CN110201143A - The external drug for treating herpesvirus infection - Google Patents
The external drug for treating herpesvirus infection Download PDFInfo
- Publication number
- CN110201143A CN110201143A CN201910534860.6A CN201910534860A CN110201143A CN 110201143 A CN110201143 A CN 110201143A CN 201910534860 A CN201910534860 A CN 201910534860A CN 110201143 A CN110201143 A CN 110201143A
- Authority
- CN
- China
- Prior art keywords
- infection
- drug
- rgds
- herpesvirus infection
- hsv
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses the external drugs for the treatment of herpesvirus infection, and containing fibronectin inhibitor, active constituent is tetrapeptide RGDS.Infection caused by herpes simplex virus and varicella virus etc. can be treated, the pain of patient is mitigated, shortens healing stage.Tetrapeptide RGDS is without side-effects to epidermis, and humans and animals can be used.Drug of the present invention has reliable therapeutic effect to guinea pig skin bleb and mouse propagation device bleb, can significantly reduce the lesion degree of HSV-1 infection guinea pig skin bleb and HSV-2 infecting mouse genital herpes, can inhibit disease, shorten cure time, mitigate patient suffering.The present invention contains a variety of dosage forms such as ointment and solution, all has preferable curative effect to the infection of herpesviral.
Description
Technical field
The present invention relates to biomedicine technical field, in particular to a kind of external drugs for treating herpesvirus infection.
Background technique
Herpesviral is a kind of tunicary DNA virus of tool, is widely present in nature, causes the sense of people and many animals
Dye, the tissue of main infection host's ectodermal origin, including skin, mucous membrane and nerve fiber.Herpesviral generally passes through skin
Contact is propagated.Herpesvirus infection has serious and lasting threat, the especially most common herpe simplex for public health
The mouth face, genital herpes of viral (including HSV-1 and HSV-2 type) initiation, in addition there are varicellazoster virus (VZV)
Infect the shingles zoster etc. caused, and a large amount of animal herpes virus infection.
Herpes simplex virus is latent in holding in sensory neurone in the remaining years of patient after primary infection, and can
Be reactivated under numerous conditions, so that virus through nerve is transported to skin, then again result in damage, cause herpes zoster pain,
The recurrence of the symptoms such as tingling.In the case where recurrent infection, clinical symptoms will continue 1-2 weeks.Treatment herpesvirus infection at present
Drug mainly have: acyclovir (ACV), interferon (IFN), virazole (ribavirin) etc., there are also monoclonal antibodies to control
The methods of treat.Outer partial medication has zinc ointment or mud cream, Asian puccoon Radix Sangusorbae ointment, 0.5% neomycin ointment, idoxuridine
(IDU) ointment etc., main function are dry, convergence, protection affected part, secondary infection are prevented, not directly against virus, without disease-resistant
Cytotoxic activity.
Fibronectin (fibronectin, FN) is the widely distributed more structures for being positioned at extracellular matrix
The macromolecule glycoprotein in domain.Its molecular weight about 230KD-250KD, in addition to the content in extracellular matrix, in serum
Also very abundant.There is a RGD motif in the structure of FN, FN can be combined by this motif with the integrin of cell surface, from
And be attached on cell surface, play important biological function.And artificial synthesized tetrapeptide RGDS (Arg-Gly-Asp-Ser) can
To make FN removing cell surface become extracellular free state with FN competitive binding to cell surface, so RGDS can be used as FN
Inhibitor block FN be integrated to cell surface.Integrating fibroin and can identify the receptor egg with RGD motif on cell membrane
It is white, and RGDS polypeptide can inhibit the function of integrin receptor with emulative same integrin receptor in conjunction with integrin.It is this kind of
Integrin receptor albumen often takes part in the invasion stage of virus, so tetrapeptide RGDS can inhibit the continuation of virus infection deep
Enter, prevents virus diffusion, invade healthy cell, mitigate symptom, reduce the pain of patient, and uneasy to recur.
Summary of the invention
In view of the deficiencies of the prior art, the object of the present invention is to provide a kind of external drugs for treating herpesvirus infection.
To achieve the above object, the external drug for the treatment of herpesvirus infection provided by the invention, it is characterised in that: contain
Fibronectin inhibitor, active constituent are tetrapeptide RGDS.
As scheme, the external drug dosage forms are any in ointment, solution, gelling agent or cream.
Further, the external drug is applied to treatment herpesvirus infection；The herpesvirus infection includes skin
Or the relapse herpesvirus infection of mucous membrane.
Further, institute's external drug is topical drug.
Advantages of the present invention and have the beneficial effect that: drug of the invention be made medicament can be used for human skin or
Various pharmaceutical carriers, the adjuvant of mucous membrane, such as penetration enhancers.Preferred pharmaceutical composition is part, mucous membrane or cross-film approach
The drug of administration such as can be made into creme, lotion, gelling agent, cream (soft) cream, lotion, gelling agent, solution, plaster, patch, stick
Agent or pencil.Pharmaceutical composition can also be made on plaster or patient skin applied to herpes infection to be treated, or be packed into
It is applied to skin or mucous membrane in pen or stick.It is confirmed by guinea pig skin infection experiment and mouse vagina infection experiment, medicine of the present invention
Object has reliable therapeutic effect to guinea pig skin bleb and mouse propagation device bleb, can significantly reduce HSV-1 infection cavy
The lesion degree of skin bleb and HSV-2 infecting mouse genital herpes can inhibit disease, shorten cure time, mitigate
Patient suffering.
Detailed description of the invention
Fig. 1 tetrapeptide RGDS of the present invention can inhibit the duplication experimental result picture of HSV-1；
In figure: control group RGES and experimental group inhibitor RGDS is in I herpes simplex virus type (HSV-1) infection human lung cancer
The influence (rna level and DNA level) of chrotoplast (A549)；
Fig. 2 tetrapeptide RGDS of the present invention can inhibit the duplication experimental result picture of HSV-2；
In figure: control group RGES and experimental group inhibitor RGDS infects human lung cancer to II herpes simplex virus type (HSV-2)
The influence (rna level and DNA level) of epithelial cell (A549)；
Fig. 3 tetrapeptide RGDS of the present invention can inhibit the duplication experimental result picture of VZV.
In figure: control group RGES and experimental group inhibitor RGDS is in varicella virus (VZV) infection human lung cancer
The influence (Vero) (virus titer detection) of chrotoplast.
Specific embodiment
Below in conjunction with the drawings and specific embodiments, invention is further explained.
1 tetrapeptide RGDS solution of embodiment
Tetrapeptide RGDS 500ug, which is dissolved in 100ml sterile saline, to be uniformly mixed, and active constituent tetrapeptide RGDS concentration is
5ug/mL。
2 tetrapeptide RGDS ointment of embodiment
Active constituent: tetrapeptide RGDS 500ug
Other ingredients: PEG400 10g, PEG600060g, water add to 100g.
Preparation method: tetrapeptide RGDS is dissolved in PEG400 and obtains PEG400 drug solution, is poured slowly into heating melting
PEG6000 in, be uniformly mixed, add water to 1000g, obtain tetrapeptide RGDS ointment.
3 tetrapeptide RGDS gel of embodiment
Active constituent: tetrapeptide RDGS 500ug
Other ingredients: Acritamer 940 1g, sodium hydroxide, appropriate sterile distilled water add to 100g.
Preparation method: quickly Acritamer 940 1g dispersion is swollen in appropriate sterile distilled water under stirring, uses sodium hydroxide
PH to 7.0 is adjusted, gel-type vehicle is obtained.Tetrapeptide RDGS is dissolved in a small amount of sterile distilled water, then the solution is added to aforementioned
It in gel-type vehicle, is uniformly mixed, obtains tetrapeptide RGDS gel.
4 tetrapeptide RGDS emulsifiable paste of embodiment
Active constituent: tetrapeptide RGDS 500ug
Other ingredients: liquid paraffin 2g, glycerin monostearate 1.5g, paregal O -203.5g, P-hydroxybenzoic acid first
Ester 0.1g, propylparaben 0.01g, glycerol 3g, water add to 100g.
Preparation method: by tetrapeptide RGDS, liquid paraffin, glycerin monostearate, paregal O -20, P-hydroxybenzoic acid first
Ester, the dissolution of propylparaben heating stirring, keep the temperature to 80 DEG C or so；Glycerol and water are uniformly mixed and are heated to 80 DEG C of left sides
It is right；Two kinds of solution mix quick stirring and emulsifying 10 minutes, are down to room temperature up to tetrapeptide RGDS emulsifiable paste.
The test of 5 Anti-herpesvirus infection of embodiment -- tetrapeptide RGDS can inhibit a variety of herpesviral (HSV-1, HSV-2
And VZV) duplication
Experimental material: human lung cancer epithelial cell (A549), Vero cell
Experimental drug: tetrapeptide RGDS solution (embodiment 1)
Experimental method
1, virus infected cell: recovery human lung cancer epithelial cell (A549) is expanded to needed for experiment, is paved with 80% to cell
When again respectively by two kinds of virus inoculations of HSV-1 and HSV-2.Before virus infected cell, by the complete medium containing fetal calf serum
Change serum free medium into, the dosage of virus infection is 1MOI, after infecting 12-24h, collects cell and culture medium supernatant carries out down
The experiment of one step.
2, the expression of the gene mRNA of reverse transcription fluorescence quantitative PCR detection virales
The total serum IgE of cell and supernatant is extracted respectively, and reverse transcription obtains cDNA, using obtained cDNA as template fluorescent quantitation
PCR detection.
3, the titre of Plaque Technique Detected measurement virus
Vero cell is uniformly layered in 24 orifice plates, by cell culture supernatant according to 10-3、10-4、10-5、10-6Ratio
Dilution.The supernatant abandoned in Vero cell is inhaled, viral dilution is added in Vero cell, 200 microlitres of every hole, cell culture is placed
2h is adsorbed in case.It inhales and abandons virus liquid, cell is washed again one time with PBS.1.5% low melting-point agarose of heat preservation will be melted in advance
It is uniformly mixed with DMEM complete medium according to the ratio of 1:1, at 37 DEG C or so, every 300 μ L of hole adds the temperature of object to be mixed
Enter into tissue culture plate；20 minutes or so are placed at room temperature for, after agarose media solidification, is put into incubator and cultivates.About 3
After it, there is apparent pathological effect in cell, stops culture, and every hole is added 2 hours of violet staining of 200 μ L, then uses
Tap water rinses cell plates and agarose is removed；Calculate the plaque number in each hole.PFU/ml=(plaque number × extension rate)/
0.2ml。
Experimental result and discussion: tetrapeptide RGDS (5 μ g/ml) or control polypeptide RGES pretreatment cell 6 hours are used, then
Virus infection, detects Virus Infection after 12-24 hours, the cell of discovery RGDS processing compared with the cell that RGES is handled,
The levels of replication of virus is significantly inhibited, and the virus that we are tested includes I herpes simplex virus type, II type herpe simplex disease
Poison, varicella virus.This illustrates that RGDS polypeptide has the anti-herpesvirus effect of wide spectrum, it is presumed that its is antiviral
Effect may be with being modified with more significant raising.
6 guinea pig skin of embodiment infects the test of HSV-1 Primary treatment
1, test material
Animal: albino guinea-pig 40, weight 250-300g, half male and half female.
Virus: HSV-1 virus is purchased from Wuhan University's collection (CCTCC).
Trial drug: tetrapeptide RGDS solution (embodiment 1), tetrapeptide RGDS ointment (embodiment 2), tetrapeptide RGDS gel are (real
Apply example 3), tetrapeptide RGDS emulsifiable paste (embodiment 4)
Control drug: the sterile water without chemical substance tetrapeptide RGDS/sky ointment/sky gel/sky emulsifiable paste
2, test method
40 cavys are randomly divided into 8 groups every group 5, respectively solution group, sterile water group, ointment group, sky by gender weight
Emulsifiable paste group, emulsifiable paste group, empty emulsifiable paste group, gel group, empty gel group.
Guinea pig back depilation, hair removal section skin are divided into 5 pieces.After 75% alcohol disinfecting, pierced deeply with sterile 7 needle cutaneous acupuncture
Each depilation district center, after stopping needle 2 minutes, with 30 μ L virus stock solution useds drop in stabbing on skin, with sterile glass rod friction make its into
Enter and generates infection in cavy body.After 2 hours, it is evenly coated in cavy respectively using different drugs (or sterile water) by marshalling and carries on the back
5, portion hair removal section.Daily coating 3 times, totally 5 days.The symptom for observing each hair removal section daily, to bleb eruption number and skin shape
State is registered, and is grown after all bleb affected part incrustations and without new blister and is judged as recovery from illness, finally carries out synthesis again and comment
Sentence.
3, experimental result
1 guinea pig skin of table infects HSV-1 therapeutic test
Conclusion: after cavy is using the drug of the RGDS containing tetrapeptide, skin condition is greatly improved compared with control group, eruption number
Amount is also greatly reduced, and healing days significantly reduce, and preliminary experiment shows what tetrapeptide RGDS drug local topical infected HSV-1
Skin has therapeutic effect.
7 mouse vagina of embodiment infects HSV-2 therapeutic test
1, test material
Experimental animal: SPF grades female mice 100, weight 18-22g.
Test virus: HSV-2 virus is purchased from Wuhan University's collection.
Trial drug: tetrapeptide RGDS solution (embodiment 1), tetrapeptide RGDS ointment (embodiment 2), tetrapeptide RGDS gel are (real
Apply example 3), tetrapeptide RGDS emulsifiable paste (embodiment 4)
2, test method
45 female mices, are randomly divided into 9 groups, and every group 5, in addition to one group of negative control, remaining each group group technology
With embodiment 6,.
The gelfoam fritter for being adsorbed with sterile PBS solution 0.03ml is sent into control group mice vagina with ophthalmology tweezers,
The gelfoam fritter for being adsorbed with virus liquid 0.03ml is sent into mouse vagina with ophthalmology tweezers by remaining each group mouse.Except control group
Outside, remaining each group coating medicine-feeding after virus infection 2 hours, 3 times a day, successive administration 5 days.Daily observation mouse vagina disease
Become, recorded, is observed 2 weeks altogether.Mouse lesion degree remembers 4 grades, is normally " 1 "；Vulva is rubescent, swelling is " 2 "；Vulva is red and swollen
Even rotten to the corn with bleb is " 3 "；Death is " 4 ".After 2 week observation period, each group mouse invasion number and death toll are counted, is calculated
Morbidity and mortality.
3, test result
3.1 drugs infect mouse vagina the influence of HSV-2 disease incidence and the death rate
Treatment of the 2 tetrapeptide RGDS of table to mouse vagina infection HSV-2
| Group | Death toll (only) | It falls ill number (only) | Average lesion degree |
| Negative control | 0 | 0 | 1 |
| Solution | 0 | 5 | 2 |
| Sterile water | 1 | 5 | 3 |
| Ointment group | 0 | 5 | 2 |
| Empty ointment | 1 | 5 | 3 |
| Emulsifiable paste group | 0 | 4 | 2 |
| Empty emulsifiable paste | 0 | 5 | 3 |
| Gel group | 0 | 4 | 2 |
| Empty gel | 0 | 5 | 3 |
4, conclusion (of pressure testing)
Compared with each group negative control blank drug, pathological development speed of the tetrapeptide RGDS to the mouse of vagina infection HSV-2
Degree and degree have good inhibiting effect, and herpesvirus infection degree receives apparent inhibition, and lesion degree is significantly lower than
Respective control group, illustrating that homemade tetrapeptide RGDS external application has herpesvirus infection must curative effect.
Claims (5)
1. a kind of external drug for treating herpesvirus infection, it is characterised in that: contain fibronectin inhibitor, activity
Ingredient is tetrapeptide RGDS.
2. the external drug for the treatment of herpesvirus infection according to claim 1, it is characterised in that: the externally applied drug agent
Type is any in ointment, solution, gelling agent or cream.
3. the external drug for the treatment of herpesvirus infection according to claim 1 or claim 2, it is characterised in that: the external drug
Applied to treatment herpesvirus infection；The herpesvirus infection includes the relapse herpesvirus infection of skin or mucous membrane.
4. the external drug for the treatment of herpesvirus infection according to claim 1 or 2, it is characterised in that: institute's external drug
For topical drug.
5. the external drug for the treatment of herpesvirus infection according to claim 3, it is characterised in that: institute's external drug is office
Portion's drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910534860.6A CN110201143A (en) | 2019-06-20 | 2019-06-20 | The external drug for treating herpesvirus infection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910534860.6A CN110201143A (en) | 2019-06-20 | 2019-06-20 | The external drug for treating herpesvirus infection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110201143A true CN110201143A (en) | 2019-09-06 |
Family
ID=67793763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910534860.6A Pending CN110201143A (en) | 2019-06-20 | 2019-06-20 | The external drug for treating herpesvirus infection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110201143A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963675A (en) * | 2016-05-17 | 2016-09-28 | 武汉大学 | Application of fibronectin (FN) inhibitor-tetrapeptide RGDS in preparation of anti-EV71 virus medicine |
-
2019
- 2019-06-20 CN CN201910534860.6A patent/CN110201143A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963675A (en) * | 2016-05-17 | 2016-09-28 | 武汉大学 | Application of fibronectin (FN) inhibitor-tetrapeptide RGDS in preparation of anti-EV71 virus medicine |
Non-Patent Citations (3)
| Title |
|---|
| VAN DE WALLE等: "Equine Herpesvirus 1 Entry via Endocytosis Is Facilitated by alpha V Integrins and an RSD Motif in Glycoprotein D", 《JOURNAL OF VIROLOGY》 * |
| VISSER, MR等: "HERPES-SIMPLEX VIRUS INHIBITS ENDOTHELIAL-CELL ATTACHMENT AND MIGRATION TO EXTRACELLULAR-MATRIX PROTEINS", 《AMERICAN JOURNAL OF PATHOLOGY》 * |
| 金进: "《新药临床应用手册》", 30 April 1999, 第二军医大学出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU746756B2 (en) | A method of inhibiting formation of infectious herpes virus particles | |
| CN102416023B (en) | Periplaneta Americana L. gel externally applied medicinal composition and preparation method and use thereof in preparation of externally applied medicines for treating scalding | |
| CN104922130B (en) | It is a kind of to be used to treat gelling agent of herpes zoster and preparation method thereof | |
| VON KROGH | Penile condylomata acuminata: an experimental model for evaluation of topical self-treatment with 0.5–1.0% ethanolic preparations of podophyllotoxin for three days | |
| CN103079561B (en) | The topical antiviral preparation propagated for preventing HSV-2 | |
| RU2394586C2 (en) | Application of skeleton of nocardia rubra cell wall for obtaining medication against human papilloma virus (hpv) | |
| CN106822377B (en) | Compound osteitis cataplasm patch and preparation method thereof | |
| CN108042589A (en) | The new application of Pien Tze Huang and its preparation in the drug for preparing treatment herpes zoster | |
| CN101152320B (en) | Traditional Chinese medicine preparation for treating gynecology pelvic inflammatory disease | |
| CN110201143A (en) | The external drug for treating herpesvirus infection | |
| CN101062085B (en) | Condyloma acuminata treating medicine | |
| Du et al. | 5-Aminolevulinic acid photodynamic therapy stimulates local immunity in patients with condylomata acuminata via activation of T lymphocytes. | |
| CN103230581B (en) | For treating compositions and the method for traumatic brain injury | |
| CN110292621A (en) | The antitoxin antibacterial complexing agent of anti-HPV viruse infection and its preparation method of phase inversion gel | |
| CN103070956B (en) | Biological adhesion colon positioning micro-chip for treating ulcerative colitis | |
| CN101461817A (en) | Use of 1,2,3,4,6-five-O-gallnut acyl radical-b-D-glucose | |
| JP5916300B2 (en) | In vitro test system for virus infection | |
| CN112294868B (en) | Medicine for inactivating virus, sterilizing and activating immunity of organism | |
| CN1267522A (en) | Chemotaxis factor generation accelerator | |
| CN109223801A (en) | A kind of new the killing agent of gastric cancer tumor stem cell and its application | |
| Jaiswal | TO STUDY THE ROLE OF AUTO-IMPLANTATION THERAPY IN CUTANEOUS VIRAL WARTS | |
| CN112691167B (en) | Traditional Chinese medicine composition for treating depression and preparation and application thereof | |
| CN111643606B (en) | Gel plaster for treating insomnia and preparation method thereof | |
| CN102366446B (en) | Self-heated traditional Chinese medicine (TCM) emplastrum for improving pelvic inflammation | |
| CN102526238A (en) | Chinese medicinal composition for preventing and treating rheumatoid arthritis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190906 |
|
| RJ01 | Rejection of invention patent application after publication |