CN104546839B - The purposes of quinoline promise Li Xiding alkaloids - Google Patents
The purposes of quinoline promise Li Xiding alkaloids Download PDFInfo
- Publication number
- CN104546839B CN104546839B CN201510062300.7A CN201510062300A CN104546839B CN 104546839 B CN104546839 B CN 104546839B CN 201510062300 A CN201510062300 A CN 201510062300A CN 104546839 B CN104546839 B CN 104546839B
- Authority
- CN
- China
- Prior art keywords
- xiding
- alkaloids
- quinoline promise
- quinoline
- promise
- 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.)
- Active
Links
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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
Landscapes
- Health & Medical Sciences (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to the new application of field of medicaments, more particularly to quinoline promise Li Xiding alkaloids.The invention provides under conditions of the infection of EV71 viruses or not infecting, quinoline promise Li Xiding alkaloids improve the application in T cell level, and are preparing the application during preventing and treating EV71 infection triggers the medicine of disease there is provided quinoline promise Li Xiding alkaloids.Research shows, the quinoline promise Li Xiding alkaloids of final concentration of 60mg/kg/ days, and T cell level can be made in Mice Body to be significantly improved (p<0.01).To EV71 infecting mouse models, the quinoline promise Li Xiding alkaloids of 15mg/kg body weight doses being given daily, being administered continuously 7 days, the T cell level in mouse model body is significantly improved (p<0.01) symptom of infecting mouse hind limb paralysis and weight loss weakens, and the death rate is down to 30%.And the death rate for not giving the model mice of quinoline promise Li Xiding alkaloids is 100%.
Description
Technical field
The present invention relates to the purposes of field of medicaments, more particularly to quinoline promise Li Xiding alkaloids.
Background technology
Quinoline promise Li Xiding alkaloids (quinolizidine) are distributed mainly in legume, large number of, are broadly divided into
Seven major classes：Plumage French beans bases, Spartium junceum bases, broom top bases, matrine, lycopod bases and tricyclic antidepressants.Wherein, matrine
Class with extensive pharmacological activity because being applied to clinic, and representative compound has matrine, oxymatrine, sophoramine, Chinese scholartree
Determine alkali, sophocarpine, N-Oxysophocarpine, structure is as follows：
Western class D alkaloid is large number of in quinoline promise, and physiologically active has diversity, by taking matrine as an example, and its physiology is lived
Property is related generally to：1st, the effect of Central nervous system；2nd, to the effect of cardiovascular system；3rd, antitumor action；4th, anti-hepatitis
And effect of anti hepatic fibrosis；5th, antiinflammatory action；6th, antibacterial, antivirus action.Wherein, antivirus action is shown：Sophocarpine can
Resist Coxsackie B virus, SARS virus；Sophoridine can resist Coxsackie virus B 3.
T cell is the key component of lymphocyte, and it has various biological function, such as direct killing target cell, auxiliary
Or suppress B cell generation antibody, to specific antigen and the former responsing reaction of mitogenesis and generation cell factor etc..When
When body is attacked by adventive, T cell is activated, increased.T cell surface carries leukocyte differentiation antigen (CD), wherein,
CD3 developed by molecule is in whole T cells, and CD4 molecular distributions are sub- in the auxiliary cell induction subgroup and suppression cell induction of T cell
Group surface, CD8 molecular distributions are in suppressive lymphocyte T and cytotoxic T lymphocyte surface.
Human enterovirus 71 is the member of Picornaviridae enterovirus genus, belongs to Human enterovirus virus A, referred to as
EV71, often causes hand-foot-and-mouth disease, herpangina, viral meningitis, viral encephalitis, slowness paralysis, pulmonary edema, disease
The diseases such as viral myocarditis, are referred to as enterovirns type 71 infection.Result of study shows that T is thin in infection EV71 Virus patients' bodies
Born of the same parents' content is reduced, and the percentage reduction of CD4+T lymphocyte subgroups and CD8+T lymphocyte subgroups.
The multiple infant for being born in less than 6 years old of EV71 virus infection, a small number of state of an illness are more serious, or even can cause death.
The disease can all occur throughout the year, be common in 4-9 months.EV71 virus infection infants are more with onset of generating heat, a generally 38 DEG C left sides
Simultaneously, there is fash, or ulcer in oral cavity, enanthem occur in oral cavity, brothers, buttocks in the right side, heating.Some patients cough early stage
The flu such as cough sample performance.A small number of infants may occur in which severe complication.This kind of patient continues hyperpyrexia mostly, and disease development is rapid, many
There is central nervous system, respiratory system, circulatory system severe complication in 3-5 days after morbidity, and death can be caused, it is dead
Reason is mainly encephaledema, hernia cerebri, central breathing, circulatory failure.EV71 viruses worldwide repeatedly outburst, via stomach
Enteron aisle or respiratory infectious, according to the data of the Ministry of Public Health, from 2008 in October, 2012, interior ground hand foot and mouth disease incidence
Remain high always, patient is more than 5,000,000 people, and death toll is more than 2000, and epidemic situation is still severe.At present, feel for EV71
Specific medicament or vaccine that dye is not generally acknowledged still.
The content of the invention
In view of this, the technical problem to be solved in the present invention is the new application for providing quinoline promise Li Xiding alkaloids.
The invention provides application of the quinoline promise Li Xiding alkaloids in T cell level is improved.
Preferably, quinoline promise Li Xiding alkaloids are matrine.
Preferably, quinoline promise Li Xiding alkaloids are matrine, oxymatrine, sophoramine, Sophoridine, sophocarpine or oxygen
Change sophocarpine.
Preferably, the dosage that quinoline promise Li Xiding alkaloids improve T cell level is 60mg/kg.
Traditionally to the anti-SRBC antibody responses of dependence T cell, matrine, oxymatrine, sophoramine have substantially
Inhibitory action, sophocarpine, Sophoridine depression effect be not obvious.And have test result indicate that, matrine, oxymatrine can press down
T lymphocytes acidαnaphthy acetate esterase processed, so as to produce immunosuppressive action.Separately there is result of study to show, high concentration (1mg/mL)
Oxymatrine has inhibitory action to mice spleen T, bone-marrow-derived lymphocyte, and low concentration shows, there is obvious humidification.
And result of study of the present invention shows, in the quinoline promise of final concentration of 60mg/kg/ days (60mg is daily per kg the weight of animals)
Western fourth alkaloid, can make in Mice Body T cell level be significantly improved (p<0.01).
At present, the research to the immunoregulation effect of quinoline promise Li Xiding alkaloids is normal in tumour or hepatites virus infections condition
It is lower to carry out.And the experimental results show, quinoline promise Li Xiding alkaloids are unrelated with immunoregulation effect to the inhibitory action of tumour,
I.e. under tumour existence condition, do not show to strengthen the effect of immunologic function or show immunosuppressive effect.It is embodied in,
Under the conditions of tumour or hepatites virus infections, quinoline promise Li Xiding alkaloids are in inhibitory action to the acidαnaphthy acetate esterase of T cell.
The present invention experiments prove that and there is provided quinoline promise Li Xiding alkaloids under EV71 infectious conditions, improve T cell
Application in level.
Preferably, quinoline promise Li Xiding alkaloids are matrine.
Preferably, quinoline promise Li Xiding alkaloids are matrine, oxymatrine, sophoramine, Sophoridine, sophocarpine or oxygen
Change sophocarpine.
Preferably, quinoline promise Li Xiding alkaloids are N-Oxysophocarpine.
Preferably, T cell is CD4+T lymphocyte subgroups or CD8+T lymphocyte subgroups.
Preferably, quinoline promise Li Xiding alkaloids are under EV71 infectious conditions, the dosage for improving T cell level is 15mg/
Kg/ days.
The present invention test result indicate that：To EV71 infecting mouse models, 15mg/kg is given daily, and (15mg is per kg animals
Body weight is daily) the quinoline promise Li Xiding alkaloids of body weight dose, it is administered continuously 7 days, the T cell level in mouse model body is shown
Write and improve (p<0.01).
Answering during preventing and treating EV71 infection triggers the medicine of disease is being prepared present invention also offers quinoline promise Li Xiding alkaloids
With.
Preferably, quinoline promise Li Xiding alkaloids are matrine.
Preferably, quinoline promise Li Xiding alkaloids are matrine, oxymatrine, sophoramine, Sophoridine, sophocarpine or oxygen
Change sophocarpine.
Preferably, quinoline promise Li Xiding alkaloids are N-Oxysophocarpine.
Preferably, EV71 infection triggers disease is hand-foot-and-mouth disease, herpangina, viral meningitis, viral
Encephalitis, slowness paralysis, pulmonary edema or vital myocarditis.
The present invention experiments prove that；To EV71 infecting mouse models, give daily in the quinoline promise of 15mg/kg body weight doses
Western fourth alkaloid, is administered continuously 7 days, and the symptom of infecting mouse hind limb paralysis and weight loss weakens, and the death rate is down to 30%.And
The death rate for not giving the model mice of quinoline promise Li Xiding alkaloids is 100%.Illustrate quinoline promise Li Xiding alkaloids to EV71 institutes
Causing infection has therapeutic action.
The medicine of preventing and treating EV71 infection initiation diseases includes quinoline promise Li Xiding alkaloids and pharmaceutically acceptable auxiliary material.
Preferably, it is injection or oral formulations that preventing and treating EV71 infection, which triggers the formulation of the medicine of disease,.
Preferably, oral formulations are tablet, capsule, pill, granule, decoction, paste, distillate medicinal water, oral solutions, drop
Pill or syrup.
The invention provides under conditions of the infection of EV71 viruses or not infecting, quinoline promise Li Xiding alkaloids improve T cell
Application in level, and provide quinoline promise Li Xiding alkaloids answering in the medicine for preparing preventing and treating EV71 infection initiation diseases
With.And result of study of the present invention shows, the quinoline promise Li Xiding of final concentration of 60mg/kg/ days (60mg is daily per kg the weight of animals)
Alkaloid, can make in Mice Body T cell level be significantly improved (p<0.01).To EV71 infecting mouse models, give daily
The quinoline promise Li Xiding alkaloids of 15mg/kg (15mg is daily per kg the weight of animals) body weight dose are given, are administered continuously 7 days, mouse mould
T cell level in type body is significantly improved (p<0.01) symptom of infecting mouse hind limb paralysis and weight loss weakens, extremely
The rate of dying is down to 30%.And the death rate for not giving the model mice of quinoline promise Li Xiding alkaloids is 100%.
Embodiment
The invention provides the new application of quinoline promise Li Xiding alkaloids, those skilled in the art can use for reference present disclosure,
It is suitably modified technological parameter realization.In particular, all similar replacements and change come to those skilled in the art
Say it is it will be apparent that they are considered as being included in the present invention.The method of the present invention and application pass through preferred embodiment
It is described, related personnel substantially can be not departing from present invention, in spirit and scope to method described herein and should
With being modified or suitably changing with combining, to realize and apply the technology of the present invention.
The raw material that the present invention is used is all common commercially available product, can all be bought by market.
With reference to embodiment, the present invention is expanded on further：
The quinoline promise Li Xiding alkaloids of embodiment 1 improve the T cell level in Mice Body
Take the BALC/c mouse of adult, body weight 18-22g, every group 6.Quinoline promise Li Xiding alkaloid physiological saline solutions,
Every mouse gives final concentration of 60mg/kg quinoline promise Li Xiding alkaloids respectively, and quinoline promise is replaced with isometric physiological saline
Li Xiding alkaloids once a day, are administered continuously 7 days as negative control.Blood is taken to carry out flow cytometer point with CD3 antibody
Analysis, its result is as shown in table 1：
Table 1 be administered 7 days after flow cytomery result
| CD3+T cell percentages | |
| Cloudy control group | 36.92%a |
| Matrine | 38.46%a |
| Oxymatrine | 43.84%b |
| Sophoramine | 49.36%b |
| Sophoridine | 39.17%a |
| Sophocarpine | 50.56%bc |
| N-Oxysophocarpine | 53.52%c |
Note：The different letters of similar shoulder mark, which are represented, has significant difference (p<0.01)
As a result show：T cell level is significantly improved in the Mice Body for the quinoline promise Li Xiding alkaloids for giving 60mg/kg
(p<0.01)。
The quinoline promise Li Xiding alkaloids of embodiment 2 improve the T cell level of EV71 infecting mouses
The use of mouse is SPF grades of ICR mouse, 10 ages in days, male and female half and half, every group 20.First, abdominal cavity injection EV71 viruses
Viral infection is carried out to mouse, EV71 virus stains are adapted strains of the clinical separation strain FY0805 in Mice Body, and strain is entitled
MP10, storage number of the gene order in NCBI is HQ712020.It is biological that quinoline promise Li Xiding is given in infection pneumoretroperitoneum injection in 2 hours
Alkali or physiological saline.With quinoline promise Li Xiding alkaloid physiological saline solutions, its dosage is 15 mg kg of body weight/day；Daily
It is administered once, is administered continuously 7 days.Using the mouse of uninfecting virus as negative control；To infect virus and give physiological saline
Mouse is positive control；To infect virus and give the mouse of quinoline promise Li Xiding alkaloids as experimental group., will the 8th day after infection
Mouse takes off neck and put to death, and takes blood to carry out flow cytometry analysis with CD3, CD4, CD8 antibody, wherein, to giving N-Oxysophocarpine
Mouse testing result it is as shown in table 2：
Table 2 be administered 7 days after flow cytomery result
Note：The different letters of similar shoulder mark, which are represented, has significant difference (p<0.01)
As shown in Table 2, infection EV71 can cause T cell level in Mice Body to decline, and giving N-Oxysophocarpine can carry
Total T cell level of high EV71 infecting mouses, and internal CD4+T lymphocyte subgroups or CD8+T lymphocytes Asia can be improved
Group's level.Influence of other quinoline promise Li Xiding alkaloids to total T cell level of EV71 infecting mouses is similarly.
The quinoline promise Li Xiding alkaloids of embodiment 3 are to EV71 virus infected mice survival rates
The purpose of this experiment is the therapeutic effect for verifying quinoline promise Li Xiding alkaloids to EV71 virus infection in Mice Body,
Model used is the model of the age in days ICR mouse of CONTINENTAL AREA OF CHINA EV71 virus strain infections 10.Strain is clinical separation strain FY0805
Adapted strain in Mice Body, the entitled MP10 of strain, storage number of the gene order in NCBI is HQ712020.With 1 ×
107TCID50The MP10 viruses of dosage can cause after mouse showed in 4 days after the age in days ICR mouse of abdominal cavity infectable infection 10
The symptom of acroparalysis and weight loss, and in all dead in after infection 10 days.
Using above-mentioned model, the therapeutic effect to quinoline promise Li Xiding alkaloids carries out interior evaluating.The use of mouse it is SPF grades
ICR mouse, 10 ages in days, male and female half and half, every group 20.First, abdominal cavity injection MP10 viruses carry out viral infection, infection to mouse
Quinoline promise Li Xiding alkaloids, quinoline promise Li Xiding alkaloid physiological saline solutions are given in pneumoretroperitoneum injection in 2 hours, and its dosage is 15
Mg kg of body weight/day；It is administered once a day, is administered continuously 7 days.Using infect virus give the mouse of normal saline as
Control group.From virus infection, continuous observation 14 days records body weight, symptom and the survival rate of mouse, evaluates quinoline Nuo Lixi
Therapeutic effect of the fourth alkaloid to EV71 virus infection.As a result it is as shown in table 3：
Therapeutic effect of the quinoline promise Li Xiding alkaloids of table 3 to EV71 virus infection
| Survival rate (%) | |
| Control group | 0 |
| Matrine | 20 |
| Oxymatrine | 25 |
| Sophoramine | 25 |
| Sophoridine | 20 |
| Sophocarpine | 25 |
| N-Oxysophocarpine | 30 |
As a result show：The quinoline promise Li Xiding alkaloids of 15 mg kg of body weight dosage are given daily, are administered continuously 7 days, sense
The symptom of the Body weight loss or hind limb paralysis that contaminate mouse weakens, and the death rate of mouse is significantly reduced.And control group mice is after 14 days
It is all dead.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (5)
1. N-Oxysophocarpine is in the case where preparing EV71 infectious conditions, the application in the medicine of T cell level is improved.
2. application according to claim 1, it is characterised in that the T cell is CD4+T lymphocyte subgroups or CD8+T
Lymphocyte subgroup.
3. quinoline promise Li Xiding alkaloids are preparing the application during preventing and treating EV71 infection triggers the medicine of disease；The quinoline promise Li Xiding
Alkaloid is oxymatrine, sophoramine, Sophoridine, sophocarpine or N-Oxysophocarpine.
4. application according to claim 3, it is characterised in that the quinoline promise Li Xiding alkaloids are N-Oxysophocarpine.
5. application according to claim 3, it is characterised in that it is hand-foot-and-mouth disease, bleb that the EV71 infection, which triggers disease,
Property angina, viral meningitis, viral encephalitis, slowness paralysis, pulmonary edema or vital myocarditis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510062300.7A CN104546839B (en) | 2015-02-05 | 2015-02-05 | The purposes of quinoline promise Li Xiding alkaloids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510062300.7A CN104546839B (en) | 2015-02-05 | 2015-02-05 | The purposes of quinoline promise Li Xiding alkaloids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104546839A CN104546839A (en) | 2015-04-29 |
| CN104546839B true CN104546839B (en) | 2017-07-14 |
Family
ID=53064620
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510062300.7A Active CN104546839B (en) | 2015-02-05 | 2015-02-05 | The purposes of quinoline promise Li Xiding alkaloids |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104546839B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110251514A (en) * | 2019-07-22 | 2019-09-20 | 山西大学 | The application of matrine |
| CN113288896A (en) * | 2021-05-28 | 2021-08-24 | 成都中医药大学 | Application of sophoridine in preparation of anti-herpes virus medicine |
| CN115850265A (en) * | 2021-11-22 | 2023-03-28 | 赣江中药创新中心 | Method for selectively enriching quinolizidine alkaloids in sophora flavescens medicinal material |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1234359C (en) * | 2003-03-10 | 2006-01-04 | 刘平 | Use of oxidized matrine in preparation of chemicals for treating viral myocarditis |
| CN1537852A (en) * | 2003-04-14 | 2004-10-20 | 中国科学院上海药物研究所 | Anti coxsackie viruse action of quinolixiding kind alkaloid |
| CN100379417C (en) * | 2004-12-10 | 2008-04-09 | 上海第二医科大学附属仁济医院 | Application of sophocarpine in use of making medicines |
| CN102240286B (en) * | 2011-05-17 | 2012-12-12 | 武汉大学 | Application of matrine to medicament for treating or preventing enterovirus 71 type infection |
-
2015
- 2015-02-05 CN CN201510062300.7A patent/CN104546839B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN104546839A (en) | 2015-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107106525A (en) | Treatment for suppressing single strand RNA virus duplication | |
| CN104546839B (en) | The purposes of quinoline promise Li Xiding alkaloids | |
| CN102178678B (en) | Application of lycorine in preparing medicament for treating diseases caused by human enterovirus 71 type infection | |
| CN102423350B (en) | Medicine for treating childhood bronchial asthma and application of medicine | |
| CN102274234B (en) | Application of ganoderic acid Y to preparation of medicament for treating or preventing enterovirus 71 infection | |
| CN107753823B (en) | Traditional Chinese medicine composition for treating or preventing hand-foot-and-mouth disease | |
| CN106309455A (en) | Application of peimisine | |
| WO2022148202A1 (en) | Application of traditional chinese medicine composition in preparation of anti-sars virus drugs | |
| CN106344549B (en) | Application of the Rhein in preparation prevention and/or treatment hand-foot-and-mouth disease drug | |
| CN111617183B (en) | Application of traditional Chinese medicine composition in preparation of rotavirus resisting medicine | |
| CN102670636B (en) | Application of geraniin in preparing medicament for treating diseases caused by human enterovirus 71 type infection | |
| CN102885841B (en) | Application of punicalagin | |
| CN114732853A (en) | Application of Chinese medicinal composition in preparing medicine for resisting coronavirus, protecting viscera and enhancing immunity | |
| CN105920026A (en) | Application of cynaroside to preparation of medicine for treating or preventing hand-foot-and-mouth diseases | |
| US20080102140A1 (en) | Use of solidago virgaurea in the treatment and prevention of viral infections | |
| CN103054867B (en) | Application of fangchinoline for preparing medicine for treating or preventing HIV | |
| CN102440988B (en) | Application of arbidol hydrochloride in preparation of anti-enterovirus medicines | |
| CN106243102B (en) | The application of alkaloid compound | |
| CN106377537B (en) | Application of acetyl astragaloside | |
| CN110179785B (en) | Application of widmanone in preparation of medicine for treating or preventing hand-foot-and-mouth disease | |
| CN108542940A (en) | A kind of Chinese medicine composition prepare prevent and/or treatment hand-foot-and-mouth disease drug in application | |
| TWI803229B (en) | Compound tsyi-zac is used to inhibit dengue virus infection and its medicinal use | |
| WO2022237145A1 (en) | Use of traditional chinese medicine composition in preparation of drug for resisting novel coronavirus with d614g mutation in s protein | |
| CN115475196B (en) | Application of Fuan granule extract in preparation of medicine for treating hand-foot-mouth disease | |
| CN103110652B (en) | Application of chebulagic acid in preparation of medicament for treating diseases resulted from human enterovirus type 71 infection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |