A compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation and a preparation method thereof

Abstract

The application provides a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. The compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation is prepared from the following components in a mass fraction: 0.5-2.0 parts of paclitaxel powder with a purity of 99%, 18-30 parts of Herba Lysimachiae, 18-30 parts of Herba Impatientis, 18-30 parts of Radix Scrophulariae, 14-25 parts of Radix Curcumae, 14-25 parts of Radix Pini Strobil, 14-25 parts of Gynostemma pentaphyllum, 14-25 parts of Citrus medica, 10-18 parts of Radix Paeoniae Alba, 10-18 parts of Radix Paeoniae Rubra, 10-18 parts of Radix Rabdosiae, 6-12 parts of Fructus Schisandrae, 6-12 parts of Lumbricus, and 6-12 parts of Radix Glycyrrhizae. The compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation can not only significantly inhibit the growth of tumor cells on a lung cancer patient, but also significantly reduce bone marrow suppression and immune function damage caused by paclitaxel.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation and a preparation method thereof. BACKGROUND

[0002] Cancer is one of the major diseases that seriously threaten human survival and health, and its incidence is on the rise, with a very high mortality rate. Traditional methods for treating cancer include surgery, radiotherapy and chemical drug therapy, and currently, chemical therapy is one of the main treatment methods for advanced cancer. However, the currently widely used chemotherapeutic drugs have limited efficacy and large toxic effects, and drug resistance occurs after multiple administrations. Paclitaxel is a single diterpene compound extracted from the bark of natural plants of the Taxus genus, which is a complex secondary metabolite and the only drug known to date that can promote microtubule polymerization and stabilize the polymerized microtubules. Through clinical studies, paclitaxel is mainly suitable for ovarian cancer and breast cancer, and also has certain efficacy for lung cancer, colorectal cancer, melanoma, head and neck cancer, lymphoma and brain tumor. However, pure paclitaxel has various toxic side effects: 1. allergic reactions: rash, respiratory distress, bronchospasm, hypotension occur within a few minutes after administration; 2. nervous system reactions: numbness of hands and feet, hypersensitivity, muscle spasm, joint pain; 3. digestive system reactions: nausea, vomiting, diarrhea, oral inflammation, gastritis; 4. cardiovascular system reactions: tachycardia, ventricular arrhythmia, or bradycardia, atrioventricular block; 5. alopecia; 6. bone marrow suppression reactions: white blood cell reduction, thrombocytopenia and anemia occur after administration. The toxic side effects limit the clinical application of paclitaxel.

[0003] Therefore, there is an urgent need in the market for a traditional Chinese medicine preparation that can significantly reduce the side effects of paclitaxel and significantly enhance the anticancer effect. SUMMARY

[0004] The present application aims to provide a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation and a preparation method thereof.

[0005] In order to achieve the above-mentioned purpose, the present application provides the following technical solutions:

[0006] The present application provides a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation, which is prepared from the following components with the following mass fractions:

[0007] Paclitaxel powder with a purity of 99% 0.5-2.0 parts, Herba Houttuyniae 18-30 parts, Herba Impatientis 18-30 parts, Radix Scrophulariae 18-30 parts, Radix Curcumae 14-25 parts, Rhizoma Atractylodis 14-25 parts, Herba Gynostemmatis Pentaphylli 14-25 parts, Fructus Citri Sarcodactylis 14-25 parts, Radix Paeoniae Alba 10-18 parts, Radix Puerariae 10-18 parts, Radix Paeoniae Rubra 10-18 parts, Radix Stachys 10-18 parts, Fructus Schisandrae 6-12 parts, Lumbricus 6-12 parts, Radix Glycyrrhizae 6-12 parts.

[0008] Preferably, the dosage form of the traditional Chinese medicine preparation is a capsule, a tablet, a granule or a pill.

[0009] The application also provides a preparation method of the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation, comprising the following steps:

[0010] 1) mixing and crushing each traditional Chinese medicine raw material except paclitaxel to obtain a mixture;

[0011] 2) mixing the mixture with water, and then sequentially decocting and filtering to obtain a filtrate I and a residue;

[0012] 3) mixing the residue with water, and then sequentially decocting and filtering to obtain a filtrate II;

[0013] 4) combining the filtrate I, the filtrate II and paclitaxel powder, and then sequentially reducing pressure concentrating, drying the combined mixture to obtain the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation.

[0014] Preferably, the particle size of the crushing in the step 1) is 80-120 mesh.

[0015] Preferably, the mass ratio of the mixture to water in the step 2) is 1:8-14.

[0016] Preferably, the decocting time in the step 2) is 80-120 min, and the decocting temperature is 65-75℃.

[0017] Preferably, the mass ratio of the residue to water in the step 3) is 1:4-6.

[0018] Preferably, the decocting time in the step 3) is 40-60 min, and the decocting temperature is 55-68℃.

[0019] Preferably, the mixture is reduced pressure concentrated to a thick paste with a relative density of 1.2-1.3 at 24-28℃.

[0020] Preferably, the drying mode is vacuum drying.

[0021] The application has the following beneficial technical effects:

[0022] The paclitaxel added in the present application can inhibit mitosis of cancer cells, effectively prevent proliferation of cancer cells, and has broad-spectrum anticancer effect; Houttuynia cordata Thunb. is used for treating boils, sore throat, snake bite, sprain, edema, and jaundice, etc., and is recorded in "Mingjing Shiyi Fu" as "Houttuynia cordata Thunb. is a magical herb for treating snake bite". Yixingcao has the effects of astringing and hemostasis, tonifying deficiency, detoxification, stopping diarrhea, malaria, insect killing, cough relieving, and anticancer. Scutellaria baicalensis Georgi is used for treating dampness-heat, summer dampness, chest distress, vomiting, constipation, jaundice, lung heat, high fever, blood heat, and carbuncle, etc. The present application uses the above four herbs as the monarch herbs, and has the effects of detoxification, resolving masses, anticancer, and the like.

[0023] Radix Anemarrhena Asphodeloides is used for treating chest and breast pain, chest distress, menstrual pain, heat-induced coma, epilepsy, blood heat-induced vomiting, and jaundice. The main effective components of Radix Atractylodis Macrocephalae include polysaccharides, flavonoids, lactones, volatile components, and glycosides, etc., and have the effects of anti-inflammatory and analgesic, anti-tumor, immune regulation, hypoglycemic, lipid-lowering, and liver protection, etc. Gynostemma pentaphyllum is used for tonifying qi and invigorating the spleen, reducing phlegm and relieving cough, and nourishing the heart and tranquilizing the mind. Pharmacological researches show that Gynostemma pentaphyllum has the effects of anti-fatigue, anti-hypoxia, anti-high temperature, anti-low temperature, reducing the content of lipofuscin in heart, brain, and liver cells, and preventing normal cells from canceration. Citrus medica is used for treating liver stagnation and qi stagnation, spleen and stomach qi stagnation, and cough with much phlegm. The present application uses the above four herbs as the ministerial herbs, and has the effects of invigorating the spleen and tonifying qi, soothing the liver and resolving stagnation, analgesia, and anticancer.

[0024] Radix Astragali is used for tonifying qi and ascending yang, stopping sweating, reducing edema, promoting blood circulation, and has the effects of improving antioxidant capacity and eliminating free radicals in the body. Caulis Spatholobi is used for activating blood and tonifying blood, regulating menstruation and relieving pain, relaxing the tendons and activating the collaterals, and reducing peripheral nerve toxicity. Radix Paeoniae Alba is used for tonifying blood and regulating menstruation, astringing yin and stopping sweating, soothing the liver and relieving pain, and suppressing liver yang. Rhizoma Sinodendri is used for expelling wind and dampness, relaxing the tendons and activating the collaterals, and activating blood and reducing swelling, and is most suitable for treating wind-cold-dampness arthralgia, joint pain, and flexion and extension difficulty, and can be selected for treating sprain and swelling. The present application uses the above four herbs as the auxiliary herbs, and has the effects of tonifying blood and stomach, and tonifying qi and activating blood, and the qi flow can promote blood flow, and can tonify deficiency of cancer patients.

[0025] Schisandra contains lignans, volatile oil, also contains polysaccharide, amino acid and other components, can be used for astringent, Yiqi Shengjin, Bushen Ningxin. Modern research shows that earthworms mainly contain earthworm heat-dissolving base, earthworm toxin, 6-hydroxy purine, xanthine, adenine, guanine, choline, etc.; also contains a variety of amino acids, fatty acids, etc., earthworms have antipyretic, sedative, anticonvulsant, antithrombotic, hypotensive, anti-inflammatory, analgesic, antiasthmatic, enhance immunity and other pharmacological effects. Gansheng licorice can be used for the treatment of food, weak spleen and stomach, abdominal pain and diarrhea, fatigue, palpitation, shortness of breath, cough and sputum, abdominal, limbs, and can also be used for the treatment of carbuncle, sore, drug toxicity and violent. The above three medicines are used in the present application, which can tonify the kidney and calm the heart, enhance immunity, adjust the drug property, and relieve the toxicity and violence of the whole medicine.

[0026] The compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation fully embodies the scientific drug principle of regulating the balance of the whole physiological function of the body to play the role of anticancer and cancer treatment according to the theory of traditional Chinese medicine, and mainly detoxifies and dispels stasis, prevents and resists cancer, and effectively reduces the drug toxicity and violence while tonifying the spleen, invigorating qi, and nourishing blood to support the healthy and treat the root. It can not only significantly inhibit the growth of tumor cells on the body of lung cancer patients, but also significantly reduce the bone marrow suppression and immune function damage caused by paclitaxel. DETAILED DESCRIPTION

[0027] In order to better understand the present application, the following examples are further illustrated, but the content of the present application is not limited to the following examples. The paclitaxel in the present application is a commercially available medical grade paclitaxel powder with a purity of 99%.

[0028] Example 1

[0029] The present application provides a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation, which is prepared from the following components with mass fraction:

[0030] 0.5 parts of paclitaxel powder with a purity of 99%, 18 parts of Jinping, 18 parts of Xianhecao, 18 parts of Huangqin, 14 parts of Yujin, 14 parts of Baishu, 14 parts of Jiaogulou, 14 parts of Foshou, 10 parts of Huangqi, 10 parts of Jixueteng, 10 parts of Baishao, 10 parts of Shentongcao, 6 parts of Wuweizi, 6 parts of Dilong, and 6 parts of Gansheng.

[0031] The preparation method of the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation comprises the following steps:

[0032] 1) Mix and crush all the traditional Chinese medicine raw materials except paclitaxel to 80 mesh to obtain a mixture;

[0033] 2) Mix the mixture with water at a mass ratio of 1:8, and then cook at 65℃ for 80min. After cooking, filter to collect filtrate I and drug residue;

[0034] 3) the dregs are mixed with water at a mass ratio of 1:4, decocted at 55°C for 40 min, filtered after decoction, and the filtrate II is collected;

[0035] 4) the filtrate I and the filtrate II are combined with the paclitaxel powder, the combined mixture is concentrated under reduced pressure to a thick paste with a relative density of 1.2 at 24°C, and then vacuum dried to 200 mesh to prepare the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation.

[0036] Example 2

[0037] The application provides a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation, which is prepared from the following components with the following mass fractions:

[0038] 2.0 parts of paclitaxel powder with a purity of 99%, 30 parts of Herba Lysimachiae, 30 parts of Herba Reineckiae, 30 parts of Radix Scrophulariae, 25 parts of Radix Paeoniae Alba, 25 parts of Rhizoma Bletillae, 25 parts of Herba Gynostemmatis Pentaphylli, 25 parts of Citrus medica, 18 parts of Radix Astragali, 18 parts of Caulis Spatholobi, 18 parts of Radix Paeoniae Alba, 18 parts of Herba Sedi, 12 parts of Fructus Schisandrae, 12 parts of Lumbricus, and 12 parts of Radix Glycyrrhizae.

[0039] The preparation method of the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation comprises the following steps:

[0040] 1) mixing and crushing all the traditional Chinese medicine raw materials except paclitaxel to 120 mesh to obtain a mixture;

[0041] 2) mixing the mixture with water at a mass ratio of 1:14, decocting at 75°C for 120 min, filtering after decoction, and collecting the filtrate I and the dregs;

[0042] 3) mixing the dregs with water at a mass ratio of 1:6, decocting at 68°C for 60 min, filtering after decoction, and collecting the filtrate II;

[0043] 4) combining the filtrate I and the filtrate II with the paclitaxel powder, concentrating the combined mixture under reduced pressure to a thick paste with a relative density of 1.3 at 28°C, and then vacuum drying to 400 mesh to prepare the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation.

[0044] Example 3

[0045] The application provides a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation, which is prepared from the following components with the following mass fractions:

[0046] 1.2 parts of paclitaxel powder with a purity of 99%, 24 parts of Herba Lysimachiae, 24 parts of Herba Reineckiae, 24 parts of Radix Scrophulariae, 18 parts of Radix Paeoniae Alba, 18 parts of Rhizoma Bletillae, 18 parts of Herba Gynostemmatis Pentaphylli, 18 parts of Citrus medica, 14 parts of Radix Astragali, 14 parts of Caulis Spatholobi, 14 parts of Radix Paeoniae Alba, 14 parts of Herba Sedi, 8 parts of Fructus Schisandrae, 8 parts of Lumbricus, and 8 parts of Radix Glycyrrhizae.

[0047] The preparation method of the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation comprises the following steps:

[0048] 1) Mix and crush each traditional Chinese medicine raw material except paclitaxel into 100 mesh to obtain a mixture;

[0049] 2) Mix the mixture with water at a mass ratio of 1:12, and then boil at 70 DEG C for 100 min; after boiling, filter to collect filtrate I and dregs;

[0050] 3) Mix the dregs with water at a mass ratio of 1:5, and then boil at 62 DEG C for 50 min; after boiling, filter to collect filtrate II;

[0051] 4) Combine filtrate I, filtrate II and paclitaxel powder, and then reduce pressure to concentrate the combined mixture into a thick paste with a relative density of 1.25 at 25 DEG C; vacuum dry to 300 mesh to obtain the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation.

[0052] Comparative Example 1

[0053] The same as Example 3, except that the raw material paclitaxel is removed.

[0054] Comparative Example 2

[0055] The same as Example 3, except that the amount of paclitaxel powder with a purity of 99% is replaced by 0.2 parts.

[0056] Experimental Example 1

[0057] 1. Experimental grouping:

[0058] Select 50 male healthy C57BL / 6 mice with a body weight of 18-22 g and an age of 6-8 weeks, and model them by injecting Lewis lung cancer cells (adjust the cell concentration to 1x10 7 / ml, 0.2 mL per mouse) through the tail vein. After successful modeling, the mice are grouped as follows:

[0059] Model group: physiological saline, dose of 30 g / kg, gavage once a day;

[0060] Experimental group: the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation described in Example 3 of the present application, dose of 30 g / kg, gavage once a day;

[0061] Control group 1: the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation described in Comparative Example 1 of the present application, dose of 30 g / kg, gavage once a day;

[0062] Control group 2: the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation described in Comparative Example 2 of the present application, dose of 30 g / kg, gavage once a day;

[0063] Prior art group: conventional dose of paclitaxel chemotherapy group, 30 mg / kg intraperitoneal injection, 5 days / time;

[0064] During the experiment, the mice were normally fed, and the feeding temperature was set to 24-26 DEG C, and the humidity was 45-65%; continuously administered for 10 days, and after the last administration, the mice were fasted without water, and the mice were weighed and killed after 24 hours.

[0065] 2, the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation of lung cancer transplantation inhibition experiment

[0066] The tumor mass of the killed mouse in step 1 is completely stripped, weighed and the tumor inhibition rate is calculated, the tumor inhibition rate = (tumor weight of the model group - tumor weight of the treatment group) / tumor weight of the model group, and the results are shown in Table 1.

[0067] Table 1

[0068] Experimental group Tumor weight (x ± s) Tumor inhibition rate (%) Model group 3.25±0.22 / Experimental group 0.89 ± 0.26 a ]] 72.61 Control group 1 1.86 ± 0.12 a ]] 42.77 Control group 2 1.63 ± 0.33 a ]] 49.85 Prior art group 1.14 ± 0.16 a ]] 64.92

[0069] a: P < 0.05; compared with the model group;

[0070] As shown in Table 1, the tumor inhibition rate of the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation of the present application is significantly higher than that of the prior art group and the control group, and the traditional Chinese medicine preparation of the present application has a significant inhibitory effect on the growth of lung cancer.

[0071] 2, the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation of bone marrow inhibition experiment

[0072] The femur of one side of the killed mouse in step 1 is completely removed, the femoral head and tibial end are cut off, and all bone marrow cells in the femur are flushed out with red blood cell lysis solution, and repeatedly washed until the bone marrow is white. The flushed bone marrow cells are made into a single cell suspension, and 8 ml of physiological saline is added to terminate lysis, and after centrifugation at 1200 rpm for 6 min, the supernatant is discarded, and the cells are resuspended with 1 ml of physiological saline, and 20 μL of cell sediment is added to the counting plate to determine the number of nucleated cells in the bone marrow, and the results are shown in Table 2.

[0073] Table 2 Number of nucleated cells in bone marrow (BMN)

[0074]

[0075]

[0076] a: P < 0.05; compared with the model group;

[0077] b: P < 0.05; compared with the prior art group;

[0078] The results are shown in Table 2, the number of nucleated cells in the bone marrow of the mice injected with paclitaxel alone is significantly reduced, while the number of nucleated cells in the bone marrow of the mice in the experimental group is significantly higher than that of the mice injected with paclitaxel alone, so it can be known that the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation can significantly reduce the bone marrow suppression caused by paclitaxel chemotherapy.

[0079] 3, the influence of the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation on immune function

[0080] The spleen and thymus of the mice killed in step 1 are completely stripped, and the spleen index and thymus index of the mice in each experimental group are calculated according to the formula; the spleen index = the weight of the spleen of the mouse / the weight of the mouse; the thymus index = the weight of the thymus of the mouse / the weight of the mouse, and the results are shown in Table 3.

[0081] Table 3: Results of mouse weight, thymus / spleen index (x ± s)

[0082] Experimental group Body weight (g) Spleen index (mg / g) Thymus index (mg / g) Model group 26.12±1.25 10.59±0.43 0.52±0.38 Experimental group 22.87±2.12 11.08±0.33 0.46 ± 0.22 b ]] Control group 1 23.68±3.97 12.24±0.56 0.51 ± 0.16 b ]] Control group 2 23.06±3.22 11.93±0.28 0.48 ± 0.32 b ]] Prior art group 19.64±1.58 9.45±0.27 0.26 ± 0.12 a ]]

[0083] a: P < 0.05, compared with the model group;

[0084] b: P < 0.05, compared with the prior art group;

[0085] As can be known from the results in Table 3, compared with the mice injected with paclitaxel alone, the thymus index and spleen index of the mice in the experimental group are significantly increased, so it can be known that the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation can reduce the atrophy of the spleen and thymus induced by paclitaxel chemotherapy, and further resist the inhibitory effect of paclitaxel on immune function.

[0086] The above is only the preferred embodiment of the present application, and it should be noted that for those skilled in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation, characterized in that, It is prepared from the following components by mass fraction: Paclitaxel 0.5–2.0 parts, Scutellaria barbata 18–30 parts, Agrimonia pilosa 18–30 parts, Scutellaria baicalensis 18–30 parts, Curcuma longa 14–25 parts, Atractylodes macrocephala 14–25 parts, Gynostemma pentaphyllum 14–25 parts, Citrus medica 14–25 parts, Astragalus membranaceus 10–18 parts, Spatholobus suberectus 10–18 parts, Paeonia lactiflora 10–18 parts, Lycopodium clavatum 10–18 parts, Schisandra chinensis 6–12 parts, Pheretima aspergillum 6–12 parts, Glycyrrhiza uralensis 6–12 parts.

2. The compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation according to claim 1, characterized in that, The dosage form of the traditional Chinese medicine preparation is capsule, tablet, granule or pill.

3. A method for preparing a compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation according to claim 1 or 2, characterized in that, Includes the following steps: 1) Mix and pulverize all Chinese herbal raw materials except paclitaxel to obtain a mixture; 2) After mixing the ingredients with water, boil and filter them sequentially to obtain filtrate I and dregs; 3) Mix the dregs with water, then decoct and filter to obtain filtrate II; 4) After combining filtrate I and filtrate II with paclitaxel, the combined mixture is concentrated under reduced pressure and dried sequentially to obtain the compound paclitaxel broad-spectrum anticancer traditional Chinese medicine preparation.

4. The preparation method according to claim 3, characterized in that, The particle size of the pulverized material in step 1) is 80-120 mesh.

5. The preparation method according to claim 3, characterized in that, In step 2), the mass ratio of the mixture to water is 1:8 to 14.

6. The preparation method according to claim 3, characterized in that, The simmering time in step 2) is 80-120 minutes, and the simmering temperature is 65-75℃.

7. The preparation method according to claim 3, characterized in that, The mass ratio of the dregs to water in step 3) is 1:4 to 6.

8. The preparation method according to claim 3, characterized in that, The simmering time in step 3) is 40-60 minutes, and the simmering temperature is 55-68°C.

9. The preparation method according to claim 3, characterized in that, In step 4), the mixture is concentrated under reduced pressure to a thick paste with a relative density of 1.2 to 1.3 at 24 to 28°C.

10. The preparation method according to claim 3, characterized in that, The drying method in step 4) is vacuum drying.

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