CN110876802B - Anti-cancer pharmaceutical composition - Google Patents
Anti-cancer pharmaceutical composition Download PDFInfo
- Publication number
- CN110876802B CN110876802B CN201911193760.8A CN201911193760A CN110876802B CN 110876802 B CN110876802 B CN 110876802B CN 201911193760 A CN201911193760 A CN 201911193760A CN 110876802 B CN110876802 B CN 110876802B
- Authority
- CN
- China
- Prior art keywords
- linolenic acid
- lactoferrin
- alpha
- pharmaceutical composition
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1722—Plasma globulins, lactoglobulins
-
- 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
- A61K38/38—Albumins
-
- 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
-
- 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 milk protein and alpha-linolenic acid. The two compounds are natural compounds, are both derived from food, have small toxic and side effects, can effectively inhibit the survival rate of cancer, particularly colon cancer cells by multiple targets and multiple mechanisms, play the sensitizing and detoxifying activities when being applied in combination with the chemotherapeutic drug taxol, and can be used for treating and assisting in treating the cancer, particularly the colon cancer clinically by the combination of the two or three active ingredients.
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
Cancer is a well-known serious disease that seriously harms human life and health and threatens the development of human society. With the increasing pollution of the living environment of people in the current society, the living pressure of people is improved, the death rate of cancer is increased due to aging of population, the change of daily dietary habits of people and the like. Digestive tract tumors are common malignant tumors worldwide, and mainly comprise gastric cancer, esophageal cancer, colorectal cancer, liver cancer and the like.
The chemotherapy drugs are traditional drugs for treating tumors, and most of the current clinical chemotherapy drugs kill normal cells of an organism while killing tumor cells, lack targeting property and cause great damage to a hematopoietic system, an immune system and the like.
The natural compound has various biological activities such as anti-tumor, immunoregulation, antivirus, antioxidation, radioresistance and the like, and has low toxicity, and is one of important sources for developing cancer treatment medicines. After the discovery that polysaccharides have antitumor activity started in the late 50 s, research on the pharmacological effects of polysaccharides and other natural compounds has been gradually conducted. Research shows that the natural compound has immunoregulation effect on body, including macrophage activation, B cell and T cell activation, complement activation, interferon formation promotion, interleukin formation promotion, tumor necrosis factor induction, tumor inhibiting effect, etc.
However, finding and obtaining natural drugs with excellent therapeutic effects and low toxic effects remains a great challenge for scientists.
Disclosure of Invention
The invention provides a pharmaceutical composition containing milk protein and alpha-linolenic acid, which has the advantages of excellent cancer cell inhibiting effect and low liver and kidney toxicity when being used for treating cancers, particularly colon cancers. In addition, the milk protein and the alpha-linolenic acid in the pharmaceutical composition are both natural compounds, and have stable properties and rich sources.
The technical scheme of the invention is as follows:
a pharmaceutical composition for the treatment of cancer comprising milk protein and alpha-linolenic acid.
According to one embodiment of the invention, the milk protein is selected from one or more of alpha-lactalbumin, alpha-casein, beta-casein, kappa-casein, lactoferrin, and beta-lactoglobulin, preferably lactoferrin.
According to one embodiment of the invention, the lactoferrin structure is as follows:
according to one embodiment of the invention, the α -linolenic acid has the structure shown below:
according to one embodiment of the invention, the cancer is preferably colon cancer.
According to one embodiment of the present invention, the ratio of milk protein to alpha-linolenic acid in the pharmaceutical composition is 10:1 by mass.
According to one embodiment of the present invention, the pharmaceutical composition further comprises paclitaxel.
According to one embodiment of the present invention, when paclitaxel is further included in the pharmaceutical composition, the weight ratio of milk protein, α -linolenic acid, and paclitaxel in the drug is 10: 1: (0.1 to 0.5), for example, 10: 1: 0.2.
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 application of the pharmaceutical composition in preparing a medicament for treating cancers, particularly colon cancer.
The present invention also provides a method of treating colon cancer comprising administering to an individual in need thereof the above-described pharmaceutical composition.
Advantageous effects
The invention provides a pharmaceutical composition for treating cancer, in particular colon cancer, which comprises milk protein and alpha-linolenic acid, wherein the two compounds are natural compounds, are derived from food, have small toxic and side effects, can effectively inhibit the cancer, in particular the survival rate of colon cancer cells by multiple target points and multiple mechanisms, and play a role in enhancing sensitivity and reducing toxicity when being applied in combination with a chemotherapeutic drug taxol.
Drawings
FIG. 1 shows the results of the detection of the effect of various concentrations of lactoferrin, alpha-linolenic acid, lactoferrin in combination with alpha-linolenic acid on the survival rate of colon cancer cells (HT29) in example 1.
FIG. 2 shows the results of the assay of the effect of lactoferrin and alpha-linolenic acid on the survival of colon cancer cells (HT29) according to different mass ratios in example 1.
FIG. 3 shows the results of the effect of lactoferrin, alpha-linolenic acid, lactoferrin in combination with alpha-linolenic acid, paclitaxel, lactoferrin, and alpha-linolenic acid in combination with the chemotherapeutic paclitaxel in example 2 on the growth of colorectal tumor (HT29) in nude mice (where "+" indicates that the drug is administered and "-" indicates that the drug is not administered).
FIG. 4 shows the pathological staining results of liver and kidney tissues of the combination of lactoferrin, alpha-linolenic acid, lactoferrin combined with alpha-linolenic acid, paclitaxel, lactoferrin, and alpha-linolenic acid combined with the chemotherapeutic paclitaxel 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 Colon cancer cell survival
To examine the effect of lactoferrin, alpha-linolenic acid and lactoferrin in combination with alpha-linolenic acid on the survival of HT29 cells, HT29 cells were plated in 96-well dishes (10)5100mL of medium per well) for 24h, and then divided into fractions10mg/L, 50mg/L, 100mg/L, 500mg/L and 1g/L of lactoferrin, 10mg/L, 50mg/L, 100mg/L, 500mg/L and 1g/L of alpha-linolenic acid, and a combined group of lactoferrin and alpha-linolenic acid (200mg/L dose of lactoferrin combined with 10mg/L dose of alpha 0-linolenic acid (mass ratio 20:1), 100mg/L dose of lactoferrin combined with 10mg/L dose of alpha 1-linolenic acid (mass ratio 10:1), 100mg/L dose of lactoferrin combined with 100mg/L dose of alpha 2-linolenic acid (mass ratio 1:1), 10mg/L dose of lactoferrin combined with 100mg/L dose of alpha-linolenic acid (mass ratio 1: 10)), Combining 10mg/L dose of lactoferrin with 200mg/L dose of alpha-linolenic acid (mass ratio is 1:20)) (20 microliter is given in each group, 10 microliter is given in each drug in the combined administration group) for acting for 24 hours, then abandoning the culture medium, adding MTT (final concentration is 5g/L) for acting for 4 hours, detecting the absorbance (OD) value by a microplate reader, and calculating the cell survival rate. A blank set is also set, i.e. no drug is administered. As shown in FIGS. 1 and 2, it can be seen from FIGS. 1 and 2 that the lactoferrin group, the α -linolenic acid group, and the lactoferrin α -linolenic acid combination group [200mg/L dose of lactoferrin in combination with 10mg/L dose of α -linolenic acid (mass ratio: 20:1), 100mg/L dose of lactoferrin in combination with 100mg/L dose of α -linolenic acid (mass ratio: 1), 10mg/L dose of lactoferrin in combination with 100mg/L dose of α -linolenic acid (mass ratio: 1:10), 10mg/L dose of lactoferrin in combination with 200mg/L dose of α -linolenic acid (mass ratio: 1:20) ]]All had inhibitory effect on HT29 cells, and the graph in figure 2 indicates that P < 0.05, compared to the level of the control group without any treatment, had a significant statistical difference.
The experimental results show that: after lactoferrin at a dose of 100mg/L-1g/L and alpha-linolenic acid at a dose of 10mg/L-1g/L are respectively acted on colon cancer HT29 cells for 24 hours, the cell survival rate is found to be remarkably reduced (compared with a control group, P is less than 0.05). Meanwhile, in the combined action group, the lactoferrin in a dose of 100mg/L and the alpha-linolenic acid in a dose of 10mg/L (in a mass ratio of 10:1) have the most obvious effect of inhibiting the survival rate of HT29 cells, and the inhibition rate is 46.7% (compared with a control group, P is less than 0.05). The inhibition ratio was 41.1% in the mass ratio of 20:1 and 25.0% in the mass ratio of 1: 1. Symbol indicates that there was a significant statistical difference from the level of the control group without any treatment, P < 0.05.
Example 2 Effect of Lactoferrin and alpha-linolenic acid in combination with the chemotherapeutic drug paclitaxel on inhibiting the growth of HT29 tumor in nude mice and reducing the toxicity of paclitaxel
The following groups are set: the growth of the nude mouse load HT29 tumor was detected in a non-treated control group, 50mg/kg of lactoferrin, 5mg/kg of alpha-linolenic acid, 50mg/kg of lactoferrin in combination with 5mg/kg of alpha-linolenic acid, 1mg/kg of paclitaxel, 50mg/kg of lactoferrin, and 5mg/kg of alpha-linolenic acid in combination with 1mg/kg of paclitaxel.
The experimental method comprises the following steps: HT29 cells were cultured in 24 10cm culture dishes on a large scale until the cell density reached about 90%, and the cells were collected and injected subcutaneously into the right axilla of 24 BALB/C nude mice. After about two weeks, the tumor volume reached 90-100mm3. Mice were divided into 6 groups of 4 mice each. Orally administering lactoferrin at a dose of 50mg/kg and alpha-linolenic acid at a dose of 5mg/kg to mice (0.2 mL per mouse) once a day for 28 consecutive days, and intraperitoneally administering paclitaxel at a dose of 1mg/kg to mice once a day for 28 consecutive days. After sacrifice of the mice on day 29, the tumors were dissected out, photographed and weighed.
In addition, pathological conditions of the liver and the kidney of the mouse are observed through hematoxylin-eosin staining of pathological sections of the liver and the kidney tissues.
The experimental results are as follows:
FIG. 3 shows the effect of different groups on the weight of a colon cancer HT29 tumor. Symbol denotes the level ratio with respect to the control without any treatment, P < 0.05, with significant statistical differences; the symbol # represents the independent action group ratio of the lactoferrin or alpha-linolenic acid, P is less than 0.05, and the statistical difference is significant; symbol & represents the significant statistical difference with P < 0.05 compared to the paclitaxel alone group.
As can be seen from the figure, the combined group of lactoferrin, alpha-linolenic acid, lactoferrin combined alpha-linolenic acid and paclitaxel has obvious inhibiting effect on HT29 tumor weight (compared with a control group, P is less than 0.05). The inhibiting effect of the combination of the lactoferrin and the alpha-linolenic acid is better than that of the lactoferrin or the alpha-linolenic acid group (P is less than 0.05), and the inhibiting effect of the combination group of the lactoferrin and the alpha-linolenic acid is obviously better than that of the other groups (P is less than 0.05).
FIG. 4 shows the results of pathological staining of liver and kidney tissues of different groups of mice. As shown in FIG. 4, the degree of edema of liver and kidney of mice treated with lactoferrin at a dose of 50mg/kg in combination with alpha-linolenic acid at a dose of 5mg/kg and paclitaxel at a dose of 1mg/kg is lower, the number of bleeding regions in tissues is smaller, and the number of deformed cells is smaller.
The results show that when the lactoferrin and the alpha-linolenic acid are combined at a mass ratio of 10:1, the survival of colon cancer HT29 cells and the growth of colon cancer tumors can be effectively inhibited, moreover, the effect of the lactoferrin and alpha-linolenic acid combined group is obviously stronger than that of the lactoferrin or alpha-linolenic acid combined group, the liver and kidney injury caused by chemotherapeutic drugs can be obviously relieved when the lactoferrin and alpha-linolenic acid are combined with taxol, and the combined administration can play a role in sensitizing and attenuating. It follows that the combination of lactoferrin and alpha-linolenic acid or with paclitaxel can be a safe and effective treatment under the present high incidence of colon cancer.
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 (6)
1. The pharmaceutical composition for treating colon cancer is characterized by comprising lactoferrin and alpha-linolenic acid, wherein the mass ratio of the lactoferrin to the alpha-linolenic acid is 10:1 or 20: 1; the pharmaceutical composition does not contain other active ingredients except lactoferrin and alpha-linolenic acid.
2. A pharmaceutical composition for the treatment of colon cancer, wherein said pharmaceutical composition comprises lactoferrin, α -linolenic acid and paclitaxel;
the mass ratio of the lactoferrin to the alpha-linolenic acid to the paclitaxel in the pharmaceutical composition is 10: 1: 0.2.
3. the pharmaceutical composition of claim 1 or 2, wherein the pharmaceutical composition is an oral formulation.
4. The pharmaceutical composition of claim 1 or 2, wherein the pharmaceutical composition is an injection.
5. The pharmaceutical composition according to claim 4, wherein the injection is selected from intravenous, intraperitoneal or subcutaneous injection.
6. Use of a pharmaceutical composition according to any one of claims 1 to 5 in the manufacture of a medicament for the treatment of colon cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911193760.8A CN110876802B (en) | 2019-11-28 | 2019-11-28 | Anti-cancer pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911193760.8A CN110876802B (en) | 2019-11-28 | 2019-11-28 | Anti-cancer pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110876802A CN110876802A (en) | 2020-03-13 |
| CN110876802B true CN110876802B (en) | 2021-01-05 |
Family
ID=69730773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911193760.8A Active CN110876802B (en) | 2019-11-28 | 2019-11-28 | Anti-cancer pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110876802B (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103372202B (en) * | 2012-07-23 | 2015-09-16 | 任发政 | A kind of composition and method of making the same and application containing lactoprotein and fatty acid |
| CN106578094A (en) * | 2016-12-31 | 2017-04-26 | 东北农业大学 | Old-aged formula milk powder for preventing osteoporosis |
-
2019
- 2019-11-28 CN CN201911193760.8A patent/CN110876802B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110876802A (en) | 2020-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101074158B1 (en) | Composition comprising polysaccharide extracted from panax ginseng preventing and treating liver diseases | |
| Chen et al. | Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil–based chemotherapy in colorectal cancer | |
| JPH10130153A (en) | Anti-malignant tumor agent useful for cancer selected from colon cancer, esophagus cancer and breast cancer | |
| US9901602B2 (en) | Ejaculum of animals as medicinal material and uses thereof in medicaments for treatment of diseases such as tumors, depression, etc | |
| EP1103263A2 (en) | Poly-L-lactates as antitumour agents | |
| CN105796608A (en) | Compound fullerene healthcare drinking water and preparation method thereof | |
| CN110876802B (en) | Anti-cancer pharmaceutical composition | |
| CN113694085A (en) | Application of slug extract in preparation of combined medicine for cancer chemotherapy scheme | |
| CN111840523B (en) | An anticancer pharmaceutical composition containing active protein and active fatty acid | |
| US20200375943A1 (en) | Cytocidal method of cancer cells selectively in human patients clinically by depletion of l-ascorbic acid, primarily, with its supplementation alternately augmenting its cytocidal effect | |
| CN111558045A (en) | Medicine composition for treating lung cancer | |
| CN112618569A (en) | Medicine for treating urothelial cancer | |
| CN110613716B (en) | Pharmaceutical composition for treating cancer and application thereof | |
| CN109045052B (en) | Pharmaceutical formulation for treating colon cancer and application | |
| CN105412155A (en) | Application of trichoderma pseudokoningii exopolysaccharide in preventing and treating colon cancer and application of chemotherapeutic drug combined with trichoderma pseudokoningii exopolysaccharide in treating colon cancer | |
| CN111700900A (en) | Natural immune activator, TIL cell promoter and application thereof | |
| CN110876803B (en) | Pharmaceutical composition containing milk protein and oleic acid | |
| CN1120002C (en) | Application of ammonium nilrate in pharmaceutical industry, food and health-care product | |
| CN114642675B (en) | Application of L-sorbose in preparing medicine for treating tumor | |
| CN107970437A (en) | Cordyceps sinensis gram oncogene peptide | |
| CN105012366B (en) | A kind of bright moon grass polysaccharide and its application in preparing for immunological regulation and anti-tumor drug and functional food | |
| CN111544580B (en) | Anti-cancer pharmaceutical composition | |
| CN114831312B (en) | Traditional Chinese medicine composition composed of ganoderma lucidum polysaccharide and cicada fungus polysaccharide and application thereof | |
| CN115227690B (en) | Application of alantolactone in double-expression type B cell lymphoma | |
| JPH11228440A (en) | Medicament such as anticancer agent or immunostimulator and health food/drink |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |