CN116444617A - 一种驴皮寡肽及其应用 - Google Patents
一种驴皮寡肽及其应用 Download PDFInfo
- Publication number
- CN116444617A CN116444617A CN202310407569.9A CN202310407569A CN116444617A CN 116444617 A CN116444617 A CN 116444617A CN 202310407569 A CN202310407569 A CN 202310407569A CN 116444617 A CN116444617 A CN 116444617A
- Authority
- CN
- China
- Prior art keywords
- donkey
- alpha
- arg
- oligopeptide
- donkey skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 241000283074 Equus asinus Species 0.000 title claims abstract description 72
- 108010038807 Oligopeptides Proteins 0.000 title claims abstract description 56
- 102000015636 Oligopeptides Human genes 0.000 title claims abstract description 56
- 108010028144 alpha-Glucosidases Proteins 0.000 claims abstract description 20
- 102100024295 Maltase-glucoamylase Human genes 0.000 claims abstract description 19
- 239000003392 amylase inhibitor Substances 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 12
- 229940079593 drug Drugs 0.000 claims abstract description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 9
- 241000486679 Antitype Species 0.000 claims abstract description 5
- 235000013305 food Nutrition 0.000 claims abstract description 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 6
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 5
- 230000036541 health Effects 0.000 claims description 2
- 239000008280 blood Substances 0.000 abstract description 26
- 210000004369 blood Anatomy 0.000 abstract description 26
- 102000004139 alpha-Amylases Human genes 0.000 abstract description 16
- 108090000637 alpha-Amylases Proteins 0.000 abstract description 16
- 229940024171 alpha-amylase Drugs 0.000 abstract description 16
- 230000002401 inhibitory effect Effects 0.000 abstract description 16
- 230000001603 reducing effect Effects 0.000 abstract description 10
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 101710171801 Alpha-amylase inhibitor Proteins 0.000 abstract description 2
- 210000003491 skin Anatomy 0.000 description 45
- 108090000765 processed proteins & peptides Proteins 0.000 description 35
- 102000008186 Collagen Human genes 0.000 description 23
- 108010035532 Collagen Proteins 0.000 description 23
- 229920001436 collagen Polymers 0.000 description 23
- 229920002472 Starch Polymers 0.000 description 20
- 239000008107 starch Substances 0.000 description 20
- 235000019698 starch Nutrition 0.000 description 20
- 230000000694 effects Effects 0.000 description 17
- 238000000926 separation method Methods 0.000 description 15
- 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 description 13
- 239000008103 glucose Substances 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000010828 elution Methods 0.000 description 11
- 229920005654 Sephadex Polymers 0.000 description 10
- 239000012507 Sephadex™ Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 108010010803 Gelatin Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- 229920000159 gelatin Polymers 0.000 description 8
- 239000008273 gelatin Substances 0.000 description 8
- 235000019322 gelatine Nutrition 0.000 description 8
- 235000011852 gelatine desserts Nutrition 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 206010012601 diabetes mellitus Diseases 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 239000004382 Amylase Substances 0.000 description 5
- 102000013142 Amylases Human genes 0.000 description 5
- 108010065511 Amylases Proteins 0.000 description 5
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 5
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 235000019418 amylase Nutrition 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 238000004007 reversed phase HPLC Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 230000003914 insulin secretion Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229940097043 glucuronic acid Drugs 0.000 description 3
- 239000000413 hydrolysate Substances 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000004885 tandem mass spectrometry Methods 0.000 description 3
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 2
- IFBHRQDFSNCLOZ-IIRVCBMXSA-N 4-nitrophenyl-α-d-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-IIRVCBMXSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 2
- 108090000145 Bacillolysin Proteins 0.000 description 2
- 108091005658 Basic proteases Proteins 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- OYIFNHCXNCRBQI-BYPYZUCNSA-N L-2-aminoadipic acid Chemical compound OC(=O)[C@@H](N)CCCC(O)=O OYIFNHCXNCRBQI-BYPYZUCNSA-N 0.000 description 2
- 102000035092 Neutral proteases Human genes 0.000 description 2
- 108091005507 Neutral proteases Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 229940126904 hypoglycaemic agent Drugs 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- 108010007337 Azurin Proteins 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 230000010736 Chelating Activity Effects 0.000 description 1
- 102100023336 Chymotrypsin-like elastase family member 3B Human genes 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 108010088406 Glucagon-Like Peptides Proteins 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 241000276701 Oreochromis mossambicus Species 0.000 description 1
- 241000276703 Oreochromis niloticus Species 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- FBQHKSPOIAFUEI-OWLDWWDNSA-N Thr-Trp-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(O)=O FBQHKSPOIAFUEI-OWLDWWDNSA-N 0.000 description 1
- 241000276707 Tilapia Species 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 102000016679 alpha-Glucosidases Human genes 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229910001448 ferrous ion Inorganic materials 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000000491 multivariate analysis Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108010043524 protease E Proteins 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Polymers & Plastics (AREA)
- Biochemistry (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明公开了一种驴皮寡肽,该驴皮寡肽的氨基酸序列为Arg‑Arg‑Glu‑Val‑Pro。本发明还公开了其应用。本发明公开的驴皮寡肽具有α‑葡萄糖苷酶和α‑淀粉酶抑制活性,能辅助降血糖,对开发具有降血糖的食品、保健品和药品具有十分重要的意义,可用于制备α‑葡萄糖苷酶、α‑淀粉酶抑制剂及抗Ⅱ型糖尿病药物。
Description
技术领域
本发明涉及寡肽技术领域,具体涉及一种驴皮寡肽及其应用。
背景技术
驴皮,为马科动物驴(Equus asinus L.)的表皮,富含优质胶原蛋白,阿胶是驴皮(干燥皮或鲜皮)经煎熬、浓缩等工艺加工炮制而成的中药饮片,具有补血滋阴,润燥,止血等功能,可用于主治血虚萎黄、眩晕心悸等,已收录于《中华人民共和国药典》(一部)、《中药大辞典》等,因此,驴皮胶原蛋白的氨基酸组成及氨基酸序列可能有别于其他动物来源的胶原蛋白。
驴皮胶原肽是以驴皮为原料,利用酶法制得而成的一类蛋白质、多肽、寡肽和氨基酸的混合物(含量以寡肽为主)。其中的寡肽是一类氨基酸残基数目在2~10个的小肽,有报道称阿胶中分子量在1000Da以下的寡肽和一些蛋白质分子是阿胶发挥其药理作用的主要物质基础。
如申请号为CN202111417049.3的中国专利文献中公开了一种低促炎症反应阿胶肽的制备方法及产品,包括:(1)将阿胶块粉粹;(2)粉粹后的阿胶在非特异性酶链酶蛋白酶E作用下酶解3-5小时;(3)糖酶解液加入蛋白酶进行酶解,使得酶解产物分子量在1000-3000Da之间,高温灭酶;(4)酶解液冷冻干燥,获得一种促炎症反应的阿胶肽。
申请号为CN202011410008.7的中国专利文献中公开了一种驴皮胶原蛋白的制备方法,包括:(1)驴皮预处理;(2)酶解膜循环分离;(3)脱色及脱醒处理;(4)冷冻干燥,得到分子量2-5kD驴皮胶原蛋白粉末,该胶原蛋白的三股螺旋结构没有被破坏,仍保留原生物活性。
再如申请号为CN202110143314.7的中国专利文献,公开了一种高谷氨酸驴胶原肽的制备方法,采用(1)复合酶解技术(2)亲和层析方法,从驴胶原蛋白中分离得到高谷氨酸胶原活性肽,其对亚铁离子、钙离子和锌离子具有较强的螯合活性。
但以上技术方案得到的驴皮胶原蛋白肽或驴胶原活性肽属于胶原蛋白原料利用活性酶水解后得到的酶解产物,其主要由不同分子量的肽、蛋白质和氨基酸等组成的混合物,具有一定分子量分布范围的特点。
酶解产物组成的肽之间分子量较为接近,依靠单一的分离方法难以达到分离的目的,目前肽的分离方法主要根据肽的分子量大小、带电性、疏水性等物性之间的差别,采用膜分离、层析、色谱等多种分离手段相结合的方法达到分离的目的。
目前已报道的活性寡肽的生物活性有抗氧化、降血糖、提高免疫功能等,如XU等(XU Q Y,ZHENG L,HUANG M T,et al.Exploring structural features of potentdipeptidyl peptidaseⅣ(DPP-Ⅳ)inhibitory peptides derived from tilapia(Oreochromis niloticus)skin gelatin by an integrated approach of multivariateanalysis and Gly-Pro-based peptide library[J])将罗非鱼的鱼皮进行水解,经分离纯化后得到几种二肽基肽酶-Ⅳ抑制活性的寡肽,其肽链结构带有-Gly-Pro-残基,可以促进胰高血糖素样肽和胰岛素的分泌,提高胰岛素水平,降低血糖的作用。
Mudgil P等(Mudgil P,Jobe B,Kamal H,et al.Dipeptidyl peptidese-Ⅳ,α-amylase,and angiotensinIconverting enzyme inhibitory properties of novelcamel skin gelatin hydrolysates[J])利用三种酶解方式(碱性蛋白酶、中性蛋白酶、碱性蛋白酶和中性蛋白酶的混合物)对骆驼皮胶原蛋白进行了水解,得到具有二肽基肽酶-Ⅳ抑制活性和α-淀粉酶抑制活性的水解产物,其不仅可以促进胰岛素的分泌,还可以抑制淀粉酶和葡萄糖苷酶的分解,维持体内血糖正常水平。
糖尿病是一组以高血糖为特征的代谢性疾病,高血糖则是由于胰岛素分泌缺陷或其生物作用受损,或两者兼有引起。降糖药按照降糖机理大致分为三种:(1)刺激胰岛素的分泌,如磺脲类药物;(2)增加外周组织对葡萄糖的利用,如双胍类降糖药;(3)α-葡萄糖苷酶抑制剂,如临床上常用的阿卡波糖等。
但是,目前尚未有报道对驴皮酶解产物进行分离纯化获得具有具体氨基酸序列并具有α-葡萄糖苷酶和α-淀粉酶抑制活性,能够应用于Ⅱ型糖尿病的胶原肽。
发明内容
本发明针对现有技术中存在的问题,提供了具有新型氨基酸序列的一种驴皮寡肽,经活性试验和降血糖动物试验发现,该驴皮寡肽具有α-葡萄糖苷酶和α-淀粉酶抑制活性,能辅助降血糖。
本发明采用如下技术方案:
本发明第一方面提供了一种驴皮寡肽,其氨基酸序列为Arg-Arg-Glu-Val-Pro。
本发明第二方面提供了上述驴皮寡肽在制备降糖食品、保健品、药品中的应用
本发明第三方面提供了上述驴皮寡肽在制备α-葡萄糖苷酶和α-淀粉酶抑制剂中的应用。
本发明第四方面提供了上述驴皮寡肽在制备抗Ⅱ型糖尿病药物中的应用。
本发明的有益效果:
1、本发明得到了三种具有新型氨基酸序列结构的驴皮寡肽Arg-Arg-Glu-Val-Pro、Glu-Thr-Trp-Arg、Ala-Tyr-Phe-Pro-Lys,该三种驴皮寡肽具有α-葡萄糖苷酶和α-淀粉酶抑制活性,能辅助降血糖,对开发具有降血糖的食品、保健品和药品具有十分重要的意义,可用于制备α-葡萄糖苷酶、α-淀粉酶抑制剂及抗Ⅱ型糖尿病药物。优选地,氨基酸序列为Arg-Arg-Glu-Val-Pro的驴皮寡肽具有更佳的α-葡萄糖苷酶、α-淀粉酶抑制效果和更佳的降血糖效果。
2、本发明针对酶解法制备的驴皮胶原肽混合肽分子量小,而且混合肽的分子量集中,分散性小的特点,采用由填料为葡聚糖凝胶树脂Sephadex G-15的层析分离方法对其进行粗分,再经反相高效液相色谱技术进一步分离,最终经LC-TOF-MS/MS肽结构分析鉴定得到三种新型的驴皮寡肽,经活性试验和降血糖动物试验发现,该三种驴皮寡肽具有α-葡萄糖苷酶和α-淀粉酶抑制活性,能辅助降血糖。
附图说明
图1为采用填料为葡聚糖凝胶树脂Sephadex G-15的葡聚糖凝胶色谱柱分离得到的分离组分的洗脱曲线,横坐标为洗脱体积(mL),纵坐标为波长为254nm处的吸光值。
图2为采用填料为葡聚糖凝胶树脂Sephadex G-10的葡聚糖凝胶色谱柱分离得到的分离组分的洗脱曲线,横坐标为洗脱体积(mL),纵坐标为波长为254nm处的吸光值。
图3为采用填料为葡聚糖凝胶树脂Sephadex G-25的葡聚糖凝胶色谱柱分离得到的分离组分的洗脱曲线,横坐标为洗脱体积(mL),纵坐标为波长为254nm处的吸光值。
图4为组分C的Re-HPLC谱图,横坐标为保留时间(min),纵坐标为响应值。
图5为LC-TOF-MS/MS肽结构分析鉴定的质谱图,从上至下分别是Arg-Arg-Glu-Val-Pro、Glu-Thr-Trp-Arg、Ala-Tyr-Phe-Pro-Lys。
具体实施方式
下面结合实施例和附图对本发明做更进一步地解释。下列实施例仅用于说明本发明,但并不用来限定本发明的实施范围。
以下涉及的α-葡萄糖苷酶抑制活性测定,方法如下:以4-硝基苯-α-吡喃葡萄糖苷(PNPG)为底物,反应体系为:2mL的0.1mol/L磷酸盐缓冲液(pH6.8),加入0.5mL待测样品水溶液、50μL 1mg/mL还原谷胱甘肽和10μLα-葡萄糖苷酶(TypeⅠ,from Saccharomycescerevisiae,11.4U/mL),摇匀后,37℃温浴10min,然后加入200μL温浴好的底物PNPG(20mmol/L),37℃温浴20min后,加入10mL 0.1mol/LNa2CO3溶液终止反应,在波长400nm处测吸光度。
α-葡萄糖苷酶抑制率(%)=(1-A样/A空)×100%,A空表示空白试剂的吸光度(不加样品,以去离子水替代),A样表示样品吸光度。
以下涉及的α-淀粉酶抑制活性测定,方法如下:1ml待测样品水溶液、1ml淀粉天青(用0.05mol/L、pH6.9Tris-HCl缓冲液配成2mg/mL悬液,煮沸5min)和50μLα-淀粉酶(TypeⅥ-B,from porcine pancrcase,4.71U/mL,0.05mol/L、pH6.9Tris-HCl缓冲溶液配制)混合,38℃温浴10min,加0.2mL50%v/v冰乙酸水溶液终止反应,6000rpm离心5min,上清液于595nm处测吸光度。
α-淀粉酶抑制率(%)=(1-A样/A空)×100%,A空表示空白试剂的吸光度(不加样品,以去离子水替代),A样表示样品吸光度。
实施例1
(1)原料处理:取新鲜健康驴皮,剔除残肉,置清水中浸泡3-5天,每天换水1-2次,剔除驴毛,洗净杂物,切成10cm×10cm左右的小块,放入沸水中煮10min,至驴皮卷时捞出。
煎熬浓缩:按料液质量比1:5加入清水,煎熬36h左右,随时添足蒸发的水分,每2-3h搅拌1次,待驴皮烧至软化,用组织捣碎机打碎成糊状,无明显颗粒物,加热蒸发浓缩,每300克原始驴皮制成500克驴皮原料。
酶解:将上述得到的驴皮原料100g、胰酶(南宁庞博生物工程有限公司,4000U/g)0.35g和水300mL置于1000mL玻璃烧杯中,混合均匀,将玻璃烧杯置于55℃恒温水浴中,用1mol/LNaOH或1mol/LHCl调节酶解反应体系pH值至6.0,并用搅拌器搅拌反应液,控制转速至300rpm,反应8h,升温至90℃灭酶20min,取出反应液,冷却,过滤,得到滤液即为驴皮酶解产物(驴皮胶原肽混合肽),驴皮胶原肽混合肽得率达70.0%。经活性测试发现,该驴皮胶原肽混合肽对α-葡萄糖苷酶的抑制活性IC50为38.13mg/mL,α-淀粉酶抑制活性为55.56mg/mL。
经测试,该驴皮胶原肽混合肽中,分子质量为180-1000Da的物质占73%,由此可见,得到的驴皮胶原肽混合肽主要是氨基酸残基在2-10个之间的寡肽。
(2)将滤液用截留分子量3000Da的中空纤维聚砜超滤膜进行超滤,取滤过液,并对其进行减压蒸馏浓缩、冷冻干燥,得到分子量<3000Da的驴皮胶原肽;
(3)称取驴皮胶原肽2g,加水2mL溶解,取1mL驴皮胶原肽水溶液上葡聚糖凝胶色谱柱,该葡聚糖凝胶色谱柱规格为2.6cm×88cm,填料为葡聚糖凝胶树脂Sephadex G-15,流动相为去离子水,柱流速为1.0mL/min,洗脱后得到分离组分A、B、C和D(四分离组分的洗脱曲线见图1,波长为254nm)。
经活性试验发现,分离组分A、B、C和D对α-葡萄糖苷酶的抑制活性IC50分别为40.15mg/mL、38.30mg/mL,22.8mg/mL、60.59mg/mL,对α-淀粉酶的抑制活性IC50分别为62.37mg/mL,48.26mg/mL,40.09mg/mL,无活性。
将填料换为葡聚糖凝胶树脂Sephadex G-10,观察其洗脱曲线(图2)发现,该分离工艺无法实现有效分离。
将填料换为葡聚糖凝胶树脂Sephadex G-25,观察其洗脱曲线(图3)发现,该分离工艺也无法实现有效分离。
(4)利用反相高效液相色谱(Re-HPLC)技术进一步分离步骤(3)得到的α-葡萄糖苷酶和α-淀粉酶抑制活性最强的组分C,分离条件为:色谱柱:Angilent Eclipse XDB-C18柱(250×4.6mm,5μm),流动相:A液:0.1%v/v三氟乙酸(TFA)水溶液,B液:80%v/v乙腈水溶液,线性梯度洗脱:0-5min,100%-80%A;5-50min,80%-0%A,50-60min,0%A,60-70min,100%A,流速:1.0mL/min,柱温:30℃,检测波长:340nm。Re-HPLC谱图如图4所示。
如图5所示,经LC-TOF-MS/MS肽结构分析鉴定,本实施例分离得到三种驴皮寡肽,氨基酸序列分别为Arg-Arg-Glu-Val-Pro(RREVP)、Glu-Thr-Trp-Arg(ETWR)、Ala-Tyr-Phe-Pro-Lys(AYFPK)。
经活性试验发现,以上三者的α-葡萄糖苷酶抑制活性IC50分别为6.8mg/mL、9.3mg/mL、12.5mg/mL,α-淀粉酶抑制活性IC50分别为11.4mg/mL、20.1mg/mL、27.7mg/mL。
因此,所述三种驴皮寡肽均可应用于制备α-葡萄糖苷酶和α-淀粉酶抑制剂。优选地,氨基酸序列为Arg-Arg-Glu-Val-Pro的驴皮寡肽具有更佳的α-葡萄糖苷酶和α-淀粉酶抑制效果。
α-葡萄糖苷酶抑制剂作用机制为:竞争性抑制位于小肠的各种α-葡萄糖苷酶,使淀粉类分解为葡萄糖的速度减慢,从而减缓肠道内葡萄糖的吸收,降低餐后高血糖。Ⅱ型糖尿病是由于餐后高血糖的葡萄糖毒性可加重胰岛素抵抗及胰岛素分泌缺陷,当胰岛β细胞功能仅剩约50%时,出现空腹血糖升高,糖耐量受损。
α-淀粉酶抑制剂作用机制为:封闭α-淀粉酶的作用位点抑制其活性,阻止淀粉被消化;抑制淀粉酶的合成,降低其在肠道内的活性;抑制淀粉酶的集聚阻止其活化,抑制体内血糖升高。体内淀粉酶的作用是催化淀粉类的化合物,将其催化成葡萄糖醛酸,葡萄糖醛酸在体内糖醛酸酶的作用下被分解成葡萄糖,葡萄糖醛酸和葡萄糖都是机体可直接利用的糖类物质,淀粉酶活性的增强直接影响人体内血糖水平的高低。
基于以上研究发现,本发明公开的三种驴皮寡肽还可进一步用于制备抗Ⅱ型糖尿病药物,优选地,氨基酸序列为Arg-Arg-Glu-Val-Pro的驴皮寡肽具有更佳的降血糖效果。
以下对分离得到的三种驴皮寡肽Arg-Arg-Glu-Val-Pro、Glu-Thr-Trp-Arg、Ala-Tyr-Phe-Pro-Lys分别进行了降血糖动物试验:Arg-Arg-Glu-Val-Pro设置了0.5g/kg剂量驴皮寡肽组、0.2g/kg剂量驴皮寡肽组,Glu-Thr-Trp-Arg设置了0.5g/kg剂量驴皮寡肽组、0.2g/kg剂量驴皮寡肽组,Ala-Tyr-Phe-Pro-Lys设置了1.0g/kg剂量驴皮寡肽组、0.5g/kg剂量驴皮寡肽组;Arg-Arg-Glu-Val-Pro、Glu-Thr-Trp-Arg、Ala-Tyr-Phe-Pro-Lys均设置了正常对照组、模型对照组,并均设置了0.01g/kg剂量拜糖平组作为阳性对照。各驴皮寡肽组、模型对照组、拜糖平组所用动物为四氧嘧啶型糖尿病模型小鼠(Ⅱ型糖尿病),各正常对照组所用动物为ICR小鼠。降血糖动物试验用的寡肽利用固相合成法获得,委托吉尔生化(上海)有限公司进行。
各动物禁食3-5h,测定给淀粉前(0h)血糖值,各驴皮寡肽组给予同体积相应浓度受试样品(水溶液),拜糖平组给予同体积0.01g/kg剂量拜糖平,正常对照组、模型对照组给予同体积无菌水,15-20min后各组经口给予淀粉3-5g/kgBW,测定给予淀粉后0.5、1、2、3h的血糖值,观察模型对照组与各驴皮寡肽组给予淀粉后各时间点血糖值和曲线下面积的变化,同时以拜糖平为阳性对照。
结果发现:这三种驴皮寡肽均能降低糖的吸收速度,明显改善糖耐量,实验结果如表1、表2、表3所示。
表1为Arg-Arg-Glu-Val-Pro对四氧嘧啶型糖尿病模型小鼠淀粉负荷耐量的影响,表1结果显示,0.5g/kg剂量驴皮寡肽组给淀粉后0.5、1、2、3h时间点、0.2g/kg剂量驴皮寡肽组给淀粉后0.5h时间点,血糖值明显低于模型对照组(P<0.05)。各剂量驴皮寡肽组与模型对照组比较,血糖值上升缓慢,峰值降低;而且均能减少曲线下面积,并呈明显的剂量关系。
表1Arg-Arg-Glu-Val-Pro对四氧嘧啶型糖尿病模型小鼠淀粉负荷耐量的影响( n=10)
注:表示均数±标准差,n表示每组10只小鼠,P<0.05表示差异有显著性,△△P<0.05与模型对照组比较,**P<0.05与正常对照组比较。
表2为Glu-Thr-Trp-Arg对四氧嘧啶型糖尿病模型小鼠淀粉负荷耐量的影响,表2结果显示,0.5g/kg剂量驴皮寡肽组给淀粉后0.5、1、2、3h时间点、0.2g/kg剂量驴皮寡肽组给淀粉后0.5、1、2h时间点,血糖值明显低于模型对照组(P<0.05)。各剂量驴皮寡肽组与模型对照组比较,血糖值上升缓慢,峰值降低;而且均能减少曲线下面积,并呈明显的剂量关系。
表2Glu-Thr-Trp-Arg对四氧嘧啶型糖尿病模型小鼠淀粉负荷耐量的影响(n=10)
注:表示均数±标准差,n表示每组10只小鼠,P<0.05表示差异有显著性,△△P<0.05与模型对照组比较,**P<0.05与正常对照组比较。
表3为Ala-Tyr-Phe-Pro-Lys对四氧嘧啶型糖尿病模型小鼠淀粉负荷耐量的影响,表3结果显示,1.0g/kg剂量驴皮寡肽组给淀粉后0.5、1、2、3h时间点、0.5g/kg剂量驴皮寡肽组给淀粉后0.5、1、3h时间点,血糖值明显明显低于模型对照组(P<0.05)。各剂量驴皮寡肽组与模型对照组比较,血糖值上升缓慢,峰值降低;而且均能减少曲线下面积,并呈明显的剂量关系。
表3Ala-Tyr-Phe-Pro-Lys对四氧嘧啶型糖尿病模型小鼠淀粉负荷耐量的影响(n=10)
注:表示均数±标准差,n表示每组10只小鼠,P<0.05表示差异有显著性,△△P<0.05与模型对照组比较,**P<0.05与正常对照组比较。
Claims (4)
1.一种驴皮寡肽,其特征在于,其氨基酸序列为Arg-Arg-Glu-Val-Pro。
2.权利要求1所述的驴皮寡肽在制备降糖食品、保健品、药品中的应用。
3.权利要求1所述的驴皮寡肽在制备α-葡萄糖苷酶和α-淀粉酶抑制剂中的应用。
4.权利要求1所述的驴皮寡肽在制备抗Ⅱ型糖尿病药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310407569.9A CN116444617A (zh) | 2023-04-12 | 2023-04-12 | 一种驴皮寡肽及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310407569.9A CN116444617A (zh) | 2023-04-12 | 2023-04-12 | 一种驴皮寡肽及其应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116444617A true CN116444617A (zh) | 2023-07-18 |
Family
ID=87135243
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310407569.9A Pending CN116444617A (zh) | 2023-04-12 | 2023-04-12 | 一种驴皮寡肽及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116444617A (zh) |
-
2023
- 2023-04-12 CN CN202310407569.9A patent/CN116444617A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104450839B (zh) | 具有ace抑制活性的米糠蛋白肽的制备方法 | |
CN103052717A (zh) | 一种工业化生产玉米降压活性肽的方法 | |
CN109776652B (zh) | 鳕鱼皮寡肽及其分离纯化方法和在制备ɑ-葡萄糖苷酶抑制剂及抗Ⅱ型糖尿病药物中的应用 | |
CA3203208A1 (en) | Multifunctional panax quinquefolius hydrolyzed peptide and preparation method and application thereof | |
CN112342260A (zh) | 一种利用脱脂南极磷虾粉制备降血糖肽的方法及其产品 | |
CN112501229B (zh) | 一种牛骨胶原肽的生产工艺 | |
CN113845567B (zh) | 一种金枪鱼鱼卵二肽基肽酶ⅳ抑制寡肽 | |
CN114107418B (zh) | 一种人参多肽的制备方法 | |
CN116444617A (zh) | 一种驴皮寡肽及其应用 | |
CN116444606A (zh) | 驴皮寡肽及其应用 | |
CN1384090A (zh) | 丹参总酚酸的提取方法及其制剂的制法与用途 | |
CN114891065B (zh) | 一种具有α-淀粉酶抑制活性的降血糖海参肽及其制备方法和应用 | |
CN113087773B (zh) | 一种具有降血糖和抗氧化功能的牦牛骨肽及其制备方法 | |
CN110810852A (zh) | 一种调节心血管功能的蚯蚓冻干粉的制备方法 | |
CN110776556B (zh) | 兼具ace抑制和抗氧化活性的肽及其制备方法和应用 | |
CN110655553B (zh) | 一种芝麻来源的ace抑制肽、制备方法及其在制备降血压药物方面的应用 | |
CN114032267A (zh) | 一种活性肽的制备方法和应用 | |
JPS61171431A (ja) | アミラ−ゼ阻害物質およびその製造法 | |
CN113880916B (zh) | 一种牦牛皮抗氧化多肽及其制备方法和应用 | |
CN117551167B (zh) | 一种富含支链氨基酸的牡蛎dpp-ⅳ抑制肽及其制备方法和应用 | |
CN110787287B (zh) | 一种鱼鳞胶原蛋白多肽在制备治疗慢性心力衰竭药物中的应用 | |
CN108686200A (zh) | 用于治疗代谢系统疾病的多肽及其组合物 | |
CN110734471B (zh) | 一种具有α-葡萄糖苷酶抑制活性的七肽及其应用 | |
JP2001206893A (ja) | 新規α−アミラーゼ阻害活性物質、その製造方法及びその用途 | |
Chen et al. | Two novel angiotensin‐converting enzyme (ACE) and dipeptidyl peptidase IV (DPP‐IV) inhibiting peptides from tilapia (Oreochromis mossambicus) skin and their molecular docking mechanism |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |