CN110559287A

CN110559287A - Pharmaceutical composition for treating cancer and application thereof

Info

Publication number: CN110559287A
Application number: CN201910875638.2A
Authority: CN
Inventors: 卞兆祥; 关晓仪; 龚锐洪; 陈敏婷; 胡显镜; 法蒂玛莎瓦特; 黄春华; 肖海涛
Original assignee: Institute for Research and Continuing Education HKBU
Current assignee: Institute for Research and Continuing Education HKBU
Priority date: 2019-09-17
Filing date: 2019-09-17
Publication date: 2019-12-13

Abstract

The invention discloses a pharmaceutical composition for treating cancer, and belongs to the field of biological medicines. The medicine composition comprises wogonin and sweet wormwood succinate, and the molar concentration ratio of the wogonin to the sweet wormwood succinate in the medicine composition is 1: 3-3: 1. the invention also discloses the application of wogonin and artesunate in preparing the medicine for treating cancer. The pharmaceutical composition or the medicament can more effectively treat cancer, simultaneously reduces toxic and side effects, and has remarkable medical value.

Description

Pharmaceutical composition for treating cancer and application thereof

Technical Field

The invention belongs to the field of biological medicines, and particularly relates to a pharmaceutical composition for treating cancer and application thereof.

Background

worldwide, cancer has a high incidence and mortality rate. In recent decades, there has been a constant effort in humans to treat cancer, and cancer research has focused on developing new treatments and reducing the side effects of treatments on patients. The currently used method for treating cancer is mainly surgery or chemotherapy, but in many cases, the method cannot effectively treat patients and has high risk of complications, and some cancer treatment drugs not only have multiple side effects, but also can cause multiple drug resistance. In recent years, the combined medication gradually becomes a research hotspot of cancer treatment, and the combined medication can achieve the aim of reducing the toxic and side effects of chemotherapy drugs and simultaneously increasing the anticancer effect of the drugs by playing the synergistic anticancer role of the drugs.

Wogonin (WOG), also known as 5, 7-dihydroxy-8-methoxy-2-phenyl-4H-1-benzofuran-4-one, is a flavonoid compound from the root of medicinal plant Scutellaria baicalensis Georgi (Scutellaria baicalensis Georgi), the molecular formula of which is C₁₆H₁₂O₅It is yellow needle-shaped crystal. Research shows that wogonin has wide bioactivity, such as antioxidant activity, anti-inflammatory activity, neuroprotection, antitumor activity, antiviral activity and the like, and especially has antitumor activity, so that wogonin is a research hotspot at present. In vivo and in vitro research on various tumor cells shows that wogonin has an inhibiting effect on the proliferation of tumor cells. Wogonin has been shown to induce apoptosis and differentiation, affect cell cycle and inhibit tumor angiogenesis. The artesunate is sesquiterpene lactone medicine with peroxy group extracted from stem and leaf of Artemisia annua. In recent years, researches show that artesunate has good activity in anticancer, and particularly as an anticancer drug, two application modes are possible: one is as a sheetA single use anti-tumor drug; the other is an anti-tumor drug which is used as a sensitizer in combination with other tumor chemotherapy drugs.

The artesunate is sesquiterpene lactone medicine with peroxy group extracted from stem and leaf of Artemisia annua. In recent years, researches show that artesunate has good activity in anticancer, and particularly as an anticancer drug, two application modes are possible: one is used as an antitumor drug used alone; the other is an anti-tumor drug which is used as a sensitizer in combination with other tumor chemotherapy drugs.

However, for cancer treatment, there is still a lack of very effective drugs.

Disclosure of Invention

In order to solve the above technical problems, the inventors have unexpectedly found that the combined use of artesunate and wogonin produces a synergistic effect, thereby treating cancer more effectively while reducing toxic and side effects. Thus, the present invention has been completed.

The invention aims to provide a novel combination drug for resisting hepatocellular carcinoma, and for the purpose,

In one aspect, the present invention provides a pharmaceutical composition for treating cancer, comprising wogonin and artesunate.

In some embodiments of the invention, the molar concentration ratio of wogonin to artesunate in the pharmaceutical composition is 1: 3-3: 1. for example, 1: 3. 1: 2. 1: 1. 2: 1. 3: 1. in some preferred embodiments of the present invention, the molar concentration ratio of wogonin to artesunate in the pharmaceutical composition is 1: 1 and 1: 2.

In a second aspect the invention provides the use of wogonin and artesunate for the manufacture of a medicament for the treatment of cancer.

In some embodiments of the invention, the molar concentration ratio of wogonin to artesunate in the medicament is 1: 3-3: 1. for example, 1: 3. 1: 2. 1: 1. 2: 1. 3: 1. in some preferred embodiments of the present invention, the molar concentration ratio of wogonin to artesunate in the medicament is 1: 1 and 1: 2.

in the present invention, the cancer is liver cancer.

in some embodiments of the invention, the cancer is primary liver cancer.

The invention has the advantages of

Compared with the prior art, the invention has the beneficial technical effects that: the combination of wogonin and artesunate has obvious synergistic effect, can effectively treat cancer, and simultaneously reduces toxic and side effects.

Drawings

Figure 1 shows a comparison of tumor size in combination of wogonin and artesunate compared to single drug in nude mice inoculated with primary hepatocellular carcinoma tumors.

Figure 2 shows a comparison of tumor weight in combination of wogonin and artesunate in nude mice vaccinated with primary hepatocellular carcinoma tumors after single administration.

Detailed Description

In order to make the technical problems, technical solutions and advantageous effects solved by the present invention more apparent, the present invention is further described in detail below with reference to the following embodiments.

Examples

The following examples are used herein to demonstrate preferred embodiments of the invention. It will be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function in the invention, and thus can be considered to constitute preferred modes for its practice. Those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit or scope of the invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs and the disclosures and references cited herein and the materials to which they refer are incorporated by reference.

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Example 1 inhibition of the combination of wogonin and artesunate on primary human hepatocellular carcinoma cells HepG2

Human hepatocellular carcinoma cells HepG2 were seeded into 96-well plates at 100 μ L cell suspension per well. The culture medium was DMEM medium supplemented with 10% FBS and 2mM glutamate. After 24 hours of inoculation, wogonin, artesunate and a combination of wogonin and artesunate were added, respectively, with no drug added to the control medium. Cell viability was assessed using the MTT method 72 hours after addition of compound; the synergy index (CI) of the wogonin and parthenote combination drug was calculated using the Calcusyn software. Tumor cell survival rate was 100% OD value in experimental/ODX in control. Table 1 shows the inhibition of hepatocellular carcinoma cells HepG2 by the combination of wogonin and fleabane.

TABLE 1

As can be seen from Table 1, wogonin and artesunate at different concentrations both have certain inhibitory effects on the growth of hepatocellular carcinoma cell HepG2, wherein the effect is better when both are used simultaneously, indicating that both have certain synergistic effects.

Example 2 inhibition of the combination drug of wogonin and sweet-scented osmanthus on primary human hepatocellular carcinoma cell SMMC7721

Human hepatocellular carcinoma cells SMMC7721 were seeded into 96-well plates at 100 μ L cell suspension per well. The culture medium was DMEM medium supplemented with 10% FBS and 2mM glutamate. After 24 hours of inoculation, wogonin, artesunate and a combination of wogonin and artesunate were added, respectively, with no drug added to the control medium. Cell viability was assessed using the MTT method 72 hours after addition of compound; the synergy index (CI) of the wogonin and artesunate combined drug was calculated using Calcusyn software. Tumor cell survival rate was 100% OD value in experimental/ODX in control. Table 2 shows the inhibitory effect of wogonin in combination with artesunate on hepatocellular carcinoma cells SMMC 7721.

TABLE 2

As can be seen from Table 2, wogonin and artesunate at different concentrations both have certain inhibitory effects on the growth of hepatocellular carcinoma cell SMMC7721, wherein the effect is better when both are used simultaneously, indicating that both have certain synergistic effects.

example 9 Effect of the combination of Wogonin and Artesunate on tumors in nude mice inoculated with human hepatoma tumors

The experimental animals are 18-24 g male nude mice, and 1 × 10 axilla is inoculated to the left armpit of each nude mouse⁶After one week of inoculation, nude mice are randomly divided into 4 groups according to tumor volume, namely a solvent control group and an artesunate group, wherein the administration dose is 60mg/kg, the administration dose is 30mg/kg, the artesunate and wogonin combined drug group is 60mg/kg and 30mg/kg, the administration dose is once a day, and the administration mode is intraperitoneal injection. Body weights of nude mice were recorded daily, and the longest (L) and shortest (W) diameters of tumors were measured, and the tumor volume was calculated by the formula: v ═ lxw²/2. After 15 days of administration, each nude mouse was first measured for tumor size, then, the eyeball was removed and blood was taken, the tumor tissue was isolated, and the weight of each tumor tissue was weighed.

the results show (fig. 1 and fig. 2) that the tumor volume and weight of the control group are the largest, the artesunate and the wogonin are administered once alone, and the tumor volume and weight of the nude mice are significantly smaller after the combination treatment of the wogonin and the artesunate, which indicates that the tumor inhibition effect of the combination of the two drugs is better, and the wogonin and the artesunate have significant synergistic effect.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims

1. A pharmaceutical composition for treating cancer, comprising wogonin and artesunate.

2. The pharmaceutical composition of claim 1, wherein the molar concentration ratio of wogonin to artesunate in the pharmaceutical composition is 1: 3-3: 1.

3. The pharmaceutical composition of claim 2, wherein the molar concentration ratio of wogonin to artesunate in the pharmaceutical composition is 1: 1 and 1: 2.

4. The pharmaceutical composition of any one of claims 1-3, wherein the cancer is liver cancer.

5. The pharmaceutical composition of claim 3, wherein the cancer is primary liver cancer.

6. Application of wogonin and artesunate in preparing medicine for treating cancer is provided.

7. The use of claim 6, wherein the molar concentration ratio of wogonin to artesunate in the medicament is 1: 3-3: 1.

8. The use of claim 7, wherein the molar concentration ratio of wogonin to artesunate in the medicament is 1: 1 and 1: 2.

9. The use according to any one of claims 6 to 8, wherein the cancer is liver cancer.

10. The use of claim 9, wherein the cancer is primary liver cancer.