CN106511437A - Preparation method and pharmaceutical application of effective part of rhodiola rosea - Google Patents
Preparation method and pharmaceutical application of effective part of rhodiola rosea Download PDFInfo
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- CN106511437A CN106511437A CN201611222778.2A CN201611222778A CN106511437A CN 106511437 A CN106511437 A CN 106511437A CN 201611222778 A CN201611222778 A CN 201611222778A CN 106511437 A CN106511437 A CN 106511437A
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- radix rhodiolae
- rhodiola
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/41—Crassulaceae (Stonecrop family)
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
The invention discloses a preparation method and pharmaceutical application of an effective part of rhodiola rosea. The preparation method comprises the following steps that the rhodiola rosea is extracted by ethanol after being smashed; and an extract is subjected to separation through macroporous adsorption resin and gradient elution through water and ethanol systems, an eluent is subjected to decomperssion concentration, and after freeze drying, the effective part of the rhodiola rosea is obtained. According to the application of the effective part of the rhodiola rosea, the effective part is used for preparing medicine for treating and/or preventing pulmonary arterial hypertension, health care products for treating and/or preventing the pulmonary arterial hypertension, medicine for promoting vascular endothelial cell repair and protection, health care products for promoting vascular endothelial cell repair and protection, medicine for treating cell line grain damage, and health care products for treating cell line grain damage. The raw material supply of the effective part is stable, the cost is low, the preparation cost is low, and the medicine effect is reliable.
Description
Technical field
The present invention relates to pharmaceutical technology field, and in particular to isolated Radix Rhodiolae in a kind of root from Rhodida plant
Effective site and the purposes in preparation treatment pulmonary hypertension medicine and health product.
Background technology
Rhodida plant is Crassulaceae (Crassulaceae) rhodiola (Rhodiola) plant, is perennial grass
This or semishrub plant, there are about kind more than 90, and China has 73 kinds, main product in North China, northeast, southwest, northwest and Central China and other places,
Reserves are enriched, and occupy first of the world, and Qinghai is one of main producing region of Radix Rhodiolae, with Rhodiola kirilowii (Regel) Maxim.Rhodiola Kirilowii And Rhodiola CrassulaceaeRhodiola algidaReserves are big.Radix Rhodiolae has had long medicine in China
Use history.《Compendium of Materia Medica》Reputation for " Hylotelephium erythrostictum (Miq.) H.Ohba grass ", " flame grass ", " top grade in Jing ", have " strengthening the body resistance, refreshment eyesight improving, light
Logical god is not old for body QI invigorating, long term usage " the effect of.《Four doctor's allusion quotations》Record Deng Tibetan medicine and pharmacology ancient books and records, Radix Rhodiolae has lung moistening, the kidney invigorating, helps
Just consolidate, qi-regulating blood-nourishing, nourishing the brain and improving intelligence and the effects such as nourishing and fit keeping function.In rhodiola plant, chemical composition species is more, according to text
Report is offered, main component has butyl alcohol and glycoside；Flavone and its glycoside；Coumarinses；Phenylpropanoid Glycosides class；Terpenoid；Volatile oil；
Phenolic acids；Polysaccharide etc..
Pulmonary hypertension (pulmonary arterial hypertension, PAH) is that different pathogeny is caused with lung
Arterial pressure and pulmonary vascular resistance raise with the characteristics of one group of disease or clinical syndrome, its pathogenesis include vasoconstriction,
Vascular remodeling and thrombosiss.Pulmonary hypertension is divided by the categorizing system that international primary pulmonary hypertension symposium is proposed
Into 5 types:1) pulmonary hypertension relevant with respiratory system disease and/or hypoxemia；2) pulmonary venous hypertension；3) it is chronic
Thrombosis and/or embolism class diseases；4) lung arteriolar hypertension；5) directly affect the pulmonary hypertension caused by Pulmonary Vascular tissue disease.
If PAH is not added with treatment, right heart failure, volume load can be finally caused to increase and the death that arrives.At present, treat pulmonary hypertension
Medicine is mainly vasodilation, such as α receptor blocking agents, calcium antagonist angiotensin converting enzyme inhibitor, phosphodiesterase
Inhibitor, prostaglandinss (PG) medicine, nitro class vasodilation etc..Although these medicines are stranded with patient respiratory is improved
The effect of the aspect such as difficult, 6 minutes walking distances (6MWD) and pulmonary hemodynamicses, but therapeutic effect, preparation and medication into
Originally, there are different defects in terms for the treatment of convenience.
The content of the invention
The present invention is mainly to provide a kind of preparation method of Radix Rhodiolae effective site；
It is a further object of the present invention to provide aforementioned Radix Rhodiolae effective site is in the medicine for preparing treatment and/or prophylaxis of pulmonary hypertension
Application in thing and/or health product；
The 3rd purpose of the present invention is to provide aforementioned Radix Rhodiolae effective site and is preparing treatment and/or preventing pulmonary artery reconstruct
Medicine and/or health product in application；
The 4th purpose of the present invention is to provide aforementioned Radix Rhodiolae effective site and is preparing treatment and/or preventing Pulmonary Vascular epithelial cell
Application in the medicine and/or health product of damage；
The 5th purpose of the present invention is to provide the aforementioned Radix Rhodiolae effective site and is preparing treatment and/or preventing mitochondrial injury
Application in medicine and/or health product.
For solving above-mentioned technical problem, the present invention is adopted the following technical scheme that：A kind of preparation side of Radix Rhodiolae effective site
Method, it is characterised in that：Carry out according to the following steps,
1) dry rhizome of Rhodida plant is crushed, is extracted with methanol or ethanol, extracting solution concentrating under reduced pressure into extractum,
Obtain Radix Rhodiolae total extract；
2) Radix Rhodiolae total extract is dispersed in pure water, and is staticly settled, precipitation is filtered, filtrate is obtained；
3) filtrate Jing macroporous adsorbent resins are separated, and carry out gradient elution with water, ethanol system, by eluent concentrating under reduced pressure,
Radix Rhodiolae effective site is obtained after lyophilization.
Further, step 1) in the concentration of Extraction solvent be 10-100%, its consumption is 5-10 times of medical material weight；Carry
Take process to repeat 2-3 time, each extraction time is 1-2 hours；Step 2) in precipitation process at room temperature stand 12-24 it is little
When, the amount of required pure water is 5-10 times of Radix Rhodiolae total extract weight；Step 3) in the macroporous adsorbent resin that adopts for
Any one during HP20 series, HPD series, D101 series, AB-8 are serial；Gradient elution carries out eluting, Ran Houyong with water first
Ethanol, water mixed solvent carry out gradient elution；It is preferred that terraced using water, 30% ethanol, 70% ethanol and 95% ethanol four successively
Degree carries out eluting；The eluting agent of each gradient is 3 to 5 column volumes；It is preferred that collects that 70% ethanol elution obtains washes
De- thing.
Preferably, the Rhodida plant for being adopted includes but is not limited to Radix Rhodiolae, Rhodiola kirilowii (Regel) Maxim., the red scape of high mountain
My god, Rhodiola rosea L., Rhodiola atuntsuensis, Rhodiola himalensis, Rhodiola phariensis, Rhodiola henryi, Rhodiola quadrifida, YUNNANHONG scape
My god, Rhodiola wallichiana var. cholaensis, Rhodiola fastigiata, Rhodiola Crassulaceae, Radix Rhodiolae, Rhodiola dumulosa and Rhodiola sachalinensis.
Radix Rhodiolae effective site is obtained by preceding method.
A kind of pharmaceutical composition based on aforementioned Radix Rhodiolae effective site, which includes Radix Rhodiolae effective site and pharmaceutically
Acceptable carrier.Further relate to containing the Radix Rhodiolae effective site as active ingredient and customary pharmaceutical excipients or adjuvant
Pharmaceutical composition, usual Radix Rhodiolae effective site account for the 0.1～99% of pharmaceutical composition gross weight.
The pharmaceutical composition route of administration can be Jing gastrointestinal tract or non-Jing gastrointestinal tract, such as oral, lung, nasal cavity, subcutaneous, tongue
Under, skin, muscle, rectum etc., preferably oral administration；The route of administration of the pharmaceutical composition can be also drug administration by injection, inject bag
Include intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, lumbar injection and acupoint injection therapy etc..
The form of administration of the pharmaceutical composition can be liquid dosage form, solid dosage formss or semisolid dosage form.Liquid dosage form can
Being solution, Emulsion, suspensoid, injection, eye drop, nasal drop, lotion and liniment etc..Solid dosage formss can be tablet (
Including ordinary tablet, enteric coatel tablets, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, oral cavity disintegration tablet), capsule is (including hard capsule, soft
Capsule, enteric coated capsule), granule, powder, micropill, drop pill, suppository, membrane, paster, gas (powder) mist agent, spray etc.；Half
Solid dosage formss can be ointment, gel, paste etc..
Aforementioned Radix Rhodiolae effective site can be made ordinary preparation, can also be slow releasing preparation, controlled release preparation, targeting preparation
And various particulate delivery systems.
The dosage of the pharmaceutical composition depends on many factors, for example, will prevent or treat the property and sternly of disease
The sex of weight degree, patient or animal, age, body weight, personality and individual reaction, route of administration, administration number of times, therapeutic purposes,
Therefore the therapeutic dose of the present invention can have change on a large scale.The daily Suitable dosage ranges of the Radix Rhodiolae effective site are：
Consumption is 0.1～100mg/Kg body weight, and above-mentioned dosage with ingle dose form or can be divided into several, such as two, three or four
Dosage forms for administration.The present invention compound or pharmaceutical composition individually can take, or with other treatment medicine or symptomatic drugs
Merging is used and adjusts dosage.
For reaching medication purpose, strengthen therapeutic effect, the Radix Rhodiolae effective site of the present invention or available of pharmaceutical composition
What known medication administration.
Additionally, if desired, can also add in pharmaceutical preparation coloring agent, preservative, spice, correctivess, sweeting agent or
Other materials.
The present invention makes filtrate after extractum is obtained using Rhodida plant again, extracts the effective portion of Radix Rhodiolae by filtrate
Position, and it is used for preparing treatment and/or prophylaxis of pulmonary hypertension medicine, treatment and/or pre- according to the characteristic of Radix Rhodiolae effective site
The health product of anti-pulmonary hypertension, the medicine for promoting vascular endothelial cell reparation and protection, promote vascular endothelial cell reparation and
The health product that the medicine and cell line grain that the health product of protection, cell line grain are damaged is damaged, its raw material supply is stable, cost
It is low, and preparation cost is low, drug effect reliability.
Description of the drawings
Fig. 1 is the impact that Rhodiola Crassulaceae active site stimulates lower pulmonary arterial pressure in rats to hypoxia；
Fig. 2 is the impact after Rhodiola Crassulaceae active site is administered 15 days to lung small artery vascular remodeling caused by hypoxia；
Fig. 3 is the impact after Rhodiola Crassulaceae active site is administered 30 days to lung small artery vascular remodeling caused by hypoxia；
Fig. 4 is the impact that Rhodiola Crassulaceae active site is damaged to Pulmonary Microvascular Endothelial Cells in Rats caused by hypoxia（Wherein, A
For 15 days, B was 30 days）.
Specific embodiment
With reference to specific embodiment, the present invention will be further described, but this does not imply that any limit to the present invention
System.
First, the preparation of Radix Rhodiolae effective site
Embodiment 1
Using dry Rhodiola Crassulaceae rhizome as crude drug in whole, with 95% alcohol reflux 3 times after crushing, every time
5 times for crude drug in whole weight of consumption, extraction time is 1.5 hours every time, filters, filtrate reduced in volume after extracting solution is merged
Ethanol is reclaimed to without alcohol taste, extractum is obtained；Add the water of 5 times of amounts to carry out water precipitating, at 5 DEG C, stand 24 hours, precipitation is filtered,
Filtrate Jing D101 macroporous adsorbent resins are separated, and carry out eluting using pure water, 30% ethanol, 70% ethanol, three gradients, by 70%
The eluent concentrating under reduced pressure of ethanol, it is freeze-dried after obtain the effective site of Rhodiola Crassulaceae.
Embodiment 2
Using dry Radix Rhodiolae rhizome as crude drug in whole, with 100% alcohol reflux 3 times after crushing, use every time
10 times for crude drug in whole weight are measured, extraction time is that filter after extracting solution is merged, filtrate reduced in volume is reclaimed 2 hours every time
Ethanol obtains extractum to without alcohol taste；Add the water of 10 times of amounts to carry out water precipitating, at 15 DEG C, stand 24 hours, precipitation is filtered, filter
Liquid Jing HP20 macroporous adsorbent resins are separated, and carry out eluting using pure water, 30% ethanol, 70% ethanol, 95% ethanol, four gradients,
By the eluent concentrating under reduced pressure of 70% ethanol, it is freeze-dried after obtain the effective site of Radix Rhodiolae.
Embodiment 3
Using dry Rhodiola himalensis rhizome as crude drug in whole, with 10% alcohol reflux 2 times after crushing, use every time
5 times for crude drug in whole weight are measured, extraction time is that filter after extracting solution is merged, filtrate reduced in volume is reclaimed 1 hour every time
Ethanol obtains extractum to without alcohol taste；Add the water of 5 times of amounts to carry out water precipitating, at 20 DEG C, stand 12 hours, precipitation is filtered, filtrate
Jing HPD macroporous adsorbent resins are separated, and carry out eluting using pure water, 70% ethanol, 95% ethanol, three gradients, by washing for 70% ethanol
De- liquid concentrating under reduced pressure, it is freeze-dried after obtain the effective site of Rhodiola himalensis.
Embodiment 4
Using dry Yunnan spy's Radix Rhodiolae rhizome as crude drug in whole, with 45% alcohol reflux 3 times after crushing, every time
7 times for crude drug in whole weight of consumption, extraction time is 1.5 hours every time, filters, filtrate reduced in volume after extracting solution is merged
Ethanol is reclaimed to without alcohol taste, extractum is obtained；Add the water of 7 times of amounts to carry out water precipitating, at 25 DEG C, stand 15 hours, precipitation is filtered, filter
Liquid Jing AB-8 macroporous adsorbent resins are separated, and carry out eluting using pure water, 30% ethanol, 95% ethanol, three gradients, by 30% ethanol
Eluent concentrating under reduced pressure, it is freeze-dried after obtain the effective site of Rhodiola yunnanensiss.
Embodiment 5
Using dry Rhodiola Crassulaceae rhizome as crude drug in whole, with 75% alcohol reflux 3 times after crushing, every time
9 times for crude drug in whole weight of consumption, extraction time is 3 hours every time, filters after extracting solution is merged, and filtrate reduced in volume is reclaimed
Ethanol obtains extractum to without alcohol taste；Add the water of 10 times of amounts to carry out water precipitating, at 10 DEG C, stand 20 hours, precipitation is filtered, filtrate
Jing D101 macroporous adsorbent resins are separated, and carry out eluting using pure water, 70% ethanol, 95% ethanol, three gradients, by 70% second
The eluent concentrating under reduced pressure of alcohol, it is freeze-dried after obtain the effective site of Rhodiola Crassulaceae.
2nd, pharmacologically active experiment
Test example：Rhodiola Crassulaceae extract reduces the effect of development of hypoxic pulmonary arterial pressure
Laboratory animal：Healthy male Sprague-Dawley（SD）Rat, purchases in Xi'an Communications University's animal experimental center（It is real
Test animal and use credit number SCXK (Shan) 2012-003）, 6-8 week old, body weight are 250-300 g.
Experimental apparatus：Electronics chessboard：SHANGPING (YP601N), Biopac polygraphs, rotary-type microtome
（Card -2016 are come, Germany）；II type Full automatic closed tissue processors of TSJ-（Changzhou Texlab Electronic Instrument Co., Ltd.）；
III type embedding machines of BMJ-（Changzhou suburb Zhong Wei Electronic Instruments Plants）；Instrument is dried in the drift of III type pathological tissues of PHY-（Prestige electronics in Changzhou
Instrument Ltd.）；Digital three mesh photographic microscopes（BA400 Digital, Maike Aodi Industry Group Co Ltd）Deng；Figure
As analysis software Motic Images Advanced.
Model copy SD rats are grouped Hypoxic Pulmonary Hypertension in Rats at random, 6 per group, respectively：1. normal oxygen group
（Normal）：Rat was in the same day with 20% urethane intraperitoneal anesthesia（0.5 ml/0.1kg）And pulmonary artery pressure is determined, lie on the back after fixing
Thoracic cavity is opened, cardiopulmonary is quickly removed, is drawn materials and is kept sample.2. hypoxia group（Hypoxia）：It is divided into hypoxia 1 day, hypoxia 3 days, hypoxia 7
My god, hypoxia 15 days, five groups of hypoxia 30 days, 6 per group, rat is placed in low-pressure oxygen cabin and raises（Height above sea level 5000m）, continuous 1,3,
7th, 15,30 days, rat HPH models are replicated.3. hypoxia gives Radix Rhodiolae effective site group（Hypoxia+HJT）：Rat hypoxia is sudden and violent
After dew, Radix Rhodiolae medicine height (55.00mg/ml) that daily gastric infusion is extracted, in (27.50mg/ml), low (13.75mg/ml)
Three dosage 1ml/200 g body weight, continuously give 1,3,7,15,30 days.
Tremie method measures right ventricular systolic pressure：Behind 1 day, 3 days, 7 days, 15 days, 30 days, each group rat is used
The pentobarbital sodium of 10g/L（40mg/kg）After anesthesia, operating-table is fixed on, isolates right external jugular vein, ligature distal end, moved
Arteries and veins folder blocking proximal part, using polyethylene catheter（0.5% heparin solution is full of in conduit）The right jugular vein intubation of row, connection
Pressure transducer and physiograph.After conduit intravasation, it is slowly advanced, and while observational record instrument shows, the right side to be shown
After ventricle arterial pressure curve, A/C, and record 30s pressure curves.Recorded instrument analysis software calculates right ventricle
End-systolic pressure（Right-ventricular systolic pressure, RVSP).
The measurement of right ventricle plumpness index：After mPAP measurements are finished, rat thoracic cavity is cut off immediately, and determines conduit position
Put in right ventricle, take out heart, cut off left atrium tissue, and along right ventricular tissues under interventricular septum edge scissor, weigh respectively.Meter
Calculate right ventricle and add interventricular septum ratio with left ventricle（RV/LV+S）, i.e., right ventricle plumpness index（right ventricular
Hypertrophy index, RVHI）, determine right ventricle whether there is plumpness with this.
Tissue sampling and fixation：Lung thin vessels reinvent observation and image procossing, rats with left lung tissue Jing neutral buffered good fortune
Your Malin fixes, specimens paraffin embedding slices, and situation is reinvented in HE dyeing, light Microscopic observation lung thin vessels.Take the lung of 100 μm or so of diameter
Tremulous pulse, carries out MORPHOMETRIC ANALYSIS OF EXFOLIATED with image analysis system, accounts for vessel cross-section product ratio (WA%) with blood vessel wall area of section
As the index that measurement hypoxic pulmonary vascular is reinvented.
Electron microscopic observation：Apparatus and fixative needed for being ready in advance, and it is put pre- cold standby in 4 DEG C of refrigerators.Rat
Left side lung tissue is rapid with after normal saline flushing or direct plungeing into 2.5% glutaraldehyde fixative of pre-cooling Jing after in vitro（Shelf-life
For 1 month）It is interior, and it is put preservation in 4 DEG C of refrigerators, fixative is dropped on stencil plate, then the internal organs scalpel for scaling off
It is cut into small pieces, is placed in the fixative on stencil plate, tissue is cut into into about 1 cubic millimeter of size or cross section in fixative then
About 1 square millimeter of strip, afterwards in the bottle equipped with fixative, the fully shaking in fixative so as to sink to bottom of bottle completely
Till carry out morphological analyses with image analysis system, it is thin with the swelling degree of mitochondrion and endoplasmic reticulum and I type, II type alveolar epithelium
The index that born of the same parents are reinvented as measurement hypoxic pulmonary vascular.
Statistical analysiss：Experimental result is with mean ± standard error（Mean ± SEM) represent, data use SPSS13.0 softwares
Analysis.Group difference is analyzed using One-way ANOVA, P<0.05 has significant difference.
Experimental result：Rhodiola Crassulaceae active site stimulates the impact of lower pulmonary arterial pressure in rats to hypoxia：With normal oxygen group
Relatively, hypoxia makes pulmonary arterial pressure in rats increase substantially（32.20±3.89vs17.31±1.60 mmHg）, while right ventricle is plump
Index also substantially increases（22.65±1.30vs15.29±3.11）；Refer to the two after Rhodiola Crassulaceae effective site intervention
Mark has substantially reduction（18.1±2.07vs16.47±1.45）, as shown in Fig. 1 and following table.
Impact of the Rhodiola Crassulaceae active site to pulmonary artery pressure and right ventricle（）：
| PAP（mmHg） | (RV/LV+S)% | |
| Number | 8 | 6 |
| Normal | 17.31±1.60 *** | 12.8±2.7 *** |
| Hypoxia | 32.20±3.89 *** | 22.6±1.1 |
| High Dose | 18.1±2.07 *** | 16.5±1.5 *** |
| Middle Dose | 20.34±1.90 *** | 17.8±1.2 *** |
| Low Dose | 21.46±1.95 | 23.0±2.4 |
| F | 49.14 | 31.31 |
| P | < 0.0001 | < 0.0001 |
Note：* represent and compare P ＜ 0.05 with hypoxia group
Impact of the Rhodiola Crassulaceae active site to lung small artery vascular remodeling caused by hypoxia：Hypoxia result in pulmonary artery
Substantially thicken（Fig. 2, Fig. 3）, dramatically increasing for arteria pulmonalis smooth muscle aspect product is simultaneously resulted in, while thickening with adventitia
And blood vessel epimatrix deposition, and after Rhodiola Crassulaceae intervention, substantially alleviate the increasing of the lung small artery blood vessel wall that hypoxia causes
It is thick.
The impact that Rhodiola Crassulaceae active site is damaged to Pulmonary Microvascular Endothelial Cells in Rats caused by hypoxia：Body anoxia
When, intracellular endoplasmic reticulum and mitochondrion are most made a response soon, and the phenomenons such as swelling occur, and from Fig. 4, anoxic treatment was to 15 days
When, it is observed that normal group compared with hypoxia injury group notable difference, I types epithelial cell in normal group, core ovalize, in core
Distribution of chromatin is uniform.The organelle structures such as endochylema mitochondrial, ribosome are clear.II type epithelial nucleus ovalizes, core
Interior Distribution of chromatin is uniform, lamellated granule in endochylema, and the organelle structure such as mitochondrion is normal.And hypoxia injury group Mitochondria goes out
Now significantly swelling.Jing after Rhodiola Crassulaceae active site is intervened, endochylema mitochondrial, the organelle structure such as ribosome are clear
And normal, accidental mitochondrial mild swelling.
Below the present invention is described in detail, the above, only the preferred embodiments of the invention, when can not
Limit the scope of the present invention, i.e., it is all according to the made impartial change of the application scope and modification, all should still belong to covering scope of the present invention
It is interior.
Claims (10)
1. a kind of preparation method of Radix Rhodiolae effective site, it is characterised in that：Carry out according to the following steps,
1) dry rhizome of Rhodida plant is crushed, is extracted with methanol or ethanol, extracting solution concentrating under reduced pressure into extractum,
Obtain Radix Rhodiolae total extract；
2) Radix Rhodiolae total extract is dispersed in pure water, and is staticly settled, precipitation is filtered, filtrate is obtained；
3) filtrate Jing macroporous adsorbent resins are separated, and carry out gradient elution with water, ethanol system, by eluent concentrating under reduced pressure,
Radix Rhodiolae effective site is obtained after lyophilization.
2. the preparation method of Radix Rhodiolae effective site according to claim 1, it is characterised in that：Step 1) in Extraction solvent
Concentration be 10-100%, its consumption is 5-10 times of medical material weight；Extraction process repeats 2-3 time, and each extraction time is 1-2
Hour；Step 2) in precipitation process for standing 12-24 hours at room temperature, the amount of required pure water is Radix Rhodiolae total extract weight
5-10 times；Step 3) in the macroporous adsorbent resin that adopts be HP20 series, HPD is serial, D101 is serial, AB-8 it is serial in
Any one；Gradient elution carries out eluting with water first, then carries out gradient elution with ethanol, water mixed solvent；Each gradient
Eluting agent is 3-5 column volume.
3. the preparation method of Radix Rhodiolae effective site according to claim 1, it is characterised in that：The rhodiola for being adopted
Plant includes Radix Rhodiolae, Rhodiola kirilowii (Regel) Maxim., Radix Rhodiolae, Rhodiola rosea L., Rhodiola atuntsuensis, Rhodiola himalensis, handkerchief
In Radix Rhodiolae, Rhodiola henryi, Rhodiola quadrifida, Rhodiola yunnanensiss, Rhodiola wallichiana var. cholaensis, Rhodiola fastigiata, Rhodiola Crassulaceae,
Radix Rhodiolae, Rhodiola dumulosa and Rhodiola sachalinensis.
4. the Radix Rhodiolae effective site obtained by any one of claim 1-3.
5. a kind of pharmaceutical composition, which includes Radix Rhodiolae effective site and pharmaceutically acceptable load described in claim 5
Body, Radix Rhodiolae effective site account for the 0.1～99% of pharmaceutical composition gross weight.
6. pharmaceutical composition according to claim 5, it is characterised in that：The dosage form of the pharmaceutical composition can for tablet,
Capsule, pill, granule, oral liquid or suspensoid.
7. the Radix Rhodiolae effective site described in claim 4 is preparing medicine and/or the guarantor for the treatment of and/or prophylaxis of pulmonary hypertension
Application in strong product.
8. the Radix Rhodiolae effective site described in claim 4 prepare treatment and/or prevent pulmonary artery reconstruct medicine and/
Or the application in health product.
9. the Radix Rhodiolae effective site described in claim 4 is preparing treatment and/or is preventing the medicine of Pulmonary Vascular epithelial cell damage
Application in product and/or health product.
10. the Radix Rhodiolae effective site described in claim 4 prepare treatment and/or prevent mitochondrial injury medicine and/or
Application in health product.
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| JP2021020880A (en) * | 2019-07-30 | 2021-02-18 | 株式会社東洋新薬 | Tie2 ACTIVATOR, AND AGENT FOR PREVENTING OR IMPROVING SWELLING |
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