Miltiorrhizae in percolating extractor, and under 65 DEG C ± 5 DEG C conditions, laminated heat-preserving carries out continuous seepage pressure effects, and is provided with condensing unit and prevents ethanol from volatilizing; Through the percolate of continuous seepage pressure effects through qualitative detection TANSHINONES, percolate up to standard heating under reduced pressure under-35KPa to-70KPa condition reclaims ethanol and to be concentrated into relative density be 1.15-1.25, Salvia mitiorrhiza liquid is dry through vacuum continuous low temperature band drier, and obtained Radix Salviae Miltiorrhizae dried cream powder is for subsequent use;

C1, the preparation of residue medical material dried cream powder: by weight, residue medical material is added pure water boiling and extraction 2 times: the pure water adding the 3-4 times amount of the weight of residue medical material for the first time, boil 2-3h, extracting solution filters, second time extracts the pure water adding 2-3.5 times amount, boil and extract 1-2.5h, filter except medicinal residues, extracted twice filtrate merges, under-35KPa to-70KPa condition, heating under reduced pressure reclaims ethanol and is concentrated into relative density is 1.20-1.35, add 95% ethanol the ethanol content of filtrate to be reached be no less than 70%, 4-14 DEG C of cold preservation, staticly be no less than 24h, filter, filtrate decompression recycling ethanol to be concentrated into filtrate relative density be 1.20-1.35 under-35KPa to-70KPa condition, concentrated solution is dry through vacuum belt low temperature continuous drier, and obtained residue medical material dried cream powder is for subsequent use,

(2) preparation of soft capsule content:

By Radix Notoginseng dried cream powder obtained for above-mentioned A1, B1, C1 step, Radix Salviae Miltiorrhizae dried cream powder, residue medical material dried cream powder mix homogeneously, add Cera Flava and soybean oil by weight, heated and stirred is even, all enters colloid mill grinding 40-120 minute, porphyrize mix homogeneously, obtained soft capsule content;

(3) preparation of softgel shell

A2, by weight, gelatin, water, glycerol are put into glue pot and is mixed into gelatin solution, stir, jacketed pan insulation 70-85 DEG C, gelatin is dissolved completely, and under-35KPa to-70KPa condition, heating under reduced pressure is to gelatin solution bubble-free, obtains gelatin solution for subsequent use;

The preparation of B2, soft capsule: adopt automatic rotation flexible glue bag pressure capsule machine to produce, operate continuously under driven by motor, gelatin solution is flowed in glue runner by conduit through storage tank, makes gelatin film and sends into pelleting sphenoid both sides; Soft capsule content quantitatively injects the crevice place of two colyliform moulds through dosing pump, because the wheel mould rotated rotates continuously, gelatin film and soft capsule content are pressed in the groove of two colyliform moulds, gelatin film is made to be two dome-types, soft capsule content is wrapped up, form streamlined bladder up to specification, make soft capsule.

9. a kind of preparation technology preventing and treating the soft capsule of hepatic fibrosis according to claim 8, it is characterized in that: the preparation of B1, Radix Salviae Miltiorrhizae dried cream powder: by weight, Radix Salviae Miltiorrhizae is dropped in percolating extractor, under 65 DEG C ± 5 DEG C conditions, laminated heat-preserving carries out continuous seepage pressure effects, and is provided with condensing unit and prevents ethanol from volatilizing; Through the percolate of continuous seepage pressure effects through qualitative detection TANSHINONES, percolate up to standard heating under reduced pressure under-35KPa to-70KPa condition reclaims ethanol and to be concentrated into relative density be 1.15-1.25, dry through vacuum continuous low temperature belt drying system, obtained Radix Salviae Miltiorrhizae dried cream powder is for subsequent use.

10. a kind of preparation technology preventing and treating the soft capsule of hepatic fibrosis according to claim 9, it is characterized in that: the soft capsule of control hepatic fibrosis is under the condition of 35 DEG C of temperature, 30% relative humidity, with 75% washing with alcohol, drying, in the soft capsule of every control hepatic fibrosis, contained Radix Notoginseng is no less than 36.0mg with total saponins.