CN106902125A - CD8 can be suppressed+Inhibitor, inhibitor combination and application that T cell is killed to melanocyte - Google Patents
CD8 can be suppressed+Inhibitor, inhibitor combination and application that T cell is killed to melanocyte Download PDFInfo
- Publication number
- CN106902125A CN106902125A CN201710099856.2A CN201710099856A CN106902125A CN 106902125 A CN106902125 A CN 106902125A CN 201710099856 A CN201710099856 A CN 201710099856A CN 106902125 A CN106902125 A CN 106902125A
- Authority
- CN
- China
- Prior art keywords
- cell
- inhibitor
- melanocyte
- killed
- suppress
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom
Abstract
The invention belongs to biotechnology and medical domain, it is related to one kind to suppress CD8+Inhibitor that T cell is killed to melanocyte, inhibitor combination and as the application prevented and treated in leucoderma medicament；Triptolide, Celastrol and wilforlide A can suppress CD8 in 5 10nM levels+T cell can suppress the expression of STAT1 transcription factors in keratinocyte to the inhibitor that melanocyte is killed, and then lower IRF1 expressions, suppress to secrete CXCL10 and CXCL16 in keratinocyte, further reduce CXCL10 and CXCL16 to CD8+The chemotaxis of T cell, so as to suppress CD8+T cell is killed to melanocyte；CD8 can be suppressed+T cell is thunder godvine terpenoid, especially triptolide to the inhibitor that melanocyte is killed, Celastrol or triptonide.
Description
Technical field
The invention belongs to biotechnology and medical domain, it is related to a kind of inhibitor and the application in anti-curing vitiligo disease,
More particularly to one kind can suppress CD8+Inhibitor that T cell is killed to melanocyte, inhibitor combination and white as preventing and treating
Application on purplish or white patches on the skin expelling wind drug thing.
Background technology
Leucoderma is a kind of common depigmentation dermatoses, and population of China illness rate is about 0.1%-2%.Leucoderma
It is characterized with leukoderma caused by melanocyte destruction, pathogenesis is still not clear, and extreme difficulties are brought to treatment.Conventional
Research thinks, many factors such as the generation of leucoderma and heredity, oxidative stress, cryptorrhea are related.Existing treatment means
Such as hormone, calcineurin inhibitors, antioxidant, Chinese patent drug, phototherapy curative effect are limited, it is difficult to which acquisition makes Patients' satisfaction
Treatment results.Therefore, it is difficult medical problem urgently to be resolved hurrily to probe into the new therapy target of leucoderma and develop targeted drug.
It is to observe T lymphocyte infiltrations to active stage that cellular immunity participates in one of important clue of leucoderma pathogenesis
Leucoderma skin damaged area melanocyte edges of regions.
A large amount of autoimmunities, the CD that melanocyte is special are may detect that in patients with vitiligo blood and skin8 +T is thin
Born of the same parents.The article for being published in J Invest Dermatol Symp Proc for 2004 reports the infiltrating cells of leucoderma perilesional
Mainly by CD8 +And CD4 +T cell is constituted, it will usually CD occur8 +/CD4 +Ratio increases.Research in recent years shows, CD8 +Participated in
Immune response plays important lethal effect in melanocyte destruction.CD caused by autoimmune disorder8 +T cell activation is simultaneously moved
It is the immediate cause for causing hickie to occur to move to skin and kill melanocyte.These specific Cs D8 +T cell can in vitro by dividing
Perforin, granzyme and Fas/FaL are secreted by way of killing melanocyte, and the change of leucoderma sample can occur by inducing mouse in vivo.
Chemotactic factor (CF) is put down as one of important cell factor in mediated cell interphase interaction and regulation vivo immunization
Weighing apparatus plays vital effect.Patients with vitiligo skin keratin forms cell under various factors induction (such as ROS, IFN-γ)
It is CD8 to produce Chemokines CC XCL10 and CXCL16+T cell chemotactic to skin damaged key link.CXCL10 belongs to non-ELR CXC
Chemotactic factor (CF), also known as interferon inducible protein (IP10), refer to exogenous (LPS etc.) and endogenous inflammatory factor (IL-1,
IFN-α, IFN-γ etc.) stimulate under, by the cell into the various kinds of cell secreting, expressing such as BMDC, keratinocyte because
Son.The research that Mehdi Rashighi in 2014 et al. are published in Science Translational Medicine finds leucoderma
Find that CXCL10 expressions are higher in wind patients serum and skin, on T cells with antigenic specificity CXCR3 expression it is also corresponding on
Adjust.The function of CXCL10 is furtherd investigate, researchers study the function and of CXCL10 by leucoderma model mice
Correlation between CXCL10 and CXCR3, find mouse and the CXCL10 shortage of the T cell phenotype of defect containing CXCR3 mouse or
Compared using the mouse of CXCL10 neutralizing antibodies, hickie quantity occurs and significantly reduces on skin.Additionally, forming hickie disease
There is the phenomenon of pigment regeneration in mouse after CXCL10 neutralizing antibodies are continuing with the mouse of shape.
CXCL16 can be expressed in antigen presenting cell, macrophage, lymph node epithelial cell, cornu cutaneum on people in normal structure
Cell plastid etc..CXCL16 participates in chemotactic of the inflammatory cell to pathological tissues by CXC types chemokine receptors 6 (CXCR6).
CXCL16/CXCR 6 is relevant with a series of diseases associated with inflammation of the mankind.Mikiko Tohyama in 2007 et al. are published in
A researcher on International Immunology has found that CXCL16 passes through induced activation T cell and NKT cell tables
Face CXCR6 expresses to mediate epidermal keratinocyte to be so immunized.And Li Chunying professors team is published in J Allergy in 2016
Article on Clin Immunol. (IF.12.485) thinks that keratinocyte can activate NF- κ B letters under the conditions of oxidative stress
The induction CXCL16 expression of number approach and secrete, recruit CD8+T cell is to migration of melanocytes and kills melanocyte.The research is first
The secondary CXCL16-CXCR6 that proposes is CD8 under mediation leucoderma oxidative stress microenvironment+The crucial letter that T cell is migrated to skin
Number, and propose for the leucoderma targeted therapy new strategy that CXCL16 axles are anti-oxidant and regulation and control are immune.
Future, the expression and its function for suppressing CXCL10 and CXCL16 in leucoderma keratinocyte is likely to become leucoderma
The Critical policies of wind treatment.But the medicine for not yet having targeted inhibition CXCL10 and CXCL16 at present occurs.
Thunder godvine is a kind of conventional anti-inflammatory, immunosupress class Chinese medicine, and clinic is usually used in systemic loupus erythematosus, rheumatoid
The treatment of the autoimmunity diseases such as property arthritis, but application in therapy of vitiligo is there is not yet wide coverage.Previously study and show,
Thunder godvine can suppress the expression of the chemotactic factor (CF) such as MCP-1, CCL5 in panimmunity cell, relevant with its immunosuppressive action.And
Chemical composition various structures in thunder godvine, structure-activity relationship is also still not clear.Studies have found that its representative monomers compound Thunder God
Rattan A prime can raise the expression that intracellular cytokine signaling suppresses molecule SOCS1, so as to lower the work of STAT1 signal paths
Property；And STAT1 and transcription factor IRF-1 downstream have been found to be activated by IFN-γ, play transcription and promote CXCL10 tables
The effect for reaching.
Analyzed according to more than, propose following hypothesis：Prepared from active ingredients of tripterygium wilfordii suppresses in leucoderma keratinocyte
The activation of STAT1/IRF-1 and NF- κ B signal paths, lowers the generation and release of CXCL10 and CXCL16, further prevents CD8 +
T cell chemotactic, so as to protect melanocyte from immunologic cytotoxicity, plays treatment leucoderma wind action to skin.
The content of the invention
In order to solve above-mentioned technical problem present in background technology, the invention provides a kind of system research thunder godvine system
Row compound suppresses the specific molecule machine of the further expression for reducing CXCL10 and CXCL16 of activation of STAT1/IRF-1 paths
System, acquired results treat the suppressed CD8 for providing theoretical foundation and crucial target spot for leucoderma immunological regulation+T cell is thin to melanocyte
Inhibitor, inhibitor combination and application that born of the same parents kill.
To achieve the above object, the present invention is adopted the following technical scheme that：
One kind can suppress CD8+The inhibitor that T cell is killed to melanocyte, it is characterised in that：It is described to suppress CD8+T is thin
Born of the same parents can suppress the expression of STAT1 transcription factors in keratinocyte to the inhibitor that melanocyte is killed, and then under
Adjust IRF1 expressions, suppress keratinocyte in secrete CXCL10 and CXCL16, further reduce CXCL10 and
CXCL16 is to CD8+The chemotaxis of T cell, so as to suppress CD8+T cell is killed to melanocyte；It is described to suppress CD8+T is thin
Born of the same parents are thunder godvine terpenoids to the inhibitor that melanocyte is killed.
It is above-mentioned to suppress CD8+T cell is half terpenoid alkaloid, the Thunder God of thunder godvine times to the inhibitor that melanocyte is killed
The diterpene-kind compound of rattan and/or the triterpene compound of thunder godvine.
It is above-mentioned to suppress CD8+T cell is half terpenoid alkaloid, the Thunder God of thunder godvine times to the inhibitor that melanocyte is killed
The monomeric compound of the diterpene-kind compound of rattan and/or the triterpene compound of thunder godvine.
Above-mentioned monomeric compound is triptolide, Celastrol and/or triptonide.
The effective dose of above-mentioned monomeric compound is not higher than 80nM, preferably 1-60nM；More preferably 5-10nM.
One kind is based on that CD8 can be suppressed as previously described+The inhibitor that T cell is formed to the inhibitor that melanocyte is killed
Composition, it is characterised in that：The inhibitor combination contains can suppress CD8 as previously described+T cell is killed to melanocyte
Inhibitor as active component.
Above-mentioned inhibitor combination also includes that the suppressed CD8 described in claim 1-5 any claims can be made+T
Inhibitor that cell is killed to melanocyte stabilization and/or can strengthen and described can suppress CD8+T cell is killed to melanocyte
Inhibitor effect auxiliary material.
Above-mentioned auxiliary material is one or more pharmaceutically acceptable carrier and/or excipient.
According to CD8 can be suppressed as previously described+T cell how the inhibitor that melanocyte is killed is prepared for prevent and/
Or the application in the medicine for the treatment of leucoderma.
It is an advantage of the invention that：
Can suppress CD8 the invention provides one kind+Inhibitor that T cell is killed to melanocyte, inhibitor combination and
Using this can suppress CD8+T cell the inhibitor that melanocyte is killed can be suppressed in keratinocyte STAT1 transcriptions because
The expression of son, and then IRF1 expressions are lowered, suppress to secrete CXCL10 and CXCL16 in keratinocyte, enter one
Step reduces CXCL10 and CXCL16 to CD8+The chemotaxis of T cell, so as to suppress CD8+T cell is killed to melanocyte；This can
Suppress CD8+T cell is the hemiterpene life again of thunder godvine terpenoid, especially thunder godvine to the inhibitor that melanocyte is killed
The triterpene compound of alkaloids, the diterpene-kind compound of thunder godvine and/or thunder godvine.Triptolide, triptonide, thunder
Celastrol is representational diterpene, triterpene compound in thunder godvine, is from 3 kinds of chemical structural type (sequiterpenes of thunder godvine
Alkaloid, diterpene, triterpene totally 7 monomers) in screen 3 there is the monomer chemical combination for significantly inhibiting CXCL10 and CXCL16
Thing；The structure type of active ingredient in thunder godvine is determined.In the case where same consumption is ensured, curative effect can be improved and reduced
The toxic and side effect of thunder godvine；The present invention illustrates thunder godvine for suppressing the molecular mechanism of CXCL10 and CXCL16 secretions first,
I.e. effective monomer lowers IRF1 by suppressing the expression of STAT1, so as to suppress CXCL10 and CXCL16 secretions and its to CD8+T
The chemotaxis of cell, protects melanocyte.The present invention provides a new way for the preventing and treating of leucoderma, in medicine
Have a extensive future.The present invention is expressed as crucial point of penetration with keratinocyte CXCL10 and CXCL16, with maturation
Cell model carry out the screening of prepared from active ingredients of tripterygium wilfordii, further with molecular cytobiology technology, molecule, cell,
Animal and leucoderma crowd's level, the activation that system research thunder godvine series compound suppresses STAT1/IRF-1 paths enter one
Step reduce CXCL10 and CXCL16 expression specific molecular mechanism, acquired results be leucoderma immunological regulation treat provide theory according to
According to crucial target spot.
Brief description of the drawings
Fig. 1 is to test to determine triptolide by CCK-8, Celastrol, and triptonide is in horn cell
Suitable dosage range；
Fig. 2 is tested by CCK-8 and is determined triptolide, Celastrol, and triptonide is to oxidative stress status
The protective effect of lower melanocyte (PIG1, PIG3V)；
Fig. 3 is to test to investigate thunder godvine series compound to STAT1, p-STAT1, IRF1, NF- κ by WesternBlot
The influence of B expressions；
Fig. 4 is that horn cell is secreted after ELISA is tested and investigated thunder godvine series compound to inflammatory factor stimulation
Change the influence of factor CXCL10；
Fig. 5 is that horn cell is secreted after ELISA is tested and investigated thunder godvine series compound to inflammatory factor stimulation
Change the influence of factor CXCL16.
Specific embodiment
Can suppress CD8 the invention provides one kind+The inhibitor that T cell is killed to melanocyte, the inhibitor can press down
The expression of STAT1 transcription factors in keratinocyte processed, and then IRF1 expressions are lowered, suppress keratinocyte
Middle secretion CXCL10 and CXCL16, further reduces CXCL10 and CXCL16 to CD8+The chemotaxis of T cell, so as to suppress
CD8+T cell is killed to melanocyte；CD8 can be suppressed+T cell is thunder godvine terpenoid to the inhibitor that melanocyte is killed
Thing；This can suppress CD8+T cell is half terpenoid alkaloid, the diterpene of thunder godvine of thunder godvine times to the inhibitor that melanocyte is killed
Class compound and/or the triterpene compound of thunder godvine, especially thunder godvine half terpenoid alkaloid, the Diterpenes of thunder godvine again
The monomeric compound of the triterpene compound of compound and/or thunder godvine, such as triptolide, Celastrol and/or Thunder God
Rattan lactone ketone.The effective dose of these monomeric compounds is not higher than 80nM, preferably 1-60nM；More preferably 5-10nM.
Meanwhile, the present invention can suppress CD8 in offer+While the inhibitor that T cell is killed to melanocyte, additionally provide
One kind is based on that CD8 can be suppressed as previously described+The inhibitor combination that T cell is formed to the inhibitor that melanocyte is killed,
The inhibitor combination contains can suppress CD8 as previously described+The inhibitor that T cell is killed to melanocyte as activity into
Point, and can make that CD8 can be suppressed+The inhibitor that T cell is killed to melanocyte is stablized and/or can be strengthened can suppress CD8+T
The auxiliary material of the inhibitor effect that cell is killed to melanocyte；Auxiliary material be one or more pharmaceutically acceptable carrier and/
Or excipient.
In addition, present invention also offers CD8 can be suppressed as previously described+How is the inhibitor that T cell is killed to melanocyte
Prepare for prevent and/or treat leucoderma medicine in application.
3 kinds of effective monomer components suppress CXCL10 and CXCL16 secretion molecular mechanisms in thunder godvine provided by the present invention,
And its application in terms of therapy of vitiligo, wherein, triptolide (Triptolide), Celastrol (Celastrol)
With the transcription factor expression that triptonide (Triptonide) can suppress STAT1 in keratinocyte, IRF1 water is lowered
It is flat, the secretion of Chemokines CC XCL10 and CXCL16 is reduced, play treatment leucoderma wind action.
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited
In this.
Test sample of the present invention employed in embodiment：(1) wilfordine (LGT-1), (2) wilforine
(LGT-2), (3) wilforgine (LGT-3), (4) triptolide (LGT-4), (5) thunder godvine ester first (LGT-5), (6) thunder
Celastrol (LGT-6), (7) triptonide (LGT-7), (8) triptolide+Celastrol+triptonide
(LGT-8).Sample preparation：DMSO is solvent, and it is 1.0 × 10 to prepare compound initial concentration-2M/L；Each compound sets three
Working solution concentration, respectively 10-3、10-4And 10-5M/L。
Embodiment 1
Tested by CCK-8 and determine triptolide, Celastrol, triptonide suitable agent in horn cell
Amount scope, its result is shown in Figure 1.Cell culture：The cell density in 6000/hole is to plant in 96 orifice plates；37 DEG C, 5%CO2
Under the conditions of cultivate 24h in constant incubator after suck culture medium, then add each test sample 0.2uL (dense eventually per hole per hole
Degree DMSO 0.1%), the test sample of each concentration needs 5 multiple holes, adds 200uL fresh cultures and continues to cultivate 24h.So
After suck culture medium, add CCK-8 reagents (1：10 are diluted in culture medium) 100uL, after 37 DEG C of lucifuge temperature incubate 1h, ELIASA is surveyed
Determine OD450Light absorption value.
It will be seen from figure 1 that triptolide (LGT-4), Celastrol (LGT-6) and triptonide (LGT-
7) (5-10nM) is do not have influential, three kinds of monomer joints on the propagation of melanocyte PIG1 and PIG3V in the range of low dosage
Effect is also more notable after medication.Other compound wilfordines (LGT-1), wilforine (LGT-2), wilforgine
(LGT-3), thunder godvine ester first (LGT-5) has no significant effect in 1uM concentration level cell growths.
Embodiment 2
By CCK-8 test determine triptolide, Celastrol, triptonide to melanocyte system (PIG1,
PIG3V) protective effect under oxidative stress model, as a result refers to Fig. 2.Cell culture：The cell density in 6000/hole is
Plant in 96 orifice plates；37 DEG C, 5%CO2Under the conditions of cultivate 24h in constant incubator after suck culture medium, then added per hole each
Test sample 0.2uL (every hole final concentration DMSO 0.1%), the test sample of each concentration needs 5 multiple holes, adds 200uL new
Fresh culture medium continues to add H after cultivating 2h2O2Its final concentration is reached 800uM, continue to cultivate 24h.Then culture medium is sucked,
Add CCK-8 reagents (1：10 are diluted in culture medium) 100uL, after 37 DEG C of lucifuge temperature incubate 1h, ELIASA determines OD450Light absorption value.
Figure it is seen that triptolide (LGT-4), Celastrol (LGT-6) and triptonide (LGT-
7) Valid concentration protected to melanocyte is in 5nM~10nM.
Embodiment 3
With IFN-γ+TNF-α collective effect in after keratinocyte 24h, collection cell is carried thunder godvine series compound
Take albumen, STAT1, pSTAT1, IRF1 albumen in Western Blot analysis thunder godvine series compound Human Keratinocytes
The influence of expression, its result refers to Fig. 3.Collect cell protein, first through SDS electrophoresis after, by protein delivery to pvdf membrane
On, 1h is closed with 5%BSA room temperatures, the albumen of detection corresponding primary antibody (wherein Anti-pSTAT1, Anti- needed for applying
STAT1, Anti-IRF1, Anti-SOCS3, Anti- β-Actin are purchased from CST companies), 4 DEG C of overnight incubations.Reclaim within second day
Primary antibody, film is cleaned 3 times with TBST, each 10min, after apply secondary antibody (Goat anti-rabbit IgG-HRPGoat anti-
Mouse IgG-HRP are purchased from SANTA companies), it is incubated at room temperature 1h.Cleaned with TBST 3 times afterwards, each 10min.It is uniformly coated with afterwards
Luminescent solution, in observation on gel imaging system.
Result is as shown in figure 3, IFN-γ joint TNF-α can significantly raise the protein expression water of cell p-STAT1 and IRF1
It is flat.Compared with DMSO groups, thunder godvine series compound p-STAT1 and STAT1 level has been lowered, especially with LGT-4, LGT-
It is the most obvious that 7 and LGT-8 lowers effect.These three compounds also have significant downward to IRF1 protein expression levels simultaneously.
Embodiment 4
Test to investigate after thunder godvine series compound stimulates horn cell to IFN-γ and joint TNF-α by ELISA and divide
The influence of Chemokines CC XCL10, CXCL16 is secreted, its result refers to Fig. 4 and Fig. 5.
Result is as shown in FIG. 4 and 5：(1) after IFN-γ and medicine are incubated 24h altogether, compared with DMSO groups, LGT-6
(0.1uM levels) and LGT-8 (100ng/mL) can significantly lower the secretion of horn cell CXCL10；(2) after adjustment drug concentration,
Again with IFN-γ+After TNF-α is incubated 24h altogether, LGT-4, LGT-7 and LGT-8 can significantly lower horn cell CXCL10 and
The secretion of CXCL16.
Experimental data shows, after triptolide, Celastrol, triptonide and drug combination, can show
The generation for reducing keratinocyte secretion Chemokines CC XCL10 and CXCL16 is write, its mechanism of action is probably to lower CXCL10
With the expression of CXCL16 upstreams regulatory molecules STAT1 and NF-kB；And three kinds of later effects of monomeric compound drug combinations are more
Significantly, point out it can be used as the drug candidate of therapy of vitiligo.
Above-described embodiment is the present invention preferably implementation method, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from Spirit Essence of the invention and the change, modification, replacement made under principle, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (9)
1. one kind can suppress CD8+The inhibitor that T cell is killed to melanocyte, it is characterised in that：It is described to suppress CD8+T cell
The expression of STAT1 transcription factors in keratinocyte can be suppressed to the inhibitor that melanocyte is killed, and then lowered
IRF1 expressions, suppress to secrete CXCL10 and CXCL16 in keratinocyte, further reduce CXCL10 and CXCL16
To CD8+The chemotaxis of T cell, so as to suppress CD8+T cell is killed to melanocyte；It is described to suppress CD8+T cell is to black
The inhibitor of plain cell killing is thunder godvine terpenoid.
2. it is according to claim 1 to suppress CD8+The inhibitor that T cell is killed to melanocyte, it is characterised in that：It is described
CD8 can be suppressed+T cell is half terpenoid alkaloid, the Diterpenes of thunder godvine of thunder godvine times to the inhibitor that melanocyte is killed
Compound and/or the triterpene compound of thunder godvine.
3. it is according to claim 2 to suppress CD8+The inhibitor that T cell is killed to melanocyte, it is characterised in that：It is described
CD8 can be suppressed+T cell is half terpenoid alkaloid, the Diterpenes of thunder godvine of thunder godvine times to the inhibitor that melanocyte is killed
The monomeric compound of the triterpene compound of compound and/or thunder godvine.
4. it is according to claim 3 to suppress CD8+The inhibitor that T cell is killed to melanocyte, it is characterised in that：It is described
Monomeric compound is triptolide, Celastrol or triptonide.
5. it is according to claim 4 to suppress CD8+The inhibitor that T cell is killed to melanocyte, it is characterised in that：It is described
The effective dose level of monomeric compound is not higher than 80nM, preferably 1-60nM；More preferably 5-10nM.
6. a kind of suppressed CD8 based on described in claim 1-5 any claims+The suppression that T cell is killed to melanocyte
The inhibitor combination that agent is formed, it is characterised in that：The inhibitor combination contains claim 1-5 any claims
Described suppressed CD8+The inhibitor that T cell is killed to melanocyte is used as active component.
7. inhibitor combination according to claim 6, it is characterised in that：The inhibitor combination also includes making
Suppressed CD8 described in claim 1-5 any claims+Inhibitor stabilization and/or energy that T cell is killed to melanocyte
Can suppress CD8 described in enough enhancings+The auxiliary material of the inhibitor effect that T cell is killed to melanocyte.
8. inhibitor combination according to claim 7, it is characterised in that：The auxiliary material be one or more pharmaceutically
Acceptable carrier and/or excipient.
9. the suppressed CD8 according to claim 1-5 any claims+How is the inhibitor that T cell is killed to melanocyte
Prepare for treat leucoderma medicine in application.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710099856.2A CN106902125A (en) | 2017-02-23 | 2017-02-23 | CD8 can be suppressed+Inhibitor, inhibitor combination and application that T cell is killed to melanocyte |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710099856.2A CN106902125A (en) | 2017-02-23 | 2017-02-23 | CD8 can be suppressed+Inhibitor, inhibitor combination and application that T cell is killed to melanocyte |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106902125A true CN106902125A (en) | 2017-06-30 |
Family
ID=59208848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710099856.2A Pending CN106902125A (en) | 2017-02-23 | 2017-02-23 | CD8 can be suppressed+Inhibitor, inhibitor combination and application that T cell is killed to melanocyte |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106902125A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3095754A1 (en) * | 2019-05-10 | 2020-11-13 | Pierre Fabre Dermo-Cosmetique | Pentacyclic triterpenes in the treatment of vitiligo |
| CN112748247A (en) * | 2020-12-23 | 2021-05-04 | 复旦大学附属华山医院 | Application of antibody binding agent in preparation of auxiliary detection product for vitiligo stage and detection kit for vitiligo stage identification |
| CN113980896A (en) * | 2021-10-27 | 2022-01-28 | 中国人民解放军军事科学院军事医学研究院 | Application of IRF1 in regulating and controlling immune regulation effect of mesenchymal stem cells and product |
| RU2816950C2 (en) * | 2019-05-10 | 2024-04-08 | Пьер Фабр Дермо-Косметик | Pentacyclic triterpenes in vitiligo treatment |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101564415A (en) * | 2009-03-12 | 2009-10-28 | 江西中医学院 | Chinese medicine microemulsion preparation with enhanced percutaneous permeability and preparation method thereof |
-
2017
- 2017-02-23 CN CN201710099856.2A patent/CN106902125A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101564415A (en) * | 2009-03-12 | 2009-10-28 | 江西中医学院 | Chinese medicine microemulsion preparation with enhanced percutaneous permeability and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 周晓慧: "雷公藤对免疫功能影响的研究进展", 《长春中医学院学报》 * |
| 李俊轩等: "雷公藤搽剂外涂治疗儿童初发白癜风60例观察", 《岭南皮肤性病科杂志》 * |
| 鲁燕侠等: "白癜风治疗药物概况", 《现代生物医学进展》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3095754A1 (en) * | 2019-05-10 | 2020-11-13 | Pierre Fabre Dermo-Cosmetique | Pentacyclic triterpenes in the treatment of vitiligo |
| WO2020229403A1 (en) * | 2019-05-10 | 2020-11-19 | Pierre Fabre Dermo-Cosmetique | Pentacyclic triterpenes in the treatment of vitiligo |
| CN113905752A (en) * | 2019-05-10 | 2022-01-07 | 皮埃尔·法布尔皮肤化妆品公司 | Pentacyclic triterpenoid for treating leucoderma |
| RU2816950C2 (en) * | 2019-05-10 | 2024-04-08 | Пьер Фабр Дермо-Косметик | Pentacyclic triterpenes in vitiligo treatment |
| CN112748247A (en) * | 2020-12-23 | 2021-05-04 | 复旦大学附属华山医院 | Application of antibody binding agent in preparation of auxiliary detection product for vitiligo stage and detection kit for vitiligo stage identification |
| CN113980896A (en) * | 2021-10-27 | 2022-01-28 | 中国人民解放军军事科学院军事医学研究院 | Application of IRF1 in regulating and controlling immune regulation effect of mesenchymal stem cells and product |
| CN113980896B (en) * | 2021-10-27 | 2023-10-20 | 中国人民解放军军事科学院军事医学研究院 | Application of IRF1 in regulation and control of mesenchymal stem cell immunoregulation and product |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Raychaudhuri et al. | Revisiting the Koebner phenomenon: role of NGF and its receptor system in the pathogenesis of psoriasis | |
| Huh et al. | The natural flavonoid galangin inhibits osteoclastic bone destruction and osteoclastogenesis by suppressing NF-κB in collagen-induced arthritis and bone marrow-derived macrophages | |
| Na Takuathung et al. | Antipsoriatic effects of wannachawee recipe on imiquimod-induced psoriasis-like dermatitis in BALB/c mice | |
| Krebs et al. | Wormwood (Artemisia absinthium) suppresses tumour necrosis factor alpha and accelerates healing in patients with Crohn’s disease–a controlled clinical trial | |
| Aubdool et al. | Neurovascular aspects of skin neurogenic inflammation | |
| Unahabhokha et al. | Molecular signalings in keloid disease and current therapeutic approaches from natural based compounds | |
| Diao et al. | Astilbin protects diabetic rat heart against ischemia–reperfusion injury via blockade of HMGB1-dependent NF-κB signaling pathway | |
| Keppel Hesselink et al. | Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics | |
| Kourilová et al. | Cercarial dermatitis caused by bird schistosomes comprises both immediate and late phase cutaneous hypersensitivity reactions | |
| Kamio et al. | Vaspin attenuates RANKL-induced osteoclast formation in RAW264. 7 cells | |
| Wen et al. | Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse | |
| CN104208114A (en) | Plant extract rich in galactolipids and uses thereof | |
| CN106902125A (en) | CD8 can be suppressed+Inhibitor, inhibitor combination and application that T cell is killed to melanocyte | |
| Kant et al. | Topical application of quercetin improves wound repair and regeneration in diabetic rats | |
| Jo et al. | Antiallergic effect of fisetin on IgE-mediated mast cell activation in vitro and on passive cutaneous anaphylaxis (PCA) | |
| Ilhan et al. | Promising activity of Anthemis austriaca Jacq. on the endometriosis rat model and isolation of its active constituents | |
| Lv et al. | Portulaca oleracea L. extracts alleviate 2, 4-dinitrochlorobenzene-induced atopic dermatitis in mice | |
| Chuang et al. | 2, 4-dimethoxy-6-methylbenzene-1, 3-diol, a benzenoid from Antrodia cinnamomea, Mitigates Psoriasiform inflammation by suppressing MAPK/NF-κB phosphorylation and GDAP1L1/Drp1 translocation | |
| Durand et al. | Persistent visceral allodynia in rats exposed to colorectal irradiation is reversed by mesenchymal stromal cell treatment | |
| Bian et al. | DGT, a novel heterocyclic diterpenoid, effectively suppresses psoriasis via inhibition of STAT3 phosphorylation | |
| Singh et al. | Anti-inflammatory, anti-proliferative and anti-psoriatic potential of apigenin in RAW 264.7 cells, HaCaT cells and psoriasis like dermatitis in BALB/c mice | |
| Fan et al. | DT-13 ameliorates TNF-α-induced nitric oxide production in the endothelium in vivo and in vitro | |
| Bäumer et al. | Effects of cyclosporin A and cilomilast on activated canine, murine and human keratinocytes | |
| Chiricozzi et al. | Effective topical agents and emerging perspectives in the treatment of psoriasis | |
| Kwon et al. | Anti-atopic dermatitis effects of Parasenecio auriculatus via simultaneous inhibition of multiple inflammatory pathways |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170630 |