CN107661418A - A kind of application of Cyanotis arachnoides P.E in pulmonary hypertension medicine is prevented and treated - Google Patents
A kind of application of Cyanotis arachnoides P.E in pulmonary hypertension medicine is prevented and treated Download PDFInfo
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Abstract
The present invention relates to a kind of new application of Cyanotis arachnoides P.E in medicine, belong to pharmaceutical technology field.The invention provides a kind of new application of Cyanotis arachnoides P.E in terms of pharmacy, the i.e. application in prevention and/or treatment pulmonary hypertension medicine is prepared.Cyanotis arachnoides P.E is administered in the pulmonary hypertension model in rats of monocrotaline induction, pulmonary artery flow velocity, the internal diameter of pulmonary artery root of each group animal substantially reduce；The mean pulmonary arterial pressure power of Cyanotis arachnoides P.E group is less than model group（P<0.05）, pulmonary hypertension symptom caused by display Cyanotis arachnoides P.E can significantly reduce monocrotaline, have the function that to treat pulmonary hypertension.Cyanotis arachnoides P.E is administered in hypoxia-induced pulmonary hypertension model in rats, result of study shows that the pulmonary arterial pressure rise of rat significantly reduces effect, prompts Cyanotis arachnoides P.E to suppress the rise of Chronic Hypoxic Rats pulmonary arterial pressure.
Description
Technical field
The present invention relates to a kind of new application of Cyanotis arachnoides P.E in medicine, specifically prepare prevention and/or
Treat the new opplication in pulmonary hypertension medicine.Belong to pharmaceutical technology field.
Background technology
Pulmonary hypertension is as a kind of Multiple Chronic disease in angiocardiopathy, secondary to the heart, lung, systemic disease or original
Because failing to understand, it is mainly shown as that pulmonary artery pressure and pulmonary vascular resistance continuation increase, causes progressive to be had difficulty in breathing, be modern society
One of principal disease of human health can be threatened.According to European Society of Cardiology's Diagnosis of Pulmonary Hypertension in 2009 and practice guidelines
The newest clinical classification that (hereinafter referred to as guide) proposes, pulmonary hypertension (Pulmonary Arterial Hypertension,
PAH it is) a kind of rare chronic fatal disease for having a strong impact on patient vitals' health in PH, is referred to as " in angiocardiopathy
Malignant tumour ", due to Pulmonary Vascular shrink, pulmonary artery endometrial hyperplasia or reconstruct cause pulmonary hemodynamics to change, finally
Cause patient's right heart failure even dead, the life and health of the mankind is caused and had a strong impact on.There are some researches show PAH patient's
Average age of onset is between 25 to 40 years old, but because it is clinically more rare, the incidence of disease is about that two million peoples are annual, and category is rare
See disease category.It is dead within 75% patients with pulmonary hypertension after diagnosis 5 years, such as treat not in time, life span only have 2 to
3 years.With the continuous progress for the treatment of means, the survival of patients time is also extending year by year.If diagnosis and treatment early can be obtained, at least
The 20% sufferer state of an illness can be made be improved, or even recovery from illness.
Blackspiked lovegrass herb with root (Cyanotis, arachnoidea, C.B.Clarke) is Commelianaceae orchid cerastium perennial plant,
Blackspiked lovegrass herb with root also known as arachnoid cyanotis root, it is distributed in the ground such as Yunnan, Taiwan, Guangdong.Its property is pungent, slight bitter, has dispelling, collateral-activating, and dampness removing disappears
The effect of swollen.
Patent document（Authorization Notice No. CN1070077C and CN102526151B）Report Cyanotis arachnoides P.E may act on
Human body, there is the synthesis for promoting protein, exclude internal cholesterol, reducing blood lipid, suppress the physiologically actives such as blood glucose rising, patent text
Offer（Publication number CN104415068A）Report blackspiked lovegrass herb with root has the effect for the treatment of cerebral apoplexy.In sericulture, for promoting silkworm age
Shorten, promote spinning to cocoon；In aquaculture, it is widely used in the cultivation of shrimp, crab；In cosmetics, Cyanotis arachnoides P.E
Its additive can be used as after treatment, prevented dry skin, made skin more delicate.
At present, on application of the Cyanotis arachnoides P.E in sitaxsentan sodium thing field there is not yet relevant report.
The content of the invention
The invention provides a kind of new application of Cyanotis arachnoides P.E in terms of pharmacy, that is, is preparing prevention and/or treatment
Application in pulmonary hypertension medicine.
Present invention also offers Cyanotis arachnoides P.E to prepare prevention and/or treatment chronic thromboembolic pulmonary hypertension
Application in medicine.
Present invention also offers Cyanotis arachnoides P.E prepare prevention and/or treatment hypoxemia caused by pulmonary hypertension medicine
Application in thing.
Present invention also offers Cyanotis arachnoides P.E prepare prevention and/or treatment PUD D caused by pulmonary hypertension medicine
Application in thing.Wherein pulmonary disorders include COPD, Interstitial Lung Disease and other with dysfunction of ventilation
PUD D.
The present invention also illustrates Cyanotis arachnoides P.E in pulmonary hypertension prevention and/or therapy field by animal model
Effect.
Described Cyanotis arachnoides P.E can be carried out individual administration by number of ways, and method of administration includes oral, intravenous injection
Deng.Correspondingly, described Cyanotis arachnoides P.E can be prepared into oral formulations and injection with pharmaceutical carrier.Wherein, oral system
Agent includes tablet, capsule, microcapsule formulations, granule, dripping pill, oral liquid and powder.Injection includes intravenous injection and powder pin
Agent.Can also be needed to be equipped with no pharmaceutical acceptable carrier according to formulation, at the same can add antioxidant, emulsifying agent, stabilizer and
Mould inhibitor.
Below by embodiment, the present invention will be further described, but is not used for limiting the effective range of the present invention.
Embodiment
The Cyanotis arachnoides P.E of embodiment 1（Hereinafter referred to as LSC）In the pulmonary hypertension model in rats of monocrotaline induction
Effect
Male SD rat, body weight 220g ± 20g, using hypodermic injection monocrotaline（60mg/kg）Method prepare induced lung move
Arteries and veins High Pressure Model right cardiac catheter detection assay pulmonary artery blood pressure and hemodynamic index.Two weeks detection pulmonary artery bloods after injection
Pressure, determines whether modeling succeeds, the successful animal of modeling is divided into following each group（n=10）：
Sham-operation group：The ml/kg of physiological saline 2 is given in injection；
Model group：The ml/kg of physiological saline 2 is given in injection；
LSC high dose groups：6 mg/kg are given in injection；
LSC middle dose groups：3 mg/kg are given in injection；
LSC low dose groups：1 mg/kg is given in injection；
Start to be administered after determining modeling success, continuous gavage is administered 2 weeks, and each group animal lung artery root is detected after last dose
Footpath, pulmonary artery flow velocity, pulmonary artery and arteria carotis mean pressure.
Rat pulmonary artery root footpath, the measurement of pulmonary artery flow velocity：Rat weight, 1% barbital sodium intraperitoneal injection of anesthesia, lies on the back
After fixation, CDFI measurement each group rat pulmonary artery flow velocity, pulmonary artery root footpath.
Pulmonary artery and arteria carotis mean pressure measure：Neck median incision is done, from the askew venous cannula of right side neck to pulmonary artery, simultaneously
Row left common carotid is intubated, and determines mean pulmonary arterial pressure（mPAP）With mean carotid pressure（MCAP）.
Result of the test：It is shown in Table 1 and table 2.
In pulmonary hypertension model in rats rat pulmonary artery flow velocity that the LSC of table 1 is induced monocrotaline, pulmonary artery root
Footpath acts on
| Group | n | Pulmonary artery flow velocity（cm/s） | Pulmonary artery root internal diameter（mm） |
| Sham-operation group | 10 | 51±4.9 | 2.22±0.07 |
| Model group | 10 | 86.32±5.9 | 2.98±0.07 |
| LSC high dose groups | 10 | 57.6±4.3** | 2.31±0.14** |
| LSC middle dose groups | 10 | 64.8±4.8** | 2.51±0.11* |
| LSC low dose groups | 10 | 76.5±5.8* | 2.74±0.12 |
* the P compared with model group<0.05；* P compared with model group<0.01
Pulmonary hypertension model in rats rat mPAP and mCAP that the LSC of table 2 is induced monocrotaline effect
| Group | n | mPAP（mmHg） | mCAP（mmHg） |
| Sham-operation group | 10 | 18.1±2.1 | 131±4 |
| Model group | 10 | 35.1±4.5 | 132±5 |
| LSC high dose groups | 10 | 20.4±1.9** | 132±5 |
| LSC middle dose groups | 10 | 25.7±2.8* | 131±5 |
| LSC low dose groups | 10 | 31.1±3.1 | 130±4 |
* the P compared with model group<0.05；* P compared with model group<0.01
It is administered it can be seen from above-mentioned result of the test after LSC, pulmonary artery flow velocity, the internal diameter of pulmonary artery root of each group animal
Substantially reduce.The mean pulmonary arterial pressure power of LSC groups is less than model group（P<0.05）；Model group mean pulmonary arterial pressure compared with control group,
Treatment group substantially increases（P<0.01）；And sham-operation group, model group, LSC each group mean carotid pressure gaps are anticipated without statistics
Justice.It can be seen that pulmonary hypertension symptom caused by can significantly reducing monocrotaline after administration LSC, has treatment pulmonary artery
The effect of high pressure.
The Cyanotis arachnoides P.E of embodiment 2（Hereinafter referred to as LSC）Effect in hypoxia-induced pulmonary hypertension model in rats
Male SD rat, body weight 220g ± 20g, rat is placed in self-control normal pressure low oxygen cabin, nitrogen is poured into cabin, regulates and controls cabin
Interior oxygen concentration maintains（10±0.5）%, progress Induced by Intermittent Hypoxia, daily 8h, 6 days weekly, totally 21 days；Treatment group：Before daily anoxic
Drug administration by injection LSC, continuous 21 days, while give anoxic treatment（Same model group）；Control group：It is without any processing.
Each group administration is as follows（n=10）：
Control group：Gavage gives the ml/kg of physiological saline 2；
Model group：Gavage gives the ml/kg of physiological saline 2；
LSC high dose groups：Gavage gives 6 mg/kg；
LSC middle dose groups：Gavage gives 3 mg/kg；
LSC low dose groups：Gavage gives 1 mg/kg；
After last day administration, right ventricular mean pressure is determined（mRVP）And mean pulmonary arterial pressure（mPVP）.After the completion of pressure measurement, left side neck
Total artery collection blood sample, 1500rpm/min centrifugation 10min, takes blood plasma to be measured.Right lung leaf is taken after animal is put to death immediately, it is raw
Manage salt solution to clean 3 times, filter paper is weighed after blotting, and 10% lung homogenate, 2500rpm/min centrifugations are made in glass homogenizer
10min, take supernatant Cord blood to be measured.Core Zang Cheng right ventricles simultaneously（RV）With left room（LV）+ interventricular septum（S）Weight in wet base, calculate
Ratio.
Biochemical indicator detects：Blood plasma and lung homogenate nitric oxide（NO）Measure and nitricoxide synthase（NOS）Activity
Measure is operated using kit.
Blood plasma and lung homogenate superoxide dismutase MDA（SOD/LPO）Measure：SOD uses adjacent benzene three
Phenol method, LPO use TBA colorimetric methods.
Result of the test：It is shown in Table 3, table 4 and table 5.
The LSC of table 3 is acted on hypoxia-induced pulmonary hypertension model in rats pulmonary arterial pressure in rats
| Group | n | mPAP（mmHg） | mRVP（mmHg） | RV/LV+S |
| Control group | 10 | 22±4 | 18±3 | 0.26±0.20 |
| Model group | 10 | 38±8 | 37±4 | 0.65±0.18 |
| LSC high dose groups | 10 | 23±3** | 22±4** | 0.37±0.34** |
| LSC middle dose groups | 10 | 29±4* | 28±3* | 0.51±0.26* |
| LSC low dose groups | 10 | 35±5 | 32±4* | 0.60±0.14 |
* the P compared with model group<0.05；* P compared with model group<0.01
The LSC of table 4 to hypoxia-induced pulmonary hypertension model in rats rat plasma NO NOS SOD LPO effect
| Group | n | NO | NOS | SOD | LPO |
| Control group | 10 | 52±5 | 3.5±0.7 | 44±4 | 2.4±1.0 |
| Model group | 10 | 24±4 | 2.0±0.6 | 29±4 | 6.8±1.4 |
| LSC high dose groups | 10 | 28±3** | 3.2±0.7** | 36±5* | 2.6±0.9** |
| LSC middle dose groups | 10 | 36±4** | 2.8±0.9 | 39±3 | 4.0±0.8* |
| LSC low dose groups | 10 | 48±5 | 2.0±0.5 | 41±5 | 4.7±0.9 |
* the P compared with model group<0.05；* P compared with model group<0.01
The LSC of table 5 to hypoxia-induced pulmonary hypertension model in rats lung tissue of rats NO NOS SOD LPO effect
| Group | n | NO | NOS | SOD | LPO |
| Control group | 10 | 123±11 | 4.8±0.7 | 87±9 | 7.0±0.6 |
| Model group | 10 | 69±8 | 2.1±0.6 | 57±4 | 17.0±0.7 |
| LSC high dose groups | 10 | 104±10** | 3.6±0.9** | 81±5* | 7.2±0.6** |
| LSC middle dose groups | 10 | 79±5* | 2.5±0.7* | 62±6 | 15.0±0.6 |
| LSC low dose groups | 10 | 68±7 | 2.1±0.8 | 61±4 | 16.0±0.7 |
* the P compared with model group<0.05；* P compared with model group<0.01
The study show that pulmonary arterial pressure rises of the LSC to Chronic hypoxia rat significantly reduces effect, LSC is prompted to suppress slow
Property the rise of Hypoxic Rats pulmonary arterial pressures.
Hypoxemia is that pulmonary artery endothelial cell NOS activity reduces, and it is the main reason for hypoxemia Pulmonary Vascular shrinks that NO, which produces reduction,
One of.The research of this group finds that hypoxia rats lung homogenate and blood plasma NOS activity, NO are substantially reduced, and both changes are consistent.
LSC treatment groups rat NOS, NO are significantly higher than model group（P<0.05）, the activity with increase lung tissue NOS is prompted, promotes NO
Generation and release, so as to play expansion pulmonary artery, reduce the effect of pulmonary hypertension.
Free radical plays an important role in the forming process of pulmonary hypertension.In this experiment, model group rats lung group
Knit LPO in homogenate and blood plasma significantly to raise, SOD is significantly reduced, and LPO significantly drops in treatment group's lung tissue of rats homogenate and blood plasma
Low, SOD is significantly raised, and illustrates that LSC has Green Tea Extract, lipoid peroxidization resistant, it is believed that it is high to Hypoxic Rats pulmonary artery
The effect of pressure may have certain relation with its Green Tea Extract.
Claims (6)
- A kind of 1. application of Cyanotis arachnoides P.E in prevention and/or treatment pulmonary hypertension disease medicament is prepared.
- 2. Cyanotis arachnoides P.E according to claim 1 is in prevention and/or treatment pulmonary hypertension disease medicament is prepared Application, it is characterized in that, described prevention and/or treatment pulmonary hypertension disease medicament is prevent and/or treatment Chronic Thrombotic Application in embolic pulmonary hypertension medicine.
- 3. Cyanotis arachnoides P.E according to claim 1 is in prevention and/or treatment pulmonary hypertension disease medicament is prepared Application, it is characterized in that, described prevention and/or treatment pulmonary hypertension disease medicament are prevention and/or treat hypoxa institute Cause the application in pulmonary hypertension medicine.
- 4. Cyanotis arachnoides P.E according to claim 1 is in prevention and/or treatment pulmonary hypertension disease medicament is prepared Application, it is characterized in that, described prevention and/or treatment pulmonary hypertension disease medicament is prevent and/or treatment pulmonary disorders Application in caused pulmonary hypertension medicine.
- 5. Cyanotis arachnoides P.E according to claim 4 pulmonary artery caused by prevention and/or treatment pulmonary disorders is prepared is high Application in pressing thing, it is characterized in that, described pulmonary hypertension disease includes COPD, Interstitial Lung Disease PUD D with other with dysfunction of ventilation.
- 6. the Cyanotis arachnoides P.E according to right 1-5 any claims is preparing prevention and/or treatment pulmonary hypertension Application in disease medicament, it is characterized in that, described Cyanotis arachnoides P.E is prepared into oral formulations or injection with pharmaceutical acceptable carrier Agent.
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