CN109223790A - UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug - Google Patents
UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug Download PDFInfo
- Publication number
- CN109223790A CN109223790A CN201811118579.6A CN201811118579A CN109223790A CN 109223790 A CN109223790 A CN 109223790A CN 201811118579 A CN201811118579 A CN 201811118579A CN 109223790 A CN109223790 A CN 109223790A
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- China
- Prior art keywords
- colon
- colitis
- drug
- ucf
- traumatic
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Classifications
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Abstract
The embodiment of the invention discloses UCF-101 to prepare the purposes in Traumatic Colon treatment or prevention drug and the drug for treating or preventing Traumatic Colon.The embodiment of the present invention, which has the advantages that, provides new treatment or prevention drug for Traumatic Colon, can be used for the treatment of colitis, especially ulcerative colitis, has a good application prospect.
Description
Technical field
The present invention relates to pharmaceutical technologies, and in particular to UCF-101 is in preparing Traumatic Colon treatment or prevention drug
Purposes.
Background technique
Ulcerative colitis is a kind of colon that the cause of disease is not still fully aware of and rectum chronic nonspecific inflammation disease,
Lesion is confined to colorectal mucosa and submucosa.It is now recognized that inflammatory bowel disease is that allogenic material causes host response, gene to be lost
Pass the result with immune imbalance interaction.
Currently, the treatment about ulcerative colitis mainly has drug therapy and operative treatment.Drug therapy includes: (1)
Salicylazosulfapyridine, Salicylic Acid Formulations are primary treatment therapeutic agents；(2) corticosteroid, such as dexamethasone or prednisone,
But long-term hormone maintenance can not prevent from recurring；And whether should continue still to disagree using hormone in chronic phase, and have certain
Side effect；(3) immunosuppressor, but its curative effect remain it is doubtful.Moreover, these drugs cannot reach long-term prevention or treatment at present
Effect.
Therefore, the mechanism for studying ulcerative colitis excavates new therapy target, for blocking the disease of ulcerative colitis
Cheng Jinzhan and improvement prognosis have important clinical value.
Summary of the invention
The UCF-101 that is designed to provide of the embodiment of the present invention is preparing the use in Traumatic Colon treatment or prevention drug
On the way, to provide new treatment or prevention drug for Traumatic Colon.
To achieve the above object, first aspect of the embodiment of the present invention provide UCF-101 prepare Traumatic Colon treatment or
Purposes in prophylactic agent.
UCF-101 is referred to as:
Dihydro-5-[[5-(2-nitrophenyl)-2-furanyl]methylene]-1,3-diphenyl-2-
thioxo-4,6(1H,5H)-pyrimidinedione。
The molecular formula of UCF-101 is C27H17N3O5S, structural formula are
Preferably, the Traumatic Colon includes colitis.
Further, the colitis includes ulcerative colitis.
Preferably, the Traumatic Colon, which treats or prevents drug, at least has any one of following or multinomial effect: reducing
The death rate caused by colitis, weight loss caused by reduction colitis, colon lengths caused by reduction colitis are shortened, are reduced
Colon epithelial cell barrier function destroys.
The Traumatic Colon therapeutic agent necessarily includes UCF-101, and take UCF-101 as the effective component of above-mentioned effect.
Preferably, UCF-101 be the Traumatic Colon treat or prevent drug one of effective component or it is unique effectively at
Point.
It can be single composition substance that the Traumatic Colon, which treats or prevents drug, or multi-component compound.
The Traumatic Colon treats or prevents the form of drug without specifically limited, can be solid-state, liquid, gel, semi-fluid
Matter, the various material forms such as haze.
The Traumatic Colon treat or prevent drug mainly for object be mammal, as rodent, spirit are long
Class animal etc..
Second aspect of the embodiment of the present invention, which provides UCF-101, has effects that any one of following or multinomial drug in preparation
In purposes: reduce colitis caused by the death rate, reduce colitis caused by weight loss, reduce colitis caused by colon
Length shortens, reduces the destruction of colon epithelial cell barrier function.
The third aspect of the embodiment of the present invention provide it is a kind of for treating or preventing the drug of Traumatic Colon, it is described for controlling
It treats or the drug of prevention Traumatic Colon includes a effective amount of UCF-101.
Preferably, the Traumatic Colon includes colitis.
Further, the colitis includes ulcerative colitis.
Preferably, described for treating or preventing daily dose >=10mg/Kg effective object weight of the drug of Traumatic Colon.
Effective object is mammal, and the mammal is preferably that rodent, artiodactylous animals, Perissodactyla are dynamic
Object, Lagomorph, primate etc..The primate is preferably monkey, ape or people.Rodent can be small
Mouse.
The embodiment of the present invention, which has the advantages that, provides new treatment or prevention drug for Traumatic Colon, can be used for tying
The treatment of enteritis, especially ulcerative colitis, has a good application prospect.
Detailed description of the invention
Fig. 1 is each group mouse weight result of variations display diagram in the embodiment of the present invention 1.
Fig. 2 is each group mouse Colon length sequences display diagram in embodiment 2.
Fig. 3 is the extent of the destruction result of each group mouse Colon epithelial cell barriers in embodiment 3.
Specific embodiment
Embodiments of the present invention are illustrated by particular specific embodiment below, those skilled in the art can be by this explanation
Content disclosed by book is understood other advantages and efficacy of the present invention easily.
It should be clear that this specification structure depicted in this specification institute accompanying drawings, ratio, size etc., only to cooperate specification to be taken off
The content shown is not intended to limit the invention enforceable qualifications so that those skilled in the art understands and reads, therefore
Do not have technical essential meaning, the modification of any structure, the change of proportionate relationship or the adjustment of size are not influencing the present invention
Under the effect of can be generated and the purpose that can reach, it should all still fall in disclosed technology contents and obtain the model that can cover
In enclosing.Meanwhile cited such as "upper", "lower", " left side ", the right side in this specification ", the term of " centre ", be merely convenient to chat
That states is illustrated, rather than to limit the scope of the invention, relativeness is altered or modified, and is changing skill without essence
It is held in art, when being also considered as the enforceable scope of the present invention.
Unless otherwise stated, disclosed in this invention experimental method, detection method, preparation method be all made of this technology neck
Molecular biology, biochemistry, chromatin Structure and the analysis of domain routine, analytical chemistry, cell culture, recombinant DNA technology and
The routine techniques of related fields.These technologies have perfect explanation in the prior art, and for details, reference can be made to Sambrook etc.
MOLECULAR CLONING:A LABORATORY MANUAL, Second edition, Cold Spring Harbor
Laboratory Press, 1989and Third edition, 2001；Ausubel etc., CURRENT PROTOCOLS IN
MOLECULAR BIOLOGY, John Wiley&Sons, New York, 1987and periodic updates；the
Series METHODS IN ENZYMOLOGY, Academic Press, San Diego；Wolffe, CHROMATIN
STRUCTURE AND FUNCTION, Third edition, Academic Press, San Diego, 1998；METHODS IN
ENZYMOLOGY, Vol.304, Chromatin (P.M.Wassarman and A.P.Wolffe, eds.), Academic
Press, San Diego, 1999；With METHODS IN MOLECULAR BIOLOGY, Vol.119, Chromatin
Protocols (P.B.Becker, ed.) Humana Press, Totowa, 1999 etc..
The present inventor has found that UCF-101 being capable of highly significant inhibition DSS induction by many experiments explorative experiment
The death of mouse, the mitigation of mouse weight, colon shorten and the destruction of colon epithelial cell barrier, so as to be used for
Colitis is treated, especially for treating ulcerative colitis, completes the invention on this basis.
Embodiment 1
In the present embodiment carry out UCF-101 to dextran sulfate sodium (Dextran Sulfate Sodium Salt,
DSS the variation of ulcerative colitis mouse weight and the research of survival rate) induced.
Contrast agents select 10% (v/v) dimethyl sulfoxide (Dimethyl sulfoxide, DMSO).
27 22-24g male C57BL/6 mouse are taken, 3 groups (every group of 9 mouse), respectively control group, DMSO group are divided into
And UCF-101 group.
Control group feeds water daily.
DMSO group feeds 3% (w/v) DSS daily, and 10% (v/v) DMSO is injected intraperitoneally daily.After seven days, no longer feed
3% (w/v) DSS, but feed and DSS isometric water and continue injection 10% (v/v) DMSO and no longer injected after 3 days, stop real
It tests.
UCF-101 group feeds 3% (w/v) DSS daily, and UCF-101 (injection volume 10mg/Kg is injected intraperitoneally daily
Mouse).After seven days, no longer feed 3% (w/v) DSS, but feed with DSS isometric water and continue inject UCF-101, after 3 days, no longer
Injection stops experiment.
Control group feeds water with DSS isometric water daily.
When since experiment, weigh daily to each group mouse, and calculate the average weight of same group of mouse.It calculates daily
Percentage of the DMSO group average weight relative to the control group average weight of this day calculates daily UCF-101 group average weight phase
For the percentage of the control group average weight of this day.
As a result as shown in Figure 1.Wherein " * " indicates P < 0.05, and " * * " indicates P < 0.01, and " * * * " indicates P < 0.001.From Fig. 1
It is found that UCF-101 can significantly inhibit the mitigation of mouse weight.
When since experiment, the death condition of each group mouse is counted daily, continues 16 days altogether.
DMSO group: the 9th day, two dead mouses, remaining 7 mouse survivals；11st day, and have two dead mouses, it remains
Remaining 5 mouse survivals；12nd day, and have three dead mouses, remaining 2 mouse survivals.
UCF-101 group, mouse all survives without a death in 16 days.
Control group, mouse all survives without a death in 16 days.
It is found that UCF-101 is remarkably improved the survival rate of mouse.
Embodiment 2
Influence of the research UCF-101 to the DSS ulcerative colitis mouse Colon length induced in the present embodiment.
15 22-24g male C57BL/6 mouse are taken, 3 groups (every group of 5 mouse), respectively control group, DMSO group are divided into
And UCF-101 group.
DMSO group feeds 3% (w/v) DSS daily, and 10% (v/v) DMSO is injected intraperitoneally daily.After seven days, no longer feed
3% (w/v) DSS, but feed and DSS isometric water and continue injection 10% (v/v) DMSO, after 3 days, the colon for measuring mouse is long
Degree, and calculate DMSO group mouse Colon length average value.
UCF-101 group feeds 3% (w/v) DSS daily, and UCF-101 (10mg/Kg mouse) is injected intraperitoneally daily.After seven days,
No longer feed 3% (w/v) DSS, but feed with DSS isometric water and continue inject UCF-101, after 3 days, the colon for measuring mouse is long
Degree, and calculate UCF-101 group mouse Colon length average value.
Control group feeds water with DSS isometric water daily.After 10 days, the colon lengths of mouse are measured, and calculate control group
Mouse Colon length average value.
Each group mouse Colon length average value is as shown in Figure 2.Wherein, " * * " indicates P < 0.01, and " * * * " indicates P < 0.001.
Corresponding reagent is not injected in "-" expression, and "+" indicates to inject corresponding reagent.
Fig. 2 shows that UCF-101 can significantly inhibit the mouse Colon that DSS is induced and shorten.
Embodiment 3
Shadow of the research UCF-101 to the DSS ulcerative colitis enterocyte barrier breakdown induced in the present embodiment
It rings.
24 22-24g male C57BL/6 mouse are taken, are divided into 3 groups；It is control group 8, DMSO group 8, UCF-101 group 8
Only.
DMSO group feeds 3% (w/v) DSS daily, and 10% (v/v) DMSO is injected intraperitoneally daily, continues seven days.
UCF-101 group feeds 3% (w/v) DSS daily, and UCF-101 (10mg/Kg mouse) is injected intraperitoneally daily, continues seven
It.
Control group feeds water with DSS isometric water daily.
8th day, it is each group intragastric administration on mice FITC- dextran (FITC-Dextran) (4kD, 0.6mg/g mouse), 3 hours
Blood is taken after time, is stored at room temperature 30min, and 3000rpm is centrifuged 10min, takes serum, and microplate reader detects FITC-Dextran in serum
Content (excitation wavelength 488nm, wavelength of transmitted light 520nm).As a result as shown in Figure 3.
In Fig. 3, " * * " indicates P < 0.01, and " * * * " indicates P < 0.001.Corresponding reagent is not injected in "-" expression, and "+" indicates note
Penetrate corresponding reagent.
Fig. 3 shows that UCF-101 can significantly inhibit the raising of FITC-Dextran concentration in the serum of DSS induction, explanation
UCF-101 can significantly inhibit destruction of the DSS to colon epithelial cell barrier.
Although above having used general explanation and specific embodiment, the present invention is described in detail, at this
On the basis of invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Therefore,
These modifications or improvements without departing from theon the basis of the spirit of the present invention are fallen within the scope of the claimed invention.
Claims (10)
1.UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug.
2. purposes according to claim 1, which is characterized in that the Traumatic Colon includes colitis.
3. purposes according to claim 2, which is characterized in that the colitis includes ulcerative colitis.
4. purposes according to claim 1, which is characterized in that the Traumatic Colon treat or prevent drug at least have with
Any one of lower or multinomial effect:
The death rate caused by colitis is reduced, weight loss caused by colitis is reduced, reduces colon lengths caused by colitis
It shortens, reduce the destruction of colon epithelial cell barrier function.
5. purposes according to claim 1, which is characterized in that UCF-101 is that the Traumatic Colon treats or prevents drug
One of effective component or sole active ingredient.
6.UCF-101 has effects that the purposes in any one of following or multinomial drug in preparation:
The death rate caused by colitis is reduced, weight loss caused by colitis is reduced, reduces colon lengths caused by colitis
It shortens, reduce the destruction of colon epithelial cell barrier function.
7. a kind of for treating or preventing the drug of Traumatic Colon, which is characterized in that described for treating or preventing Traumatic Colon
Drug include a effective amount of UCF-101.
8. according to claim 7 for treating or preventing the drug of Traumatic Colon, which is characterized in that the Traumatic Colon
Including colitis.
9. according to claim 8 for treating or preventing the drug of Traumatic Colon, which is characterized in that the colitis packet
Include ulcerative colitis.
10. according to claim 7 for treating or preventing the drug of Traumatic Colon, which is characterized in that described for controlling
Daily dose >=10mg/Kg effective object weight of the drug for the treatment of or prevention Traumatic Colon.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811118579.6A CN109223790A (en) | 2018-09-20 | 2018-09-20 | UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811118579.6A CN109223790A (en) | 2018-09-20 | 2018-09-20 | UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug |
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| Publication Number | Publication Date |
|---|---|
| CN109223790A true CN109223790A (en) | 2019-01-18 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811118579.6A Pending CN109223790A (en) | 2018-09-20 | 2018-09-20 | UCF-101 is preparing the purposes in Traumatic Colon treatment or prevention drug |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109925316A (en) * | 2019-03-26 | 2019-06-25 | 广州医科大学附属第二医院 | A kind of drug for treating ulcerative colitis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040171629A1 (en) * | 2002-02-28 | 2004-09-02 | Antonis Zervos | Method and compounds for inhibition of cell death |
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2018
- 2018-09-20 CN CN201811118579.6A patent/CN109223790A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040171629A1 (en) * | 2002-02-28 | 2004-09-02 | Antonis Zervos | Method and compounds for inhibition of cell death |
Non-Patent Citations (2)
| Title |
|---|
| CHONG ZHANG等: "Inhibition of HtrA2 alleviated colitis by preventing necroptosis of intestinal epithelial cells", 《BIORXIV，HTTPS://WWW.BIORXIV.ORG/CONTENT/10.1101/395897V1.FULL》 * |
| F.G. PRUEFER等: "Participation of Omi Htra2 serine-protease activity in the apoptosis induced by cisplatin on SW480 colon cancer cells", 《JOURNAL OF CHEMOTHERAPY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109925316A (en) * | 2019-03-26 | 2019-06-25 | 广州医科大学附属第二医院 | A kind of drug for treating ulcerative colitis |
| CN109925316B (en) * | 2019-03-26 | 2021-09-14 | 广州医科大学附属第二医院 | Medicine for treating ulcerative colitis |
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Application publication date: 20190118 |
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