CN108245664A - Application of the Liraglutide in periodontitis drug is treated - Google Patents
Application of the Liraglutide in periodontitis drug is treated Download PDFInfo
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- CN108245664A CN108245664A CN201711406798.XA CN201711406798A CN108245664A CN 108245664 A CN108245664 A CN 108245664A CN 201711406798 A CN201711406798 A CN 201711406798A CN 108245664 A CN108245664 A CN 108245664A
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- liraglutide
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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Abstract
The present invention relates to pharmaceutical technology fields, are related to the new application of Liraglutide, and in particular to treatment of the Liraglutide to periodontitis.The Liraglutide is the hypoglycemic medicine for being widely used in treating type II diabetes.Present invention discover that Liraglutide can significantly increase the proliferation activity and transfer ability of people's periodontal ligament cell, simulation periodontitis is co-cultured using lipopolysaccharides (LPS) and people's periodontal ligament cell simultaneously, observe the anti-inflammatory effect and osteogenic action of Liraglutide, as a result, it has been found that Liraglutide can significantly inhibit the inflammatory reaction of LPS inductions, and promote the Osteoblast Differentiation of people's periodontal ligament cell, restore damages of the LPS to people's periodontal ligament cell Osteoblast Differentiation.The present invention provides a kind of new application, while clinically more reasonably to provide more experimental datas using Liraglutide for Liraglutide.
Description
Technical field
The present invention relates to pharmaceutical technology field, the new application more particularly to Liraglutide for being related to Liraglutide are treating tooth
Application in all inflammation drugs.
Background technology
Periodontitis is a kind of chronic inflammation disease caused by Periodontal Pathogens infection and local factor stimulation, is mainly faced
Bed is characterized as the forfeiture of periodontal attachment, and the destruction absorption and tooth for causing Periodontal Supporting Tissue constantly loosen, and are that tooth is caused to lack
The Etiological of mistake.2010, the data of the Center for Disease Control publication were shown：About 47.2% American is with various types of
The periodontal disease of type, the incidence of the population of over-65s are even more to have reached 70.1%；And the incidence then higher of our countries,
For the third time《National oral health epidemiological survey report》Statistics indicate that：Adult more than 80% all suffers from various types of
Cementopathia.Therefore, the prophylactic treatment for carrying out periodontitis is most important.In addition, periodontitis more with diabetes, myocardial infarction, height
The systemic diseases such as blood pressure, atherosclerosis of aorta are closely related.More and more researchs confirm periodontitis and diabetes it
Between two-way correlation, it is believed that periodontitis is the sixth-largest complication of diabetes.The patients with NIDDM of light moderate needs long-term
Oral hypoglycemic agents controls blood glucose level, and common antidiabetic drug has sulfonylurea, biguanides and thiazolidinediones etc..Assuming that clothes
It is equally helpful to the treatment of periodontitis with these hypoglycemic medicines, then to avoid diabetic periodontitis patient and take a variety of medicines
Object.It is therefore desirable to seek a kind of hypoglycemic medicine that can treat periodontitis.
Liraglutide is glucagon-like-peptide-1 in wide clinical application as a kind of novel blood sugar lowing drug
The analog of (Glucagon-like peptide, GLP-1).Liraglutide as GLP-1 in addition to blood sugar reducing function, more
There is the physiological function outside a variety of pancreas, including anti-inflammatory effect and bone protective effect.Liraglutide can reduce diabetic's
Inflammation index, the expression for reducing the inflammatory factors such as adipocyte, vascular endothelial cell inhibit the air flue of ovalbumin induction scorching
Disease.Meanwhile research is found under high saccharide ring border, Liraglutide can increase the proliferative capacity and differentiation capability of osteoblast, and
Animal experiments show that Liraglutide can increase the expression of osteocalcin and osteoprotegerin, improve the bone loss of diabetes-induced.Lu etc.
The research of people finds that Liraglutide acts on ovariectomized mice, and lumbar vertebrae and long bone trabecular volume, thickness, number increase
Add, show protective effect of the Liraglutide to non-DM bone loss, and this bone protective effect is not from its anti-blood glucose effect.
However, Liraglutide does not have been reported that the therapeutic effect of periodontitis.The present invention is by in-vitro simulated periodontitis, thin
Therapeutic effect of the Liraglutide to periodontitis is inquired into born of the same parents' level.
Invention content
The object of the present invention is to provide Liraglutide treatment periodontitis new application, for clinically more reasonably using profit
Shandong peptide is drawn to provide more experimental datas and scientific basis.
The present invention relates to application of the Liraglutide in product is prepared, the function of the product has in following (1) to (6)
It is at least one：
(1) inhibit the expression of IL-6, promote the expression of Runx2；
(2) regeneration of periodontium is promoted to rebuild；
(3) promote the reconstruction of alveolar bone；
(4) promote people's periodontal ligament cell proliferation；
(5) promote the migration of people's periodontal ligament cell；
(6) periodontitis is treated.
Preferably, the periodontitis is chronic periodontitis and/or diabetic keratopathy periodontitis.
Preferably, the product is drug.
The invention further relates to a kind of product, active constituent is Liraglutide；The function of the product has following (1) extremely
At least one of (6)：
(1) inhibit the expression of IL-6, promote the expression of Runx2；
(2) regeneration of periodontium is promoted to rebuild；
(3) promote the reconstruction of alveolar bone；
(4) promote people's periodontal ligament cell proliferation；
(5) promote the migration of people's periodontal ligament cell；
(6) periodontitis is treated.
Preferably, the periodontitis is chronic periodontitis and/or diabetic keratopathy periodontitis.
Preferably, the product is drug
To achieve the above object, we select people's periodontal ligament cell of original cuiture, and mtt assay analyzes Liraglutide to people's tooth
The influence of all theca cell proliferation activities；Scratch test analyzes influence of the Liraglutide to people's periodontal ligament cell transfer ability；It selects
The LPS and people's periodontal ligament cell of classical gram-negative bacteria E.Coli co-cultures the pathogenic process to simulate periodontitis, Jin Eryong
Western Blot analyze Liraglutide to LPS stimulation servant's periodontal ligament cell inflammatory Cytokines Expressions (IL-6) and osteogenic factor
Express the influence of (Runx2).
The present invention is confirmed by the experiment of specific embodiment：Liraglutide can significantly increase the increasing of people's periodontal ligament cell
Ability is grown, and in dose dependent, while 100nmol/L is that Liraglutide increases the best of people's periodontal ligament cell proliferative capacity
Drug concentration；Liraglutide can significantly increase the transfer ability of people's periodontal ligament cell；The LPS of classical gram-negative bacteria E.Coli makees
The disease process of periodontitis can be effectively simulated for people's periodontal ligament cell, and after adding in Liraglutide simultaneously, IL-6 expression then by
To inhibition, and the expression of Runx2 significantly increases.
One of basal cell rebuild due to people's periodontal ligament cell as periodontium, analyzed in vitro drug effect descendant's tooth
The various change of all theca cells is to inquire into curative effect of medication most easily method.The purpose of periodontitis treatment is the disease that diminishes inflammation
Become and the regeneration of periodontium is promoted to rebuild, the especially reconstruction of alveolar bone.Liraglutide can dramatically increase people's periodontal ligament cell
Proliferation and transfer ability, this is the premise of paradenlal tissue regeneration, at the same Liraglutide can inhibit people's periodontal ligament cell inflammation because
The expression of son, and promote the expression of its osteogenic factor.The above results show that Liraglutide has potential treatment to people's periodontitis
Effect, and Liraglutide also has diabetes significant curative effect, and Liraglutide also has the effect of more preferable to diabetic keratopathy periodontitis.
Description of the drawings
Fig. 1 is the influence that various concentration Liraglutide is proliferated people's periodontal ligament cell.* it is P<0.05, * * is P<0.01.
Fig. 2 is that Fig. 2 is influence of the Liraglutide to people's periodontal ligament cell transfer ability；Wherein A is each for micro- Microscopic observation
The cut healing rate of group；B is the average healing distance that Image Pro Plus analyze quantum chemical method each group.* is P<0.01.
Fig. 3 is the influence that Liraglutide acts on LPS servant's periodontal ligament cell inflammatory factor and osteogenic factor expression；Wherein
A is the expression that Western Blot detect IL-6；B is the variation of Image J analysis quantization IL-6 expression；C is Western
Blot detects the expression of Runx2；D is the variation of Image J analysis quantization Runx2 expression.* it is P<0.05, * * is P<0.01.
Specific embodiment
In the following, technical scheme of the present invention is described in detail by specific embodiment.
Following Liraglutides are bought from Novo Nordisk drugmaker.
Following institute's employment periodontal ligament cells are obtained for original cuiture, and are identified with immunohistochemistry, anti-waveform silk
Protein positive resists angular protein negative.
Following material, reagents used etc., are commercially available unless otherwise specified.
1 Liraglutide of embodiment promotes the growth of people's periodontal ligament cell
Liraglutide concentration gradient is divided into 6 groups, set gradually for：0nmol/L、25nmol/L、50nmol/L、
75nmol/L, 100nmol/L, 125nmol/L, every group sets 6 multiple holes.The 4th generation people's periodontal ligament cell is taken after pancreatin digests, with
3×103/ hole is inoculated in 96 well culture plates, per 100 μ L of hole, after culture for 24 hours, replaces liquid, is separately added into the drawing of profit containing various concentration
α-MEM the culture mediums of Shandong peptide continue to cultivate at (containing 10%FBS).20 μ L MTT (5g/L) are added in after for 24 hours per hole, are cultivated in incubator
4h sucks culture solution, and 150 μ LDMSO are added per hole, the abundant mixing 15min of shaking table is placed, with enzyme-linked immunosorbent assay instrument at 570nm
It measures per hole absorbance value (A570), takes each cell mean, number of viable cells is reacted with A570 values.Cell proliferation rate=(experiment
Group A570- control group As 570)/control group A 570.
The results are shown in Figure 1 for it, and Fig. 1 is the influence that various concentration Liraglutide is proliferated people's periodontal ligament cell.It can by Fig. 1
Know, Liraglutide can significantly increase the proliferative capacity of people's periodontal ligament cell, and in dose dependent, while 100nmol/L
Increase the optimum medicine concentration of people's periodontal ligament cell proliferative capacity for Liraglutide.
2 Liraglutide of embodiment promotes the migration of people's periodontal ligament cell.
After well-grown 4th generation people's periodontal ligament cell pancreatin is digested, be inoculated in 6 orifice plates, experiment be divided into control group and
Liraglutide group treats that cell growth to 80-90%, is tested.Cut is made using 200 μ L pipette tips, then according to grouping point
The culture solution of FBS Jia Ru be free of, is changed the liquid once for 24 hours, after continuing culture for 24 hours, each group cut distance is observed under microscope
Variation.With the healing distance of 6.0 softwares of Image-Pro Plus analysis cut.
The results are shown in Figure 2 for it, and Fig. 2 is that Fig. 2 is influence of the Liraglutide to people's periodontal ligament cell transfer ability.By Fig. 2
It is found that Liraglutide can significantly increase the transfer ability of people's periodontal ligament cell.
3 Liraglutide of embodiment inhibits the expression of IL-6, and promotes the expression of Runx2.
The 4th generation people's periodontal ligament cell is taken to be inoculated in 100mm culture dishes and cultivated after pancreatin digests.By experiment point
It is three groups：Control group, LPS groups and LPS+ Liraglutide joint groups.After cell length to 80%, it is separately added into different pharmaceutical；Its
In middle LPS groups in a concentration of 10 μ g/mL, LPS+ the Liraglutide joint group of LPS LPS a concentration of 10 μ g/mL, LPS+ Li Lalu
A concentration of 100nmol/L of Liraglutide in peptide joint group.Continue culture for 24 hours, cell is collected by centrifugation, extract holoprotein, add in
Lysate containing PMSF, cracks on ice, supernatant is taken after centrifugation, and illustrate that time-and-motion study is carried according to BCA protein quantification kits
The concentration of albumen, after measuring protein content, the volume for calculating the protein solution containing 50mg is applied sample amount, and appropriate albumen adds in buffering
Liquid is placed in EP pipes, and 95 DEG C are boiled 5min denaturation, -80 DEG C of preservations.Working solution, 15% separation gel and 5% spacer gel needed for preparation.Add
Sufficient amount electrophoretic buffer loading, 160V voltages 80min are run to bottom end, cut glue, and 12V voltages 1h is gone on pvdf membrane, are added respectively
IL-6, β-actin antibody, 4 DEG C of overnight incubations, TBST washings 10min × 3 time are separately added into secondary antibody, are incubated at room temperature 2h later,
TBST washs 10min × 3 time, the exposure colour developing of ECL gel imaging systems again.
Runx2 is detected with above-mentioned same method, culture solution is changed to osteogenic induction liquid.
LPS is the lipopolysaccharides of classical gram-negative bacteria E.Coli in the present embodiment.
The results are shown in Figure 3 for it, Fig. 3 LPS is acted on for Liraglutide servant's periodontal ligament cell inflammatory factor and skeletonization because
The influence that sublist reaches.As shown in Figure 3：LPS acts on people's periodontal ligament cell, can dramatically increase the expression of IL-6, inhibits Runx2
Expression, this shows that the co-cultivation of LPS and people's periodontal ligament cell can effectively simulate the disease process of periodontitis, and adds in sharp drawing simultaneously
After the peptide of Shandong, IL-6 expression is then suppressed, and the expression of Runx2 significantly increases.
In conclusion one of basal cell that people's periodontal ligament cell is rebuild as periodontium, analyzed in vitro drug effect
The various change of descendant's periodontal ligament cell is to inquire into curative effect of medication most easily method.The purpose of periodontitis treatment is to eliminate
Inflammatory disorders simultaneously promote the regeneration of periodontium to rebuild, the especially reconstruction of alveolar bone.Liraglutide can dramatically increase people's periodontal
The proliferation and transfer ability of theca cell, this is the premise of paradenlal tissue regeneration, while Liraglutide can inhibit people's periodontal ligament cell
The expression of inflammatory factor, and promote the expression of its osteogenic factor.It is potential that the above results show that Liraglutide has people's periodontitis
Therapeutic effect, and Liraglutide also has diabetes significant curative effect, and Liraglutide also has diabetic keratopathy periodontitis more preferably
The effect of.
The foregoing is only a preferred embodiment of the present invention, but protection scope of the present invention be not limited thereto,
Any one skilled in the art in the technical scope disclosed by the present invention, according to the technique and scheme of the present invention and its
Inventive concept is subject to equivalent substitution or change, should be covered by the protection scope of the present invention.
Claims (6)
1. application of the Liraglutide in product is prepared, the function of the product has at least one of following (1) to (6)：
(1) inhibit the expression of IL-6, promote the expression of Runx2；
(2) regeneration of periodontium is promoted to rebuild；
(3) promote the reconstruction of alveolar bone；
(4) promote people's periodontal ligament cell proliferation；
(5) promote the migration of people's periodontal ligament cell；
(6) periodontitis is treated.
2. application of the Liraglutide in product is prepared according to claim 1, which is characterized in that the periodontitis is chronic
Periodontitis and/or diabetic keratopathy periodontitis.
3. application of the Liraglutide according to claim 1 or claim 2 in product is prepared, which is characterized in that the product is medicine
Object.
4. a kind of product, active constituent is Liraglutide；The function of the product has at least one of following (1) to (6)：
(1) inhibit the expression of IL-6, promote the expression of Runx2；
(2) regeneration of periodontium is promoted to rebuild；
(3) promote the reconstruction of alveolar bone；
(4) promote people's periodontal ligament cell proliferation；
(5) promote the migration of people's periodontal ligament cell；
(6) periodontitis is treated.
5. product according to claim 4, which is characterized in that the periodontitis is chronic periodontitis and/or diabetic keratopathy tooth
Zhou Yan.
6. product according to claim 4, which is characterized in that the product is drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711406798.XA CN108245664A (en) | 2017-12-22 | 2017-12-22 | Application of the Liraglutide in periodontitis drug is treated |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201711406798.XA CN108245664A (en) | 2017-12-22 | 2017-12-22 | Application of the Liraglutide in periodontitis drug is treated |
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| CN108245664A true CN108245664A (en) | 2018-07-06 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113769064A (en) * | 2021-09-28 | 2021-12-10 | 上海交通大学医学院附属第九人民医院 | Application of thiostrepton in preparation of medicine for treating periodontitis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103536907A (en) * | 2013-07-18 | 2014-01-29 | 上海交通大学医学院附属瑞金医院 | Application of liraglutide in preparation of drug for treating osteoporosis |
| CN103800301A (en) * | 2013-12-27 | 2014-05-21 | 深圳市健元医药科技有限公司 | Pulsatile delivery composition for treating diabetes mellitus and preparation method thereof |
-
2017
- 2017-12-22 CN CN201711406798.XA patent/CN108245664A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103536907A (en) * | 2013-07-18 | 2014-01-29 | 上海交通大学医学院附属瑞金医院 | Application of liraglutide in preparation of drug for treating osteoporosis |
| CN103800301A (en) * | 2013-12-27 | 2014-05-21 | 深圳市健元医药科技有限公司 | Pulsatile delivery composition for treating diabetes mellitus and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| NAN LU等: "Glucagon-like peptide-1 receptor agonist Liraglutide has anabolic bone effects in ovariectomized rats without diabetes", 《PLOS ONE》 * |
| 庞云清等: "利拉鲁肽对人牙周膜细胞增殖、迁移及成骨分化潜能的影响", 《第十一次全国牙周病学术会议摘要汇编》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113769064A (en) * | 2021-09-28 | 2021-12-10 | 上海交通大学医学院附属第九人民医院 | Application of thiostrepton in preparation of medicine for treating periodontitis |
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