CN115737695A

CN115737695A - Pharmaceutical preparation for treating various malignant tumors, leukemia and chronic bronchitis, and its preparation method and quality control method

Info

Publication number: CN115737695A
Application number: CN202211460727.9A
Authority: CN
Inventors: 郎伟君
Original assignee: Letai Pharmaceutical Co ltd
Current assignee: Letai Pharmaceutical Co ltd
Priority date: 2022-11-17
Filing date: 2022-11-17
Publication date: 2023-03-07

Abstract

The invention discloses a pharmaceutical preparation for treating various malignant tumors, leukemia and chronic bronchitis, and a preparation method and a quality control method thereof, wherein the pharmaceutical preparation is prepared from 1-1000 parts of marsdenia tenacissima, 1-200 parts of dextrin, 1-30 parts of starch and 1-20 parts of magnesium stearate. According to the method, the soaking solution in the marsdenia tenacissima extraction process is changed from water to ethanol solution, the extraction temperature is controlled in different ranges each time, the lifting filter screen device is used for extraction, and the steam distillation method and the decocting method are combined, so that the palmitic acid in the extract is removed, and the transfer rate of the extract is greatly improved. Secondly, the invention changes the adding amount and the adding sequence of the auxiliary materials and the extract in the granulating process, gradually dilutes the extract, and finally adds three layers of propellers for stirring when evenly mixing in a swing type granulator, thereby leading the content of chlorogenic acid in the prepared medicinal preparation to be even and achieving stable treatment effect.

Description

Pharmaceutical preparation for treating various malignant tumors, leukemia and chronic bronchitis, and its preparation method and quality control method

Technical Field

The invention relates to a pharmaceutical preparation for treating various malignant tumors, leukemia and chronic bronchitis, a preparation method and a quality control method thereof, belonging to the technical field of medicines.

Background

Cancer has become a common disease in human life, namely the disease of cancer discoloration, and the nightmare is met by all families after the diagnosis is confirmed. It not only can destroy the patient, but also can bring mental, life and economic pressure to the family members and relatives and friends of the patient. Cancer is a group of cells growing rapidly, because the DNA of the cells in vivo is mutated, or the internal environment and external environment are changed, resulting in the sudden growth of the cells and uncontrolled reproduction. Moreover, these cells are invasive and tend to run around the body. Cancer cells are caused by DNA chain gene mutation, and the abnormality of these proteins leads to protein destruction variation and DNA change, and then leads to protein change, the protein is the generated cells, the cells grow fiercely, and the internal environment is changed into the general cachexia state. Cancer can cause pain to patients, and space occupying diseases can cause pressure pain, local lumps and discomfort to patients, and is the most important thing. Cachexia affects absorption normal function, affects all normal functions, leads to loss of life, survivability, and finally death due to cancer. The mortality rate of cancer is generally above 80%, and most children have already metastasized when they are found, so most cancers are very serious. Cancer, a space-occupying lesion, refers to a local mass formed by abnormal proliferation of local tissue cells under the action of various tumorigenic factors, and can be divided into benign tumors and malignant tumors according to the pathological morphology, differentiation maturity, growth mode and degree of harm to patients, wherein benign tumors are generally called tumors, malignant tumors are generally called cancers, cancers are malignant tumors originating from epithelial tissues, sarcomas are malignant tumors originating from mesenchymal tissues, and cancers in popular terms refer to all malignant tumors practically. The types of malignant tumors are also diverse and generally include several aspects: first, malignant tumors derived from epithelial tissues are clinically called true cancers, such as breast cancer, bronchogenic lung cancer, primary liver cancer, pancreatic cancer, colon cancer, and the like. Second, malignant tumors derived from mesenchymal tissues are called sarcomas, such as osteosarcoma, ewing's sarcoma, and the like. Third, malignant tumors derived from embryonic tissues are called blastoma, such as nephroblastoma, neuroblastoma, and the like. Fourth, malignant tumors derived from lymphohematopoietic origin are called malignant lymphoma.

Leukemia is mostly acquired in the acquired days, and most of leukemia is caused by chromosome aberration caused by acquired factors, so that acute leukemia and chronic leukemia appear. The acquired factors include exposure to harmful substances such as benzene, chlorine, pesticides, and chemicals in hair dye, and excessive accumulation of the harmful substances can cause chromosome aberration and tumor diseases. In addition, the contact rays accumulated to a certain dosage can also cause chromosome aberration and the appearance of blood tumor. And repeated inflammatory stimuli, such as persistent viral infections, repeatedly affecting immune function, and in the case of immunodeficiency, leukemia is likely to occur. Some patients are genetically predisposed to the tumor family, i.e., they are predisposed to neoplastic disease throughout the family, including both body and hematological tumors. However, the disease is not immediate after birth, and may be induced by some causes at a certain age.

The number of people suffering from bronchitis, asthma and respiratory diseases, particularly bronchitis, is increasing, most of the people do not pay attention to the disease when the symptoms are mild, and serious consequences are caused. Chronic bronchitis is actually a group of diseases. The symptoms of chronic bronchitis mainly include tracheitis, cough, chronic cough, expectoration, some people are accompanied by asthma, and other diseases may be complicated by the patients. Since this was previously thought to be a disease and now is thought to be a combination of diseases, it is necessary for chronic bronchitis to be closely identified whether it is a complication of other diseases. Chronic bronchitis is often caused by smoking, and also by dust exposure, for example to particular species, and also by problems with bronchial development or bronchiectasis during childhood. This group of diseases is therefore referred to as the manifestation of chronic bronchitis. Chronic bronchitis may be a complex manifestation of three or four diseases in terms of diagnosing a single disease.

The occurrence of diseases is always sudden due to the accelerated pace of life, and the prevention and treatment of the above three diseases are the most important. Therefore, the invention provides a medicinal preparation for treating various malignant tumors, leukemia and chronic bronchitis, a preparation method and a quality control method thereof. The product achieves better treatment effect by various operations such as preparation process, parameter control, quality control and the like, thereby relieving the pain of patients suffering from malignant tumor, leukemia and chronic bronchitis.

Disclosure of Invention

The invention aims to provide a medicinal preparation for treating various malignant tumors, leukemia and chronic bronchitis, and a preparation method and a quality control method thereof.

In order to achieve the above object, the present invention adopts the following technical means

The invention relates to a medicinal preparation for treating various malignant tumors, leukemia and chronic bronchitis, which is prepared from the following raw materials in parts by weight:

1-1000 parts of marsdenia tenacissima, 1-200 parts of dextrin, 1-30 parts of starch and 1-20 parts of magnesium stearate.

Preferably, the pharmaceutical preparation is prepared from the following raw materials in parts by weight:

400-550 parts of marsdenia tenacissima, 30-60 parts of dextrin, 3-15 parts of starch and 2-6 parts of magnesium stearate.

Furthermore, the invention also provides a method for preparing the pharmaceutical preparation, which comprises the following steps:

(1) Extraction of

The first extraction comprises the steps of taking 1-1000 parts of Tongguantengjing medicinal materials, adding 20-50% ethanol water solution with 2-5 times of weight of the Tongguangjing medicinal materials, soaking for 8-24 hours, putting the soaked Tongguangjing medicinal materials into an extraction tank with a lifting filter screen device, adding water with 2-5 times of weight of the Tongguangjing medicinal materials, recording the position of the water surface, extracting by using a straight extraction tank, opening a steam valve for heating until the whole extraction tank begins to boil, extracting for 0.5-1.5 hours, starting the lifting device, adjusting a filter screen to be above the water level, reducing the filter screen device to the bottom after extracting for 0.5-1.5 hours, continuously extracting for 0.5-1.5 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-110 ℃;

and (3) second extraction: adding water with the weight of 4-10 times of that of the Tongguanteng medicinal material into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins to be recorded, extracting for 0.5-1.0 h, starting a lifting device, adjusting a filter screen to be above the water level, lowering the filter screen device to the bottom after extracting for 0.5-1.0 h, continuously extracting for 0.5-1.0 h, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 105-110 ℃;

and (3) extracting for the third time: adding water with the weight of 4-10 times of that of the Tongguanteng medicinal material into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 1-3 hours, controlling the steam pressure to be less than or equal to 0.2MPa and the extraction temperature to be 100-105 ℃ to obtain an extracting solution;

(2) Concentrating

Pumping the extracting solution into a liquid storage tank, sucking the extracting solution into a double-effect evaporator by vacuum, opening a steam valve for heating, controlling the pressure of one-effect steam to be 0.08-0.1 MPa, the temperature to be 50-90 ℃, the vacuum degree to be-0.03-0.10 Mpa, the temperature to be two-effect steam to be 30-70 ℃, the vacuum degree to be-0.03-0.10 Mpa, and concentrating the extracting solution to thick paste with the relative density of 1.10-1.30;

(3) Ingredients

Weighing 1-200 parts of dextrin, 1-30 parts of starch and 1-20 parts of magnesium stearate for later use;

(4) Granulating

Putting 1-100 parts of dextrin and 1-15 parts of starch into a wet granulator, setting the mixing speed at a low speed, cutting the mixture at a low speed, and dry-mixing the mixture for 4-6 min; mixing the thick paste with 95% ethanol in a stainless steel barrel, stirring for 1-5 min, mixing uniformly, and adding into a wet granulator; adding 1-100 parts of dextrin and 1-15 parts of starch, and continuously stirring for 2-4 min; washing the stainless steel barrel with 95% ethanol for 3-5 times, adding into a wet granulator, stirring for 2-4 min to obtain soft material, and discharging; adding the mixture into a swing granulator, uniformly mixing for 15-30 min, stopping mixing every 5min during the uniform mixing, stirring for 1-3 min by adopting a three-layer propeller stirring device, and then adding a 15-30 mesh screen after the uniform mixing is finished to prepare wet granules;

(5) Drying the mixture

Adding the wet granules into a baking pan, placing the baking pan in a special drug baking oven, drying the granules by using a through-flow type hot air circulation baking oven at the temperature of between 40 and 70 ℃ until the moisture is less than 5.0 percent, carrying out cold blowing, and receiving the materials;

(6) Whole grain

Installing a screen mesh of 15-30 meshes, adding the dry particles into a granulating machine for granulating, and uniformly mixing. Barreling the granules after finishing the granules for later use;

(7) Total mixture

Adding the granulated dry granules and 1-20 parts of magnesium stearate into a pyramid mixer, fully and uniformly mixing for 5-20 min, and discharging;

(8) Tabletting

And (3) performing tabletting by using a shallow concave die with the diameter of 9.5mm, wherein the weight difference of the plain tablets is controlled to be 0.31 g/tablet +/-4%.

Wherein, preferably, the method also comprises a quality control method of the pharmaceutical preparation, which comprises the following steps:

(1) Authentication

(1) Taking 5 tablets or 1g of the prepared medicinal preparation or extract, grinding, taking 1g, adding 10ml of methanol, carrying out ultrasonic treatment for 30min, filtering, evaporating filtrate to dryness, adding 10ml of water into residues for dissolving, adding 10ml of trichloromethane for shaking extraction, taking trichloromethane liquid, concentrating to 1ml, and taking the trichloromethane liquid as a test solution; preparing another 1g of marsdenia tenacissima reference medicinal material, and preparing a reference medicinal material solution by the same method; taking the marsdenia tenacissima glycoside H reference substance, adding trichloromethane to prepare a solution containing 0.5mg per 1ml, and taking the solution as a reference substance solution; according to the thin-layer chromatography test, sucking 5ul of each solution, respectively dropping on the same silica gel G thin-layer plate, developing by using chloroform-acetone-methanol (volume ratio 20; spots of the same color appear in the chromatogram of the test solution at the positions corresponding to the chromatograms of the reference medicinal material and the reference solution;

(2) taking 5 tablets or 1g of the medicinal preparation or extract, grinding, taking about 1g, adding 10mL of n-hexane, carrying out ultrasonic treatment for 30min, adding 1-2 mL of 0.02% BHA antioxidant, carrying out ultrasonic treatment at room temperature for 1-5 h, mixing the extracting solution with 10-20 mL of water-n-hexane (volume ratio of 6: 4), standing, layering, collecting an upper n-hexane layer containing extracted components, extracting the lower liquid layer with n-hexane for multiple times until the extraction is complete, combining the upper extracting solutions, blowing nitrogen to be nearly dry, adding 0.2% BHA ethyl acetate to dissolve, fixing the volume to 10mL, and filtering with a 0.45 mu m microporous filter membrane to obtain a test solution; preparing another 1g of marsdenia tenacissima reference medicinal material, and preparing a reference medicinal material solution by the same method; accurately weighing 5.0mg of palmitic acid control, adding 0.2% BHA ethyl acetate to the volume of 10mL, preparing a control stock solution of 0.5mg/mL for use, diluting before use, sucking 5ul of the solution according to a thin layer chromatography test, respectively spotting on the same silica gel G thin layer plate, developing with petroleum ether-ethyl acetate (volume ratio of 9: 1) as a developing agent, taking out, air drying, and inspecting under an ultraviolet lamp (365 nm);

(2) Content detection

Chromatographic conditions and system applicability test: and (3) chromatographic column: SB-C18, 250mm 4.6mm,5 μm; acetonitrile-0.5% phosphoric acid solution (volume ratio 8; the column temperature is 30 ℃; the flow rate is 0.8ml/min; the detection wavelength is 324nm; the number of theoretical plates is not less than 5000 calculated according to chlorogenic acid peak;

preparation of control solutions: precisely weighing appropriate amount of chlorogenic acid reference substance, placing in brown bottle, and adding 50% methanol to obtain solution containing 36 μ g per 1 ml;

preparing a test solution: precisely weighing 10 prepared medicinal preparations, grinding, precisely weighing 1g of the medicinal preparations, precisely adding 25ml of 50% methanol into a conical flask with a plug, sealing the conical flask, weighing, ultrasonically treating for 40min, cooling, weighing again, supplementing the weight loss with 50% methanol, shaking, filtering, and collecting the subsequent filtrate;

the determination method comprises the following steps: precisely sucking 10 μ l of the reference solution and 10 μ l of the test solution, respectively, injecting into a liquid chromatograph, and recording chromatogram.

Furthermore, the invention also provides the application of the medicinal preparation in preparing medicaments for treating various malignant tumors, leukemia and chronic bronchitis. Preferably, the malignant tumor includes lung cancer and gastric cancer.

Compared with the prior art, the invention has the beneficial effects that:

1. the invention discloses a pharmaceutical preparation for treating various malignant tumors, leukemia and chronic bronchitis and a preparation method thereof, wherein the pharmaceutical preparation is prepared from 400-550 parts of marsdenia tenacissima, 30-60 parts of dextrin, 3-15 parts of starch and 2-6 parts of magnesium stearate. The product achieves better treatment effect from various operations such as preparation process, parameter control, quality control and the like.

2. The method changes the soaking solution in the marsdenia tenacissima extraction process from water to 20-50% ethanol solution, controls the extraction temperature in different ranges each time, simultaneously uses a lifting filter screen device for extraction, and combines a steam distillation method and a decoction method, thereby removing palmitic acid in the extract and greatly improving the transfer rate of the extract.

3. The invention firstly changes the adding amount and adding sequence of auxiliary materials and extract in the granulating process, secondly dilutes the extract in times, and finally adds three layers of propellers to stir when uniformly mixing in a swing type granulator, thereby ensuring that the content of chlorogenic acid in the prepared medicinal preparation is uniform and the stable treatment effect is achieved.

4. According to the invention, the existence of the marsdenia tenacissima glycoside H component in the marsdenia tenacissima is effectively detected through a marsdenia tenacissima glycoside H identification experiment, so that the quality effectiveness of the marsdenia tenacissima is determined; detecting harmful substances in the extract and the medicinal preparation by a palmitic acid identification experiment; the effective components in the medicinal preparation are detected by a chlorogenic acid content measuring means, and the uniformity can be detected, so that the medicinal effect of the medicinal preparation is relatively stable.

5. The invention proves that the medicine preparation has obvious treatment effect on various malignant tumors, leukemia and chronic bronchitis through pharmacodynamic tests and clinical tests.

Drawings

FIG. 1 shows the identification of Marsdenia tenacissima glycoside H in the extract;

wherein, the reference substance is represented by S, the marsdenia tenacissima reference medicinal material is represented by T, and the extraction methods 1-4 are represented by corresponding numbers;

FIG. 2 shows the identification of Marsdenia tenacissima glycoside H in the pharmaceutical preparation;

wherein, the reference substance is represented by S, the marsdenia tenacissima reference medicinal material is represented by T, and the preparation methods 1-4 are represented by corresponding numbers;

FIG. 3 shows the identification of palmitic acid in the extract;

FIG. 4 is a graph of palmitic acid identification in a pharmaceutical formulation;

wherein, the reference substance is represented by S, the marsdenia tenacissima reference medicinal material is represented by T, and the preparation methods 1-4 are represented by corresponding numbers.

Detailed Description

The invention is further described below with reference to specific examples. These examples are illustrative only and do not limit the scope of the present invention in any way.

EXAMPLE 1 preparation of a pharmaceutical preparation for the treatment of various malignant tumors, leukemia, chronic bronchitis

1. Extraction of

The first extraction comprises the steps of taking 500 parts by weight of a marsdenia tenacissima medicinal material, adding 35% ethanol water solution with the weight 4 times that of the marsdenia tenacissima medicinal material, soaking for 12 hours, putting the soaked marsdenia tenacissima medicinal material into an extraction tank with a lifting filter screen device, adding water with the weight 4 times that of the marsdenia tenacissima medicinal material, recording the position of the water surface, extracting by using a straight extraction tank, opening a steam valve to heat until the whole extraction tank begins to boil, extracting for 1 hour, starting a lifting device, adjusting the filter screen to be above the water level, reducing the filter screen device to the bottom after extracting for 1 hour, continuously extracting for 1 hour, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-110 ℃.

And (3) second extraction: and adding water into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 0.5h, starting a lifting device, adjusting a filter screen to be above the water level, lowering the filter screen device to the bottom after extracting for 0.5h, continuously extracting for 0.5h, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 105-110 ℃.

And (3) extracting for the third time: adding 6 times of water by weight of the clean medicinal material of marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 2 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-105 ℃.

2. Concentrating

Pumping the tertiary extract into a liquid storage tank, sucking the tertiary extract into a double-effect evaporator by vacuum, opening a steam valve to heat, controlling the pressure of single-effect steam to be 0.08-0.1 MPa, the temperature to be 50-90 ℃, the vacuum degree to be-0.03-0.10 Mpa, the temperature to be 30-70 ℃, the vacuum degree to be-0.03-0.10 Mpa, and concentrating the primary extract into thick paste with the relative density of 1.10-1.30.

3. Ingredients

45 parts of dextrin, 10 parts of starch and 10 parts of magnesium stearate are weighed for later use.

4. Granulating

Putting 30 parts by weight of dextrin and 5 parts by weight of starch into a wet granulator, setting the mixing speed at a low speed, cutting the mixture at a low speed, and dry-mixing the mixture for 5min; mixing the soft extract with 95% ethanol in a stainless steel barrel, stirring for 4min, mixing, and adding into wet granulating machine; adding 15 parts by weight of dextrin and 5 parts by weight of starch, and continuously stirring for 3min; washing the stainless steel barrel with 95% ethanol for 4 times, adding into wet granulating machine, stirring for 3min to obtain soft material, and discharging; adding into a swing granulator, mixing for 30min, stopping once every 5min, stirring with three-layer propeller stirring device for 2min, and sieving with 30 mesh sieve to obtain wet granule.

5. Drying

Adding the wet granules into a baking pan, placing the baking pan in a special drug baking oven, drying by using a through-flow type hot air circulation baking oven at the temperature of 70 ℃ until the moisture is below 5.0%, cooling by blowing, and collecting.

6. Whole grain

And (4) installing a 30-mesh screen, adding the dry particles into a granulating machine for granulating, and uniformly mixing. And (4) barreling the granules after finishing the granules for later use.

7. Total mixing

Adding the granulated dry granules and 10 parts by weight of magnesium stearate into a pyramid mixer, fully and uniformly mixing for 15min, and discharging.

8. Tabletting

EXAMPLE 2 preparation of a pharmaceutical preparation for the treatment of various malignant tumors, leukemia, chronic bronchitis

1. Extraction of

The first extraction comprises the steps of taking 500 parts by weight of a marsdenia tenacissima clean medicinal material, adding 50% ethanol aqueous solution with the weight being 3 times that of the marsdenia tenacissima clean medicinal material, soaking for 10 hours, putting the soaked marsdenia tenacissima clean medicinal material into an extraction tank with a lifting filter screen device, adding water with the weight being 3 times that of the marsdenia tenacissima clean medicinal material, recording the position of the water surface, extracting by using a straight-tube extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins to be recorded, extracting for 0.5 hours, starting a lifting device, adjusting the filter screen to be above the water level, reducing the filter screen device to the bottom after extracting for 1.5 hours, continuously extracting for 0.5 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-110 ℃.

And (3) second extraction: adding water with the weight 5 times that of the marsdenia tenacissima medicinal material into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins to be recorded, extracting for 0.5h, starting a lifting device, adjusting a filter screen to be above the water level, reducing the filter screen device to the bottom after extracting for 0.5h, continuously extracting for 0.5h, controlling the steam pressure to be less than or equal to 0.2MPa and controlling the extraction temperature to be 105-110 ℃.

And (3) extracting for the third time: adding water 5 times the weight of the clean medicinal material of marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 1h, controlling the steam pressure to be less than or equal to 0.2MPa and controlling the extraction temperature to be 100-105 ℃.

2. Concentrating

3. Ingredients

60 parts of dextrin, 5 parts of starch and 5 parts of magnesium stearate are weighed for later use.

4. Granulating

Putting 30 parts by weight of dextrin and 2.5 parts by weight of starch into a wet granulator, setting the mixing speed at a low speed, cutting the mixture at a low speed, and dry-mixing the mixture for 6min; mixing the soft extract with 95% ethanol in a stainless steel barrel, stirring for 3min, mixing, and adding into wet granulating machine; adding dextrin 30 weight parts and starch 2.5 weight parts, and stirring for 3min; washing the stainless steel barrel with 95% ethanol for 4 times, adding into wet granulating machine, stirring for 4min to obtain soft material, and discharging; adding into a swing granulator, mixing for 20min, stopping once every 5min, stirring with a three-layer propeller stirring device for 1min, and sieving with a 15-mesh sieve to obtain wet granules.

5. Drying

And (3) adding the wet granules into a baking pan, placing the baking pan into a special medicine baking oven, drying the granules by using a through-flow type hot air circulation baking oven at the temperature of 40-70 ℃ until the moisture is below 5.0%, cooling by blowing, and collecting the granules.

6. Whole grain

Installing a 15-mesh screen, adding the dry particles into a granulator for granulation, and uniformly mixing. And (4) barreling the granules after finishing the granules for later use.

7. Total mixing

Adding the granulated dry granules and 5 parts by weight of magnesium stearate into a pyramid mixer, fully and uniformly mixing for 10min, and discharging.

8. Tabletting

EXAMPLE 3 preparation of a pharmaceutical preparation for the treatment of various malignant tumors, leukemia, chronic bronchitis

1. Extraction of

The first extraction comprises the steps of taking 500 parts by weight of a marsdenia tenacissima medicinal material, adding 45% ethanol water solution with the weight 5 times that of the marsdenia tenacissima medicinal material, soaking for 24 hours, putting the soaked marsdenia tenacissima medicinal material into an extraction tank with a lifting filter screen device, adding water with the weight 5 times that of the marsdenia tenacissima medicinal material, recording the water surface position, extracting by using a straight extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins to be recorded, extracting for 1.5 hours, starting a lifting device, adjusting the filter screen to be above the water level, reducing the filter screen device to the bottom after extracting for 1.5 hours, continuously extracting for 0.5 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-110 ℃.

And (3) second extraction: adding water with the weight 8 times that of the marsdenia tenacissima medicinal material into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins to be recorded, extracting for 1.0h, starting a lifting device, adjusting a filter screen to be above the water level, reducing the filter screen device to the bottom after extracting for 1.0h, continuously extracting for 0.5h, controlling the steam pressure to be less than or equal to 0.2MPa and controlling the extraction temperature to be 105-110 ℃.

And (3) extracting for the third time: adding 6 times of water by weight of the clean medicinal material of marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 1 hour, controlling the steam pressure to be less than or equal to 0.2MPa and controlling the extraction temperature to be 100-105 ℃.

2. Concentrating

Pumping the tertiary extract into a liquid storage tank, sucking the tertiary extract into a double-effect evaporator by vacuum, opening a steam valve to heat, controlling the pressure of the first-effect steam to be 0.08-0.1 MPa, the temperature to be 50-90 ℃, the vacuum degree to be-0.03-0.10 MPa, the temperature to be 30-70 ℃, the vacuum degree to be-0.03-0.10 MPa, and concentrating the primary extract into thick paste with the relative density of 1.10-1.30.

3. Ingredients

30 parts of dextrin, 15 parts of starch and 15 parts of magnesium stearate are weighed for later use.

4. Granulating

Putting 20 parts by weight of dextrin and 7 parts by weight of starch into a wet granulator, setting the mixing speed at a low speed, cutting the mixture at a low speed, and dry-mixing the mixture for 5min; mixing the soft extract with 95% ethanol in a stainless steel barrel, stirring for 5min, mixing, and adding into wet granulating machine; adding 10 parts by weight of dextrin and 8 parts by weight of starch, and continuously stirring for 4min; washing the stainless steel barrel with 95% ethanol for 3 times, adding into wet granulating machine, stirring for 4min to obtain soft material, and discharging; adding into a swing granulator, mixing for 20min, stopping once every 5min, stirring for 3min with a three-layer propeller stirring device, and sieving with a 20-mesh sieve to obtain wet granules.

5. Drying

Adding the wet granules into a baking pan, placing into a special medicine oven, drying with a through-flow hot air circulation oven at 60 deg.C until the water content is below 5.0%, cooling by blowing, and collecting.

6. Whole granule

And (3) installing a 20-mesh screen, adding the dry particles into a granulating machine for granulating, and uniformly mixing. And barreling the granules after finishing the granules for later use.

7. Total mixture

Adding the granulated dry granules and 15 parts by weight of magnesium stearate into a pyramid mixer, fully and uniformly mixing for 10min, and discharging.

8. Tabletting

Example 4 study of the drug efficacy of tumor inhibition

1. Test method

Establishment of tumor animal model under aseptic condition, tumor solution is extracted from corresponding parts of NCI-H460 (lung cancer cell line) tumor-derived mice, SGC-7901 (gastric cancer cell line) tumor-derived mice and K562 (leukemia cell line) tumor-derived mice with passage of 7d, and the diluted tumor solution is injected into experimental mice. The experiment is carried out according to 3 groups of different tumor sources, 30 healthy mice with uniform weight are taken in each group of experiment, and the mice are randomly divided into 3 groups, a blank group, a control group and an experimental group.

Blank group: taking 10 mice without injecting tumor cells;

control group: 10 mice were taken, 1ml of tumor cell fluid was injected, 5ml of physiological saline was administered daily, and intragastric administration was performed 2 times daily. The administration is continued for 20 days;

experimental groups: 10 mice were each injected with 1ml of tumor cell fluid, and 5ml of physiological saline solution containing 1 tablet of the present pharmaceutical preparation (prepared in example 1) was administered daily for 2 times of intragastric administration per day. The administration is continued for 20 days;

weighing the weight of the mice on the 0 th day, the 10 th day and the 20 th day and the weight of the tumor on the 21 st day respectively; the leukemia cell strain group detects the quantity of white blood cells and platelets on the 0 th day, the 10 th day and the 20 th day.

2. Results of the experiment

The mice were subjected to the corresponding project testing according to the time nodes described in the above experiments, and the testing results are shown in tables 1, 2, and 3.

TABLE 1 test group for NCI-H460 tumor fluid infusion

TABLE 2 test group for SGC-7901 tumor fluid infusion

TABLE 3 test group for injection of K562 tumor solution

Calculating the formula: tumor inhibition rate = (average tumor mass in control group-average tumor mass in experimental group)/average tumor mass in control group × 100%

3. Conclusion of the experiment

According to the test data, the inhibition rate of the pharmaceutical preparation on NCI-H460 tumor is 69.26%; the inhibition rate of the SGC-7901 tumor is 68.05 percent; the medicine preparation has obvious improvement effect on K562 leukemia, and compared with a control group, the increase of the white blood cells of mice in an experimental group taking the medicine preparation is obviously slower, and the number of the blood platelets is not greatly reduced. All 3 groups of test data show that the pharmaceutical preparation can effectively kill or inhibit the propagation of tumor cells.

Example 5 clinical trial for Chronic bronchitis

1. Case selection

50 patients with different degrees of chronic bronchitis were selected as the subjects of this study. It was divided into control and test groups by randomization, with 25 patients in each group. 10 male control cases, 15 female control cases, 20-65 years old, 10 mild patients, 8 moderate patients and 7 severe patients; the experimental groups consisted of 12 men, 13 women, aged 23-60 years, 8 mild patients, 9 moderate patients and 8 severe patients. The general data comparison of two groups of patients shows that the difference is not statistically significant (P > 0.05), and is comparable.

Patient inclusion criteria:

(1) The clinical diagnosis standard of chronic bronchitis is met, and corresponding symptoms of chronic bronchitis exist;

(2) Before the experiment, the medicine preparations for relieving cough and reducing sputum are not taken;

(3) The patients voluntarily participate in the test and are highly matched;

(4) Approved by the hospital, and all the family members of the patients voluntarily sign informed consent after fully understanding the experiment.

2. Method of treatment

Conventional therapeutic drugs such as antitussive, expectorant, and anti-infection drugs are administered to the control group;

the test group orally administered the present pharmaceutical preparation (prepared in example 1) 5 tablets/time 3 times a day on the basis of the above-mentioned conventional therapy. Both groups were treated for 1 month with continued dosing.

3. Evaluation criteria for therapeutic Effect

The effect is shown: the sputum amount is obviously reduced, the symptoms disappear, all physical signs are recovered to be normal, and the white blood cell amount is obviously reduced; the method has the following advantages: the sputum volume is relatively reduced, the symptoms are obviously improved but not disappeared, and the white blood cell count is relatively reduced; and (4) invalidation: clinical symptoms and white blood cell counts were unchanged.

4. Results

The clinical test result shows that: the number of cases treated with obvious effect in the test group is 15, the number of cases treated with effective effect is 8, and the effective rate is 92%; the number of the control group treatment cases with obvious effect is 10, the number of the treatment cases with effective effect is 9, and the effective rate is 76%; the effective rate of the test group is far higher than that of the control group. The results are shown in Table 4.

TABLE 4 comparison of two sets of clinical trial data

Name(s)	Number of cases	Show effect	Is effective	Nullification	Effective rate (%)
						Test group	25	15	8	2	92
Control group	25	10	9	6	76

Experimental example 1 optimization of Marsdenia tenacissima extraction method

The extraction method 1:

taking 500 parts by weight of Tongguanteng clean medicinal materials, adding water, soaking for 12h, adding water, decocting for three times, 2h for the first time, 1.5h for the second time and 1h for the third time, combining the decoctions, filtering, and concentrating the filtrate to obtain an extract with the relative density of about 1.23 (70-80C), thus obtaining the extract 1.

The extraction method 2 comprises the following steps:

the first extraction comprises the steps of taking 500 parts by weight of a marsdenia tenacissima medicinal material, adding 35% ethanol water solution with the weight 4 times that of the marsdenia tenacissima medicinal material, soaking for 12 hours, putting the soaked marsdenia tenacissima medicinal material into an extraction tank, adding water with the weight 4 times that of the marsdenia tenacissima medicinal material, extracting by using a straight-tube extraction tank, opening a steam valve to heat until the whole extraction tank begins to boil, extracting for 3 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-105 ℃.

And (3) second extraction: adding 6 times of water by weight of the medicinal material of the marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 2 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-105 ℃.

Mixing the extracting solutions, filtering, and concentrating the filtrate to obtain an extract with the relative density of about 1.23 (70-80C), namely the extract 2.

The extraction method 3 comprises the following steps:

the first extraction comprises the steps of taking 500 parts by weight of a Tongguanteng pure medicinal material, adding 35% ethanol water solution with the weight 4 times that of the Tongguanteng pure medicinal material, soaking for 12 hours, putting the soaked Tongguanteng pure medicinal material into an extraction tank, adding water with the weight 4 times that of the Tongguanteng pure medicinal material, extracting by adopting a straight-barrel extraction tank, opening a steam valve for heating until the whole extraction tank begins to boil, extracting for 3 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 105-110 ℃.

And (3) second extraction: adding 6 times of water by weight of the clean medicinal material of marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 2 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 105-110 ℃.

And (3) extracting for the third time: adding 6 times of water by weight of the medicinal material of the marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 2 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-105 ℃.

Mixing the extracting solutions, filtering, and concentrating the filtrate to obtain an extract with the relative density of about 1.23 (70-80C), namely the extract 3.

The extraction method 4 comprises the following steps:

extracting for the first time: taking 500 parts by weight of a marsdenia tenacissima medicinal material, adding 35% ethanol aqueous solution with the weight 4 times that of the marsdenia tenacissima medicinal material, soaking for 12 hours, putting the soaked marsdenia tenacissima medicinal material into an extraction tank with a lifting filter screen device, adding water with the weight 4 times that of the marsdenia tenacissima medicinal material, recording the position of a water surface, extracting by adopting a straight-barrel extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank is started, extracting for 1 hour, starting the lifting device, adjusting a filter screen to be above a water level, reducing the filter screen device to the bottom after extracting for 1 hour, continuously extracting for 1 hour, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-110 ℃.

And (3) second extraction: adding 6 times of water by weight of the clean medicinal material of marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins to be recorded, extracting for 0.5h, starting a lifting device, adjusting a filter screen to be above the water level, lowering the filter screen device to the bottom after extracting for 0.5h, continuously extracting for 0.5h, controlling the steam pressure to be less than or equal to 0.2MPa and controlling the extraction temperature to be 105-110 ℃.

And (3) extracting for the third time: adding 6 times of water by weight of the medicinal material of the marsdenia tenacissima into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 2 hours, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be about 100-105 ℃.

Mixing the extracting solutions, filtering, and concentrating the filtrate to obtain an extract with the relative density of about 1.23 (70-80C), namely an extract 4.

The marsdenia tenacissima medicinal materials used in the experiment and the extract prepared in the extraction methods 1-4 are detected according to the content detection method in the quality control method, and the detection results are shown in table 5.

TABLE 5 detection results of chlorogenic acid content in the extract

Name(s)	Caulis Marsdeniae Tenacissimae	Extract	1	Extract 2	Extract 3	Extract 4
							Content (g)	6.48	0.41	0.79	0.93	1.39
Conversion (%)	-	6.33	12.19	14.35	21.45

And (4) conclusion: the detection result shows that the extract prepared by the extraction method 4 has the highest content of chlorogenic acid, the content is 1.39g, the conversion rate of the extract is as high as 14.51 percent, and the content is equivalent to 0.39mg of chlorogenic acid in each tablet of medicinal preparation. Is much higher than the quality standard requirement (standard requirement: chlorogenic acid content in single tablet is more than 0.1 mg). Therefore, the method of the extraction method 4 is selected for extracting the marsdenia tenacissima.

Experimental example 2 optimization of granulation Process

The preparation method 1 comprises the following steps:

1. extraction of

The first extraction comprises the steps of taking 500 parts of marsdenia tenacissima clean medicinal materials, adding 35% ethanol water solution with the weight 4 times that of the marsdenia tenacissima clean medicinal materials, soaking for 12 hours, putting the soaked marsdenia tenacissima clean medicinal materials into an extraction tank with a lifting filter screen device, adding water with the weight 4 times that of the marsdenia tenacissima clean medicinal materials, recording the position of the water surface, extracting by using a straight-tube extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins to be recorded, extracting for 1 hour, starting a lifting device, adjusting a filter screen to be above the water level, reducing the filter screen device to the bottom after extracting for 1 hour, continuously extracting for 1 hour, controlling the steam pressure to be less than or equal to 0.2MPa, and controlling the extraction temperature to be 100-110 ℃.

2. Concentrating

3. Ingredients

4. Granulating

Putting 45 parts of dextrin and 10 parts of starch into a wet granulator, setting a mixing low speed, cutting the mixture at a low speed, performing dry mixing for 5min, adding the thick paste and 95% ethanol for wetting, continuously stirring the mixture for 3min to prepare a soft material, and discharging the material; packing into 30 mesh sieve to obtain wet granules.

5. Drying

Adding the wet granules into a baking pan, placing into a special medicine oven, drying with a through-flow hot air circulation oven at 70 deg.C until the water content is below 5.0%, cooling by blowing, and collecting.

6. Whole grain

7. Total mixing

Adding the granulated dry granules and 10 parts of magnesium stearate into a pyramid mixer, fully and uniformly mixing for 15min, and discharging.

8. Tabletting

And (3) performing tabletting by using a shallow concave die with phi 9.5mm, wherein the weight difference of the plain tablets is controlled to be 0.31 g/tablet +/-4%.

The preparation method 2 comprises the following steps:

the method is the same as the first preparation method, and is characterized in that the granulating steps are as follows:

putting 30 parts of dextrin and 5 parts of starch into a wet granulator, setting the mixing low speed, cutting the mixture at the low speed, dry-mixing the mixture for 5min, adding the thick paste and 95% ethanol for wetting, stirring the mixture for 4min, adding 15 parts of dextrin and 5 parts of starch, continuously stirring the mixture for 3min to prepare a soft material, and discharging the soft material; packing into 30 mesh sieve to obtain wet granules.

The preparation method 3 comprises the following steps:

putting 30 parts of dextrin and 5 parts of starch into a wet granulator, setting the mixing speed at a low speed, cutting the mixture at a low speed, and dry-mixing the mixture for 5min; mixing the soft extract with 95% ethanol in a stainless steel barrel, stirring for 4min, mixing, and adding into wet granulating machine; adding 15 parts of dextrin and 5 parts of starch, and continuously stirring for 3min; washing the stainless steel barrel with 95% ethanol for 4 times, adding into the wet granulating machine, stirring for 3min to obtain soft material, and discharging; packing into 30 mesh sieve to obtain wet granules.

The preparation method 4 comprises the following steps:

putting 30 parts of dextrin and 5 parts of starch into a wet granulator, setting the mixing speed at a low speed, cutting the mixture at a low speed, and dry-mixing the mixture for 5min; mixing the soft extract with 95% ethanol in a stainless steel barrel, stirring for 4min, mixing, and adding into wet granulating machine; adding 15 parts of dextrin and 5 parts of starch, and continuously stirring for 3min; washing the stainless steel barrel with 95% ethanol for 4 times, adding into wet granulating machine, stirring for 3min to obtain soft material, and discharging; adding into a swing granulator, mixing for 30min, stopping once every 5min, stirring for 2min with a three-layer propeller stirring device, and sieving with a 30-mesh sieve to obtain wet granules.

The pharmaceutical preparations prepared in the above preparation methods 1 to 4 were subjected to content uniformity detection, and the content detection results are shown in table 6.

TABLE 6 chlorogenic acid content uniformity test results

And (4) conclusion: according to the content detection results, the average content of chlorogenic acid in the pharmaceutical preparation prepared by the preparation method 4 is 0.34 mg/tablet, which is far higher than the quality standard requirement (standard requirement: the content of chlorogenic acid in a single tablet is more than 0.1 mg), the RSD is less than 5%, and the content is uniform. Therefore, the present invention employs the granulation method of preparation method 4 for granulation.

Experimental example 3 quality control

The volatile oil component of caulis Marsdeniae Tenacissimae contains palmitic acid. Palmitic acid is a fatty acid constituting palmitate and is not present in palm oil alone. Adipose tissue can increase oxidative stress, promote cell proliferation, and alter the mechanisms of blood lipids (such as increasing low density lipoprotein cholesterol, etc.), so palmitic acid alone increases the risk of cancer, obesity, type 2 diabetes, and cardiovascular disease.

The extractum extracted by the extraction method 1-4 in the experimental example 1 and the medicinal preparation prepared by the preparation method 1-4 in the experimental example 2 are taken for respectively carrying out the identification experiment of the marsdenia tenacissima glycoside H and the palmitic acid.

1. Marsdenia tenacissima glycoside H identification

Collecting 5 tablets (extract 1 g) of the medicinal preparation, grinding, collecting about 1g, adding 10ml of methanol, performing ultrasonic treatment for 30min, filtering, evaporating filtrate, dissolving residue with 10ml of water, adding 10ml of chloroform, shaking for extraction, collecting chloroform solution, and concentrating to 1ml to obtain sample solution. Preparing another 1g of marsdenia tenacissima reference medicinal material, and preparing a reference medicinal material solution by the same method. And adding chloroform into the marsdenia tenacissima H reference substance to obtain a solution containing 0.5mg per 1ml, and using the solution as the reference substance solution. Performing thin layer chromatography (2015 edition general rule 0502) test, sucking 5ul of the above solutions, respectively dropping on the same silica gel G thin layer plate, developing with chloroform acetone-methanol (20.

2. Palmitic acid identification

Taking 5 tablets (extract 1 g) of the medicinal preparation, grinding, taking about 1g, adding 10mL of n-hexane, carrying out ultrasonic treatment for 30min, adding 1-2 mL of 0.02% BHA antioxidant, carrying out ultrasonic treatment at room temperature for 1-5 h, mixing the extracting solution with 10-20 mL of water-n-hexane (6: 4, V/V), standing, layering, collecting an upper n-hexane layer containing the extracted components, extracting the lower liquid layer with n-hexane for multiple times until the extraction is complete, combining the upper extracting solutions, blowing nitrogen to be nearly dry, adding 0.2% BHA ethyl acetate to dissolve and fix the volume to 10mL, and filtering by using a 0.45 mu m microporous filter membrane to obtain a sample solution; preparing another 1g of marsdenia tenacissima reference medicinal material, and preparing a reference medicinal material solution by the same method; further, 5.0mg of the palmitic acid control was precisely weighed, and 0.2% BHA ethyl acetate was added thereto to a constant volume of 10mL to prepare a control stock solution of 0.5mg/mL for use, which was diluted immediately before use. Performing thin layer chromatography (2015 year, general editions of Chinese pharmacopoeia 0502), sucking 5ul of the above solutions, respectively spotting on the same silica gel G thin layer plate, developing with petroleum ether-ethyl acetate (9) as developing solvent, taking out, air drying, and inspecting under ultraviolet lamp (365 nm).

3. The result of the detection

The assay result of the marsdenia tenacissima glycoside H shows that the extract extracted by the extraction method 1-4 in the experimental example 1 and the medicinal preparation prepared by the preparation method 1-4 in the experimental example 2 show spots with the same color at the positions corresponding to the chromatogram of the reference substance and the chromatogram of the reference medicinal material; the results of the palmitic acid identification tests show that spots with the same color appear in the extract obtained by the extraction method 1 in the experimental example 1 at positions corresponding to the chromatogram of the reference substance and the chromatogram of the reference medicinal material, the extract contains palmitic acid substances, and the extract obtained by the extraction methods 2 to 4 and the medicinal preparation prepared by the preparation methods 1 to 4 do not contain the palmitic acid substances. The detection pattern of the differential test is shown in FIG. 1, FIG. 2, FIG. 3 and FIG. 4.

Claims

1. A pharmaceutical preparation for treating various malignant tumors, leukemia and chronic bronchitis is characterized by being prepared from the following raw materials in parts by weight:

2. The pharmaceutical preparation according to claim 1, wherein the pharmaceutical preparation is prepared from the following raw materials in parts by weight:

3. A method of preparing the pharmaceutical formulation of claim 1, comprising the steps of:

(1) Extraction of

and (3) extracting for the third time: adding water with the weight of 4-10 times of that of the marsdenia tenacissima medicinal material into the extraction tank, opening a steam valve to heat until the boiling of the whole extraction tank begins, extracting for 1-3 h, controlling the steam pressure to be less than or equal to 0.2MPa and the extraction temperature to be 100-105 ℃, and obtaining an extracting solution;

(2) Concentrating

(3) Ingredients

(4) Granulating

Putting 1-100 parts of dextrin and 1-15 parts of starch into a wet granulator, setting the mixing speed at a low speed, cutting the mixture at a low speed, and dry-mixing the mixture for 4-6 min; mixing the thick paste with 95% ethanol in a stainless steel barrel, stirring for 1-5 min, mixing uniformly, and adding into a wet granulator; adding 1-100 parts of dextrin and 1-15 parts of starch, and continuously stirring for 2-4 min; washing the stainless steel barrel with 95% ethanol for 3-5 times, adding into a wet granulator, stirring for 2-4 min to obtain soft material, and discharging; adding into a swing granulator, mixing for 15-30 min, stopping once every 5min during mixing, stirring for 1-3 min by using a three-layer propeller stirring device, and then adding a 15-30 mesh screen after mixing to prepare wet granules;

(5) Drying the mixture

Adding the wet granules into a baking pan, placing the baking pan in a special medicine baking oven, drying by using a through-flow type hot air circulation baking oven at the temperature of 40-70 ℃ until the moisture is below 5.0%, cooling by blowing, and receiving materials;

(6) Whole granule

(7) Total mixture

Adding the granulated dry granules and 1-20 parts of magnesium stearate into a pyramid mixer to be fully and uniformly mixed for 5-20 min, and discharging;

(8) Tabletting

4. The method of claim 3, wherein the pharmaceutical formulation is prepared from the following raw materials in parts by weight:

5. The method of claim 3, further comprising a method of quality control of the pharmaceutical formulation, comprising the steps of:

(1) Authentication

(1) Grinding 5 tablets or 1g of the prepared medicinal preparation or 1g of the extract, adding 10ml of methanol into 1g of the medicinal preparation, carrying out ultrasonic treatment for 30min, filtering, evaporating the filtrate to dryness, adding 10ml of water into the residue to dissolve the residue, adding 10ml of trichloromethane, shaking for extraction, collecting trichloromethane liquid, and concentrating the trichloromethane liquid to 1ml to obtain a sample solution; preparing another 1g of marsdenia tenacissima reference medicinal material, and preparing a reference medicinal material solution by the same method; taking the marsdenia tenacissima glycoside H reference substance, adding trichloromethane to prepare a solution containing 0.5mg per 1ml, and taking the solution as a reference substance solution; according to the thin-layer chromatography test, sucking 5ul of each solution, respectively dropping on the same silica gel G thin-layer plate, developing by using chloroform-acetone-methanol (volume ratio 20; spots of the same color appear in the chromatogram of the test solution at the positions corresponding to the chromatograms of the reference medicinal material and the reference solution;

(2) taking 5 tablets or 1g of extract of the medicinal preparation, grinding the medicinal preparation into fine powder, taking about 1g, adding 10mL of n-hexane, carrying out ultrasonic treatment for 30min, adding 1-2 mL of 0.02% BHA antioxidant, carrying out ultrasonic treatment at room temperature for 1-5 h, mixing the extracting solution with 10-20 mL of water-n-hexane (volume ratio of 6: 4), standing, layering, collecting an upper n-hexane layer containing the extracted components, extracting the lower liquid layer for multiple times by using the n-hexane until the extracting is complete, combining the upper extracting solutions, blowing nitrogen to be nearly dry, adding 0.2% BHA ethyl acetate to dissolve and fix the volume to 10mL, and filtering by using a 0.45 mu m microporous filter membrane to obtain a sample solution; preparing another 1g of marsdenia tenacissima reference medicinal material, and preparing a reference medicinal material solution by the same method; accurately weighing 5.0mg of palmitic acid reference substance, adding 0.2% BHA ethyl acetate to the volume of 10mL, preparing a reference substance stock solution of 0.5mg/mL for later use, diluting the solution before use, absorbing 5ul of the solution according to a thin-layer chromatography test, respectively dropping the solution on the same silica gel G thin-layer plate, developing the solution by using petroleum ether-ethyl acetate (volume ratio of 9 to 9) as a developing agent, taking out the solution, drying the solution in the air, and inspecting the solution under an ultraviolet lamp (365 nm);

(2) Content detection

Chromatographic conditions and system applicability test: a chromatographic column: SB-C18, 250mm 4.6mm,5 μm; acetonitrile-0.5% phosphoric acid solution (volume ratio 8; the column temperature is 30 ℃; the flow rate is 0.8ml/min; the detection wavelength is 324nm; the number of theoretical plates is not less than 5000 calculated according to the peak of chlorogenic acid;

preparation of a test solution: taking 10 prepared tablets of the pharmaceutical preparation, precisely weighing, grinding, taking 1g, precisely weighing, placing in a conical flask with a plug, precisely adding 25ml of 50% methanol, sealing the plug, weighing, ultrasonically treating for 40min, cooling, weighing again, complementing the weight loss by 50% methanol, shaking up, filtering, and taking the subsequent filtrate;

6. Use of a pharmaceutical formulation according to claim 1 or 2 for the preparation of a medicament for the treatment of various malignancies, leukemia, chronic bronchitis.

7. The use of claim 6, wherein said malignant tumor comprises lung cancer and gastric cancer.