CN109620843A - A kind of Ethylmercurichlorendimide silver oral solution and preparation method thereof and its application in the treatment of gastric cancer - Google Patents
A kind of Ethylmercurichlorendimide silver oral solution and preparation method thereof and its application in the treatment of gastric cancer Download PDFInfo
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Abstract
The invention discloses a kind of Ethylmercurichlorendimide silver oral solutions and preparation method thereof and its application in the treatment of gastric cancer, the Ethylmercurichlorendimide silver oral solution is prepared by Ethylmercurichlorendimide grade simple substance silver powder, medical cane sugar, high-purity distilled water, specific step is as follows: Ethylmercurichlorendimide grade simple substance silver powder being added in high-purity distilled water, Ethylmercurichlorendimide silver solution is obtained；Decentralized processing is carried out to Ethylmercurichlorendimide silver solution；Medical cane sugar is added into the Ethylmercurichlorendimide silver solution after dispersion, and carries out decentralized processing again；Ethylmercurichlorendimide silver solution after dispersion is subjected to heat sterilization, natural cooling obtains Ethylmercurichlorendimide silver oral solution.Ethylmercurichlorendimide silver injection of the invention has the proliferation and transfer ability for significantly inhibiting stomach cancer cell.Ethylmercurichlorendimide galactic longitude takes orally successive administration after 15 days, and the appearance and weight of main organs are without substantially changeing；H&E dyeing and immunohistochemical analysis show the expression quantity of the Caspase-3 of the institutional framework and activation of main organs after the administration of Ethylmercurichlorendimide silver without substantially changeing.
Description
Technical field
The invention belongs to pharmaceutical technology fields, are related to a kind of applied to the Ethylmercurichlorendimide for inhibiting stomach cancer cell, promoting tissue repair
Silver-colored oral solution and preparation method thereof and its application in the treatment of gastric cancer.
Background technique
In the latest 20 years, the incidence gastric cancer rate and the death rate of Asia (especially China, South Korea and Japan) are in year by year
Ascendant trend, and it is apparently higher than the countries such as America and Europe.Moreover, the disease incidence of gastric cancer occupies the 4th in world's cancer morbidity
Position, the death rate occupy second, seriously threaten human health.China is the High Risk For Gastric Cancer country, incidence gastric cancer number of cases and death
Number of cases accounts for global incidence gastric cancer and dead 42.6% and 45.0% respectively, is located at disease incidence the 5th in global 183 countries
Position, the death rate the 6th.Therefore, gastric cancer is to seriously endanger one of the principal disease of Chinese residents health.China is for gastric cancer at present
Treatment method be to first pass through relevant inspection, then clear pathological staging after making a definite diagnosis gastric cancer.For the disease of I, II, III phase
People, it is postoperative also to be assisted according to factors such as pathological staging, the states of patient if state allows suggestion operative treatment
Chemicotherapy, immunization therapy etc.；The patients with terminal namely usually said for the IV phase, it is proposed that releive treatment of the row based on chemotherapy.
Some patients are according to pathogenic factor, it may be considered that joint targeted therapy participates in clinical research.Above-mentioned treatment method is general
Need cut-out or even whole stomaches dirty, postoperative chemotherapy can also seriously affect the quality of life of cancer patient.Advanced stage is suffered from
The treatment side effect of releiving of person is also big, cannot be considered in terms for the treatment of and quality of life, therefore finds one kind newly in curing gastric cancer field
The drug of high effect nontoxic be still extremely urgent thing.
Summary of the invention
In order to solve the problems, such as that above-mentioned treatment method exists, the present invention provides a kind of Ethylmercurichlorendimide silver oral solution and its preparation sides
Method and its application in the treatment of gastric cancer.
The purpose of the present invention is what is be achieved through the following technical solutions:
A kind of Ethylmercurichlorendimide silver oral solution, composition proportion are as follows: Ethylmercurichlorendimide grade simple substance silver powder: 0.5~1.0g/L；Medicinal sugarcane
Sugar: 50.0~100.0g/L；High-purity distilled water: 899.0~949.5g/L；Wherein: silver-colored in the Ethylmercurichlorendimide grade simple substance silver powder
Purity >=99.99%, Argent grain partial size is 1~30 Ethylmercurichlorendimide (Ang), and Argent grain shape is spherical or ellipse, oval
Partial size refers to its long diameter.
A kind of preparation method of above-mentioned Ethylmercurichlorendimide silver oral solution, includes the following steps:
Step 1: Ethylmercurichlorendimide grade simple substance silver powder is added in high-purity distilled water, Ethylmercurichlorendimide silver solution is obtained；
Step 2: carrying out decentralized processing using Ethylmercurichlorendimide silver solution of the ultrasonic equipment to step 1, ultrasonic power is controlled
For 5~15KW, frequency is 30~60KHz, and jitter time is 50~70s；
Step 3: medical cane sugar is added into the Ethylmercurichlorendimide silver solution after step 2 dispersion, and reuse ultrasonic equipment
Decentralized processing is carried out to Ethylmercurichlorendimide silver solution, control ultrasonic power is 10~20KW, and frequency is 110~150KHz, jitter time
For 10~20s；
Step 4: Ethylmercurichlorendimide silver solution after step 3 is dispersed carries out heat sterilization, control heat sterilization temperature is 100~
120 DEG C, the time is 30~60 minutes, and the natural cooling under cleaning sterile environment obtains Ethylmercurichlorendimide silver oral solution.
Above-mentioned Ethylmercurichlorendimide silver oral solution has the function of inhibiting stomach cancer cell, promotes tissue repair, can be used for treating gastric cancer,
Usage mode is directly to swallow, and taking dose need to be determined according to the specific state of an illness, usually 0.0002mg/kg, twice a day, 6 days
One course for the treatment of.
Compared with the prior art, the present invention has the advantage that
1, Ethylmercurichlorendimide silver injection of the invention has the proliferation and transfer ability for significantly inhibiting stomach cancer cell.Malignant tumour is thin
After birth surface is in higher negative electrical charge, and the increase of negative electrical charge and acid mucopolysaccharide, DNA, the side chain of protein of film surface are electric
Lotus is related, especially with the increase of sialic acid amount or appear related.And Ethylmercurichlorendimide silver and silver ion be because have positive charge, it can be with
The electronegative albumen of intraor extracellular and nucleic acid molecules combine, and the synthesis of albumen and the duplication and transcription of DNA are interfered, to destroy cancer
The normal vital movement of cell.Curing gastric cancer oral medication such as the 5-FU class drug, Ka Peita used compared to a current clinical line
Shore or S-1, side effect are more slight.
2, the pharmaceutical raw material and solvent that the present invention takes are nontoxic, and preparation process is simple, can be whole using full-automatic
Metaplasia producing line is produced in batches, and generated waste liquid contains only fructose and micro silver ion in production process, need to only be gone
Except organising and taking the useless silver of precipitation method recycling, process is simply environmentally protective.
Detailed description of the invention
Fig. 1 is influence of the Ethylmercurichlorendimide silver oral solution to stomach cancer cell vigor；
Fig. 2 is influence of the Ethylmercurichlorendimide silver oral solution to stomach cancer cell clonality；
Fig. 3 is influence of the Ethylmercurichlorendimide silver oral solution to stomach cancer cell migration and invasive ability；
Fig. 4 is each group mouse weight and each tissue weight；
Fig. 5 is internal structure and form of the Ethylmercurichlorendimide silver to stomach wall structure, liver and spleen；
Fig. 6 is influence of the Ethylmercurichlorendimide silver to the Caspase-3 expression quantity activated in stomach, liver and spleen.
Specific embodiment
Below with reference to embodiment, further description of the technical solution of the present invention, and however, it is not limited to this, all right
Technical solution of the present invention is modified or replaced equivalently, and without departing from the range of technical solution of the present invention, should all be covered at this
In the protection scope of invention.
Embodiment 1:
A kind of Ethylmercurichlorendimide silver oral solution is present embodiments provided, the Ethylmercurichlorendimide silver oral solution can be used for treating gastric cancer, contain
The ingredient of following concentration: Ethylmercurichlorendimide grade simple substance silver powder: 1.0g/L；Medical cane sugar: 100.0g/L；High-purity distilled water: 899.0g/
L。
Ethylmercurichlorendimide ag material is a kind of Ethylmercurichlorendimide technology emerging in recent years, is by elemental metals silver and other Ag-containing compounds
It is made the metal powder of Ethylmercurichlorendimide rank using method physically or chemically, partial size is mostly 100 Ethylmercurichlorendimides hereinafter, therefore referred to as Ethylmercurichlorendimide
Silver.Obtain process approximately as: input certain size wire below to explosion chamber simultaneously use high pressure ionization explosion, then lead to
Wind collects metallic vapour, is sent using ventilating system to buffer area, carries out cooling, demagnetization, ultrasonic wave are broken up, cyclone type wind-force separates
Classification collects powder to tank is saved, and adds inert gas and is passivated work acquisition finished product.
In the present embodiment, silver-colored purity >=99.99% in the Ethylmercurichlorendimide grade simple substance silver powder, Argent grain partial size is 50 Ethylmercurichlorendimides
(Ang), Argent grain shape is ellipse.
In the present embodiment, the preparation step of the Ethylmercurichlorendimide silver oral solution is as follows:
Step 1: the oval Ethylmercurichlorendimide grade simple substance silver powder that partial size is 5Ang is added in high-purity distilled water, obtain
Spherical Ethylmercurichlorendimide grade elemental silver powder concn is the oval Ethylmercurichlorendimide silver solution of 1.0g/L；
Step 2: carrying out decentralized processing, control ultrasound using oval Ethylmercurichlorendimide silver solution of the ultrasonic equipment to step 1
Wave power is 5KW, frequency 40KHz, jitter time 60s；
Step 3: medical cane sugar is added into the oval Ethylmercurichlorendimide silver solution after step 2 dispersion, medical cane sugar is controlled
Concentration is 100g/L, then reuses ultrasonic equipment and carries out decentralized processing to oval Ethylmercurichlorendimide silver solution, controls ultrasonic wave
Power is 10KW, frequency 120KHz, jitter time 10s；
Step 4: the oval Ethylmercurichlorendimide silver solution after step 3 is dispersed is heated to 100 DEG C, sterilize 30 minutes, then in
Natural cooling under cleaning sterile environment obtains Ethylmercurichlorendimide silver oral solution.
Embodiment 2:
Unlike the first embodiment, the Ethylmercurichlorendimide silver oral solution contains the ingredient of following concentration: Ethylmercurichlorendimide grade list to the present embodiment
Matter silver powder: 0.8g/L；Medical cane sugar: 80.0g/L；High-purity distilled water: 919.2g/L, specific preparation process is as follows:
Step 1: the spherical Ethylmercurichlorendimide grade simple substance silver powder that partial size is 25Ang is added in high-purity distilled water, ball is obtained
Shape Ethylmercurichlorendimide grade elemental silver powder concn is the spherical Ethylmercurichlorendimide silver solution of 0.8g/L；
Step 2: carrying out decentralized processing using spherical Ethylmercurichlorendimide silver solution of the ultrasonic equipment to step 1, ultrasonic wave is controlled
Power is 15KW, frequency 50KHz, jitter time 60s；
Step 3: medical cane sugar is added into the spherical Ethylmercurichlorendimide silver solution after step 2 dispersion, the dense of medical cane sugar is controlled
Degree is 80g/L, then reuses ultrasonic equipment and carries out decentralized processing to spherical Ethylmercurichlorendimide silver solution, control ultrasonic power is
15KW, frequency 140KHz, jitter time 15s；
Step 4: the spherical Ethylmercurichlorendimide silver solution after step 3 is dispersed is heated to 100 DEG C, sterilize 30 minutes, then in clean
Natural cooling under net gnotobasis, obtains Ethylmercurichlorendimide silver oral solution.
Embodiment 3:
Unlike the first embodiment, the Ethylmercurichlorendimide silver oral solution contains the ingredient of following concentration: Ethylmercurichlorendimide grade list to the present embodiment
Matter silver powder: 0.5g/L；Medical cane sugar: 50.0g/L；High-purity distilled water: 949.5g/L, specific preparation process is as follows:
Step 1: the spherical Ethylmercurichlorendimide grade simple substance silver powder that partial size is 10Ang is added in high-purity distilled water, ball is obtained
Shape Ethylmercurichlorendimide grade elemental silver powder concn is the spherical Ethylmercurichlorendimide silver solution of 0.5g/L；
Step 2: carrying out decentralized processing using spherical Ethylmercurichlorendimide silver solution of the ultrasonic equipment to step 1, ultrasonic wave is controlled
Power is 8KW, frequency 50KHz, jitter time 60s；
Step 3: medical cane sugar is added into the spherical Ethylmercurichlorendimide silver solution after step 2 dispersion, the dense of medical cane sugar is controlled
Degree is 50g/L, then reuses ultrasonic equipment and carries out decentralized processing to spherical Ethylmercurichlorendimide silver solution, control ultrasonic power is
15KW, frequency 150KHz, jitter time 15s；
Step 4: the spherical Ethylmercurichlorendimide silver solution after step 3 is dispersed is heated to 100 DEG C, sterilize 30 minutes, then in clean
Natural cooling under net gnotobasis, obtains Ethylmercurichlorendimide silver oral solution.
The anticancer mechanism of Ethylmercurichlorendimide silver oral solution can substantially be attributed to following three points: 1, can be with the surface protein of cancer cell
Equal contacts either Ethylmercurichlorendimide silver enters cell space directly through cell membrane, and the rupture of mediated cancerous cell cell membrane is thin so as to cause cancer
Tolerant release intracellular, induces the death of cancer cell；2, Ethylmercurichlorendimide silver surface energy sustained release silver ion, cause regional area silver from
Sub- concentration is higher, and then mediates stronger anticarcinogenic effect；3, Ethylmercurichlorendimide silver and its silver ion discharged can induce intracellular reactive oxygen species generation
(ROS) it generates, causes cancer cell DNA damage and protein oxidation, cancer cell specific induction of apoptosis.
In cell experiment research, present invention uses SGC-7901 stomach cancer cell lines.Firstly, using cell viability reagent
Box (CCK-8 method) analyzes Ethylmercurichlorendimide silver to the toxicity of stomach cancer cell.As shown in Figure 1, when being located respectively with the Ethylmercurichlorendimide silver of gradient concentration
After stomach cancer cell 24 hours or 48 hours, calculate Ethylmercurichlorendimide silver is respectively reason to the half lethal concentration of stomach cancer cell
31ng/ μ l and 13ng/ μ l.
Meanwhile influence of the Ethylmercurichlorendimide silver to proliferation of human gastric cancer cell ability is analyzed using cell plates colony formation.Just
Normal single stomach cancer cell is capable of forming cell clone colony, but the Ethylmercurichlorendimide silver of 2ng/ μ l can inhibit about 80% cell gram
Grand, the Ethylmercurichlorendimide silver of 4ng/ μ l can even inhibit about 100% cell clone (Fig. 2).
The migration of tumour cell and invasive ability are the important indicators for evaluating tumour occurrence and development in vivo.The present invention adopts
Migration and the invasion energy of stomach cancer cell are inhibited in cellular level with scratch experiment with demonstrating the Ethylmercurichlorendimide silver gradient of various concentration
Power (Fig. 3).
The present invention establishes the oral administration model of Ethylmercurichlorendimide silver using C57BL/6 mouse.Mouse is randomly divided into 3 groups:
Solvent control group, low dosage Ethylmercurichlorendimide silver group (500ppm) and high dose Ethylmercurichlorendimide silver group (1000ppm).3 groups of mouse are by continuous oral
Give corresponding dosage drug 15 days.At the 16th day, above-mentioned 3 groups of mouse were euthanized, collect the serum of mouse, stomach, liver,spleen,kidney,
The main organs such as lung, brain and the heart, and record the weight of mouse weight and each internal organs.From macroscopic analysis, each main organs
Appearance does not have notable difference.Meanwhile the weight of above-mentioned 3 groups of mouse and the weight of main organs do not have larger change (Fig. 4).
The stomach, liver and spleen of mouse are fixed and paraffin section, using the group inside H&E decoration method analysis internal organs
Knit structure and cellular morphology.The experimental results showed that the Ethylmercurichlorendimide silver of high low dosage is not all in stomach wall structure, liver and spleen
Portion's structure and form cause significant difference (Fig. 5).Mainly reflect the index total bilirubin and reflection injury of kidney of hepatic injury in serum
Index creatinine also without obviously rise (table 1).
The content of total bilirubin and creatinine in 1 different disposal group mice serum of table
Since the molecular mechanism that Ethylmercurichlorendimide silver kills tumour cell is the apoptosis for promoting tumour cell, the present invention also adopts
Stomach is analyzed with immunohistochemical method, whether there is or not increases for the quantity of apoptotic cell in liver and spleen.Caspase-3 is that one kind is withered
GAP-associated protein GAP is died, is the important component of most important terminal shearing enzyme and cell killing mechanism in apoptosis process.
Caspase-3 is mainly expressed in cytoplasm, and Caspase-3 positive expression is higher, indicates that the cell that apoptosis occurs is more.Experiment knot
Fruit shows that the Ethylmercurichlorendimide silver of high low dosage does not all cause the expression quantity of the Caspase-3 in stomach wall, liver and spleen to rise and wither
Die the increase (Fig. 6) of cell.
In conclusion Ethylmercurichlorendimide silver injection has the proliferation and transfer ability for significantly inhibiting stomach cancer cell.Ethylmercurichlorendimide galactic longitude mouth
After taking successive administration 15 days, the appearance and weight of main organs are without substantially changeing；H&E dyeing and immunohistochemical analysis show angstrom
The expression quantity of the Caspase-3 of the institutional framework and activation of main organs is without substantially changeing after rice silver administration.
Claims (10)
1. a kind of Ethylmercurichlorendimide silver oral solution, it is characterised in that the composition proportion of the Ethylmercurichlorendimide silver oral solution is as follows: Ethylmercurichlorendimide grade elemental silver
Powder: 0.5~1.0g/L；Medical cane sugar: 50.0~100.0g/L；High-purity distilled water: 899.0~949.5g/L.
2. Ethylmercurichlorendimide silver oral solution according to claim 1, it is characterised in that the composition proportion of the Ethylmercurichlorendimide silver oral solution is such as
Under: Ethylmercurichlorendimide grade simple substance silver powder: 0.5g/L；Medical cane sugar: 50.0g/L；High-purity distilled water: 949.5g/L.
3. Ethylmercurichlorendimide silver oral solution according to claim 1 or 2, it is characterised in that silver in the Ethylmercurichlorendimide grade simple substance silver powder
Purity >=99.99% of grain, Argent grain partial size are 1~30 Ethylmercurichlorendimide.
4. Ethylmercurichlorendimide silver oral solution according to claim 3, it is characterised in that the Argent grain shape is spherical or ellipse.
5. the preparation method of Ethylmercurichlorendimide silver oral solution described in a kind of claim 1-4 any claim, it is characterised in that described
Method and step is as follows:
Step 1: Ethylmercurichlorendimide grade simple substance silver powder is added in high-purity distilled water, Ethylmercurichlorendimide silver solution is obtained；
Step 2: carrying out decentralized processing using Ethylmercurichlorendimide silver solution of the ultrasonic equipment to step 1；
Step 3: to step 2 dispersion after Ethylmercurichlorendimide silver solution in medical cane sugar is added, and reuse ultrasonic equipment to angstrom
The silver-colored solution of rice carries out decentralized processing；
Step 4: the Ethylmercurichlorendimide silver solution after step 3 is dispersed carries out heat sterilization, natural cooling obtains Ethylmercurichlorendimide silver oral solution.
6. the preparation method of Ethylmercurichlorendimide silver oral solution according to claim 5, it is characterised in that in the step 2, ultrasonic wave
Power is 5~15KW, and frequency is 30~60KHz, and jitter time is 50~70s.
7. the preparation method of Ethylmercurichlorendimide silver oral solution according to claim 5, it is characterised in that in the step 3, ultrasonic wave
Power is 10~20KW, and frequency is 110~150KHz, and jitter time is 10~20s.
8. the preparation method of Ethylmercurichlorendimide silver oral solution according to claim 5, it is characterised in that in the step 4, heating is gone out
Bacterium temperature is 100~120 DEG C, and the time is 30~60 minutes.
9. the application of Ethylmercurichlorendimide silver oral solution in the treatment of gastric cancer described in claim 1-4 any claim.
10. the application of Ethylmercurichlorendimide silver oral solution according to claim 9 in the treatment of gastric cancer, it is characterised in that the Ethylmercurichlorendimide silver
The usage mode of oral solution is directly to swallow.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111388501A (en) * | 2020-03-06 | 2020-07-10 | 深圳埃米迦医药生物科技有限公司 | Application of silver amethoxide antiviral solution in preparation of COVID-19 virus resisting medicine |
| CN111388414A (en) * | 2020-03-06 | 2020-07-10 | 深圳埃米迦医药生物科技有限公司 | Application of silver amethoxide antiviral solution in preparation of medicine for resisting HPV (human papillomavirus) |
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