CN111544580A - Anti-cancer pharmaceutical composition - Google Patents
Anti-cancer pharmaceutical composition Download PDFInfo
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- CN111544580A CN111544580A CN202010176118.5A CN202010176118A CN111544580A CN 111544580 A CN111544580 A CN 111544580A CN 202010176118 A CN202010176118 A CN 202010176118A CN 111544580 A CN111544580 A CN 111544580A
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- nandinine
- lactoferrin
- pharmaceutical composition
- cancer
- liver cancer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/40—Transferrins, e.g. lactoferrins, ovotransferrins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention belongs to the technical field of medicaments for treating cancers, and particularly relates to an anti-cancer pharmaceutical composition. The pharmaceutical composition comprises nandinine and lactoferrin. The two compounds are natural compounds, are respectively derived from plant and animal source foods, have small toxic and side effects, can effectively inhibit the survival rate of cancer, particularly liver cancer cells by multiple targets and multiple mechanisms, can play a role in synergy compared with a single compound (nandinine or lactoferrin) action group, and can be used for treating and assisting in treating the clinical cancer, particularly the liver cancer.
Description
Technical Field
The invention belongs to the technical field of medicaments for treating cancers, and particularly relates to an anti-cancer pharmaceutical composition.
Background
Liver cancer is the sixth most common cancer worldwide and also the fourth leading cause of cancer-related death worldwide, constituting a serious threat to human health (dubec, et al. amer. j. gateway., 2017.). Liver cancer can be divided into primary and secondary categories. Primary liver malignancies originated in epithelial or mesenchymal tissues of the liver, including hepatocellular carcinoma, cholangiocellular carcinoma and mixed types thereof, wherein hepatocellular carcinoma is the most common liver malignancy, accounting for 45% of primary liver cancer (El-Serag, et al. Secondary or metastatic liver cancer refers to liver metastasis of malignant tumor of multiple organ origins usually found in stomach, biliary tract, pancreas, colon and rectum, ovary, uterus, lung, and breast.
At present, liver cancer is clinically treated by a common method through an operation, but the problems of high wound, easy residual and relapse of cancer cells and the like exist, so that the medicine is more generally adopted for treatment. Drug therapy mainly includes chemotherapy and interventional drugs. The common clinical chemotherapy drugs for liver cancer are more in types and comprise cis-chloramine, adriamycin, mitomycin, fluorouracil, gemcitabine, oxaliplatin, bevacizumab and the like. These drugs are usually administered by intravenous drip, and can control the disease deterioration to some extent (Huabin et al, Chinese pharmacy 2011; girl et al, Chinese New drug journal 2007). However, these chemotherapy drugs have some disadvantages, firstly, they have certain requirements on the constitution and immunity of patients, patients with weak body and low resistance are not recommended to use the therapy, the chemotherapy drugs have large side effects, which may cause nausea, vomiting, inappetence and other gastrointestinal reactions of patients, and may cause rare and serious symptoms such as ketonuria, heart disease, liver disease, renal failure and the like (butyl shou is bright, china general foundation and clinical journal, 2016; songxu, journal of practical medical technology, 2006); secondly, chemotherapy drugs lack certain selectivity on normal cells and cancer cells, have the defects of' enemy, drinking \40489, thirst and the like, and generate serious toxic and side effects on patients, for example, the content of white blood cells and platelets in most patients is seriously reduced in a chemotherapy intermediate, infection and bleeding are caused, and even the life is endangered (Wangweian and the like, China journal of tumor control, 1999, Wangze, medical asking for medicine, 2012, Belgium and the like, and clinical rational journal of medication, 2018); finally, chemotherapy drugs cannot transform the living environment of cancer foci, so that the problem of temporary solution and permanent solution exists, the long-term treatment effect is poor, and the patients are difficult to be helped to recover thoroughly.
Because liver cancer onset involves each link of human metabolism, the onset causes are widely described as < 32429and the action targets are rich, the optimal therapeutic drug is difficult to be regulated by a single mechanism and a single method. The natural components with plant sources and pharmacological activity have the action mechanism of multi-target joint intervention, are more in line with the pathogenesis characteristics of liver cancer, and are superior to chemotherapeutic drugs in terms of safety and economy.
The nandinine is derived from nandina domestica, belongs to berberidaceae of Ranunculaceae, is common woody flower in southern China, and is also named as nandinine, aporphine alkaloid, nandinine, and nandinine. Nandina domestica alkaloid belongs to aporphine alkaloid, and has chemical formula C20H21NO4And the molecular weight is 339.39. As for the few reports related to nandinine antitumor, a study finds that nandinine has the effect of inhibiting cell survival in a human colon cancer (HCT-116 and Caco-2) cell model, and suggests that nandinine plays an anti-colon tumor activity (Ponnala, et al, Bioorganic)&Medicinal chemistry letters, 2011.). Another study found that nandinine was cytotoxic to mouse fibroblast tumor cell L-929 (Philipov, et al. Die Pharmazie, 2000.). But its effect on other types of tumor cells, especially the selective inhibition of hepatoma cellsThe survival and migration of (2) have not been reported.
Disclosure of Invention
In order to solve the technical problems, the invention provides a pharmaceutical composition containing nandinine and lactoferrin, and the pharmaceutical composition has the advantage of excellent effect of inhibiting cancer cells when used for treating cancers, particularly liver cancers. In addition, the nandinine and the lactoferrin in the pharmaceutical composition are natural compounds, and have stable properties and rich sources.
The technical scheme of the invention is as follows:
a pharmaceutical composition for treating cancer comprises nandinine and lactoferrin.
According to one embodiment of the present invention, the nandinine structure is as follows:
according to one embodiment of the invention, the lactoferrin structure is as follows:
according to one embodiment of the present invention, the cancer is liver cancer.
According to one embodiment of the invention, the mass ratio of nandinine to lactoferrin in the pharmaceutical composition is (5-1): 1-5, such as 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, or 1: 5.
According to one embodiment of the present invention, the pharmaceutical composition is an oral preparation, including various dosage forms for oral administration.
According to one embodiment of the present invention, the pharmaceutical composition is an injection.
According to one embodiment of the present invention, the injection is selected from intravenous injection, intraperitoneal injection, or subcutaneous injection.
The invention also provides the application of the pharmaceutical composition in preparing medicines for treating cancers, particularly liver cancer.
The invention also provides a method for treating liver cancer, which comprises the step of administering the pharmaceutical composition to an individual in need thereof.
Advantageous effects
The invention provides a pharmaceutical composition for treating cancer, in particular liver cancer, which comprises nandinine and lactoferrin, wherein the two compounds are natural compounds and are respectively derived from plant and animal-derived foods, so that the toxic and side effects are small, the multi-target multi-mechanism cancer inhibition effect can be effectively achieved, in particular the survival rate of liver cancer cells, the synergistic activity can be exerted compared with the action group of a single compound (nandinine or lactoferrin), and the pharmaceutical composition containing the two components can be used for treating and assisting in treating the clinical cancer, in particular the liver cancer.
Drawings
FIG. 1 shows the results of the detection of the effect of various concentrations of nandinine, lactoferrin, and nandinine in combination with lactoferrin on the survival rate of liver cancer cells (HepG 2) in example 1.
FIG. 2 shows the results of the test of the effect of nandinine and lactoferrin on the survival rate of liver cancer cells (HepG 2) according to different mass ratios in example 1.
FIG. 3 shows the results of the test of the effect of nandinine, lactoferrin, nandinine in combination with lactoferrin on the growth of liver-bearing tumor (HepG 2) in nude mice for half dose of nandinine in combination with half dose of lactoferrin in the group of nandinine and lactoferrin in example 2.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to specific embodiments. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
Example 1 Effect of inhibiting survival of hepatoma cells
To examine the effect of nandinine, lactoferrin, and a combination of nandinine and lactoferrin on the survival of HepG2 cells, HepG2 cells were plated in 96-well dishes (10)5100 mL of culture medium per well), after 24h of culture, 10 mg/L, 50 mg/L, 100mg/L, 200mg/L, 500 mg/L and 1 g/L of nandinine, 10 mg/L, 50 mg/L, 100mg/L, 200mg/L, 500 mg/L and 1 g/L of lactoferrin, and a combination of nandinine and lactoferrin (200 mg/L of nandinine in combination with 100mg/L of lactoferrin (mass ratio 2: 1), 100mg/L of nandinine in combination with 100mg/L of lactoferrin (mass ratio 1: 1), 100mg/L of nandinine in combination with 200mg/L of lactoferrin (mass ratio 1: 2) (total 20 microliters per group, 10 microliters of each drug in the combined administration group) for 24 hours, then abandoning the culture medium, adding MTT (with the final concentration of 5 g/L) for 4 hours, detecting the absorbance value by an enzyme-labeling instrument, and calculating the cell survival rate. A blank set was also set, i.e. no drug treatment was given.
As shown in FIGS. 1 and 2, it is understood from FIGS. 1 and 2 that the inhibitory activities of the nandinine group and the lactoferrin group are significantly lower than those of the nandinine-lactoferrin combined group [200 mg/L dose of nandinine combined with 100mg/L dose of lactoferrin (mass ratio: 2: 1), 100mg/L dose of nandinine combined with 100mg/L dose of lactoferrin (mass ratio: 1), 100mg/L dose of nandinine combined with 200mg/L dose of lactoferrin (mass ratio: 1: 2) ]]FIG. 2 symbol indicates the level ratio to the control group without any treatment,Pis less than 0.05, and has significant statistical difference.
The experimental results show that: after 100 mg/L-1 g/L dosage of nandinine and 100 mg/L-1 g/L dosage of lactoferrin act on the liver cancer HepG2 cells for 24 hours respectively, the cell survival rate is reduced (compared with a control group,P< 0.05). Meanwhile, in the combined action group, the 100mg/L dose nandinine and 200mg/L dose lactoferrin group have the most obvious inhibition effect on the survival rate of HepG2 cells, and the survival rate is higherThe survival rate was 52.3% (compared to the control,P< 0.05). The survival rate of the nandinine group and the lactoferrin combined group is 60.4% in a mass ratio of 2:1, and the survival rate of the nandinine group and the lactoferrin combined group is 57.5% in a mass ratio of 1: 1. Symbol denotes the level ratio to the control group without any treatment,Pis less than 0.05, and has significant statistical difference.
Example 2 the effect of nandinine in combination with lactoferrin on inhibiting the growth of nude mouse HepG2 tumor
The following groups are set: and (3) carrying out tumor growth detection on a nude mouse with HepG2 in a non-treated control group, 25mg/kg of nandinine, 50 mg/kg of lactoferrin, 25mg/kg of nandinine combined with 50 mg/kg of lactoferrin, and 12.5 mg/kg of nandinine combined with 25mg/kg of lactoferrin.
The experimental method comprises the following steps: HepG2 cells were cultured in 20 10cm dishes on a large scale until the cell density reached about 80%, and the cells were collected and injected subcutaneously into the right axilla of 20 BALB/C nude mice. After about three weeks, the tumor volume reached 90-110mm3. Mice (body weight 20 ± 1 g) were divided into 5 groups of 4 mice each. The mice are orally drenched with 25mg/kg of nandinine, 50 mg/kg of lactoferrin, 25mg/kg of nandinine combined with 50 mg/kg of lactoferrin and 12.5 mg/kg of nandinine combined with 25mg/kg of lactoferrin, once a day for 28 consecutive days, and after the mice are sacrificed on day 29, the tumors are dissected out, photographed and weighed.
The experimental results are as follows:
FIG. 3 shows the effect of different groups on the weight of HepG2 tumor from liver cancer. Symbol denotes the level ratio to the control group without any treatment,Pless than 0.05, with significant statistical differences; symbol # represents the ratio of the single action of nandinine or lactoferrin,Pis less than 0.05, and has significant statistical difference.
As can be seen from the figure, nandinin, lactoferrin, nandinin combined with lactoferrin (combined group), and half dose of nandinin combined with half dose of lactoferrin (combined group) all had inhibitory effects on HepG2 tumor weight (compared to control group,P< 0.05). And half dosage of NantianThe combined effect of the Ningzhu alkali (12.5 mg/kg) and the lactoferrin (25 mg/kg) in half dose is better than that of the single nandinzhu alkali or lactoferrin group (the group)P< 0.05), both show excellent synergistic effects.
The results show that the nandinine and the lactoferrin can effectively inhibit the survival of liver cancer HepG2 cells and the growth of liver cancer tumors when combined in a mass ratio of 1:1, 1:2 and 2:1, and the effect of the nandinine and the lactoferrin is obviously stronger than that of a single-acting group of the nandinine or the lactoferrin, and the combined administration can play a synergistic effect. Therefore, under the condition that the incidence rate of liver cancer is high nowadays, the combination of nandinin and lactoferrin can be used as a safe and effective liver cancer treatment scheme.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (9)
1. A pharmaceutical composition for treating cancer, comprising nandinine and lactoferrin.
2. The pharmaceutical composition of claim 1, wherein the cancer is liver cancer.
3. The pharmaceutical composition of claim 2, wherein the mass ratio of the nandinine to the lactoferrin in the pharmaceutical composition is (5-1): (1-5).
4. The pharmaceutical composition of claim 3, wherein the mass ratio of nandinine to lactoferrin in the pharmaceutical composition is 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, or 1: 5.
5. The pharmaceutical composition of claim 3, wherein the pharmaceutical composition is an oral formulation.
6. The pharmaceutical composition of claim 3, wherein the pharmaceutical composition is an injection.
7. The pharmaceutical composition of claim 6, wherein the injection is selected from intravenous, intraperitoneal, or subcutaneous injection.
8. Use of a pharmaceutical composition according to any one of claims 1 to 7 in the manufacture of a medicament for the treatment of cancer.
9. The use according to claim 8, wherein the medicament is a medicament for the treatment of liver cancer.
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| CN202010176118.5A CN111544580B (en) | 2020-03-13 | 2020-03-13 | Anti-cancer pharmaceutical composition |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000229881A (en) * | 1999-02-10 | 2000-08-22 | Morinaga Milk Ind Co Ltd | Prognosis-improving agent for cancerous disease |
| CN102600459A (en) * | 2011-01-20 | 2012-07-25 | 上海转基因研究中心 | Usage of lactoferrin in prevention and treatment of tumor metastasis |
| CN104478888A (en) * | 2014-12-16 | 2015-04-01 | 陕西嘉禾植物化工有限责任公司 | Method for extracting O-methyl nandinine from Nandina domestica |
| CN106890190A (en) * | 2015-12-18 | 2017-06-27 | 江西中医药大学 | A kind of preparation of new component with arsenic trioxide composition and purposes |
| WO2019128611A1 (en) * | 2017-12-29 | 2019-07-04 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
-
2020
- 2020-03-13 CN CN202010176118.5A patent/CN111544580B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000229881A (en) * | 1999-02-10 | 2000-08-22 | Morinaga Milk Ind Co Ltd | Prognosis-improving agent for cancerous disease |
| CN102600459A (en) * | 2011-01-20 | 2012-07-25 | 上海转基因研究中心 | Usage of lactoferrin in prevention and treatment of tumor metastasis |
| CN104478888A (en) * | 2014-12-16 | 2015-04-01 | 陕西嘉禾植物化工有限责任公司 | Method for extracting O-methyl nandinine from Nandina domestica |
| CN106890190A (en) * | 2015-12-18 | 2017-06-27 | 江西中医药大学 | A kind of preparation of new component with arsenic trioxide composition and purposes |
| WO2019128611A1 (en) * | 2017-12-29 | 2019-07-04 | Suzhou Ribo Life Science Co., Ltd. | Conjugates and preparation and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| SALEHA Y. M. ALAKILLI等: ""Evaluation of the Chemopreventive Impacts of Lactoferrin on the Initiation of Liver Cancer Induced by Diethylnitrosamine in Male Mice"", 《INT. J. PHARM. SCI. REV. RES.》 * |
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