CN109925316B - Medicine for treating ulcerative colitis - Google Patents
Medicine for treating ulcerative colitis Download PDFInfo
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- CN109925316B CN109925316B CN201910235424.9A CN201910235424A CN109925316B CN 109925316 B CN109925316 B CN 109925316B CN 201910235424 A CN201910235424 A CN 201910235424A CN 109925316 B CN109925316 B CN 109925316B
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- 239000003814 drug Substances 0.000 title claims abstract description 23
- 206010009900 Colitis ulcerative Diseases 0.000 title claims abstract description 21
- 201000006704 Ulcerative Colitis Diseases 0.000 title claims abstract description 21
- 229940079593 drug Drugs 0.000 title claims description 9
- 230000037396 body weight Effects 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 241000699670 Mus sp. Species 0.000 abstract description 24
- 210000001072 colon Anatomy 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 10
- 230000004888 barrier function Effects 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 230000004083 survival effect Effects 0.000 abstract description 6
- 238000004904 shortening Methods 0.000 abstract description 4
- 210000004922 colonic epithelial cell Anatomy 0.000 abstract description 3
- 230000004580 weight loss Effects 0.000 abstract description 3
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 abstract 2
- 241001529936 Murinae Species 0.000 abstract 1
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 229940024473 salicylic acid emollient and protective preparations Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Images
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种治疗溃疡性结肠炎的药物，所述药物的结构式如下所示：采用本发明的药物治疗溃疡性结肠炎具有显著的疗效，包括能显著抑制小鼠体重的减轻，显著提高小鼠的存活率，显著抑制DSS诱导的小鼠结肠变短，显著抑制DSS诱导的小鼠结肠上皮细胞屏障的破坏。The invention discloses a medicine for treating ulcerative colitis, and the structural formula of the medicine is as follows: 
Using the medicine of the present invention to treat ulcerative colitis has significant curative effects, including significantly inhibiting the weight loss of mice, significantly improving the survival rate of mice, significantly inhibiting DSS-induced shortening of the colon in mice, and significantly inhibiting DSS-induced microscopic Disruption of the murine colonic epithelial cell barrier.
Description
Technical Field
The invention relates to a medicament for treating colitis, in particular to a medicament for treating ulcerative colitis.
Background
The therapeutic means of ulcerative colitis mainly include drug therapy and surgical therapy. The drug treatment comprises: (1) sulfasalazine and salicylic acid preparations are main medicines for treating ulcerative colitis, but the long-term treatment effect is poor; (2) corticosteroids, such as dexamethasone or prednisone, however long-term hormone maintenance does not prevent recurrence of ulcerative colitis; and whether the hormone can be continuously used in the chronic period is different, and has certain side effects (the steroid medicine can increase the risk of infection); (3) immunosuppressive agents, however, have questionable efficacy and may also increase the risk of infection and cancer. In conclusion, none of the current drugs for treating ulcerative colitis can achieve the effect of long-term prevention or treatment; on the other hand, after the ulcerative colitis patient is treated by the total resection of the rectum, the patient still needs to pay special attention to the care in life, and the patient must pay special attention to the combination of labor and ease, so that the patient cannot be tired too much, and particularly some patients with serious illness should be bedridden for rest in time.
Disclosure of Invention
Based on the problems, the invention aims to overcome the defects of the prior art and provide a medicament with remarkable effect on treating ulcerative colitis.
In order to achieve the purpose, the invention adopts the technical scheme that: a medicament for the treatment of ulcerative colitis, wherein the formula of said medicament (LY3009120) is as follows:
as a further optimization of the above protocol, the drug (LY3009120) was used in a dose of 20mg/KG body weight. According to needs, the medicine for treating ulcerative colitis can be prepared into tablets, pills, powder granules and the like by adding corresponding auxiliary materials on the basis of LY 3009120.
As a further optimization of the above protocol, the drug (LY3009120) was administered by intraperitoneal injection.
In conclusion, the beneficial effects of the invention are as follows:
the medicament (LY3009120) has obvious curative effects on treating ulcerative colitis, including remarkably inhibiting the weight loss of mice, remarkably improving the survival rate of the mice, remarkably inhibiting the shortening of the colon of the mice induced by DSS and remarkably inhibiting the damage of the colon epithelial cell barrier of the mice induced by DSS.
Drawings
FIG. 1 is a graph showing the results of the weight change of the mice of each group in example 1;
FIG. 2 is a graph showing the survival rate of each group of mice in example 1;
FIG. 3 is a graph showing the results of colon length in each group of mice in example 2;
FIG. 4 is a graph showing the results of the degree of disruption of the colonic epithelial cell barrier in each group of mice in example 3.
Detailed Description
The invention finds a compound LY3009120 with obvious curative effect on ulcerative colitis from the pathogenesis of the ulcerative colitis, wherein the structural formula of the LY3009120 is as follows:
this compound (LY3009120) is an anticancer drug and has been used in first-phase clinical trials. The inventor of the application finds that the application dose of LY3009120 is 20mg/Kg mouse, and the mouse has obvious curative effect on ulcerative colitis when being injected by an abdominal cavity, and the application dose is specifically embodied in the following aspects: the mouse colon epithelial cell barrier inhibitor can obviously inhibit the weight loss of mice, obviously improve the survival rate of the mice, obviously inhibit the shortening of the mouse colon induced by DSS and obviously inhibit the damage of the mouse colon epithelial cell barrier induced by DSS.
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the accompanying drawings and specific embodiments. Unless otherwise specified, the experimental methods in the present invention are all conventional methods; unless otherwise specified, the concentrations of the reagents in the present invention are mass concentrations; the materials or agents of the present invention are commercially available or may be obtained from other publicly available sources, unless otherwise specified.
Example 1 study of LY3009120 on the changes in body weight and survival rates of DSS-induced ulcerative colitis mice
The experimental method comprises the following steps: 22-24g male C57BL/6 mice, divided into 2 groups (8 mice per group): vehicle group (PBS containing 10% DMSO and 20% cyclodextin) and LY3009120 group (20mg/Kg mic dissolved in PBS containing 10% DMSO and 20% cyclodextin). 3% DSS (dextran sulfate sodium) was fed daily and Vehicle or LY3009120(20mg/Kg mice) was intraperitoneally injected daily, seven days later, the DSS was withdrawn and the intraperitoneal injection of Vehicle or LY3009120 was continued, 3 days later, no more injections were given. Mice were weighed daily and counted for mortality, and the results are shown in figures 1 and 2.
The experimental results are as follows: figure 1 shows that LY3009120 significantly inhibited the reduction of body weight in mice, P <0.05, > P <0.01, > P < 0.001; fig. 2 shows that LY3009120 can significantly improve the survival rate of mice.
Example 2 Effect of LY3009120 on Colon Length in DSS-induced ulcerative colitis mice
The experimental method comprises the following steps: 22-24g male C57BL/6 mice, divided into 3 groups: control group 4, DMSO group 4, LY3009120 group 4. The control group was fed water daily; the group of Vehicle and LY3009120 was fed 3% DSS daily and Vehicle or LY3009120(20mg/Kg mice) was intraperitoneally injected daily, seven days later, the DSS was removed and the length of the colon of the mice was measured. The experimental result is shown in figure 3, and the result shows that LY3009120 can obviously inhibit DSS-induced colon shortening of mice.
Example 3 Effect of LY3009120 on DSS-induced disruption of the intestinal epithelial cell barrier in ulcerative colitis
The experimental method comprises the following steps: 22-24g male C57BL/6 mice, divided into 3 groups: control group 4, DMSO group 4, LY3009120 group 4. The control group was fed water daily; groups of Vehicle and LY3009120 were fed 3% DSS daily and Vehicle or LY3009120(10mg/Kg mice) were intraperitoneally injected daily, seven days later, the DSS was removed, colon tissue was removed, fixed with 4% paraformaldehyde, and HE stained. The experimental results are shown in fig. 4, and fig. 4 shows that LY3009120 can significantly inhibit DSS-induced disruption of the mouse colonic epithelial cell barrier.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910235424.9A CN109925316B (en) | 2019-03-26 | 2019-03-26 | Medicine for treating ulcerative colitis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910235424.9A CN109925316B (en) | 2019-03-26 | 2019-03-26 | Medicine for treating ulcerative colitis |
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| CN109925316A CN109925316A (en) | 2019-06-25 |
| CN109925316B true CN109925316B (en) | 2021-09-14 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111803618B (en) * | 2020-06-03 | 2023-05-05 | 桂林医学院附属医院 | Application of GPRP acetate in preparation of medicines for treating ulcerative colitis |
| CN116509876B (en) * | 2023-04-24 | 2024-08-30 | 大连理工大学 | Corticosteroid drug loaded polycyclodextrin-tannic acid nanoparticle as well as preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016184999A1 (en) * | 2015-05-20 | 2016-11-24 | Pamgene Bv | Method for predicting the response of melanoma patients to targeted pharmacotherapy |
| CN109072311A (en) * | 2016-04-15 | 2018-12-21 | 豪夫迈·罗氏有限公司 | Diagnostic and therapeutic method for cancer |
| CN109223790A (en) * | 2018-09-20 | 2019-01-18 | 广州医科大学附属第二医院 | UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug |
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2019
- 2019-03-26 CN CN201910235424.9A patent/CN109925316B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016184999A1 (en) * | 2015-05-20 | 2016-11-24 | Pamgene Bv | Method for predicting the response of melanoma patients to targeted pharmacotherapy |
| CN109072311A (en) * | 2016-04-15 | 2018-12-21 | 豪夫迈·罗氏有限公司 | Diagnostic and therapeutic method for cancer |
| CN109223790A (en) * | 2018-09-20 | 2019-01-18 | 广州医科大学附属第二医院 | UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug |
Non-Patent Citations (1)
| Title |
|---|
| pan—RAF抑制剂LY3009120对分化型甲状腺癌细胞增殖、侵袭和迁移;樊新龙等;《Modem 0ncology》;20181231;第26卷(第22期);第3554-3557页 * |
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