CN107281492B - Application of composition - Google Patents

Application of composition Download PDF

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CN107281492B
CN107281492B CN201710707121.3A CN201710707121A CN107281492B CN 107281492 B CN107281492 B CN 107281492B CN 201710707121 A CN201710707121 A CN 201710707121A CN 107281492 B CN107281492 B CN 107281492B
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carbonaceous material
composition
composition according
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colorectal cancer
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CN107281492A (en
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柯泽豪
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/36—Arsenic; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof

Abstract

The invention provides an application of a composition, wherein the composition is used for preparing a medicine for treating or preventing colorectal cancer, the composition comprises a carbonaceous material and active particles, and the active particles are carried on the carbonaceous material and are made of silver, gold, zinc, copper, magnesium, selenium, platinum, arsenic, cobalt, calcium or silicon.

Description

Application of composition
Technical Field
The invention relates to application of a composition for treating or preventing colorectal cancer.
Background
According to World Health Organization (WHO), colorectal cancer is the second most common cancer in women and the third most common cancer in men in the World in 2012, and the mortality rate is behind that of lung cancer, gastric cancer and liver cancer in all cancers, and ranks fourth. Clinically, the colorectal cancer is mainly treated by means of surgery, radiotherapy, chemotherapy, targeted therapy and the like; however, the high mortality rate of large bowel cancer reflects an overall less than expected therapeutic effect.
In view of the above, there is a real need to develop new drugs for treating or preventing colorectal cancer.
Disclosure of Invention
The invention aims to provide application of a composition, which can inhibit the growth of colorectal cancer cells, thereby providing more choices for treating colorectal cancer.
To achieve the above and/or other objects, the present invention provides a use of a composition for preparing a medicine for treating or preventing colorectal cancer, wherein the composition comprises a carbonaceous material and an active particle, and the active particle is supported on the carbonaceous material and is made of silver, gold, zinc, copper, magnesium, selenium, platinum, arsenic, cobalt, calcium or silicon.
According to the present invention, after the pharmaceutical is administered to an individual in need of treatment or prevention, the carbonaceous material adsorbs colon cancer cells or adheres to colon cancer tissues. In addition, due to the large number of negative charges on the surface of colorectal cancer cells, the cations released by the active particles will adhere to the cell surface. In this way, the cell membrane of the colorectal cancer cell can be disrupted, and the growth of the colorectal cancer cell can be suppressed. Therefore, the composition provided by the present invention is extremely useful as a pharmaceutical for treating or preventing colon cancer.
Drawings
FIG. 1 is a photograph taken with a Scanning Electron Microscope (SEM) showing the appearance (X100,000) of the composition of preparation example 1.
FIG. 2 is a photograph of an optical microscope showing the appearance of human colon cancer cells HCT-116 after 24 hours of treatment with the composition of preparation example 1 at a concentration of 0.1 mg/mL.
FIG. 3 is a photograph of an optical microscope showing the appearance of human colon cancer cells Caco-2 after 24 hours of treatment with the composition of preparation example 1 at a concentration of 0.1 mg/mL.
FIG. 4 is a photograph of an optical microscope showing the appearance of human colon cancer cells HCT-116 after 24 hours of treatment with the composition of preparation example 1 at a concentration of 0.5 mg/mL.
FIG. 5 is a photograph of an optical microscope showing the appearance of human colon cancer cells Caco-2 after 24 hours of treatment with the composition of preparation example 1 at a concentration of 0.5 mg/mL.
The specific implementation mode is as follows:
in order to make the aforementioned and/or other objects, features, and advantages of the present invention comprehensible, preferred embodiments accompanied with figures are described in detail below:
one embodiment of the present invention provides a use of a composition for preparing a medicine for treating or preventing colorectal cancer, the composition comprising a carbonaceous material and an active particle, wherein the active particle is supported on the carbonaceous material and is made of silver, gold, zinc, copper, magnesium, selenium, platinum, arsenic, cobalt, calcium or silicon. After the medicament is administered into a subject in need of treatment or prevention, the carbonaceous material adsorbs colon cancer cells or adheres to colon cancer tissues. Furthermore, the surface of colorectal cancer cells is largely negatively charged, so cations released by the active particles adhere to the cell surface and disrupt the cell membrane. Through this mechanism, the medicine can inhibit the growth of colorectal cancer cells to achieve the purpose of treating or preventing colorectal cancer.
The term treating, as used herein, means to reduce, slow, or stop the growth, spread, or metastasis of tumor cells; the term treating, as used herein, is intended to mean preventing the growth, spread, or metastasis of tumor cells; the term colorectal cancer as used herein means colon cancer (colon cancer), rectal cancer (rectal cancer) or colorectal cancer (colotectal cancer). Further, examples of the carbonaceous material may be, but are not limited to, activated carbon fiber, activated carbon powder, charcoal, bamboo charcoal particles, carbon black, graphite powder, expanded graphite powder, graphene, nano carbon powder, or carbon powder made of phenolic resin or synthetic resin. In the present embodiment, the weight percentages of the carbonaceous material and the active particles may be 80% to 99.999% and 0.001% to 20%, respectively, based on the total weight of the composition. In the present embodiment, the carbonaceous material may have a BET specific surface area of 0.1 to 2500m2A/g, preferably 600 to 1800m2(ii) in terms of/g. In the present embodiment, the particle size of the active particles may be 1nm to 200 μm, preferably 5nm to 100 μm.
According to the examples below, an effective dose of 0.1 to 30g per kg of subject per day, preferably 0.1 to 24g per kg of subject per day, more preferably 0.1 to 1g per kg of subject per day, particularly preferably 0.5 to 1g per kg of subject per day, is administered to the subject. Furthermore, the medicament can be administered orally or tumor into a subject and can be presented in different dosage forms, such as: capsules, lozenges, powders, suspensions, or emulsions.
In order to make the medicine in different dosage forms, the composition may further comprise an additive, such as: a nutrient (vitamin), a flavoring agent (citric acid, malic acid, acetic acid, or lactic acid), a sweetening agent (glucose, oligosaccharide, fructose, maltose, aspartame, saccharin, acesulfame potassium, glycyrol, acesulfame potassium, stevioside, glycyrrhizin, sorbitol, maltitol, or xylitol), a thickener (starch, protein, carrageenan, carboxymethyl cellulose, sodium alginate, carageenan, sodium carboxymethyl cellulose, acidified starch, gelatinized starch, bleached starch, oxidized starch, starch acetate, or starch phosphate), a solvent (propylene glycol or glycerin), an emulsifier (fatty acid glyceride), or a moisture controlling agent (sorbitol, lactic acid, glycerin, hexitol, or propylene glycol).
In addition, in order to promote the absorption of the colorectal cancer cells, the carbonaceous material may further have at least one hole. Generally, the carbonaceous material can adsorb normal cells or beneficial substances (such as vitamins, enzymes, or probiotics) in addition to colorectal cancer cells. To avoid adsorption of other normal cells or beneficial substances, the pores have a radius of less than 2.5nm, preferably 0.5 to 2.3 nm. In order to facilitate administration of the medicine to an individual, the carbonaceous material may have a particle size of more than 1nm but less than 3mm under the condition that the carbonaceous material is in the form of particles; in the case where the carbonaceous material is in the form of a rod, the length thereof may be more than 1nm but less than 3mm, and the cross-sectional diameter thereof may be more than 1nm but less than 3 mm; in the case where the carbonaceous material is irregular, the maximum length thereof may be more than 1nm but less than 3 mm. In order to provide different degrees of hydrophilicity to the medicine, the carbonaceous material can further have different acidic groups or basic groups; under these conditions, the content of acidic or basic groups can be 0.3mEq/g or more.
The production of the composition of the present embodiment is explained in detail below:
first, an active solution containing an active salt is provided. The active salt is mainly used as a source of the subsequent active particles, and the concentration thereof may be, but is not limited to, 0.00001M to 20M, and examples thereof may be, but are not limited to, silver salt, gold salt, zinc salt, copper salt, magnesium salt, selenium salt, platinum salt, arsenic salt, cobalt salt, calcium salt, or silicon salt. Specifically, the active salt may be a halide salt (e.g., silver fluoride, silver chloride, silver bromide, or silver iodide), an acetate salt (e.g., silver acetate), a nitrate salt (e.g., silver nitrate, copper nitrate, or zinc nitrate), a phosphate salt (e.g., silver phosphate), or a sulfonate salt (e.g., silver sulfonate). In order to uniformly distribute the active particles on the carbonaceous material, the active solution may further contain a reducing agent, such as, but not limited to, glacial acetic acid, ammonia, ascorbic acid, or glucose.
Next, the carbonaceous material is dipped into the active solution or the active solution is sprayed to the carbonaceous material. The soaking step may be performed by soaking the carbonaceous material in the active solution with stirring for about 0.5 to 24 hours, preferably about 1 to 12 hours. In addition, the weight percentages of the active salt and the carbonaceous material can be respectively 0.01% to 1% and 0.01% to 20% based on the total weight of the active solution and the carbonaceous material. Under the condition that the active solution contains the reducing agent, the weight percentages of the active salt, the reducing agent and the carbonaceous material are respectively 0.01-1%, 0.01-30% and 0.01-20% based on the total weight of the active solution and the carbonaceous material.
The activated solution is then thermally dried to adhere the activated salt to the carbonaceous material. The heat drying step is carried out by maintaining the active solution at 80 to 500 ℃ for about 0.5 to 6 hours, preferably about 1 to 4 hours.
The active salts are then thermally cracked to reduce them to active particles and obtain the composition. The thermal cracking step may be carried out by maintaining the active salts at 200 to 1000 ℃ for about 0.5 to 10 hours. In addition, the thermal cracking may be carried out in the presence of nitrogen or an inert gas, or under vacuum.
The composition is then washed with water to remove free active particles. The cleaning step may be carried out by rinsing the composition with water or soaking the composition in water for about 0.5 to 6 hours.
Finally, the composition is thermally dried to remove moisture. The thermal drying step herein may be carried out while maintaining the composition at 80 to 120 ℃ for about 0.5 to 6 hours.
The above embodiments are illustrated by way of example in the following examples:
preparation example 1
Firstly, a Polyacrylonitrile (PAN) series activated carbon fiber cloth is provided, which is characterized in that: BET specific surface area 1,100m2/g, carbon content 80.7 wt.%. Subsequently, the fiber cloth was immersed in a 0.0025M silver nitrate aqueous solution for 2 hours, and then thermally dried at 100 ℃ for 2 hours to attach silver nitrate to the fiber cloth. Silver nitrate was thermally cracked at 600 c in the presence of nitrogen for 1.5 hours to be reduced into silver particles and attached to the fiber cloth. Thereafter, the fiber cloth was washed with water for 2 hours to remove free silver particles. Then, the fiber cloth and the silver particles attached thereto are thermally dried to remove moisture. Finally, the fiber cloth was ground to obtain a composition (shown in fig. 1) containing silver particles and activated carbon fiber powder carrying the silver particles, and the composition was characterized as follows: 78.1% by weight of carbon, 0.3% by weight of silver, a length of 0.1mm or less, a BET specific surface area of 980m2/g, a pore diameter of 2.41nm in the activated carbon fiber powder, and a particle diameter of 100nm or less in the silver particles.
Preparation example 2
Firstly, providing polyacrylonitrile-based activated carbon fiber cloth, which is characterized in that: BET specific surface area 1,100m2/g, carbon content 80.7 wt.%. Then, the fiber cloth was immersed in an aqueous solution of 0.0025M silver nitrate and 0.0025M copper nitrate for 2 hours, and then thermally dried at 100 ℃ for 2 hours to attach the silver nitrate and the copper nitrate to the fiber cloth. And thermally cracking silver nitrate and copper nitrate at 600 ℃ in the presence of nitrogen for 1.5 hours to reduce the silver nitrate and the copper nitrate into silver particles and copper particles, and attaching the silver particles and the copper particles to the fiber cloth. Thereafter, the fiber cloth was washed with water for 2 hours to remove free silver particles and copper particles. Then, the fiber cloth and the silver particles and copper particles attached thereto are thermally dried to remove moisture. Finally, the fiber cloth is ground to obtain a composition containing silver particles, copper particles, and activated carbon fiber powder carrying the silver particles and the copper particles, and the composition is characterized in that: 78.0% by weight of carbon, 0.32% by weight of silver, 0.30% by weight of copper, a length of 0.1mm or less, a BET specific surface area of 980m2/g, a pore diameter of the activated carbon fiber powder of 2.41nm, a particle diameter of silver particles of 100nm or less, and a particle diameter of copper particles of 200nm or less.
Analytical example 1
The toxicity analysis was performed by culturing the composition of each example with mouse fibroblasts L-929 for 24 hours according to International Organization for Standardization (ISO) 10993-5:2009(E) specification, and the dose of the composition was 24mg/1mL of the total volume of cells and culture solution. As shown in Table 1, the compositions of each example were not significantly toxic to normal cells at high doses.
TABLE 1 toxicity of the compositions obtained in each example to mouse fibroblasts
Figure BDA0001381758480000071
Analytical example 2
MTT (3- (4, 5-dimethylthiozol-2-yl) -2,5-diphenyltetrazolium bromide) assay was performed after culturing the composition of preparation example 1 with human colon cancer cells HCT-116, Caco-2, or SW-480 or human colorectal cancer cells HT-29 for 24 hours, wherein the dose was as shown in Table 2, which is the weight of the composition for 1mL of cells and the total volume of the culture solution. As shown in FIGS. 2 to 5 and Table 2, the composition of preparation example 1 was significantly toxic to human colorectal cancer cells at a low dose. It is expected that the composition of preparation example 1 must have significant toxicity to human colorectal cancer cells at high doses as shown in analytical example 1.
TABLE 2 toxicity of the composition obtained in preparation example 1 to human colorectal cancer cells at various doses
Figure BDA0001381758480000081
From the above, it is demonstrated that the composition of the present embodiment is extremely useful as a pharmaceutical for treating or preventing colorectal cancer.
The above description is only a preferred embodiment of the present invention, but should not be taken as limiting the scope of the invention; therefore, all the equivalent changes and modifications made according to the claims and the content of the specification of the present invention are still within the scope covered by the present invention.

Claims (10)

1. Use of a composition for the preparation of a medicament for the treatment of colorectal cancer, characterized in that it is administered orally or tumorally to a subject and can be in different dosage forms, the composition comprising:
a carbonaceous material having different acidic groups or basic groups, which makes the medicine exhibit different degrees of hydrophilicity, and the content of the acidic groups or basic groups is more than 0.3 mEq/g;
an active particle carried on the carbonaceous material and made of silver, gold, zinc and copper; and
the effective dose for the pharmaceutical administration to a subject in need of treatment is 0.1 to 1g per kg of subject per day.
2. The use of a composition according to claim 1, wherein the colorectal cancer is selected from the group consisting of colon cancer, rectal cancer, and colorectal cancer.
3. Use of a composition according to claim 1, wherein the carbonaceous material is selected from the group consisting of carbon powder made of activated carbon fiber, activated carbon powder, charcoal, bamboo charcoal particles, carbon black, graphite powder, graphene, nano carbon powder, phenol resin and synthetic resin.
4. Use of a composition according to claim 1, wherein the active particles have a particle size of 1nm to 200 μm.
5. Use of a composition according to claim 1, wherein the dosage form is a capsule, a tablet, a powder, a suspension, or an emulsion.
6. Use of a composition according to claim 1, wherein the weight percentage of the carbonaceous material is 80 to 99.999% and the weight percentage of the active particles is 0.001 to 20% based on the total weight of the composition.
7. The use of a composition according to claim 1, wherein the carbonaceous material has at least one pore with a radius of less than 2.5 nm.
8. Use of a composition according to claim 1, wherein the carbonaceous material has a BET specific surface area of 0.1 to 2500m2/g。
9. Use of a composition according to claim 1, wherein, in the case where the carbonaceous material is in particulate form, the carbonaceous material has a particle size of more than 1nm but less than 3 mm; under the condition that the carbonaceous material is rod-shaped, the length of the carbonaceous material is more than 1nm but less than 3mm, and the diameter of the cross section of the carbonaceous material is more than 1nm but less than 3 mm; under the condition that the carbonaceous material is irregular, the maximum length thereof is more than 1nm but less than 3 mm.
10. The use of a composition according to claim 1, further comprising an additive selected from the group consisting of nutritional agents, flavoring agents, viscosity agents, solvents, emulsifiers, and moisture control agents.
CN201710707121.3A 2017-08-17 2017-08-17 Application of composition Active CN107281492B (en)

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CN1726782A (en) * 2005-04-07 2006-02-01 中国人民解放军第二军医大学 Composite antibiotic material in medical use of active carbon fiber-Nano silver, and prepearation method
CN103182098B (en) * 2006-01-09 2014-10-01 逢甲大学 Antimicrobial composition and wound coverture
CN101348952B (en) * 2008-09-17 2010-12-01 天津工业大学 Active carbon fibre and preparation thereof
CN102370989B (en) * 2010-08-19 2013-05-29 逢甲大学 Medicinal composition for treating urinary system diseases
CN103316043B (en) * 2013-06-07 2015-10-28 逢甲大学 Containing the medicinal usage of the compositions of carbonaceous material and active particle
CN103316044B (en) * 2013-06-07 2015-11-04 逢甲大学 For suppressing the compositions structure of intestines and stomach bacteriological infection
CN104784736A (en) * 2015-04-22 2015-07-22 深圳市源兴纳米医药科技有限公司 Compound silver-zinc antibacterial composition-containing activated carbon fiber dressing and preparation method thereof

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