CN103908657A - Use of glucagons-like peptide-1 analogue in preparation of ophthalmic disease drug - Google Patents
Use of glucagons-like peptide-1 analogue in preparation of ophthalmic disease drug Download PDFInfo
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- CN103908657A CN103908657A CN201210595101.9A CN201210595101A CN103908657A CN 103908657 A CN103908657 A CN 103908657A CN 201210595101 A CN201210595101 A CN 201210595101A CN 103908657 A CN103908657 A CN 103908657A
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Abstract
The invention belongs to the field of medicine, relates to a use of a glucagons-like peptide-1 analogue in pharmacy, and particularly relates to the use of the glucagons-like peptide-1 analogue Exendin-4 in preparation of an ophthalmic disease drug. With adopting of the exogenous glucagons-like peptide-1 analogue Exendin-4, a diabetic retinopathy animal model experiment is carried out, and results show that the Exendin-4 can inhibit retinal inflammatory responses caused by glial cell activation, resists retinal cell apoptosis caused by diabetes and the like, significantly improves visual functions, can be used as the drug for treating some ophthalmic diseases and especially as the drug for treating ocular ischemic and optic nerve injury diseases, and treats ophthalmic diseases comprising diabetic retinopathy, hypertensive retinopathy, retinal vein occlusion and the like.
Description
Technical field
The invention belongs to field of medicaments, relate to the purposes of glucagon like peptide-1 analog in pharmacy, be specifically related to the purposes of glucagon like peptide-1 analog Exendin-4 in preparation ophthalmic diseases medicine, relate in particular to the purposes of glucagon like peptide-1 analog Exendin-4 in preparation treatment ischemic or nerve injury ophthalmic diseases (as diabetic retinopathy etc.) medicine.
Background technology
It is a kind of GLP-1 extracting from Eremiatis argi salivary gland (glucagon like peptide-1, glucagons-like peptide-1) analog that prior art discloses Exendin-4, has 53% homology with the aminoacid sequence of mammal GLP-1.It has the secretion of promotion pancreas insulin, the effect that increases insulin sensitivity and improve islet cell function simultaneously, and do not decomposed by DPP IV (DPP-IV), plasma half-life is longer, it is reported, at present for the clinical treatment of diabetes.
Diabetes (DM) are the third-largest disease after cardiovascular disease and tumor as China, the threat on human health and self-evident on social impact.In many complication of diabetes, diabetic retinopathy (is called for short sugar net sick, diabetic retinopathy, DR) there is special critical role, its pathological change is from microangioma, hard exudate, macular edema, cotton-wool patches, breed even detachment of retina to new vessels, vitreous body, think at present, the sick pathogeny of sugar net mainly comprises the inflammatory reaction of retinal microvascular pathological changes and neuron pathological changes and middle minuent.Its morbidity is very general, is one of main in the world diseases causing blindness, and statistics shows, the sick global sickness rate of sugar net is about 4.8%, and its sickness rate increases with the development of the DM course of disease, and in 5 years, DR incidence rate is after 44.4%, 7 year to be 56%.Expecting the year two thousand thirty U.S. will have 2,500 ten thousand, and will there be 300,000,000 DR patients in the whole world.Research is demonstration also, and sugar net sick (DR) is DM metabolism disorder and hormonal system and the reflection of hematological on retina, has become one of the most common and serious microvascular complication of diabetes (DM).According to investigations, no matter 1 type or type 2 diabetes mellitus patient, wherein more than 90% patient exists generation can cause blind sugar to net the danger of disease in the time that the course of disease is longer, has had a strong impact on patient's orthobiosis.In clinical practice to sugar net sick and cause blindly still lack effective treatment measure, it is main at present that what adopt is the therapeutic schemes such as intravitreal hormone, Fundus laser and Vitrectomy.Although these treatment meanss can delay to a certain extent the progress of the state of an illness or improve symptom, due to wherein be mostly that the sick pathogenic factor of sugar net still can not be fundamentally eliminated in the intervention in relative late period, therefore prognosis is not satisfactory.
Therefore, understanding the sick pathogenesis of sugar net in depth and find effective Therapeutic Method and medicine, is one of the focus of attention of current international ophthalmology research field research worker and significant challenge problem.
Summary of the invention
The object of this invention is to provide the new purposes of glucagon like peptide-1 analog in pharmacy; be specifically related to the purposes of glucagon like peptide-1 analog Exendin-4 in preparation ophthalmic diseases medicine, relate in particular to the purposes of glucagon like peptide-1 analog Exendin-4 in the protection medicine of preparation treatment ischemic or nerve injury ophthalmic diseases (as diabetic retinopathy etc.) and visual function.
The present invention adopts exogenous glucagon like peptide-1 analog Exendin-4, carry out diabetic retinopathy animal model test, impact experiment by intraocular injection Exendin-4 on rat blood sugar, body weight, result shows, the blood glucose of intraocular injection E4 on rat and body weight are without impact; Protect GK rat flash electroretinogram (FERG) experiment by Exendin-4; result shows; Exendin-4 eye drops can significantly reduce ERG b wave component amplitude and lower; experimental result also shows; Exendin-4 can suppress GK rat retina cell apoptosis; increase the expression of Bcl-xl/Bax and Bcl-2/Bax gene; reduce the expression of retinal gliocytes acidic protein and reduce the expression of GK rat retina Claudin-5, occludin, ICAM-1, PIGF; experimental result shows, described glucagon like peptide-1 analog Exendin-4 has:
1, alleviate retinal morphology damage and change, maintain the effect of ganglionic cell and inner molecular layer and whole retinal thickness;
2, have and reduce the effect that retinal ganglial cells is lost;
3, there is the effect of protection visual function, visual electrophysiology is comprised to electroretinogram has protective effect;
4, there is the effect that suppresses the retina injury that causes of Glial Activation;
5, there is the effect that suppresses retinal cell apoptosis;
6, there is the effect of protection blood-retina barrier function.
The results show; glucagon like peptide-1 analog Exendin-4 of the present invention can be used as the medicine of ophthalmic diseases; retinal morphology and visual function are had to protective effect; relate in particular to the Drug therapy of diabetic retinopathy; and can significantly improve visual function; suppress the caused retina inflammation reaction of Glial Activation; to the caused retinal cell apoptosis of anti-diabetic; treatment comprises diabetic renal papillary necrosis; the diseases such as Retinopathy of Hypertension, and can improve visual function.
Exogenous glucagon like peptide-1 analog Exendin-4 of the present invention can obtain by commercial channel.
Accompanying drawing explanation
Fig. 1 is the affect experimental result of intraocular injection Exendin-4 on rat blood sugar, body weight, wherein,
A is fasting glucose, and B is post-prandial glycemia, and C is body weight, and the fasting glucose of two groups of rats after GK and GK+Exendin-4 treatment and post-prandial glycemia are respectively 1.7-2.8 times and 1.3-1.8 times of Wistar group rat; And the body weight of two groups is respectively than the light 4.3%-9% of Wistar rat; GK group and GK+Exendin-4 organize between both fasting glucose, post-prandial glycemia, body weight all no difference of science of statistics (* P < 0.05, * * P < 0.01, #P < 0.001, n=12);
In figure, control:Wistar rat;
G+NS:GK rat+physiology eye water intraocular injection;
G+E4:GK rat+Exendin-4 intraocular injection.
Fig. 2 is Exendin-4 protection GK rat flash electroretinogram (FERG) experimental result, wherein,
A is the comparison that in three groups of rat FERG, b wave-amplitude changes; C be Ops AMPLITUDE RATIOS; B and D are the changes of three groups of rat typical case ERG; Diabetic groups b wave component amplitude compared with normal group significantly decline (P < 0.01); Exendin-4 eye drops significantly reduces ERG b wave component amplitude and lowers (* P < 0.05, * * P < 0.01, #P < 0.001, n=12);
Control:Wistar rat in figure;
G+NS:GK rat+physiology eye water intraocular injection;
G+E4:GK rat+Exendin-4 intraocular injection.
Fig. 3 is that Exendin-4 suppresses GK rat retina cell apoptosis, increases the expression of Bcl-xl/Bax and Bcl-2/Bax gene, wherein,
A is each group of retina cell counting; B is each group of GLP-1R protein expression situation; C is that Immunohistochemical Method shows the expression of GLP-1R in retina; D is Bcl-xl, Bax, Bcl-2 gene the expression of each group; Wherein, GCL: ganglion-cell layer; INL: inner nuclear layer; ONL: outer nuclear layer;
Control:Wistar rat in figure; G+NS:GK rat+physiology eye water intraocular injection; G+E4; GK rat+Exendin-4 intraocular injection; (* P < 0.05, * * P < 0.01, #P < 0.001, n=12).
Fig. 4 is the expression that Exendin-4 reduces retinal gliocytes acidic protein, wherein,
A is the protein expression situation of each group of retina GFAP; B is the protein expression situation of each group of retina Vimentin; C be Immunohistochemical Method show each group of retina GFAP expression;
Control:Wistar rat in figure; G+NS:GK rat+physiology eye water intraocular injection; G+E4:GK rat+Exendin-4 intraocular injection; (* P < 0.05, * * P < 0.01, #P < 0.001, n=12).
Fig. 5 is the expression that Exendin-4 reduces GK rat retina Claudin-5, occludin, ICAM-1, PIGF, wherein,
A is the protein expression situation of each group of retina Claudin-5, occludin; B is the expression that Immunohistochemical Method shows each group of retina Claudin-5, occludin; C is the protein expression situation of each group of retina ICAM-1; D is the protein expression situation of each group of retina PIGF and VEGF;
Control:Wistar rat in figure; G+NS:GK rat+physiology eye water intraocular injection; G+E4:GK rat+Exendin-4 intraocular injection; (* P < 0.05, * * P < 0.01, #P < 0.001, n=12).
The specific embodiment
Set up laboratory animal diabetes model and intravitreal Exendin-4:
Experiment adopts 8 week age, body weight to be about Wistar and the GK rat of 150 grams, rat is divided into 3 groups: Normal group (Wistar), diabetic groups (GK rat) and diabetes E4 (GK+E4) treatment group;
(E4 is dissolved in normal saline, PH=5), 12 every group;
Medication: intravitreal E4 carried out in the time of 12 weeks, in the laggard oozy glass body cavity of experimental animal model temporo side angle limbus of sclera, Exendin-4 intervenes according to a conventional method, the volume of medication is 2 μ L/ eyes, the dosage of E4 is 0.1MG/ eye, gives isopyknic normal saline to diabetic groups and rats in normal control group; Injection is front by animal general anesthesia (2% pentobarbital sodium, 50mg/Kg BW), and coordinates eye local anesthesia (lignocaine or tetracaine).
Embodiment 1 intravitreal Exendin-4 has the effect of protection rat retina function, makes ERG b ripple and 0ps net amplitude approach normal level
Adopt the method for full visual field flash of light ERG detect the degree of rat diabetes retinopathy and detect amphiblestroid functional status, result shows, 16 weeks time, b ripple and the Ops wave-amplitude of the rat of GK normal saline injection group obviously decline, decline respectively 43.9 ± 4.7% (as Fig. 2 A compared with Wistar rat, shown in B) and 37.4 ± 6.8% (as Fig. 2 C, shown in D), the amplitude of GK rat E4 treatment group obviously improves, b wave-amplitude is that (GK rat is 121.2 ± 12.9mV to 206.7 ± 21.5mV, P < 0.05), Ops amplitude is that (GK rat is 49.6 ± 9.1mV to 91.7 ± 9.0mV, P < 0.05), the significant significant difference of nothing between the b ripple of GK rat E4 treatment group and Ops amplitude and Wistar rat, prompting E4 has protective effect to rat diabetes retinopathy.
Embodiment 2 intravitreal Exendin-4 can prevent the cell loss of the attenuation of diabetic retina thickness and each stratum nucleare, make the morphological indexes such as diabetic retinal tissue in rat thickness, outer nuclear layer cell counting approach normal level.
HE dyeing morphological examination result shows, in the retina of 16 weeks big or small GK rats, GCL, INL, ONL layer has remarkable minimizing compared with Wistar, initial cell loss appear at ganglion-cell layer (be 61.3% ± 4.8% of Wistar rat, n=12; P < 0.05, as shown in Fig. 3 A, B) and outer nuclear layer (be 72.5 ± 1.8% of Wistar rat, n=12; P < 0.05, as shown in Figure 3A), at inner nuclear layer of retina, also having obvious cell loss (is 78.7 ± 5.3% of Wistar rat, n=12; P < 0.05, as shown in Figure 3A), Exendin-4 can significantly reduce the Leukopenia amount of ganglion-cell layer, outer nuclear layer, ganglion cell's counting of Exendin-4 treatment group and outer nuclear layer cell counting are respectively 147.8 ± 14.3% and 131.6 ± 4.2% (as shown in Figure 3A) of GK normal saline injection group, and inner nuclear layer is 119.6 ± 8.7% (n=12 of GK normal saline injection group; P < 0.05, as shown in Figure 3A; The ganglion-cell layer of Exendin-4 treatment group and Wistar rat retina, outer nuclear layer, inner nuclear layer counting there was no significant difference.
Embodiment 3 intravitreal Exendin-4 can increase the expression of GLP-1R, thereby the expression of increase anti-apoptotic genes expression Bcl-xL Bcl-2 has the effect that suppresses diabetic retinal cell apoptosis
It (is 75.1 ± 2.8% of Wistar rat that the expression of GLP-1R is obviously lowered compared with Wistar rat the GK rat of 16 weeks sizes, as shown in Figure 3 B), but Exendin-4 treatment group have obvious rise (for GK rat 131.3 ± 6.2% as shown in Figure 3 B), the immunostaining of retina GLP-1R and Western blot detect the expression consistent (as shown in Figure 3 C) of GLP-1R, SABC shows that GLP-1R mainly expresses at retinochrome and (comprises ganglion-cell layer, inner molecular layer, inner nuclear layer) and the internal segment (as shown in Figure 3 C) of photoreceptor,
Apoptosis-related genes (the Bcl-2 that Western blot detection line plastochondria relies on, Bcl-xL and Bax) expression demonstration, with the comparison of Wistar rat, it (is 72.3 ± 2.7% and 54.7 ± 6.1% of Wistar rat that the expression ratio of the Bcl-xL/Bax of GK rat and Bcl-2/Bax all has decline, as shown in Figure 3 D), but it (is 131 ± 3.1% and 150 ± 9.5% of GK rat, as shown in Figure 3 D) that Exendin-4 treatment group is significantly increased.
Embodiment 4 intravitreal Exendin-4 have the effect that suppresses retinal gliocytes activation
Glial fibrillary acidic protein (GFAP) is the important symbol thing of Muller cell and astrocyte in retinal tissue, it act as RGC metabolism and nutritional support is provided, and maintain the stable state of extracellular ion and neurotransmitter, in the time of retina injury, also can bring into play cytophagous effect, bring out inflammation and immunne response, in retina environment, serve as the key factor of immune surveillance and regulation and control, glial cell excessive activation can cause amphiblestroid damage; As shown in Figure 4, after damage, the expression of GFAP is significantly raised, and in Exendin-4 treatment group, described medicine Exendin-4 is in the effect of transcribing and translation skill all has significant inhibition glial cell to activate.
Claims (8)
1. the purposes of analog Exendin-4 in glucagon like peptide-1 in preparation ophthalmic diseases medicine.
2. by purposes claimed in claim 1, it is characterized in that, described ophthalmic diseases is diabetic retinopathy.
3. by purposes claimed in claim 2, it is characterized in that, described diabetic retinopathy is that ischemic lesions or nerve injury sexually transmitted disease (STD) become.
4. by purposes claimed in claim 1, it is characterized in that, described described medicine is to improve visual function medicine.
5. by purposes claimed in claim 1, it is characterized in that, described glucagon like peptide-1 analog Exendin-4 alleviates retinal morphology damage and changes, and maintains ganglionic cell and inner molecular layer and whole retinal thickness.
6. by purposes claimed in claim 1, it is characterized in that, described glucagon like peptide-1 analog Exendin-4 reduces retinal ganglial cells and loses.
7. by purposes claimed in claim 1, it is characterized in that, described glucagon like peptide-1 analog Exendin-4 suppresses the retina injury that Glial Activation causes.
8. by purposes claimed in claim 1, it is characterized in that, described glucagon like peptide-1 analog Exendin-41 suppresses retinal cell apoptosis.
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9670261B2 (en) | 2012-12-21 | 2017-06-06 | Sanofi | Functionalized exendin-4 derivatives |
| CN106822182A (en) * | 2016-12-27 | 2017-06-13 | 广州姿生生物科技有限公司 | A kind of cell extract and application thereof |
| US9694053B2 (en) | 2013-12-13 | 2017-07-04 | Sanofi | Dual GLP-1/glucagon receptor agonists |
| US9751926B2 (en) | 2013-12-13 | 2017-09-05 | Sanofi | Dual GLP-1/GIP receptor agonists |
| US9750788B2 (en) | 2013-12-13 | 2017-09-05 | Sanofi | Non-acylated exendin-4 peptide analogues |
| US9758561B2 (en) | 2014-04-07 | 2017-09-12 | Sanofi | Dual GLP-1/glucagon receptor agonists derived from exendin-4 |
| US9771406B2 (en) | 2014-04-07 | 2017-09-26 | Sanofi | Peptidic dual GLP-1/glucagon receptor agonists derived from exendin-4 |
| US9775904B2 (en) | 2014-04-07 | 2017-10-03 | Sanofi | Exendin-4 derivatives as peptidic dual GLP-1/glucagon receptor agonists |
| US9789165B2 (en) | 2013-12-13 | 2017-10-17 | Sanofi | Exendin-4 peptide analogues as dual GLP-1/GIP receptor agonists |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| US9982029B2 (en) | 2015-07-10 | 2018-05-29 | Sanofi | Exendin-4 derivatives as selective peptidic dual GLP-1/glucagon receptor agonists |
| CN111166870A (en) * | 2020-03-18 | 2020-05-19 | 复旦大学附属眼耳鼻喉科医院 | Application of exenatide in preparation of medicine for treating ocular ischemic diseases and improving ocular blood circulation through eye drops |
| US10758592B2 (en) | 2012-10-09 | 2020-09-01 | Sanofi | Exendin-4 derivatives as dual GLP1/glucagon agonists |
| US10806797B2 (en) | 2015-06-05 | 2020-10-20 | Sanofi | Prodrugs comprising an GLP-1/glucagon dual agonist linker hyaluronic acid conjugate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1737150A (en) * | 2005-07-22 | 2006-02-22 | 浙江大学 | Adiponectin-Glucagon-like peptide-1-like peptide recombinant protein expression vector and construction |
| CN102153652A (en) * | 2010-12-10 | 2011-08-17 | 浙江大学 | Expression method and application of fusion protein |
-
2012
- 2012-12-31 CN CN201210595101.9A patent/CN103908657A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1737150A (en) * | 2005-07-22 | 2006-02-22 | 浙江大学 | Adiponectin-Glucagon-like peptide-1-like peptide recombinant protein expression vector and construction |
| CN102153652A (en) * | 2010-12-10 | 2011-08-17 | 浙江大学 | Expression method and application of fusion protein |
Non-Patent Citations (1)
| Title |
|---|
| 张瑜: ""Exendin-4类似物对糖尿病大鼠视网膜电图的保护作用"", 《中国博士学位论文全文数据库（医药卫生科技辑）》, 15 April 2010 (2010-04-15), pages 065 - 9 * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10758592B2 (en) | 2012-10-09 | 2020-09-01 | Sanofi | Exendin-4 derivatives as dual GLP1/glucagon agonists |
| US9670261B2 (en) | 2012-12-21 | 2017-06-06 | Sanofi | Functionalized exendin-4 derivatives |
| US10253079B2 (en) | 2012-12-21 | 2019-04-09 | Sanofi | Functionalized Exendin-4 derivatives |
| US9745360B2 (en) | 2012-12-21 | 2017-08-29 | Sanofi | Dual GLP1/GIP or trigonal GLP1/GIP/glucagon agonists |
| US9751926B2 (en) | 2013-12-13 | 2017-09-05 | Sanofi | Dual GLP-1/GIP receptor agonists |
| US9750788B2 (en) | 2013-12-13 | 2017-09-05 | Sanofi | Non-acylated exendin-4 peptide analogues |
| US9789165B2 (en) | 2013-12-13 | 2017-10-17 | Sanofi | Exendin-4 peptide analogues as dual GLP-1/GIP receptor agonists |
| US9694053B2 (en) | 2013-12-13 | 2017-07-04 | Sanofi | Dual GLP-1/glucagon receptor agonists |
| US9758561B2 (en) | 2014-04-07 | 2017-09-12 | Sanofi | Dual GLP-1/glucagon receptor agonists derived from exendin-4 |
| US9771406B2 (en) | 2014-04-07 | 2017-09-26 | Sanofi | Peptidic dual GLP-1/glucagon receptor agonists derived from exendin-4 |
| US9775904B2 (en) | 2014-04-07 | 2017-10-03 | Sanofi | Exendin-4 derivatives as peptidic dual GLP-1/glucagon receptor agonists |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| US10806797B2 (en) | 2015-06-05 | 2020-10-20 | Sanofi | Prodrugs comprising an GLP-1/glucagon dual agonist linker hyaluronic acid conjugate |
| US9982029B2 (en) | 2015-07-10 | 2018-05-29 | Sanofi | Exendin-4 derivatives as selective peptidic dual GLP-1/glucagon receptor agonists |
| CN106822182A (en) * | 2016-12-27 | 2017-06-13 | 广州姿生生物科技有限公司 | A kind of cell extract and application thereof |
| CN111166870A (en) * | 2020-03-18 | 2020-05-19 | 复旦大学附属眼耳鼻喉科医院 | Application of exenatide in preparation of medicine for treating ocular ischemic diseases and improving ocular blood circulation through eye drops |
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Application publication date: 20140709 |