A composition and its use in the manufacture of a medicament having an anti-colorectal cancer effect

Abstract

The present application relates to the technical field of biological medicine, and specifically discloses a composition and application thereof in preparation of a medicine with an anti-colorectal cancer effect. Research shows that three known compounds, i.e., methoxyeudesmin, orsellinic acid glucoside and aspernolide, have an anti-colorectal cancer effect; the inventors have also found that the composition obtained by combining methoxyeudesmin, orsellinic acid glucoside and aspernolide has a much higher anti-colorectal cancer effect than methoxyeudesmin, orsellinic acid glucoside or aspernolide alone, and has a more excellent anti-colorectal cancer effect. Therefore, methoxyeudesmin, orsellinic acid glucoside, aspernolide and the composition thereof as active ingredients for preparing a medicine with an anti-colorectal cancer effect have important application value.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, in particular to a composition and application thereof in preparation of a drug with anti-colorectal cancer effect. BACKGROUND

[0002] The conquest of colorectal cancer is an urgent problem to be solved in today's medicine. The previous surgical treatment, supplemented by radiotherapy and chemotherapy, is the main treatment for colorectal cancer, but the effect is still not satisfactory, which is mainly due to the complex genetic regulation network of the tumor itself and the genetic heterogeneity of the tumor itself, thereby reducing the effectiveness and sensitivity of treatment. In recent years, with the continuous deepening of the research on tumor molecular biology, various target drugs have emerged, greatly enriching the treatment of colorectal cancer, prolonging the survival of patients and improving the quality of life.

[0003] At present, the drugs for treating colorectal cancer include bevacizumab, ranibizumab, aflibercept, ramucirumab, conbercept, sorafenib, sunitinib, sorafenib, sunitinib, pazopanib, etc.; but these drugs are not suitable for all patients. Therefore, it is of important application value to develop more drugs with anti-colorectal cancer effect and provide more drug options for patients. SUMMARY

[0004] In order to overcome at least one of the technical problems in the prior art, the present application provides the following technical solutions:

[0005] The present application first provides the use of norartemisin in the preparation of a drug with anti-cancer effect.

[0006] Preferably, the cancer is colorectal cancer.

[0007] The present application also provides the use of orsellin glucoside in the preparation of a drug with anti-cancer effect.

[0008] Preferably, the cancer is colorectal cancer.

[0009] The present application also provides the use of trichocarpon in the preparation of a drug with anti-colorectal cancer effect.

[0010] The inventors found in a large number of experimental screening that methoxyartemisin, orsellin glucoside and trichocarpon, etc. have anti-colorectal cancer effect; among them, orsellin glucoside has the best anti-colorectal cancer effect, which is significantly higher than that of methoxyartemisin and trichocarpon.

[0011] The present application also provides a composition comprising a combination of any two or three of norartemisin, orsellin glucoside and trichocarpon.

[0012] Since the three compounds of methoxy-atratractin, orsellin glucoside and labdane diterpene ketone all have the effect of resisting colorectal cancer, the composition obtained by combining any two or three of them also has the effect of resisting colorectal cancer.

[0013] Preferably, the composition consists of methoxy-atratractin, orsellin glucoside and labdane diterpene ketone.

[0014] Preferably, the mass ratio of methoxy-atratractin, orsellin glucoside and labdane diterpene ketone is 1~3:1~5:1~3.

[0015] 1~3:1~5:1~3.

[0016] Most preferably, the mass ratio of methoxy-atratractin, orsellin glucoside and labdane diterpene ketone is 2:3:2.

[0017] The inventors have found in further research that the composition obtained by combining methoxy-atratractin, orsellin glucoside and labdane diterpene ketone has a colorectal cancer resisting effect much higher than that of methoxy-atratractin, orsellin glucoside or labdane diterpene ketone alone; and that the combination of methoxy-atratractin, orsellin glucoside and labdane diterpene ketone can produce a synergistic colorectal cancer resisting effect.

[0018] The inventors have also found in research that the composition obtained by combining any two of methoxy-atratractin, orsellin glucoside and labdane diterpene ketone does not have a colorectal cancer resisting effect higher or much higher than that of methoxy-atratractin, orsellin glucoside or labdane diterpene ketone alone; and that only the composition obtained by combining methoxy-atratractin, orsellin glucoside and labdane diterpene ketone can have a colorectal cancer resisting effect much higher than that of methoxy-atratractin, orsellin glucoside or labdane diterpene ketone alone; and that only the combination of methoxy-atratractin, orsellin glucoside and labdane diterpene ketone can produce a synergistic colorectal cancer resisting effect.

[0019] The application also provides use of the above composition in the preparation of a medicament having an anticancer effect.

[0020] Preferably, the cancer is colorectal cancer.

[0021] Beneficial effects: The present application firstly provides a novel application of methoxy-eudesmin, orsellin glucoside and labdane diterpene ketone in preparing a drug with an anti-colorectal cancer effect. In addition, the inventors have found that the composition obtained by combining methoxy-eudesmin, orsellin glucoside and labdane diterpene ketone has a significantly higher anti-colorectal cancer effect than methoxy-eudesmin, orsellin glucoside or labdane diterpene ketone alone, and has a more excellent anti-colorectal cancer effect. Therefore, methoxy-eudesmin, orsellin glucoside, labdane diterpene ketone and the composition thereof as active ingredients for preparing a drug with an anti-colorectal cancer effect have important application value. DETAILED DESCRIPTION

[0022] The present application will be further explained in combination with specific examples, but the examples do not limit the present application in any form.

[0023] The methoxy-eudesmin, orsellin glucoside and labdane diterpene ketone in the following examples are all known compounds in the art.

[0024] Example 1 Preparation of the composition

[0025] The methoxy-eudesmin, orsellin glucoside and labdane diterpene ketone are mixed uniformly at a mass ratio of 2:3:2 to obtain the composition.

[0026] Example 2 Preparation of the composition

[0027] The methoxy-eudesmin and orsellin glucoside are mixed uniformly at a mass ratio of 2:3 to obtain the composition.

[0028] Example 3 Preparation of the composition

[0029] The methoxy-eudesmin and orsellin glucoside are mixed uniformly at a mass ratio of 2:3 to obtain the composition.

[0030] Example 4 Preparation of the composition

[0031] The methoxy-eudesmin and orsellin glucoside are mixed uniformly at a mass ratio of 2:3 to obtain the composition.

[0032] Experimental Example 1 Anti-colorectal cancer experiment

[0033] Take human colon cancer HT29 cells at 1x10 5The individual addition amount is added into a 96-well plate, then RPMI1640 cell culture medium is added, and incubation is carried out at 37°C in a 5% CO2 incubator for 24 h; after incubation, the medium is aspirated after adhesion, RPMI1640 cell culture medium containing different concentrations of the to-be-tested drug in a multiple dilution is added, and incubation is continued for 48 h; then 20 μL of MTT (4 mg / mL) is added to each well, and incubation is continued for 6 h, the supernatant is aspirated, 100 μL of DMSO is added to each well, and oscillation is carried out for 10 min, and then the absorbance of each well at 570 nm is tested by an enzyme-labeled instrument, and the experiment is repeated three times. The cell survival rate of the to-be-tested drug on human colon cancer cells is calculated according to the absorbance value (cell survival rate (%) = ΔOD to-be-tested drug treatment group / ΔOD blank group x 100); finally, the half-inhibitory concentration (IC 50 value) of the to-be-tested drug on human colon cancer cells is calculated according to the dose-effect curve, and the results are shown in Table 1.

[0034] The to-be-tested drug of the experimental group 1 is methoxy-eudesmin; the to-be-tested drug of the experimental group 2 is orsellin; the to-be-tested drug of the experimental group 3 is asukalonone; the to-be-tested drug of the experimental group 4 is the composition prepared in Example 1; the to-be-tested drug of the experimental group 5 is the composition prepared in Example 2; the to-be-tested drug of the experimental group 6 is the composition prepared in Example 3; and the to-be-tested drug of the experimental group 7 is the composition prepared in Example 4.

[0035]

[0036] As can be seen from the IC 50 values of the experimental groups 1-3 in Table 1, methoxy-eudesmin, orsellin and asukalonone alone all have certain anti-colorectal cancer effects; the IC 50 value of the experimental group 2 is significantly smaller than that of the experimental groups 1 and 3; this shows that methoxy-eudesmin, orsellin and asukalonone, three known compounds, all have anti-colorectal cancer effects; among them, orsellin has the best anti-colorectal cancer effect, and its anti-colorectal cancer effect is significantly higher than that of methoxy-eudesmin and asukalonone.

[0037] As can be seen from the experiment in Table 1, the IC 50 value of the experimental group 4 is significantly lower than that of the experimental groups 1-3; this shows that the composition obtained by combining methoxy-eudesmin, orsellin and asukalonone has a significantly higher anti-colorectal cancer effect than methoxy-eudesmin, orsellin or asukalonone alone; after the combination of methoxy-eudesmin, orsellin and asukalonone, a synergistic anti-colorectal cancer effect can be produced.

[0038] As can be seen from the experiment in Table 1, the IC50 The values are not lower or substantially lower than the experimental groups 1-3; this shows that: after the combination of any two of demethoxyhumulon, orobanchin and asclepiadon, the composition obtained cannot be higher or substantially higher than the anti-colorectal cancer effect of demethoxyhumulon, orobanchin or asclepiadon alone; only after the combination of demethoxyhumulon, orobanchin and asclepiadon, the composition obtained can be substantially higher than the anti-colorectal cancer effect of demethoxyhumulon, orobanchin or asclepiadon alone; only after the combination of demethoxyhumulon, orobanchin and asclepiadon, can a synergistic anti-colorectal cancer effect be produced.

Claims

1. A composition, characterized in that, The composition comprises demethoxycapsanthin, styraxanol glucoside, and gentamicin lactone; wherein the mass ratio of demethoxycapsanthin, styraxanol glucoside, and gentamicin lactone is 2:3:

2.

2. The use of the composition of claim 1 in the preparation of a medicament with anticancer activity; wherein the cancer is colorectal cancer.

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