CN105001139A - Antihypertensive active peptide, preparation method thereof and application thereof - Google Patents
Antihypertensive active peptide, preparation method thereof and application thereof Download PDFInfo
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- CN105001139A CN105001139A CN201510398942.4A CN201510398942A CN105001139A CN 105001139 A CN105001139 A CN 105001139A CN 201510398942 A CN201510398942 A CN 201510398942A CN 105001139 A CN105001139 A CN 105001139A
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- active peptide
- antihypertensive
- aminobutyric acid
- antihypertensive active
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 30
- 230000003276 anti-hypertensive effect Effects 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims description 10
- 230000008878 coupling Effects 0.000 claims description 10
- 238000010168 coupling process Methods 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- -1 fluorenylmethyloxycarbonyl γ-aminobutyric acid Chemical compound 0.000 claims description 10
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 10
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutanoic acid Natural products NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 239000013067 intermediate product Substances 0.000 claims description 9
- 230000000975 bioactive effect Effects 0.000 claims description 7
- 239000007822 coupling agent Substances 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 5
- 239000011347 resin Substances 0.000 claims description 5
- 229920005989 resin Polymers 0.000 claims description 5
- 239000000470 constituent Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 235000013305 food Nutrition 0.000 claims description 3
- 150000001413 amino acids Chemical group 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 230000036772 blood pressure Effects 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 4
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 241000700159 Rattus Species 0.000 description 19
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 13
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 206010020772 Hypertension Diseases 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 150000003053 piperidines Chemical class 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
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- 238000003304 gavage Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
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- 238000000034 method Methods 0.000 description 5
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- 238000006243 chemical reaction Methods 0.000 description 4
- 108010025306 histidylleucine Proteins 0.000 description 4
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- 238000004007 reversed phase HPLC Methods 0.000 description 4
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- MMFKFJORZBJVNF-UWVGGRQHSA-N His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CN=CN1 MMFKFJORZBJVNF-UWVGGRQHSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000004531 blood pressure lowering effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
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- 230000001631 hypertensive effect Effects 0.000 description 3
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- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- 239000002160 alpha blocker Substances 0.000 description 2
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
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- 238000001802 infusion Methods 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 210000003462 vein Anatomy 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
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 101001044245 Arabidopsis thaliana Insulin-degrading enzyme-like 1, peroxisomal Proteins 0.000 description 1
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- 206010019280 Heart failures Diseases 0.000 description 1
- 206010019468 Hemiplegia Diseases 0.000 description 1
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- 208000004880 Polyuria Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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- 241001083492 Trapa Species 0.000 description 1
- 235000014364 Trapa natans Nutrition 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- JZWZACGUZVCQPS-RNJOBUHISA-N Val-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N JZWZACGUZVCQPS-RNJOBUHISA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
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- 238000006555 catalytic reaction Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention relates to an antihypertensive active peptide, a preparation method thereof and an application thereof. The amino acid sequence of the active peptide is gamma-aminobutyric acid-gamma-aminobutyric acid-proline. The invention provides a different active peptide, the ACE inhibition activity of which can reach 57.8%. When a dose of 2mg/kg of the peptide is administered for 5 days, a blood pressure value can be substantially stabilized at approximately 170mmHg.
Description
Technical field
The present invention relates to a kind of antihypertensive active peptide, its preparation method and application.
Background technology
Hypertension is the modal cardiovascular disorder of China, its incidence in grownup up to 20%, hyperpietic is because arteriotony is for a long time higher than normal arterial pressure, headache, giddy, cardio palmus shape can not only be caused, and the organ injuries such as patient's heart, brain, kidney can be caused, cause hemorrhagic apoplexy, myocardial infarction, heart failure and cerebral thrombosis complication, make patient's hemiplegia or death, obviously reduce patients ' life quality.The cause of disease of essential hypertension is complicated, and in known body, the adjustment of many systems and blood pressure has substantial connection, and antihypertensive drug can act on arbitrary link of affecting blood pressure regulation and make blood pressure drops.The hypertensive medicine of current common treatment has following six kinds: diuretic(s) (may cause hypokalemia, affect carbohydrate metabolism, sugar tolerance is declined), beta-Blocking agent (untoward reaction of central nervous system, Digestive tract and vascular system can be brought), α-blockers, calcium antagonist (oedema, headache, flush, diuresis, ypotension and cardiac conduction can be caused to be obstructed), angiotensin-ii receptor retarding agent (can cause dry cough, blood potassium are high, even angioedema) and angiotensin converting enzyme inhibitor (ACEI).Because existing most of medicine has stronger side effect, so scientists is devoted to medicine or the food of developing high-efficiency low-toxicity always, functional food containing the little peptide suppressing Zinc metallopeptidase Zace1 (ACE) active or medicine, hyperpietic is benefited, research shows, such medicine is better than general vasodilator, and when making blood pressure drops, the heart, renal blood flow do not decline; Be better than calcium antagonist, can not water-sodium retention be caused, not accelerate heart rate; Be better than α-blockers, can not postural hypotension be caused; Be better than older generation's depressor, without central action; Be better than nitrate esters medicine, have no drug resistance, without liver first-pass effect and without drug withdrawal rebound phenomenon [Wu Jinshan, Li Jia. the progress of antihypertensive drug and clinical application [J]. the practical medicine of China, 2009,4 (23): 231-232.].The antihypertensive active kyrine Asn-Pro-Trp that patent CN200710047836.7 is obtained by caseinhydrolysate, it has certain blood pressure lowering effect, particularly, this active kyrine is 85.5% to ACE inhibitory activity, it adopts the dosed administration of 5mg/kg after 5 days, the blood pressure stabilization of rat is at 176mmHg, and subsequent blood pressure gos up to some extent; Also have patent CN201210247822.0 to prepare antihypertensive active kyrine by synthetic method: VAL-ILE-PRO, its ACE inhibitory activity is for being only 36.58 ± 4.66%.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of structure difference and has the antihypertensive active peptide of good ACE inhibitory activity and obvious blood pressure lowering effect, its preparation method and application.
For solving above technical problem, the present invention takes following technical scheme:
A kind of antihypertensive active peptide, the aminoacid sequence of described bioactive peptide is: γ-aminobutyric acid-γ-aminobutyric acid-proline(Pro).
A preparation method for antihypertensive active peptide, its by by proline(Pro) dichloro resin and fluorenylmethyloxycarbonyl γ-aminobutyric acid under the existence of coupling agent and organic solvent, carry out coupling and obtain intermediate product; Again by described intermediate product and fluorenylmethyloxycarbonyl γ-aminobutyric acid under the existence of coupling agent and organic solvent, carry out coupling, after purified, obtain described antihypertensive active peptide.
Particularly, a kind of preparation method of antihypertensive active peptide, its by by proline(Pro) dichloro resin and fluorenylmethyloxycarbonyl γ-aminobutyric acid under the existence of coupling agent and organic solvent, carry out coupling 50 ~ 70 minutes, then obtain intermediate product through washing; Again by described intermediate product and fluorenylmethyloxycarbonyl γ-aminobutyric acid under the existence of coupling agent and organic solvent, carry out coupling 50 ~ 70 minutes, after washing, purifying, obtain described antihypertensive active peptide.
Further, described coupling agent is O-benzotriazole-N, N, N', N'-tetramethyl-urea Tetrafluoroboric acid, and described organic solvent is DIPEA.
Further; the concrete grammar obtaining described intermediate product through described washing is: after described proline(Pro) dichloro resin and described fluorenylmethyloxycarbonyl γ-aminobutyric acid are carried out linked reaction; with volume ratio be the piperidines of 1:4 ~ 6 and the washing of dimethyl formamide mixed solution repeatedly; then deprotection is carried out with hexahydropyridine; after deprotection terminates again with volume ratio be the piperidines of 1:4 ~ 6 and the washing of dimethyl formamide mixed solution repeatedly, obtain described intermediate product.
Further; the concrete grammar obtaining described antihypertensive active peptide after described washing, purifying is: after described intermediate product and described fluorenylmethyloxycarbonyl γ-aminobutyric acid are carried out linked reaction; with volume ratio be the piperidines of 1:4 ~ 6 and the washing of dimethyl formamide mixed solution repeatedly; then deprotection is carried out with hexahydropyridine; after deprotection terminates again with volume ratio be the piperidines of 1:4 ~ 6 and the washing of dimethyl formamide mixed solution repeatedly, then through draining, obtain described antihypertensive active peptide after purifying.
Further, semi-preparative reverse-phase high performance liquid chromatography is adopted to carry out described purifying.
Further, the reversed-phase column of described semi-preparative reverse-phase high performance liquid chromatography is: VYDAC-C18 post; Moving phase is: solution A is the trifluoroacetic acid of 0.05% ~ 0.15% (v/v) being dissolved in analytical pure level acetonitrile, and solution B is the trifluoroacetic acid of 0.05% ~ 0.15% (v/v) being dissolved in pure water; Gradient is: the solution A of 0min ~ 25min:5% ~ 30%, the solution B of 95% ~ 70%; The solution A of 26min ~ 55min:100%; Flow velocity: 0.5 ~ 1.5 ml/min.
In addition, the invention still further relates to the application of this antihypertensive active peptide in the antihypertensive medicine of preparation or food.
In addition, the invention still further relates to a kind of antihypertensive pharmaceutical composition, it comprises effective constituent and auxiliary material, and described effective constituent comprises antihypertensive active peptide as claimed in claim 1.
Auxiliary material wherein comprises conventional pharmaceutical excipient or foodstuff additive.
Due to the employing of above technical scheme, the present invention compared with prior art has following advantage:
The present invention proposes a kind of different bioactive peptide, the ACE inhibitory activity of this bioactive peptide can reach 57.8%, adopt 2mg/kg dosed administration after 5 days pressure value can be basically stable at about 170mmHg.
Accompanying drawing explanation
Accompanying drawing 1 is hypertension rat experiment detected result figure.
Embodiment
Below in conjunction with specific embodiment, the present invention will be further described in detail, but the invention is not restricted to following examples.In following examples, when being not particularly illustrated, " % " all refers to mass percent.
Experiment material:
New zealand white rabbit: pharmaceutical college of Shanghai Communications University animal experimental center provides;
Male hypertension pattern rat in 20 week age (SHR): Shanghai Experimental Animal Center provides;
Micropipet (100 ~ 1000 μ L, 20 ~ 200 μ L, 10 ~ 100 μ L, 0.5 ~ 10 μ L), EppendorfLtd;
Strainer (Φ 50mm), Shanghai institute of Pharmaceutical Industry;
Millipore filtration (Φ 50mm, aperture is 0.22 μm), rub fast science equipment company limited in Shanghai;
Centrifuge 5415 D small-sized high speed centrifugal machine, Eppendorf Ltd;
10 chromatographic systems, Superdex 30prep grade chromatography column (GE Healthcare, USA);
Zorbax SB-C18 reverse-phase chromatographic column (Agilent);
Mole ultrapure water machine, Shanghai Moller scientific instrument company limited;
GL-22M high speed freezing centrifuge, Shanghai Lu Xiang instrument whizzer instrument plant;
JY2002 type electronic balance, upper current chart level instruments and meters company limited;
Portable pressure steam sterilizing device, Shanghai Medical Nuclear Instrument Factory;
HWS26 type electric-heated thermostatic water bath, the permanent Science and Technology Ltd. in Shanghai one;
Lab Dancer test tube oscillator, IKA Works Guangzhou; Electrolux BCD-252T type refrigerator, Elex (China) Appliances Co., Ltd.;
DW-HW138 type Ultralow Temperature Freezer, middle section U.S. water chestnut low temperature science and technology limited Company;
Analytical balance, Meitelei-tolido, German;
Rat blood pressure meter: SoftronBP-98A, Beijing Ruan Long Bioisystech Co., Ltd.
The synthesis of embodiment 1 γ-aminobutyric acid-γ-aminobutyric acid-proline(Pro)
First on proline(Pro) dichloro resin, fluorenylmethyloxycarbonyl γ-aminobutyric acid is accessed; add TBTU (O-benzotriazole-N simultaneously; N; N'; N'-tetramethyl-urea Tetrafluoroboric acid) and DIEA (N; N-diisopropylethylamine) carry out coupling; coupling time is 60 minutes; and wash 3 removal end fluorenylmethyloxycarbonyl groups with piperidines/dimethyl formamide that volume ratio is 20%; then carry out deprotection with hexahydropyridine, after deprotection terminates, wash 6 times with piperidines/dimethyl formamide that volume ratio is 20% again.Fluorenylmethyloxycarbonyl γ-aminobutyric acid is added after draining, TBTU and DIEA carries out coupling, coupling time is 60 minutes, and wash 3 times with the piperidines/dimethyl formamide of 20%, deprotection is carried out with hexahydropyridine, wash 6 times with piperidines/dimethyl formamide that volume ratio is 20% again to drain, carry out purifying (reversed-phase column: VYDAC-C18 post (4.6 × 250mm, 5 μm) finally by semi-preparative reverse-phase high performance liquid chromatography; Moving phase: solution A (being dissolved in 0.1% (v/v) trifluoroacetic acid of analytical pure level acetonitrile), solution B (being dissolved in 0.1% (v/v) trifluoroacetic acid of pure water).Gradient is as follows: 0min ~ 25min:5% ~ 30%A, 95 ~ 70%B; 26min ~ 55min:100%A, 0%B.
Flow velocity: 1.0 ml/min; Separated and collected elution peak, for subsequent use after freeze-drying.
Structure determination:
C
13H
23N
3O
4，Mw：285.3
1H-NMR(CD
3OD,500MHz)δ:2.65(2H,t),1.83(2H,m),2.18(2H,m),3.20(2H,t),3.51(1H,m),3.41(1H,m),2.02(1H,m),1.92(1H,m),2.08(1H,m),2.33(1H,m),4.33(1H,t),8.1(1H,s)。
13C-NMR(CD
3OD,125MHz)δ:41.1,29.1,33.6,172.7,39.4,26.7,31.4,174.7,61.2,28.6,22.6,46.1,174.8。
Concrete structure formula is as shown in Equation 1:
Formula 1: γ-aminobutyric acid-γ-aminobutyric acid-proline(Pro)
The in vitro tests of embodiment 2 hypertension
Horse urea acyl histidyl-leucine (hippuryl-L-histidyl-L-leucine, HHL) under the catalysis of ACE enzyme, fast decoupled produces urobenzoic acid (Hippuric Acid, and dipeptides histidyl-leucine (HL) HA), after adding ACE enzyme inhibitors, the activity of ACE enzyme is suppressed, the growing amount of HA and HL reduces, in the present embodiment, ACE is extracted by rabbit lung, enzyme activity is 0.76mU/mL, by RP-HPLC method (chromatographic column: ZorbaxSB-C18 post (5 μm, 4.6mm × 250mm; Moving phase: 20% (v/v) analytical pure acetonitrile+0.1% (v/v) trifluoroacetic acid; Flow velocity: 1.0 ml/min)) measure the growing amount of HA under 228nm, evaluate ACE enzyme inhibitors to the inhibiting rate of ACE enzyme by following formula.
ACE inhibitory activity (%)=[(B-A)/(B-C)] × 100%
A: sample sets HA peak area
B: control group HA peak area
C: blank group HA peak area
Concrete reaction system and condition are in table 1:
Table 1
The present embodiment method records active kyrine of the present invention and is respectively 57.8% (γ-aminobutyric acid-γ-aminobutyric acid-proline(Pro)) to ACE inhibitory activity.
Embodiment 3 hypertension animal vivo test
Adopt SoftronBP-98A type rat blood pressure instrument to carry out the method that tail vein measures blood pressure, measure the systolic pressure (SBP) of rat.
1, under SHR rat (spontaneous hypertensive rat) waking state, first mouse is placed in mouse bag, keep constant temperature, adopt SoftronBP-98A type rat blood pressure instrument to carry out the method that tail vein measures blood pressure, measure the systolic pressure (SBP) of rat.Starting the blood pressure measuring rat every other day the last week in testing, after the stable adaptation of rat, starting experimental record.First measure the rat blood pressure before gavage, then 2mg/kg dosage (the body weight gavage according to rat) sample (active kyrine) gavage, the same dosage of control group gavage pure water, continuous gavage sample 10 days, measures 1d, 3d, 5d, 7d, 9d, 10d rat blood pressure after gavage sample.Each test point all measures the blood pressure of 2 rats, and the interval time measured for 2 times is about 1min, gets the blood pressure (see Fig. 1) of mean value as this test point rat of 2 measured values.
Fig. 1 is the blood pressure situation after control rats and two kinds of bioactive peptide gastric infusions, and its data measured SPSS system software carries out system process, adopts the t method of inspection.From experimental result, compared with control group, two kinds of bioactive peptide gastric infusions are after 1 day, and SHR Hypertensive Rats is all decreased significantly at rear pressure value, administration is after 5 days, and γ-aminobutyric acid-γ-aminobutyric acid-proline(Pro) sample sets pressure value is basically stable at about 170mmHg.Illustrate that bioactive peptide of the present invention all has good blood pressure lowering effect.
Above to invention has been detailed description; its object is to allow the personage being familiar with this art can understand content of the present invention and be implemented; can not limit the scope of the invention with this; the equivalence change that all spirit according to the present invention are done or modification, all should be encompassed in protection scope of the present invention.
Claims (4)
1. an antihypertensive active peptide, is characterized in that: the aminoacid sequence of described bioactive peptide is: γ-aminobutyric acid-γ-aminobutyric acid-proline(Pro).
2. a preparation method for antihypertensive active peptide as claimed in claim 1, is characterized in that: its by by proline(Pro) dichloro resin and fluorenylmethyloxycarbonyl γ-aminobutyric acid under the existence of coupling agent and organic solvent, carry out coupling and obtain intermediate product; Again by described intermediate product and fluorenylmethyloxycarbonyl γ-aminobutyric acid under the existence of coupling agent and organic solvent, carry out coupling, after purified, obtain described antihypertensive active peptide.
3. the application of antihypertensive active peptide as claimed in claim 1 in the antihypertensive medicine of preparation or food.
4. an antihypertensive pharmaceutical composition, it comprises effective constituent and auxiliary material, it is characterized in that: described effective constituent comprises antihypertensive active peptide as claimed in claim 1.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105777866A (en) * | 2016-04-12 | 2016-07-20 | 南京大学 | Anti-hypertension bioactive peptide and preparing method thereof |
| CN107312064A (en) * | 2017-07-26 | 2017-11-03 | 盐城卫生职业技术学院 | A kind of antihypertensive active peptide GABA The Pro and application and pharmaceutical composition |
| CN107325153A (en) * | 2017-07-26 | 2017-11-07 | 盐城卫生职业技术学院 | A kind of antihypertensive active peptide Citn Hyp Pro and application and pharmaceutical composition |
| CN107337711A (en) * | 2017-07-26 | 2017-11-10 | 盐城卫生职业技术学院 | A kind of antihypertensive active peptide Citn Pro Hyp and application and pharmaceutical composition |
| CN107337712A (en) * | 2017-07-26 | 2017-11-10 | 盐城卫生职业技术学院 | A kind of antihypertensive active peptide Orn Hyp Pro and application and pharmaceutical composition |
| CN107337710A (en) * | 2017-07-26 | 2017-11-10 | 盐城卫生职业技术学院 | A kind of antihypertensive active peptide The The Pro and application and pharmaceutical composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107337710A (en) * | 2017-07-26 | 2017-11-10 | 盐城卫生职业技术学院 | A kind of antihypertensive active peptide The The Pro and application and pharmaceutical composition |
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