CN113577099A - Use of molybdenum and/or tungsten containing compounds against Human Papilloma Virus (HPV) or herpes virus (HSV) and pharmaceutical compositions thereof - Google Patents

Use of molybdenum and/or tungsten containing compounds against Human Papilloma Virus (HPV) or herpes virus (HSV) and pharmaceutical compositions thereof Download PDF

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CN113577099A
CN113577099A CN202110961745.4A CN202110961745A CN113577099A CN 113577099 A CN113577099 A CN 113577099A CN 202110961745 A CN202110961745 A CN 202110961745A CN 113577099 A CN113577099 A CN 113577099A
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hpv
virus
molybdenum
tungsten
hsv
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林玉平
孙卓然
林春平
林雪
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Beijing Anbatec Biotechnology Co ltd
Sanhe Anba Biotechnology Co ltd
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Beijing Anbatec Biotechnology Co ltd
Sanhe Anba Biotechnology Co ltd
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    • 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
    • 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
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • 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
    • A61P31/22Antivirals for DNA viruses for herpes viruses

Abstract

The present invention provides the use of molybdenum and/or tungsten containing compounds in the treatment of human papillomavirus HPV or herpes virus HSV. The molybdenum and/or tungsten-containing compound of the invention can be used as an antiviral substance to rapidly kill and durably inhibit pathogenic microorganisms (bacteria, viruses and molds) and multidrug-resistant bacteria; can treat and relieve various symptoms caused by Human Papilloma Virus (HPV) and herpes virus (HSV), has quick response and strong virus killing activity, and antiviral substances are not absorbed by human bodies and do not generate toxic or side effect; can be used for reducing the load of Human Papillomavirus (HPV) and herpes virus (HSV) on local parts of a human body, and can also be used for preparing medicines, medical devices, disinfectants and other auxiliary care products for treating various human skin or skin mucosa diseases caused by pathogenic microorganisms.

Description

Use of molybdenum and/or tungsten containing compounds against Human Papilloma Virus (HPV) or herpes virus (HSV) and pharmaceutical compositions thereof
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to application of a molybdenum and/or tungsten-containing compound in resisting Human Papilloma Virus (HPV) or herpes virus (HSV) and a pharmaceutical composition thereof.
Background
Scientific research finds that dermatosis caused by microorganisms, such as psoriasis, Human Papilloma Virus (HPV), herpes virus (HSV) and other lesions, are caused by the reproduction and growth of pathogenic microorganisms (bacteria, fungi and viruses) on the skin. The diseases have the advantages of wide population, large number of people, long duration, high recurrence rate, difficult radical cure and no specific medicine, and bring serious harm to the health and life of people. Currently, the main way to treat fungal infections is to apply hormonal drugs (e.g. ketoconazole) to the affected area, and the potential disadvantages include: the toxicity and the sensitization of the components easily cause the hyperfunction of the cortex, the treatment course is long, the effect is slow and the like.
For low-risk human papilloma virus HPV infection, some medicines have certain effects. Such as imiquimod, is an immunomodulator that acts by modulating the cellular immune function locally at the lesion; podophyllotoxin can inhibit virus and prevent cell proliferation caused by virus. However, for high-risk HPV infection, no antiviral drug which is proved to be fully effective by clinical practice is on the market at present. Some physicians attempt to treat high-risk HPV infections with interferon and may be theoretically effective, but it is not clearly concluded whether it is effective. Therefore, no specific drug is recommended for direct killing of HPV virus in the current clinical guidelines for the treatment of cervical lesions. The HPV vaccine has a certain prevention effect, but the existing HPV vaccine not only has age limitation, but also cannot completely cover the typing of the high-risk HPV (the high-risk HPV has at least 15 types, and the existing vaccine can cover at most 9 types), and the effective period of the vaccine is only 6-8 years.
Because there is no medicine capable of directly killing herpes virus, the treatment principle of herpes virus HSV infection is to take antiviral medicine, such as acyclovir, take mecobalamin to nourish nerve and relieve pain, and prevent complications such as postherpetic neuralgia. Long-term administration of the antiviral drug acyclovir may cause damage to liver or kidney function. Symptoms such as arthralgia, diarrhea, headache, nausea, vomiting, dizziness, etc. appear.
Disclosure of Invention
In view of the above problems in the prior art, the present invention provides the use of molybdenum and/or tungsten metal oxide, or molybdenum and/or tungstate, or polyoxometallate containing molybdenum and/or tungsten in resisting Human Papillomavirus (HPV) or herpes virus (HSV), and pharmaceutical compositions thereof.
Specifically, the present invention relates to the following aspects:
1. use of molybdenum-and/or tungsten-containing compounds against human papillomavirus HPV or herpes virus HSV.
2. The use according to item 1, wherein the molybdenum and/or tungsten-containing compound is one or more selected from the group consisting of an oxide of molybdenum and/or tungsten, a tungstate of molybdenum and/or tungsten, and a polyoxometalate of molybdenum and/or tungsten.
3. Use according to item 2, characterized in that the polyoxometallate containing molybdenum and/or tungsten is a tungsten molybdate.
4. The use according to item 1, wherein the anti-HPV is selected from the group consisting of anti-HPV high-risk type HPV or anti-HPV low-risk type HPV, wherein the anti-HPV high-risk type HPV is selected from one or more of HPV-1, HPV-2, HPV-3, HPV-4, HPV-7, HPV-10, HPV-12, HPV-15, HPV-16, HPV-18, HPV-30, HPV-31, HPV-33, HPV-35, HPV-39, HPV-53 and HPV-61, preferably HPV-16, HPV18 or HPV31, and the anti-HPV low-risk type HPV is selected from the group consisting of HPV-6, HPV-11, HPV-40, HPV-42, HPV-43, HPV-44, HPV-54, HPV-61, One or more of HPV-70, HPV-72, HPV-81 and CP 6108, preferably HPV-6 or HPV 11.
5. The use according to item 1, wherein the herpes virus HSV is selected from one or more of herpes simplex virus HSV-1, herpes simplex virus HSV-2, varicella-zoster virus VZV, epstein barr virus EBV, human cytomegalovirus HCMV, human herpesvirus 6 HHV-6, human herpesvirus 7 HHV-7, and kaposi's sarcoma-associated virus KSHV, preferably herpes simplex virus HSV or varicella-zoster virus VZV.
6. A pharmaceutical composition comprising a molybdenum and/or tungsten containing compound, wherein the molybdenum and/or tungsten containing compound is selected from one or more of molybdenum and/or tungsten oxides, molybdenum and/or tungstates, and molybdenum and/or tungsten containing polyoxometallates.
7. The pharmaceutical composition of item 6, wherein the pharmaceutical composition is a gel.
8. The pharmaceutical composition according to item 7, wherein the content of the molybdenum and/or tungsten containing compound in the gel is 0.05 to 30 wt%, preferably 0.1 to 1.0 wt%.
9. The pharmaceutical composition according to item 7, wherein the matrix of the gel is one or more selected from carbomer, gelatin, xanthan gum, locust bean gum, guar gum, chitosan, sodium alginate, cellulose derivatives, glycerol, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP).
10. The pharmaceutical composition of item 6, wherein the molybdenum and/or tungsten containing compound is a tungsten molybdate.
11. The pharmaceutical composition according to item 10, wherein the tungsten molybdate is present in the pharmaceutical composition in the form of solid particles having a particle size of 10nm to 50 μm.
12. The pharmaceutical composition according to item 6, wherein the pharmaceutical composition or the functional dressing is in the form of an ointment, a solution, a powder, a liniment, a drop, a cream, a suppository, a paste, a spray, a film coating agent, a lotion, a water aqua, an effervescent tablet, a tape-shaped agent or a patch.
13. The pharmaceutical composition according to item 6, wherein the pharmaceutical composition is for use against Human Papillomavirus (HPV) or herpes virus (HSV).
14. The pharmaceutical composition according to item 13, wherein the anti-HPV is selected from the group consisting of anti-HPV high-risk type HPV or anti-HPV low-risk type HPV, wherein the anti-HPV high-risk type HPV is selected from the group consisting of HPV-1, HPV-2, HPV-3, HPV-4, HPV-7, HPV-10, HPV-12, HPV-15, HPV-16, HPV-18, HPV-30, HPV-31, HPV-33, HPV-35, HPV-39, HPV-53 and HPV-61, preferably is HPV-16, HPV18 or HPV31, and the anti-HPV low-risk type is selected from the group consisting of HPV-6, HPV-11, HPV-40, HPV-42, HPV-43, HPV-44, HPV-54, HPV-61, HPV-7, HPV-12, HPV-16, HPV-11, HPV-18, HPV-30, HPV-31, HPV-3, HPV-42, HPV-43, HPV-44, HPV-54, HPV-61, or HPV-61, One or more of HPV-70, HPV-72, HPV-81 and CP 6108, preferably HPV-6 or HPV 11.
15. The pharmaceutical composition according to item 13, wherein the herpes virus HSV is selected from one or more of herpes simplex virus type 1 HSV-1, herpes simplex virus type 2 HSV-2, varicella-zoster virus VZV, epstein barr virus EBV, human cytomegalovirus HCMV, human herpesvirus type 6 HHV-6, human herpesvirus type 7 HHV-7, and kaposi's sarcoma-associated virus KSHV, preferably herpes simplex virus HSV or varicella-zoster virus VZV.
The compounds containing molybdenum and/or tungsten of the invention can quickly kill and durably inhibit pathogenic microorganisms (bacteria, fungi and viruses) and multi-drug-resistant bacteria, has quick response, high efficiency and strong virus killing activity for resisting viruses, particularly Human Papilloma Virus (HPV) and herpes virus (HSV), and can not be absorbed by human body and generate toxic or side effect. The product is used for resisting Human Papilloma Virus (HPV) and herpes virus (HSV), and can also be used for preparing medicines, medical devices, disinfectants and other auxiliary care products for treating various human skin or skin mucosa diseases caused by pathogenic microorganisms.
Detailed Description
The present invention is further illustrated by the following examples, which are intended to be purely exemplary of the invention and are not intended to be limiting.
Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Although methods and materials similar or equivalent to those described herein can be used in experimental or practical applications, the materials and methods are described below. In case of conflict, the present specification, including definitions, will control, and the materials, methods, and examples are illustrative only and not intended to be limiting. The present invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
The present invention provides the use of molybdenum and/or tungsten containing compounds in the treatment of human papillomavirus HPV or herpes virus HSV.
Human papillomavirus HPV is a papillomavirus A belonging to the family papovaviridae, a papillomavirus A genus, a spherical DNA virus, which causes the proliferation of the squamous epithelium of the human skin mucosa. More than 130 types have been isolated, with different types leading to different clinical manifestations. Different types cause different clinical manifestations, and can be classified into (1) skin low-risk type: including HPV-1, 2, 3, 4, 7, 10, 12, 15, etc., associated with common warts, flat warts, plantar warts, etc.; (2) skin high risk type: including HPV-5, 8, 14, 17, 20, 36, 38, are associated with epidermodysplasia verruciformis, and other malignancies also associated with possible HPV infections include: vulvar, penile, anal, prostate, bladder cancer; (3) mucosal low risk types such as HPV-6, 11, 13, 32, 34, 40, 42, 43, 44, 54, etc. and infected genital, anal, oropharyngeal, and esophageal mucosa; (4) mucosa high-risk HPV-16, 18, 30, 31, 33, 35, 53 and 39 and cervical cancer, rectal cancer, oral cancer, tonsil cancer and the like. The present invention provides the use of molybdenum and/or tungsten containing compounds against human papillomavirus HPV.
Herpes viruses HSV (herpes viruses) are a type of enveloped virus whose genome is double-stranded DNA. There are 8 types of herpes viruses currently found to infect humans, including: herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), Varicella Zoster Virus (VZV), EB virus (Epstein-Barr virus, EBV), Human Cytomegalovirus (HCMV), human herpes virus type 6 (HHV-6), human herpes virus type 7 (HHV-7) and Kaposi's sarcoma-associated virus (KSHV). Patients and healthy carriers are sources of infection, primarily through direct intimate and sexual contact. HSV invades the body through various ways such as oral cavity, respiratory tract, genital tract mucosa and damaged skin. Human infection is very common, the infection rate reaches 80-90%, the common clinical manifestation is herpes accumulated on local mucosa or skin, and occasionally serious systemic diseases can also occur and viscera can be affected. The invention provides the use of molybdenum and/or tungsten containing compounds against herpes virus HSV.
Wherein "molybdenum and/or tungsten containing compound" as used herein refers to a molybdenum containing compound, a tungsten containing compound, or a molybdenum and tungsten containing compound.
In a preferred embodiment, the molybdenum and/or tungsten containing compound is selected from one or more of oxides, tungstates, and polyoxometallates of molybdenum and/or tungsten. Wherein, the oxide of molybdenum and/or tungsten can be tungsten oxide and molybdenum oxide. The molybdenum and/or tungstate may be molybdate, tungstate. The polyoxometallate comprising molybdenum and tungsten may be a tungsten polyoxometallate.
Polyoxometalates (POMs) are a class of polyoxometalate compounds formed by the attachment of early transition metal ions through oxygen. Polyoxometalates range primarily from higher valence early transition metals (primarily V, Nb, Ta, Mo, W) with the ability to form metal-oxygen cluster anions. After the 20 th century and the 70 th era, with the improvement of scientific level, especially with the leap development of electronic computer technology, the detection sensitivity and speed of a physical testing instrument processed by computer data are greatly improved, the amount of information provided is greatly increased, and the development of polyacid chemistry is greatly promoted. As a multinuclear complex containing an oxygen bridge, various related researches are increasingly emphasized by people. The interactions between metal ions through electron transfer in these systems and their coordination and influence with the bridging groups, end-group ligands, make them exhibit many different physical functions, chemical properties and biological activities from those of mononuclear complexes. The synthesis of polyacid compounds enters the stage of cutting and assembling rapid development, a large number of polyacid compounds with novel structures are synthesized, the high polymerization degree, chain type, micropore, layered polyacid complex and nano structure, sandwich type, inorganic double helix polyacid complex are layered, the synthesis and development of functional polyacid compounds are still the power for the great development of polyacid chemistry, and the functionalization of polyoxometallate almost relates to all fields, such as catalysis, photoelectromagnetic functional materials and medicinal chemistry, in particular to the research of antivirus, antitumor and AIDS resistance.
Among them, tungsten molybdate has an antiviral effect as a member of polyoxometallate, which effectively kills bacteria, viruses and molds by virtue of quadruple antimicrobial activity generated in situ. The 1 st activity, forming acidified water molecules which can be permanently reserved on the surface of an object on the surface of the object, thereby forming a weak acid environment with a lower pH value, effectively inhibiting the cell growth process, destroying a microbial phospholipid membrane and realizing protein denaturation; as the potential of the viral membrane decreases, no more effective energy is generated, causing membrane damage. The 2 nd type of activity can react with water on the surface of an object and in the air to generate active substances such as active oxygen (peroxide anions) and hydroxyl radicals to form free radicals. The active hydroxyl group is a strong oxidizing agent, and has decomposing and inactivating effects on nucleic acids, proteins and metabolic enzymes of bacteria, resulting in the death of microorganisms. 3 rd Activity, using electron paramagnetic resonance spectrometer EPR to detect Mo on the surface of tungsten molybdate object5+The metal cations exceed the living range of various pathogenic microorganisms due to the low pH value, so that the living environment of the microorganisms is seriously damaged, the cell membrane permeability of the microorganisms is enhanced, and cell metabolic enzymes and the cell nucleus structure are damaged by the rapid penetration of the hydrogen ions and the metal cations, thereby killing the microorganisms. Activity No. 4: the tungstomolyoxometalate antiviral agent exhibits high antiviral activity. The high Zeta potential of the tungsten molybdate is an important factor for generating electrostatic action, and the energy of electrostatic combination is strong, so that the tungsten molybdate is stable. Therefore, the excellent antiviral activity can be generated. Can kill various pathogenic microorganisms including MRSA and bacterial spores, and has the characteristics of high efficiency, rapidness, broad spectrum, durability, environmental protection and the like.
Tungsten molybdate as antiviral substance and water moleculeMolybdic acid and/or tungstic acid, and other by-products generated by the reaction, reduce the pH value of the skin contacted with the antiviral substance; meanwhile, antiviral substances can generate free radicals (such as superoxide radical and hydroxyl radical) and positive Zeta potential. The above mechanisms can produce synergistic effect, thereby achieving the effect of broad-spectrum and high-efficiency anti-pathogenic microorganisms. For example, molybdenum oxide reacts with water to form molybdic acid (H)2MoO4) Which in turn is reacted with H2Reaction of O to form H3O+And MoO4 -Or MoO4 2-. Tungsten oxide is also H2Formation of tungstic acid (H) from O2WO4) Of which is in contact with H2Reaction of O to form H3O+And WO4 -Or WO4 2-
In a specific embodiment, the anti-human papillomavirus HPV is selected from anti-human papillomavirus high risk type HPV or anti-human papillomavirus low risk type HPV, wherein the anti-human papillomavirus high risk type HPV is selected from one or more of HPV-1, HPV-2, HPV-3, HPV-4, HPV-7, HPV-10, HPV-12, HPV-15, HPV-16, HPV-18, HPV-30, HPV-31, HPV-33, HPV-35, HPV-39, HPV-53 and HPV-61, preferably HPV-16, HPV18 or HPV31, and the anti-human papillomavirus low risk type HPV is selected from HPV-6, HPV-11, HPV-40, HPV-42, HPV-43, HPV-44, HPV-54, HPV-61, HPV-70, HPV-42, HPV-6, HPV-11, HPV-40, HPV-42, HPV-43, HPV-44, HPV-54, HPV-61, HPV-70, One or more of HPV-72, HPV-81 and CP 6108, preferably HPV-6 or HPV 11.
In a specific embodiment, the herpes virus HSV is selected from one or more of herpes simplex virus HSV-1, herpes simplex virus HSV-2, varicella-zoster virus VZV, EBV, human cytomegalovirus HCMV, human herpes virus HHV-6, human herpes virus HHV-7 and Kaposi sarcoma-associated virus KSHV, preferably herpes simplex virus HSV or varicella-zoster virus VZV.
The invention also provides a pharmaceutical composition which comprises a molybdenum and/or tungsten containing compound, wherein the molybdenum and/or tungsten containing compound is selected from one or more of molybdenum and/or tungsten oxide, molybdenum and/or tungstate and molybdenum and/or tungsten polyoxometallate.
The molybdenum and/or tungsten containing compounds may be used in combination with other oxides or salts. Other oxides or salts, including, but not limited to, alumina, silica, zirconia, tungsten oxide, titania, zinc molybdate, and the like. Taking molybdenum oxide as an example, the combination form of the molybdenum oxide and other oxides can be as follows: molybdenum oxide/tungsten oxide mixtures, molybdenum oxide/zinc molybdate mixtures, and the like. The combination may be mixing, dispersing, stirring, etc.
The form of the pharmaceutical composition of the present invention is not limited, and in a specific embodiment, the pharmaceutical composition is a gel. Under certain conditions, colloidal particles or macromolecules in a sol or solution are connected with each other to form a spatial network structure, and the structural voids are filled with a liquid (in a xerogel, a gas can be used, and the xerogel is also called an aerogel) serving as a dispersion medium, so that a special dispersion system is called a gel.
In a particular embodiment, the content of the molybdenum and/or tungsten containing compound in the gel is 0.05 to 30 wt%, for example 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, preferably 0.1 to 1.0 wt%.
The matrix of the gel can be one or more selected from carbomer, gelatin, guar gum, xanthan gum, locust bean gum, chitosan, sodium alginate, cellulose derivatives, glycerol, polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP).
In a particular embodiment, the molybdenum and/or tungsten containing compound in the pharmaceutical composition is a tungsten molybdate.
In a particular embodiment, the tungsten molybdate is present in the pharmaceutical composition in the form of solid particles, said particles having a particle size of 10nm to 50 μm. The particle size of the tungsten molybdate particles can be measured by using a sieving method, a laser diffraction method or a microscope image method, for example, the tungsten molybdate particles can exist in the form of solid particles, especially micron-sized solid particles, in the pharmaceutical composition in the form of 10nm, 50nm, 100nm, 1 μm, 5 μm, 10 μm, 20 μm and 50 μm, and the tungsten molybdate is not absorbed by human tissues and therefore does not generate toxicity. In a specific embodiment, the above combination of gel forms is prepared according to the following method: adding a compound containing molybdenum and/or tungsten into a gel matrix, uniformly stirring, adding purified water and a neutralizing agent, uniformly mixing to form gel, and standing. Wherein the pH value of the gel is 1-7, and can be 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 and 7. Preferably, the pH value ranges from 3 to 6.5; more preferably, the pH ranges from 4.5 to 6; most preferably, the pH range is 4.5-5.5.
The weak acid microenvironment on the surface of the gel can quickly kill and durably inhibit pathogenic microorganisms (bacteria, viruses and fungi) and multiple drug-resistant bacteria under the synergistic action of the multiple antiviral mechanisms, has quick response and lasting antiviral action time, and the antiviral agent is not absorbed by human body and does not generate toxic or side effect.
The pharmaceutical composition or functional dressing of the present invention may be administered in various dosage forms, for example, as an ointment, solution, powder, liniment, drop, cream, suppository, paste, spray, film coating agent, lotion, aqueous agent, effervescent tablet, tape, or patch.
The pharmaceutical composition also comprises pharmaceutically acceptable auxiliary materials. Such adjuvants are known in the art and may be preservatives, humectants, stabilizers, neutralizing agents and the like.
The pharmaceutical composition is used for resisting Human Papilloma Virus (HPV) or herpes virus (HSV). Wherein the selection against human papillomavirus HPV and herpes virus HSV is as described above for the use of molybdenum and/or tungsten containing compounds.
The compound and the pharmaceutical composition containing molybdenum and/or tungsten of the invention have the advantages of antibiosis and antivirus by means of multiple mechanisms, no toxic or side effect, effective resistance to common pathogenic microorganisms and super bacteria, and the antibacterial rate to escherichia coli and staphylococcus aureus is more than 99.2 percent, and the antibacterial rate to candida albicans is more than 95.5 percent; the antiviral agent is safe and harmless, does not change the cell genetic characteristics, does not cause cancer, does not generate drug resistance, and is efficient and durable in antiviral; can be used for resisting Human Papilloma Virus (HPV) or herpes virus (HSV), has antiviral activity rate of more than 99.9%, and can also be used for preparing medicines, medical devices, disinfectants and other auxiliary care products for treating various human skin or skin mucosa diseases caused by pathogenic microorganisms.
Examples
Example 1
Preparing a molybdenum oxide aqueous solution with the mass concentration of 0.45%, adding 0.5g of tungsten molybdate into 95.5ml of the molybdenum oxide aqueous solution for uniform dispersion, adding 3.0g of carbomer 940 and 1.0g of glycerol as gel substrates, mixing, uniformly stirring, and standing for 2 hours to obtain the antiviral gel. Wherein the particle size of the tungsten molybdate in the gel is 2 μm, and the pH value of the antiviral gel is 4.5.
The prepared antiviral gel is subjected to an antibacterial performance test by committing Guangzhou city microbiology research institute limited company according to national sanitation industry standard WS/T650-2019 antibacterial and bacteriostatic effect evaluation method, and the result shows that the antibacterial rate of the antiviral gel to escherichia coli and staphylococcus aureus is more than 99.9%, and the antibacterial rate to candida albicans is 99.1%. Has strong antibacterial effect.
The prepared antiviral gel is placed in a thermostat at 54-57 ℃ for 14 days according to a test method specified in appendix C of national standard GB 15979-1995 hygienic Standard for Disposable hygienic articles, and then sterilization performance is tested. The results show that the antibacterial stability is not less than 1 year.
The prepared antiviral gel was tested against human papillomavirus HPV16 (host name: Vero-E6 cell) by Shanghai micro-spectral chemical engineering services, Inc., Committed in technical Specification for Disinfection (2002) for antiviral activity. The results show that the antiviral gel has an antiviral activity value of 3.01 in 2 hours and an antiviral activity rate of more than 99.9%.
Example 2
Adding 0.5g of tungsten molybdate into gel matrix 1.0g of carbomer 940, stirring uniformly, adding 97.3ml of purified water, adding 0.2g of neutralizing agent triethanolamine, stirring uniformly for forming, adding 1.0g of glycerol, stirring uniformly, and standing for 2 hours to obtain the antiviral gel. Wherein the particle size of the tungsten-molybdenum-oxygen acid in the gel is 2 μm, and the pH value of the antiviral gel is 5.5.
The prepared antiviral gel is subjected to an antibacterial performance experiment according to the national sanitation industry standard WS/T650 plus 2019 'antibacterial and bacteriostatic effect evaluation method', and the result shows that the antibacterial rate of the antiviral gel to escherichia coli and staphylococcus aureus is greater than 99.20%, and the antibacterial rate to candida albicans is greater than 95.5%.
The prepared antiviral gel is put in an incubator at 54-57 ℃ for 14 days according to a test method specified in appendix C of national standard GB 15979-1995 hygienic Standard for Disposable sanitary articles or other test methods specified in international standards, national standards or industry standards with the same efficacy, and a sterilization performance test result shows that the antibacterial stability is not less than 1 year.
The prepared antiviral gel was tested by Shanghai micro-spectral chemical engineering service Co., Ltd according to Sterilization Specification (2002) to detect the anti-herpes virus activity of the antiviral gel against herpes simplex virus HSV-2 (host name: Vero-E6 cell). The results showed that the antiviral gel had an antiviral activity value of 4.03 for 2 hours and an antiviral activity rate of more than 99.99%.
Example 3
Adding 0.8g of tungsten molybdate into 4.0g of guar gum as gel matrix, stirring uniformly, adding 94.2ml of purified water and 1.0g of glycerol, stirring uniformly and forming to obtain the antiviral gel. Wherein the particle size of the tungsten-molybdenum-oxygen acid in the gel is 2 μm, and the pH value of the antiviral gel is 6.0.
The prepared antiviral gel is subjected to an antibacterial performance experiment according to the national sanitation industry standard WS/T650 plus 2019 antibacterial and bacteriostatic effect evaluation method, and the result shows that the antibacterial rate of the antiviral gel to escherichia coli and staphylococcus aureus is greater than 99.50%, and the antibacterial rate to candida albicans is greater than 95.85%.
The prepared antiviral gel is put in an incubator at 54-57 ℃ for 14 days according to a test method specified in appendix C of national standard GB 15979-1995 hygienic Standard for Disposable sanitary articles or other test methods specified in international standards, national standards or industry standards with the same efficacy, and a sterilization performance test result shows that the antibacterial stability is not less than 1 year.
The prepared antiviral gel was tested according to technical Specification for Disinfection (2002), and the antiviral activity of the antiviral gel was examined against human papillomavirus HPV16 (host name: Vero-E6 cell). The results show that the antiviral gel has an antiviral activity value of 3.05 in 2 hours and an antiviral activity rate of more than 99.9%.
Example 4
0.6g of molybdenum oxide powder and 0.4g of zinc molybdate powder are dissolved in 73ml of purified water and stirred uniformly. And adding 5.0g of chitosan and 20.0g of gelatin into the gel matrix, mixing, adding 1.0g of glycerol, standing, uniformly stirring and forming to obtain the antiviral gel. The particle size of the molybdenum oxide powder and the zinc molybdate powder was 1 μm. The pH of the antiviral gel was 3.5.
Antibacterial performance experiments are carried out on the prepared antiviral gel according to the national sanitary industry standard WS/T650 plus 2019 'evaluation method for antibacterial and bacteriostatic effects', and the results show that the antibacterial rates of the antiviral gel on escherichia coli and staphylococcus aureus are both more than 99.35%, and the antibacterial rate on candida albicans is more than 96.6%
The prepared antiviral gel is put in an incubator at 54-57 ℃ for 14 days according to a test method specified in appendix C of national standard GB 15979-1995 hygienic Standard for Disposable sanitary articles or other test methods specified in international standards, national standards or industry standards with the same efficacy, and a sterilization performance test result shows that the antibacterial stability is not less than 1 year.
The prepared antiviral gel was tested according to technical Specification for Disinfection (2002), and the antiviral activity of the antiviral gel was examined against human papillomavirus HPV16 (host name: Vero-E6 cell). The results show that the antiviral gel has an antiviral activity value of 3.01 in 2 hours and an antiviral activity rate of more than 99.9%.
Example 5
0.6g of tungsten-molybdenum oxysalt is put into 95.37ml of purified water for even dispersion, 0.03g of polyhexamethylene hydrochloric acid (PHMB) is added, 4.0g of sodium alginate is added into the gel matrix, and the mixture is stirred and formed evenly to obtain the antiviral gel. Wherein the particle size of the tungsten molybdate in the antiviral gel is 2 μm, and the pH value of the antiviral gel is 5.5.
The prepared antiviral gel is subjected to an antibacterial performance experiment according to the national sanitation industry standard WS/T650 plus 2019 antibacterial and bacteriostatic effect evaluation method, and the result shows that the antibacterial rate of the antiviral gel to escherichia coli and staphylococcus aureus is more than 99.75%, and the antibacterial rate to candida albicans is more than 96.5%.
The prepared antiviral gel is put in an incubator at 54-57 ℃ for 14 days according to a test method specified in appendix C of national standard GB 15979-1995 hygienic Standard for Disposable sanitary articles or other test methods specified in international standards, national standards or industry standards with the same efficacy, and a sterilization performance test result shows that the antibacterial stability is not less than 1 year.
Like most virus infections, HPV or HSV infection has high morbidity and is difficult to cure radically, and no specific medicine capable of directly killing HPV or HSV virus exists globally. In the market, various antiviral drugs indirectly inhibit viruses through an immune regulation or hormone (interferon) mode, and the effect of resisting HPV is not ideal or has no effect. For low-risk HPV infection, a plurality of medicines have certain effects. Such as imiquimod, is an immunomodulator that acts by modulating the cellular immune function locally at the lesion; podophyllotoxin can inhibit virus and prevent cell proliferation caused by virus. However, no effective antiviral drug is available on the market for high-risk HPV infection. Therefore, no specific drug is recommended for direct killing of HPV virus in current clinical guidelines for the treatment of cervical lesions. The effective component of the gel product for resisting high-risk HPV virus in the market is beta-glucan interferon or animal ovoglobulin. The treatment of HPV by using interferon has long period, side effect and undesirable effect; the use of the animal ovovitellin is not only very costly, but also unsatisfactory in efficacy.
The compound containing molybdenum and/or tungsten and the pharmaceutical composition have no toxic or side effect, can effectively resist common pathogenic microorganisms and super bacteria, and have the antibacterial rate of more than 99.2 percent on escherichia coli and staphylococcus aureus and the antibacterial rate of more than 95.5 percent on candida albicans; the antiviral agent is safe and harmless, does not change the cell genetic characteristics, does not cause cancer, does not generate drug resistance, and is efficient and durable in antiviral; can be used for resisting Human Papilloma Virus (HPV) or herpes virus (HSV), and has antiviral activity rate of more than 99.9%.

Claims (10)

1. Use of molybdenum-and/or tungsten-containing compounds against human papillomavirus HPV or herpes virus HSV.
2. Use according to claim 1, wherein the molybdenum and/or tungsten containing compound is selected from one or more of molybdenum and/or tungsten oxides, molybdenum and/or tungstates, and molybdenum and/or tungsten containing polyoxometallates.
3. Use according to claim 2, characterized in that the polyoxometallate containing molybdenum and/or tungsten is tungsten molybdate.
4. The use according to claim 1, wherein the anti-HPV is selected from the group consisting of anti-HPV high-risk type selected from HPV-1, HPV-2, HPV-3, HPV-4, HPV-7, HPV-10, HPV-12, HPV-15, HPV-16, HPV-18, HPV-30, HPV-31, HPV-33, HPV-35, HPV-39, HPV-53 and HPV-61, preferably HPV-16, HPV18 and HPV31, or anti-HPV low-risk type selected from HPV-6, HPV-11, HPV-40, HPV-42, HPV-43, HPV-44, HPV-54, HPV-61, One or more of HPV-70, HPV-72, HPV-81 and CP 6108, preferably HPV-6 or HPV11, or
The herpes virus HSV is selected from one or more than two of herpes simplex virus 1 type HSV-1, herpes simplex virus 2 type HSV-2, varicella-zoster virus VZV, EB virus EBV, human cytomegalovirus HCMV, human herpes virus 6 type HHV-6, human herpes virus 7 type HHV-7 and Kaposi sarcoma related virus KSHV, and is preferably herpes simplex virus HSV or varicella-zoster virus VZV.
5. A pharmaceutical composition comprising a molybdenum and/or tungsten containing compound, wherein the molybdenum and/or tungsten containing compound is selected from one or more of molybdenum and/or tungsten oxides, molybdenum and/or tungstates, and molybdenum and/or tungsten containing polyoxometallates, preferably the molybdenum and/or tungsten containing compound is a tungsten molybdenate.
6. Pharmaceutical composition according to claim 5, wherein the pharmaceutical composition is a gel, preferably wherein the content of the molybdenum and/or tungsten containing compound in the gel is 0.05-30 wt.%, preferably 0.1-1.0 wt.%.
7. The pharmaceutical composition of claim 6, wherein the matrix of the gel is one or more selected from carbomer, gelatin, xanthan gum, locust bean gum, guar gum, chitosan, sodium alginate, cellulose derivatives, glycerol, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP).
8. The pharmaceutical composition of claim 5, wherein the tungsten molybdate is present in the pharmaceutical composition as solid particles having a particle size of 10nm to 50 μm.
9. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition or functional dressing is in the form of an ointment, a solution, a powder, a liniment, drops, a cream, a suppository, a paste, a spray, a film coating agent, a lotion, an aqueous agent, an effervescent tablet, a tape-shaped agent or a patch.
10. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is for use against Human Papillomavirus (HPV) or herpes virus (HSV),
preferably, the anti-human papilloma virus HPV is selected from anti-human papilloma virus high-risk type HPV or anti-human papilloma virus low-risk type HPV, wherein the anti-human papilloma virus high-risk type HPV is selected from one or more of HPV-1, HPV-2, HPV-3, HPV-4, HPV-7, HPV-10, HPV-12, HPV-15, HPV-16, HPV-18, HPV-30, HPV-31, HPV-33, HPV-35, HPV-39, HPV-53 and HPV-61, preferably HPV-16, HPV18 or HPV31, and the anti-human papilloma virus low-risk type HPV is selected from HPV-6, HPV-11, HPV-40, HPV-42, HPV-43, HPV-44, HPV-54, HPV-61, HPV-70, HPV-72, HPV-81, One or more than two of CP 6108, preferably HPV-6 or HPV 11; or
Preferably, the herpes virus HSV is selected from one or more than two of herpes simplex virus HSV-1, herpes simplex virus HSV-2, varicella-zoster virus VZV, EBV, human cytomegalovirus HCMV, human herpes virus HHV-6, human herpes virus HHV-7 and Kaposi sarcoma related virus KSHV, and preferably is herpes simplex virus HSV or varicella-zoster virus VZV.
CN202110961745.4A 2021-08-20 2021-08-20 Use of molybdenum and/or tungsten containing compounds against Human Papilloma Virus (HPV) or herpes virus (HSV) and pharmaceutical compositions thereof Pending CN113577099A (en)

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