CN111388414A - Application of silver amethoxide antiviral solution in preparation of medicine for resisting HPV (human papillomavirus) - Google Patents

Application of silver amethoxide antiviral solution in preparation of medicine for resisting HPV (human papillomavirus) Download PDF

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CN111388414A
CN111388414A CN202010151545.8A CN202010151545A CN111388414A CN 111388414 A CN111388414 A CN 111388414A CN 202010151545 A CN202010151545 A CN 202010151545A CN 111388414 A CN111388414 A CN 111388414A
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silver
solution
angstrom
application
sucrose
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谢辉
殷豪
司徒伟怡
陈春媛
王振兴
王杨
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Shenzhen Aimijia Medical Biotechnology Co ltd
Xiangya Hospital of Central South University
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Xiangya Hospital of Central South University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/38Silver; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/20Antivirals for DNA viruses

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Abstract

The invention discloses an application of an Hermitian silver antiviral solution in preparation of an anti-HPV (human papillomavirus) medicament, wherein the Hermitian silver antiviral solution comprises an Hermitian silver simple substance, anhydrous sucrose and distilled water, the concentration of the Hermitian silver simple substance is 0.5-1.0 g/L, and the concentration of the sucrose is 5.0-10.0 g/L.

Description

Application of silver amethoxide antiviral solution in preparation of medicine for resisting HPV (human papillomavirus)
Technical Field
The invention relates to the technical field of medicines, in particular to application of an angstrom silver antiviral solution in preparation of a medicine for treating HPV virus.
Background
Human Papilloma Virus (HPV) is a spherical DNA virus with interpersonal infectivity. Data published by the world health organization indicate that the global population for HPV infection reaches as many as 6.3 million people, accounting for about 10% of the human population, with a greater probability of female infection reaching 80%. In China, cervical tumors caused by HPV infection are the first gynecological malignant tumors and gradually show a trend of youthfulness, and huge losses are caused to the health and economy of China. HPV has high tropism to human skin and mucous epithelium cells, and can be self-replicated in cells or integrated into host cell DNA after infecting host cells, and performs replication and transcription synchronously with the host cells. The high-risk HPV (such as HPV16 and 18) has the capacity of inducing cell transformation, and after DNA is integrated into the chromosome of a host cell, the DNA synthesis of the host cell is promoted, so that the host cell (mainly mucosal epithelial cells) is converted into immortalized cells, and precancerous lesion and malignant tumor are induced. At present, the treatment aiming at the diseases caused by HPV infection mainly adopts physical means (such as freezing treatment, laser treatment, microwave treatment, operation treatment and the like) and is assisted by drug treatment. However, the physical method is difficult to operate and causes epidermal loss and scar, and the interferon and interleukin-based drug therapy is expensive and the curative effect thereof is controversial in academia. Therefore, it is urgent to find a new anti-HPV drug with definite therapeutic effect and moderate price.
Disclosure of Invention
In order to solve the problems, the invention aims to provide an application of an angstrom silver antiviral solution in preparing a medicine for resisting HPV virus.
In order to achieve the purpose, the invention provides an application of an Hermitian antiviral solution in preparation of a medicine for resisting HPV virus, wherein the Hermitian antiviral solution comprises an Hermitian simple substance, anhydrous sucrose and distilled water, the concentration of the Hermitian simple substance is 0.5-1.0 g/L, and the concentration of the sucrose is 5.0-10.0 g/L.
In the application, the particle size of silver particles in the angstrom silver simple substance is 1-30 angstrom meters, the silver particles are spherical or elliptical, and the purity of the silver particles is more than or equal to 99.99%.
In the application, the concentration of the angstrom silver simple substance is 0.5 g/L, the concentration of the cane sugar is 5.0 g/L, and the concentration of the double distilled water is 994.5 g/L.
The application is further that the preparation method of the angstrom silver antiviral solution comprises the following steps:
s1, adding the Hermite-grade simple substance silver powder into sterile distilled water to obtain a Hermite silver solution;
s2, carrying out first ultrasonic dispersion treatment on the angstrom silver solution to obtain an angstrom silver aqueous solution;
s3, adding anhydrous sucrose, and performing secondary ultrasonic dispersion treatment to obtain a sucrose-coated Eimeria silver dispersion liquid;
s4, heating and sterilizing to obtain the angstrom silver antiviral solution.
In the application, further, in the first ultrasonic dispersion treatment process, the ultrasonic power is 5-15 KW, the frequency is 30-60 KHz, and the dispersion time is 50-70 s.
In the second ultrasonic dispersion treatment, the ultrasonic power is 10-20 KW, the frequency is 110-150 KHz, and the dispersion time is 10-20 s.
In the application, the temperature for heating and sterilizing in the step S4 is 100-130 ℃, and the time is 15-60 min.
The above application, further, the HPV virus is a HPV16pp and/or HPV18pp type virus.
The application is further characterized in that the anti-HPV virus medicine is an anti-HPV virus injection.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention provides an application of an angstrom silver antiviral solution in resisting HPV virus. The Hermitia silver antiviral solution consists of Hermitia silver, cane sugar and distilled water, and on the premise of ensuring curative effect, the component varieties of the Hermitia silver antiviral solution composition are reduced as far as possible, so that the medication safety is improved, the strong antiviral ability is retained, and meanwhile, the addition of the cane sugar enables silver particles to be uniformly distributed in the solution in a simple substance manner, so that the defect of simple silver particle agglomeration is overcome. The application adopts the silver particles in the angstrom level, and the angstrom silver has the comprehensive effect of high strength, high effect and high stability, so that the antiviral efficacy of the angstrom silver is stronger under the same concentration, and the curative effect can be achieved only by lower concentration.
(2) The invention provides an application of an angstrom silver antiviral solution in resisting HPV virus. In the preparation process, the adopted medicine raw materials and solvents are nontoxic and harmless, the preparation process is simple, the full-automatic production line can be used for batch production in the whole process, the waste liquid generated in the production process only contains trace silver ions, only organic compounds need to be removed, and the waste silver is recovered by adopting a precipitation method, so that the process is simple, green and environment-friendly.
(3) The invention provides an application of an angstrom silver antiviral solution in resisting HPV virus. During the preparation process of the Herminium silver antiviral solution, sucrose is added into the Herminium silver, so that the Herminium silver powder is wrapped by sucrose molecules, and the Herminium silver can have good suspension stability in the solution. Under the control of the preparation method, the angstrom silver particles in the solution can be uniformly coated by the sucrose.
(4) The invention provides an application of an angstrom silver antiviral solution in resisting HPV virus, wherein the antiviral mechanism of the angstrom silver is related to the following mechanisms: 1. after the virus is mechanically adsorbed and fixed, the virus loses survival conditions and dies; 2. inhibiting the binding of the virus to cellular receptors, preventing the virus from entering and infecting host cells; 3. binding with viral nucleic acid to alter the structure of viral DNA or RNA and inhibit viral replication; 4. silver ions released by the silver amethodes have direct killing effect on viruses. Meanwhile, the silver amethodes has small side effect, and can overcome the inconvenience brought by long-term administration and the risk brought by virus drug resistance.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. Modifications or substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and scope of the invention.
Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art; all reagents used in the examples are commercially available unless otherwise specified.
The percentage "%" referred to in the present invention means mass% unless otherwise specified; but the percentage of the solution, unless otherwise specified, refers to the grams of solute contained in 100ml of the solution.
The weight parts in the invention can be the weight units known in the art such as mu g, mg, g, kg, and the like, and can also be multiples thereof, such as 1/10, 1/100, 10, 100, and the like.
The anhydrous sucrose is medicinal anhydrous sucrose, and the Hermitian silver material is prepared by making single metal silver and other silver-containing compounds into Hermitian-grade metal powder by physical or chemical methods, and has a particle size of below 100 Hermitian, so the Hermitian silver is called. The acquisition procedure is roughly as follows: the preparation method of the silver angstromate comprises the following steps:
(1) filling inert gas argon into the explosion chamber to keep the gas pressure in the explosion chamber at 1 × 106Pa, and stabilizing the working temperature in the reactor at 8-12 ℃.
(2) Continuously pushing a silver wire with the diameter of 0.5mm and the length of 8-12 cm into an explosion chamber, and exploding the silver wire under the high voltage of 25kV generated when the silver wire is contacted with the positive electrode electroplate to instantaneously evaporate the silver wire into silver vapor plasma.
(3) And pumping the silver vapor accompanied with argon to a quenching chamber with the temperature set to be 0-4 ℃, wherein the silver vapor is rapidly solidified when cooled and forms silver particles.
(4) Dispersing the obtained silver particles by high-intensity ultrasonic waves (the ultrasonic power is 15KW, and the frequency is 15 KHz), and pumping the dispersed silver particles to a demagnetizing device (the related parameters are set to be 36V, 23Hz and 1000mA) for demagnetizing.
(5) The degaussed silver particles are collected through a particle collecting system, the particles with different particle sizes have different settling velocities, the particle sizes are 0-30 angstrom meters according to the different settling velocities, the particles are collected to a storage tank, and inert gas is added into the storage tank for passivation to obtain a finished product.
The purity of silver particles in the Hermite-grade simple substance silver powder prepared by the method is more than or equal to 99.99%, the particle size of the silver particles is 0-30 Hermite, the shape of the silver particles is spherical or elliptical, and the elliptical particle size refers to the long diameter of the silver particles.
Example 1:
the invention relates to an angstrom silver antiviral solution, which comprises 0.5 g/L angstrom-level simple substance silver powder, 5 g/L medicinal anhydrous cane sugar and 994.5 g/L high-purity distilled water, and the preparation method comprises the following steps:
(1) adding 1-30 Ang-meter-grade elementary silver powder into high-purity distilled water to obtain an angmeter-grade silver solution with the concentration of 0.5 g/L.
(2) And (2) carrying out ultrasonic dispersion on the angstrom silver solution obtained in the step (1) by using an ultrasonic oscillator, wherein the ultrasonic power is 5KW, the frequency is 60KHz, and the dispersion time is 60s to obtain the angstrom silver dispersion liquid.
(3) Adding sucrose into the Eimeria silver dispersion liquid to enable the concentration of the sucrose to be 50 g/L, and performing ultrasonic dispersion by using an ultrasonic oscillator, wherein the ultrasonic power is 15KW, the frequency is 150KHz, and the time is 20s to obtain the Eimeria silver dispersion liquid wrapped by the sucrose.
(4) And (4) heating and sterilizing the sucrose-coated angstrom silver dispersion liquid obtained in the step (3) at 120 ℃ for 60min, and naturally cooling to obtain the angstrom silver antiviral solution.
Example 2:
the application of the silver amethode antiviral solution in the embodiment 1 in resisting HPV16 and 18 viruses comprises the following steps:
(1) and (3) inoculating the recovered 293FT cells into a 96-well plate, co-culturing with the silver amethode antiviral solution for 72h, and detecting the toxic effect of the silver amethode antiviral solution on the cells by adopting a CellTiler-GloTM (Promega) kit.
(3) After 293FT is infected by HPV16 or 18 pseudovirus particles containing reporter gene GFP, infected cells express green fluorescent protein, and the infection condition of HPV virus can be reflected by observing data of cells expressing GFP green fluorescence under a fluorescence microscope. We added HPV16pp or 18pp virus solution to 293FT cells seeded in 96-well plates, and after 72h of coculture with the Aglaia anglica antiviral solution, the effect of the Aglaia anglica antiviral solution against HPV16pp or 18pp was examined by photographing and counting by fluorescence microscopy.
(3) As a result:
table 1 shows CC50 for 293FT cells and EC for HPV16pp for the Agkistrodon acutus antiviral solution of example 1 of the present invention50
Table 1: toxicity of the silver amethole antiviral solution to cells and inhibition of HPV16pp results are shown
Figure BDA0002402612860000051
Table 2 shows the CC50 for 293FT cells and the EC for HPV18pp for the Agium angstromatum antiviral solution of example 3 of the present invention50
TABLE 2 toxicity of the Aglaia angstromata antiviral solution to cells and inhibition of HPV18pp results
Figure BDA0002402612860000052
From the results of tables 1 and 2, it can be seen that: the silver amethoxide antiviral solution has certain toxicity to 293FT cells under the condition of high concentration, and has inhibitory activity to infection of HPV16pp and 18pp under the conditions of low toxicity and non-toxic concentration.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims (9)

1. The application of the Hermitia argentiviral solution in preparation of anti-HPV (human papillomavirus) drugs is characterized in that the Hermitia argentiviral solution comprises a Hermitia argentiviral simple substance, anhydrous sucrose and distilled water, wherein the concentration of the Hermitia argentiviral simple substance is 0.5-1.0 g/L, and the concentration of the sucrose is 5.0-10.0 g/L.
2. The application of claim 1, wherein the silver particles in the angstrom silver simple substance have a particle size of 1-30 angstrom, are spherical or elliptical, and have a purity of not less than 99.99%.
3. The use of claim 1, wherein said angstrom silver has an elemental concentration of 0.5 g/L, said sucrose has a concentration of 5.0 g/L, and said double distilled water has a concentration of 994.5 g/L.
4. Use according to any one of claims 1 to 3, characterized in that the preparation process of the silver amethode antiviral solution comprises the following steps:
s1, adding the Hermite-grade simple substance silver powder into sterile distilled water to obtain a Hermite silver solution;
s2, carrying out first ultrasonic dispersion treatment on the angstrom silver solution to obtain an angstrom silver aqueous solution;
s3, adding anhydrous sucrose, and performing secondary ultrasonic dispersion treatment to obtain a sucrose-coated Eimeria silver dispersion liquid;
s4, heating and sterilizing to obtain the angstrom silver antiviral solution.
5. The application of claim 4, wherein in the first ultrasonic dispersion treatment process, the ultrasonic power is 5-15 KW, the frequency is 30-60 KHz, and the dispersion time is 50-70 s.
6. The application of claim 4, wherein in the second ultrasonic dispersion treatment process, the ultrasonic power is 10-20 KW, the frequency is 110-150 KHz, and the dispersion time is 10-20 s.
7. The use according to claim 4, wherein the temperature for heat sterilization in S4 is 100-130 ℃ for 15-60 min.
8. Use according to claim 1, wherein the HPV virus is a virus of the HPV16pp and/or HPV18pp type.
9. The use according to any one of claims 1 to 8, wherein the anti-HPV virus medicament is an anti-HPV virus injection.
CN202010151545.8A 2020-03-06 2020-03-06 Application of silver amethoxide antiviral solution in preparation of medicine for resisting HPV (human papillomavirus) Pending CN111388414A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
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CN113813287A (en) * 2021-08-27 2021-12-21 中国医学科学院皮肤病医院(中国医学科学院皮肤病研究所) Preparation method of compound medicinal liquid for treating verruca vulgaris

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CN108096277A (en) * 2018-01-15 2018-06-01 深圳埃米迦医药生物科技有限公司 Inhibit Ethylmercurichlorendimide silver parenteral solution of cancer and preparation method thereof, application
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Publication number Priority date Publication date Assignee Title
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Cited By (1)

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CN113813287A (en) * 2021-08-27 2021-12-21 中国医学科学院皮肤病医院(中国医学科学院皮肤病研究所) Preparation method of compound medicinal liquid for treating verruca vulgaris

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