CN116870069A - Compound preparation and preparation method and application thereof - Google Patents

Abstract

The invention provides a compound preparation and its preparation method and application. The active ingredient of the compound preparation is a product obtained by sequentially subjecting raw materials including Rubia cordata, Houttuynia cordata and Licorice root to water extraction and alcohol precipitation; the Rubia cordata, The mass ratio of Houttuynia cordata and licorice is (3-30): (5-50): (3-30) Furthermore, based on the mass of Rubia cordata, the mass percentage of Rubiacin in the compound preparation is not less than 0.4 %. The compound preparation has the characteristics of high efficiency and low toxicity in the protective treatment of radiation damage lesions.

Description

A compound preparation and its preparation method and application

Technical field

The present invention relates to a compound preparation, in particular to a compound preparation and its preparation method and application, and belongs to the field of medical technology.

Background technique

Radiation therapy is the main treatment for thoracic malignant tumors (lung cancer, esophageal cancer, breast cancer and other malignant tumors). It is reported that more than 80% of patients with thoracic malignant tumors choose radiation therapy. However, while radiotherapy kills tumor cells, it also causes side effects such as extensive radiation pneumonitis, pulmonary fibrosis, decreased immune function and white blood cells on normal lung tissue within the radiation field. Patients are often forced to discontinue treatment or treatment fails. Pulmonary fibrosis is a refractory disease, and there is currently no cure. In order to alleviate the pain caused to patients by radiation pneumonitis, pulmonary fibrosis, etc., domestic and foreign researchers and clinical personnel have done a lot of research on its occurrence mechanism, prevention, and treatment. But the results were unsatisfactory. With the progress of modern research on traditional Chinese medicine, the research results of traditional Chinese medicine in preventing and treating radiation pneumonitis, pulmonary fibrosis and anti-tumor have opened up broad prospects for this field.

Furthermore, the World Health Organization (WHO) believes that “during a radiation emergency, people may be exposed to doses of radiation ranging from negligible to life-threatening. Governments should be able to provide treatment to those who need it. It is vital that governments Be prepared to protect people's health and respond immediately to emergencies." Therefore, in 2023, WHO also updated the list of stockpiles of drugs used to prevent or reduce radiation exposure, or treat after the occurrence of radiation, as well as policy recommendations for their appropriate management.

Motherland’s medicine is broad and profound. In recent years, the progress of modern research on traditional Chinese medicine has made certain achievements in anti-radiation damage drugs, but there are still problems of balancing toxicity and effectiveness in preventing and treating radiation loss. Therefore, it is of great clinical and practical significance to find radiation damage protection drugs that are efficient, low-toxic, and capable of both prevention and treatment.

Contents of the invention

The invention provides a compound preparation. The particularity of raw materials and composition of the compound preparation enable it to have the characteristics of high efficiency and low toxicity in the protective treatment against radiation damage lesions.

The present invention also provides a method for preparing a compound preparation. By selecting appropriate raw materials and regulating the processing technology of the raw materials, a compound preparation with low toxicity and high efficiency in preventing and treating radiation damage lesions can be obtained.

The present invention also provides a preparation composition. By combining the above compound preparation with hormones and cell growth factors in clinical practice, the prevention and treatment effect on radiation damage lesions is further enhanced.

The present invention also provides the above compound preparation or preparation composition in the preparation of medicines for treating lung lesions caused by radiation damage, leukopenia caused by radiotherapy, chemotherapy or chemical poisons, and lung or respiratory tract lesions caused by viral infections. Applications.

A first aspect of the present invention provides a compound preparation. The active ingredient of the compound preparation is a product obtained by sequentially subjecting raw materials including madder, Houttuynia cordata and licorice to water extraction and alcohol precipitation; the madder, Houttuynia cordata The mass ratio of grass and licorice is (3-30): (5-50): (3-30) Moreover, based on the quality of the Rubia grass, the mass percentage of Rubiacin in the compound preparation is quite a lot at 0.4%.

The active ingredients of the compound preparation of the present invention come from raw materials including madder, Houttuynia cordata and licorice, and the mass ratio of madder, Houttuynia cordata and licorice in the raw materials is (3-30): (5-50): (3-30) , among them, the quality control standards of madder meet the 2015 edition of the Chinese Pharmacopoeia, Part 1, and the quality control standards of Houttuynia cordata and licorice meet the 2020 edition of the Chinese Pharmacopoeia, Part 1. Specifically, the product obtained by sequentially carrying out water extraction treatment and alcohol precipitation treatment on the raw material is the active ingredient of the compound preparation, and based on the quality of rubia in the raw material, the quality of rubiadin in the compound preparation is The input mass of madder raw materials shall not be less than 0.4%.

The active ingredients in the compound preparation of the present invention come from three grasses with a special mass ratio as raw materials (rudder, Houttuynia cordata and licorice). By subjecting them to water extraction and alcohol precipitation, special extracts of each of the three grasses are obtained. The mutual synergy and mutual complementation between the extracts make the compound preparation of the present invention have low toxicity and high efficiency for the prevention and treatment of radiation damage lesions. It can especially increase the number of white blood cells after radiation damage and reduce radiation pneumonitis and radiation lung disease caused by radiation damage. Incidence of fibrosis. In addition, it also has satisfactory clinical efficacy in the prevention and treatment of reduced white blood cell counts caused by chemical poisons and pulmonary or respiratory diseases caused by viral infections.

In detail, the above-mentioned water extraction treatment is a process of extracting raw materials using water as an extractant and obtaining a water extract. The alcohol precipitation treatment is a process of adding alcohol solvent to the water extract to precipitate the active ingredients. It can be understood that after the alcohol precipitation treatment, the alcohol precipitation system also needs to be filtered, concentrated and dried to obtain a final product containing no less than 0.4% (the quality of rubiadin in the compound preparation is based on the input quality of Rubia raw materials) Not less than 0.4%) compound preparations.

Further, when the mass ratio of madder, Houttuynia cordata and licorice in the raw material is (10-15): (30-40): (10-15), furthermore, the mass ratio of madder, Houttuynia cordata and licorice is At 10:30:10, the compound preparation of the present invention is more conducive to promoting the growth of white blood cells.

In a specific embodiment, the above-mentioned active ingredients can be mixed with pharmaceutically acceptable excipients, diluents and other auxiliary materials to prepare granules, capsules, tablets, pills, oral liquids, sprays, and teas. form. Specific preparations in various preparation forms can be prepared by conventional pharmaceutical methods.

The above excipients may be those used in conventional pharmaceutical methods. Examples of useful pharmaceutical excipients include excipients (e.g., sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, dextrin, and carboxymethyl starch; cellulose Derivatives such as crystalline cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium; gum arabic; dextran; silicate derivatives such as magnesium aluminum metasilicate; Phosphate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate, etc.), binders (such as gelatin, polyvinylpyrrolidone and polyethylene glycol), disintegrants (such as cellulose derivatives such as carboxymethyl cellulose Sodium, polyvinylpyrrolidone), lubricants (such as talc, calcium stearate, magnesium stearate, spermaceti, boric acid, sodium benzoate, leucine), stabilizers (methyl paraben, paraben Propyl ester, etc.), flavoring agents (such as commonly used sweeteners, sour agents, spices, etc.), diluents and solvents for injections (such as water, ethanol, glycerin, etc.). When the preparation type is tea, the above-mentioned auxiliary materials can be tea leaves.

In a specific embodiment, the above-mentioned water extraction treatment includes boiling and leaching the raw materials at least once to obtain a water extract.

Specifically, boiling extraction is a process in which the raw materials are immersed in water (extractant) and then heated until boiling and kept warm. The invention does not limit the number of times of boiling and leaching. It can only be boiled and leached once, or it can be boiled and leached multiple times. When boiling and leaching are carried out multiple times, fresh water needs to be replaced each time, and the raw materials after the previous water extraction are boiled and leached again, and finally the extracts of each time are combined. Among them, the time of each boiling and extraction is controlled within 1-2 hours.

Since the extract contains a large amount of extractant, in order to reduce the workload of subsequent processing including alcohol precipitation, the extract obtained by boiling and leaching can be concentrated under reduced pressure to remove most of the extractant to obtain water extraction. things.

Furthermore, controlling the mass ratio of raw materials and extractant to not exceed 1g:10ml in each water extraction process can not only ensure the effectiveness of the water extraction process, but also reduce the workload of reducing the pressure concentration to remove the extractant. Furthermore, when multiple water extraction treatments are performed, the amount of extractant used can be reduced compared with the previous time.

In a specific embodiment, in order to ensure the effectiveness of the compound preparation and improve the operability of the preparation process, the alcohol precipitation treatment includes: adding ethanol to the water extract to obtain an alcohol precipitation system and then performing alcohol precipitation for 12-24 hours. , the volume concentration of ethanol in the alcohol precipitation system is 60-80%.

The inventor found that the volume concentration of ethanol in the alcohol precipitation system has a crucial impact on the effectiveness of the compound preparation, so the amount of ethanol added needs to be strictly controlled. Specifically, when the volume concentration of ethanol in the alcohol precipitation system is 60-80%, and further, when the volume concentration of ethanol in the alcohol precipitation system is 75%, the addition of ethanol is stopped. At this time, the concentration of ethanol is Ethanol can achieve precipitation of active ingredients from water extracts within 12-24 hours. It can be understood that when performing alcohol precipitation treatment, the volume concentration of ethanol selected should be greater than 80%, thereby ensuring that the alcohol precipitation system has an ethanol concentration of 60-80% after adding ethanol. The specific amount of ethanol added needs to be calculated based on the actual volume concentration of the selected ethanol and the volume of the water extract (during the calculation process, the volume of the water extract is regarded as the volume of water).

A second aspect of the present invention provides a method for preparing the above compound preparation, which includes the following steps: boiling and leaching raw materials including madder, Houttuynia cordata and licorice at least once, and filtering and recovering the water extract after alcohol precipitation. Alcohol solvent is used to collect the extract; the extract is processed to obtain the compound preparation; wherein, the mass ratio of the madder, Houttuynia cordata and licorice is (3-30): (5-50): (3-30 ), and, based on the mass of Rubia cordata, the mass percentage of Rubiacin in the compound preparation is not less than 0.4%.

In the specific implementation process of the present invention, raw materials are obtained by mixing madder, Houttuynia cordata and licorice according to the mass ratio of (3-30): (5-50): (3-30), and the raw materials are boiled and soaked at least once. After extracting and separating the boiled and leached raw materials to obtain the extract, the extract is precipitated using an alcohol solvent to separate out the effective components in the extract. Then filter and collect the precipitated active ingredients, then recover the alcohol solvent in the active ingredients (for example, by concentrating under reduced pressure), dry, and finally obtain the extract (that is, the raw material after boiling, leaching, and alcohol precipitation) product). The extract is the active ingredient in the compound preparation, and based on the quality of Rubia in the raw materials, the mass of Rubiacin in the compound preparation is not less than 0.4% of the input mass of Rubia in raw materials. Thereafter, the extract is processed with pharmaceutically acceptable auxiliary materials to obtain the compound preparation of the present invention.

In the specific preparation process, it is usually necessary to crush the raw materials and then boil and extract the crushed raw materials, which helps to improve the efficiency of boiling and leaching.

The boiling and leaching of the present invention refers to the process of immersing the raw materials in water and then heating to boil the system. The time of each boiling and leaching is 1-2 hours. In the specific implementation process, the mass ratio of raw materials and water does not exceed 1g:10ml. When multiple boiling and extraction are performed, the amount of water in each boiling and extraction can be reduced compared with the previous one.

In addition, in order to improve the efficiency of alcohol precipitation, the extract needs to be concentrated (for example, concentrated under reduced pressure) before alcohol precipitation to remove most of the extractant in the extract and obtain an aqueous extract with less water content.

Furthermore, the preparation method of the present invention includes boiling and leaching the raw materials for at least two times, adding ethanol to the water extract to obtain an alcohol precipitation system, and then alcohol precipitation for 12-24 hours. The volume concentration of ethanol in the alcohol precipitation system is 60-80 %.

Specifically, the extracts after each boiling extraction are combined, the extracts are concentrated to remove most of the extractant to obtain a water extract, and ethanol is added to the water extract to obtain an alcohol precipitation system. When ethanol When the volume concentration in the alcohol precipitation system is 60-80%, the addition of ethanol is stopped and the system is allowed to stand to allow the effective components in the system to separate out. Subsequently, it is filtered, concentrated under reduced pressure, and dried to obtain an extract. Among them, the resting time is controlled within 12-24h, for example, 15h, 16h, 17h, 18h, 19h, 20h.

Further, the addition of ethanol was stopped when the volume concentration of ethanol in the alcohol precipitation system was 75%. The actual amount of ethanol added can be calculated based on the actual volume concentration of ethanol added and the volume of the water extract (considered as the volume of water). For example, the volume of the water extract is 10 ml, and the actual volume concentration of ethanol added is 95%. When you want to control the volume concentration of ethanol in the alcohol precipitation system to 75%, you need to add 37.5 ml of actual volume to 10 ml of water extract. Ethanol with a concentration of 95% is obtained to obtain the alcohol precipitation system of the present invention.

For the compound preparation prepared in the first aspect of the present invention and the compound preparation prepared in the second aspect, the quality control of the sources of raw materials and active ingredients can be carried out using the methods recorded in the "Chinese Pharmacopoeia".

Specifically, the method for identifying whether the raw materials of compound preparations contain madder includes: take 0.4g of this product powder, add 5ml of diethyl ether, shake for a few minutes, filter, add 1ml of sodium hydroxide to the filtrate, shake, and let stand to separate the layers. , the water layer appears red, and the ether layer is colorless. Check it under a UV lamp (365nm). If it shows sky blue fluorescence, it proves that the raw materials of the compound preparation contain madder.

The method to identify whether the raw materials of compound preparations contain Houttuynia cordata include: take 25g of this product, chop it into pieces, put it in a round-bottomed flask, add 250m of water, and connect the volatile oil meter. Add water from the upper end of the measuring instrument to fill the scale, add 1ml of ethyl acetate, continuously reflux the condenser, heat and reflux for 4 hours, stop heating, leave it for a while, separate the ethyl acetate layer as the test solution; take another methyl N-nonanone reference substance, add ethyl acetate to make a solution containing 10ug per 1ml, as a control solution. Using thin layer chromatography (Appendix VI B) test, take 5 ul of the above test solution and 2 ul of the reference solution, and place them on the same silica gel G thin layer plate with sodium carboxymethyl cellulose as the adhesive. Hexane-ethyl acetate (9:1) was used as a developing agent, unfolded, taken out, dried, and sprayed with dinitrophenylhydrazine for testing. In the chromatogram of the test product, if the same yellow spots appear at the corresponding positions as the chromatogram of the reference substance, it proves that the raw materials of the compound preparation contain Houttuynia cordata.

The method to identify whether the raw materials of compound preparations contain licorice include: take 1g of this product powder, add 40ml of ether, heat and reflux for 1 hour, filter, add 30ml of methanol to the residue, heat and reflux for 1 hour, evaporate the filtrate to dryness, and add 40ml of water to the residue. , add n-butanol to extract 3 times, 20ml each time, combine the n-butanol solution, wash 3 times with water, evaporate to dryness, dissolve the residue in 5ml of methanol, and use it as the test solution; take another 1g of licorice control medicinal material, and follow the same method as the sample Method: Make a reference medicinal material solution; then take the ammonium glycyrrhizinate reference substance, add methanol to make a solution containing 2 mg per 1 ml, and use it as the reference substance solution. Use thin layer chromatography (Appendix VI B) test, absorb 1-2ul of each of the above three solutions, and place them on the same silica gel G thin layer plate prepared with 1% sodium hydroxide solution, and use ethyl acetate-formic acid-ice. Acetic acid-water (15:1:1:2) is used as the developing agent. Unfold, take out, dry, spray with 10% methyl sulfuric acid ethanol solution, heat at 105°C until the spots are clearly colored, and place under ultraviolet light (365nm) View. If the same orange-yellow fluorescent spot appears at the same position as the reference substance chromatogram, it proves that the raw materials of the compound preparation contain licorice.

The high-performance liquid chromatography method for detecting the content of Rubiacin in compound preparations includes: 1) using octadecylsilane bonded silica gel as the filler; using methanol-acetonitrile-0.2% phosphoric acid solution (25:50:25) as the flow phase; the detection wavelength is 250nm; the number of theoretical plates should not be less than 4000 based on the peaks of Rubiadin and Rubiadin; 2) Preparation of reference solution: Precisely weigh the Rubiadin reference substance and Rubiadin reference substance , weigh accurately, add methanol to prepare a solution containing 0.1 mg of rubiadin and 40ug of hydroxyrubberin per 1 ml, to obtain the rubiadin reference solution and hydroxyrubberin reference solution; 3) test solution Preparation: Take about 0.5g of the powder of this product (passed through No. 2 sieve), weigh it accurately, place it in a stoppered Erlenmeyer flask, accurately add 100ml of methanol with a stopper, weigh it, leave it overnight, and ultrasonicate (power 250W, frequency 40kHz) for 30 minutes, let cool, weigh again, make up for the lost weight with methanol, shake evenly, filter, accurately measure 50ml of the additional filtrate, evaporate to dryness, add methanol-25% hydrochloric acid (4:1) mixed solution to the residue Dissolve 20ml, heat and hydrolyze in a water bath for 30 minutes, cool immediately, add 3ml of triethylamine, mix well, transfer to a 25ml measuring bottle, add methanol to the mark, shake well, filter, the filtrate is the test solution; 4) Precisely pipette 10ul of the two reference solution and 20ul of the test solution and inject them into the liquid chromatograph for detection.

A third aspect of the present invention also provides a preparation composition, including the compound preparation of the first aspect, and hormones and/or cell growth factors. Among them, the hormones include at least one of estriol, nilestriol, ethinylestradiol, and E838, and the cell growth factors include interleukin IL-11, colony-stimulating factor, mesenchymal stem cells MSC, stem cell growth factor SCF, At least one of the thrombopoietic factors.

Specifically, the preparation composition of the present invention includes three different preparation composition forms: compound preparation and hormone, compound preparation and cell growth factor, and compound preparation, hormone and cell growth factor.

Compared with using hormones and/or cell growth factors independently, by combining hormones and/or cell growth factors with the aforementioned compound preparation of the present invention, radiation damage can be further reduced and the effect of anti-radiation damage can be improved.

Furthermore, in the process of using hormones in combination with the aforementioned compound preparations, a more significant anti-radiation damage effect can be achieved at the lowest cost by limiting the dosage of various hormones. Specifically, the usage amount of estriol is 0.01-0.5g, the usage amount of nilestriol is 0.01-0.5g, the usage amount of ethinylestradiol is 0.01-0.5g, and the usage amount of E838 is 0.01-0.5g. .

The fourth aspect of the present invention also provides the aforementioned compound preparation or preparation composition for the treatment of lung lesions caused by radiation damage, leukopenia caused by radiotherapy, chemotherapy or chemical poisons, and lung or respiratory tract lesions caused by viral infection. , application in drugs for thoracic tumors.

Further, the pulmonary lesions caused by radiation damage include pneumonia or pulmonary fibrosis disease, and the pulmonary or respiratory tract lesions caused by viral infection include pneumonia or respiratory diseases caused by coronavirus infection.

Among them, the present invention is not limited to radioactive sources of radiation damage, including but not limited to radioactive sources from the medical and military fields. For example, radioactive sources in the medical field include radioactive sources received during detection and treatment, and radioactive sources in the military field include bomb radiation.

The recurrence preparation provided by the present invention is an innovation in the form of the "Jun, Chen, Zuo, Shi" formula in the field of traditional Chinese medicine. It uses three herbs including a special proportion as raw materials and undergoes water extraction and alcohol precipitation. The three herbs complement each other and synergize. Improving lung lesions caused by radiation damage, leukopenia caused by radiotherapy, chemotherapy or chemical poisons, and lung or respiratory tract lesions caused by viral infections have opened up broad prospects for the research and development of new traditional Chinese medicine drugs.

Detailed ways

In order to make the purpose, technical solutions and advantages of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are part of the implementation of the present invention. examples, not all examples. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention.

Example 1

The preparation method of the extract (active ingredient in the compound preparation) of this embodiment includes the following steps:

1) Take 15g of madder, 40g of Houttuynia cordata and 15g of licorice. After crushing and mixing, the mixture is boiled and extracted with 500ml of water. After 1 hour, press filter to obtain the medicinal residue and extract; use 400ml of water to hydrate the medicinal residue. Boil and extract, after 1 hour, press filter, combine the extracts of the two boiling and leaching, and then concentrate under reduced pressure to obtain 10 ml of water extract;

2) Add an appropriate amount of ethanol to the water extract to obtain an alcohol precipitation system (the amount of ethanol added is subject to achieving a volume concentration of ethanol in the alcohol precipitation system of 75%), let it stand for 16 hours, filter, and concentrate the filtrate under reduced pressure. , after drying, the extract of this example is obtained. After testing, the ratio of the mass of rubiadin in the extract to the mass of Rubia raw materials input is not less than 0.4%.

Among them, the quality standards of compound preparations meet the relevant requirements of the Chinese Pharmacopoeia for madder, Houttuynia cordata and licorice.

Example 2

The preparation method of the extract in this embodiment is basically the same as that in Example 1. The difference is that in step 1), 15g of madder, 40g of Houttuynia cordata and 10g of licorice are used. After testing, the ratio of the mass of rubiadin in the extract to the mass of Rubia raw materials input is not less than 0.4%. Among them, the quality standards of compound preparations meet the relevant requirements of the Chinese Pharmacopoeia for madder, Houttuynia cordata and licorice.

Example 3

The preparation method of the extract in this embodiment is basically the same as that in Example 1. The difference is that in step 1), 15g of madder, 40g of Houttuynia cordata and 5g of licorice are used. After testing, the ratio of the mass of rubiadin in the extract to the mass of Rubia raw materials input is not less than 0.4%. Among them, the quality standards of compound preparations for screening tests meet the relevant requirements of the Chinese Pharmacopoeia for madder, Houttuynia cordata and licorice.

Example 4

The preparation method of the extract in this embodiment is basically the same as that in Example 1. The difference is that in step 1), 15g of madder, 30g of Houttuynia cordata and 10g of licorice are used. After testing, the ratio of the mass of rubiadin in the extract to the mass of Rubia raw materials input is not less than 0.4%. Among them, the quality standards of compound preparations meet the relevant requirements of the Chinese Pharmacopoeia for madder, Houttuynia cordata and licorice.

Example 5

The preparation method of the extract in this embodiment is basically the same as that in Example 1. The difference is that in step 1), 15g of madder, 20g of Houttuynia cordata and 10g of licorice are used. After testing, the ratio of the mass of rubiadin in the extract to the mass of Rubia raw materials input is not less than 0.4%. Among them, the quality standards of compound preparations meet the relevant requirements of the Chinese Pharmacopoeia for madder, Houttuynia cordata and licorice.

Example 6

The preparation method of the extract in this embodiment is basically the same as that in Example 1, except that in step 1), 10g of madder, 30g of Houttuynia cordata and 10g of licorice are used. After testing, the ratio of the mass of rubiadin in the extract to the mass of Rubia raw materials input is not less than 0.4%. Among them, the quality standards of compound preparations meet the relevant requirements of the Chinese Pharmacopoeia for madder, Houttuynia cordata and licorice.

Example 7

The preparation method of the extract in this embodiment is basically the same as that in Example 1. The difference is that in step 1), 5g of madder, 30g of Houttuynia cordata and 10g of licorice are used. After testing, based on the quality of Rubia cordata, the ratio of the quality of Rubiadin in the extract to the mass input of Rubia cordata raw materials is not less than 0.4%. Among them, the quality standards of the compound preparation meet the requirements of the "Chinese Pharmacopoeia" for Rubia cordata, Houttuynia cordata and Glycyrrhiza uralensis. Require.

Test Example 1 Effect of Compound Preparation on the Total Number of Peripheral White Blood Cells in Mice

1. Material preparation

The extracts in Examples 1-7 were added to 2wt% starch aqueous solution to prepare 7 groups of sample solutions with a concentration of 20 mg/0.2 ml (each 0.2 ml of starch aqueous solution contains 20 mg of extract).

Experimental animals: A total of 70 male and female KM mice, 6-8 weeks old and weighing 20-24 grams. All were purchased from Beijing Keyu Experimental Animal Center, experimental animal production license number: SCXK (Beijing) 2018-0010. The mice were randomly divided into 7 groups, with 10 mice in each group.

2. Test method

Among the 7 groups of mice, each group of mice was administrated with 1 group of the above-mentioned sample solutions, and each mouse was administrated with a gastric volume of 0.2 ml.

The total number of peripheral blood leukocytes Q was measured before gavage and 4, 8, 12, and 16 hours after gavage, and the peripheral blood leukocyte achievement rate D was calculated.

3. Test results

The total number of peripheral blood leukocytes Q and the achievement rate of peripheral blood leukocytes D are shown in Table 1.

Table 1

In Table 1, compared with each test group **P<0.01

As can be seen from Table 1, the compound preparation of the present invention has a significant effect on increasing the number of white blood cells in mice, especially when the mass ratio of madder, Houttuynia cordata and licorice is (10-15): (30-40): (10- 15), the effect is better. Among them, when the mass ratio of madder, Houttuynia cordata and licorice is 10:30:10, the effect is most prominent.

Test Example 2 Effects of different doses of compound preparations on peripheral blood leukocytes of dogs

Purpose: This test case mainly observes the effect of different doses of the compound preparation on increasing the peripheral blood leukocytes of normal dogs.

1. Material preparation

Test drug: the extract in Example 6.

Comparative drug: Rubia bifat tablets produced by Jiangsu Jibel Pharmaceutical Co., Ltd., 100mg/tablet.

Experimental animals: 80 normal healthy male grass dogs, divided into four groups, 20 in each group. Among them, three groups (Sancao 15g group, Sancao 10g group, Sancao 5g group) were used as the testing objects for the test drug, and one group (Rudera grass group) were used as the testing objects for the control drug. In the Sancao 15g group, each dog weighed 7.71±0.61 kg; in the Sancao 10g group, each dog weighed 7.91±0.66 kg; in the Sancao 5g group, each dog weighed 7.91±0.66 kg; in the Rubia grass group , each dog weighed 7.7 ± 0.77 kg. Comparing the general conditions of each group, the differences were not statistically significant and were comparable.

2. Test method

Sancao 15g group: the dogs were given the experimental drug orally at one time, 15g/dog

Sancao 10g group: the dogs were given the test drug orally at one time, 10g/dog

Sancao 5g group: the dogs were given the test drug orally at one time, 5g/dog

Rubia group: Dogs are given Rubia bifat tablets orally at one time, 100mg/dog

The total number of peripheral blood leukocytes Q was measured before administration and 12, 24, 48, and 72 hours after administration, and the peripheral blood leukocyte attainment rate D was calculated. The results are shown in Table 2.

Table 2

In Table 2, compared with the madder group, **P＜0.01, compared with the Sancao 10g group, #P＜0.05

As can be seen from Table 2, peripheral blood leukocytes in each group began to increase 12 hours after administration, reached a peak at 24 hours, began to decrease 48 hours after administration, and gradually returned to pre-drug levels. Among them, the three-grass 15g group and three-grass 10g group had a more obvious effect on increasing white blood cells, and were better than the madder group, and the difference was statistically significant (P<0.01). Except for 72 hours after treatment, the three-grass 15g group was better than the three-grass 10g group, and other differences were not statistically significant.

Test Example 3 Effect of Compound Preparation on Peripheral Blood Leukocytes of Patients with Benzene Poisoning

Objective: To mainly observe the effect of compound preparation on increasing peripheral blood leukocytes in patients with chronic benzene poisoning.

1. Material preparation

Test drug: Take the compound preparation in Example 6 and add appropriate auxiliary materials to prepare a Sancao granule compound preparation weighing 10g per bag. Each bag of Sancao granule compound preparation contains 5g of extract.

Comparative drug: Rubia bifat tablets produced by Jiangsu Jibel Pharmaceutical Co., Ltd., 100mg/tablet.

Patients tested: 40 patients with chronic benzene poisoning, 20 in each group, all of whom were in line with the diagnosis of leukopenia in "Practical Internal Medicine", with the total number of peripheral blood white blood cells <4×10 ⁹ /L. The patients were divided into two groups at a ratio of 1:1 according to the order of treatment, namely the Sancao group and the Madder group.

Among them, there were 20 cases in the three-grass group, 7 women and 13 men, aged 33-56, with an average age of 44.1±7.42, 12 cases were exposed to benzene, and 8 cases were exposed to petroleum gas benzene.

There were 20 cases in the madder group, 12 men and 8 women, aged 35-55, with an average age of 45.1±5.33. 11 cases were exposed to benzene and 9 cases were exposed to petroleum gas benzene.

Comparing the general conditions of the two groups, the differences were not statistically significant and were comparable.

2. Test method

Sancao group: Each person takes 2 bags of Sancao granule compound preparation orally every day.

Rubia group: 100 mg of Rubia bis-fat is taken orally per person per day.

A course of treatment is 28 days, and the efficacy is evaluated after one course of treatment. The two groups of patients underwent routine peripheral blood leukocyte detection before treatment and 3 days, 7 days, 14 days, 21 days, and 28 days after treatment, and the peripheral blood leukocyte achievement rate D was calculated. Before and after treatment, patients in both groups were examined with chest X-rays, electrocardiograms, liver and kidney functions, and changes in clinical symptoms were recorded.

3. Test results (SPSS17.0 software is used to process data, measurement data uses t test, and counting data uses x2 test)

1) The clinical efficacy is the total effective rate. The results are shown in Table 3.

Markedly effective: After stopping exposure to pathogenic factors, the time for the white blood cell count to return to the normal range (≧5×10 ⁹ /L) or rise from <2×10 ⁹ /L to above 4×10 ⁹ /L for two consecutive times is shorter than the control and Significant;

Effective: The white blood cell count increased by 100% in two consecutive examinations compared with before treatment;

Invalid: There is no significant increase in the number of white blood cells after treatment, and the increase is <100% compared with before treatment;

Total effective rate = (markedly effective + effective) number of cases/total number of cases × 100%.

table 3

Group Number of examples Effective efficient invalid Total effectiveness (%) Sancao group 20 16(80.0) 2(10.0) 2(10.0) 18(90.0)** Rubia group 20 9(45.0) 4(20.0) 7(35.0) 13(65.0)

In Table 3, compared with the madder group, **P＜0.01

It can be seen from Table 3 that the total effective rate of the Sancao group was 90% and that of the Rubia cordata group was 65%. The difference between the two groups was statistically significant (P<0.01). It is suggested that the compound preparation of the present invention has a better effect on increasing peripheral blood leukocytes in patients with chronic benzene poisoning than Rubia bispermum.

2) Total peripheral leukocyte count Q (mean ± standard deviation) and peripheral leukocyte achievement rate D, the results are shown in Table 4

Table 4

In Table 4, compared with the madder group, **P＜0.01

It can be seen from Table 4 that the three-grass group showed a significant increase in leukocyte effects after 7 days of treatment, and the madder group showed a significant increase in leukocyte effects after 14 days of treatment. The total number of white blood cells in the Sancao group at 7, 14, 21, and 28 days after treatment was significantly higher than that in the Rubia cordata group, and the difference between the two groups was statistically significant (P<0.01).

3) Changes in clinical symptoms and drug side effects

The clinical symptoms of the Sancao group improved rapidly. After 2 weeks of treatment, the symptoms of dizziness, fatigue and other complaints of most patients were alleviated or disappeared. Most patients in the Rubia grass group only experienced partial relief of clinically relevant symptoms after 3 weeks of treatment. Comparing the patients' electrocardiogram, liver and kidney function and clinical symptoms before and after treatment, no obvious side effects were found in the two groups.

Test Example 4 Effect of Compound Preparation on Leukopenia Caused by Radiotherapy and Chemotherapy

Objective: To mainly observe the therapeutic effect of compound preparations on peripheral blood leukopenia in cancer patients undergoing radiotherapy and chemotherapy.

1. Material preparation

Test drug: Same as Test Example 3.

Comparative drug: Rubia bifat tablets produced by Jiangsu Jibel Pharmaceutical Co., Ltd., 100mg/tablet.

Subjected patients: 64 cancer patients with leukopenia caused by chemotherapy and radiotherapy, all of whom met the criteria

"Practical Internal Medicine" Diagnosis of Leukopenia: The total number of peripheral blood white blood cells is <4×10 ⁹ /L. According to the order of admission, they were randomly divided into Sancao group and Rubia grass group, with 32 cases in each group.

Among them, there were 30 cases in the Sancao group, 10 women and 22 men, aged 39-72, with an average age of 58.6±9.601. In general, the Karnofsky score was 60.6±6.19. Among the 30 cases, 22 were chemotherapy cases and 8 were radiotherapy cases. Among the 32 cases, there were 8 cases of lung cancer, 7 cases of gastric cancer, 6 cases of colon cancer, 7 cases of rectal cancer, and 4 cases of breast cancer.

There were 32 patients in the madder group, 11 females and 21 males, aged 35-77, with an average age of 56.4±9.524. In general, the Kaspersky mean score was 60.9±6.41. Among the 32 cases, 23 were chemotherapy cases and 9 were radiotherapy cases. Among the 32 cases, 9 were lung cancer, 8 were gastric cancer, 6 were colon cancer, 6 were rectal cancer, and 3 were breast cancer.

Comparing the general conditions of the two groups, the differences were not statistically significant and were comparable.

2. Test method

Sancao group: Each person takes 2 bags of Sancao granule compound preparation orally every day.

Rubia group: 100 mg of Rubia bis-fat is taken orally per person per day.

A course of treatment is 28 days, and the efficacy is evaluated after one course of treatment. Radiotherapy and chemotherapy are stopped during the treatment. Routine detection of peripheral blood leukocytes was performed on the two groups of patients 3 days, 7 days, 14 days, 21 days, and 28 days after treatment. Before and after treatment, the patients in both groups were examined with chest X-rays, electrocardiograms, liver and kidney functions, and changes in clinical symptoms were recorded.

3. Test results (SPSS17.0 software is used to process data, measurement data uses t test, and counting data uses x2 test)

1) Overall clinical effectiveness, the results are shown in Table 5

Markedly effective: After stopping exposure to pathogenic factors, the time for the white blood cell count to return to the normal range (≧5×10 ⁹ /L) or rise from <2×10 ⁹ /L to above 4×10 ⁹ /L for two consecutive times is shorter than the control and Significant;

Effective: The white blood cell count increased by 100% in two consecutive examinations compared with before treatment;

Invalid: There is no significant increase in the number of white blood cells after treatment, and the increase is <100% compared with before treatment;

Total effective rate = (markedly effective + effective) number of cases/total number of cases × 100%.

table 5

Group Number of examples Effective efficient invalid Total effectiveness (%) Sancao group 32 23(71.9) 7(21.9) 2(6.25) 93.8** Rubia group 32 15(46.9) 6(18.8) 11(34.4) 65.6

In Table 5, compared with the madder group, **P＜0.01

As can be seen from Table 5, the total effective rate of the Sancao group was 93.8%, and the total effective rate of the Rubia group was 65.6%. The difference between the two groups was statistically significant (P<0.01). It is suggested that the effect of the compound preparation of the present invention on increasing peripheral blood leukocytes is better than that of Rubia dilipid.

2) Total number of peripheral white blood cells (mean ± standard deviation), the results are shown in Table 6

Table 6

In Table 6, compared with before treatment, **P＜0.01

It can be seen from Table 6 that the three-grass group showed a significant increase in leukocyte effects after 7 days of treatment, and the madder group showed a significant increase in leukocyte effects after 14 days of treatment. The total number of white blood cells in the Sancao group at 7, 14, 21, and 28 days after treatment was significantly higher than that in the Rubia cordata group, and the difference between the two groups was statistically significant (P<0.01).

3) Changes in clinical symptoms and drug side effects

The clinical symptoms of the Sancao group improved rapidly. After 2 weeks of treatment, the symptoms of dizziness, fatigue and other complaints of most patients were alleviated or disappeared. Most patients in the Rubia grass group only experienced partial relief of clinically relevant symptoms after 3 weeks of treatment. Comparing the patients' electrocardiogram, liver and kidney function and clinical symptoms before and after treatment, no obvious side effects were found in the two groups.

Test Example 5: Effect of Compound Preparation on Patients with Chest Tumors

Objective: To observe the effects of compound preparations on preventing and treating radiation pneumonitis pulmonary fibrosis, anti-tumor, reducing the incidence of respiratory tract infections, increasing peripheral blood white blood cells, enhancing immune function, and improving quality of life in patients with thoracic tumors during radiotherapy.

1. Material preparation

Test drug: Same as Test Example 3.

Comparative drug: Rubia bifat tablets produced by Jiangsu Jibel Pharmaceutical Co., Ltd., 100mg/tablet.

Subject patients: The cases come from 60 thoracic tumor patients who were hospitalized and determined to need radiotherapy. The cases met the following inclusion criteria:

①KPS equals ≧80 points;

②Patients with thoracic malignant tumors (lung cancer, esophageal cancer, thymus cancer) confirmed by pathology;

③No treatment that has a definite impact on immune function was received before radiotherapy;

④ The radiotherapy process ends successfully, the radiotherapy interval should not exceed 1 week, and blood should be collected promptly before and after radiotherapy to check the immune function.

Using a completely random grouping design method, 60 patients with thoracic tumors were assigned to the Sancao group and the Madder group according to the order of treatment, with 30 cases in each group.

Among them, in the Sancao group, there were 20 males and 10 females, with an average age of 58.6±9.91 (39-72) years, 19 cases of lung cancer, 7 cases of esophageal cancer, and 4 cases of adenocarcinoma.

In the madder group, there were 21 males and 9 females, with an average age of 56.8±9.67 (35-77) years. There were 21 cases of lung cancer, 6 cases of esophageal cancer, and 3 cases of adenocarcinoma.

Comparing the general conditions of the two groups, the differences were not statistically significant and were comparable.

2. Test method

Both groups of cases were treated with three-dimensional conformal or intensity-modulated local radiotherapy, with a course of 6 weeks. Patients in the Sancao group were orally given 2 bags of Sancao Granules compound preparation per person per day while undergoing radiotherapy; patients in the Rubiacao group were orally administered Rubia bisphospholipid, 100 mg/day/per person, at the same time as radiotherapy.

1) Collect blood samples

Venous blood was used to detect the total number of white blood cells and lymphocytes in the patient's peripheral blood before, during and after radiotherapy. Peripheral blood was measured with Epics-XL-Ⅱ flow cytometer for CD3, CD4, CD8, CD4/CD8 and CD56.

2) Immune function diagnosis

The normal range of each indicator of immune function is determined by the flow cytometry laboratory of the hospital and analyzed to establish standards for immune function indicators of normal people. Diagnostic criteria for immune function: If any one of CD3, CD4, and CD4/CD8 is lower than the normal range, the patient is diagnosed as having low immune function.

3) Anti-tumor clinical efficacy standards

After radiotherapy, chest + abdominal CT will be reviewed to compare the changes in lesions before and after radiotherapy for clinical efficacy evaluation. The clinical efficacy evaluation standard adopts the RBCIST solid cancer efficacy evaluation system, and the clinical efficacy is divided into four levels.

4) Grading standards for acute radiation injury to the lungs

For the evaluation of the efficacy of acute radiation injury in the lungs, the incidence of radiation pneumonitis and the incidence of radiation-induced pulmonary fibrosis were the main indicators, and the American Radiation Therapy Oncology Group (RTOG) acute radiation injury grading standard was used to evaluate the degree of acute radiation injury in the lungs.

5) Observation and evaluation of clinical symptoms

During radiotherapy, clinical symptoms of respiratory tract infection were observed at the same time, and the incidence of respiratory tract infection was compared between the two groups.

3. Test results (use SPSS13.0 statistical software for data processing, perform variance analysis and t test according to the data characteristics, and P<0.05 is considered a statistically significant difference)

1) Incidence rates of radiation pneumonitis and radiation pulmonary fibrosis. The results are shown in Table 7

Table 7

In Table 7, compared with the madder group, *P＜0.05, **P＜0.01

As can be seen from Table 7, the incidence rates of radiation pneumonitis and pulmonary fibrosis in the Sancao group were 23.33% and 13.33% respectively, and the incidence rates in the Rubia grass group were 53.33% and 30.0% respectively. Comparing the two groups, the difference was statistically significant (P<0.01 , P<0.05). It is suggested that the compound preparation of the present invention can significantly reduce the incidence of radiation pneumonitis and reflex pulmonary fibrosis caused by radiotherapy for thoracic malignant tumors.

2) Incidence of respiratory tract infection, the results are shown in Table 8

Table 8

Group Respiratory tract infections (number of cases) Incidence rate (%) Sancao group 2 6.67** Rubia group 8 26.7

In Table 8, compared with the madder group, **P＜0.01

It can be seen from Table 8 that during the treatment period, the incidence rate of respiratory tract infection in the Sancao group was 6.67%, and the incidence rate of respiratory tract infection in the Rubia grass group was 26.7%. The difference between the two groups was statistically significant (P<0.05), indicating that the compound preparation of the present invention is beneficial to reducing Incidence of respiratory infections.

3) The total number of white blood cells and lymphocytes in peripheral blood, the results are shown in Table 9

Table 9

In Table 9, compared with the madder group, *P＜0.05; **P＜0.01

It can be seen from Table 9 that the proportion of normal peripheral leukocytes and lymphocytes in the Sancao group was higher than that in the Rubia cordifolia group, and the differences between the two groups were statistically significant (P<0.05, P<0.01).

4) Immune function, the results are shown in Table 10

Table 10

Three Grass Group 30 Rubia group CD3(%) 69.6±2.36 70.2±1.84 CD4(%) 36.8±1.20** 21.0±2.92 CD8(%) 37.4±1.33** 41.9±2.39 CD56(%) 69.8±2.21** 23.0±1.93 CD4/CD8 0.985±0.05** 0.502±0.06

In Table 10, compared with the madder group, **P＜0.01

As can be seen from Table 10, compared with the Rubia cordata group, the immune function of the Sancao group had an increase in CD4 and CD4/CD8, and a decrease in CD8. The differences were statistically significant (P<0.01).

5) Anti-tumor clinical efficacy, the results are shown in Table 11

Table 11

Group Number of cases CR PR PD Efficient(%) Sancao group 29 3 twenty four 2 93.1** Rubia group 28 0 11 17 39.3

In Table 11, compared with the madder group, **P>0.01

As can be seen from Table 11, the efficacy evaluation of the two groups of patients at the end of radiotherapy showed that there were 3 cases of CR, 24 cases of PR, and 2 cases of PD in the Sancao group, with an effective rate of 93.1%. There were 0 cases of CR, 11 cases of PR, and 17 cases of PD in the madder group, with an effective rate of 39.3%. There was no statistically significant difference in the effective rates between the two groups (P>0.01).

Test Example 6 Observation on the efficacy of compound preparation on acute radiation sickness in mice

Objective: To observe the effects of compound preparations and the combined use of compound preparations + estriol + interleukin (IL-11) on the 30-day survival rate and hematopoietic function of exposed mice.

1. Material preparation

Test drug: Add the extract in Example 6 to a 2wt% starch aqueous solution to prepare a test drug solution with a concentration of 100 mg/0.2 ml (each 0.2 ml of starch aqueous solution contains 100 mg of extract).

Estriol raw material: Estriol is prepared into a concentration of 0.1mg/0.2ml (0.1mg estriol per 0.2ml of 2wt% starch aqueous solution), 0.05mg/0.2ml (per 0.2ml of 2wt% starch aqueous solution) Estriol solution containing 0.05 mg estriol). Estriol raw materials are provided by the laboratory of the Academy of Military Medical Sciences.

IL-11 raw material: 3.0 mg/tube, IL-11 is prepared into an IL-11 solution with a concentration of 0.1 mg/0.2 ml (each 0.2 ml of 2wt% starch aqueous solution contains 0.1 mg IL-11). IL-11 raw material is produced by Qilu Pharmaceutical Co., Ltd.

Experimental animals: 270 male KM mice, 6-8 weeks old, 22-26 grams in weight. Purchased from Beijing Keyu Experimental Animal Center, experimental animal production license number: SCXK (Beijing) 2018-0010. Among them, 180 were used to observe the survival rate of animals after irradiation, and the animals were randomly divided into 9 groups, with 20 animals in each group; 90 animals were used to observe the hematopoietic function indicators after irradiation, and the animals were randomly divided into 9 groups, with 10 animals in each group.

2. Test method

The survival rate of animals and hematopoietic function indicators after exposure were observed 30 days after exposure. The administration methods for animals in the same group were the same. The ⁶⁰ Cor ray irradiation source of the Institute of Military Medical Radiation Medicine was used, and the irradiated mice were placed in a plexiglass partition, 4.00m away from the source. The animals to observe the survival rate were irradiated with 8.5Gy to the whole body at one time; the animals to observe the hematopoietic function indicators were irradiated to the whole body with 7.5Gy at a time, and the irradiation dose rate was 200-220c Gy/min.

Group 1: Normal control group, without any treatment;

Group 2: Blank control, intragastric administration immediately and on the 3rd day after exposure, normal saline/0.2ml/animal;

Group 3: Test drug, 0.2ml/animal was administered by gavage immediately after exposure and on the 3rd day after exposure;

Group 4: 0.1mg/0.2ml estriol solution, 0.2ml/animal was administered by gavage immediately after exposure;

Group 5: IL-11 solution, intraperitoneal injection of 0.2ml/animal immediately after irradiation;

Group 6: Test drug (the dosage is the same as that of Group 3) + 0.1mg/0.2ml estriol solution (the dosage is the same as Group 4);

Group 7: Test drug (the dosage is the same as that of Group 3) + IL-11 solution (the dosage is the same as Group 5);

Group 8: Test drug (the dosage is the same as the 3rd group) + 0.05mg/0.2ml estriol solution (0.2ml/animal) + IL-11 solution (the dosage is the same as the 5th group);

Group 9: Test drug (the dosage is the same as Group 3) + 0.1 mg/0.2 ml estriol solution (the dosage is the same as Group 4) + IL-11 solution (the dosage is the same as Group 5)

1) Observation of survival rate of mice 30 days after exposure

Observe the survival of mice within 30 days from the start of irradiation, record the status and number of deaths of mice every day, and calculate the 30-day survival rate of mice according to the following formula.

30-day survival rate = number of surviving animals after treatment/number of experimental animals

2) BMNC and splenic nodule determination:

On the 8th day after irradiation, the mice were killed by cervical dislocation. BMNC (X106) (The number of nucleated callin bone marrow): Take the right femur, wash the femoral cavity with leukocyte diluent, collect the bone marrow cells to make a suspension, and use Trypan blue was used to identify cell viability above 95%, and the total number of nucleated cells in the bone marrow was calculated under a microscope. The mouse spleen was removed from the splenic nodule (colong forming unit of spleen, CFU-S) aseptically, weighed, and the spleen weight index was calculated according to the formula. Spleen weight index = spleen weight (mg)/mouse weight (g). The spleen was fixed in Bouin's solution and taken out after 6 hours to count the CFU-S number of hematopoietic foci on the surface of the spleen.

3. Test results

1) 30-day survival rate of irradiated mice, the results are shown in Table 12

Table 12

Group Number of experiments Number of survivors Survival rate (%) Average survival time of dead animals Group 1 20 20 100 - Group 2 20 1 0.5 7.37±1.30 Group 3 20 15 75.0 ^** 17.6±1.34 Group 4 20 13 65.0 ^** 15.4±2.44 Group 5 20 9 45.0 ^** 13.9±2.87 Group 6 20 16 80.0 ^** 16.7±1.53 Group 7 20 15 75.0 ^** 16.6±3.20 Group 8 20 18 90.0 ^** 20.5±0.71 Group 9 20 19 95.0 ^**# 22.0

In Table 12, ** is compared with the blank control group, # is compared with the three-herb single drug group

2) The effect on the hematopoietic function of the exposed mice, the results are shown in Table 13

Table 13

Group Number of animals BMNC(X10 ⁶ )/femur CFU-S(piece/spleen) Spleen weight index (mg/g) Group 1 10 --- --- --- Group 2 10 1.20±0.92 1.09±0.12 0.97±0.07 Group 3 10 2.63±0.41 ^** 4.50±1.58 ^** 1.17±0.07 ^** Group 4 10 2.17±0.23 ^** 2.8±1.23 ^* 1.04±0.04 ^* Group 5 10 2.14±0.18 ^** 2.6±1.65 ^* 1.05±0.06 ^* Group 6 10 2.21±0.18 ^** 4.60±1.96 ^** 1.13±0.07 ^** Group 7 10 2.33±0.15 ^** 5.70±1.77 ^** 1.17±0.06 ^** Group 8 10 5.68±1.03 ^**## 13.8±3.74 ^**## 1.69±0.15 ^**## Group 9 10 6.60±1.10 ^**## 14.1±3.64 ^**## 1.73±0.06 ^**##

Note: ** compared with the blank control group, # compared with the three-herb single drug group

It can be seen from Table 12 and Table 13 that the 30-day survival rate, bone marrow nucleated cell number, CFU-S number and spleen index of the irradiated mice in the test drug solution single drug group were significantly better than those in the blank control group, and the differences were statistically significant. (P<0.01); When the experimental drug is combined with estriol (0.05 mg or 0.1 mg) and interleukin-11, the anti-radiation damage effect is significantly improved. Estriol and IL-11 alone also have certain anti-radiation damage effects.

Therefore, the compound preparation of the present invention can be used for patients with tumor radiotherapy and chemotherapy to improve the therapeutic effect of tumor radiotherapy and chemotherapy, increase peripheral blood leukocytes, and reduce the incidence of bacterial infection; it can be used alone or in combination with estrogen, interleukin and other drugs in emergencies.

Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention, but not to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: The technical solutions described in the foregoing embodiments can still be modified, or some or all of the technical features can be equivalently replaced; and these modifications or substitutions do not deviate from the essence of the corresponding technical solutions from the technical solutions of the embodiments of the present invention. scope.

Claims (10)

1. A compound preparation, characterized in that the active ingredient of the compound preparation is a product obtained by sequentially subjecting raw materials including madder, Houttuynia cordata and licorice to water extraction and alcohol precipitation; the madder, fish The mass ratio of cordyceps and licorice is (3-30): (5-50): (3-30) And, based on the mass of Rubia cordata, the mass percentage of Rubiacin in the compound preparation is not Less than 0.4%. 2. The compound preparation according to claim 1, characterized in that the mass ratio of madder, Houttuynia cordata and licorice is (10-15): (30-40): (10-15). 3. The compound preparation according to claim 1 or 2, further comprising acceptable auxiliary materials; the dosage forms of the compound preparation include granules, capsules, tablets, pills, oral liquids, sprays, and teas. . 4. The compound preparation according to claim 1, wherein the water extraction treatment includes: boiling and leaching the raw material at least once to obtain a water extract. 5. The compound preparation according to claim 4, characterized in that the alcohol precipitation treatment includes: Ethanol is added to the water extract to obtain an alcohol precipitation system, followed by alcohol precipitation for 12-24 hours. The volume concentration of ethanol in the alcohol precipitation system is 60-80%. 6. A method for preparing the compound preparation according to any one of claims 1 to 5, characterized in that it includes the following steps: The raw materials including madder, Houttuynia cordata and licorice are boiled and extracted at least once, the water extract is filtered after alcohol precipitation and the alcohol solvent is recovered, and the extract is collected; the extract is processed to obtain the compound preparation; Wherein, the mass ratio of the madder, Houttuynia cordata and licorice is (3-30): (5-50): (3-30), and based on the quality of the madder, the large leaves in the compound preparation The mass percentage of rubiacin is not less than 0.4%. 7. The preparation method according to claim 6, characterized in that the raw material is boiled and leached at least twice, the water extract is added with ethanol to obtain an alcohol precipitation system, and then the alcohol precipitation system is followed by alcohol precipitation for 12-24 hours. The volume concentration of ethanol in the medium is 60-80%. 8. A preparation composition, characterized in that it includes the compound preparation according to any one of claims 1-5, hormones and/or cell growth factors; The hormone includes at least one of estriol, nilestriol, ethinylestradiol, and E838; The cell growth factors include at least one of interleukin IL-11, colony-stimulating factor, mesenchymal stem cells MSC, stem cell growth factor SCF, and thrombopoietic factor. 9. A compound preparation according to any one of claims 1 to 5 or a preparation composition according to claim 8 for the treatment of pulmonary lesions caused by radiation damage, leukopenia caused by radiotherapy, chemotherapy or chemical poisons, Application in medicines for lung or respiratory tract lesions and chest tumors caused by viral infection. 10. The application according to claim 9, wherein the lung lesions caused by radiation damage include pneumonia or pulmonary fibrosis; the lung or respiratory tract lesions caused by viral infection include those caused by coronavirus infection. of pneumonia or respiratory illness.