CN109395065A - A kind of polypeptide is used to prepare the purposes of slimming medicine - Google Patents
A kind of polypeptide is used to prepare the purposes of slimming medicine Download PDFInfo
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- CN109395065A CN109395065A CN201710714470.8A CN201710714470A CN109395065A CN 109395065 A CN109395065 A CN 109395065A CN 201710714470 A CN201710714470 A CN 201710714470A CN 109395065 A CN109395065 A CN 109395065A
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- A—HUMAN NECESSITIES
- 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
- A61K38/22—Hormones
- A61K38/26—Glucagons
Abstract
The present invention relates to the purposes that a kind of polypeptide is used to prepare slimming medicine, the sequences of the polypeptide are as follows: HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRGSSGAPPPS.The present invention is that known peptide develops new purposes, and new healing potion is also had found for obesity.
Description
Technical field
The present invention relates to the purposes that a kind of polypeptide is used to prepare slimming medicine, are used to prepare and subtract in particular to polypeptide P8
The purposes of fertile drug belongs to biochemical pharmacy technical field.
Background technique
Obesity has become a kind of epidemic disease for seriously threatening health in the world, and either developed country is still sent out
Country is faced with the puzzlement of obesity accelerated development in exhibition, brings huge medical expense and burden on society therewith.According to statistics,
Existing 1,500,000,000 overweight and 500,000,000 obese patients in the whole world at present.For the crowd high for these BMI indexes, obesity can cause other
The rising of some diseases disease incidence, wherein being the most significantly cardiovascular disease, diabetes and cancer.
Mainly there are surgical operation and two kinds of drug therapy about fat medical treatments, stomach is reduced by bariatric surgery
Size, the amount that increases feeling of repletion, reduce food intake, to achieve the effect that weight-reducing, but bariatric surgery has serious hand
The risk of art and Metabolic complication, and it is very expensive to perform the operation, therefore drug therapy is more main selection.
Application No. is CN201610805193.7, application publication numbers to be in 2016.09.06 application by inventor
The Chinese invention patent application of CN106279400A, entitled " design of P8 incretin peptide and application thereof ", the hypoglycemic being directed to
Lipopeptid P8 is adjusted, half-life period can be increased, play the effect of its GLP1 receptor agonist, while the work of GLP1 class pancreas islet can be played
Use hypoglycemic fat-regulating;P8 peptide is able to suppress the feed of STZ diabetic mice, reduces fasting blood-glucose, reduces triglycerides and trip
From fatty acid levels, pancreas islet form is kept, increases beta Cell of islet area, improves the C peptide level of blood, play its hypoglycemic fat-regulating
Effect.
On the basis of above-mentioned be fruitful, inventor has obtained new research achievement through further practical studies.
Summary of the invention
The technical problems to be solved by the present invention are: being based on the newest research achievement of inventor, propose that a kind of polypeptide is used for
Prepare the purposes of slimming medicine, the purposes that specifically polypeptide P8 is used to prepare slimming medicine.
Main research process of the invention is as follows: in practical studies, inventor, which filters out, can be used to prepare slimming drugs
The polypeptide of object has attempted several polypeptides having been developed that, and finds that the hypoglycemic fat-regulating peptide P8 previously obtained meets the requirements.
Technical scheme is as follows:
A kind of polypeptide is used to prepare the purposes of slimming medicine, the sequence of the polypeptide are as follows:
HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRGSSGAPPPS.Note: the polypeptide is the polypeptide P8 being mentioned above.
A kind of polypeptide is used to prepare the purposes of pharmaceutical composition for slimming, the sequence of the polypeptide are as follows:
HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRGSSGAPPPS。
In such use, described pharmaceutical composition includes the polypeptide itself or its pharmaceutical salts.
In such use, described pharmaceutical composition includes pharmaceutical carrier and/or pharmaceutically active substance.
Inventor has found that polypeptide P8 has curative effect to obesity through experiment confirmation in practical studies.
The present invention is that polypeptide P8 develops new purposes, and new healing potion is also had found for obesity.
Detailed description of the invention
Fig. 1 to Fig. 4 be respectively the embodiment of the present invention in intervention mouse heavyweight vehicle amount, percent weight, accumulate into
The change curve of appetite, fasting blood-glucose.
Fig. 5, Fig. 6 are respectively that empty stomach sugar tolerance result curve, the fasting insulin of mouse after the embodiment of the present invention is intervened are resistance to
Measure result curve.
Fig. 7 is the oxygen demand result curve of mouse after the embodiment of the present invention is intervened.
Fig. 8 and Fig. 9 is respectively that the MRI scan image of mouse after the embodiment of the present invention is intervened shows result, according to MRI scan
As a result the statistical result being calculated.
In above each figure, Vehicle or Ve indicate model control group, and P8 indicates P8 intervention group, Exendin-4 or Ex4 table
Show Exendin-4 intervention group.
Specific embodiment
Present invention is further described in detail with reference to the accompanying drawings and in conjunction with the embodiments.But the present invention is not limited to be given
Example out.
Embodiment: influence of the polypeptide P8 to obese model mouse
Several male c57 mouse adaptable fed 1 week are randomly divided into two groups, and standard normal diet feeds 10, feeding high in fat
Material feeds quantity and is greater than 30, the equal free water of each group.
(1) the successful mouse of modeling is selected
In the 12nd weekend, high lipid food nursing group mouse, empty body weight is more than or equal to 35g, and (be above standard common feeding
Expect nursing group average mice body weight 20%) mouse be obese model mouse, select 30 and be only used as model group.
(2) model group mouse is intervened respectively with polypeptide P8, Exendin-4
Since the 13rd week, continue to give standard normal diet nursing 10 mouse of group to normal diet nursing as normal
30 mouse of model group are randomly divided into 3 groups by control group (NC group), and every group 10, wherein 1 group is model control group (HFD group),
1 group is P8 intervention group (HFD+P8 group), and 1 group is Exendin-4 intervention group (HFD+Exendin-4 group).
Each group is pressed respectively to be stated experimental program and is intervened:
Normal group (NC group) 10, standard normal diet are fed, and duration 6 weeks;Model control group (HFD group) 10,
High lipid food nursing+physiological saline 0.2ml/kg intraperitoneal injection, duration 6 weeks;P8 intervention group (HFD+P8 group) 10, high lipid food
Nursing+P8 peptide 50nmol/kg, 0.2ml/kg intraperitoneal injection, duration 6 weeks;Exendin-4 intervention group (HFD+Exendin-4 group)
10, high lipid food nursing+Exendin-4 peptide 50nmol/kg, 0.2ml/kg intraperitoneal injection, duration 6 weeks.The present embodiment uses
Polypeptide P8:HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRGSSGAPPPS.Notice that the hair of observation mouse changes during intervention
Become, the situations of change such as appetite, stool and urine, activity, weight.
(3) variation of mouse fasting blood-glucose, weight, food-intake when intervening
To the mouse in (two), each mouse fasting blood-glucose, weight are detected weekly, and record to its food-intake.
The result shows that as shown in Figures 1 to 4, compared with the control group, P8 group and Exendin-4 group can significantly reduce fertilizer
Fat mouse weight, and its food-intake is declined slightly compared with control group;By its fasting blood-glucose it is found that obesity mice has slight high blood
Sugar, insulin resistance, after treating, P8 group and Exendin-4 group are down to mouse blood sugar normally.
(4) the empty stomach sugar tolerance and fasting insulin tolerance of mouse after intervening
To the mouse in (two), after intervention, model control group, P8 intervention group, Exendin-4 intervention group are distinguished
Carry out empty stomach sugar tolerance and the detection of fasting insulin tolerance.
Empty stomach sugar tolerance detection process is as follows: obesity mice empty stomach 12h, surveys fasting blood-glucose, and injectable dextrose monohydrate immediately
(1.0g/kg) records blood glucose value, draws 15 after injectable dextrose monohydrate, 30,45,60,120min detection blood glucose respectively later
Curve, area under calculated curve.
Fasting insulin tolerance detection process is as follows: obesity mice empty stomach 4h, surveys fasting blood-glucose, and insulin injection immediately
(0.5U/kg) records blood glucose value, draws curve 15 after injectable dextrose monohydrate, 30,45,60min detection blood glucose respectively later,
Area under calculated curve.
The result of empty stomach sugar tolerance is as shown in figure 5, from the point of view of glucose tolerance test area under the curve (GTT AUC), P8
Group is significantly less than control group with the area under the curve of Exendin-4 group, and compared with the control group with notable difference (P8:P <
0.005;Exendin-4:P < 0.001).
The result of fasting insulin tolerance from insulin tolerance tests area under the curve (ITT AUC) as shown in fig. 6, come
It sees, the area under the curve of P8 group and Exendin-4 group is significantly less than control group, and has notable difference compared with the control group
(P8:P < 0.005;Exendin-4:P < 0.001).
The result shows that obesity mice significantly improves glucose tolerance and insulin is resistance to after P8 and Exendin-4 treatment
Amount, this illustrates that polypeptide P8 can improve glucose tolerance and insulin tolerance, increases the sensibility of insulin.
(5) the oxygen demand variation of mouse after intervening
Mouse metabolism index is acquired and analyzed using open Oxymax indirect calorimetry system (Columbus company, the U.S.),
Assess the whole metabolism status of mouse.Rearing conditions in whole experiment process are as follows: 1/cage;Mouse high lipid food, is loaded on
In the included feeder of system;Mouse drinking water and routine are same with water phase, in the drinking bottle carried loaded on system;6:00-18:00
For daylight time (opening light), 18:00-6:00 is night hours (closing light);Program operation keeps surveying as far as possible after starting
It is quiet to try room.
Take mouse totally 9 after intervening in (two), model control group, P8 intervention group, Exendin-4 intervention group each 3
Only, in case oxygen demand variation detection.
Change to eliminate environment, single cage is raised, character of feed changes caused stress reaction to mouse entirety metabolic condition
Influence, test it is formal start first 3 days, 9 mouse are transferred in indirect calorimetry cage from daily rearging cage, which is made
For the laundering period, data are discarded.The data of formal experiment the l days are discarded, and are collected the 2nd day and the 3rd day data, are taken it
Average value is included in statistical analysis, carries out within the 4th day the measurement of resting metabolic rate.
The computer automatic data collection carried in each measurement circulation by system, measurement sequence is l cage, No. 2 cages, 3
Number No. 9 cages of cage ... automatically correct each parameter of 1 subsystem after 3 cages of every measurement, move in circles.Key data is collected and is divided
The shorthand method of analysis is as follows:
(1) food ration (food intake): system collects the weight change of feeder in each circulation automatically, with 12h
Or accumulating weight changing value interior for 24 hours is corrected as day night or whole day food ration with mouse weight, unit is g/kg
Body weight/day (g/kg per day).
(2) oxygen consumption (oxygen consumption, VO2): collecting mouse automatically by system, interior oxygen disappears for 24 hours
Consumption is corrected with mouse lean body mass weight (1ean mass), and unit is milliliter/lean body mass weight (kilogram)/hour (ml/
kg lean mass/h)。
The result shows that for the food ration of three groups of mouse without significant difference, this illustrates that Energy intaking is reduced during entire measurement
It is not the main reason for causing obese mouse weight and fat content to reduce.As shown in fig. 7, compared with control group mice, P8
Group and Exendin-4 group mouse oxygen consumption (VO round the clock2) dramatically increase (P < 0.05);In 24 hours, P8 group and
The energy consumption values of Exendin-4 group mouse are consistently higher than control group mice.This illustrates that mouse metabolism water can be improved in polypeptide P8
It is flat.
(6) the fat mass variation of mouse after intervening
To the mouse in (two), after intervention, model control group, P8 intervention group, Exendin-4 intervention group are distinguished
Carry out following experimentation.
Mouse body component analysis is inhaled using Lunar PIXImus penetron (Lunar company) and Dual X-ray
It receives measuring instrument (DEXA).All image analyses are all made of respiration gate control method.In entire test process, mouse temperature is protected with animal
Warm system (SA Instruments company) maintains 37 DEG C.Every mouse acquires 20 frame coronal images and 20 frame shaft-like faces
Image, thickness 1.0mm.Better adipose tissue contrast effect in order to obtain is imaged using T1-weighted spin-echo
Method detection, imaging parameters are repetition time (TR)=500ms, echo time (TE)=10.7ms, field of
View=50.0 × 45.0mm (coronal-plane), 45.0 × 45.0mm (shaft-like face), size=256 × 256. matrix are every small
Mouse at least detects twice, its mean value is taken to enter statistical analysis.
In addition, all mouse carried out magnetic resonance (MRI) analysis, instrument be Echo MRI-100 whole body form at
Point analyzer (Echo Medicine Systems company), by body scan obtain mouse body fat content (fat mass) and
Lean body mass (1ean mass) content results, and calculate its ratio with weight.Every mouse at least detects three times, takes its mean value
Into statistical analysis.
The result shows that compared with model control group mouse, fat and subcutaneous fat in P8 group and Exendin-4 group mouse abdomen
Substantially reduce;Wherein, MRI scan image shows result as shown in figure 8, the statistics knot being calculated according to MRI scan result
Fruit is as shown in Figure 9.The anatomical results of three groups of mouse also support the above results.
In conclusion P8 group mouse weight significantly mitigates compared with Vehicle group mouse, and main and body fat content is reduced
It is related.
The experimental results showed that, polypeptide P8 has curative effect to obesity above.
<110>China Medicine University
<120>a kind of polypeptide is used to prepare the purposes of slimming medicine
<160> 1
<210> 1
<211> 39
<212> PRT
<213>artificial sequence
<400> 1
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly
1 5 10 15
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Ser
20 25 30
Ser Gly Ala Pro Pro Pro Ser
35
Claims (4)
1. a kind of polypeptide is used to prepare the purposes of slimming medicine, the sequence of the polypeptide are as follows:
HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRGSSGAPPPS。
2. a kind of polypeptide is used to prepare the purposes of pharmaceutical composition for slimming, the sequence of the polypeptide are as follows:
HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRGSSGAPPPS。
3. the purposes addressed according to claim 2, characterized in that described pharmaceutical composition includes the polypeptide itself or its is medicinal
Salt.
4. the purposes addressed according to claim 2, characterized in that described pharmaceutical composition includes that pharmaceutical carrier and/or drug are living
Property substance.
Priority Applications (2)
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CN201710714470.8A CN109395065A (en) | 2017-08-18 | 2017-08-18 | A kind of polypeptide is used to prepare the purposes of slimming medicine |
PCT/CN2017/098674 WO2018045872A1 (en) | 2016-09-06 | 2017-08-23 | Polypeptide and uses thereof |
Applications Claiming Priority (1)
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CN201710714470.8A CN109395065A (en) | 2017-08-18 | 2017-08-18 | A kind of polypeptide is used to prepare the purposes of slimming medicine |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111138552A (en) * | 2020-01-15 | 2020-05-12 | 中国药科大学 | Lipid-lowering polypeptide and pharmaceutical application thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102552883A (en) * | 2010-12-09 | 2012-07-11 | 天津药物研究院 | Polypeptide compound, pharmaceutical composition, its preparation method and application thereof |
CN106279400A (en) * | 2016-09-06 | 2017-01-04 | 中国药科大学 | Design of P8 incretin peptide and application thereof |
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2017
- 2017-08-18 CN CN201710714470.8A patent/CN109395065A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102552883A (en) * | 2010-12-09 | 2012-07-11 | 天津药物研究院 | Polypeptide compound, pharmaceutical composition, its preparation method and application thereof |
CN106279400A (en) * | 2016-09-06 | 2017-01-04 | 中国药科大学 | Design of P8 incretin peptide and application thereof |
Non-Patent Citations (3)
Title |
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刘庆春等: "高血糖素样肽-1受体激动剂长期减肥效果研究", 《肠外与肠内营养》 * |
王晓婧等: "GLP-1及其受体激动剂Exendin-4临床适应症的扩展", 《生物技术通报》 * |
陈诚等: "胰高血糖素样肽1受体激动剂作用机制及其临床应用进展", 《山东医药》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111138552A (en) * | 2020-01-15 | 2020-05-12 | 中国药科大学 | Lipid-lowering polypeptide and pharmaceutical application thereof |
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