CN116870069A - Compound preparation and preparation method and application thereof - Google Patents
Compound preparation and preparation method and application thereof Download PDFInfo
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- CN116870069A CN116870069A CN202310773301.7A CN202310773301A CN116870069A CN 116870069 A CN116870069 A CN 116870069A CN 202310773301 A CN202310773301 A CN 202310773301A CN 116870069 A CN116870069 A CN 116870069A
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
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- A—HUMAN NECESSITIES
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- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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Abstract
The invention provides a compound preparation, a preparation method and application thereof, wherein the active ingredients of the compound preparation are products obtained by sequentially carrying out water extraction treatment and alcohol precipitation treatment on raw materials comprising madder, cordate houttuynia and liquorice; the mass ratio of the madder, the cordate houttuynia and the liquorice is (3-30): (5-50): (3-30) and the mass percentage of the alizarin in the compound preparation is not less than 0.4 percent based on the mass of the madder. The compound preparation has the characteristics of high efficiency and low toxicity for the protection and treatment of radiation injury lesions and the like.
Description
Technical Field
The invention relates to a compound preparation, in particular to a compound preparation and a preparation method and application thereof, belonging to the technical field of medicines.
Background
Radiation therapy is the primary treatment for breast malignancies (lung cancer, esophageal cancer, breast cancer and other malignancies). It has been reported that more than 80% of patients with breast malignancy undergo selective radiation therapy. However, while the radiation therapy kills tumor cells, the radiation therapy has the side effects of extensive radiation pneumonitis pulmonary fibrosis, immune function, leucocyte decline and the like on normal lung tissues in the radiation field, and patients are often forced to stop the therapy or fail the therapy. Pulmonary fibrosis is a refractory disease, and no radical cure drug exists at present. In order to relieve the pain of patients caused by pulmonary fibrosis and the like of radiation pneumonitis, a great deal of researches are carried out around the occurrence mechanism, prevention and treatment by domestic and foreign scientific researches and clinical staff. But the results were not satisfactory. With the development of modern research of traditional Chinese medicines, the research results of the traditional Chinese medicines for preventing and treating pulmonary fibrosis and resisting tumors of radiation pneumonitis open up a wide prospect in the field.
Furthermore, the world health organization WHO considers that "in case of radiation emergency, people may be subjected to radiation in varying doses from trivial to life threatening. The governments should be able to provide treatment to the person in need thereof. It is vital that governments in various countries make preparations for protecting the health of the public and immediately cope with emergency situations. Thus, WHO has also updated a list of stock drugs for preventing or reducing radiation exposure, or for treatment after radiation has occurred, and policy recommendations for proper management thereof, in 2023.
Traditional Chinese medicine is profound. In recent years, the progress of modern research on traditional Chinese medicines has achieved a certain achievement in the aspect of anti-radiation injury medicines, but the problems of toxicity and effectiveness in preventing and treating radiation loss are still difficult to achieve. Therefore, the search of the radiation injury protection medicine with high efficiency, low toxicity and prevention and treatment has very important clinical significance and practical significance.
Disclosure of Invention
The invention provides a compound preparation, which has the characteristics of high efficiency and low toxicity aiming at the protection and treatment of radiation injury lesions and the like due to the raw material specificity and the composition specificity of the compound preparation.
The invention also provides a preparation method of the compound preparation, which can obtain the compound preparation with low toxicity and high efficiency for preventing and treating radiation injury lesions and the like by selecting proper raw materials and regulating and controlling the treatment process of the raw materials.
The invention also provides a preparation composition, and the compound preparation is clinically combined with hormone and cell growth factor, so that the prevention and treatment effect on the radiation injury lesions is further enhanced.
The invention also provides application of the compound preparation or the preparation composition in preparing medicines for treating lung lesions caused by radioactive injury, leukopenia caused by radiotherapy and chemotherapy or chemical poison and lung or respiratory tract lesions caused by virus infection.
The first aspect of the invention provides a compound preparation, the active ingredients of which are products obtained by sequentially carrying out water extraction treatment and alcohol precipitation treatment on raw materials comprising madder, cordate houttuynia and liquorice; the mass ratio of the madder, the cordate houttuynia and the liquorice is (3-30): (5-50): (3-30) and, based on the mass of the madder, the mass percentage of the alizarin in the compound preparation is not less than 0.4%.
The active ingredients of the compound preparation of the invention are from the raw materials comprising madder, cordate houttuynia and liquorice, and the mass ratio of the madder, cordate houttuynia and liquorice in the raw materials is (3-30): (5-50): (3-30), wherein the quality control standard of the madder root meets the first edition of 2015 of Chinese pharmacopoeia, and the quality control standard of the cordate houttuynia and the liquorice meets the first edition of 2020 of Chinese pharmacopoeia. Specifically, the product obtained by sequentially carrying out water extraction treatment and alcohol precipitation treatment on the raw materials is the active ingredient of the compound preparation, and the mass of the alizarin in the compound preparation is not less than 0.4% of the input mass of the alizarin raw materials based on the mass of the alizarin in the raw materials.
The effective components in the compound preparation are from three grasses with special mass ratio (madder, cordate houttuynia and liquorice) as raw materials, and the water extraction and alcohol precipitation treatment is carried out on the three grasses to obtain respective special extracts of the three grasses, and the special extracts are mutually cooperated and mutually complemented, so that the compound preparation has the characteristics of low toxicity and high efficiency for preventing and treating the radiation injury lesions, and can especially improve the white blood cell number after the radiation injury and reduce the incidence rate of radiation pneumonia and radiation pulmonary fibrosis caused by the radiation injury. In addition, the composition has satisfactory clinical effects on the prevention and treatment of lung or respiratory diseases caused by leucocyte reduction caused by chemical toxicants and virus infection.
Specifically, the water extraction treatment is a process of extracting a raw material with water as an extractant to obtain an aqueous extract, and the alcohol precipitation treatment is a process of precipitating an active ingredient by adding an alcohol solvent to the aqueous extract. It can be understood that after the alcohol precipitation treatment, the post-treatment of filtering, concentrating and drying the alcohol precipitation system is also needed, and finally the compound preparation containing not less than 0.4% (the mass of the alizarin in the compound preparation is not less than 0.4% based on the input mass of the alizarin raw material) is obtained.
Further, when the mass ratio of the madder, the cordate houttuynia and the liquorice in the raw materials is (10-15): (30-40): (10-15), and further, the mass ratio of the madder, the cordate houttuynia and the liquorice is 10:30:10, the compound preparation of the invention is more beneficial to promoting the growth of white blood cells.
In one specific embodiment, the above effective components can be mixed with pharmaceutically acceptable excipient, diluent and other adjuvants to make into granule, capsule, tablet, pill, oral liquid, spray, and tea. The preparation in various preparation forms can be prepared by a conventional pharmaceutical method.
The above adjuvants can be used in conventional pharmaceutical method. Examples of useful pharmaceutical excipients include excipients (e.g., saccharide 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 calcium, sodium carboxymethyl cellulose; acacia; dextran; silicate derivatives such as magnesium aluminum metasilicate; phosphate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate and the like), binders (e.g., gelatin, polyvinylpyrrolidone and polyethylene glycol), disintegrants (e.g., cellulose derivatives such as sodium carboxymethyl cellulose, polyvinylpyrrolidone), lubricants (e.g., talc, calcium stearate, magnesium stearate, spermaceti, boric acid, sodium benzoate, leucine and the like), stabilizers (e.g., commonly used sweeteners, acidulants and flavors and the like), diluents and solvents for injections (e.g., water, ethanol and glycerin and the like). When the preparation type is tea, the auxiliary material can be tea.
In one embodiment, the water extraction treatment comprises at least one water boiling and leaching of the raw materials to obtain an aqueous extract.
Specifically, the water-boiling leaching is a process in which water (extractant) is immersed in the raw material, and then heated until boiling and heat preservation is continued. The invention is not limited to the number of times of water-boiling leaching, and can be carried out only once or a plurality of times of water-boiling leaching. When the water-boiling leaching is carried out for a plurality of times, fresh water is needed to be replaced each time, the water-boiling leaching is carried out again on the raw materials after the water-extracting treatment for the previous time, and finally, the extracting solutions of each time are combined. Wherein the time of each water decoction leaching is controlled within 1-2 h.
Since the extract contains a large amount of extractant, in order to reduce the workload of subsequent treatments including alcohol precipitation treatment, the extract obtained by water-boiling leaching may be concentrated under reduced pressure to remove most of extractant, thereby obtaining an aqueous extract.
Furthermore, the mass ratio of the raw materials to the extractant is controlled to be not more than 1g to 10ml in each water extraction treatment, so that the effectiveness of the water extraction treatment can be ensured, and the workload of removing the extractant by decompression concentration can be reduced. Furthermore, when the water extraction treatment is performed a plurality of times, the amount of the extractant can be reduced as compared with the previous one.
In one embodiment, in order to ensure the effectiveness of the compound preparation and to improve the operability of the preparation process, the alcohol precipitation treatment comprises: and adding ethanol into the water extract to obtain an ethanol precipitation system, and then carrying out ethanol precipitation for 12-24 hours, wherein the volume concentration of the ethanol in the ethanol precipitation system is 60-80%.
The inventor finds that the volume concentration of the ethanol in an ethanol precipitation system has a critical influence on the effectiveness of the compound preparation, so that the addition amount of the ethanol needs to be strictly controlled. In detail, when the volume concentration of the ethanol in the ethanol precipitation system is 60-80%, further, when the volume concentration of the ethanol in the ethanol precipitation system is 75%, the ethanol is stopped, and at this time, the ethanol with the concentration can realize the precipitation and precipitation of the effective components from the water extract within 12-24 hours. It can be understood that the volume concentration of the ethanol is more than 80% when the ethanol precipitation treatment is carried out, so that the ethanol concentration of the ethanol precipitation system can be ensured to be 60-80% after the ethanol is added. The specific ethanol addition amount is calculated by the actual volume concentration of the selected ethanol and the volume of the water extract (in the calculation process, the volume of the water extract is regarded as the volume of water).
The second aspect of the invention provides a preparation method of the compound preparation, which comprises the following steps: decocting and leaching the raw materials including radix Rubiae, herba Houttuyniae and Glycyrrhrizae radix at least once, precipitating with ethanol, filtering, recovering ethanol solvent, and collecting extract; the extractum is processed to obtain the compound preparation; wherein the mass ratio of the madder, the cordate houttuynia and the liquorice is (3-30): (5-50): (3-30), wherein the mass percentage of the alizarin in the compound preparation is not less than 0.4 percent based on the mass of the madder.
In the practice of the invention, the following is used (3-30): (5-50): mixing radix Rubiae, herba Houttuyniae and Glycyrrhrizae radix at a mass ratio of (3-30) to obtain raw materials, decocting and leaching the raw materials in water at least once, separating the decoction and leached raw materials to obtain extractive solution, and precipitating the extractive solution with alcohol solvent to separate out effective components. And then filtering and collecting the separated active ingredients, recovering alcohol solvents in the active ingredients (for example, by a decompression concentration mode), and drying to finally obtain extractum (namely, a product obtained by carrying out water decoction leaching and alcohol precipitation on the raw materials). The extract is the effective component in the compound preparation, and the mass of the alizarin in the compound preparation is not less than 0.4% of the input mass of the alizarin based on the mass of the alizarin in the raw materials. And then, processing the extract by adopting pharmaceutically acceptable auxiliary materials to obtain the compound preparation.
In a specific preparation process, the crushed raw materials are generally required to be subjected to water boiling leaching after being crushed, so that the efficiency of water boiling leaching is improved.
The water-boiling leaching of the invention refers to the process of immersing raw materials in water and heating to boil the system, and the time of each water-boiling leaching is 1-2h. In a specific implementation process, the mass ratio of raw materials to water is not more than 1g to 10ml, and when the water boiling leaching is carried out for a plurality of times, the water quantity of each water boiling leaching can be reduced compared with the previous time.
In addition, in order to improve the efficiency of the alcohol precipitation, the extract solution needs to be concentrated (for example, reduced pressure concentration) before the alcohol precipitation to remove most of the extractant in the extract solution, so as to obtain an aqueous extract with a low water content.
Furthermore, the preparation method of the invention comprises the steps of carrying out at least two times of water decoction leaching on the raw materials, adding ethanol into the water extract to obtain an ethanol precipitation system, and carrying out ethanol precipitation for 12-24 hours, wherein the volume concentration of the ethanol in the ethanol precipitation system is 60-80%.
Specifically, the extracting solutions obtained after each water boiling and leaching are combined, the extracting solutions are concentrated to remove most of the extracting agent to obtain an aqueous extract, ethanol is added into the aqueous extract to obtain an ethanol precipitation system, when the volume concentration of the ethanol in the ethanol precipitation system is 60-80%, the ethanol is stopped being added and the mixture is kept stand to separate out the effective components in the system, and then the extract is obtained through filtration, reduced pressure concentration and drying. Wherein the standing 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 ethanol precipitation system was 75%. The actual amount of ethanol added can be calculated from the actual volume concentration of ethanol added and the volume of the aqueous extract (considered as the volume of water). For example, when the volume of the aqueous extract is 10ml and the actual volume concentration of the added ethanol is 95%, and when the volume concentration of the ethanol in the ethanol precipitation system is to be controlled to be 75%, 37.5ml of the ethanol with the actual volume concentration of 95% needs to be added to 10ml of the aqueous extract to obtain the ethanol precipitation system of the invention.
The compound preparation of the first aspect and the compound preparation prepared by the second aspect of the invention can adopt the method recorded in Chinese pharmacopoeia to control the quality of raw material sources and active ingredients.
Specifically, the method for identifying whether the raw materials of the compound preparation contain the madder comprises the following steps: taking 0.4g of the product powder, adding 5ml of diethyl ether, shaking for several minutes, filtering, adding 1ml of sodium hydroxide into the filtrate, shaking, standing to separate layers, enabling the water layer to be red, enabling the ether layer to be colorless, putting under an ultraviolet lamp (365 nm) for inspection, and enabling the light-blue fluorescence to prove that the raw materials of the compound preparation contain the madder.
The method for identifying whether the raw materials of the compound preparation contain houttuynia cordata comprises the following steps: 25g of the product is taken, chopped and placed in a round-bottomed flask, 250m of water is added, and a volatile oil tester is connected. Adding water from the upper end of the measuring instrument to fill the scale part, adding 1ml of ethyl acetate, continuously refluxing to the condenser tube, heating and refluxing for 4 hours, stopping heating, standing for a while, and separating an ethyl acetate layer to obtain a sample solution; the methyl n-nonone reference substance was additionally taken and ethyl acetate was added to prepare a 10ug solution per 1ml as a reference solution. And (3) performing a thin-layer chromatography (appendix VI B) test, taking 5ul of the sample solution and 2ul of the reference substance solution, respectively spotting on the same silica gel G thin-layer plate using sodium carboxymethylcellulose as an adhesive, spreading with n-hexane-ethyl acetate (9:1) as a developing agent, taking out, airing, and spraying dinitrophenylhydrazine for a test. In the chromatogram of the test sample, the same yellow spots appear at the positions corresponding to the chromatogram of the reference sample, so that the raw materials of the compound preparation are proved to contain cordate houttuynia.
The method for identifying whether the raw materials of the compound preparation contain liquorice comprises the following steps: taking 1g of the product powder, adding 40ml of diethyl ether, heating and refluxing for 1 hour, filtering, adding 30ml of methanol into the residues, heating and refluxing for 1 hour, evaporating filtrate to dryness, adding 40ml of water into the residues, extracting 3 times with 20ml of n-butanol each time, mixing n-butanol solutions, washing 3 times with water, evaporating to dryness, and dissolving 5ml of residue methanol to obtain a sample solution; preparing a control medicinal material solution by taking 1g of licorice control medicinal material according to the same method as the sample; and adding methanol into ammonium glycyrrhizate reference substance to prepare a solution containing 2mg per 1ml, wherein the solution is used as reference substance solution. By thin layer chromatography (appendix VI B) test, sucking 1-2ul of each of the above three solutions, respectively spotting on the same silica gel G thin layer plate prepared by 1% sodium hydroxide solution, spreading with ethyl acetate-formic acid-glacial acetic acid-water (15:1:1:2) as developing agent, taking out, air drying, spraying 10% ethanol solution of terahertz acid, heating at 105deg.C until the spots develop clearly, and inspecting under ultraviolet lamp (365 nm). The same orange fluorescent spot is displayed on the same position as the chromatogram of the reference substance, so that the liquorice is proved to be contained in the raw materials of the compound preparation.
The high performance liquid chromatography detection method for the content of the alizarin in the compound preparation comprises the following steps: 1) Octadecylsilane chemically bonded silica is used as a filler; methanol-acetonitrile-0.2% phosphoric acid solution (25:50:25) is used as a mobile phase; the detection wavelength is 250nm; the theoretical plate number is not lower than 4000 according to the peak of the alizarin and the alizarin hydroxyl; 2) Preparation of a control solution: precisely weighing alizarin reference substance and hydroxy alizarin reference substance, precisely weighing, adding methanol to prepare solutions containing 0.1mg of alizarin and 40ug of hydroxy alizarin per 1ml, respectively, to obtain alizarin reference substance solution and hydroxy alizarin reference substance solution; 3) Preparation of test solution: taking about 0.5g of the product powder (sieving with a second sieve), precisely weighing, placing in a conical bottle with a plug, precisely adding 100ml of methanol for sealing, weighing, standing overnight, performing ultrasonic treatment (power is 250W, frequency is 40 kHz) for 30 minutes, cooling, weighing again, supplementing the weight of the product with methanol, shaking uniformly, filtering, precisely measuring 50ml of the subsequent filtrate, evaporating to dryness, dissolving the residue in 20ml of a mixed solution of methanol and 25% hydrochloric acid (4:1), heating in a water bath for hydrolysis for 30 minutes, immediately cooling, adding 3ml of triethylamine, mixing uniformly, transferring to a 25ml measuring bottle, adding methanol to a scale, shaking uniformly, filtering, and obtaining the filtrate as a sample solution; 4) Respectively precisely sucking 10ul of two reference solutions and 20ul of test solution, and injecting into a liquid chromatograph for detection.
The third aspect of the present invention also provides a formulation composition comprising the compound formulation of the first aspect, and a hormone and/or a cell growth factor. Wherein the hormone comprises at least one of estriol, niestrol, ethinyl estradiol and E838, and the cell growth factor comprises at least one of interleukin IL-11, colony stimulating factor, mesenchymal stem cell MSC, stem cell growth factor SCF and thrombopoietin.
Specifically, the preparation composition comprises a compound preparation and hormone, a compound preparation and cell growth factor, and three different preparation composition forms of the compound preparation, the hormone and the cell growth factor.
Compared with the independent use of hormone and/or cell growth factor, the combination of the hormone and/or cell growth factor and the compound preparation provided by the invention can further reduce radiation damage and promote the effect of resisting radiation damage.
Further, in the process of combining the hormone with the compound preparation, more remarkable radiation damage resistance can be realized 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 nieiestrol is 0.01-0.5g, the usage amount of ethinyl estradiol is 0.01-0.5g, and the usage amount of E838 is 0.01-0.5g.
The fourth aspect of the invention also provides an application of the compound preparation or the preparation composition in preparing medicines for treating lung lesions caused by radioactive injury, leukopenia caused by radiotherapy and chemotherapy or chemical poison, lung or respiratory tract lesions caused by virus infection and chest tumors.
Further, the lung lesions caused by radiation injury include pneumonia or pulmonary fibrosis diseases, and the lung or respiratory lesions caused by virus infection include pneumonia or respiratory diseases caused by coronavirus infection.
The invention is not limited to radiation sources for radiation injury, and includes, for example, but is not limited to, radiation sources from medical and military fields. Illustratively, the radiation sources in the medical field include radiation sources that are received during detection and treatment, and the radiation sources in the military field include burial bomb radiation.
The recurrent preparation provided by the invention is an innovation in the form of 'monarch, minister, assistant and guide' formula in the traditional Chinese medicine field, and is prepared by taking three herbs with special proportions as raw materials for water extraction and alcohol precipitation treatment, and the three herbs complement each other to synergistically improve lung lesions caused by radioactive injury, leukopenia caused by chemoradiotherapy or chemical poison and lung or respiratory tract lesions caused by virus infection, thereby developing a broad prospect for the research and development of new traditional Chinese medicines.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
The preparation method of the extract (the active ingredient in the compound preparation) of the embodiment comprises the following steps:
1) Respectively pulverizing radix Rubiae 15g, herba Houttuyniae 40g and Glycyrrhrizae radix 15g, mixing, decocting with 500ml water, leaching for 1 hr, and press filtering to obtain residue and extractive solution; decocting the residue with 400ml water for 1 hr, press filtering, mixing the two decoctions, and concentrating under reduced pressure to obtain 10ml water extract;
2) Adding a proper amount of ethanol into the water extract to obtain an ethanol precipitation system (the addition amount of the ethanol is based on the volume concentration of the ethanol in the ethanol precipitation system of 75 percent), standing for 16 hours, filtering, concentrating the filtrate under reduced pressure, and drying to obtain the extract of the embodiment. Through detection, the ratio of the mass of the alizarin in the extract to the input mass of the alizarin raw material is not less than 0.4 percent.
Wherein, the quality standard of the compound preparation meets the related requirements of Chinese pharmacopoeia of madder, cordate houttuynia and liquorice.
Example 2
The preparation method of the extract of this example is basically the same as that of example 1, except that in step 1), 15g of madder, 40g of houttuynia cordata and 10g of licorice are used. Through detection, the ratio of the mass of the alizarin in the extract to the input mass of the alizarin raw material is not less than 0.4 percent. Wherein, the quality standard of the compound preparation meets the related requirements of Chinese pharmacopoeia of madder, cordate houttuynia and liquorice.
Example 3
The preparation method of the extract of this example is basically the same as that of example 1, except that in step 1), 15g of madder, 40g of houttuynia cordata and 5g of licorice are used. Through detection, the ratio of the mass of the alizarin in the extract to the input mass of the alizarin raw material is not less than 0.4 percent. Wherein, the quality standard of the compound preparation for the screening test meets the related requirements of Chinese pharmacopoeia of madder, cordate houttuynia and liquorice.
Example 4
The preparation method of the extract of this example is basically the same as that of example 1, except that in step 1), 15g of madder, 30g of houttuynia cordata and 10g of licorice are used. Through detection, the ratio of the mass of the alizarin in the extract to the input mass of the alizarin raw material is not less than 0.4 percent. Wherein, the quality standard of the compound preparation meets the related requirements of Chinese pharmacopoeia of madder, cordate houttuynia and liquorice.
Example 5
The preparation method of the extract of this example is basically the same as that of example 1, except that in step 1), 15g of madder, 20g of houttuynia cordata and 10g of licorice are used. Through detection, the ratio of the mass of the alizarin in the extract to the input mass of the alizarin raw material is not less than 0.4 percent. Wherein, the quality standard of the compound preparation meets the related requirements of Chinese pharmacopoeia of madder, cordate houttuynia and liquorice.
Example 6
The preparation method of the extract of this example is basically the same as that of example 1, except that 10g of madder, 30g of houttuynia cordata and 10g of licorice are used in step 1). Through detection, the ratio of the mass of the alizarin in the extract to the input mass of the alizarin raw material is not less than 0.4 percent. Wherein, the quality standard of the compound preparation meets the related requirements of Chinese pharmacopoeia of madder, cordate houttuynia and liquorice.
Example 7
The preparation method of the extract of this example is basically the same as that of example 1, except that in step 1), 5g of madder, 30g of houttuynia cordata and 10g of licorice are used. Through detection, based on the mass of the madder, the ratio of the mass of the madder element in the extract to the input mass of the madder raw material is not less than 0.4%, wherein the quality standard of the compound preparation meets the related requirements of Chinese pharmacopoeia of madder, cordate houttuynia and liquorice.
Test example 1 Effect of Compound preparation on total number of peripheral white blood cells of mice
1. Material preparation
The extracts of examples 1-7 were added to 2wt% aqueous starch solutions, respectively, to prepare 7 sample solutions having a concentration of 20mg/0.2ml (20 mg of extract per 0.2ml of aqueous starch solution).
Experimental animals: 70 male and female half KM mice are used, the day-old is 6-8 weeks, and the weight is 20-24 g. All purchased from beijing laboratory animal center, laboratory animal production license number: SCXK (Beijing) 2018-0010. Mice were randomly divided into 7 groups of 10 mice each.
2. Test method
Of the 7 groups of mice, each group of mice corresponds to 1 group of the above sample solutions for gastric lavage, and the amount of gastric lavage of each mouse is 0.2ml.
The total number Q of peripheral blood leucocytes before and after the intragastric administration for 4, 8, 12 and 16 hours was detected and the peripheral blood leucocyte 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, P < 0.01 compared with each test group
As can be seen from table 1, the compound preparation of the present invention has a remarkable effect on increasing the white blood cell count of mice, especially when the mass ratio of madder, cordate houttuynia and licorice is (10-15): (30-40): (10-15) wherein the effect is better when the mass ratio of the madder, the cordate houttuynia and the liquorice is 10:30: at 10, the effect is most prominent.
Test example 2 Effect of different doses of Compound preparation on peripheral blood leukocytes of dogs
The purpose is as follows: the test example mainly observes the effect of different doses of the compound preparation on increasing the peripheral blood leucocytes of normal dogs
1. Material preparation
Test drug: the extract of example 6.
Control drug: madder double-fat tablet, 100 mg/tablet produced by Jiangsu Ji Beier pharmaceutical company limited.
Experimental animals: normal healthy male puppies 80, in four groups of 20. Three groups (15 g group of three herbs, 10g group of three herbs and 5g group of three herbs) are used as detection objects of test drugs, and one group (madder group) is used as detection objects of control drugs. In the group of 15g of Sancao, the weight of each dog is 7.71+/-0.61 kg; in the 10g group of the three grass, the weight of each dog is 7.91+/-0.66 kg; in the group of 5g of Sancao, the weight of each dog is 7.91+/-0.66 kg; in the madder group, each dog had a weight of 7.7.+ -. 0.77 kg. The differences are not statistically significant and comparable in comparison with the general cases of the groups.
2. Test method
Three grass 15g group: disposable oral test drug for dogs, 15 g/dog
Three grass 10g group: disposable oral test drug for dogs, 10 g/dog
Three grass 5g group: disposable oral test drug for dogs, 5 g/dog
Madder group: making dog take radix Rubiae double lipid tablet at a time, 100 mg/dog
The total number of peripheral blood leukocytes Q was measured before and after administration for 12, 24, 48 and 72 hours, and the peripheral blood leukocyte achievement rate D was calculated, and the results are shown in table 2.
TABLE 2
In Table 2, P < 0.01 compared to the madder group and #P < 0.05 compared to the Sancao 10g group
As can be seen from Table 2, peripheral blood leukocytes began to rise for 12 hours after each group administration, and began to fall for 48 hours after the administration, gradually returning to the pre-drug level. Wherein, the effect of increasing white blood cells of the group of 15g of the three grass and the group of 10g of the three grass is obvious, and is superior to that of the group of the madder, and the difference has statistical significance (P is less than 0.01). Except 72 hours after the medicine, the three grass 15g group is better than the three grass 10g group, and other differences have no statistical significance.
Test example 3 Effect of Compound preparation on peripheral blood leukocytes of patients suffering from benzene poisoning
The purpose is as follows: the effect of the compound preparation on the increase of peripheral blood leucocytes of patients suffering from chronic benzene poisoning is mainly observed.
1. Material preparation
Test drug: taking the compound preparation in the example 6, adding proper auxiliary materials, and preparing the three-herb medicinal granule compound preparation with the weight of 10g per bag, wherein each bag of three-herb medicinal granule compound preparation contains 5g of extractum.
Control drug: madder double-fat tablet, 100 mg/tablet produced by Jiangsu Ji Beier pharmaceutical company limited.
Test patient: 40 cases of chronic benzene poisoning patients, 20 cases of each group, accord with the diagnosis of leucopenia of practical science, and the total number of peripheral blood leucocytes is less than 4 multiplied by 10 9 and/L. Two groups, three groups and madder groups are distributed according to the order of 1:1.
Wherein, the three grass groups are 20 cases, 7 cases, 13 cases, 33-56 cases, 44.1+/-7.42 cases, 12 cases with benzene and 8 cases with petroleum gas.
20 cases of madder groups, 12 cases of men, 8 cases of women, ages 35-55, average ages of 45.1+/-5.33, 11 cases of benzene contact and 9 cases of petroleum gas benzene contact.
The two groups of general conditions are compared, and the difference has no statistical significance and is comparable.
2. Test method
Three grass groups: each person orally takes 2 bags of the three-herb medicinal granule compound preparation every day.
Madder group: about 100mg of madder double fat is taken per person every day.
The treatment effect was evaluated after 1 course of treatment, 28 days. Two groups of patients were subjected to conventional peripheral blood leukocyte detection and peripheral blood leukocyte achievement rate D was calculated 3 days, 7 days, 14 days, 21 days, and 28 days before treatment. Before and after treatment, 2 groups of patients were examined for chest film, electrocardiogram, liver and kidney functions, and changes in clinical symptoms were recorded.
3. Detection result (SPSS 17.0 software is adopted to process data, t test is adopted to metering data, and x2 test is adopted to counting data)
1) The total effective rate of clinical effects is shown in Table 3
The effect is shown: continuous 2 times white blood cell meter after stopping exposure to pathogenic factors Number recovery normal range (+.gtoreq.5X10) 9 /L) or < 2X 10 9 The rise of/L reaches 4X 10 9 Time above/L is shorter and meaningful than control;
the method is effective: the white blood cell count is increased by 100% compared with the white blood cell count before treatment for 2 continuous examinations;
invalidation: the number of white blood cells after treatment is not obviously improved, which is less than 100% higher than that before treatment;
total effective rate= (effective + effective) number of cases/total number of cases x 100%.
TABLE 3 Table 3
| Group of | Number of examples | Has obvious effect | Effective and effective | Invalidation of | Total effective rate (%) |
| Three grass groups | 20 | 16(80.0) | 2(10.0) | 2(10.0) | 18(90.0)** |
| Rubiae group | 20 | 9(45.0) | 4(20.0) | 7(35.0) | 13(65.0) |
In Table 3, P < 0.01 compared to the Rubia group
As shown in Table 3, the total effective rate of the three groups is 90%, the madder group is 65%, and the difference between the two groups is statistically significant (P < 0.01). The compound preparation of the invention has better effect on peripheral blood leucocyte elevation of patients with chronic benzene poisoning than madder double fat.
2) Total peripheral leukocyte count Q (mean.+ -. Standard deviation) and peripheral leukocyte achievement rate D, the results are shown in Table 4
TABLE 4 Table 4
In Table 4, P < 0.01 compared to the Rubia group
As can be seen from table 4, the three-grass group showed a significant leukocyte-increasing effect after 7 days of treatment, and the madder group showed a significant leukocyte-increasing effect after 14 days of treatment. The total number of white blood cells is obviously higher than that of the madder group in 7, 14, 21 and 28 days after the treatment of the three grass groups, and the comparison difference of the two groups has statistical significance (P is less than 0.01).
3) Clinical symptom change and side effects of drugs
The clinical symptoms of the three grass groups are quickly improved, and the complaint symptoms such as dizziness, hypodynamia and the like of most patients are relieved or eliminated after the medicine is taken for 2 weeks; the clinically relevant symptoms were only partially alleviated after 3 weeks of treatment in most patients in the madder group. By comparing the electrocardiogram, liver and kidney functions and clinical symptoms of patients before and after treatment, no obvious side effect is found in the two groups of patients.
Test example 4 Effect of Compound preparation on leukopenia caused by radiotherapy and chemotherapy
The purpose is as follows: mainly observes the treatment effect of the compound preparation on peripheral blood leucopenia of patients with radiotherapy and chemotherapy tumor.
1. Material preparation
Test drug: the same as in test example 3.
Control drug: madder double-fat tablet, 100 mg/tablet produced by Jiangsu Ji Beier pharmaceutical company limited.
Test patient: 64 cases of tumor patients who receive radiotherapy and chemotherapy to cause leucopenia are in line with
Leucopenia diagnosis of practical internal science, total number of peripheral blood leucocyte is less than 4 x 10 9 and/L. Three groups of radix Rubiae and 32 groups of radix Rubiae were randomly separated according to the order of admission.
Of these, 30 cases of Sancao group, 10 cases of female, 22 cases of male, ages 39-72, and average ages 58.6.+ -. 9.601. Typically, the Carlsberg bisects 60.6.+ -. 6.19. Of the 30 cases, 22 cases of chemotherapy and 8 cases of radiotherapy. Of the 32 cases, 8 cases of lung cancer, 7 cases of stomach cancer, 6 cases of colon cancer, 7 cases of rectal cancer and 4 cases of breast cancer.
32 cases of madder group, 11 cases of female, 21 cases of male, ages 35-77, and average ages of 56.4+/-9.524. Typically, the Carlsberg bisects 60.9.+ -. 6.41. Of the 32 cases, 23 cases of chemotherapy and 9 cases of radiotherapy. Of the 32 cases, 9 cases of lung cancer, 8 cases of stomach cancer, 6 cases of colon cancer, 6 cases of rectal cancer and 3 cases of breast cancer.
The two groups of general conditions are compared, and the difference has no statistical significance and is comparable.
2. Test method
Three grass groups: each person orally takes 2 bags of the three-herb medicinal granule compound preparation every day.
Madder group: about 100mg of madder double fat is taken per person every day.
The treatment effect was evaluated after 1 treatment course for 28 days, and the radiotherapy and chemotherapy were stopped during the treatment period. Peripheral blood leucocytes were routinely tested 3 days, 7 days, 14 days, 21 days, 28 days after treatment of both groups of patients. Before and after treatment, the patients were examined for chest film, electrocardiogram, liver and kidney function, and changes in clinical symptoms were recorded.
3. Detection result (SPSS 17.0 software is adopted to process data, t test is adopted to metering data, and x2 test is adopted to counting data)
1) The total clinical effective rate and the results are shown in Table 5
The effect is shown: after stopping exposure to the causative agent, the normal range (+.gtoreq.5X10) was restored by 2 consecutive white blood cell counts 9 /L) or < 2X 10 9 The rise of/L reaches 4X 10 9 Time above/L is shorter and meaningful than control;
The method is effective: the white blood cell count is increased by 100% compared with the white blood cell count before treatment for 2 continuous examinations;
invalidation: the number of white blood cells after treatment is not obviously improved, which is less than 100% higher than that before treatment;
total effective rate= (effective + effective) number of cases/total number of cases x 100%.
TABLE 5
| Group of | Number of examples | Has obvious effect | Effective and effective | Invalidation of | Total effective rate (%) |
| Three grass groups | 32 | 23(71.9) | 7(21.9) | 2(6.25) | 93.8** |
| Rubiae group | 32 | 15(46.9) | 6(18.8) | 11(34.4) | 65.6 |
In Table 5, P < 0.01 compared to the Rubia group
As shown in Table 5, the total effective rate of the three groups of grass is 93.8%, the total effective rate of the madder group is 65.6%, and the difference between the two groups is statistically significant (P < 0.01). The effect of the compound preparation for increasing peripheral blood leucocyte is better than that of madder double fat.
2) Total peripheral leukocyte count (mean.+ -. Standard deviation), results are shown in Table 6
TABLE 6
In Table 6, P < 0.01 compared to prior to treatment
As can be seen from table 6, the three-grass group showed a significant leukocyte-increasing effect after 7 days of treatment, and the madder group showed a significant leukocyte-increasing effect after 14 days of treatment. The total number of white blood cells is obviously higher than that of the madder group in 7, 14, 21 and 28 days after the treatment of the three grass groups, and the comparison difference of the two groups has statistical significance (P is less than 0.01).
3) Clinical symptom change and side effects of drugs
The clinical symptoms of the three grass groups are quickly improved, and the complaint symptoms such as dizziness, hypodynamia and the like of most patients are relieved or eliminated after the medicine is taken for 2 weeks; the clinically relevant symptoms were only partially alleviated after 3 weeks of treatment in most patients in the madder group. By comparing the electrocardiogram, liver and kidney functions and clinical symptoms of patients before and after treatment, no obvious side effect is found in the two groups of patients.
Test example 5 Effect of Compound preparation on chest tumor patients
The purpose is as follows: the effects of preventing and treating radiation pneumonic pulmonary fibrosis, resisting tumor, reducing incidence rate of respiratory tract infection, increasing peripheral blood leucocyte, enhancing immunity and improving quality of life by simultaneously taking the compound preparation during radiotherapy of patients with chest tumor are observed.
1. Material preparation
Test drug: the same as in test example 3.
Control drug: madder double-fat tablet, 100 mg/tablet produced by Jiangsu Ji Beier pharmaceutical company limited.
Test patient: cases were derived from 60 breast tumor patients hospitalized and determined to be in need of radiation therapy, and met the following inclusion criteria:
(1) KPS bisects ∈ 80 minutes;
(2) the pathology proves that the medicine is a patient with malignant tumor of chest (lung cancer, esophagus cancer and thymus cancer);
(3) none of the patients received treatment with definite effects on immune function before radiotherapy;
(4) the radiotherapy process is smoothly finished, the interruption time of radiotherapy is not more than 1 week, and the immunity is checked by timely blood sampling before and after the radiotherapy.
Three groups of three herbs and 30 groups of madder are allocated to 60 patients with chest tumor according to the number of the order of treatment by adopting a completely random grouping design method.
Wherein, the three grass groups, 20 men, 10 women, the average age of 58.6+/-9.91 (39-72) years, 19 lung cancer, 7 esophageal cancer and 4 adenocarcinoma.
Madder group, 21 men, 9 women, average age 56.8±9.67 (35 to 77) years, 21 lung cancer, 6 esophageal cancer, and 3 adenocarcinoma.
The two groups of general conditions are compared, and the difference has no statistical significance and is comparable.
2. Test method
Both cases were treated with three-dimensional conformality or intensity modulation for 6 weeks of treatment. The patients in the three grass groups are orally taken with 2 bags of the three grass granule compound preparation by each person every day during radiotherapy; the madder group patients were treated with radiotherapy while orally taking madder double lipid at 100 mg/day/person.
1) Collecting blood samples
Venous blood is used for detecting total peripheral blood leucocyte and lymphocyte before, during and after radiotherapy of a patient. Determination of CD3, CD4, CD8, CD4/CD8 and CD56 in peripheral blood by Epics-XL-II type flow cytometry.
2) Immune function diagnosis
The standard is established by adopting the hospital flow cell research laboratory to detect and analyze the immune function indexes of normal people in the normal range of each immune function index. Immune function diagnostic criteria: any of CD3, CD4/CD8 below the normal range is diagnosed as hypoimmunity.
3) Clinical therapeutic standard for anti-tumor
And after the radiotherapy is finished, the chest and abdomen CT is rechecked, the clinical curative effect evaluation is carried out by comparing the changes of the focus before and after the radiotherapy, the clinical curative effect evaluation standard adopts an RBCIST solid cancer curative effect evaluation system, and the clinical curative effect is divided into four grades.
4) Grading standard for acute radiation injury of lung
For the curative effect evaluation of the lung acute radiation injury, the incidence rate of radiation pneumonitis and the incidence rate of radiation pulmonary fibrosis are taken as main indexes, and the degree of the lung acute radiation injury is evaluated by adopting an American tumor radiation therapy cooperative group (RTOG) acute radiation injury grading standard.
5) Clinical symptom observation and evaluation
Clinical symptoms of respiratory tract infection were observed simultaneously during radiotherapy, and the incidence of respiratory tract infection was compared in both groups.
3. Detection result (SPSS 13.0 statistical software is adopted for data processing, analysis of variance and t test are carried out according to data characteristics, and P < 0.05 is taken as difference to have statistical significance)
1) The incidence of radiation pneumonitis and radiation pulmonary fibrosis is shown in Table 7
TABLE 7
In Table 7, P < 0.05, P < 0.01 compared to the Rubia group
As shown in Table 7, the incidence of radiation pneumonitis and pulmonary fibrosis was 23.33% and 13.33% respectively, and the incidence of madder was 53.33% and 30.0% respectively, and the difference was statistically significant (P < 0.01, P < 0.05) in the two groups. The compound preparation provided by the invention can obviously reduce the incidence rate of radiation pneumonitis and reflex pulmonary fibrosis in chest malignant tumor radiotherapy.
2) Incidence of respiratory tract infections, results are shown in Table 8
TABLE 8
| Group of | Respiratory tract infection (example number) | Incidence (%) |
| Three grass groups | 2 | 6.67** |
| Rubiae group | 8 | 26.7 |
In Table 8, P < 0.01 compared to the Rubia group
As shown in Table 8, the incidence rate of respiratory tract infection of the three grass groups during treatment is 6.67%, the incidence rate of respiratory tract infection of the madder group is 26.7%, and the difference between the two groups has statistical significance (P is less than 0.05), which suggests that the compound preparation of the invention is beneficial to reducing the incidence rate of respiratory tract infection.
3) The total number of peripheral blood leukocytes and lymphocytes, the results are shown in Table 9
TABLE 9
In table 9, P < 0.05 compared to the madder group; * P < 0.01
As shown in Table 9, the ratio of the normal numbers of peripheral leucocytes and lymphocytes of the three grass groups was higher than that of the madder group, and the differences were statistically significant (P < 0.05, P < 0.01) in both groups.
4) Immune function, results are shown in Table 10
Table 10
| Sancao group 30 | Rubiae 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, P < 0.01 compared to the Rubia group
As can be seen from Table 10, the immune function of the three grass groups increased and CD8 decreased in comparison with the madder group, and the differences were all statistically significant (P < 0.01).
5) Clinical therapeutic effect of anti-tumor, the results are shown in Table 11
TABLE 11
| Group of | Number of cases | CR | PR | PD | Effective rate (%) |
| Three grass groups | 29 | 3 | 24 | 2 | 93.1** |
| Rubiae group | 28 | 0 | 11 | 17 | 39.3 |
In Table 11, P > 0.01 compared with the Rubia group
As shown in Table 11, the efficacy of the treatment was evaluated at the end of radiotherapy in two groups of patients, and the efficacy was 93.1% in the three groups of CR 3, PR 24 and PD 2. The effective rate of the madder group CR 0 cases, PR 11 cases and PD 17 cases is 39.3%, and the difference has no statistical significance (P is more than 0.01) when the two groups are compared.
Test example 6 observation of the efficacy of Compound preparation on acute radiation disease in mice
The purpose is as follows: the effect of the combination of the compound preparation, estriol and interleukin (IL-11) on the survival rate and hematopoietic function of the mice under control for 30 days was observed.
1. Material preparation
Test drug: the extract of example 6 was added to a 2wt% aqueous starch solution to prepare a test drug solution having a concentration of 100mg/0.2ml (100 mg extract per 0.2ml aqueous starch solution).
Estriol raw material: estriol was formulated as a solution of estriol at a concentration of 0.1mg/0.2ml (0.1 mg estriol per 0.2ml of 2wt% starch in water) and 0.05mg/0.2ml (0.05 mg estriol per 0.2ml of 2wt% starch in water). Estriol feed stock is provided by the military medical sciences laboratory.
IL-11 raw material: IL-11 was formulated at a concentration of 0.1mg/0.2ml (0.1 mg IL-11 per 0.2ml of 2wt% aqueous starch solution). IL-11 raw material Qilu pharmaceutical Co.
Experimental animals: male KM mice, day-old 6-8 weeks, body weight 22-26 g, 270. Purchased from the beijing laboratory animal center, laboratory animal production license number: SCXK (Beijing) 2018-0010. 180 animals are randomly divided into 9 groups, and 20 animals in each group are observed after irradiation; 90 were used to observe hematopoietic indicators after irradiation, animals were randomly divided into 9 groups of 10 animals each.
2. Test method
Animal survival and post-irradiation hematopoietic index at 30 days post-irradiation observation are the sameThe animals in the group were dosed in the same manner. Using the military medical radiology institute 60 The Cor radiation source irradiates the mice in the organic glass partition, and the distance from the source is 4.00m. Observing the survival rate of the animal by one whole body irradiation of 8.5Gy; observing hematopoietic function index animal, and irradiating the animal with whole body at a dose rate of 200-220 cGy/min at a time of 7.5 Gy.
Group 1: normal control group, without any treatment;
group 2: blank, immediately after irradiation and on day 3 after irradiation, administration by gastric lavage, physiological saline/0.2 ml/dose;
group 3: test drug, immediately after irradiation and on day 3 after irradiation, was administered by gavage at 0.2 ml/dose;
group 4: 0.1mg/0.2ml of estriol solution, and immediately after irradiation, 0.2 ml/dose is administered by gastric lavage;
group 5: IL-11 solution, immediately after irradiation, was injected intraperitoneally with 0.2 ml/l;
group 6: test drug (dose with group 3) +0.1mg/0.2ml estriol solution (dose with group 4);
group 7: test drug (dose with group 3) +il-11 solution (dose with group 5);
group 8: test drug (dose with group 3) +0.05mg/0.2ml estriol solution (0.2 ml/min.)) +IL-11 solution (dose with group 5);
Group 9: test drug (dose with group 3) +0.1mg/0.2ml estriol solution (dose with group 4) +IL-11 solution (dose with group 5)
1) Survival observations of mice 30 days after irradiation
The mice were observed for memory activity for 30 days from the start of irradiation, the state and death number of the mice were recorded daily, and the survival rate of the mice for 30 days was calculated as follows.
Survival rate after 30 days = survival number after irradiation/experimental number
2) BMNC and spleen nodule determination:
mice were cervical spin-killed on day 8 post-irradiation, BMNC (X106) (The number of nucleated call in bone marrow): the bone marrow is washed with a white blood cell dilution to obtain a suspension, and the bone marrow cells are collected to obtain a bone marrow cell suspension, wherein the cell activity is 95% or more by trypan blue identification, and the total number of nucleated cells in the bone marrow is calculated under a microscope. Spleen nodules (colong forming unit of spleen, CFU-S) were obtained from mice in a sterile condition, weighed, and spleen weight index calculated according to the formula. Spleen weight index = spleen weight (mg)/mouse weight (g). Spleen was fixed in Bouin' S solution, and after 6 hours, the CFU-S number of the surface hematopoietic foci of spleen was measured.
3. Test results
1) Survival of the mice under control for 30 days, and the results are shown in Table 12
Table 12
| Group of | Number of experiments | Number of survival | Survival (%) | Average survival day 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, comparison of #, with the blank control group, comparison of # with the three herbal single drug group
2) The results of the effect on hematopoietic function of the mice are shown in Table 13
TABLE 13
| Group of | Number of animals | BMNC(X10 6 ) Femur | CFU-S (individual/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 that: * Comparison with the blank control group, # comparison with the three herbal single drug group
As can be seen from tables 12 and 13, the survival rate, the bone marrow nucleated cell number, the CFU-S number and the spleen index of the single-drug group of the test drug solution controlled mice are all obviously superior to those of the blank control group, and the difference is statistically significant (P is less than 0.01); the test medicine is combined with estriol (0.05 mg or 0.1 mg) and interleukin-11 respectively, and the radiation damage resistance is obviously improved. Estriol and IL-11 have certain radiation damage resistance.
Therefore, the compound preparation can be used for patients with tumor radiotherapy and chemotherapy, improves the treatment effect of tumor radiotherapy and chemotherapy, increases peripheral blood leucocytes and reduces the incidence rate of bacterial infection; can be used alone or in combination with estrogen, interleukin, etc. for emergency.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (10)
1. A compound preparation is characterized in that the effective components of the compound preparation are products obtained by sequentially carrying out water extraction treatment and alcohol precipitation treatment on raw materials comprising madder, cordate houttuynia and liquorice; the mass ratio of the madder, the cordate houttuynia and the liquorice is (3-30): (5-50): (3-30) and, based on the mass of the madder, the mass percentage of the alizarin in the compound preparation is not less than 0.4%.
2. The compound preparation according to claim 1, wherein the mass ratio of the madder, the houttuynia cordata and the licorice is (10-15): (30-40): (10-15).
3. The compound preparation according to claim 1 or 2, further comprising acceptable excipients; the dosage forms of the compound preparation comprise granules, capsules, tablets, pills, oral liquid, spray and tea.
4. The compound preparation according to claim 1, wherein the water extraction treatment comprises: and (3) carrying out at least one-time water decoction leaching on the raw materials to obtain an aqueous extract.
5. The compound formulation of claim 4, wherein the alcohol precipitation treatment comprises:
adding ethanol into the water extract to obtain an ethanol precipitation system, and precipitating with ethanol for 12-24 hours, wherein the volume concentration of ethanol in the ethanol precipitation system is 60-80%.
6. A method for preparing the compound preparation according to any one of claims 1 to 5, comprising the steps of:
decocting and leaching the raw materials including radix Rubiae, herba Houttuyniae and Glycyrrhrizae radix at least once, precipitating with ethanol, filtering, recovering ethanol solvent, and collecting extract; the extractum is processed to obtain the compound preparation;
wherein the mass ratio of the madder, the cordate houttuynia and the liquorice is (3-30): (5-50): (3-30), and the mass percentage of the alizarin in the compound preparation is not less than 0.4 percent based on the mass of the madder.
7. The method according to claim 6, wherein the raw materials are subjected to at least two times of water decoction leaching, ethanol is added into the water extract to obtain an ethanol precipitation system, and then the ethanol precipitation system is subjected to ethanol precipitation for 12-24 hours, wherein the volume concentration of the ethanol in the ethanol precipitation system is 60-80%.
8. A formulation composition comprising a compound formulation, hormone and/or cell growth factor according to any one of claims 1 to 5;
the hormone comprises at least one of estriol, niestrol, ethinyl estradiol and E838;
the cell growth factor comprises at least one of interleukin IL-11, colony stimulating factor, mesenchymal stem cell MSC, stem cell growth factor SCF and thrombopoietin.
9. Use of a compound preparation according to any one of claims 1-5 or a preparation composition according to claim 8 for the preparation of a medicament for the treatment of lung lesions due to radiation damage, leukopenia due to chemoradiotherapy or chemical toxicants, lung or respiratory lesions due to viral infections, breast tumors.
10. The use according to claim 9, wherein the lung lesions caused by radiation injury comprise pneumonia or pulmonary fibrosis disease; lung or respiratory lesions caused by viral infections include pneumonia or respiratory diseases caused by coronavirus infections.
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| CN1108567A (en) * | 1994-11-18 | 1995-09-20 | 浙江天野保健品有限公司 | Cordate houttuynia nutrient oral liquor |
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| CN1108567A (en) * | 1994-11-18 | 1995-09-20 | 浙江天野保健品有限公司 | Cordate houttuynia nutrient oral liquor |
| CN101234181A (en) * | 2008-02-04 | 2008-08-06 | 邵振启 | Medicament for preventing and treating leukopenia used in tumor radiotherapy and chemotherapy course |
| CN103211269A (en) * | 2013-05-20 | 2013-07-24 | 武汉药谷科技开发有限公司 | Distillate medicinal water for preventing and resisting electromagnetic radiation |
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