CN105640986A - Silver nanoparticle composition for control of lung cancer and prostate cancer - Google Patents
Silver nanoparticle composition for control of lung cancer and prostate cancer Download PDFInfo
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- CN105640986A CN105640986A CN201410724410.0A CN201410724410A CN105640986A CN 105640986 A CN105640986 A CN 105640986A CN 201410724410 A CN201410724410 A CN 201410724410A CN 105640986 A CN105640986 A CN 105640986A
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Abstract
The invention provides a silver nanoparticle composition with lung cancer and prostate cancer resistant activity. The composition contains 20-500mg/kg nano-silver and pharmaceutically acceptable injection excipients (a suspending aid, a dispersing agent, a surfactant, an analgesic, a pH adjustment buffer agent, an osmotic pressure regulator, and water). In the spherical silver nanoparticle powder, the purity of silver is greater than or equal to 99%, and the particle size of silver nanoparticles is 8-75. The experimental result shows that the silver nanoparticle involved in the invention has very strong inhibitory activity on lung cancer H1299 cells and prostate cancer PC-3 cells, and can significantly inhibit H1299 tumor cell transplanted SCID mouse tumor growth in vivo. Therefore, the silver nanoparticle anticancer composition can be used as an antitumor active ingredient individually or in combination for prevention of lung cancer and prevention and treatment of prostate cancer.
Description
Technical field
The present invention relates to and a kind of there is the nanometer silver composition preventing and treating lung cancer and prostate cancer, can be used as antitumor activity component separately or conbined usage.
Background technology
Cancer has become first cause of the death of the mankind, and whole world cancer burden increases with surprising speed at present. According to " world's cancer report in 2014 " of the up-to-date announcement of WHO, within 2012, the newly-increased cases of cancer in the whole world reaches more than 1,400 ten thousand examples, within 2025, will increase to 1,900 ten thousand, and the year two thousand thirty will increase to 2,200 ten thousand, within 2035, will increase to 2,400 ten thousand. China stands in the breach, and within 2012, new diagnosing cancer case is 3,070,000, accounts for the 21.8% of whole world sum, cancer mortality number about 2,200,000, accounts for the 26.9% of whole world cancer mortality number. And over nearly 20 years, cancer presents the high trend of rejuvenation, sickness rate and mortality ratio.
Wherein whether global or Chinese, lung cancer morbidity rate and mortality ratio are high to rank first. In China every year because the number of lung cancer death is more than the summation of mammary cancer, prostate cancer and intestinal cancer death toll, wherein especially the highest with the morbidity of nonsmall-cell lung cancer. Its control and treatment have all been dropped into huge financial resource and material resource by a lot of country, but its sickness rate and mortality ratio still remain high. The treatment of current lung cancer can be passed through operative treatment, chemicotherapy, biotherapy and medicine and realize control to a certain degree, but general curative effect is still not fully up to expectations, each methods for the treatment of is all very big to the damage of human body, and these methods for the treatment of all can not make lung cancer effect a radical cure completely, also there is risk of recurrence to a certain extent. One of them major cause is that lung cancer is one of worst malignant tumour of prognosis, and patient's section of examining of more than 80% or treatment too late, miss the best moment of surgical operation and radical cure. Therefore, the exploitation of the preventive means of lung cancer is most important. Prostate cancer is the most common malignant tumour of male reproductive system, and morbidity increased with the age, and its sickness rate has obvious regional disparity, and European and American areas is higher. It is reported and it is only second to lung cancer, be the 2nd of cancer mortality the male sex. Before China, sickness rate is lower, but due to aging population, sickness rate increases to some extent in recent years.Prostate cancer has multiple therapy methods, and often kind of methods for the treatment of has its pros and cons. Object according to treatment, prostate cancer therapy method is divided into the treatment of healing property and palliative therapy. Palliative therapy refers to that those to delay tumour progression and alleviate the therapy for the purpose of tumor-related symptoms. These methods for the treatment of all can not prevent and Tumor suppression Preventive well.
Nanometer silver nanometer silver (Silvernanoparticles is called for short AgNPs) is always deeply by the concern of people since coming out, and particle diameter is mostly less than 100 nanometers. Environment is had potential harm by conventional chemical preparation process, and along with the development of green synthesis techniques, nanometer silver is more and more extensive in the application of different field. Existing investigator's Successful utilization such as plant milk extracts such as aloe, Flos Pelargonii, Radix Glycyrrhizae prepare nanometer silver. Nanometer silver antimicrobial effect and the antitumor properties to multiple cancer cell, and human body is nontoxic by lower concentration nanometer silver, is considered to have potentiality and the value of exploitation in cancer diagnosis and treatment. Having studies have reported that nanometer silver is to lung cancer A549 cell, mammary cancer MCF-7 cell, the kinds of tumor cells such as colorectal carcinoma HT29 cell and cervical carcinoma cell HeLa show stronger restraining effect. Domestic have one section to treat patent application (a kind of nanometer silver anti-cancer composition and preparation thereof treating lung cancer of lung cancer about nanometer silver; Application number 201410194184.X), setting forth nanometer silver particle diameter in this patent in claim book is 1-5nm, and suppresses A549 active mainly for nanometer silver. In a word, at present not nanometer silver to the relevant report of H1299 and prostate cancer cell and patent etc. Inventor herein started the research of nanometer silver from 2010, found that lung cancer (mainly for H1299) and prostate cancer (PC-3) are had good restraining effect by nanometer silver by the systematic study of long-term inside and outside.
The present invention provides a kind of nanometer silver composition with treatment lung cancer and prostate cancer, particle size range is 5��75nm, lung cancer H1299 cell and prostate cancer PC-3 cell had very strong inhibit activities, IC50 is all less than 10 �� g/mL, lung cancer H1299 cell and prostate cancer PC-3 cell are had very strong inhibit activities by the nanometer silver in the present invention, H1299 tumor cell transplantation SCID mice tumour can be suppressed to increase in significance body. This illustrates that the nanometer silver anti-cancer composition of the application can be used as antitumor activity component separately or conbined usage, for the prevention of lung cancer, and the prevention and therapy of prostate cancer.
Summary of the invention
The present invention is intended to overcome the deficiencies in the prior art, it is provided that a kind of nanometer silver composition, and for preventing and treating the nanometer silver composition of lung cancer and prostate cancer, this nanometer silver composition can be used as antitumor activity component separately or combined utilization.
This nanometer silver composition, it is characterised in that the formulation of application is injection, auxiliary material is all or part of injection supplementary material such as suspending agent, dispersion agent, tensio-active agent, pain killer, pH adjusting agent, osmotic pressure regulator, water. This nanometer silver obtains by plant milk extract green syt, and particle size range is 8-75nm. Suspending agent has the conventional formulation production pharmaceutical excipients etc. such as Xylo-Mucine, polyvidone, methylcellulose gum, sodium alginate, aluminum monostearate. Prepare above-mentioned nanometer silver composition step as follows:
(1) nanometer silver green syt: get Arillus Longan shell powder, Litchi exocarp powder or the two arbitrary combination, add the water of (1: 5��40) in mass ratio, ethanol or different ratios ethanol-water mixture to extract, filter and obtain plant extraction liquid;The plant extraction liquid getting different ratios (mass ratio 1: 1��19) mixes with silver nitrate solution (0.5mM��2M), reaction, centrifugal (12,000rpm, 20 minutes), and washing is dry, obtains nano-Ag particles. Size scope is 8��75nm, and purity reaches 99%.
The formulation of the nanometer silver composition application in the present invention is injection, and composition consists of 1-50% nanometer silver and the shaping auxiliary material of other injections. Above-mentioned auxiliary material is all or part of injection supplementary material such as suspending agent/dispersion agent, pH adjusting agent, osmotic pressure regulator, solubilizing agent, fungistat, pain killer, oxidation inhibitor, complexing agent, emulsifying agent, emulsifying agent, solvent. Suspending agent/dispersion agent can adopt the conventional formulation production pharmaceutical excipients etc. such as Xylo-Mucine, Nitrophenols ketone (PVP), gelatin, PVA, methylcellulose gum, sodium alginate, aluminum monostearate. Suspending agent can adopt; PH adjusting agent can adopt sodium bicarbonate, hydrochloric acid, Citric Acid, sodium hydroxide, ammonium hydroxide, Sodium Citrate, Sodium phosphate dibasic, SODIUM PHOSPHATE, MONOBASIC; Osmotic pressure regulator can adopt sodium-chlor and glucose; Solubilizing agent can adopt Polysorbate 80, hydroxypropyl-beta-cyclodextrin, glucose etc.; Pain killer can adopt phenylcarbinol, vovocan, trichloro-butyl alcohol; Oxidation inhibitor can adopt S-WAT, sodium bisulfite, Sodium Pyrosulfite, Sulfothiorine, thiocarbamide, vitamins C, butyl hydroxy anisol (BHA), dibutyl phenol (BHT), Tenox PG, alpha-tocopherol, xitix, cetylate etc.; Emulsifying agent can adopt Pluronic F68, tween-80, Arlacel-80, PLURONICS F87, Yelkin TTS and fabaceous lecithin etc.; Fungistat can adopt phenol, cresols, trichloro-butyl alcohol, phenyl methylcarbamate and parabens etc.; Solvent can adopt propylene glycol, dehydrated alcohol, ethanol, water etc.
Inside and outside anti-tumor experiment result shows, the present invention provides nanometer silver composition to breed by strongly inhibited lung carcinoma cell H1299 and prostate cancer cell PC-3, its IC50All it is less than 10 �� g/mL, carries out nanometer silver anti-tumor experiment result in body further and also demonstrate that nanometer silver effect of anti-lung cancer. This illustrate this nanometer silver composition can separately or conbined usage, for prevention and therapy lung cancer and prostate cancer.
Accompanying drawing illustrates:
Fig. 1 is TEM, HRTEM, SEM and the size distribution figure (E) of AgNPs
Fig. 2 is that AgNPs is to the growth-inhibiting effect of prostate cancer PC-3 cell and lung cancer H1299 cell
Fig. 3 is nanometer silver composition antitumor action in H1299 inoculated tumour cell SCID mice
Embodiment
Embodiment 1
Take 10g longan shell powder after dry longan shell is broken, add 50mL distilled water, filter after heating in 100mL beaker. Gained plant extraction liquid is added drop-wise to AgNO by 1: 193Solution reacts, it is settled to 100mL, Silver Nitrate final concentration is 0.5mM, it is placed in encloses container, setting temperature of reaction is 25 DEG C, obtains nano silver colloidal sol, centrifugal obtain nanometer silver composition after reaction 72h, the shape looks that gained nanometer silver composition observed by transmission electron microscope (TEM) are spherical, and size scope is 8-30nm. Experimental result is shown in Fig. 1.
Embodiment 2
Take 10g Litchi exocarp powder after dry Litchi exocarp is broken, add 200mL distilled water, filter after heating in 500mL beaker. Gained plant extraction liquid is added drop-wise to AgNO by 1: 13Solution reacts, it is settled to 100mL, Silver Nitrate final concentration is 2.0M, it is placed in encloses container, setting temperature of reaction is 100 DEG C, obtains nano silver colloidal sol, centrifugal obtain nanometer silver composition after reaction 3h, the shape looks that gained nanometer silver composition observed by transmission electron microscope (TEM) are spherical, and size scope is 12-25nm.
Embodiment 3
Dry longan shell and Litchi exocarp broken after respectively take 5g dry powder, add 300mL distilled water and 100mL dehydrated alcohol, filter after heating in 1000mL beaker. Gained plant extraction liquid is added drop-wise to AgNO by 1: 13Solution reacts, it is settled to 100mL, Silver Nitrate final concentration is 1.0M, it is placed in encloses container, setting temperature of reaction is 100 DEG C, obtains nano silver colloidal sol, centrifugal obtain nanometer silver composition after reaction 3h, the shape looks that gained nanometer silver composition observed by transmission electron microscope (TEM) are spherical, and size scope is 18-37nm.
Embodiment 4
Prescription nanometer silver 10g sodium-chlor 5g sodium alginate 5g
Tween 80 1.5g carboxymethyl cellulose 10g
Water for injection adds to 1000ml
Method for making: nanometer silver is added in the water for injection of 50% amount, adds Xylo-Mucine and sodium alginate, stirs even, spends the night after dissolving, filters (200 order nylon cloth), heating. Add the chloride injection aqueous solution again, Polysorbate 80 stir even, heat 30 minutes. Taking-up is chilled to room temperature, injects water to cumulative volume, filters (210 order nylon cloth), is sub-packed in bottle, and Zha Kou seals. 100 DEG C of sterilizings 30 minutes.
Embodiment 5
Method for making: be dissolved in by sodium alginate in 500ml water for injection, filters (210 order), adds Polysorbate 80, sodium-chlor, benzylalcohol and propylene glycol, filters through No. 3 funnels after mixed even. Add nanometer silver, mixed even, filter (210 order), add water for injection and add to 1000ml, stir even, embedding. 100 DEG C of sterilizings 30 minutes.
Embodiment 6
Anti-lung carcinoma cell H1299 and the research of PC-3 tumor promotion in the body of nanometer silver composition
By H1299/PC-3 cell (0.2 �� 105Cells/ml) it is inoculated in 2cm in the culture dish of 5cm, hatches 24 hours. Add different concns AgNPs culture medium solution (2-30 �� g/mL). After process process 72h, got rid of by trypan blue and measure cell survival rate. 80 �� L cell suspending liquids after cancellationization and 20 �� L0.4% Trypan Blues 2 minutes, count under the microscope. Blue cell is considered as dead cell, and the cell of non-absorbing dye is viable cell. With the different concns of medicine to the mapping of growth of tumour cell inhibiting rate, calculate concentration and half-inhibition concentration IC that medicine cell growth inhibiting rate is 50%50��IC50More little, illustrate and make inhibitory rate of cell growth be that the drug level needed for 50% is more little, this medicine is more strong to the toxicity of cell, and namely the drug effect of this medicine is more strong. Experimental result is shown in Fig. 2.
Embodiment 7
In the inherent 1299 lung tumor cell SCID mouse of nanometer silver body, anti-tumor in vivo is active
Taking H1299 lung carcinoma cell as animal tumor transplantation model model, carry out AgNPs anti-mouse transplanted tumor pharmacodynamic study, to evaluate the antitumor action of AgNPs further. By H1299 cell cultures in containing in the RPMI-1640 substratum of 10%FBS, when cell grows to a certain amount of, digested with 0.15% pancreatin EDTA Digestive system, with containing Matrigel nutrient solution suspension cell, then it is inoculated in (SCID) mouse back. Interior animal experiment carries out in SCID mice, becomes control group (solvent, 5 �� L/g) and AgNPs group (10 �� g/g) at random, 8-10/group.
Test I:H1299 cell inoculate 14 days after (tumour size is about 0.2cm2), give control group and experimental group abdominal injection solvent or AgNPs solution respectively Monday, three, five, long run test 28 days.
After test II:H1299 cell inoculates 24 hours, give control group and experimental group abdominal injection solvent or AgNPs solution respectively Monday, three, five, long run test 36 days.
Testing index is: (1) generalized case is observed: animal behavior, reaction, diet and death condition after observation administration, and record body weight, draws the weight of animals change curve; (2) tumour size: measure tumour size (length �� wide, cm2)��
After test terminates, put to death mouse and tumor resection, by tumour soaking at room temperature at formalin phosphate buffered saline buffer 48h, then transfer in ethanol. Mann-Whimey inspection and analysis of variance is adopted to carry out statistical study.
Claims (4)
1. one kind can be used for the nanometer silver composition of lung cancer and prostate cancer control consist of 1-50% nanometer silver and the shaping auxiliary material of other injections, it is possible to be used for as antitumor drug in the prevention of lung cancer and the control of prostate cancer.
2. nanometer silver composition according to claim 1, via following route of administration administration: intravenously, flesh are interior, subcutaneous, in skin, intraperitoneal and combination thereof.
3. in nanometer silver composition according to claim 1, nanometer silver particle size range is 8-75nm, containing nanometer silver 20-500mg/kg, auxiliary material is all or part of injection supplementary material such as suspending agent/dispersion agent, pH adjusting agent, osmotic pressure regulator, solubilizing agent, fungistat, pain killer, oxidation inhibitor, complexing agent, emulsifying agent, emulsifying agent, solvent.
4. nanometer silver composition according to claim 3, suspending agent/dispersion agent can adopt the conventional formulation production pharmaceutical excipients etc. such as Xylo-Mucine, Nitrophenols ketone (PVP), gelatin, PVA, methylcellulose gum, sodium alginate, aluminum monostearate. PH adjusting agent can adopt sodium bicarbonate, hydrochloric acid, Citric Acid, sodium hydroxide, ammonium hydroxide, Sodium Citrate, Sodium phosphate dibasic, SODIUM PHOSPHATE, MONOBASIC; Osmotic pressure regulator can adopt sodium-chlor and glucose; Solubilizing agent can adopt Polysorbate 80, hydroxypropyl-beta-cyclodextrin, glucose etc.; Pain killer can adopt phenylcarbinol, vovocan, trichloro-butyl alcohol; Oxidation inhibitor can adopt S-WAT, sodium bisulfite, Sodium Pyrosulfite, Sulfothiorine, thiocarbamide, vitamins C, butyl hydroxy anisol (BHA), dibutyl phenol (BHT), Tenox PG, alpha-tocopherol, xitix, cetylate etc.; Emulsifying agent can adopt Pluronic F68, tween-80, Arlacel-80, PLURONICS F87, Yelkin TTS and fabaceous lecithin etc.; Fungistat can adopt phenol, cresols, trichloro-butyl alcohol, phenyl methylcarbamate and parabens etc.; Solvent can adopt propylene glycol, dehydrated alcohol, ethanol, water etc.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108379249A (en) * | 2018-05-15 | 2018-08-10 | 广东工业大学 | A kind of drug for treating lung cancer |
| EP3511009A1 (en) * | 2018-01-15 | 2019-07-17 | Shenzhen AMCAN Medical Biotechnology Limited | Angstrom silver injection for cancer inhibition, preparation method and application thereof |
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| CN1328827A (en) * | 2001-04-20 | 2002-01-02 | 朱红军 | Nanometer silver antimicrobial inflammation-relieving gel for curing prostatitis and its industrial production process |
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| CN103933067A (en) * | 2014-05-09 | 2014-07-23 | 湖南省轻工投资有限公司 | Nano-silver anti-cancer composition for treating lung cancer as well as preparation method and application thereof |
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| CN1328827A (en) * | 2001-04-20 | 2002-01-02 | 朱红军 | Nanometer silver antimicrobial inflammation-relieving gel for curing prostatitis and its industrial production process |
| CN1569366A (en) * | 2004-04-30 | 2005-01-26 | 杨漓 | Nano-silver aqueous solution preparation and its preparation method, use and using method |
| CN103933067A (en) * | 2014-05-09 | 2014-07-23 | 湖南省轻工投资有限公司 | Nano-silver anti-cancer composition for treating lung cancer as well as preparation method and application thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3511009A1 (en) * | 2018-01-15 | 2019-07-17 | Shenzhen AMCAN Medical Biotechnology Limited | Angstrom silver injection for cancer inhibition, preparation method and application thereof |
| CN108379249A (en) * | 2018-05-15 | 2018-08-10 | 广东工业大学 | A kind of drug for treating lung cancer |
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