Unlock instant, AI-driven research and patent intelligence for your innovation.

Antihypertensive active peptide Orn-Pro-Hyp and application and medicinal composition

An anti-hypertensive and active peptide technology, applied in the field of biomedicine, can solve problems such as low repeatability, constraints, and high costs, and achieve the effect of ensuring integrity

Inactive Publication Date: 2018-09-04
NANJING UNIV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this preparation method has high cost, low reproducibility, and low bioavailability, and there is an urgent need to develop a new alternative production technology
These studies are all based on the peptide information contained in the protein. Although as the molecular weight of the peptide increases, its structure will vary widely and its activity will become more potential. However, due to the molecular sieve effect of the intestinal mucosa and its rich peptidase, the In order to use natural protein active resources to develop ACEI peptide small molecule substances

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Antihypertensive active peptide Orn-Pro-Hyp and application and medicinal composition
  • Antihypertensive active peptide Orn-Pro-Hyp and application and medicinal composition
  • Antihypertensive active peptide Orn-Pro-Hyp and application and medicinal composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1: Synthesis of Orn-Pro-Hyp tripeptide.

[0020] The Orn-Pro-Hyp tripeptide used in the present invention can be synthesized by artificial chemical methods known in the field of polypeptide synthesis. In this embodiment, a liquid-phase synthesis method is used, and the specific operations are as follows:

[0021] First, choose the preloaded tert-butyl hydroxyproline dichlorotrityl resin (Hyp(Tbu)-2Cl(TRT)-resin) with O-benzotriazole-N,N,N', N'-Tetramethylurea tetrafluoroboric acid (TBTU) and N,N-diisopropylethylamine (DIEA) are used as condensation agents, adding fluorenylmethoxycarbonyl-L-proline (FMOC-Pro-OH), React for 1 hour. Next, use dimethylformamide (DMF) as a cleaning agent to clean the product obtained in the previous step reaction to obtain fluorenylmethoxycarbonyl prolyl tert-butyl hydroxyproline dichlorotrityl resin (FMOC-Pro- Hyp(Tbu)-2Cl(TRT)-resin). Then, adopt hexahydropyridine (PPD) as deprotecting agent, join in the resin (FMOC-Pro-Hyp(Tbu)...

Embodiment 2

[0029] Example 2: In vitro Orn-Pro-Hyp inhibition test on angiotensin-converting enzyme (ACE) activity.

[0030] Hippuryl-L-histidyl-L-leucine (hippuryl-L-histidyl-L-leucine, HHL) is rapidly decomposed under the catalysis of ACE enzyme to produce hippuric acid (Hippuric Acid, HA) and dipeptide histidyl-leucine (HL), adding After ACE enzyme inhibitor, the activity of ACE enzyme is inhibited, and the production of HA and HL is reduced. In this embodiment, ACE is extracted from rabbit lung, and the enzyme activity is 0.76mU / mL. It is developed by DAB and measured by spectrophotometer. The amount of HA produced and the activity of ACE enzyme were analyzed. Ethyl acetate extracts hippuric acid in the reactant, then reacts with a pyridine solution (DAB chromogen) containing p-dimethylaminobenzaldehyde in acetic anhydride to generate an orange-yellow compound, and directly measures its OD value at 459nm colorimetrically, It is used to evaluate the inhibition rate of ACE enzyme inhib...

Embodiment 3

[0035] Example 3: In vivo antihypertensive test in congenitally hypertensive rats (SHR).

[0036] Using SoftronBP-98A intelligent non-invasive blood pressure instrument for rats, the systolic blood pressure (SBP) of the rats was determined by the tail method.

[0037] In the awake state of SHR rats (spontaneously hypertensive rats), first put the rats in a rat bag, keep a constant temperature, and use the Softron BP-98A rat intelligent non-invasive blood pressure instrument to measure the tail vein blood pressure. Systolic blood pressure (SBP) in rats. One week before the experiment, the blood pressure of the rats was measured every other day, and the experimental records were started after the rats got used to it stably. First measure the blood pressure of the rats before gavage, then 30mg / kg body weight dose is gavaged with the sample (active tripeptide, Orn-Pro-Hyp), the blank control group is gavaged with an equal volume of normal saline (Saline), and the drug control gro...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses antihypertensive active peptide Orn-Pro-Hyp (Ornithine-Proline-4-Hydroxyl-Proline) and application and a medicinal composition. The antihypertensive active peptide Orn-Pro-Hyphas the amino acid sequence of ornithine-proline-hydroxyproline and adopts the structure shown as a formula I. The angiotensin-converting enzyme (ACE) activity inhibiting IC50 of the active peptide is1.27mmol / L; 1.5 hours after gastric perfusion of a congenital hypertensive rat according to a dose of 30mg / kg based on the body weight, the blood pressure is lowered from 200mmHg to a minimum of 171mmHg, and the blood pressure lowering effect lasts for 3 hours and then restored to the level before gastric perfusion. The active peptide can be prepared by the conventional method in the field, and afoundation is laid for low-cost and high-yield preparation in future medicine development.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically relates to an antihypertensive active peptide Orn-Pro-Hyp and its application, and an antihypertensive pharmaceutical composition. Background technique [0002] The "China Cardiovascular Disease Report 2017" pointed out that the prevalence of cardiovascular disease in my country is in a stage of continuous increase. It has become a consensus that hypertension is the main risk factor for cardiovascular disease, and it is the driving factor for the continuous increase in the prevalence of cardiovascular disease in my country. Hypertension refers to a clinical syndrome characterized by an increase in systemic arterial blood pressure (systolic and / or diastolic), which may be accompanied by functional or organic damage to the heart, brain, kidneys and other organs. Hypertension is the most common chronic disease and the main risk factor for cardiovascular and cerebrovascular diseases....

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/083A61K38/06A61P9/12A23L33/18
CPCA61P9/12A23L33/18C07K5/0806A61K38/00A23V2002/00A23V2200/326A23V2250/54
Inventor 王强郭文娜陈建群钱炳俊
Owner NANJING UNIV