CN105147703B - Application of the obakunone in the drug for preparing prevention ulcerative colitis - Google Patents
Application of the obakunone in the drug for preparing prevention ulcerative colitis Download PDFInfo
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- CN105147703B CN105147703B CN201510478406.5A CN201510478406A CN105147703B CN 105147703 B CN105147703 B CN 105147703B CN 201510478406 A CN201510478406 A CN 201510478406A CN 105147703 B CN105147703 B CN 105147703B
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- obakunone
- ulcerative colitis
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Abstract
The present invention relates to medicine, more particularly to a kind of medical usage of obakunone.The obakunone of the present invention can be used for preventing ulcerative colitis.
Description
Technical field
The present invention relates to Medicines and Health Product field, more particularly to a kind of medical usage of obakunone.
Background technology
Ulcerative colitis (Ulcerative colitis, UC) is chronic, recurrent exerbation the inflammation for betiding colon
Property enteropathy (Inflammatory bowel disease, IBD).Clinical manifestations are diarrhea, mucus pus and blood stool, abdominal pain.It is main
Complication is wanted to have：Bleeding, enterobrosis, anal fistula, intestinal obstruction, colon cancer and infectious shock etc..
The Western medicine for the treatment of UC mainly has aminosalicylic acids, glucocorticoids and immunosuppressor at present.Effect is all
It is not highly desirable, and side effect is big, is not easy to be used for a long time.Salicylazosulfapyridine (SASP) is current clinical most common Western medicine, is fitted
For moderate, slight and chronic UC patient.It is decomposed into sulfapryidine and 5-aminosalicylic acid in the intestine after oral.To colon intestinal wall
Tissue has special affinity, plays anti-inflammatory effect.Have after oral SASP 10%~40% patient occur nausea, indigestion,
The adverse reactions such as headache, leucocyte decline, occasionally have and cause arthralgia, fash, albuminuria and pancreatitis etc., most adverse reactions are all
It is attributed to the sulfapyridine moiety of SASP.
Obakunone (Obacunone) is primarily present a kind of limonin constituents in rutaceae, has anti-
Cancer, desinsection, lipid-loweringing isoreactivity.
Invention content
The purpose of the present invention is intended to provide a kind of new medical usage of obakunone.
Specifically, the present invention provides a kind of obakunone in the drug or food for preparing prevention ulcerative colitis
Using.
In a preferred example, the obakunone is to be used to prepare prevention ulcerative colitis as unique active constituent
Drug or food.
The details of various aspects of the present invention will be able to detailed description in subsequent chapters and sections.By hereafter and claim
Description, the features of the present invention, purpose and advantage will become apparent from.
Description of the drawings
Fig. 1-Fig. 4 embodies therapeutic effect of the obakunone to ulcerative colitis：
Fig. 1 embodies influence of the obakunone to ulcerative colitis mouse weight；
Fig. 2 embodies influence of the obakunone to ulcerative colitis mouse bloody stool incidence；
Fig. 3 embodies influence of the obakunone to ulcerative colitis mouse Colon length；
Fig. 4 mouse Colon tissue pathological slices embody obakunone to ulcerative colitis mouse Colon Histopathological lesions
Influence；
The scoring of Fig. 5 mouse Colons histopathology embodies obakunone to ulcerative colitis mouse Colon Histopathological lesions
Influence；
(in figure：A represents Normal group, and b represents model control group, and c represents SASP groups, and d represents obakunone group)
Specific embodiment
The appearance part of the present invention is had been surprisingly found that based on such a：Obakunone can be obviously improved ulcerative colitis
The symptoms such as weight loss, bloody stool, colon shortening and the Histopathological lesions of mouse, therefore, obakunone can be used for preparing prevention intestines
The drug or food of inflammation, particularly ulcerative colitis.
And then the application the present invention provides obakunone in the drug or health food for preparing prevention enteritis.
The molecular formula of the obakunone (obacunone) of the present invention：C26H30O7, molecular weight：454.51 structural formula is as follows：
The obakunone of the present invention can be by commercial sources from Sigma chemical companies, the limited public affairs of Chengdu Man Site biotechnologies
Department etc. purchase obtains.Its purity meets medicinal standard.The purity of obakunone with>98% is best.
The obakunone of the present invention can be used alone or be used in the form of pharmaceutical composition.Pharmaceutical composition includes conduct
The obakunone and pharmaceutical acceptable carrier of the present invention of active constituent.Preferably, the pharmaceutical composition of the present invention contains 0.1-99.9%
The obakunone of the present invention as active component of weight percent." pharmaceutical acceptable carrier " will not destroy the obakunone of the present invention
Pharmaceutical active, while its effective dose, dosage when can play pharmaceutical carrier effect are nontoxic to human body.
Described pharmaceutical acceptable carrier includes but not limited to：Soft phosphatide, aluminum stearate, aluminium oxide, ion exchange material, self-emulsifying
Drug delivery system, tween or other surfaces activator, haemocyanin, buffer substance for example phosphate, amion acetic acid, sorbic acid,
Water, salt, electrolyte such as sulfate protamine, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, magnesium silicate, saturated fatty acid
Partial glyceride mixtures etc..
Other common excipient substance such as adhesives (such as microcrystalline cellulose), filler (such as starch, glucose, anhydrous lactitol
Sugar and lactose bead), disintegrant (such as cross-linked pvp, crosslinked carboxymethyl fecula sodium, croscarmellose sodium, low-substituted hydroxypropyl
Base cellulose), lubricant (such as magnesium stearate) and sorbefacient, absorption carrier, flavouring agent, sweetener, excipient, dilution
Agent, wetting agent etc..
The obakunone of the present invention and its pharmaceutical composition can be prepared by this field conventional method and can by enteron aisle or
Non-bowel or topical routes.Oral preparation includes capsule, tablet, oral liquid, granule, pill, powder, sublimed preparation, cream
Agent etc.；Non-intestinal drug delivery agent is including parenteral solution etc.；Local administration preparation includes creme, patch, ointment, spray etc..It is excellent
It is selected as oral preparation.
The obakunone of the present invention and the administration route of its pharmaceutical composition can be oral, sublingual, percutaneous, through muscle or
Subcutaneously, mucocutaneous, vein, urethra, vagina etc..
Other than medicament is made, it is various also antioxidant, pigment, enzyme preparation etc. can be added in the obakunone of the present invention
Health food is made by the conventional method of this field in food additives.
With reference to specific embodiment, the present invention is further explained.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.Test method without specific conditions in the following example, usually according to conventional strip
Part or according to the normal condition proposed by manufacturer.Unless otherwise stated, otherwise all percentage, ratio, ratio or number is pressed
Weight meter.
Unless otherwise defined, it anticipates known to all professional and scientific terms used in text and one skilled in the art
Justice is identical.In addition, any method similar or impartial to described content and material all can be applied in the method for the present invention.Wen Zhong
The preferred implement methods and materials are for illustrative purposes only.
The feature that the features described above or embodiment that the present invention mentions are mentioned can be in any combination.Patent specification is taken off
All features shown can be used in combination with any composition form, and each feature disclosed in specification any can provide phase
The alternative characteristics substitution of same, impartial or similar purpose.Therefore except there is special instruction, revealed feature is only impartial or similar
The general example of feature.
Embodiment 1：
1st, experiment material
1.1 medicinal material
Obakunone (CAS：751-03-1, molecular weight 454.51, HPLC purity >=98%, by Chengdu Man Site biotechnologies
Co., Ltd produces)；Dextran sulfate sodium (DSS, CAS：9011-18-1, MW 36-50kDa, by U.S. MP Biomedicals
Company produces)；Salicylazosulfapyridine (SASP, CAS：599-79-1, molecular weight 398.39, HPLC purity >=98%, by the U.S.
Sigma-Aldrich companies produce).
1.2 experimental animal
The C57BL/6 female mices (8 weeks) of 20 ± 2g of weight, are provided by Shanghai Univ. of Traditional Chinese Medicine's Experimental Animal Center, are moved
Object quality certification number：SYXK (Shanghai) 2009-0069.It is placed in conventinal breeding environment, ad lib and drinking-water.
2nd, experimental method
The foundation of 2.1 Ulcerative Colitis Models
The C57BL/6 female mices (20 ± 2g) for selecting weight uniform, using international ulcerative colitis modeling
Method (Gastroenterology 2002,123:256-70；PLoS One 2012,7:E36075), the incipient stage is being studied,
Make mouse ad lib and drinking-water, after the laundering period in the early stage into, water is changed to the DSS of 4% (w/v), freely drunk 7 days, to draw
Play ulcerative colitis.
2.2 groupings and medication
Normal group：10, give normal diet.
Model control group：It 10, gives 4%DSS solution and freely drinks 7 days.
SASP groups：10, gavage gives SASP and (is converted into mouse according to quantity to use while giving 4%DSS solution
Amount：350mg/kg) continuous 7 days.
Obakunone group：10, gavage gives obakunone (50mg/kg) continuous 7 days while giving 4%DSS solution.
During the experiment, it is fresh daily to prepare dosage particles, it is dissolved with 0.5% sodium carboxymethylcellulose, and small preparing 1
When interior use.
The assessment of 2.3 enteritis
Diarrhea, bloody stool, histopathological analysis etc. publish thesis (PLoS One 2012,7 with reference to early-stage study:
e36075；J Pharmacol Exp Ther 2013,345:Method described in 473-82).During the experiment records weight change daily
Change, diarrhea and bloody stool symptom.Anesthesia and cervical dislocation put to death mouse after experiment, and opening abdominal cavity is taken out colon, measured from blind
Intestines are to the colon lengths of rectum.And terminal colon is taken to do histotomy, H＆E dyeing is carried out, disease is carried out to H＆E dyeing colon samples
Reason scoring：(1) the exudation standards of grading of inflammatory cell：There is minute quantity inflammatory cell in 0 point-mucosa lamina propria, 1 point-mucous membrane is solid
Having has the inflammatory cell in more inflammatory cell or mucosa lamina propria to increase in layer, 2 points-inflammatory cell is diffused under mucous membrane
Layer, 3 points-holostrome have inflammatory cell exudation；(2) tissue damage standards of grading：0 point-without mucosa injury, 1 point-discrete glutinous
Film epithelial lesions, 2 points-surface layer mucosal erosion, 3 points-extensive mucous membrane is damaged and is extended to intestinal wall deep layer.By oozing for inflammatory cell
Go out score to be added with tissue damage score, calculate histopathology scoring (1-6 points).
2.4 statistical analysis
All experimental datas are repeated 3 times, and are as a result represented with mean+SD, using 16.0 statistical softwares of SPSS
Experimental data is examined using One-way ANOVA (One-way ANOVA) and LSD, P<0.05 has significantly for statistically difference
Property.
3 results
The influence of 3.1 pairs of ulcerative colitis mouse weights
Fig. 1 embodies influence of the obakunone to ulcerative colitis mouse weight, as seen from Figure 1：Normal group mouse
Weight gain 0.9 ± 0.8%, the weight loss of model group mouse 8.2 ± 0.9%, the weight of positive controls mouse
Alleviate 5.0 ± 0.8%, the weight loss of obakunone group mouse 2.9 ± 0.3%；Further illustrate that obakunone can significantly press down
Weight loss (the P of ulcerative colitis mouse caused by DSS processed<0.001)；Also, in the case of being administered orally, obakunone
(50mg/kg) is better than positive control drug SASP (350mg/kg) (P to the inhibiting effect significant effect of weight loss<0.05).
The influence of 3.2 pairs of ulcerative colitis mouse bloody stool incidences
Fig. 2 embodies influence of the obakunone to ulcerative colitis mouse bloody stool incidence, as seen from Figure 2：Normal control
Group mouse occurs without bloody stool, and the bloody stool incidence of model group mouse is 96.7 ± 5.8%, and the bloody stool of positive controls mouse occurs
Rate is 60.0 ± 10.0%, and the bloody stool incidence of obakunone group mouse is 43.3 ± 5.8%；Further illustrate that obakunone can be significantly
Bloody stool rate (the P of ulcerative colitis mouse caused by reducing DSS<0.001)；Also, in the case of being administered orally, obakunone
(50mg/kg) is better than positive control drug SASP (350mg/kg) (P to the inhibiting effect significant effect of bloody stool incidence<0.05).
The influence of 3.3 pairs of ulcerative colitis mouse Colon length
Fig. 3 embodies influence of the obakunone to ulcerative colitis mouse Colon length, as seen from Figure 3：Normal group
Mouse shortens without colon and occurs, and the colon shortening rate of model group mouse is 35.3 ± 0.6%, and the colon of positive controls mouse contracts
Short rate is 19.4 ± 0.3%, and the colon shortening rate of obakunone group mouse is 14.3 ± 0.2%；Further illustrate that obakunone can be shown
The colon for writing ulcerative colitis mouse caused by improving DSS shortens symptom (P<0.01)；It is yellow also, in the case of being administered orally
The improvement result significant effect that cypress ketone (50mg/kg) shortens colon symptom is better than positive control drug SASP (350mg/kg) (P<
0.01)。。
The influence of 3.4 pairs of ulcerative colitis mouse Colon histopathologies
Fig. 4 and Fig. 5 embodies obakunone and the injury repair of ulcerative colitis mouse Colon tissue is acted on, can by Fig. 4
See：The colonic tissue of model group mouse is showed for exemplary inflammatory mucous membrane, it is seen that mucous membrane, the submucosa even a large amount of inflammatories of muscle layer are thin
Born of the same parents infiltrate, and institutional framework is disorderly, fracture, submucosa bleeding, oedema, telangiectasis；Positive controls mouse and Cortex Phellodendri
The colonic tissue lesions visible of ketone group mouse mitigates, ulcer healing, and submucosa bleeding mitigates.As seen from Figure 5：Normal group
Mouse score is 0, and the score of model group mouse is 5.7 ± 0.3, and the score of positive controls mouse is 3.4 ± 0.4, and obakunone group is small
Mouse score is 3.0 ± 0.2, compared with model group, the significant (P of difference<0.001).Illustrate that obakunone can significantly mitigate knot
Intestinal mucosa inflammatory cell infiltration and Histopathological lesions situation (P<0.001).Also, in the case of being administered orally, obakunone
(50mg/kg) is significantly better than the repairing effect of colon pathology damage positive control drug SASP (350mg/kg) (P<0.05).
To sum up result of study shows：Obakunone can be obviously improved the weight loss of ulcerative colitis mouse, bloody stool hair
Raw rate, colon shortening rate and Histopathological lesions symptom.Also, in the case of being administered orally, obakunone (50mg/kg) is to bursting
The weight loss of ulcer colitis mouse, bloody stool incidence, the improvement result of colon shortening rate and Histopathological lesions are notable
Better than positive control drug SASP (350mg/kg) (P<0.05).
Many aspects according to the present invention have been explained as above.However, it should be understood that without departing from spirit of the invention
Under the premise of, those skilled in the art can carry out it equivalent change and modification, and the change and modification equally fall into the application
The coverage area of appended claims.
Claims (2)
1. application of the obakunone in the drug for preparing prevention ulcerative colitis.
2. application as described in claim 1, which is characterized in that the obakunone is used to prepare as unique active constituent
Prevent the drug of ulcerative colitis.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510478406.5A CN105147703B (en) | 2015-08-07 | 2015-08-07 | Application of the obakunone in the drug for preparing prevention ulcerative colitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510478406.5A CN105147703B (en) | 2015-08-07 | 2015-08-07 | Application of the obakunone in the drug for preparing prevention ulcerative colitis |
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| Publication Number | Publication Date |
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| CN105147703A CN105147703A (en) | 2015-12-16 |
| CN105147703B true CN105147703B (en) | 2018-06-08 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769880B (en) * | 2016-03-09 | 2018-05-15 | 广东省中医院 | Application of the obakunone in the medicine of prevention injury of lungs and pulmonary fibrosis is prepared |
| CN115252630B (en) * | 2022-09-02 | 2024-02-09 | 深圳技术大学 | Application of phellodendron ketone in preparing medicine for preventing, improving or treating non-alcoholic fatty liver disease |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102344483A (en) * | 2010-07-29 | 2012-02-08 | 杨槐 | Preparation method for limonin analogues |
| CN103705525A (en) * | 2014-01-06 | 2014-04-09 | 江苏省中医院 | Limonin-containing medicine for treating ulcerative colitis as well as preparation method and application thereof |
-
2015
- 2015-08-07 CN CN201510478406.5A patent/CN105147703B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102344483A (en) * | 2010-07-29 | 2012-02-08 | 杨槐 | Preparation method for limonin analogues |
| CN103705525A (en) * | 2014-01-06 | 2014-04-09 | 江苏省中医院 | Limonin-containing medicine for treating ulcerative colitis as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| Obacunone exhibits anti-proliferative and anti-aromatase activity in vitro by inhibiting the p38 MAPK signaling pathway in MCF-7 human breast adenocarcinoma cells;Jinhee Kim等;《Biochimie》;20141231;第105卷;第36-44页 * |
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| CN105147703A (en) | 2015-12-16 |
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