WO2005092352A1

WO2005092352A1 - A Producing Method and Applications of Chinese Medicine Liposome Preparation for Treating Viral Hepatitis B and Preventing and Curing Fibration of Liver Cell

Info

Publication number: WO2005092352A1
Application number: PCT/CN2004/000257
Authority: WO
Inventors: Jianzhong Zhu; Zupei Cao
Original assignee: Jianzhong Zhu; Zupei Cao
Priority date: 2004-03-26
Filing date: 2004-03-26
Publication date: 2005-10-06

Abstract

The present invention relates to a Chinese medicine liposome for curing viral hepatitis B and preventing and curing fibration of liver cell and its preparation method. Said Chinese medicine liposome is a multiphase liposome formed from 34-48 wt% of Chinese medicine active component extract and 66-52 wt% of lecithin and medicinal auxiliary material, in which the Chinese medicine active component includes Curcuma tuber, Schisandra berry, white peony and liquorice. The invention package some liver-protective and immune adjustive Chinese medicine with liposome for treating chronic viral hepatitis B and preventing and curing fibration of liver cell. It combines the advantages of liposome and characteristic of Chinese medicine. Its therapeutic effect of curing viral hepatitis B and preventing and curing fibration of liver cell is reliable and its application is convenient.

Description

A treatment for viral hepatitis B,

Preparation method and application of traditional Chinese medicine liposome preparation for preventing and treating liver cell fibrosis

The invention relates to a traditional Chinese medicine preparation and a preparation method, in particular to a preparation method and application of a traditional Chinese medicine liposome preparation for treating viral hepatitis B and preventing liver fibrosis. Background technique

Diseases such as chronic hepatitis B, steatohepatitis, and fibrosis of the liver cells are common and frequently occurring. The proportion of hepatitis virus carriers in the population is close to 5%. Hepatocyte damage and liver cell fibrosis caused by viral hepatitis B chronic hepatitis pose a threat to human health.

Modern medicine believes that hepatitis originates from the invasion of the human body by the hepatitis virus. Once the body's immunity is low, it will suffer from liver disease. Long-term migration of chronic hepatitis B caused severe damage to liver cells, hepatocyte fibrosis and degeneration to hepatocyte necrosis. The main treatment methods are anti-hepatitis virus and supportive therapy. There are many types of therapeutic drugs, and several drugs are required for clinical use at the same time. Due to the different physical and chemical properties, bioavailability, and metabolites produced in the human body, these drugs are likely to interfere with each other's treatment effect and produce side effects. Therefore, it is of great significance to develop and research an economical medicine with concentrated specificity of treatment, precise curative effect, convenient use, low or no side effects.

According to the Chinese medicine of the motherland, the main pathological mechanism of liver disease is liver "stagnation" and "damp-heat stagnation" liver and spleen. The treatment is "sparse, liver," line "qi," soft "liver, so that liver depression is soft, Damp heat benefits, but stagnation becomes sparse. As a result, the condition can be relieved and the patient can recover. For a long time, traditional Chinese medicine and traditional Chinese medicine science and technology workers have created and accumulated classic prescriptions and proprietary Chinese medicines in the treatment of liver diseases. After taking the medicine, it is digested and absorbed by the gastrointestinal tract, which still has a great impact on the treatment. Liver diseases such as chronic hepatitis B virus, steatohepatitis, alcoholic liver injury, and hepatocyte fibrosis, have a long course and are prone to relapse, requiring long-term medication In addition to the commonly used proprietary Chinese medicines such as the traditional Shugan Pill, Xiaoyao San, and Biejiajian Pill, currently, the glycyrrhizin preparation Qianglining injection supplied by medical units and drug stores requires intravenous injection, which is inconvenient to use and easy to produce. Iatrogenic infections are not easy to accept. However, after oral administration of glycyrrhizin tablets, most of them decompose and degenerate in the stomach, the blood concentration is very low, and the curative effect is not good. It is necessary to explore new formulations with good bioavailability and significant curative effects.

Liposomal preparations are one of the current cutting-edge science and technology projects. Due to its natural targeting, the organs and cells of the reticuloendothelial system become the targeting area for encapsulating drug liposomes, and the therapeutic drug is effectively delivered to the diseased cells of the endothelial system to release the drug. Liposomes can stay in the abundant tissue cells of the reticuloendothelial system such as liver, spleen, and lung. Cell tissue will be engulfed by macrophages, and the uptake of macrophages will be significantly increased and effectively activated, effectively enhancing human immunity. Liposomes are one of the very few non-toxic immune activators currently used in humans. Its lipid component is easily biodegradable in the body, and is non-immunogenic and toxic. Summary of the invention

The technical problem to be solved by the present invention is to provide a traditional Chinese medicine liposome for preventing hepatitis B virus and preventing liver cell fibrosis by using scientific and reasonable compatibility and significant curative effect according to the characteristics of liposomes based on the theory of Chinese medicine and modern medicine. drug.

The traditional Chinese medicine liposome for treating viral hepatitis B and preventing and treating hepatocyte fibrosis is composed of an active ingredient extract of 34-48% of traditional Chinese medicine, 52-66% lecithin and corresponding medicinal excipients Heterophasic liposomes, in which the active ingredients of traditional Chinese medicine include turmeric, schisandra, paeony and licorice.

The active ingredient extract of traditional Chinese medicine according to the present invention is composed of an active ingredient obtained by extracting 12-16% of turmeric, 16-22% of peony, and 10-14% of Schisandra chinensis and 48-62% of licorice extract, wherein The licorice extract is made up of 1: 1 glycyrrhizin monoammonium salt and monopotassium salt.

The lecithin according to the present invention is selected from the group consisting of egg yolk and soybean lecithin.

The liposomes composed of lecithin and corresponding medical auxiliary materials according to the present invention may further include fatty acid glycerolipid, sucrose fatty acid, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, Sodium dialkyl sulfate (SLS), polyoxyethylene castor oil, polyoxyethylene-polyoxypropylene copolymer (Poloxamer Pluronics), and gum arabic, tragacanth, fructolipid, glyceryl monostearate, poly Oxyethylene stearate, polyoxyethylene 40 stearate, polyoxyethylene 400 monolaurate, polyoxyethylene 400 monostearate, polyoxyethylene lauryl ether, benzyl 30, and spanner 20 —Span 85, Tween 20—Tween 85 and other major liposomes and corresponding medical excipients.

Another technical problem to be solved by the present invention is to disclose a method for preparing the above-mentioned traditional Chinese medicine liposome.

The preparation of the traditional Chinese medicine liposome for treating viral hepatitis B and preventing and treating hepatocyte fibrosis includes the following steps:

1. Preparation of active ingredient extract

(1) Place Schisandra in a 78 ° C-85 ° C oven in a closed, dry, and cool state according to the mixing ratio; roll the coarse powder through a 10-mesh sieve, place it separately, and set aside;

(2) Place turmeric in an oven at 62 ° C-75 ° C according to the mixing ratio, keep it tightly dry, and cool; add white scallion according to the mixing ratio, roll the coarse powder, pass the powder through a 5 mesh sieve, place it separately, and set aside;

(3) Place the crude oil from steps (1) and (2) into a first-stage extraction kettle, pressure M _pa 8-18; temperature 54 ° C- 70 ° C; 65% -85% ethanol circulation 100ml h-150ml h CO ₂ flow 900ml / h-1500ml / h; after 2.5h- After 4h extraction, the pressure was reduced to 8M _pa -15M _{pa; the} temperature was 48 ° C-52 ° (:, flowed into the separation column, and then entered the analytical kettle, after decompression to normal pressure, the extract was taken out, placed in a clean vessel, and sealed; collected Drug residue, stand by

(4) Place the medicine residue in step (3) in a reaction kettle equipped with a condenser, add 4 times the amount of water, 2 times the amount of water, and fry twice. Collect the volatile oil-water mixture of the condenser and set aside; discard the residue and mix the secondary decoction, filter, add the oil-water mixture to the filtrate, stir, concentrate under reduced pressure to 1.0-1.18 thick paste, add the extract in step (3), mix, Vacuum-dried to a thousand pastes, pulverized into 380-450 mesh ultrafine powder, set aside;

Preparation of liposome preparations

(1) Put the above ultrafine powder in a container, add distilled water to the mark, keep the temperature in a water bath at 65 ° C-80 ° C, and stir until dissolved; then add glycyrrhizin monoammonium and monopotassium salts and stir until dissolved. Place the solution in a container with an ultrasonic wave length and output the ultrasonic wave length; Put lecithin and other corresponding medical auxiliary materials in a 65 ° C-100 ° C water bath, stir, melt, and transfer to a transparent pipette; 30-45 drops / min, drip into the medicine solution placed in the ultrasonic container, and moderately agitate; after the drip is completed, leave the ultrasonic wave for 12-25 minutes, turn off the generator, and suck the liposomes into a sterile canning machine, filling ;

(2) Put the canned liposome bottle in an ultra-low temperature drying box, and freeze-dry in -45 Ό--60 V for 10-15 hours, and dry in a low temperature box of 35Ό -45 4 for 4-6h. That's it.

The above preparation method only provides a preferred embodiment for preparing the traditional Chinese medicine liposome preparation of the present invention. Those skilled in the art can appropriately change and improve various parameters, conditions, and auxiliary materials used therein according to the description of the present invention, and these changes are also included in the scope of the present invention.

Yet another technical problem to be solved by the present invention is to disclose the application of the above-mentioned traditional Chinese medicine liposomes in the preparation of a medicament for treating viral hepatitis B and preventing and treating hepatocyte fibrosis.

The traditional Chinese medicine liposome can be used for the treatment of viral hepatitis B chronic hepatitis, chronic active hepatitis, acute hepatitis, steatohepatitis, alcoholic hepatitis, toxic hepatitis, and initial liver cirrhosis.

In the formulation of the invention:

Schisandra (Fructus Sehisandiae): Gathering lungs and nourishing kidneys, regenerating sweat, astringent astringent to stop diarrhea, calming heart, relieving heat and qi and yin. Dedicated to the lungs and nourish the water, the liver wood nourish the kidney water, then the liver dampness and heat evil fire can be eliminated.

Turmeric (Radix curcumae): Activating blood and relieving pain, relieving qi and stagnation, cooling serum, relieving biliary and yellowing. Can relieve liver and qi to relieve depression.

Radix Paeomiae alba: Nourishing blood and converging yin, softening liver and analgesic, calming liver yang, nourishing blood and softening liver, slowing and analgesic. In case of licorice, cure liver and spleen loss, pain in wrist and abdominal cramps.

This three-drug medicine balances yin and yang in the compatibility, and each has its own effect in the treatment, and it exerts the advantages of the synergistic effect of Chinese medicine.

The medicinal material licorice has the functions of "detoxification, double strength, slow righteousness, nourish yin and blood, nourish the spleen and stomach, and prolong life". Glycyrrhizin GL is one of the main components of glycyrrhizin. It contains monopotassium, monoammonium and dipotassium salts of diglycyrrhizinate, which can protect liver cell membrane, reduce liver cell steatosis, reduce liver cell necrosis and intermittency. Inflammatory response, inhibit liver fibrosis; and has steroid-like effects without hormone-like side effects. It has been clinically proven to neutralize hepatitis virus, anti-inflammatory, anti-allergic, subdued jaundice, improve lipid metabolism, and enhance immunity.

Liposomes are ideal targeting carriers. They can load drugs into the target organ or the active part of the drug and release the drug, increase the effective concentration of the drug in the target area, and maintain it for a long time. At the same time, other parts of the body take up very little drug. It is not only required that the drug reach the target organ, the target cell, or even the intracellular structure. The biologically processed glycyrrhizin liposomes can obviously guide the liver and increase the blood concentration in the liver, thereby increasing the specific and concentrated treatment of the drug on the liver, which is difficult to obtain by other oral glycyrrhizin preparations. treatment effect. It is a new achievement combining traditional Chinese medicine and traditional Chinese medicine with modern biomedical technology.

Clinical trials are carried out with the preparations of the invention using a multi-center, randomized controlled method. Glycyrrhizin tablets (produced by Hubei Huangshi Feiyun Co., Ltd.) each contained 75 mg of glycyrrhizin monopotassium salt as a control group.

Dosage: 150mg (2 tablets) once, twice daily.

Liposomes of the present invention: 15ml twice daily.

The two groups were administered continuously for 8 weeks as a course of treatment. The youngest patients were 18 years old and the highest 65 years old. There were 28 males and 12 females. Observed diseases: viral hepatitis B chronic hepatitis, accompanied by serum ALT and AST, serum bilirubin is greater than the normal upper limit. Patients who had used enzyme-lowering drugs within 45 days before treatment were not observed. Before treatment and two weeks after administration, routine urine ALT, AST. SB, GGT, ALP. A / G, BuN, and testing were performed to record changes in clinical symptoms and signs.

Efficacy criteria:

. Significantly effective, effective, ineffective three levels

Significant effects: 1. Conscious symptoms disappeared or significantly improved.

2, hepatosplenomegaly, shrinking or stable.

3. Liver function tests ALT, AST and SB returned to normal.

Effective: 1. The subjective symptoms are improved or stable.

2. Hepatosplenomegaly is stable and unchanged.

3. Liver function test ALT, AST and SB were reduced by more than 50% compared with the previous one.

Ineffective: no change, those who do not meet the above criteria or progress of the disease.

As a result, the effective rate of reducing ALT in the liposome group was 81.4%; the effective rate of reducing SB was 73.3%; the effective rate of albumin rising was 62.7%; the globulin was 48.8%; the negative conversion rate of HBeAg was 58.8%; the effective rate of reducing ALT in the control group was 63.2%; The effective rate of reducing SB is 57.4%; the effective rate of albumin is 28.4%; the globulin is 3.8%; the negative conversion rate of HBeAg is 27.3%; The average effective rate in the liposome group was 65.0%; the control group was 36.0%;

Liposomal group: Symptoms improved significantly 76.1%; symptoms disappeared 20.1%; effective 3.8%; liver and spleen reduced 68.1%; stable 31.9%;

Control group: Symptoms improved significantly 37.8%; symptoms disappeared 1.8%; effective 43.7%; ineffective 16.7%. No adverse reactions occurred in the two groups of patients.

The above results show that: The present invention uses liposomes to embed certain traditional Chinese medicines with liver protection and immunomodulatory effects to treat viral chronic hepatitis B and prevent liver cell fibrosis, and the advantages of liposomes (immune adjuvants, drug carriers , Reduce the dose of the embedded drug, prolong the effect of the drug in the target organ, and the characteristics of traditional Chinese medicine (exact curative effect, rich resources, cheap, low toxic side effects or non-toxic side effects) combined. It provides a novel drug with exact curative effect and convenient use for the treatment of viral chronic hepatitis B and the prevention and treatment of liver cell fibrosis. detailed description:

Example 1.

Schisandra 11.2Kg

Yujin 12.5Kg

White 芍 19.8Kg

Glycyrrhizin monoammonium salt 28.25Kg

Glycyrrhizin monopotassium salt 28.25Kg

Lecithin (Soybean) 80kg

Glycerine 150kg

Distilled water 750kg Preparation:

1. Place Schisandra in an oven at 80 ° C and dry it tightly until it can be re-grown by hand. It is taken out and spread out in a clean stainless steel plate. It is placed at room temperature in a clean environment. It is rolled and passed through a 10-mesh sieve. Spare

2. Put the turmeric in an oven at 70 ° C, dry it tightly until it feels dry, and then take it out. Spread it in a clean stainless steel pan, seal it to room temperature, add white scallion and mix, roll the coarse powder, and pass through a 5 mesh sieve;

3. Place the crude oil from steps 1 and 2 in a first-stage extraction kettle, with a pressure of 25 MPa _{; a} temperature of 55 ° C; a 75% ethanol circulation volume of 120 ml / h; 0 ₂ flow rate 1000ml / h; after 3.5h extraction, decompress _10Mpa ; temperature 40 ° C, flow into the separation column, and then enter the analytical kettle, after decompression to normal pressure, remove the extract, place another clean vessel, and seal; Collect medicine residue and set aside

4. Place the medicine residue from step 3 in a reaction pot equipped with a condenser, add 4 times the amount of water, 2 times the amount of water, and fry for 2 times. Times. Collect the volatile oil-water mixture of the condenser and set aside; discard the residue, and mix the secondary decoction, filter, add the oil-water mixture to the filtrate, and stir. Concentrated under reduced pressure to 1.12 thick paste, the extract from step 3 was added and mixed. Vacuum dry to dry paste, pulverize into 400 mesh ultrafine powder, set aside;

5. Add glycyrrhizin monoammonium salt and glycyrrhizin monopotassium salt.

6. Preparation of liposome preparations.

The percentage of the total weight of the active ingredients of traditional Chinese medicine and the total weight of lecithin (including yolks and soybeans) and other corresponding medical excipients is: (39: 61)% of standard lecithin (containing yolks, soybeans) and Other corresponding medical accessories;

7. Place the fine powder from step 4 in a container, add distilled water to the mark, keep the water bath at 65 ° C-80 ° C, stir until dissolved, then add glycyrrhizin single hinge salt and single potassium salt, and stir until Dissolve. Place the solution in a container with an ultrasonic wave length and output the ultrasonic wave length; Put lecithin (containing egg yolks, soybeans) and other corresponding medical auxiliary materials in a vessel into a 90 ° C water bath, stir, melt, and become transparent, that is, Pipette, multiply by heat at 85 drops / min, and inject it into the ultrasonic container medicine solution, moderately stir, complete the infusion, keep the ultrasound for 25 minutes, turn off the generator, and suck the liposomes into a sterile canning machine Each bottle: 15ml, covered with a medicated butyl rubber with a groove, and slightly pressed on the bottle mouth;

8. Put the 15ml liposome bottle into a clean stainless steel dish, put it into an ultra-low temperature drying box, dry freeze at -60 ° C for 12h, turn off the machine, and close the frozen bottle with the butadiene cap automatically closed tightly. Store in a low temperature box at 40 ° C for 4-6h. At this time, 15 ml of the liposome preparation had become a glass liquid crystal. Remove the box. 5 minutes before taking the patient, add clean sterile water less than 40 ° C to the 15ml mark, cover it, and shake it for 2-3min. The liposomes will be restored to the original concentration. Pour into a small cup and take it orally. Example 2,

Formula: Schisandra 14Kg

Yujin 16Kg

White 芍 22Kg

Glycyrrhizin Monoammonium Salt 24Kg

Glycyrrhizin monopotassium salt 24Kg

Glyceryl monostearate 65kg

Oleic acid 135kg

Distilled water 800kg

1. Place Schisandra in an 80Ό oven and keep it tightly dry until it is re-grown by hand without clumping, and take it out and clean it. In a rusty steel pan, put it in room temperature in a clean environment, roll the coarse powder, pass through a 10-mesh sieve, place it separately, and set aside.

2. Put the turmeric in an oven at 65 ° C, seal it tightly until it feels dry, and then take it out. Spread it in a clean stainless steel plate, seal it to room temperature, add white scallion and mix, roll the coarse powder, and pass through a 5 mesh sieve;

3, the thick end of the steps 1 and 2, a set extraction reactor, pressure 26M _pa; 58 temperature. C; 72% ethanol circulation volume 110ml / h; CO ₂ flow rate 1100ml / h; after 4h extraction, the pressure is reduced to 12M _pa ; the temperature is 44 ° C, flows into the separation column, and then enters the analytical kettle, after decompression to normal pressure, takes out Extracts, place in separate clean vessels, and seal; collect medicine residues, set aside;

4. Place the medicine residue from step 3 in a reaction pot equipped with a condenser, add 4 times the amount of water, 2 times the amount of water, and fry twice. Collect the volatile oil-water mixture of the condenser and set aside; discard the residue and mix the secondary decoction, filter, add the oil-water mixture to the filtrate, and stir. Concentrated under reduced pressure to 1.12 thick paste, add the extract from step 3 and mix. Vacuum dry to dry paste, pulverize into 400 mesh ultrafine powder, set aside;

5. Add glycyrrhizin monoammonium salt and glycyrrhizin monopotassium salt;

6. The percentage of the total weight of the active ingredients of traditional Chinese medicine and the total weight of lecithin (including egg yolks and soybeans) and other corresponding medical accessories is: (35: 65)% of standard formulated lecithin (containing egg yolks, soybeans) ) And other corresponding medical accessories.

7. Place the fine powder of step 4 in a container, add distilled water to the mark, keep the water bath at 90 ° C, stir until dissolved, and then add glycyrrhizin monoammonium salt and monopotassium salt, and stir until dissolved. Place the solution in a container with an ultrasonic wave length and output the ultrasonic wave length. Put lecithin (containing egg yolks, soybeans) and other corresponding medical auxiliary materials in a container into a 92 ° C water bath, stir, melt, and it is transparent. Pipette, multiply by heat at 85 drops / min, and inject it into the ultrasonic container medicine solution, moderately agitate, complete the infusion, keep the ultrasonic wave for 25 minutes, turn off the generator, and suck the liposomes into a sterile canning machine Each bottle: 15ml, covered with a medicated butyl rubber with grooves, and slightly pressed on the bottle mouth;

8. Put the 15ml liposome bottle into a clean stainless steel dish, put it into an ultra-low temperature drying box, dry freeze at -60 ° C for 12h, turn off the machine, and close the frozen bottle with the butadiene cap automatically closed tightly. Place in a 40Ό low temperature box for 6h to dry stably. At this time, 15 ml of the liposome preparation had become a glass liquid crystal. Remove the box. 5 minutes before taking the patient, add less than 40 ° C clean sterile water to the 15ml mark, cover it, and shake it for 2-3min. The liposome will be restored to the original concentration. Pour into a small cup and take it orally.

Claims

Rights request

1. A traditional Chinese medicine liposome, characterized in that the liposome is a heterophasic liposome consisting essentially of 34-48% extract of active ingredients of traditional Chinese medicine and 52-66% lecithin, wherein the traditional Chinese medicine activity Ingredients include turmeric, schisandra, amaranth and licorice.

2. The traditional Chinese medicine liposome according to claim 1, characterized in that said traditional Chinese medicine active ingredient extract is formulated by weight percentage as turmeric 12-16%, paeony 16-22%, and Schisandra 10-14 The active ingredients obtained by% extraction are composed of 48-62% licorice extract, wherein the licorice extract is composed of glycyrrhizin monoammonium salt and monopotassium salt in a ratio of 1: 1.

3. The traditional Chinese medicine liposome according to claim 1, wherein the lecithin is selected from the group consisting of egg yolk and soybean lecithin.

4. The traditional Chinese medicine liposome according to claim 1, characterized in that the traditional Chinese medicine liposome further comprises a member selected from the group consisting of fatty acid glycerolipid, sucrose fatty acid, sorbitan fatty acid ester, polyoxyethylene sorbitan fat Acid ester, sodium lauryl sulfate (SLS), polyoxyethylene castor oil, polyoxyethylene-polyoxypropylene copolymer (Poloxamer Pluronics), and gum arabic, tragacanth gum, fructolipid gum, monostearic acid Glycerides, polyoxyethylene stearate, polyoxyethylene 40 stearate, polyoxyethylene 400 monolaurate, polyoxyethylene 400 monostearate, polyoxyethylene lauryl ether, benzyl 30, And medical accessories from Span 20 to Span 85, Tween 20 to Tween 85.

5. The method for preparing a traditional Chinese medicine liposome according to claim 1, characterized in that the preparation of the traditional Chinese medicine liposome comprises the following steps:

a) preparing an extract of an active ingredient of a traditional Chinese medicine, the active ingredient of the traditional Chinese medicine includes turmeric, Schisandra chinensis, Paeonia lactiflora and licorice;

b) Mixing the extract of the active ingredient of the traditional Chinese medicine obtained in step (a) with lecithin to prepare a heterophasic liposome consisting essentially of 34-48% extract of the active ingredient of traditional Chinese medicine and 52-66% lecithin .

6. The method for preparing traditional Chinese medicine liposomes according to claim 5, characterized in that the preparation of traditional Chinese medicine liposomes comprises the following steps-1. Preparation of active ingredient extracts (1) Place Schisandra in a 78 ° C-85 ° C oven in a closed, dry and cooled state according to the mixing ratio, roll the coarse powder, pass through a 10-mesh sieve, and set aside;

(2) Put turmeric in an oven at 62 ° C-75 ° C, keep it dry and cool, add white scallion and mix, roll the coarse powder, pass through a 5 mesh sieve, and set aside;

(3) Put the crude oil from steps (1) and (2) into a first-stage extraction kettle, pressure M _pa 8-18; temperature 54Ό- 70; 65% -85% ethanol circulation 100ml / h-150ml / h; CO ₂ flow 900ml / h-1500ml / h; after 2.5h-4h extraction, decompress 8M _pa -15M _pa; humidity 48 ° C-52 ° C, flow into the separation column, then enter the analytical kettle, decompress to normal pressure Take out the extract, place another clean vessel, and keep it tightly closed; collect medicine residue, set aside;

(4) Put the medicine residue in step (3) into a reaction pot equipped with a condenser, add 4 times the amount of water, 2 times the amount of water, and fry twice. Collect the volatile oil-water mixture of the condenser and set aside; discard the residue and mix the secondary decoction, filter, add the oil-water mixture to the filtrate, stir, concentrate under reduced pressure to 1.0-1.18 thick paste, add the extract in step (3), mix, Vacuum-dried to a thousand pastes, pulverized into 380-450 mesh ultrafine powder, set aside;

Preparation of liposome preparations

(1) Place the above ultrafine powder in a container, add distilled water to the mark, keep the temperature in a water bath at 65 ° C-80 ° C, and stir until dissolved; then add glycyrrhizin monoammonium and monopotassium salts, stir until dissolved, Place the solution in a container with an ultrasonic wave length and output the ultrasonic wave length; Put lecithin and other medical auxiliary materials in a 65 ° C-100 ° C water bath, stir, melt, and transfer to a pipette when transparent; 45 drops / min, drip into the medicine solution placed in the ultrasonic container, and moderately agitate; after the drip is completed, leave the ultrasonic wave for 12-25 minutes, turn off the generator, and suck the liposomes into a sterile canning machine for filling;

(2) Put the canned liposome bottle into an ultra-low temperature drying box, dry it at -45 ° C ― -60 ° C for 10-15h, and dry it in 35 ° C-45 ° C low-temperature box. 6h. That's it.

7. The application of the traditional Chinese medicine liposomes according to claim 1 in the preparation of a medicament for treating viral hepatitis B and preventing fibrosis of liver cells.

8. The application of traditional Chinese medicine liposomes according to claim 7, characterized in that the medicine is used for viral hepatitis B chronic hepatitis, chronic active hepatitis, acute hepatitis, steatohepatitis, alcoholic hepatitis, toxicity Treatment of hepatitis, initial liver cirrhosis.