A traditional Chinese medicine composition for treating lung tumors and a preparation method thereof

Abstract

The present application relates to a kind of traditional Chinese medicine composition for treating lung tumor and its preparation method, it is related to the technical field of traditional Chinese medicine, the traditional Chinese medicine composition for treating lung tumor is composed of (22-27) :(3-8) of Duanxue Liu and Xihe Liu by weight ratio.This application first uses Duanxue Liu as main component, and is supplemented with appropriate proportion of Xihe Liu, and a kind of traditional Chinese medicine composition for treating lung tumor is prepared.Experimental research shows that under this proportion, Duanxue Liu and Xihe Liu are mutually synergistic, significantly enhance the inhibition effect of the obtained traditional Chinese medicine composition on lung tumor growth in lung cancer mouse in vivo, prolong its survival period, show excellent treatment potential and application prospect for lung tumor, provide new means for the treatment of lung tumor disease, also widen the application range of Duanxue Liu and Xihe Liu in traditional Chinese medicine field.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating lung tumors and a preparation method thereof. Background Art

[0002] As one of the tumors with an extremely high fatality rate, the treatment of lung tumors has always been a key research focus in the medical field. Modern medicine has a variety of therapeutic approaches for lung tumors, including surgical resection, chemotherapy and radiotherapy, but these methods all have certain limitations to varying degrees. Surgical resection has unsatisfactory curative effect on advanced lung cancer, while chemotherapy and radiotherapy may be accompanied by a series of side effects, such as nausea, vomiting, hair loss, decreased immune function, etc., all of which seriously affect the quality of life of patients. In this context, traditional Chinese medicine has gradually shown unique advantages in the treatment of lung tumors due to its characteristics of being natural, having low toxic and side effects, and good tolerance. Traditional Chinese medicine has opened up new ideas and methods for the treatment of lung tumors through multiple mechanisms such as regulating the immune function of the human body, inhibiting tumor growth and spread, and promoting the apoptosis of tumor cells.

[0003] In recent years, remarkable progress has been made in the research on the application of traditional Chinese medicine in the treatment of lung tumors. Numerous research teams are committed to the development and pharmacodynamic research of traditional Chinese medicine. By extracting and separating the active ingredients in traditional Chinese medicine and deeply exploring their pharmacological effects and mechanisms, they have provided a solid scientific basis for the clinical application of traditional Chinese medicine. For example, the components such as astragalol and ferulic acid in Radix Astragali, and the polysaccharides in Panax notoginseng, have all been proven to have significant anti-lung tumor activity. Therefore, the development of natural traditional Chinese medicine components with activity against lung tumors has become a current research hotspot.

[0004] Clinopodium herba, as a traditional Chinese medicine with a long history, was first recorded under the name "Cao Xuejie" in the Southern Song Dynasty work "Liyan Bencao", with clear records of its efficacy and usage. Nowadays, this medicinal material has been included in the Pharmacopoeia of the People's Republic of China. It is derived from the dried aerial parts of Clinopodium polycephalum or Clinopodium chinense of the Labiatae family, and has the effects of clearing heat and detoxifying, cooling the blood and activating blood circulation. Modern medical pharmacological studies have shown that Clinopodium herba is rich in a variety of active components such as flavonoids, saponins, and volatile oils, which endow Clinopodium herba with multiple pharmacological activities including hemostasis, antibacterial, anti-inflammatory and immunomodulatory effects. It is worth mentioning that the prior art (Patent No. CN114712377A) first discovered that Clinopodioside A has the effect of inhibiting the growth of colon cancer and bladder cancer cells in vitro, and can produce a significant combined effect when used in combination with clinical drugs. Subsequent research results further confirmed that Clinopodioside A also has a significant effect of inhibiting the growth of colon cancer and bladder cancer cells in nude mice.

[0005] West River Willow, also known as Tamarix chinensis Lour., is a plant in the Tamarixaceae family. It is harvested in summer before flowering and dried in the shade. Its main medicinal properties include dispelling wind, detoxifying, and promoting rash eruption, and it is used to treat symptoms such as incomplete measles eruption and rheumatic pain. In addition, it also has the effects of dispelling wind and dampness and treating itchy skin conditions.

[0006] Currently, there are no reports in existing technologies of using the combined application of thrombocytopenia and salsa in the preparation of drugs for treating lung tumors. Summary of the Invention

[0007] To address the above problems, the present invention provides a traditional Chinese medicine composition for treating lung tumors and its preparation method.

[0008] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating lung tumors, the traditional Chinese medicine composition for treating lung tumors being composed of Duanxueliu and Xiheliu in a weight ratio of (22-27):(3-8).

[0009] Furthermore, the traditional Chinese medicine composition for treating lung tumors consists of Duanxueliu and Xiheliu in a weight ratio of 25:6.

[0010] In a second aspect, the present invention provides a method for preparing the traditional Chinese medicine composition for treating lung tumors according to any one of the first aspects, the preparation method comprising the following steps:

[0011] The severed blood flow was pulverized and then added to ethyl acetate for a first reflux extraction to obtain the first extract;

[0012] The willow bark was crushed and then added to water for a second reflux extraction to obtain the second extract.

[0013] The first extract and the second extract are pulverized and mixed to obtain the traditional Chinese medicine composition for treating lung tumors.

[0014] Furthermore, the working conditions for the first reflux extraction include: a temperature of 80–90°C, a pressure of atmospheric pressure, a time of 1–2 hours, and 1–3 extractions.

[0015] Furthermore, the weight ratio of the interrupted blood flow to the ethyl acetate is 1:(5-8).

[0016] Furthermore, the operating conditions for the second reflux extraction include: a temperature of 42–50°C, a pressure of 5–10 kPa, a time of 1–2 hours, and 1–3 extractions.

[0017] Furthermore, the weight ratio of the willow branch to the water is 1:(6-10).

[0018] Further, the temperature of the second reflux extraction is 45°C, and the pressure of the second reflux extraction is 8 kPa.

[0019] Further, the particle size of the traditional Chinese medicine composition for treating lung tumors is 200 to 300 mesh.

[0020] Compared with the prior art, the above technical solutions provided by the present invention have at least the following advantages:

[0021] The present invention provides a traditional Chinese medicine composition for treating lung tumors. For the first time, the present invention uses Clinopodium polycephalum as the main component, supplemented with an appropriate proportion of Tamarix chinensis, to prepare a traditional Chinese medicine composition for treating lung tumors. Experimental studies show that under this ratio, Clinopodium polycephalum and Tamarix chinensis act synergistically to significantly enhance the inhibitory effect of the obtained traditional Chinese medicine composition on the growth of lung tumors in lung cancer mice, prolong their survival period, show excellent therapeutic potential and application prospects for lung tumors, provide a new means for the treatment of lung tumor diseases, and also broaden the application scope of Clinopodium polycephalum and Tamarix chinensis in the field of traditional Chinese medicine. Detailed Description of the Embodiments

[0022] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below in conjunction with the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by a person of ordinary skill in the art without making creative work shall fall within the protection scope of the present invention.

[0023] Unless otherwise specifically stated, various raw materials, reagents, instruments and equipment used in the present invention are all commercially available or can be prepared by existing methods.

[0024] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating lung tumors, wherein the traditional Chinese medicine composition for treating lung tumors consists of Clinopodium polycephalum and Tamarix chinensis in a weight ratio of (22 to 27):(3 to 8).

[0025] The present invention provides a traditional Chinese medicine composition for treating lung tumors. For the first time, the present invention uses Clinopodium polycephalum as the main component, supplemented with an appropriate proportion of Tamarix chinensis, to prepare a traditional Chinese medicine composition for treating lung tumors. Experimental studies show that under this ratio, Clinopodium polycephalum and Tamarix chinensis act synergistically to significantly enhance the inhibitory effect of the obtained traditional Chinese medicine composition on the growth of lung tumors in lung cancer mice, prolong their survival period, show excellent therapeutic potential and application prospects for lung tumors, provide a new means for the treatment of lung tumor diseases, and also broaden the application scope of Clinopodium polycephalum and Tamarix chinensis in the field of traditional Chinese medicine.

[0026] In some specific embodiments, preferably, the traditional Chinese medicine composition for treating lung tumors consists of Duanxueliu and Xiheliu in a weight ratio of 25:6.

[0027] It should be noted that, unless otherwise specified or indicated, the raw materials involved in the traditional Chinese medicine composition for treating lung tumors provided by this invention can be directly derived from commercially available products or prepared in-house using existing processes.

[0028] Secondly, based on a general inventive concept, the present invention provides a method for preparing the traditional Chinese medicine composition for treating lung tumors according to any one of the first aspects, the preparation method comprising the following steps:

[0029] The severed blood flow was pulverized and then added to ethyl acetate for a first reflux extraction to obtain the first extract;

[0030] The willow bark was crushed and then added to water for a second reflux extraction to obtain the second extract.

[0031] The first extract and the second extract are pulverized and mixed to obtain the traditional Chinese medicine composition for treating lung tumors.

[0032] The traditional Chinese medicine composition for treating lung tumors provided by this invention interrupts blood flow in its ethyl acetate extract form and *Salix viminalis* in its water extract form. The preparation method is simple to operate, requires no additional specific equipment, and is suitable for mass industrial production.

[0033] In some specific embodiments, the operating conditions for the first reflux extraction include: a temperature of 80–90°C, a pressure of atmospheric pressure, a time of 1–2 hours, and 1–3 extractions. Preferably, the operating conditions for the first reflux extraction include: a temperature of 86°C, a pressure of atmospheric pressure, a time of 1.5 hours, and 2 extractions.

[0034] In some specific embodiments, the weight ratio of the interrupted blood flow to the ethyl acetate is 1:(5-8). Preferably, the weight ratio of the interrupted blood flow to the ethyl acetate is 1:7.

[0035] In some specific embodiments, the operating conditions for the second reflux extraction include: a temperature of 42–50°C, a pressure of 5–10 kPa, a time of 1–2 hours, and 1–3 extraction cycles. Preferably, the temperature of the second reflux extraction is 45°C, and the pressure of the second reflux extraction is 8 kPa.

[0036] In some specific embodiments, the weight ratio of the willow branch to the water is 1:(6-10). Preferably, the weight ratio of the willow branch to the water is 1:8.

[0037] In some specific embodiments, the particle size of the traditional Chinese medicine composition for treating lung tumors is 200-300 mesh.

[0038] It should be noted that, unless otherwise specified or described, the operational steps involved in the traditional Chinese medicine composition for treating lung tumors provided by this invention can be carried out in accordance with existing traditional Chinese medicine extract preparation processes or using existing equipment, and will not be described in detail here.

[0039] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed according to national standards. If no corresponding national standard exists, then generally accepted international standards, conventional conditions, or conditions recommended by the manufacturer are followed.

[0040] Example 1

[0041] This example provides a traditional Chinese medicine composition for treating lung tumors, which is composed of Duanxueliu and Xiheliu in a weight ratio of 25:6.

[0042] The preparation method of the above-mentioned traditional Chinese medicine composition for treating lung tumors includes the following steps:

[0043] Step (1): The broken blood flow is crushed and then ethyl acetate, which accounts for 7 times the weight of the broken blood flow, is added for the first reflux extraction. The temperature of the first reflux extraction is 86°C, the pressure of the first reflux extraction is atmospheric pressure, the time of the first reflux extraction is 1.5 hours, and the first reflux extraction is performed twice. The first extracts are combined and concentrated under reduced pressure and dried to constant weight to obtain the first extract.

[0044] Step (2): The West River Willow was crushed and then water was added in a ratio of 8 times the weight of the West River Willow for a second reflux extraction. The temperature of the second reflux extraction was 45°C, the pressure of the second reflux extraction was 8 kPa, the time of the second reflux extraction was 1 hour, and the extraction was performed twice. The resulting second extracts were combined, concentrated under reduced pressure, and dried to constant weight to obtain the second extract.

[0045] Step (3): The first extract obtained in step (1) and the second extract obtained in step (2) are pulverized and mixed, and then passed through a 200-mesh sieve to obtain the traditional Chinese medicine composition for treating lung tumors.

[0046] Example 2

[0047] This example provides a traditional Chinese medicine composition for treating lung tumors, which is composed of Duanxueliu and Xiheliu in a weight ratio of 22:3.

[0048] The preparation method of the above-mentioned traditional Chinese medicine composition for treating lung tumors includes the following steps:

[0049] Step (1): The broken blood flow is crushed and then ethyl acetate, which accounts for 5 times the weight of the broken blood flow, is added for the first reflux extraction. The temperature of the first reflux extraction is 80°C, the pressure of the first reflux extraction is atmospheric pressure, the time of the first reflux extraction is 1.5 hours, and the first reflux extraction is performed twice. The first extracts are combined and concentrated under reduced pressure and dried to constant weight to obtain the first extract.

[0050] Step (2): The West River Willow was crushed and then water was added in a ratio of 6 times the weight of the West River Willow for a second reflux extraction. The temperature of the second reflux extraction was 42°C, the pressure of the second reflux extraction was 5 kPa, the time of the second reflux extraction was 1 hour, and the extraction was performed twice. The resulting second extracts were combined, concentrated under reduced pressure, and dried to constant weight to obtain the second extract.

[0051] Step (3): The first extract obtained in step (1) and the second extract obtained in step (2) are pulverized and mixed, and then passed through a 200-mesh sieve to obtain the traditional Chinese medicine composition for treating lung tumors.

[0052] Example 3

[0053] This example provides a traditional Chinese medicine composition for treating lung tumors, which is composed of Duanxueliu and Xiheliu in a weight ratio of 27:8.

[0054] The preparation method of the above-mentioned traditional Chinese medicine composition for treating lung tumors includes the following steps:

[0055] Step (1): The broken blood flow is crushed and then ethyl acetate, which accounts for 8 times the weight of the broken blood flow, is added for the first reflux extraction. The temperature of the first reflux extraction is 90°C, the pressure of the first reflux extraction is atmospheric pressure, the time of the first reflux extraction is 1.5 hours, and the first reflux extraction is performed twice. The first extracts are combined and concentrated under reduced pressure and dried to constant weight to obtain the first extract.

[0056] Step (2): The West River Willow is crushed and then water with a weight of 10 times that of the West River Willow is added for a second reflux extraction. The temperature of the second reflux extraction is 50℃, the pressure of the second reflux extraction is 10kPa, the time of the second reflux extraction is 1 hour, and the second reflux extraction is performed twice. The resulting second extracts are combined, concentrated under reduced pressure, and dried to constant weight to obtain the second extract.

[0057] Step (3): The first extract obtained in step (1) and the second extract obtained in step (2) are pulverized and mixed, and then passed through a 200-mesh sieve to obtain the traditional Chinese medicine composition for treating lung tumors.

[0058] Comparative Example 1

[0059] This example provides an ethyl acetate extract for interrupting blood flow, the specific preparation method of which is the same as step (1) in Example 1.

[0060] Comparative Example 2

[0061] This example provides a water extract of *Salix matsudana*, the specific preparation method of which is the same as step (2) in Example 1.

[0062] Comparative Example 3

[0063] This example provides a traditional Chinese medicine composition for treating lung tumors and its preparation method. The only difference from Example 1 is that the traditional Chinese medicine composition for treating lung tumors is composed of Duanxueliu and Xiheliu in a weight ratio of 6:25; the remaining steps and parameters are the same.

[0064] Comparative Example 4

[0065] This example provides a traditional Chinese medicine composition for treating lung tumors and its preparation method. The only difference from Example 1 is that the temperature of the second reflux extraction in step (2) is adjusted to 105°C and the pressure of the second reflux extraction is adjusted to atmospheric pressure; the other steps and parameters are the same.

[0066] The main differences in the specific components and dosages of the traditional Chinese medicines obtained in Examples 1-3 and Comparative Examples 1-4 are shown in Table 1.

[0067] Table 1

[0068]

[0069]

[0070] Test case

[0071] In order to evaluate the efficacy of the traditional Chinese medicines for treating lung tumors provided in Examples 1 to 3 and Comparative Examples 1 to 4, this example conducts an in vivo mouse lung cancer treatment experiment based on the prior art disclosure.

[0072] 1. Establishment of an orthotopic mouse model of lung cancer:

[0073] 1.1 Select LLC-luc cells in the logarithmic growth phase and mix them with an equal volume of Matrigel and pre-cooled PBS to resuspend the cells.

[0074] 1.2 Adjust the cell suspension concentration to 1.2×10^6 cells / ml and store at 4℃ for injection.

[0075] 1.3 Select male C57BL / 6 mice aged 4 to 6 weeks, anesthetize them with small animal breathing, and shave the hair on their left chest and underarms to fully expose the left chest wall and disinfect it.

[0076] 1.4. Make a transverse cut of about 1 cm in the skin 0.5 cm below the left anterior axillary line of the mouse, and locate the adjacent light pink lung tissue through the heart.

[0077] 1.5. Using a pre-cooled insulin syringe, draw 100 μl of cell suspension, insert the needle vertically through the pleura about 3 mm, and slowly inject the cell mixture. After the injection is completed, pause briefly before withdrawing the needle, suture the incision, and apply erythromycin eye ointment to prevent wound infection.

[0078] 1.6 After the operation, the mice were placed in an environment of 20 to 25°C, their vital signs were monitored, and they were kept awake.

[0079] 2. Grouping and administration:

[0080] 2.1 On the 4th day after modeling, based on the results of in vivo imaging of mice, the successfully modeled lung cancer mice were randomly divided into 1 saline group and 7 experimental groups, with 5 mice in each group.

[0081] 2.2 The experimental group used the traditional Chinese medicines for treating lung tumors provided in Examples 1 to 3 and Comparative Examples 1 to 4 as test samples. The drugs were administered by gavage, with a gavage volume of 200 μl and a drug concentration of 1.10 g crude drug / ml, once a day for 4 weeks or until the mice reached the human endpoint (such as rapid loss of 15 to 20% of their original body weight, loss of appetite or inability to eat, weakness, difficulty breathing, persistent hypothermia, or any other condition that occurred).

[0082] 2.3 The saline group used the same volume of saline as a control.

[0083] 3. Experimental monitoring and evaluation:

[0084] 3.1 During the experiment, the survival of mice was monitored and their lifespan was recorded, with the day of model establishment as the starting point of the lifespan and the death of the mice (including death during the administration period or humane euthanasia after administration) as the end point of the lifespan.

[0085] 3.2. Mice that died during the drug administration period or were euthanized after drug administration were dissected, and the weight of the lung tumors was measured. The tumor inhibition rate was obtained by calculating the ratio of the tumor weight of each experimental group to that of the saline group.

[0086] 3.3 The test data were statistically analyzed using software, and the test results are shown in Table 2.

[0087] Table 2

[0088] saline group 22 - Example 1 Group 47 84.7 Example 2 group 40 71.1 Example 3 Group 42 75.9 Comparative Example 1 28 40.2 Comparative Example 2 24 13.6 Comparative Example 3 Groups 31 47.4 Comparative Example 4 Groups 35 56.8

[0089] It can be seen from Table 2 that:

[0090] 1) Compared with the groups of Comparative Examples 1 to 4, the traditional Chinese medicine compositions provided by the groups of Examples 1 to 3 of the present invention exhibit a more significant effect in inhibiting the growth of lung tumors in lung cancer mice, with a tumor inhibition rate exceeding 70%. Meanwhile, the survival period of the lung cancer mice in the groups of Examples 1 to 3 of the present invention is also significantly prolonged, highlighting the excellent potential and broad application prospect for lung tumor treatment.

[0091] 2) As can be seen from the test results of the group of Comparative Example 1, the group of Comparative Example 2 and the group of Example 1, the present invention uses a suitable ratio of Clinopodium polycephalum and Tamarix chinensis in combination, and the synergistic effect of the two is remarkable. This synergistic effect makes the therapeutic effect of the traditional Chinese medicine composition on lung tumors far better than the sum of the therapeutic effects of using Clinopodium polycephalum alone and using Tamarix chinensis alone, which further verifies the unique advantages and remarkable curative effect of the present invention.

[0092] 3) As can be seen from the test results of the group of Comparative Example 1, the group of Comparative Example 2 and the group of Comparative Example 3, when Tamarix chinensis is used as the main component, for example, when the weight ratio of Clinopodium polycephalum to Tamarix chinensis is adjusted to 6:25, the therapeutic effect of the obtained traditional Chinese medicine composition on lung tumors is slightly worse than the sum of the therapeutic effects of using Clinopodium polycephalum alone and using Tamarix chinensis alone, indicating that the two exhibit a certain degree of antagonism.

[0093] In summary, the present invention provides a traditional Chinese medicine composition for treating lung tumors and a preparation method thereof. For the first time, Clinopodium polycephalum is used as the main component, supplemented with Tamarix chinensis in an appropriate ratio, to prepare the traditional Chinese medicine composition for treating lung tumors. Experimental studies show that under this ratio, Clinopodium polycephalum and Tamarix chinensis act synergistically with each other, significantly enhancing the inhibitory effect of the obtained traditional Chinese medicine composition on the growth of lung tumors in lung cancer mice, prolonging their survival period, showing excellent therapeutic potential and application prospect for lung tumors, providing a new means for the treatment of lung tumor diseases, and also broadening the application scope of Clinopodium polycephalum and Tamarix chinensis in the field of traditional Chinese medicine.

[0094] The above descriptions are merely specific embodiments of the present invention, which enable those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but is to conform to the widest scope consistent with the principles and novel features claimed in this application.

Claims

1. A traditional Chinese medicine composition for treating lung tumors, characterized in that, The traditional Chinese medicine composition for treating lung tumors is made from Duanxueliu and Xiheliu, with the weight ratio of Duanxueliu to Xiheliu being 22:3-27:

8. The preparation method of the traditional Chinese medicine composition for treating lung tumors includes the following steps: The severed blood flow was pulverized and then added to ethyl acetate for a first reflux extraction to obtain the first extract; The willow bark was crushed and then added to water for a second reflux extraction to obtain the second extract. The first extract and the second extract are pulverized and mixed to obtain the traditional Chinese medicine composition for treating lung tumors; The working conditions for the first reflux extraction include: temperature of 80-90℃, pressure of atmospheric pressure, time of 1-2 hours, and extraction times of 1-3 times. The working conditions for the second reflux extraction include: temperature of 42~50℃, pressure of 5~10kPa, time of 1~2 hours, and extraction times of 1~3 times.

2. The traditional Chinese medicine composition for treating lung tumors according to claim 1, characterized in that, The traditional Chinese medicine composition for treating lung tumors is made from Duanxueliu and Xiheliu in a weight ratio of 25:

6.

3. The method for preparing the traditional Chinese medicine composition for treating lung tumors according to claim 1, characterized in that, The weight ratio of the interrupted blood flow to the ethyl acetate is 1:(5~8).

4. The traditional Chinese medicine composition for treating lung tumors according to claim 1, characterized in that, The weight ratio of the willow and the water is 1:(6~10).

5. The traditional Chinese medicine composition for treating lung tumors according to claim 1, characterized in that, The temperature of the second reflux extraction is 45°C, and the pressure of the second reflux extraction is 8 kPa.

6. The traditional Chinese medicine composition for treating lung tumors according to claim 1, characterized in that, The particle size of the traditional Chinese medicine composition for treating lung tumors is 200-300 mesh.

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