CN111617086A - Application of taurolidine in preparing anti-HPV (human papilloma Virus) medicine - Google Patents
Application of taurolidine in preparing anti-HPV (human papilloma Virus) medicine Download PDFInfo
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- CN111617086A CN111617086A CN202010638927.3A CN202010638927A CN111617086A CN 111617086 A CN111617086 A CN 111617086A CN 202010638927 A CN202010638927 A CN 202010638927A CN 111617086 A CN111617086 A CN 111617086A
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- taurolidine
- hpv
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- hpv virus
- virus
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- AJKIRUJIDFJUKJ-UHFFFAOYSA-N taurolidine Chemical compound C1NS(=O)(=O)CCN1CN1CNS(=O)(=O)CC1 AJKIRUJIDFJUKJ-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 229960004267 taurolidine Drugs 0.000 title claims abstract description 31
- 239000003814 drug Substances 0.000 title claims abstract description 18
- 241000701806 Human papillomavirus Species 0.000 title description 16
- 241000700605 Viruses Species 0.000 claims abstract description 20
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 206010059313 Anogenital warts Diseases 0.000 claims description 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 5
- 201000010881 cervical cancer Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 239000003978 infusion fluid Substances 0.000 claims description 3
- 206010046914 Vaginal infection Diseases 0.000 claims description 2
- 201000008100 Vaginitis Diseases 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 201000003505 cervical polyp Diseases 0.000 claims description 2
- 230000003628 erosive effect Effects 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 230000009826 neoplastic cell growth Effects 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims 1
- -1 infusion Substances 0.000 claims 1
- 238000001802 infusion Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 9
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 230000001413 cellular effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract description 3
- 238000011161 development Methods 0.000 abstract description 2
- 230000000857 drug effect Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 12
- 210000002919 epithelial cell Anatomy 0.000 description 6
- 230000000120 cytopathologic effect Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 210000002200 mouth mucosa Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000009608 Papillomavirus Infections Diseases 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000554 physical therapy Methods 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- HMYABIUUQMXICR-UHFFFAOYSA-N 4-(1,2,4-thiadiazinan-4-ylmethyl)-1,2,4-thiadiazinane Chemical compound C1CSNCN1CN1CCSNC1 HMYABIUUQMXICR-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 208000031504 Asymptomatic Infections Diseases 0.000 description 1
- 208000000907 Condylomata Acuminata Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 102000007501 Thymosin Human genes 0.000 description 1
- 108010046075 Thymosin Proteins 0.000 description 1
- 108010074506 Transfer Factor Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001986 anti-endotoxic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 208000037815 bloodstream infection Diseases 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 201000004196 common wart Diseases 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 230000008508 epithelial proliferation Effects 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 201000006509 pleuropneumonia Diseases 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 201000010153 skin papilloma Diseases 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940031351 tetravalent vaccine Drugs 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to application of taurolidine, and relates to the technical field of medicines. The invention discovers the new application of the taurolidine for the first time, namely the application of the taurolidine in inhibiting HPV virus or preparing anti-HPV virus medicaments. The safety of the taurolidine to human bodies is detected by clinical practice, the invention discovers the obvious drug effect of the taurolidine to HPV virus, provides powerful theoretical basis and practical basis for resisting the HPV virus, and has development value and popularization significance. The invention detects the inhibition effect of taurolidine on HPV virus at a cellular level. The invention provides a new way for treating diseases caused by HPV virus.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of taurolidine in preparing an anti-HPV (human papilloma Virus) medicine.
Background
Human Papilloma Virus (HPV) is a papilloma vacuolatum virus A genus belonging to the papovaviridae family, is a spherical DNA virus, and can cause squamous epithelial proliferation of human skin mucosa. It is manifested by symptoms such as common wart and genital wart (condyloma acuminatum). With the rapid increase of the incidence rate of condyloma acuminatum in venereal diseases and the increase of cervical cancer, anal cancer and the like, HPV infection is attracting more and more attention.
Existing approaches to disease treatment for HPV infection mainly include: physical therapy, pharmacotherapy, immunotherapy, therapeutic vaccines. The physical therapy mainly adopts laser, microwave, freezing, excision, photodynamic therapy and the like to remove tumor bodies and subclinical infection which are visible to the naked eye. The main medicines used for the drug therapy are 0.5 percent of fogdalin tincture, 5 percent of imiquimod, 50 percent of trichloroacetic acid, fluorouracil ointment and the like. Immunotherapy uses interferon, interleukin, thymosin, transfer factor, BCG, isotretinoin, autovaccine, etc. with the purpose of reducing recurrence and accelerating the removal of lesions. The vaccine only has preventive quadrivalent vaccine which can prevent HPV6, 11, 16 and 18 virus type infection at present, and can reduce most of cervical cancer because the infection type of most of cervical cancer is 16 and 18, but has no effect on preventing vaccine for infected people.
Chinese patents CN101274921A and CN101285813A disclose that Taurolidine (Taurolidine) has a chemical name: 4,4 ' -methylenebis- (tetrahydro-2H-1, 2, 4-thiadiazine) -1,1,1 ', 1 ' tetraoxide with the molecular formula C7H16N4O4S2The molecular weight is: 284.348, is white or white-like crystalline powder, and has the following chemical formula:
can be synthesized by the following synthetic route:
taurolidine is a broad spectrum antibacterial, antifungal and antiendotoxic drug. Is mainly used for preventing the junior symptoms of patients suffering from various blood stream infections related to the catheter. It can also be used for treating otitis, pleuropneumonia, osteomyelitis, dermatitis, periodontitis, gingivitis, acne, and ulcer. But have not been found to be useful against human papillomaviruses.
Disclosure of Invention
The invention aims to provide a new application of taurolidine, namely the application of taurolidine in inhibiting HPV virus or preparing anti-HPV virus medicaments.
It is preferable that: application of taurolidine in preparing medicaments for treating cervical epithelial cell neoplasia, vaginitis, cervical erosion, cervical polyp, cervical cancer or condyloma acuminatum caused by HPV virus infection.
In the technical scheme, the taurolidine can be prepared into injection, infusion solution, tablets, capsules and other dosage forms, and the infusion solution is preferred.
The invention has the beneficial effects that:
the invention discovers the new application of the taurolidine for the first time, namely the application of the taurolidine in inhibiting HPV virus or preparing anti-HPV virus medicaments. The safety of the taurolidine to human bodies is detected by clinical practice, the invention discovers the obvious drug effect of the taurolidine to HPV virus, provides powerful theoretical basis and practical basis for resisting the HPV virus, and has development value and popularization significance. The invention detects the inhibition effect of the taurolidine on the HPV virus at the cellular level, and provides a new way for treating diseases caused by the HPV virus.
Detailed Description
To better understand the essence of the present invention, the following was made by examining the inhibitory effect of taurolidine on HPV virus at the cellular level.
Firstly, experimental materials:
1.1 cells of human oral mucosal epithelial cells, derived from the virology research laboratory of the military veterinary institute;
1.2 strain Human Papilloma Virus (HPV), derived from the virology research laboratory of the military veterinary institute;
1.3 reagent elitec primary epithelial cell culture system PriMed-elitec-001, 0.25% trypsin, FBS, PBS (FH ═ 7.0);
1.4 instrument consumable pipettor and supporting suction head, 1.5mL centrifuging tube, ice box, ice machine, biological safety cabinet, carbon dioxide incubator.
II, an experimental method:
2.1 the cell culture recovers the epithelial cells of the oral mucosa of the human body, continuously transmits the cells for three generations, and is used for experimental research after the cells grow well;
2.2 Virus culture the preserved virus liquid is placed on ice to be slowly melted and then inoculated to a monolayer of human oral mucosa epithelial cells (no more than 24 hours), the culture is continued for 72 to 96 hours, and the virus liquid is harvested according to the cytopathic state. And determining the virus content as TCID50The unit of calculation is/100. mu.L.
2.3 taurolidine inhibition
Drugs are mixed with virus and simultaneously inoculated into cells: digesting well-growing human oral mucosa epithelial cells with pancreatin, calculating cell content, inoculating to 96-well plate with 10 per well5Individual cells, seeded within 12 hours and in monolayer state for study of drug action. Inoculation virus content of 200 TCIDs50HPV and taurolidine are mixed and immediately inoculated into a paved 6-well plate, and the 2 percent taurolidine solution and the drug dosage are 50 mu L, 25 mu L, 12.5 mu L, 7.5 mu L and 3.75 mu L. Setting blank cell control and taurolidine cytotoxicity control, and repeating for 3 times;
placing the inoculated cell plate at 37 ℃ and CO2In the incubator, the culture was continued and the cytopathic effect was observed.
Third, experimental results
According to the above experimental method, CO is maintained at 37 deg.C2The cell state was observed in the incubator for 72 hours, and the cell state was good and no cytopathic effect was observed under the microscope in the case of 50. mu.L and 25. mu.L of the drug as the inoculum dose. The cytopathic effect of 12.5. mu.L, 7.5. mu.L and 3.75. mu.L appeared to different degrees, and the inoculation dose of 3.75. mu.L was used as the group and 200TCID was used50The cytopathic effect was not different.
Fourthly, judging the result
Based on the above experimental results, it was determined that 200TCID was completely inhibited when the drug was administered in a dose of 50. mu.L or 25. mu.L50200TCID was not completely inhibited by 12.5. mu.L, 7.5. mu.L of the inoculum dose50Virus-infected cells failed to inhibit 200TCID at an inoculum dose of 3.75. mu.L50The virus infects the cells.
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 (5)
1. An application of taurolidine in inhibiting HPV virus is disclosed.
2. An application of taurolidine in preparing anti-HPV virus medicine.
3. Use according to claim 2, characterized in that taurolidine is used in the preparation of a medicament for the treatment of cervical epithelial neoplasia, vaginitis, cervical erosion, cervical polyps, cervical cancer or condyloma acuminata caused by HPV viral infection.
4. The use of claim 2 or 3, wherein the taurolidine is in the form of an injection, infusion, tablet or capsule.
5. The use of claim 4, wherein said taurolidine is in the form of an infusion solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010638927.3A CN111617086A (en) | 2020-07-06 | 2020-07-06 | Application of taurolidine in preparing anti-HPV (human papilloma Virus) medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010638927.3A CN111617086A (en) | 2020-07-06 | 2020-07-06 | Application of taurolidine in preparing anti-HPV (human papilloma Virus) medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111617086A true CN111617086A (en) | 2020-09-04 |
Family
ID=72255721
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010638927.3A Pending CN111617086A (en) | 2020-07-06 | 2020-07-06 | Application of taurolidine in preparing anti-HPV (human papilloma Virus) medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111617086A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113491700A (en) * | 2020-07-06 | 2021-10-12 | 军事科学院军事医学研究院军事兽医研究所 | Application of taurolidine in antivirus |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6302108B1 (en) * | 2000-03-10 | 2001-10-16 | Carter-Wallace, Inc | Spermicidal and viricidal compositions |
| US6608051B1 (en) * | 1999-03-12 | 2003-08-19 | Medpointe Healthcare Inc. | Compositions and methods for treating blood |
| US20050013836A1 (en) * | 2003-06-06 | 2005-01-20 | Board Of Regents, The University Of Texas System | Antimicrobial flush solutions |
| CN101274921A (en) * | 2008-04-28 | 2008-10-01 | 长春迈灵生物工程有限公司 | Synthetic method for taurolidine and pharmaceutical preparations |
| CN110776479A (en) * | 2014-12-19 | 2020-02-11 | 盖斯特里希医药公司 | Thiazine-like compounds, preparation method and application thereof |
-
2020
- 2020-07-06 CN CN202010638927.3A patent/CN111617086A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6608051B1 (en) * | 1999-03-12 | 2003-08-19 | Medpointe Healthcare Inc. | Compositions and methods for treating blood |
| US6302108B1 (en) * | 2000-03-10 | 2001-10-16 | Carter-Wallace, Inc | Spermicidal and viricidal compositions |
| US20050013836A1 (en) * | 2003-06-06 | 2005-01-20 | Board Of Regents, The University Of Texas System | Antimicrobial flush solutions |
| CN101274921A (en) * | 2008-04-28 | 2008-10-01 | 长春迈灵生物工程有限公司 | Synthetic method for taurolidine and pharmaceutical preparations |
| CN110776479A (en) * | 2014-12-19 | 2020-02-11 | 盖斯特里希医药公司 | Thiazine-like compounds, preparation method and application thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113491700A (en) * | 2020-07-06 | 2021-10-12 | 军事科学院军事医学研究院军事兽医研究所 | Application of taurolidine in antivirus |
| WO2022007713A1 (en) * | 2020-07-06 | 2022-01-13 | 军事科学院军事医学研究院军事兽医研究所 | Use of taurolidine against virus |
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Application publication date: 20200904 |
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