US20090264363A1 - Leucine-Rich Peptide Compositions and Methods for Isolation - Google Patents
Leucine-Rich Peptide Compositions and Methods for Isolation Download PDFInfo
- Publication number
- US20090264363A1 US20090264363A1 US12/411,772 US41177209A US2009264363A1 US 20090264363 A1 US20090264363 A1 US 20090264363A1 US 41177209 A US41177209 A US 41177209A US 2009264363 A1 US2009264363 A1 US 2009264363A1
- Authority
- US
- United States
- Prior art keywords
- leucine
- peptides
- protein
- composition
- rich
- 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.)
- Abandoned
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 115
- 239000000203 mixture Substances 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 52
- 238000002955 isolation Methods 0.000 title description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract description 114
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract description 113
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 92
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 48
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 48
- 108010046377 Whey Proteins Proteins 0.000 claims abstract description 30
- 102000007544 Whey Proteins Human genes 0.000 claims abstract description 28
- 230000017531 blood circulation Effects 0.000 claims abstract description 20
- 241000283690 Bos taurus Species 0.000 claims abstract description 10
- 239000005862 Whey Substances 0.000 claims abstract description 9
- 235000018102 proteins Nutrition 0.000 claims description 47
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 32
- 239000012466 permeate Substances 0.000 claims description 21
- 235000021119 whey protein Nutrition 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 19
- 239000003531 protein hydrolysate Substances 0.000 claims description 19
- 108010009736 Protein Hydrolysates Proteins 0.000 claims description 18
- 102000002704 Leucyl aminopeptidase Human genes 0.000 claims description 12
- 108010004098 Leucyl aminopeptidase Proteins 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 230000024883 vasodilation Effects 0.000 claims description 12
- 235000013336 milk Nutrition 0.000 claims description 11
- 239000008267 milk Substances 0.000 claims description 11
- 210000004080 milk Anatomy 0.000 claims description 11
- 240000008042 Zea mays Species 0.000 claims description 10
- 235000002017 Zea mays subsp mays Nutrition 0.000 claims description 10
- 102000004400 Aminopeptidases Human genes 0.000 claims description 9
- 108090000915 Aminopeptidases Proteins 0.000 claims description 9
- 210000004204 blood vessel Anatomy 0.000 claims description 9
- 230000003301 hydrolyzing effect Effects 0.000 claims description 9
- 239000012141 concentrate Substances 0.000 claims description 8
- 239000012530 fluid Substances 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 241000251468 Actinopterygii Species 0.000 claims description 5
- 108010068370 Glutens Proteins 0.000 claims description 5
- 241000209140 Triticum Species 0.000 claims description 5
- 235000021307 Triticum Nutrition 0.000 claims description 5
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 5
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 claims description 5
- 235000005822 corn Nutrition 0.000 claims description 5
- 235000021312 gluten Nutrition 0.000 claims description 5
- 235000021374 legumes Nutrition 0.000 claims description 5
- 235000009973 maize Nutrition 0.000 claims description 5
- 235000013372 meat Nutrition 0.000 claims description 5
- 235000013601 eggs Nutrition 0.000 claims description 4
- 235000019688 fish Nutrition 0.000 claims description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 18
- 210000003205 muscle Anatomy 0.000 abstract description 18
- 230000003247 decreasing effect Effects 0.000 abstract description 12
- 230000036772 blood pressure Effects 0.000 abstract description 11
- 241001465754 Metazoa Species 0.000 abstract description 5
- 230000003920 cognitive function Effects 0.000 abstract description 3
- 230000009084 cardiovascular function Effects 0.000 abstract 1
- 230000009469 supplementation Effects 0.000 description 18
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 17
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 17
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 17
- 235000001014 amino acid Nutrition 0.000 description 15
- 229940024606 amino acid Drugs 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 230000008901 benefit Effects 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 10
- 235000015872 dietary supplement Nutrition 0.000 description 9
- 230000007423 decrease Effects 0.000 description 8
- 235000013305 food Nutrition 0.000 description 8
- 230000037406 food intake Effects 0.000 description 8
- 210000000245 forearm Anatomy 0.000 description 8
- 230000014616 translation Effects 0.000 description 8
- 238000005259 measurement Methods 0.000 description 7
- 235000016709 nutrition Nutrition 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 210000002302 brachial artery Anatomy 0.000 description 6
- 150000005693 branched-chain amino acids Chemical class 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 238000001243 protein synthesis Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 102400000243 Leu-enkephalin Human genes 0.000 description 5
- 108010022337 Leucine Enkephalin Proteins 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 5
- 239000004365 Protease Substances 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- URLZCHNOLZSCCA-UHFFFAOYSA-N leu-enkephalin Chemical compound C=1C=C(O)C=CC=1CC(N)C(=O)NCC(=O)NCC(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=CC=C1 URLZCHNOLZSCCA-UHFFFAOYSA-N 0.000 description 5
- 239000013589 supplement Substances 0.000 description 5
- YFGBQHOOROIVKG-BHDDXSALSA-N (2R)-2-[[(2R)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H](C(=O)N[C@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 YFGBQHOOROIVKG-BHDDXSALSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 208000002720 Malnutrition Diseases 0.000 description 4
- 102400000988 Met-enkephalin Human genes 0.000 description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 description 4
- 108010042237 Methionine Enkephalin Proteins 0.000 description 4
- 206010040047 Sepsis Diseases 0.000 description 4
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 4
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 4
- 230000032683 aging Effects 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000000378 dietary effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 235000012631 food intake Nutrition 0.000 description 4
- 239000000413 hydrolysate Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction 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
- 208000015380 nutritional deficiency disease Diseases 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- 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 3
- 102000016267 Leptin Human genes 0.000 description 3
- 108010092277 Leptin Proteins 0.000 description 3
- 102000008934 Muscle Proteins Human genes 0.000 description 3
- 108010074084 Muscle Proteins Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000035868 Vascular inflammations Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 235000003642 hunger Nutrition 0.000 description 3
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 3
- 229940039781 leptin Drugs 0.000 description 3
- 230000001071 malnutrition Effects 0.000 description 3
- 235000000824 malnutrition Nutrition 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000001223 reverse osmosis Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 102000015781 Dietary Proteins Human genes 0.000 description 2
- 108010010256 Dietary Proteins Proteins 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 206010072170 Skin wound Diseases 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 239000008122 artificial sweetener Substances 0.000 description 2
- 235000021311 artificial sweeteners Nutrition 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000003293 cardioprotective effect Effects 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 230000003931 cognitive performance Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 235000021245 dietary protein Nutrition 0.000 description 2
- 230000010339 dilation Effects 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- 230000002641 glycemic effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000001728 nano-filtration Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 208000001076 sarcopenia Diseases 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 230000037221 weight management Effects 0.000 description 2
- AAXWBCKQYLBQKY-IRXDYDNUSA-N (2s)-2-[[(2s)-2-[(2-benzamidoacetyl)amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-4-methylpentanoic acid Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)C=1C=CC=CC=1)C1=CN=CN1 AAXWBCKQYLBQKY-IRXDYDNUSA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- QUKRTJQSGPLQKQ-UHFFFAOYSA-N 5-methylsulfonyl-3h-1,3-benzoxazol-2-one Chemical compound CS(=O)(=O)C1=CC=C2OC(=O)NC2=C1 QUKRTJQSGPLQKQ-UHFFFAOYSA-N 0.000 description 1
- 102100030840 AT-rich interactive domain-containing protein 4B Human genes 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 101000984728 Chiropsoides quadrigatus Angiotensin-converting enzyme inhibitory peptide Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000018389 Exopeptidases Human genes 0.000 description 1
- 108010091443 Exopeptidases Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 208000036119 Frailty Diseases 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 101000792935 Homo sapiens AT-rich interactive domain-containing protein 4B Proteins 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000010582 Pisum sativum Nutrition 0.000 description 1
- 241000183024 Populus tremula Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 206010058990 Venous occlusion Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229940100228 acetyl coenzyme a Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000005189 cardiac health Effects 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- -1 drink mixes Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000008753 endothelial function Effects 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000002431 foraging effect Effects 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108010016268 hippuryl-histidyl-leucine Proteins 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 235000021125 infant nutrition Nutrition 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 235000004213 low-fat Nutrition 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000037257 muscle growth Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 208000030613 peripheral artery disease Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 235000021025 protein-rich diet Nutrition 0.000 description 1
- 235000021134 protein-rich food Nutrition 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 208000022064 reactive hyperemia Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000015590 smooth muscle cell migration Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000014268 sports nutrition Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 210000004269 weibel-palade body Anatomy 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
- A61K38/018—Hydrolysed proteins; Derivatives thereof from animals from milk
-
- 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
- A23L33/175—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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
-
- 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
Definitions
- the invention relates to dietary peptide compositions for stimulating protein synthesis, decreasing protein degradation, producing vasodilation, increasing nitric oxide production, and decreasing blood flow. More specifically, the invention relates to leucine-rich peptide compositions and methods for their isolation from proteins.
- Leucine also stimulates muscle protein synthesis and modulates the activity of various proteins involved in the control of mRNA translation. Leucine may stimulate protein synthesis directly or through its metabolite, ⁇ -ketoisocaproic acid. Leucine may stimulate translation either independently or by interaction with the mammalian target of rapamycin (mTOR).
- mTOR mammalian target of rapamycin
- Leucine is one of the branched-chain amino acids and is an essential amino acid. It is the only amino acid that is converted to acetyl-coenzyme A and alpha-ketoacids and is an important source of nitrogen for synthesis of glutamine. In addition to its effects on protein synthesis and degradation, leucine also stimulates glucose uptake by protein kinase C (PKC), while insulin modulates glucose uptake via protein kinase B.
- PKC protein kinase C
- Milk-derived whey is one good source of muscle-building proteins.
- Whey protein isolates and whey protein concentrates are used in protein-building dietary supplements.
- Whey proteins are a good source of leucine, but for many individuals who need the muscle-building amino acids dietary proteins can provide, it is difficult to digest and/or absorb proteins. It is therefore important to find ways to provide leucine-containing amino acid compositions that provide amino acids in a more bioavailable form for improving muscle protein synthesis.
- the present invention relates to peptides having a leucine content of from about 12% to about 40% (“leucine-rich peptides”), those peptides being isolated from a protein source by a method comprising the steps of hydrolyzing the protein in the presence of one or more leucyl aminopeptidases, optionally in combination with additional proteases, to produce a protein hydrolysate, deactivating the enzymes, and filtering the protein hydrolysate to provide a permeate comprising peptides having a molecular weight of from about 200 to about 4,000, including sub-ranges in-between, such as, for example, a molecular weight of from about 200 to about 1,000 or a molecular weight of from about 400 to about 1,000.
- leucine-rich peptides those peptides being isolated from a protein source by a method comprising the steps of hydrolyzing the protein in the presence of one or more leucyl aminopeptidases, optionally in combination with additional proteases, to produce
- the step of concentrating the leucine-rich peptides by removing the aqueous fluid from the permeate may be added.
- method of use of such peptides for a variety of beneficial effects such as producing vasodilation, increasing nitric oxide production, decreasing blood pressure, increasing blood flow, increasing muscle tissue, improving wound healing, and improving cognitive function.
- the invention also relates to a method for isolating leucine-rich peptides from a protein source, the method comprising the steps of hydrolyzing the protein in the presence of one or more leucyl aminopeptidases, optionally in combination with additional proteases, to produce a protein hydrolysate, deactivating the enzymes, filtering the protein hydrolysate to provide a permeate, and concentrating the permeate containing the leucine-rich peptides.
- the protein may be derived from animal or plant sources, including, for example, legumes such as soy or pea, fish, meat, milk, blood, egg, corn, wheat gluten, maize, or combinations thereof.
- the protein source may be bovine milk, bovine whey, whey protein concentrates, and/or whey protein isolates.
- the leucine content of the leucine-rich peptides may be within various subranges of the about 12 to about 40 percent range, such as, for example, from about 12 to about 30 weight percent leucine, from about 15 to about 20 weight percent leucine, from about 15 to about 25 weight percent leucine, and from about 20 to about 25 weight percent leucine.
- leucine-rich peptides may be isolated from a protein source by a method comprising the steps of hydrolyzing the protein in the presence of one or more (i.e., at least one) leucyl aminopeptidases, optionally in combination with additional proteases, to form a protein hydrolysate, deactivating the enzymes, filtering the protein hydrolysate to isolate leucine-rich peptides, and concentrating the leucine-rich peptides.
- the method comprises hydrolyzing the protein in the presence of one or more aminopeptidases which may act as leucyl aminopeptidases (leucine aminopeptidases), optionally supplemented with additional proteases, to form a protein hydrolysate, deactivating the enzymes, filtering the protein hydrolysate using ultrafiltration, nano-filtration, or another suitable filtration method to give a permeate containing the leucine-rich peptides, and concentrating the leucine-rich peptides in the permeate using reverse osmosis, evaporation, or another suitable method for concentrating the peptides by removing the aqueous portion of the permeate from the filtration step.
- the invention also provides compositions comprising leucine-rich peptides prepared by the method.
- Leucine appears to have a number of beneficial effects, including stimulation of muscle protein synthesis and suppression of the rate of myofibrillar protein degradation and muscle weight loss.
- Leucine also increases hypothalamic mTOR signaling and decreases food intake and body weight (Cota, D. et al. Science (2006) 312: 927-930).
- Leucine administration increases leptin levels, and leptin is known to promote lipolysis in adipose tissue, but has no apparent effect on lean tissue. Increased leptin levels result in decreased hunger, decreased food consumption, and increased cellular energy expenditure.
- Protein sources such as standard whey protein hydrolysates may contain as much as 10% leucine, but given the variety of beneficial effects of this amino acid and the fact that it is not synthesized in the body from other amino acids, it has been a goal of the food and nutritional supplement industry to develop ways to increase leucine levels in order to promote its beneficial effects, especially its effects on muscle building and inhibition of muscle wasting.
- the present invention provides amino acid compositions that are rich in leucine and such compositions may be isolated from readily-available protein sources using the method of the invention.
- leucine aminopeptidase to process whey proteins to produce bioactive/bioavailable leucine-containing peptides which they have demonstrated to have a variety of desirable effects.
- Leucine residues appear to play an important role in the distinction between the effects of remarkably similar proteins.
- Angiotensin I differs from Angiotensin II by two additional carboxyl-terminal amino acids—histidine and leucine.
- Met-enkephalin a neuropeptide, has many similar effects to those of Leu-enkephalin, which appear to be mediated by the aromatic side-chains of the amino acids in the peptides. Both peptides consist of 5 amino acid residues.
- Met-enkephalin and Leu-enkephalin differ, however, in the carboxyl-terminal fifth amino acid residue. In Met-enkephalin, it is methionine. In Leu-enkephalin it is leucine. Both appear to have effects on arterial blood pressure and vasodilation, but in this area the amino acid difference appears to be more significant, with Leu-enkephalin appearing to have a stronger effect (Moore, R. H. and D. Dowling, “Effects on Intravenously Administered Leu- or Met-Enkephalin on Arterial Blood Pressure,” Regulatory Peptides (1980) 1(2): 77-87).
- hydrolysates containing a significant percentage of leucine present as a free amino acid While others have provided hydrolysates containing a significant percentage of leucine present as a free amino acid (see, for example, U.S. Pat. No. 6,875,456 to Delest, V. et al.), the present invention provides small peptides (e.g., a hydrolysate containing a significant percentage of di- and tri-peptides) to deliver leucine in a more bioavailable/bioactive form.
- small peptides e.g., a hydrolysate containing a significant percentage of di- and tri-peptides
- These peptides have demonstrated surprising beneficial results, such as potent inhibition of angiotensin converting enzyme (ACE) inhibition, vasodilation, and stimulation of increased nitric oxide production.
- ACE angiotensin converting enzyme
- Leucine-rich peptide compositions of the present invention provide leucine in combination with other amino acids, but provide increased amounts of leucine in relation to the other amino acids. These compositions may readily be added as a powder to a drink formulation, to a food product, to a nutritional supplement composition such as a tablet, capsule, or other formulation, or to a pharmaceutical preparation, for example. Additional flavorings, carbohydrates, fats, proteins, vitamins, minerals, and other suitable food or supplement ingredients may be included in such compositions.
- Peptides of the invention may be used to provide compositions that provide a benefit to a human or animal in areas including, but not limited to, cardiac health, sarcopenia, endothelial function, maintaining healthy blood pressure or lowering blood pressure, vasodilation, muscle growth and development, sports nutrition, infant nutrition, prevention or treatment of metabolic syndrome, cognitive function, eye health, diabetes, improvement in glycemic index, mTOR activation, wound healing, and skin care/treatment of skin disorders.
- compositions of the present invention provide increased levels of the branched-chain amino acid (BCAA) leucine, in conjunction with other amino acids in a form that may be readily incorporated into tablets, capsules, food products such as, for example, nutrition bars, supplements in the form of powders, drink mixes, and other compositions for human and/or animal consumption.
- BCAA branched-chain amino acid
- compositions may provide a benefit for those individuals who desire to improve their cognitive performance.
- Studies performed with the peptides of the invention have demonstrated that supplementation with leucine-rich peptides promotes vasodilation and increases blood flow, as well as increasing the rate at which glucose is delivered to the tissues. Older individuals, students, and others may derive a particular benefit from foods, drinks, and/or supplements comprising leucine-rich peptides of the invention.
- Metabolic syndrome (Syndrome X) is a chronic disease that affects at least 1 in every 5 adults in the United States. It is often associated with obesity, but the defining characteristic is abnormal glycemic control (glucose intolerance, insulin resistance). Protein-rich diets, especially those comprising significant amounts of leucine, are beneficial for the treatment of obesity and for the treatment of the metabolic syndrome (Layman, D. K. and D. A. Walker, J. Nutr . (2006) 136: 319S-323S). Compositions of the present invention provide an excellent means by which the necessary amino acids and the higher amounts of leucine necessary to affect weight management and the metabolic syndrome may be provided to a human or animal.
- Products such as “protein water” water containing whey protein isolate in combination with sweeteners and flavorings
- Snack foods, nutrition bars, drinks, drink mixes, and other products may also be formulated with the leucine-rich peptides to provide compositions for use in weight management and loss of fat.
- Leucine-rich peptide compositions may be used to promote weight loss by incorporating those compositions into one or more food products, or may be similarly used by incorporating them into a nutritional supplement or nutritional drink for ingestion at mealtime.
- Between-meal-snacks may also be formulated with leucine-rich peptide compositions to decrease hunger and food consumption.
- Leucine-rich peptides of the invention may be added to whey compositions, whey protein isolates, whey protein concentrates, and other protein sources to improve muscle synthesis, decrease muscle breakdown, decrease hunger and food consumption, improve blood flow, and increase nitric oxide production in the blood vessels, for example. These effects may be beneficial for a large population of individuals, including those who voluntarily wish to build additional muscle mass, those who are losing muscle mass through the process of aging and/or injury, disease (e.g., sepsis, cancer) or malnutrition, and those who desire to decrease the percentage of adipose tissue to muscle mass in the body.
- disease e.g., sepsis, cancer
- Leucine-rich peptide compositions of the present invention are especially beneficial for aging individuals or others with sarcopenia.
- human muscle mass decreases.
- the frailty that is associated with aged individuals may be attributed in large part to this loss of muscle mass, and that predisposes those individuals to further disease or injury.
- Some of the muscle tissue loss in older individuals may also be the result of malnutrition—especially in terms of protein ingestion, as protein-rich foods may tend to be more expensive and less readily available to individuals on fixed incomes.
- Compositions of the present invention provide nutritional supplements with which to address the needs of individuals in whom aging or malnutrition has induced muscle loss.
- Body-building involves the combination of nutritional supplementation and exercise to increase muscle mass.
- Compositions of the present invention are ideally suited for body-building nutritional supplements.
- Leucine-rich compositions stimulate muscle synthesis while generally decreasing the desire to overeat and gain fat tissue.
- dietary leucine supplementation has been shown to significantly improve endurance performance (Crowe, M. J. et al., Eur. J. Appl. Physiol . (2006) 97(6): 664-72).
- Leucine has demonstrated cardioprotective effects, in addition to its many other beneficial effects. For example, leucine protects heart muscle against myocardial ischemia and some researchers believe it is also an anti-arrhythmic factor (Gabrys, J. et aL (2002) Pharmacology Reviews and Communications 12: 101-108). Peptides of the present invention have been shown to act as potent angiotensin converting enzyme (ACE) inhibitors.
- ACE angiotensin converting enzyme
- compositions of the invention may be provided or consumed as dietary supplements and/or pharmaceutical compositions for maintaining healthy blood pressure levels and for decreasing blood pressure in individuals who have or are predisposed to elevated blood pressure levels. Such compositions may be especially beneficial for individuals who are diabetic, for example, who may have or be predisposed to high blood pressure and who may also need the increased blood flow to tissues in order to decrease tissue damage, especially in the extremities.
- Leucine supplementation has been determined to be more beneficial than is generic supplementation with BCAAs for burn, trauma, and sepsis patients (DeBandt, J. and L Cynober, J. Nutr . (2006) 136: 308S-313S). Furthermore, leucine has an anabolic effect on proteins in skin wounds and muscle, provided that adequate additional amino acids are available. When compared with leucine supplementation alone, leucine supplementation in conjunction with protein supplementation provided a greater benefit for wound healing (Zhang, X. et al., J. Nutr . (2004) 134: 3313-8).
- compositions of the present invention provide peptides having enhanced leucine content and are therefore excellent food, pharmaceutical, or nutritional compositions for administration to patients with burns or other skin wounds, muscle injury, trauma, sepsis, and other conditions in which the beneficial effects of leucine may be enhanced by providing leucine in combination with peptides or proteins.
- These compositions may be provided in oral form, via intravenous means, or by injection.
- Leucine-rich peptide compositions may also be used either orally or topically to enhance skin tone and suppleness, and to promote overall skin health.
- Leucine-rich peptides may also provide a benefit for blood pressure regulation and inhibition of angiotensin converting enzyme (ACE).
- ACE angiotensin converting enzyme
- leucine-rich peptides of the invention may be consumed in food products, drinks and drink mixes, as food supplements such as tablets, capsules, powders, and other formulations that may be easily self-administered at or between mealtimes.
- compositions of the invention may provide a benefit by increasing microcirculation, promoting endothelial health, and improving nutrient delivery to the tissues.
- NO relaxes smooth muscle and inhibits vascular inflammation, inhibiting endothelial cells lining the blood vessels from releasing inflammatory substances. NO inhibits smooth muscle cell migration and proliferation and decreases platelet adherence and aggregation. These effects may be especially beneficial in those predisposed to the development of atherosclerosis and to stroke, autoimmune disease, etc. NO appears to regulate vascular inflammation in part by inhibiting exocytosis of Weibel-Palade bodies, which can be triggered by thrombin, histamine, fibrin, complement, leukotrienes, and ATP, for example (Matsushita, K. et al. Cell (2003) 115: 139-150).
- compositions of the invention may therefore provide a benefit by preventing the development of atherosclerotic lesions, decreasing vascular inflammation, decreasing platelet adherence and aggregation, etc.
- Compositions of the invention may therefore provide supplements that provide a significant benefit in strengthening the cardiovascular system, decreasing inflammation in the circulatory system, preventing the development of plaques in the blood vessels, and providing a more “heart-healthy” environment within the blood vessels in general.
- the method may be used to isolate leucine-rich peptides from any source comprising leucine-containing proteins.
- sources may include, but not be limited to, wheat gluten, maize/corn protein isolates, egg proteins, soy and other legume proteins (e.g., pea), fish, meat, blood/blood proteins, and milk proteins.
- leucine-rich peptides is milk-derived whey, such as, for example, bovine milk-derived whey, whey protein isolates, and/or whey protein concentrates.
- Whey protein isolates generally have a protein content of at least about 90 weight percent, while whey protein concentrates may have from at least about 35 weight percent to about 80 weight percent protein.
- Leucyl aminopeptidases are exopeptidases which hydrolyze the peptide bond adjacent to a free amino group and react most rapidly with leucine-containing peptides and proteins.
- filtration molecules are selectively passed through or transported across a membrane, and this process may be even more effective when a pressure gradient is used. Filtration is particularly effective at isolating the leucine-rich peptides.
- Methods of filtering molecules based upon molecular weight and other properties are known to those of skill in the art and include membrane filtration generally, ultrafiltration, and nano-filtration, for example.
- the isolated leucine-rich peptides are generally contained within a permeate, which is fairly low in solids.
- the percentage of solids in the composition (permeate) may be increased by removal of liquid (aqueous fluid). This may be done by means known to those of skill in the art, including but not limited to processes such as evaporation and reverse osmosis.
- a high protein, low fat, low lactose liquid whey protein isolate product was used as the beginning substrate. This product was pumped into reaction tanks at a solids level of 17%. The temperature was raised to 45° C. and pH adjusted to 7.3 with sodium hydroxide. A blend of proteases and aminopeptidases (e.g., leucine aminopeptidase) was then added at a level of 0.35% of the solids. Hydrolysis was allowed to proceed for a 6-hour period with hourly pH adjustments to maintain the pH at 7.3. The enzymes were then deactivated by heating the solution to 65° C.
- proteases and aminopeptidases e.g., leucine aminopeptidase
- Fractionation was performed using filtration, the hydrolysate being passed through the filter to retain molecules having a molecular weight of greater than 20,000.
- the permeate coming from filtration system contained the leucine peptides, having approximately 52% of the peptides in the molecular weight range of less than 1,000; 41% of the peptides in the molecular weight range of 1,000 to 4,000; and 6% of the peptides in the molecular weight range of 4,000 to 20,000. These peptides were further concentrated using reverse osmosis. The final product was then dried and packaged.
- Table 1 Analysis of six preparations (lots) of peptides of the invention is shown in Table 1, where Lot 06-187, Lot 06-257, and Lot 06-259 are small-scale lots and Lot 07-041, Lot 07-046, and 07-055 are large-scale production lots.
- the degree of hydrolysis of each lot is shown on the bottom row, with a range of hydrolysis of from about 30% to about 50% producing the desired peptides in these experiments.
- ACE inhibition is shown as the amount of peptide needed to produce 50% ACE inhibition.
- the peptide product was produced by Glanbia Nutritionals, Twin Falls, Id. A single dose of 5 g was premeasured and placed in individual packets with artificial sweetener. Individuals participating in the study were provided with a 2-week supply and instructed to consume one packet per day mixed in 300 mL water.
- Post-ingestion FMD and FBF measurements were made intermittently. Blood samples were obtained at 15, 30, 45, 60, 90, and 120 minutes post-ingestion. Subjects rested in a comfortable position for the entire duration of the test. To ensure standardization between testing trials subjects were asked to maintain their current level of physical activity during the study period and to repeat their dietary intake from previously recorded diet records the day prior to each vascular testing visit.
- Flow mediated dilation (FMD) was assessed using standardized procedures for performing high-frequency ultrasonographic imaging before (PRE) and at 30, 60, and 90 min after ingestion of the test beverage. The technique provokes the release of nitric oxide, resulting in vasodilation that can be quantitated as an index of vasomotor function.
- the cuff was inflated to 200 mm Hg for 5 min using a rapid cuff inflator (Hokanson E20, Bellevue, Wash., USA) to occlude the brachial artery, and then released. Arterial diameter was then assessed continuously for 300 heart beats after occlusion. Images of the brachial artery were obtained using an Acuson 13.0-MHz linear array transducer and an Aspen cardiac ultrasound system (Acuson Corp, Elmwood Park, N.J.).
- Forearm blood flow was measured in the same right arm using venous occlusion strain gauge plethysmography.
- the increase in forearm volume was measured after blocking the venous efflux by an upper arm cuff inflated to 50 mmHg by a rapid cuff inflator (Hokanson E20, Bellevue, Wash., USA) for 7 seconds during each 15-second cycle to determine resting forearm blood flow (R-FBF).
- ACE inhibition assay has been previously described by Cushman and Cheung (Cushman, D. W. and Cheung, H. S., Biochem. Pharmacol. (1971) 20: 1637). Briefly, substrate was prepared by dissolving 21.475 mg of Hip-His-Leu (“HHL,” Sigma, St. Louis, Mo.) in 8 ml of phosphate buffered saline, with volume adjusted to 10 ml and final pH to 8.3. A 10% w/w solution of peptide composition was prepared using buffer as diluent. Angiotensin-converting enzyme stock solution was prepared by diluting 0.1 unit of ACE (rabbit lung, Sigma Chemical, St. Louis, Mo.) with buffer.
- HHL Hip-His-Leu
- Angiotensin-converting enzyme stock solution was prepared by diluting 0.1 unit of ACE (rabbit lung, Sigma Chemical, St. Louis, Mo.) with buffer.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nutrition Science (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Mycology (AREA)
- Cardiology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/411,772 US20090264363A1 (en) | 2008-03-26 | 2009-03-26 | Leucine-Rich Peptide Compositions and Methods for Isolation |
US14/188,676 US9222117B2 (en) | 2008-03-26 | 2014-02-24 | Leucine-rich peptide compositions and methods for isolation |
US14/981,337 US20160143983A1 (en) | 2008-03-26 | 2015-12-28 | Leucine-Rich Peptide Compositions and Methods for Isolation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3942608P | 2008-03-26 | 2008-03-26 | |
US12/411,772 US20090264363A1 (en) | 2008-03-26 | 2009-03-26 | Leucine-Rich Peptide Compositions and Methods for Isolation |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/188,676 Division US9222117B2 (en) | 2008-03-26 | 2014-02-24 | Leucine-rich peptide compositions and methods for isolation |
Publications (1)
Publication Number | Publication Date |
---|---|
US20090264363A1 true US20090264363A1 (en) | 2009-10-22 |
Family
ID=41114702
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/411,772 Abandoned US20090264363A1 (en) | 2008-03-26 | 2009-03-26 | Leucine-Rich Peptide Compositions and Methods for Isolation |
US14/188,676 Active US9222117B2 (en) | 2008-03-26 | 2014-02-24 | Leucine-rich peptide compositions and methods for isolation |
US14/981,337 Abandoned US20160143983A1 (en) | 2008-03-26 | 2015-12-28 | Leucine-Rich Peptide Compositions and Methods for Isolation |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/188,676 Active US9222117B2 (en) | 2008-03-26 | 2014-02-24 | Leucine-rich peptide compositions and methods for isolation |
US14/981,337 Abandoned US20160143983A1 (en) | 2008-03-26 | 2015-12-28 | Leucine-Rich Peptide Compositions and Methods for Isolation |
Country Status (8)
Country | Link |
---|---|
US (3) | US20090264363A1 (fr) |
EP (1) | EP2274002B1 (fr) |
JP (2) | JP5750039B2 (fr) |
CN (1) | CN102014947B (fr) |
AU (1) | AU2009228250B2 (fr) |
CA (1) | CA2719857C (fr) |
PL (1) | PL2274002T3 (fr) |
WO (1) | WO2009120837A2 (fr) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110233469A1 (en) * | 2009-12-21 | 2011-09-29 | Brent Petersen | Leucine/Peptide Composition and Method of Formulation |
CN102669683A (zh) * | 2011-03-09 | 2012-09-19 | 广州加原医药科技有限公司 | 海洋鱼多肽在制备缓解视疲劳保健食品的应用 |
US20140335257A1 (en) * | 2009-12-21 | 2014-11-13 | Brent L. Petersen | Compositions and Methods for Improving Creatine Solubility and Stability |
US20180023110A1 (en) * | 2015-01-30 | 2018-01-25 | Jiangsu University | Method for preparing functional polypeptide through multimode ultrasonic enhancing enzymolysis |
CN115886076A (zh) * | 2022-11-26 | 2023-04-04 | 黑龙江飞鹤乳业有限公司 | 含亮氨酸类蛋白反应产物的组合物及在抗肌肉衰减的应用 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009120837A2 (fr) * | 2008-03-26 | 2009-10-01 | Glanbia Nutritionals (Ireland) Ltd. | Compositions de peptide riche en leucine et procédés d’isolement |
CN103014111B (zh) * | 2012-12-13 | 2014-11-12 | 内蒙古伊利实业集团股份有限公司 | 一种富含精氨酸的乳清蛋白水解物及其制备方法 |
FR3034317B1 (fr) * | 2015-03-31 | 2018-09-14 | International Nutrition Research Company | Composition pour le traitement d'un etat metabolique pathogene du microbiote intestinal et des maladies derivees |
US10188135B2 (en) | 2015-11-04 | 2019-01-29 | Stokley-Van Camp, Inc. | Method for inducing satiety |
JP7131608B2 (ja) * | 2018-04-18 | 2022-09-06 | 三菱マテリアル株式会社 | 多結晶シリコンの包装方法、多結晶シリコンの二重包装方法及び単結晶シリコン用原料製造方法 |
JP2020097537A (ja) | 2018-12-18 | 2020-06-25 | キリンホールディングス株式会社 | 脳血流を増加させるための組成物 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050075284A1 (en) * | 2000-05-22 | 2005-04-07 | Illana Gozes | Pharmaceutical compositions comprising vip-related peptides for the treatment of sexual disorders |
US20070054352A1 (en) * | 2003-05-05 | 2007-03-08 | Van Der Burg-Koorevaar Monique | Hydrolysed casein product comprising tripeptides ipp and/or vpp |
US7777074B2 (en) * | 2007-09-18 | 2010-08-17 | Thermolife International, Llc | Amino acid compounds |
US7795204B2 (en) * | 1999-10-18 | 2010-09-14 | Northern Innovations And Formulations Corp. | Food supplement for increasing lean mass and strength |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS58152498A (ja) * | 1982-03-06 | 1983-09-10 | Terumo Corp | 低分子ペプチド混合物の製造方法 |
JPS60251859A (ja) * | 1984-05-30 | 1985-12-12 | Kikkoman Corp | 卵白分解物の製造法 |
US6221423B1 (en) * | 1998-04-13 | 2001-04-24 | Protein Technologies Int'l Inc. | Short-chained peptide material |
WO1999065326A1 (fr) * | 1998-06-17 | 1999-12-23 | New Zealand Dairy Board | Hydrolysat de proteine bioactive du petit-lait |
AU1142001A (en) * | 2000-10-19 | 2002-04-29 | Dsm N.V. | Protein hydrolysates |
EP1365656A1 (fr) * | 2001-03-09 | 2003-12-03 | Unilever N.V. | Produit a base de lait fermente |
JP4376180B2 (ja) * | 2002-06-04 | 2009-12-02 | ディーエスエム アイピー アセッツ ビー.ブイ. | トリペプチドに富むタンパク水解物 |
CN1784845A (zh) * | 2003-02-11 | 2006-06-07 | 美商内数位科技公司 | 使用自适应天线以选择性重新使用共同实体信道时槽于专用信道的系统及方法 |
KR101174299B1 (ko) * | 2003-08-01 | 2012-08-16 | 칼피스가부시키가이샤 | 카세인 가수분해물, 그 제조법 및 그 용도 |
CA2631647A1 (fr) * | 2005-11-30 | 2007-06-07 | Nestec S.A. | Emploi d'acides amines a chaine ramifiee pour traiter la perte musculaire |
WO2007109681A2 (fr) * | 2006-03-20 | 2007-09-27 | Glanbia Nutritionals (Ireland) Limited | Compositions et procédés permettant d'augmenter la vasodilatation |
WO2009120837A2 (fr) * | 2008-03-26 | 2009-10-01 | Glanbia Nutritionals (Ireland) Ltd. | Compositions de peptide riche en leucine et procédés d’isolement |
-
2009
- 2009-03-26 WO PCT/US2009/038357 patent/WO2009120837A2/fr active Application Filing
- 2009-03-26 AU AU2009228250A patent/AU2009228250B2/en active Active
- 2009-03-26 CN CN200980114782.9A patent/CN102014947B/zh active Active
- 2009-03-26 EP EP09724382.8A patent/EP2274002B1/fr active Active
- 2009-03-26 US US12/411,772 patent/US20090264363A1/en not_active Abandoned
- 2009-03-26 CA CA2719857A patent/CA2719857C/fr active Active
- 2009-03-26 JP JP2011502042A patent/JP5750039B2/ja not_active Expired - Fee Related
- 2009-03-26 PL PL09724382T patent/PL2274002T3/pl unknown
-
2014
- 2014-02-24 US US14/188,676 patent/US9222117B2/en active Active
- 2014-12-10 JP JP2014249701A patent/JP6227519B2/ja not_active Expired - Fee Related
-
2015
- 2015-12-28 US US14/981,337 patent/US20160143983A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7795204B2 (en) * | 1999-10-18 | 2010-09-14 | Northern Innovations And Formulations Corp. | Food supplement for increasing lean mass and strength |
US20050075284A1 (en) * | 2000-05-22 | 2005-04-07 | Illana Gozes | Pharmaceutical compositions comprising vip-related peptides for the treatment of sexual disorders |
US20070054352A1 (en) * | 2003-05-05 | 2007-03-08 | Van Der Burg-Koorevaar Monique | Hydrolysed casein product comprising tripeptides ipp and/or vpp |
US7777074B2 (en) * | 2007-09-18 | 2010-08-17 | Thermolife International, Llc | Amino acid compounds |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110233469A1 (en) * | 2009-12-21 | 2011-09-29 | Brent Petersen | Leucine/Peptide Composition and Method of Formulation |
US20140335257A1 (en) * | 2009-12-21 | 2014-11-13 | Brent L. Petersen | Compositions and Methods for Improving Creatine Solubility and Stability |
US9445622B2 (en) * | 2009-12-21 | 2016-09-20 | Glanbia Nutritionals (Ireland) Ltd. | Compositions and methods for improving creatine solubility and stability |
CN102669683A (zh) * | 2011-03-09 | 2012-09-19 | 广州加原医药科技有限公司 | 海洋鱼多肽在制备缓解视疲劳保健食品的应用 |
US20180023110A1 (en) * | 2015-01-30 | 2018-01-25 | Jiangsu University | Method for preparing functional polypeptide through multimode ultrasonic enhancing enzymolysis |
CN115886076A (zh) * | 2022-11-26 | 2023-04-04 | 黑龙江飞鹤乳业有限公司 | 含亮氨酸类蛋白反应产物的组合物及在抗肌肉衰减的应用 |
Also Published As
Publication number | Publication date |
---|---|
CN102014947B (zh) | 2016-10-19 |
PL2274002T3 (pl) | 2015-06-30 |
EP2274002A4 (fr) | 2012-04-25 |
CN102014947A (zh) | 2011-04-13 |
JP2015110573A (ja) | 2015-06-18 |
US20140171378A1 (en) | 2014-06-19 |
US20160143983A1 (en) | 2016-05-26 |
JP5750039B2 (ja) | 2015-07-15 |
JP6227519B2 (ja) | 2017-11-08 |
EP2274002A2 (fr) | 2011-01-19 |
AU2009228250A1 (en) | 2009-10-01 |
AU2009228250B2 (en) | 2015-03-19 |
CA2719857A1 (fr) | 2009-10-01 |
JP2011517450A (ja) | 2011-06-09 |
CA2719857C (fr) | 2019-08-06 |
US9222117B2 (en) | 2015-12-29 |
WO2009120837A3 (fr) | 2009-12-30 |
EP2274002B1 (fr) | 2014-12-03 |
WO2009120837A2 (fr) | 2009-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9222117B2 (en) | Leucine-rich peptide compositions and methods for isolation | |
CA2669524C (fr) | Composition de peptide de collagene et aliment ou boisson la contenant | |
JP4669396B2 (ja) | アンジオテンシン変換酵素阻害剤、医薬及び機能性食品 | |
ES2219868T3 (es) | Agentes anti-estres y alimentos funcionales. | |
Sano et al. | Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with high-normal blood pressure or mild hypertension | |
US20120040055A1 (en) | Collagen peptide composition having good ability to enter the blood and food or beverage containing the same | |
Wang et al. | Hypertension-attenuating effect of whey protein hydrolysate on spontaneously hypertensive rats | |
Kouguchi et al. | Effects of a chicken collagen hydrolysate on the circulation system in subjects with mild hypertension or high-normal blood pressure | |
JPWO2007108554A1 (ja) | 血圧上昇抑制作用を有するペプチド | |
JP6189994B2 (ja) | ジペプチジルペプチダーゼ−iv阻害用飲食品組成物 | |
WO2017010537A1 (fr) | Composition qui contient un dipeptide dérivé de forme circulaire et qui inhibe la carnosinase sérique | |
JP4628958B2 (ja) | アンジオテンシン変換酵素阻害ペプチド | |
US6019999A (en) | Process for making liposomal ion-exchange whey protein and products thereof | |
JP2011504464A (ja) | 新規血圧降下組成物 | |
KR100653582B1 (ko) | 신규 펩티드 y-2 | |
TW200808336A (en) | Agent for preventing arteriosclerosis, agent for inhibiting vascular intimal thickening, agent for improving vascular endothelial function, and functional food | |
DK178743B1 (en) | Process for producing a shrimp hydrolysate using electrodialysis. | |
NL2021411B1 (en) | Protein hydrolysate for short term renal functioning | |
JP2005029488A (ja) | 血圧降下剤およびGly−Pro | |
KR20070019992A (ko) | 티올 항상성을 개선시키기 위한 시스테인 리치 펩티드 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |
|
AS | Assignment |
Owner name: GLANBIA NUTRITIONALS (IRELAND), LTD., IRELAND Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BASTIAN, ERIC D., DR.;WARD, LOREN S., DR;WROBEL, STANLEY, DR.;AND OTHERS;SIGNING DATES FROM 20090325 TO 20090327;REEL/FRAME:036850/0831 |