CN108354920A - A kind of application of sulfoxide compound in treating inflammatory bowel disease - Google Patents
A kind of application of sulfoxide compound in treating inflammatory bowel disease Download PDFInfo
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Abstract
The present invention provides a kind of application of sulfoxide compound in treating inflammatory bowel disease, which has logical formula (I) structure as follows,The sulfoxide compound has therapeutic effect to ulcerative colitis acute stage mouse, ulcerative colitis chronic phase mouse and Crohn disease mouse, can be applied to the drug for treating or preventing inflammatory bowel disease.
Description
Technical field
The present invention relates to the technical fields of pharmacy, and in particular, to a kind of sulfoxide compound is in treating inflammatory bowel disease
Using.
Background technology
Inflammatory bowel disease (inflammatory bowel disease, IBD) is a kind of intestinal inflammatory of chronic nonspecific
Disease, the course of disease repeatedly, are clinically mainly shown as abdominal pain, diarrhea, mucopurulent bloody stool and the symptoms such as tenesmus, pathology
Feature is colonic mucosa chronic inflammation, intestinal mucosa ulcer or has transmural granuloma to be formed.Epidemiological study finds that IBD exists
The incidence of North America and Europe is higher, but Asian-Pacific area incidence gradually rises in recent years, wherein China becomes Asia and sends out
One of sick higher country of rate.IBD is apt to occur in person between twenty and fifty, average age of onset 39 years old, and is mainly in male, and proportion up to accounts for
59%, in coming 10 years inflammatory bowel disease or will be as " mainstream " disease of digestive tract of asian population.Ulcerative colitis
(ulcerative colitis, UC) and Crohn disease (Crohn ' s disease, CD) are two kinds of main Types of IBD, and CD can
Entire alimentary canal is betided, terminal ileum and right hemicolon are common in, lesion involves intestinal wall holostrome, shows segmental, E Kou
, there is granuloma gangraenescens in sore sample ulcer.UC is mainly in rectum and sigmoid colon, and lesion involves mucous layer and submucosa, is in
Reveal continuity, diffusivity ulcer, with congested and oedema, recurrent is high.In addition, colorectal cancer occurs for UC patient
The probability of (colorectal cancer, CRC) obviously increases, and is higher than nearly 20 times of general population.UC patient more than 20% is true
Colitis correlation colon cancer (colitis-associated cancer, CAC) can be developed by examining in 30 years, the death rate is up to
50% or more.
A kind of chronic refractory diseases of the IBD as protracted course of disease, pathogenesis are still not clear, are widely considered to be at present
Caused by many factors such as environment, heredity, intestinal flora and immune response interact.Currently, can't control completely IBD
More, it there is no high specificity and the small drug of toxic side effect, inflammation control, Immunity regulation be mainly based upon to the treatment of IBD
And control breaking-out and maintenance are alleviated.Traditional medicine includes mainly Salicylic Acid Formulations, glucocorticoid and immunosupress
Agent three categories.But side effect is larger, incidence is higher, cannot be used for a long time.In biological agent, TNF-t and a monoclonal antibodies
It is the newtype drug for being applied to IBD treatments in recent years, is all shown in terms of control disease symptoms, promotion mucous membrane healing good
Effect, application at present more mainly infliximab (infliximab, IFX) and adalimumab
(adalimumab), but only resist and be suitable for maintaining treatment.
So for inflammatory bowel disease exploitation with definite therapeutic effect and the low newtype drug of toxic side effect is with important
Meaning and social demand, and wide market.
Invention content
In view of the above problems, the application the present invention provides a kind of sulfoxide compound in treating inflammatory bowel disease, wherein institute
Stating sulfoxide compound has logical formula (I) structure as follows：
In use above, the inflammatory bowel disease includes ulcerative colitis and Crohn disease.
In use above, the ulcerative colitis includes that ulcerative colitis acute stage and ulcerative colitis are chronic
Phase.
In use above, the dosage of the sulfoxide compound is 5mg/Kg to 20mg/Kg.
The present invention also provides a kind of drugs treating or preventing inflammatory bowel disease, including：Sulfoxide compound and pharmaceutically
Acceptable carrier.
In said medicine, the pharmaceutically acceptable carrier includes diluent, excipient, filler, adhesive, wet
Moisten the one or more of agent, disintegrant, sorbefacient, surfactant, absorption carrier, lubricant and synergist.
In said medicine, the preparation of the drug includes injection, tablet, pill, capsule, suspending agent or emulsion.
Through the invention it is found that sulfoxide compound is to ulcerative colitis acute stage mouse, ulcerative colitis chronic phase
Mouse and Crohn disease mouse have therapeutic effect, and sulfoxide compound effect is better than positive drug salicylazosulfapyridine (SASP)
Effect, can be applied to treat or prevent inflammatory bowel disease drug.
Description of the drawings
Fig. 1 is ulcerative colitis acute stage mouse weight curve；
Fig. 2 is ulcerative colitis acute stage mouse disease activity index curve；
Fig. 3 is ulcerative colitis acute stage mouse Colon and rectum length column diagram；
Fig. 4 A are the human colorectal general forms of ulcerative colitis acute stage mouse, and Fig. 4 B are that human colorectal general form is commented
Divide column diagram；
Fig. 5 A are ulcerative colitis acute stage mouse colorectal carcinoma degree of impairment, and Fig. 5 B are that colorectal carcinoma damage is commented
Divide column diagram；
Fig. 6 is ulcerative colitis chronic phase mouse Colon and rectum length column diagram；
Fig. 7 A are ulcerative colitis chronic phase mouse Colon and rectum general forms, and Fig. 7 B are Colon and rectum general form scoring columns
Shape figure；
Fig. 8 A are ulcerative colitis chronic phase mouse colorectal carcinoma degree of impairment, and Fig. 8 B are that colorectal carcinoma damage is commented
Divide column diagram；
Fig. 9 is Crohn disease mouse Colon and rectum length column diagram；
Figure 10 is Crohn disease mouse Colon and rectum general form scoring column diagram；
Figure 11 is Crohn disease mouse colorectal carcinoma Injury score column diagram.
Specific implementation mode
In order to better illustrate the present invention, it will be described the specific implementation mode of the present invention below.
The present invention provides a kind of application of sulfoxide compound in treating inflammatory bowel disease, wherein the sulfoxide compound has
There is following general formula (I) structure：
Ulcerative colitis acute stage model, ulcerative colitis chronic phase model and Crow is respectively adopted in the following example
Three kinds of inflammatory bowel disease models of grace disease model evaluate the drug effect of JY4, but do not limit the invention in any way.
(1) JY4 studies the therapeutic effect of ulcerative colitis acute stage mouse
1.1 experimental method
It is BALB/c mouse (albino lab mouse), female, 18~22g, SPF (nothings that animal strains are selected in this experiment
Special pathogen) rank, totally 48 only for reagent product：Compound JY4.Positive control drug：Salicylazosulfapyridine (SASP).Modeling lures
Lead agent：Dextran sulfate sodium (DSS).
1.1.1 model foundation
Using DSS induced ulcerative colitis acute models.In the laundering period, mouse ad lib and drinking-water are given, it is real
It tests and starts to change drinking water into DSS solution (except Normal group) that mass fraction is 3-5%, freely drunk to mouse.
Every mouse daily drink amount is calculated by 6mL, and next day supplements enough DSS solution Summer Solstice or the Winter Solstice amounts of drinking water, after DSS solution gives 3-5 days altogether,
It was found that soft stool, diarrhea or bloody stool phenomenon occurs in mouse, model foundation success, until experiment terminates, DSS solution is persistently drunk.
1.1.2 grouping and administration
Mouse is grouped according to weight, every group 8, including Normal group (Normal), model control group
(Model), positive controls (SASP-200mg/kg), administration group JY4 (5mg/kg), administration group JY4 (10mg/kg), administration group
JY4(20mg/kg).It is administered using gavage mode, 0.1mL or so.Dosage is respectively：Normal group and model control group are small
The medical saline solutions of 0.1mL are given once daily in mouse, and saline solutions of the 0.1mL containing salicylazosulfapyridine is given once daily in positive controls mouse
(200mg/kg), administration group mouse give 0.1mL saline solutions containing JY4 (5mg/kg, 10mg/kg, 20mg/kg) respectively daily.Often
General animation, fecal character and the diarrhea and bloody stool situation of its observation mouse, and weigh in.Peaceful and comfortable place after administration 7 days
Dead whole mouse, exposure mouse peritoneal take Colon and rectum and measure length；Along mesenterium direction will tie, rectum is longitudinally cut off, life
It manages brine and cleans excrement, be fixed using 10% neutral formalin solution.Stereomicroscope observation anatomical lesion simultaneously carries out
It after scoring, takes and makees pathologic finding at severe ulceration, be dehydrated successively, paraffin embedding, slice, HE dyeing, microscopically observation
The lesion situation of tissue simultaneously scores.
1.2. experimental result
(1) influences of the JY4 to ulcerative colitis acute stage mouse weight
As shown in Figure 1, compared with model control group, each dosage groups of JY4 and positive controls (SASP-200mg/kg) weight
It is all higher than model control group；Compared with positive controls, each dosage group weight of JY4 is more than positive controls, and difference has statistics
Learn meaning (P<0.05).The result shows that JY4 has apparent abated effect, and effect to ulcerative colitis acute stage weight loss
Better than positive drug SASP.
(2) influences of the JY4 to ulcerative colitis acute stage mouse disease activity index
Normal group mouse behavior is active, hair color is shinny, fur is smooth；Model control group mouse is apathetic, lazy move,
Rough coat is matt, and basic, normal, high group of mouse general activity of positive controls and JY4 is in order, and fur is smooth, hair
Color is shinny, appetite improves.It scores mouse disease activity index for weight loss and excrement situation, as shown in Figure 2.
As shown in Figure 2, compared with Normal group, the scoring of model control group mouse disease activity index is obviously increased, poor
Different statistically significant (P<0.05)；Compared with model control group, each dosage groups of JY4 and positive controls disease activity index
Scoring is substantially reduced, and difference all has statistical significance (P<0.05)；Compared with positive controls (SASP-200mg/kg),
The scoring of JY4 high dose group disease activity index is below positive controls, in JY4 and the scoring of low dose group disease activity index in
Positive controls are suitable, and difference all has statistical significance (P<0.05).The result shows that JY4 can be substantially reduced exedens knot
The disease activity index of enteritis chmice acute phase scores, and effect is better than positive drug SASP.
(3) influences of the JY4 to ulcerative colitis acute stage mouse Colon and rectum length
From the figure 3, it may be seen that compared with Normal group, model control group Colon and rectum is obviously shortened；Compared with model control group,
JY4 low, middle and high dose groups Colon and rectum length is considerably longer than to model control group, in addition, positive controls (SASP-200mg/
Kg) mouse Colon and rectum is also considerably longer than model control group, but is significantly shorter than the middle and high dosage group Colon and rectum length of JY4；Each dose of JY4
Colon and rectum length is compared between amount, and middle and high dosage group Colon and rectum is considerably longer than low dose group (P<0.05).The result shows that
JY4 can obviously restore the Colon and rectum length of ulcerative colitis acute stage mouse, and middle and high dosage group is with obvious effects to be better than positive drug
SASP。
(4) influences of the JY4 to ulcerative colitis acute stage mouse Colon and rectum general form
The observation of mouse Colon mucous membrane general form is as shown in Figure 4 A, and Normal group mouse mucous membrane wrinkle wall is neatly smooth.It bursts
In ulcer colitis acute stage model, model control group mouse duplicature disappears, the hyperemia of mucous membrane diffusivity, oedema, stria vascularis
Reason is disorderly, has a large amount of mucus or purulence blood secretion in enteric cavity, it is seen that rotten to the corn and ulcer is formed, and ulcer surface is larger, boundary clear, scorching
Disease significant reaction, some mouse intestinal walls thicken, and with surrounding tissue adhesion；Positive controls (SASP-200mg/kg) and
Each dosage group mouse Colon and rectums of JY4 substantially lesion is obviously lighter than the restitution of the middle and high dosage group of model group, especially JY4 more
Obviously.
General form appraisal result is as shown in Figure 4 B, and model control group score value is significantly higher；Positive controls and JY4
Low, middle and high dose groups score value is significantly lower than model control group；Middle and high dosage group lesion score is significantly lower than positive controls；
Compare between each dosage groups of JY4, middle and high dosage group scoring is significantly lower than low dose group, the statistically significant (P of difference<
0.05).The result shows that JY4 can obviously restore the mucosa ulcer situation of ulcerative colitis acute stage, middle and high dosage group effect
It is substantially better than positive drug SASP.
(5) influence that JY4 damages ulcerative colitis acute stage mouse colorectal carcinoma
The observation of mouse Colon mucous membrane tissue is as shown in Figure 5A, Normal group mouse Colon institutional framework rule, mucous layer,
Submucosa and muscle layer and placenta percreta are complete, and each layer of colon is clear in structure, body of gland marshalling, it is seen that less inflammatory cell leaching
Profit.The damage of model control group mouse Colon mucous membrane is more serious, and mucosal epithelial cells fall off, and body of gland is disorganized in mucous membrane, becomes
Shape even lacks, and crypt abscess is formed, with congested, oedema, it is seen that a large amount of neutrophil leucocyte, lymphocytic infiltrations.It is positive right
It falls off according to group (SASP-200mg/kg) and JY4 low dose group mucosal epitheliums, mild hyperaemia, oedema, inflammatory cell infiltration weaken；
The middle and high dosage group mouse lesions of JY4 are substantially reduced, and ulcer healing, mucous membrane is complete, and inflammatory cell infiltration obviously subtracts compared with model group
It is few.
Score of tissue damage result is as shown in Figure 5 B, and model control group colorectal carcinoma Injury score value is apparently higher than normally
Control group；Compared with model control group, the score of tissue damage of the basic, normal, high dosage of JY4 and positive controls is substantially reduced；
Compared with positive controls, the middle and high dosage group scorings of JY4 are substantially reduced；Compare between each dosage groups of JY4, middle and high dosage group is commented
Divide and be significantly lower than low dose group, difference has statistical significance (P<0.05).The result shows that JY4 can substantially reduced exedens knot
Enteritis acute stage mouse colorectal carcinoma damage, reduce mucous membrane fall off necrosis and cell infiltration degree, middle and high dosage group effect
It is substantially better than positive drug SASP.
(2) JY4 studies the therapeutic effect of ulcerative colitis chronic phase mouse
It is BALB/c mouse that animal strains are selected in this experiment, and female, 18~22g, SPF ranks, totally 48 only for reagent product：Change
Close object JY4.Positive control drug：Salicylazosulfapyridine (SASP).Modeling derivant：Dextran sulfate sodium (DSS).
2.1. experimental method
2.1.1 model foundation
Using DSS induced ulcerative colitis chronic models.In the laundering period, mouse ad lib and drinking-water are given, it is real
It tests and starts to change drinking water into DSS solution (except Normal group) that mass fraction is 3%, freely drunk to mouse.Often
Mouse daily drink amount is calculated by 6mL, and next day supplements enough DSS solution Summer Solstice or the Winter Solstice amounts of drinking water, and DSS solution is used instead after giving 7 days altogether
Drinking water, free water recycle a period, model successfully according to the method described above after 7 days.Until experiment terminate, always according to
Above-mentioned cycle.
2.1.2 grouping and administration
It is consistent with 1.1.2 methods；Administration time 14 days.
2.2. experimental result
(1) influences of the JY4 to ulcerative colitis chronic phase mouse Colon and rectum length
Influences of the JY4 to ulcerative colitis chronic phase mouse Colon and rectum length is as shown in fig. 6, it will be appreciated from fig. 6 that with normal
Control group is compared, and model control group Colon and rectum is obviously shortened；Compared with model control group, JY4 low, middle and high dose groups Colon and rectums
Length is considerably longer than to model control group, in addition, positive controls (SASP-200mg/kg) mouse Colon and rectum is also considerably longer than
Model control group, but it is significantly shorter than the middle and high dosage group Colon and rectum length of JY4；Colon and rectum length is compared between each dosage of JY4
Compared with middle and high dosage group Colon and rectum is considerably longer than low dose group, and difference has statistical significance (P<0.05).The result shows that JY4
The Colon and rectum length of ulcerative colitis chronic phase mouse can obviously be restored, middle and high dosage group is with obvious effects to be better than positive drug
SASP。
(2) influences of the JY4 to ulcerative colitis chronic phase mouse Colon and rectum general form
The observation of mouse Colon mucous membrane general form is as shown in Figure 7 A, and Normal group mouse mucous membrane wrinkle wall is neatly smooth.It bursts
In ulcer colitis acute stage model, model control group mouse duplicature disappears, the hyperemia of mucous membrane diffusivity, oedema, stria vascularis
Reason is disorderly, has a large amount of mucus or purulence blood secretion in enteric cavity, it is seen that rotten to the corn and ulcer is formed, and ulcer surface is larger, boundary clear, scorching
Disease significant reaction；Positive controls and each dosage group mouse Colon and rectums of JY4 substantially lesion are obviously lighter than model group, in especially JY4,
High dose group restitution becomes apparent from.
General form appraisal result is as shown in Figure 7 B, and model control group score value is significantly higher；Positive controls and JY4
Low, middle and high dose groups score value is significantly lower than model control group；Middle and high dosage group lesion score is significantly lower than positive controls,
Compare between each dosage groups of JY4, middle and high dosage group scoring is significantly lower than low dose group, the statistically significant (P of difference<
0.05).The result shows that JY4 can obviously restore the mucosa ulcer situation of ulcerative colitis chronic phase, middle and high dosage group effect
It is substantially better than positive drug SASP.
(3) influence that JY4 damages ulcerative colitis chronic phase mouse colorectal carcinoma
The observation of mouse Colon mucous membrane tissue is as shown in Figure 8 A, Normal group mouse Colon institutional framework rule, mucous layer,
Submucosa and muscle layer and placenta percreta are complete, and each layer of colon is clear in structure, body of gland marshalling, it is seen that less inflammatory cell leaching
Profit.The damage of model control group mouse Colon mucous membrane is more serious, and mucosal epithelial cells fall off, and body of gland is disorganized in mucous membrane, becomes
Shape even lacks, and crypt abscess is formed, with congested, oedema, it is seen that a large amount of neutrophil leucocyte, lymphocytic infiltrations.It is positive right
It falls off according to group and JY4 low dose group mucosal epitheliums, mild hyperaemia, oedema, inflammatory cell infiltration weaken；The middle and high dosage groups of JY4 are small
Mouse lesion is substantially reduced, and ulcer healing, mucous membrane is complete, and inflammatory cell infiltration is significantly reduced compared with model group.
Score of tissue damage result is as shown in Figure 8 B, and model control group colorectal carcinoma Injury score value is apparently higher than normally
Control group；Compared with model control group, the score of tissue damage of the basic, normal, high dosage of JY4 and positive controls is substantially reduced；
Compared with positive controls, the middle and high dosage group scorings of JY4 are substantially reduced；Compare between each dosage groups of JY4, middle and high dosage group is commented
Divide and be significantly lower than low dose group, difference has statistical significance (P<0.05).The result shows that JY4 can substantially reduced exedens knot
Enteritis chronic phase mouse colorectal carcinoma damage, reduce mucous membrane fall off necrosis and cell infiltration degree, middle and high dosage group effect
It is substantially better than positive drug SASP.
(3) JY4 studies the therapeutic effect of Crohn disease mouse
It is BALB/c mouse that animal strains are selected in this experiment, and female, 18~22g, SPF ranks, totally 42 only for reagent product：Change
Close object JY4.Positive control drug：Salicylazosulfapyridine (SASP).Modeling derivant：Trinitrobenzene sulfonic acid (TNBS).
3.1 experimental method
3.1.1 model foundation
Crohn disease model is induced using TNBS.Mouse ad lib and drinking-water are given, experiment starts to be injected intraperitoneally first
Appropriate 10% (mass fraction) chloraldurate light anesthesia mouse, the conduit for being about 2mm with diameter are inserted into after lubrication from anus
Colon about 4cm.Every mouse of Normal group injects 0.1mL physiological saline, and every mouse of solvent control group injects 0.1mL
50% ethanol solution, remaining every mouse inject 50% ethanol solution (120mg/kg) of isometric 24mg/mL TNBS.
It holds rat-tail end and is inverted 5min, be put into after drug fully absorbs in cage and continue to raise.Bowel lavage for 24 hours after, mouse i.e. occur soft stool,
Diarrhea or bloody stool phenomenon, model successfully.
3.1.2 grouping and administration
It is consistent with 1.1.2 methods；Administration time 7 days.
3.2 analysis of experimental results
(1) influences of the JY4 to the Colon and rectum length of Crohn disease mouse
Colorectal disease situation is evaluated by measuring the Colon and rectum length of mouse, as shown in Figure 9：
Compared with Normal group, model control group Colon and rectum is obviously shortened；Compared with model control group, JY4 is low, in,
High dose group Colon and rectum length is considerably longer than to model control group, in addition, positive controls (SASP-200mg/kg) mouse knot
Rectum is also considerably longer than model control group, but is significantly shorter than the middle and high dosage group Colon and rectum length of JY4；It is tied between each dosage of JY4 straight
Intestines length is compared, and middle and high dosage group Colon and rectum is considerably longer than low dose group, and difference has statistical significance (P<0.05).
The result shows that JY4 can obviously restore the Colon and rectum length of Crohn disease mouse, middle and high dosage group is with obvious effects to be better than positive drug
SASP。
(2) influences of the JY4 to Crohn disease mouse Colon and rectum general form
Mouse Colorectal mucosa general form situation is observed, and carries out general form scoring, appraisal result is as shown in Figure 10：
Compared with Normal group and ethanol control group, model control group score value is significantly higher；Positive controls and JY4 are basic, normal, high
Dosage group score value is significantly lower than model control group；Low, middle and high dose groups lesion score is significantly lower than positive controls (SASP-
200mg/kg), compare between each dosage groups of JY4, low, middle and high dose groups have dose dependent, the statistically significant (P of difference
<0.05).The result shows that JY4 can obviously restore the mucosa ulcer situation of Crohn disease mouse, it is with obvious effects to be better than positive drug
SASP。
(3) influence that JY4 damages Crohn disease mouse colorectal carcinoma
Mouse Colon mucous membrane tissue is observed, and carries out score of tissue damage, appraisal result is as shown in figure 11：
The result shows that model control group colorectal carcinoma Injury score value is apparently higher than Normal group；With model comparison
Group is compared, and the score of tissue damage of the basic, normal, high dosage of JY4 and positive controls is substantially reduced；Compared with positive controls,
The middle and high dosage group scorings of JY4 are substantially reduced；Compare between each dosage groups of JY4, middle and high dosage group scoring is significantly lower than low dosage
Group, difference have statistical significance (P<0.05).The result shows that JY4 can substantially reduced Crohn disease Mice Mice Colon and rectum group
It knits damage, reduces mucous membrane and fall off necrosis and cell infiltration degree, middle and high dosage group is with obvious effects to be better than positive drug SASP.
In summary, JY4 (sulfoxide compound) is small to ulcerative colitis acute stage mouse, ulcerative colitis chronic phase
Mouse and Crohn disease mouse have therapeutic effect, and middle and high dosage group is with obvious effects better than positive drug SASP.
In addition, JY4 and pharmaceutically acceptable carrier can be prepared into the drug for treating or preventing inflammatory bowel disease, it is subjected to
Carrier include diluent, excipient, filler, adhesive, wetting agent, disintegrant, sorbefacient, surfactant, suction
Appendix body, lubricant and synergist it is one or more；And can be made injection, tablet, pill, capsule, suspending agent or
The form of emulsion.
The specific implementation mode that these are only the present invention, is not intended to limit the invention, all spirit and original in the present invention
Within then, any modification, equivalent replacement, improvement and so on should all be included in the protection scope of the present invention.
Claims (7)
1. a kind of application of sulfoxide compound in treating inflammatory bowel disease, wherein the sulfoxide compound has logical formula (I) as follows
Structure：
2. application according to claim 1, wherein the inflammatory bowel disease includes ulcerative colitis and Crohn disease.
3. application according to claim 2, wherein the ulcerative colitis includes ulcerative colitis acute stage and bursts
Ulcer colitis chronic phase.
4. application according to claim 1, wherein the dosage of the sulfoxide compound is 5mg/Kg to 20mg/Kg.
5. a kind of drug treating or preventing inflammatory bowel disease, including：Sulfoxide compound and pharmaceutically acceptable carrier.
6. drug according to claim 5, wherein the pharmaceutically acceptable carrier includes diluent, excipient, fills out
Fill one kind of agent, adhesive, wetting agent, disintegrant, sorbefacient, surfactant, absorption carrier, lubricant and synergist
Or it is a variety of.
7. drug according to claim 5, wherein the preparation of the drug includes injection, tablet, pill, glue
Capsule, suspending agent or emulsion.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106146429A (en) * | 2015-04-21 | 2016-11-23 | 天津国际生物医药联合研究院 | The structure of isosulfocyanate precursor compound, prepare and apply |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106146429A (en) * | 2015-04-21 | 2016-11-23 | 天津国际生物医药联合研究院 | The structure of isosulfocyanate precursor compound, prepare and apply |
Non-Patent Citations (2)
| Title |
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| HUIJEONG AHN等: "Dimethyl sulfoxide inhibits NLRP3 inflammasome activation", 《IMMUNOBIOLOGY》 * |
| YING JIANG等: "Therapeutic effects of isothiocyanate prodrugs on rheumatoid arthritis", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
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