CN109276704A - Purposes of the melittin in the drug or health care product of preparation treatment and/or prevention diabetes - Google Patents
Purposes of the melittin in the drug or health care product of preparation treatment and/or prevention diabetes Download PDFInfo
- Publication number
- CN109276704A CN109276704A CN201711086519.6A CN201711086519A CN109276704A CN 109276704 A CN109276704 A CN 109276704A CN 201711086519 A CN201711086519 A CN 201711086519A CN 109276704 A CN109276704 A CN 109276704A
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- Prior art keywords
- melittin
- drug
- diabetes
- health care
- care product
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- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 title claims abstract description 58
- 108010036176 Melitten Proteins 0.000 title claims abstract description 55
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 40
- 239000003814 drug Substances 0.000 title claims abstract description 30
- 229940079593 drug Drugs 0.000 title claims abstract description 23
- 230000036541 health Effects 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 230000002265 prevention Effects 0.000 title claims abstract description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 25
- 210000004369 blood Anatomy 0.000 claims abstract description 25
- 239000008280 blood Substances 0.000 claims abstract description 25
- 239000008103 glucose Substances 0.000 claims abstract description 25
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- -1 pyrrole Ketone Chemical class 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 6
- 210000002966 serum Anatomy 0.000 claims description 6
- 229920000858 Cyclodextrin Polymers 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000012377 drug delivery Methods 0.000 claims description 4
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- 229920002472 Starch Polymers 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
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- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
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- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
- 102000009027 Albumins Human genes 0.000 claims description 2
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
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- 229960005363 aluminium oxide Drugs 0.000 claims description 2
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 claims description 2
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- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 2
- 239000003792 electrolyte Substances 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
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- 125000005456 glyceride group Chemical group 0.000 claims description 2
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- 238000001990 intravenous administration Methods 0.000 claims description 2
- 238000005342 ion exchange Methods 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000000391 magnesium silicate Substances 0.000 claims description 2
- 229910052919 magnesium silicate Inorganic materials 0.000 claims description 2
- 235000019792 magnesium silicate Nutrition 0.000 claims description 2
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 2
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- 235000013305 food Nutrition 0.000 description 1
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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
- 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
- A61K38/1767—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to biomedicine fields, and in particular to purposes of the melittin (English name Melittin) in the drug or health care product of preparation treatment and/or prevention diabetes.Animal experiments prove that, melittin of the present invention has significant anti-diabetic effect, it is embodied in, the melittin can effectively facilitate insulin secretion, to play the role of long-acting reduction blood glucose, it shows as after a period of time drug withdrawal is administered by certain frequency, still can maintain hypoglycemia for a long time, type-2 diabetes mellitus can be improved for a long time.The present invention provides a kind of completely new selection and thinking for current antidiabetic medicine, has potential potential applicability in clinical practice.
Description
Technical field
The invention belongs to biomedicine fields, and in particular to melittin (English name Melittin) is treated in preparation
And/or prevention diabetes drug or the purposes in health care product.
Background technique
Diabetes are a kind of diseases of the sugar as caused by Different types of etiopathogenises, fat and protein metabolism disorder, clinical main table
It is now hyperglycemia, typical illness is more foods, more drink, diuresis, syntexis etc..Its death rate is only second to cardiovascular disease in developed country
Disease, malignant tumour, are one of big difficult diseases of current medical field three.
In terms of global range, diabetic's growth is very rapid, and the World Health Organization predicts to 2025 global glycosuria
Patient's number will break through 300,000,000, and disease incidence also will rise to 4.4% by current 2.8%.Wherein developing diabetes patient people
Number will increase by 170%, significantly larger than the 42% of developed country.This imply that by 2025, developing diabetes patient
Shared ratio will be more than the 75% of global diabetic's sum.New cases be concentrated mainly on China, print branch subcontinent and
The developing countries such as Africa.According to incompletely statistics, diabetes mellitus in China number of patients occupies second place of the world, nearly 4.3% population at present
With diabetes.In China diabetes patient groups, type-2 diabetes mellitus accounts for 90% or more, type-1 diabetes mellitus about 5%, city gestation
Diabetes are close to 5%, other types only 0.7%.Diabetes mellitus in China prevention guideline points out that developed regions diabetes prevalence is higher than
Under-developed area, city are higher than rural area.Diabetes seriously threaten the health of the mankind, and there is inclining for extension and rejuvenation
To how to prevent and treat diabetes becomes one of the project that the world of medicine pays close attention to.
Currently, the therapeutic agent of diabetes is divided into 7 classes, including insulin and the like, sulfonylurea, biguanides, the Portugal α
Polyglycoside enzyme inhibitor, thiazolidine diketone derivative, Drugs Promoting Insulin Secretion, Chinese patent drug etc..Clinically, according to diabetes
Development process has stringent therapeutic regimen, is commonly treated more than two kinds of drugs to cooperate with, with reduce toxic side effect and
The generation of complication.However, the combination of these drugs is in the application for the treatment of diabetes, however it remains some feelings that cannot be coped with
Condition.
Melittin accounts for 50% or so of melittin dry weight, is the bipolar basic polypeptide containing 26 amino acid, molecular weight
For 2848Da, can be purified by melittin, it can also be by artificial synthesized.Without disulfide bond in secondary structure, and in side chain
Amino acid without crosslinking.It is demonstrated experimentally that there is melittin anti-inflammatory, antibacterial, antitumor, analgesia and inhibition platelet aggregation etc. to make
With having to liver fibrosis, cholangitis and biliary tract fibrosis, rheumatoid arthritis, atherosclerosis, gastric cancer, breast cancer etc.
Certain curative effect.But so far, not about the report of melittin treatment diabetes.Inventors discovered through research that bee
Phallotoxins has the function of reducing blood glucose, increases insulin, especially has the function of long-acting reduction blood glucose.It can be seen that bee venom
Peptide has the function for the treatment of and/or prevent to diabetes, can be used for drug or the health care of preparation treatment and/or prevention diabetes
Product, this provides a kind of completely new selection and thinking to treat and/or preventing diabetes, has widened the choosing for the treatment of diabetes medicament
Select field.
Summary of the invention
The purpose of the present invention is to provide melittin biomedicine field new application, and in particular to its preparation treat
And/or prevention diabetes drug or the purposes in health care product.
Wherein, the drug or health care product may include melittin and pharmaceutically acceptable carrier；
Wherein, the melittin can be artificial synthesized.
Wherein, the pharmaceutically acceptable carrier may include ion exchange material, aluminium oxide, aluminum stearate, lecithin,
Self-emulsifying drug delivery system (SEDDS) such as d- TPGS 1000, tween or other similar polymerization are situated between
The surfactants of the pharmaceutical preparations such as matter, haemocyanin such as human serum albumins, buffer substance for example phosphate, amion acetic acid,
Sorbic acid, potassium sorbate, the mixing of saturated vegetable fatty acid partial glyceride, water, salt, electrolyte such as sulfate protamine, phosphoric acid
Disodium hydrogen, potassium hydrogen phosphate, sodium chloride, zinc salt, silica gel, magnesium silicate etc..Polyvinyl pyrrolidone, cellulosic material, polyvinyl alcohol, carboxylic
Sodium carboxymethylcellulose pyce, polyacrylate, ethylene-polyoxyethylene-block polymer and lanolin, cyclodextrin such as α-, β-, γ-ring
The hydroxyalkyl cyclodextrins such as dextrin or its derivative through chemical modification such as 2- and 3- hydroxypropyl-β-cyclodextrin and its solubility are derivative
Object.
Wherein, the drug or health care product can further include pharmaceutic adjuvant, including filler (such as Lactis Anhydrous, starch,
Lactose bead and glucose), adhesive (such as microcrystalline cellulose), (such as crosslinked carboxymethyl fecula sodium, cross-linked carboxymethyl are fine for disintegrating agent
Tie up plain sodium, low-substituted hydroxypropyl cellulose and cross-linked pvp), lubricant (such as magnesium stearate), sorbefacient, flavouring agent, sweet taste
Agent, diluent, excipient, wetting agent, solvent, solubilizer and colorant etc..
Wherein, the drug-delivery preparation of the drug or health care product may include injection, creme, ointment, patch, spray
Deng.
Wherein, the administration route of the drug or health care product may include subcutaneous, intradermal, intra-arterial, intravenous, intramuscular, pass
In section, in synovia, breastbone is interior, intrathecal, intralesional, intracranial injection or infusion, oral, part, rectum, intranasal, buccal, vagina,
Sublingual, intradermal, mucous membrane, tracheae, urethral administration are administered by way of sucking aerosol, implantation accumulation and needle thorn.
Wherein, the melittin can be administered in combination with other medicines.
Wherein, the melittin may act on pancreas islet blood glucose element sample peptide-1 receptor (GLP-1R).
Wherein, the diabetes can be type-2 diabetes mellitus.
The embodiment of the present invention constructs type-2 diabetes mellitus mouse model, and applies artificial synthesized melittin to it to visit
Study carefully influence of the melittin to diabetes.Experiments verify that the invention has the following advantages:
(1) melittin of the present invention long-acting reduction blood glucose and can increase internal insulin, have the work of prevention and treatment diabetes
Property, it can be used for further preparing the drug or health care product for the treatment of and/or prevention diabetes.
(2) a kind of completely new selection and thinking are provided for current antidiabetic medicine, has widened the selection of antidiabetic medicine
Field.
Detailed description of the invention
Fig. 1 is blood glucose level variation diagram of the type-2 diabetes mellitus mouse after the intraperitoneal injection of the melittin of various concentration；
Fig. 2 is the blood glucose for melittin being persistently injected intraperitoneally one month to type-2 diabetes mellitus mouse melittin and being discontinued after two weeks
Horizontal variation diagram；
Fig. 3 is melittin to be persistently injected intraperitoneally one month to type-2 diabetes mellitus mouse melittin and be discontinued in serum after two weeks
Insulin level figure.
Fig. 4 be various concentration melittin act on MIN6 cell (mouse β cell line) after, the downstream GLP-1R ERK albumen and its
The western blot result figure of Phosphorylated products pERK.
Fig. 5 is the downstream GLP-1R AKT albumen and its phosphoric acid after 140nM melittin acts on MIN6 cell (mouse β cell line)
Change the western blot result figure of product p-AKT.
Wherein, " * " represents significant difference of the 3mg/kg melittin group compared with diabetes blank control group, and p <
0.05；" * * " represents significant difference of the 3mg/kg melittin group compared with diabetes blank control group, and p < 0.01；"***"
Represent significant difference of the 3mg/kg melittin group compared with diabetes blank control group, and p < 0.001；" # " 1mg/kg bee venom
Significant difference of the peptide group compared with diabetes blank control group, and p < 0.05.
Specific embodiment
Below with reference to embodiment, the invention will be further described.Illustrated embodiment is in order to preferably in of the invention
Appearance is illustrated, but is not that the contents of the present invention are only limitted to illustrated embodiment.So those skilled in the art according to
Foregoing invention content carries out nonessential modifications and adaptations to embodiment, still falls within protection scope of the present invention.
It is right combined with specific embodiments below in order to make those skilled in the art better understand technical solution of the present invention
The present invention is described in further detail.
1. melittin of embodiment is to the blood glucose level of type-2 diabetes mellitus mouse and the influence of insulin level in serum
1. experimental material
The preparation of 1.1 melittins
Melittin powder using chemical synthesis purity up to 98% or more.Melittin powder is dissolved in distilled water, prepares storage
The bee venom peptide solution that concentration is 1mg/ml is hidden, freezen protective is spare after packing.Respective concentration is diluted to distilled water when use.
1.2 experimental animal
4 week old type-2 diabetes mellitus mouse (C57Bksdb/db) and 4 week old wild type healthy mices.
2. experimental procedure
4 week old type-2 diabetes mellitus mouse are randomly divided into three groups of experimental groups and one group of diabetes blank control group, to three groups
The concentration of injection same volume is respectively the melittin of 3mg/kg, 1mg/kg and 0.3mg/kg in the mouse peritoneal of experimental group, to sugar
Urinate the distilled water injected in the mouse peritoneal of sick blank control group with upper volume.One group of setting normal (healthy blank) compares simultaneously
Group (this group of mouse is 4 week old wild type healthy mices), the distilled water with upper volume is injected into this group of mouse peritoneal.It will be above-mentioned
The time for injecting melittin and distilled water is to be denoted as the 0th day, is administered once later every 4 days, is administered 7 times altogether, continues 28 days, point
Not after administration the 1st day and detect within the 4th day the blood glucose levels of all mouse.After blood glucose level has rise within 4th day, again such as the
The mode of administration in 0 day injects melittin and distilled water to each group mouse respectively, and arrow is to snack made with traditional Chinese medicines, while every four in diagram
It carries out a blood glucose level detection to all mouse.It is finally stopped the blood glucose level for measuring each group mouse after two weeks again
And insulin level in serum.
3. experimental result
As shown in Figure 1, the blood glucose water through two experimental mices that intraperitoneal injection concentration is 1mg/kg and 3mg/kg melittin
It is average to be decreased significantly on day 1, average 10mmol/L level is dropped to by the average 20mmol/L elevated blood glucose levels before being administered,
It is almost the same with the blood glucose level of normal (healthy blank) control group mice.Two realities of 1mg/kg and 3mg/kg are found at the 4th day
The blood glucose level for testing the mouse of group is slightly gone up to 15mmol/L respectively, and diabetes blank control group mouse as time goes by
Blood glucose level gradually rise to 25-30mmol/L, the blood glucose level for the experimental mice being administered at this time through 3mg/kg melittin
15mmol/L is maintained, and has significant difference with the blood glucose level of diabetes blank control group mouse；Through 1mg/kg melittin
The blood glucose level of the experimental mice of administration rises to 20mmol/L, also has significant difference with 3mg/kg experimental group.
As shown in Fig. 2, melittin is discontinued 20 days after being administered continuously one month, the blood glucose water of type-2 diabetes mellitus experimental mice
It is flat to remain at reduced levels.Particularly, the blood glucose level for the experimental mice being administered through 3mg/kg melittin is right better than positive
According to medicine Exenatide.
As shown in figure 3, melittin is discontinued two weeks after being administered continuously one month, the pancreas of 1mg/kg and 3mg/kg experimental mice
Island element is horizontal to be all significantly higher than diabetes blank control group mouse and healthy blank control group mouse.
Above-mentioned experimental result illustrates that melittin is capable of the blood glucose level of (1) significant decrease type-2 diabetes mellitus mouse, and in dense
Spend dependence；(2) blood glucose of type-2 diabetes mellitus mouse is made to maintain reduced levels longer；And (3) significantly improve II type sugar
Urinate the insulin level in the serum of sick mouse.
Influence of 2. melittin of embodiment to MIN6 cell GLP-1R
1. experimental material
The preparation of 1.1 melittins
Melittin powder using chemical synthesis purity up to 98% or more.Melittin powder is dissolved in distilled water, prepares storage
The bee venom peptide solution that concentration is 7mM is hidden, freezen protective is spare after packing.Respective concentration is diluted to distilled water when use.
1.2 experimental cell
MIN6 cell (mouse β cell line)
2. experimental procedure
With 5 × 106The density in a/hole handles MIN6 cell inoculation to 6 orifice plates with the melittin of various concentration respectively,
Influence of the melittin to the downstream GLP-1R AKT albumen and ERK albumen is detected, steps are as follows:
1) to act on MIN6 respectively with the melittin of isometric 20nM, 70nM, 140nM and 10nM positive control drug Exendin-4 thin
Born of the same parents, 37 DEG C are cultivated 5 minutes and 40 minutes, and western blot detects downstream ERK phosphorylation level；
2) MIN6 cell is acted on respectively 40 minutes with isometric 140nM melittin and 10nM positive control drug Exendin-4,
Western blot detects downstream AKT phosphorylation level.
3. experimental result
As shown in figure 4, melittin has increased the phosphorylation level of the downstream GLP-1R ERK.
As shown in figure 5, melittin has increased the phosphorylation level of the downstream GLP-1R ERK.
Above-mentioned description of test, melittin play its hypoglycemic effect by acting on GLP-1R receptor.
The above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although referring to preferred embodiment to this hair
It is bright to be described in detail, those skilled in the art should understand that, it can modify to technical solution of the present invention
Or equivalent replacement, and it is detached from the objective and range of technical solution of the present invention, it should all cover in claim model of the invention
In enclosing.
Claims (9)
1. purposes of the melittin in the drug or health care product of preparation treatment and/or prevention diabetes.
2. purposes according to claim 1, which is characterized in that the drug or health care product include melittin and pharmaceutically may be used
The carrier of receiving.
3. purposes according to claim 2, which is characterized in that the melittin is artificial synthesized.
4. purposes according to claim 2, which is characterized in that the pharmaceutically acceptable carrier includes ion exchange material
Material, aluminium oxide, aluminum stearate, lecithin, self-emulsifying drug delivery system (SEDDS) such as 1000 amber of d- vitamin E polyethylene glycol
The surfactants of the pharmaceutical preparations such as amber acid esters, tween or other similar polymerisation medium, haemocyanin such as human serum albumins,
Buffer substance for example phosphate, amion acetic acid, sorbic acid, potassium sorbate, the mixing of saturated vegetable fatty acid partial glyceride, water, salt,
Electrolyte such as sulfate protamine, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, silica gel, magnesium silicate etc..Polyvinyl pyrrole
Ketone, cellulosic material, polyvinyl alcohol, sodium carboxymethylcellulose, polyacrylate, ethylene-polyoxyethylene-block polymer and sheep
The hydroxyls such as hair rouge, cyclodextrin such as α-, β-, gamma-cyclodextrin or its derivative through chemical modification such as 2- and 3- hydroxypropyl-β-cyclodextrin
Alkyl cyclodextrins and its soluble derivative.
5. purposes according to claim 2, which is characterized in that the drug or health care product further include pharmaceutic adjuvant,
Including filler (such as Lactis Anhydrous, starch, lactose bead and glucose), adhesive (such as microcrystalline cellulose), disintegrating agent (as handed over
Join sodium carboxymethyl starch, croscarmellose sodium, low-substituted hydroxypropyl cellulose and cross-linked pvp), lubricant is (as stearic
Sour magnesium), sorbefacient, flavouring agent, sweetener, diluent, excipient, wetting agent, solvent, solubilizer and colorant.
6. purposes according to claim 2, which is characterized in that the drug-delivery preparation of the drug or health care product includes injection
Agent, creme, ointment, patch, spray.
7. purposes according to claim 1, which is characterized in that the administration route of the drug or health care product include it is subcutaneous,
In intradermal, intra-arterial, intravenous, intramuscular, intra-articular, synovia, breastbone is interior, intrathecal, intralesional, intracranial injection or infusion, oral,
Part, rectum, intranasal, buccal, vagina, sublingual, intradermal, mucous membrane, tracheae, urethral administration, by sucking aerosol, implantation accumulation and
Needle thorn mode is administered.
8. purposes according to claim 1, which is characterized in that the melittin act on pancreas islet blood glucose element sample peptide -1 by
Body.
9. purposes according to claim 8, which is characterized in that the diabetes are type-2 diabetes mellitus.
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| CN111187531A (en) * | 2020-02-24 | 2020-05-22 | 南京大学 | Novel bionic antifouling paint and preparation method and application thereof |
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