Application of traditional Chinese medicine taxus chinensis non-toxic extract in cancer treatment

Abstract

The invention relates to the technical field of medicine and pharmacology, in particular to application of a traditional Chinese medicine taxus chinensis non-toxic extract in cancer treatment, the taxus chinensis non-toxic extract is prepared into a capsule medicament for quantification, and the capsule medicament is orally taken and absorbed through the stomach to treat lung cancer, liver cancer and other visceral cancers. The medicament prepared from the taxus chinensis non-toxic extract can also be converted into a liquid preparation for intragastric administration treatment of patients with swallowing difficulty, and has the beneficial effects that the taxus chinensis non-toxic extract is quantified in a capsule form and is orally taken for treating the visceral cancers such as lung cancer and liver cancer through the stomach, the curative effect is obvious, and toxic and side effects are avoided; and auxiliary treatment can be provided for the patient after western medicine operation and chemotherapy, so that the pain of the patient in treatment can be greatly relieved, and the life quality and life quality of the patient can be improved.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine, and in particular to application of a non-toxic extract of a traditional Chinese medicine, Taxus chinensis, in treating cancer. Background Art

[0002] The Chinese invention patent with application number 200910152866.3 discloses an extraction process for non-toxic yew extract, which can make the yew extract non-toxic, have an analgesic effect on cancer patients, can also be used as an additive to health products, allowing people to prevent tumors in advance, and can also be used as an additive to anti-tumor adjuvant therapy to assist in the treatment of tumors and relieve patients' pain.

[0003] However, the prior art does not disclose the use of non-toxic yew extract as a major Chinese patent medicine for treatment, which can be taken orally without side effects and can effectively and thoroughly treat visceral cancer. Therefore, a Chinese medicine non-toxic yew extract for the use in the treatment of cancer is proposed. Summary of the invention

[0004] In order to overcome the technical defects in the prior art and effectively solve the technical problems in the background technology, the present invention provides the following technical solutions:

[0005] The invention discloses an application of a non-toxic extract of a Chinese medicinal yew in treating cancer. The non-toxic extract of the yew is made into a capsule medicine for quantitative dosage, and is taken orally and absorbed through the stomach for treating visceral cancer.

[0006] As a preferred technical solution of the present invention, the visceral cancer is lung cancer.

[0007] As a preferred technical solution of the present invention, the visceral cancer is liver cancer.

[0008] As a preferred technical solution of the present invention, the medicine prepared from the non-toxic yew extract can be converted into a liquid preparation for oral administration to treat patients with dysphagia.

[0009] Compared with the prior art, the beneficial effects of the present invention are: the non-toxic extract of yew is quantitatively prepared in capsules for oral administration through the stomach to treat visceral cancers such as lung cancer and liver cancer, with obvious therapeutic effects and no toxic side effects; it can also be used as an auxiliary treatment for patients after Western medicine surgery and chemotherapy, which can greatly reduce the pain of treatment for patients and improve the quality of survival and life of patients.

[0010] In addition, under normal circumstances, the non-toxic extract of Taxus chinensis is given to patients in the form of solid capsules to exert its effect. If the patient is critically ill and cannot swallow, it can also be converted into a liquid and administered orally, with the same effect. DETAILED DESCRIPTION

[0011] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution in the embodiment of the present invention will be further clearly and completely described below. Obviously, the described embodiment is only a part of the embodiment of the present invention, not all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0012] Embodiment 1:

[0013] The present invention provides a technical solution: an application of a non-toxic extract of a traditional Chinese medicine, Taxus chinensis, in treating cancer. The non-toxic extract of Taxus chinensis is made into a capsule medicine for quantitative administration, and is taken orally and absorbed through the stomach for treating lung cancer.

[0014] Embodiment 2:

[0015] The present invention provides a technical solution: an application of a non-toxic extract of a traditional Chinese medicine, Taxus chinensis, in treating cancer. The non-toxic extract of Taxus chinensis is made into a capsule medicine for quantitative administration, and is taken orally and absorbed through the stomach for treating liver cancer.

[0016] Specifically, the experiment on the effect of non-toxic yew extract on Lewis lung cancer in mice is as follows:

[0017] 1. Experimental purpose:

[0018] The main purpose was to observe the inhibitory effect of different doses of non-toxic yew extracts on the growth of Lewis lung cancer in mice.

[0019] 2. Materials:

[0020] 2.1. Experimental animals and breeding environment

[0021] C57BL / 6 mice, SPF grade, half male and half female, weighing 18-22 g, were purchased from Beijing Weitonglihua Laboratory Animal Technology Co., Ltd., license number: SCXK (Beijing) 2012-0001.

[0022] Animal feed was provided by Beijing Keao Xieli Feed Co., Ltd. and implemented the standard GB14924.3-2010.

[0023] Animals were kept in the barrier environment of the experimental animal room of the Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences. The facility environmental license number is: SYXK(Beijing)2010-0032.

[0024] 2.2. Tumor strains:

[0025] Mouse Lewis lung cancer cells were provided by the Animal Center of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, and were used for long-term transplantation and passage.

[0026] 2.3.Medications:

[0027] Non-toxic yew extract: provided by Hangzhou Jieerwei Biotechnology Co., Ltd., prepared before daily administration.

[0028] Fluorouracil injection: produced by Beijing Zizhu Pharmaceutical Co., Ltd., national medicine standard H11020026, batch number: 1303261, 250mg / 10ml / vial, diluted with normal saline before use.

[0029] 2.4. Main reagents and instruments:

[0030] Red blood cell lysis buffer: Solarbio, China; microscope: Olympus, Japan; 3K15 high-speed refrigerated centrifuge: Sigma, USA; electronic analytical balance: Sartorius Technology Co., Ltd., China.

[0031] 3. Methods:

[0032] 3.1. Lewis lung cancer tumor-bearing mouse model preparation:

[0033] Under sterile conditions, the subcutaneous tumor of Lewis lung cancer-bearing mice was removed, and the well-growing tumor tissue was selected and cut into pieces with ophthalmic scissors. The homogenate was made into a homogenate with a cell homogenizer, and normal saline was added to make a tumor cell suspension. The suspension was filtered through a 200-mesh filter and washed twice. The cell concentration was adjusted to 1×10 by trypan blue counting. 7 Disinfect the right anterior armpit of the mouse, take 0.2 ml of tumor cell suspension and inoculate it subcutaneously in the right anterior armpit of C57BL / 6 mice, 2×10 6 A tumor cell.

[0034] 3.2. Grouping and processing:

[0035] 24 hours after inoculation, the animals were randomly divided into 6 groups: model group, positive control group, 0.92g / kg group, 0.46g / kg group, 0.23g / kg group, and 0.11g / kg group, with 12 mice in each group, half male and half female. After grouping, the positive control group was given fluorouracil by gavage once, with a concentration of 2.5mg / ml, a volume of 0.2ml / 10g body weight, and a dose of 50mg / kg body weight; the drugs were given once on the 5th day and the 10th day respectively. The yew groups were gavaged with 0.0460g / ml, 0.0230g / ml, 0.0115g / ml, and 0.0055g / ml of non-toxic yew extracts, with a volume of 0.2ml / 10g body weight, and the doses were 0.92g / kg, 0.46g / kg, 0.23g / kg, and 0.11g / kg body weight, respectively; the model group was gavaged with an equal volume of purified water. The above medications were given once a day for 14 consecutive days.

[0036] 3.3.Indicator detection:

[0037] 3.3.1. White blood cell count:

[0038] 24h after the last administration, mice were anesthetized with sodium pentobarbital, and about 0.5ml of blood was collected from the eyeball and dripped into a 2ml EP tube containing heparin (dried) and mixed. 200μl of whole blood was taken, 600μl of red blood cell lysis solution was added, and the mixture was mixed by inversion, and placed in the refrigerator for 15min, mixed twice in the middle, and centrifuged at 450g for 10min; the supernatant was discarded, and 300μl of red blood cell lysis solution was added to resuspend the cells, and the cells were centrifuged at 450g for 10min, the supernatant was discarded, and 1ml of normal saline was added to blow the white blood cells, and the white blood cells were counted under an Olympus microscope.

[0039] 3.3.2. Tumor growth inhibition rate and organ index:

[0040] The mice in each group were killed, the tumors were removed, the thymus and spleen were dissected, and weighed with an electronic analytical balance to calculate the tumor growth inhibition rate and organ index. Tumor growth inhibition rate (%) = (average tumor weight of model group - average tumor weight of drug administration group) / average tumor weight of model group × 100%; organ index = organ weight (mg) / body weight (g).

[0041] 3.4. Statistical analysis:

[0042] The experimental results are expressed as mean ± standard deviation. SPSS 20.0 statistical software was used for one-way analysis of variance.

[0043] 4. Results:

[0044] 4.1. Effect of Taxus chinensis non-toxic extract on tumor weight in Lewis lung cancer mice:

[0045] Table 1 Changes in tumor weight of mice in each group

[0046] Group n Tumor weight (g) Inhibition rate (%) Model Group 12 2.11±0.34 — Positive control group 12 0.19±0.08** 91.0 0.92g / kg group 12 0.81±0.31** 61.6 0.46g / kg group 12 1.67±0.88 20.9 0.23g / kg group 12 1.67±0.49 20.9 0.11g / kg group 12 1.93±0.49 8.5

[0047] Note: Compared with the model group: *p<0.05, **p<0.01. Same below.

[0048] As shown in Table 1, compared with the model group, the tumor weights of mice in the positive control group and the Taxus chinensis non-toxic extract 0.92 g / kg group were significantly reduced; while there were no significant changes in the tumor weights of the other dose groups of Taxus chinensis non-toxic extract.

[0049] 4.2. Effects of Taxus chinensis non-toxic extract on body weight, white blood cell count, thymus and spleen indexes in Lewis lung cancer mice:

[0050] Table 2 Changes in body weight of mice in each group

[0051] Group n Body weight before administration (g) Body weight after administration (g) Model Group 12 19.41±0.49 21.57±1.58 Positive control group 12 19.31±0.40 18.79±2.47 0.92g / kg group 12 19.31±0.54 18.31±2.82* 0.46g / kg group 12 19.43±0.52 21.46±0.91 0.23g / kg group 12 19.24±0.56 20.75±2.26 0.11g / kg group 12 19.38±0.42 21.8±1.83

[0052] Table 3 Changes of white blood cell count, thymus and spleen index in each group

[0053]

[0054] As can be seen from Tables 2 and 3, the body weight of mice in the group treated with 0.92 g / kg of Taxus chinensis non-toxic extract was significantly lower than that in the model group, indicating that the 0.92 g / kg body weight dose had a certain effect on body weight gain, but the body weight after administration was reduced by 5.2% compared with that before administration, which did not exceed 15%.

[0055] Compared with the model group, the white blood cell count, thymus and spleen indexes of the positive control group were significantly reduced, while there were no significant changes in the various doses of the non-toxic yew extract groups.

[0056] 5. Conclusion:

[0057] The non-toxic yew extract at a dose of 0.92 g / kg body weight had a certain inhibitory effect on the growth of Lewis lung cancer tumors in mice, with an inhibition rate of 61.6%. Fluorouracil could significantly reduce the number of white blood cells, thymus and spleen indexes in mice, while the non-toxic yew extract groups had no significant effect on this.

[0058] Specifically, the experiment on the inhibitory effect of the non-toxic yew extract on Heps solid tumors in mice is as follows:

[0059] 1. Purpose of the test:

[0060] To compare the in vivo antitumor effects and toxic side effects of different doses of Taxus chinensis non-toxic extracts and the marketed antitumor drug paclitaxel injection on Heps solid tumors in mice.

[0061] 2. Materials and methods

[0062] 2.1. Test substances:

[0063] Taxus non-toxic extract, provided by Dongyang Chengjie Taxus Development Co., Ltd., grind the Taxus non-toxic extract in a mortar evenly, and weigh it accurately according to the set dose. Add 50% of the total volume of polyethylene glycol 400 (PEG400) and grind until it is completely dissolved, then gradually add purified water to continue grinding, and finally dilute to the total volume with purified water. Paclitaxel injection, specification 5ml:30mg, batch number 1003211, produced by Shanxi Zhendong Taisheng Pharmaceutical Co., Ltd.

[0064] 2.2. Tumor strains:

[0065] Mouse hepatocellular carcinoma Heps solid tumor was passaged and maintained by our laboratory.

[0066] 2.3. Animals and breeding environment:

[0067] ICR mice, clean grade, half male and half female, weighing 18-22 g, were provided by Zhejiang Provincial Experimental Animal Center, with the laboratory animal qualification certificate number SCXK (Zhejiang) 2008-0033. Animal feed was provided by Zhejiang Provincial Experimental Animal Center, in accordance with the standard GB14924.1-2001. Animals were kept in clean cages, kept quiet and ventilated, with a room temperature of 19°C to 25°C, a relative humidity of 60-70%, and artificial 12-hour alternating light, and the laboratory animal facility environment qualification certificate number SYXK (Zhejiang) 2005-0074.

[0068] 2.4. Dosage design:

[0069] The experiment set up a tumor-bearing model group and three dose groups of high, medium and low doses of Taxus chinensis non-toxic extract, 6.6, 2.2 and 0.73 g / kg. The doses converted according to the paclitaxel content were 6.6, 2.2 and 0.73 mg / kg, respectively. Among them, 6.6 g / kg of Taxus chinensis non-toxic extract was converted into a crude drug dose of 120 g / kg, which was the highest safe dose for acute toxicity tests; the high and low dose groups of paclitaxel injection were 15 and 6.6 mg / kg (calculated as the active ingredient paclitaxel).

[0070] 2.5. Test methods:

[0071] Aseptically extract the ascites of Heps liver cancer mice, count the cells under a microscope, and adjust the cell suspension concentration to 4×10 7 0.2 ml of the above ascites tumor fluid was inoculated aseptically in the right axilla of mice (8×10 cells per mouse). 6 The next day, the animals were randomly divided into tumor-bearing model group (gavage with 50% PEG400, 0.3ml / 10g), three dose groups of Taxus chinensis non-toxic extract (gavage with different concentrations of the test drug dissolved in 50% PEG400, 0.3ml / 10g), and high- and low-dose groups of paclitaxel injection (intraperitoneal injection of corresponding concentrations of paclitaxel injection, 0.2ml / 10g). Each group was given once a day for 10 consecutive days. Blood was collected from the eyeballs 24 hours after the last administration to count white blood cells. After the animals were killed, the tumors were dissected and weighed to calculate the tumor inhibition rate, and the thymus and spleen were weighed.

[0072] 2.6. Statistics:

[0073] All measured data were expressed as mean ± standard deviation (Mean ± SD) and were statistically analyzed using SPSS Statistics 17.0 software. One-way analysis of variance was used for comparison among groups, and P < 0.05 was considered statistically significant.

[0074] 3. Results

[0075] 3.1. Anti-tumor effect and toxic side effects of paclitaxel injection on Heps liver cancer mice (preliminary test):

[0076] The results are shown in Table 1. Compared with the tumor-bearing model group, intraperitoneal injection of 10-15 mg / kg paclitaxel injection had a significant inhibitory effect on Heps liver cancer in mice (P<0.001), with an inhibition rate of 32.0-53.9%, and a significant inhibitory effect on the body weight, thymus and spleen of mice (P<0.01). Intraperitoneal injection of 5 mg / kg paclitaxel injection had no significant inhibitory effect on Heps liver cancer in mice (P>0.05), and had no significant effect on the body weight, thymus and spleen of mice (P>0.05). This shows that paclitaxel injection can significantly inhibit Heps liver cancer in mice with increasing doses, but at the same time has a significant inhibitory effect on the body weight, thymus and spleen of mice, showing strong toxicity.

[0077] Table 1 Effects of paclitaxel on tumors and organs in Heps liver cancer mice.

[0078]

[0079] Mean±SD, **P<0.01, ***P<0.001 vs. tumor-bearing model, t-test.

[0080] 3.2 Antitumor effects of Taxus chinensis non-toxic extract and paclitaxel injection on Heps liver cancer mice:

[0081] The results are shown in Table 2. Compared with the tumor-bearing model group, oral administration of 0.73-6.6 g / kg of non-toxic yew extract had a significant inhibitory effect on Heps liver cancer in mice (P<0.001), with an inhibition rate of 22.7-43.6%; intraperitoneal injection of 6.6-15 mg / kg paclitaxel injection had a significant inhibitory effect on Heps liver cancer in mice (P<0.001), with an inhibition rate of 29.8-57.1%; oral administration of 6.6 g / kg non-toxic yew extract (equivalent to 6.6 mg / kg paclitaxel) had a significantly stronger inhibitory effect on Heps liver cancer in mice than intraperitoneal injection of 6.6 mg / kg paclitaxel injection (P<0.05), indicating that at equivalent doses, oral administration of non-toxic yew extract has a significantly stronger anti-tumor effect than intraperitoneal injection of paclitaxel injection.

[0082] Table 2 Inhibitory effects of Taxus chinensis non-toxic extract and paclitaxel injection on tumors in Heps liver cancer mice.

[0083] Group n Average tumor weight (g) Tumor inhibition rate (%) Tumor-bearing model 15 2.15±0.25 -- Taxus chinensis ig6.6g / kg 11 1.21±0.29 43.6 Taxus chinensis ig 2.2g / kg 11 1.46±0.25 32.1 Taxus chinensis ig 0.73g / kg 11 1.66±0.23 22.7 Paclitaxel ip 15 mg / kg 11 0.92±0.10 57.1 Paclitaxel ip 6.6 mg / kg 11 <![CDATA[1.51±0.25 # ]]> 29.8

[0084] Mean±SD, ***P<0.001 vs. tumor-bearing model; # P<0.05vs.6.6g / kg Taxus, t-test.

[0085] 3.3 Toxic effects of Taxus chinensis non-toxic extract and paclitaxel injection on Heps liver cancer mice:

[0086] The results are shown in Table 3. Compared with the tumor-bearing model group, intraperitoneal injection of 6.6-15 mg / kg paclitaxel injection had a significant inhibitory effect on the body weight, spleen index and white blood cell count of Heps liver cancer mice (P<0.001). Intraperitoneal injection of 15 mg / kg paclitaxel injection also had a significant inhibitory effect on the thymus index of Heps liver cancer mice (P<0.001). Oral administration of 0.73-6.6 g / kg non-toxic yew extract had a significant inhibitory effect on the body weight and thymus index of Heps liver cancer mice. , spleen (P>0.05), and only had a certain inhibitory effect on the number of white blood cells (P<0.05). However, the inhibitory effect of 6.6g / kg Taxus chinensis non-toxic extract (equivalent to 6.6mg / kg paclitaxel) by oral gavage on the number of white blood cells in Heps liver cancer mice was significantly weaker than that of 6.6mg / kg paclitaxel injection by intraperitoneal injection (P<0.001), indicating that at equivalent doses, the toxic and side effects of Taxus chinensis non-toxic extract by oral gavage are significantly weaker than those of paclitaxel injection by intraperitoneal injection.

[0087] Table 3 Effects of Taxus chinensis non-toxic extract and paclitaxel injection on organs and leukocyte counts in Heps liver cancer mice.

[0088]

[0089] Mean±SD, *P<0.05, **P<0.01, ***P<0.001 vs. tumor-bearing model, # P<0.05,

[0090] ### P<0.001vs.6.6g / kg Taxus, t-test.

[0091] 4. Conclusion

[0092] Intragastric administration of 0.73-6.6 g / kg of Taxus chinensis non-toxic extract had a significant inhibitory effect on Heps solid tumors in mouse liver cancer. Intragastric administration of 6.6 g / kg of Taxus chinensis non-toxic extract (equivalent to 6.6 mg / kg paclitaxel) had a stronger anti-tumor effect than intraperitoneal injection of 6.6 mg / kg paclitaxel injection, while having fewer toxic side effects.

[0093] Clinical pathology:

[0094] Case 1: Ni, who suffered from breast cancer that had metastasized to the esophagus and brain, had been unable to eat for four days and was in a state of confusion. The hospital declared her in critical condition. She was then given non-toxic yew extract and was discharged from the hospital after fifty days. She continued to take the extract for fifteen months and was completely cured.

[0095] Case 2: Xie Moumou suffered from rectal cancer and could not be cured after two years of treatment. He then took non-toxic extract of yew and was completely cured in six months.

[0096] Case 3: Xu, who suffered from rectal cancer, took red bean and non-toxic cedar extract and recovered completely in six months.

[0097] Case 4: Qi Moumou, who suffered from lymphoma, was hospitalized for treatment. His condition continued to deteriorate and he was declared critically ill. He then took red bean and non-toxic fir extract and recovered within five and a half months.

[0098] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

[0099] Main references

[0100] [1] Xu Shuyun. Pharmacological Experimental Methodology. 3rd edition. Beijing: People's Medical Publishing House, 2001. 1757-1760 [2] Chen Qi. Methodology of Traditional Chinese Medicine Pharmacological Research. 2nd edition. Beijing: People's Medical Publishing House, 2006. 1018-1019.

Claims

1. Application of a non-toxic extract of Chinese medicinal yew in treating cancer, characterized in that: The non-toxic extract of Taxus chinensis is made into capsule medicine for quantitative use, and is taken orally for absorption through the stomach to treat visceral cancer.

2. The use of the non-toxic Chinese medicinal yew extract in treating cancer according to claim 1, characterized in that: The visceral cancer is lung cancer.

3. The use of the non-toxic Chinese medicinal yew extract in treating cancer according to claim 1, characterized in that: The visceral cancer is liver cancer.

4. The use of the non-toxic Chinese medicinal yew extract in treating cancer according to claim 1, characterized in that: The medicine prepared from the non-toxic yew extract can be transformed into a liquid preparation for intragastric administration to treat patients with dysphagia.

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