CN106236801A - Pseudo-ginseng activity medicine that super-micro wall-broken crushing technology is made and health product and preparation method thereof - Google Patents
Pseudo-ginseng activity medicine that super-micro wall-broken crushing technology is made and health product and preparation method thereof Download PDFInfo
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- CN106236801A CN106236801A CN201610527349.XA CN201610527349A CN106236801A CN 106236801 A CN106236801 A CN 106236801A CN 201610527349 A CN201610527349 A CN 201610527349A CN 106236801 A CN106236801 A CN 106236801A
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- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
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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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- 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
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- 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
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
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- Health & Medical Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to the field of Chinese medicines, be specifically related to a kind of pseudo-ginseng activity pharmaceutical composition and preparation method thereof and pharmaceutical applications.This pharmaceutical composition is made up of the raw material of following weight portion: flower of Radix Notoginseng 0.5~10 weight portion, Radix Notoginseng 0.5~10 weight portion.This pharmaceutical composition is prepared as tablet, pill, powder, hard capsule, soft capsule, granule, oral liquid, drop pill, injection.Present invention also offers the quality determining method of this pharmaceutical composition.This pharmaceutical composition has the multiple efficacies such as raising immunity, antitumor, treatment hypertension, cardiovascular diseases, cerebrovascular, diabetes, hyperlipidemia, metabolism syndrome, cyclomastopathy, depression, defying age, looks improving and the skin nourishing.
Description
Technical field
The present invention relates to the field of Chinese medicines, be specifically related to a kind of Radix Notoginseng and the active pharmaceutical compositions of flower of Radix Notoginseng and preparation side thereof
Method.
Background technology
Present patent application be with on July 22nd, 2015 submit to No. 201510433658.6 Chinese invention patent be preferential
Power patent in rear patent application.
One, the chemical composition of Radix Notoginseng and pharmacological action
Radix Notoginseng is panax araliaceae plant panaxnotoginseng(Burk.) dry root of F.H.Chen, main product in Guangxi, cloud
South, the ground such as Sichuan, Guangdong, Hunan also has introduces a fine variety on a small quantity.This product is warm in nature, sweet in the mouth, micro-hardship, returns liver, stomach, the heart, large intestine channel, only has
Blood dissipating blood stasis, effect of subduing swelling and relieving pain, cure mainly haematemesis, hemoptysis, hematuria, have blood in stool, dysentery, metrorrhagia, postpartum hemorrhage, traumatic hemorrhage, fall
Fall forward damage, obstruction of qi in the chest and cardialgia, the gastral cavity side of body for a long time bitterly, abdominal mass amasss block, blood stasis amenorrhea, dysmenorrhea, the stagnant stomachache of the stasis of blood in puerperal, skin infection swell and ache.Dissipate with Radix Notoginseng
The pharmacological action that stasis of blood hemostasis, subduing swelling and relieving pain effect are correlated with is quite varied, including hemostasis, antithrombotic, promotion hemopoietic, expands blood vessel, fall
Blood pressure, resist myocardial ischemia, anti-cerebral ischemia, arrhythmia, atherosclerosis, antiinflammatory, protect the liver, antitumor, analgesia etc..
1 effective ingredient
Radix Notoginseng be mainly composed of dammarane type four-ring triterpenoid class, triterpene saponin and triterpenes oligosaccharide glycosides, possibly together with dencichine,
Cupreol, cupreol-3-O-β-D-pyranglucoside, Radix Notoginseng glucosides etc..Additionally, Radix Notoginseng contains multiple volatile oil,
Mainly there are the alkenes such as α and γ-Cananga odorata oil alkene, Rhizoma Cyperi alkene, Flos Caryophylli alkene, the esters such as methyl hexadecanoate, the acids such as octanoic acid, acetic acid,
Ketone and the multiple alkanes such as 3-nonene-2-ketone.
2 Pharmacological Advancements
2.1 blood coagulation resisting function in vitro testses show with the test of internal duodenal administration, and protoparaxotriol saporlirs can substantially suppress glue
Former, the rat of arachidonic acid-induction and Platelet Aggregation in Rabbits.Radix Notoginseng total arasaponins is incubated altogether with porcine aorta vascular endothelial cell,
Endothelial cells secrete tissue plasminogen activator can be promoted.
2.2 impacts on cardiovascular system
Radix Notoginseng total arasaponins has many effects to cardiovascular system, it is possible to decrease the generation quivered in irreversibility room, improves heart
Systolic and diastolic function, reduces myocardial ischemic injury, resists myocardial hypertrophy, suppresses left ventricular remodeling;The effect of Human Umbilical Vein Endothelial Cells is main
For increasing free calcium ion concentration in it, protect endothelium;For vascular smooth muscle cell, Radix Notoginseng total arasaponins has suppression and promotes
The two-way function of hyperplasia.
2.3 on cerebral tissue and neural impact
The line brush using improvement prepares rat transient middle cerebral artery thromboembolism re-perfusion model, after detection ischemia-reperfusion not
Same convalescent period (3,7,28d) rat functional rehabilitation, cerebral infarction volume, Nogo-AmRNA and the expression of albumen.Result shows,
Protoparaxotriol saporlirs can suppress the expression of Nogo-A after global cerebral ischemia-reperfusion, thus after playing promotion cerebral infarction, function of nervous system is extensive
The effect that multiple, brain function is reinvented.
Use the rat cerebral cortex neurocyte of original cuiture, after the Radix Notoginseng total arasaponins pretreatment of variable concentrations, build
Vertical oxygen sugar deprives (OGD) model, reoxygenation complex sugar after 2h, simulates re-perfusion model.The survival feelings of neuron are compared by mtt assay
Condition, and measure superoxide dismutase (SOD), the activity change of malonaldehyde (MDA), and the change of Bcl-2 protein expression.Knot
Fruit shows, Radix Notoginseng total arasaponins is to the protected effect of rat layer neurocyte under the conditions of Anoxia, and its protective effect may
Suppress neurocyte lipid peroxidation, raising Bcl-2 protein expression relevant with it.
The protective effect of 2.4 pairs of spinal cord injury
By healthy adult female sd inbred rats 63, it is randomly divided into normal group, solvent control group, Radix Notoginseng total arasaponins group, rat spinal cord
15min after Hemisected injany on the right side of T10, lumbar injection Radix Notoginseng total arasaponins, dosage is 20mg/kg, is administered once daily later, molten
Agent matched group injection normal saline.Postoperative 1,3,7,14,21,28d carry out the detection of BBB scoring behavioristics, and use immunity
The change that histochemical method's detection spinal cord injury distal end portion glial fibrillary acidic protein (GFAP) expresses.Result shows, Radix Notoginseng
Total saponins can suppress the activation of astrocyte after spinal cord hemisection, and this is probably it and promotes motion merit after spinal cord injury
One of mechanism that can recover.
By 25 adult female rats implement spinal cord half cross-section postoperative, be divided into matched group, Radix Notoginseng total arasaponins low dose group,
Dosage group, Radix Notoginseng total arasaponins high dose group and NG-nitro-L-arginine group in Radix Notoginseng total arasaponins.Radix Notoginseng total arasaponins group stomach every day is raised
The Radix Notoginseng total arasaponins of doses, L-NNA group intraperitoneal injection every day L-NNA.Postoperative 30d takes out spinal cord and brain row freezing is cut
Sheet, does Nicotinamideadeninedinucleotide (NADPH) histochemical staining and neutral red staining.Result shows, Radix Notoginseng is total
Saponin can promote dorsal nucleus neuron and the survival of Red nucleus neurons of damaged, can suppress the dorsal nucleus neuron table of damaged simultaneously
Reach nitricoxide synthase (NOS).
2.5 impacts on nephridial tissue
Rat is randomly divided into sham operated rats, model group and Radix Notoginseng total arasaponins treatment group, sets up renal artery stenosis renal ischaemia rat
Model, after modeling, the 7th, 28,45,60d puts to death rat, observes renal interstitial morphological changes of various tissue components, applies immuning tissue
Chemical method detection renal tubulointerstitial α-smooth muscle actin (α-SMA) is at the expression of different time points, radio immunoassay
The content of the content of detection serum interleukin II (IL-2), ELISA detection serum platelets source property somatomedin (PDGF).
Result shows, Radix Notoginseng total arasaponins may reduce cytokine platelet derived by suppression renal tubular interstitium Cell surface
The level of the level of somatomedin and in early days interleukin II, alleviates and improves chronic renal ischemia kidney region fibrosis.
Replicating diabetes rat model with alloxan, animal is divided into normal group, model group, Radix Notoginseng total arasaponins high dose to control
Treatment group, low dose therapy group, biochemistry detection fasting glucose, blood urea nitrogen, creatinine, T-CHOL, triglyceride and urine protein level,
HE and PAS dyeing, om observation Renal Morphology change, RT-PCR method detection nephridial tissue transforminggrowthfactor-β1 (TGF β 1),
Plasminogen activator-1(PAI-1) mrna expression.Result shows, arasaponin may be by reducing TGF β 1 He
PAI-1mRNA expresses, and then protection Renal of Diabetic Rats.
2.6 other effects
Radix Notoginseng has certain improvement result to memory acquisition disturbance, memory consolidation obstacle, and Hemorrhagic Shock In Rabbits is had certain curative effect,
Arasaponin A has certain diuresis to dog.Arasaponin lumbar injection, can improve the mice threshold of pain, has antiinflammatory and immunity
Regulation effect, naloxone can its effect of part blocks.Mice scalds pneumoretroperitoneum injection arasaponin liquid, to macrophage inositol fat
Matter signaling system IP3-CaM approach has opsonic action.Radix Notoginseng total arasaponins lumbar injection can increase scald rat heart muscle Gs α in early days
Mrna expression amount, cAMP content, adenyl cyclase activity.Arasaponin lumbar injection can make alloxan diabetes Mouse Blood
Sugar reduces.
3 conclusions
The effective ingredient kind of Radix Notoginseng is a lot, these effective ingredient alone or associated with pharmacological action the most extensive.The most not only
The structure of compound components of panax notoginseng to be verified, separation method, pharmacological action, also to verify its mechanism of action, in order to further for facing
Bed treatment, prevention and health care and basic research provide scientific basis.
Two, flower of Radix Notoginseng chemical composition and pharmacological action
1 introduction
Flower of Radix Notoginseng is dry flower [the F1ower buds of Panax of tradition rare Chinese medicine panax araliaceae plant
Notoginseng (Burk) F.H.Chen], flower of Radix Notoginseng nature and flavor are sweet cool, have effect of heat clearing away, suppressing the hyperactive liver, blood pressure lowering, have preferably
Medical value and health-care effect.Flower of Radix Notoginseng as medical material loaded " choosing of Yunnan Chinese herbal medicine ", " sweet cool, heat clearing away suppressing the hyperactive liver, blood pressure lowering.
Treatment hypertension, dizzy, dizzy, tinnitus, acute pharyngolaryngitis ";" property sugariness is cool for " China is herbal " record flower of Radix Notoginseng simultaneously.Heat clearing away
Promote the production of body fluid, suppressing the hyperactive liver blood pressure lowering.Cure mainly Tianjin wound thirsty, pharyngalgia hoarseness, hypertension ".Main chemical compositions and medicine to flower of Radix Notoginseng herein
Reason Effect study is summarized, and provides useful reference for its further investigation and exploitation.
2 chemical compositions
Isolated ginsenoside F2, Rd, Rc, Rb2 and Rb1 from Panax notoginseng flower bud.The research of flower of Radix Notoginseng ruscogenin, by extracting
Be refining to obtain flower of Radix Notoginseng thick Saponin precipitate, thicker Saponin be hydrolyzed and separate, respectively obtain flower of Radix Notoginseng glycoside unit A, B,
C, D and E.Panax notoginseng flower bud contains U-sitosterol, daucosterol, arasaponin Fe, gypenoside Ⅸ, ginsenoside Rc and Radix Ginseng
The Multiple components such as Saponin Rb3.16 kinds of compositions are obtained through gas chromatography, including terpenes, hydro carbons and ester from notoginseng flower essential oil.
Use gas chromatography mass spectrometry method to identify from notoginseng flower essential oil and include hydro carbons, monoterpenes, sesquiterpenoids, alcohol, aldehyde, ketone, acid, ester etc.
Compound 37 kinds, wherein monoterpene 3 kinds, sesquiterpenoids 16 kinds, identify that composition is total volatile oil content 67%.Shanghai Chinese is big
Learn and useL 9(34) Orthogonal Experiment and Design, with the eluate rate of transform and purity as inspection target, go out flower of Radix Notoginseng with AB-8 Resin sieving selection
The optimum process condition of total saponins is: sample concentration is 0.2g crude drug/mL, with 70% ethanol solution of 3 times of resin column volumes (BV)
Eluting, absorption and elution flow rate are 2 times of resin column volumes (BV h per hour-1), eluent i.e. obtains the Radix Notoginseng of purification after being evaporated
Alabastrum total saponin extracts, Panax notoginseng flower bud total saponin content is 87.60% after purification.Yunnan mountain of papers different sources, different growth year
Total saponins and the Changing Pattern of monomer saponin in the flower of Radix Notoginseng of limit, find that the place of production is different with growth year, total soap contained by flower of Radix Notoginseng
The content of glycosides and ginsenoside Rb1, Rb3 has significant difference.
3 pharmacological actions
3.1 antiinflammatory action
In the mechanism of action of Radix Notoginseng total arasaponins may stop inflammatory cell with Radix Notoginseng total arasaponins, free calcium level raises and suppresses perfusion
In liquid phospholipase A2 activity thus reduce dinoprostone and must discharge relevant.And sanchi flower total saponine and Radix Notoginseng total arasaponins are at chemistry
There is similarity on composition, find 50~100mg kg-1Flower of Radix Notoginseng saponin can substantially suppress rat foot caused by multiple proinflammatory agent swollen
Swollen and Mice Auricle inflammation, has stronger anti-inflammatory activity;And the solution utilizing flower of Radix Notoginseng saponin f to prepare carries out antiinflammatory experiment, also
Find that it all has inhibitory action to acute inflammation and chronic inflammatory disease.Carry out with the Ii _ i_iLLci _ i_ model that the proinflammatory agents such as Oleum Tiglii are set up
The anti-inflammatory effect assessment of sanchi flower total saponine, finds that sanchi flower total saponine all has inhibitory action to inflammatory reaction, and can resist
The mouse peritoneal capillary permeability caused by acetic acid is hyperfunction.Guangxi Medical Uneversity Cancer Hospital's flower of Radix Notoginseng ice cube enters
The laboratory observation of row Prophylactic chemotherapy stomatitis, the stomatitis incidence rate of observation group is 8%, and the incidence rate of matched group is 24%,
Observation group is substantially less than matched group, and also explanation flower of Radix Notoginseng has effect of functions of detumescence, relieving inflammation.
3.2 analgesic activity
Sanchi flower total saponine is carried out analgesic experiment, it was observed that sanchi flower total saponine can substantially suppress to be turned round by the mice caused by acetic acid
Precursor reactant, extends the mice latency of pain response caused because of thermostimulation, shows that sanchi flower total saponine has the analgesic efficacy;Mice side
The ventricles of the brain inject after (icv) trace sanchi flower total saponine, remain to significantly improve its pain and close value, point out its analgesic activity position may be
Maincenter.Research shows that the pain that chemical and thermostimulation are caused by Radix Notoginseng total arasaponins all has obvious analgesic activity, and Radix Notoginseng
Total saponins is a kind of opioid peptide sample receptor stimulating agent, does not have the side effect of addiction.
3.3 sedation
Radix Notoginseng aerial parts has inhibitory action to nervus centralis, and sanchi flower total saponine also can substantially suppress the outward appearance behavior of mice to live
Moving and spontaneous activity, sanchi flower total saponine can significantly strengthen the chlorpromazine inhibitory action to spontaneous activity in mice, flower of Radix Notoginseng simultaneously
Total saponins pentetrazole and strychinine-induced convulsion unprotect effect, show that sanchi flower total saponine has suppression effect to central nervous system
Energy.Carry out sedative experiment also with flower of Radix Notoginseng water decoction, test result indicate that flower of Radix Notoginseng can be used for treating dizzy, dizzy and ear
Ring.
3.4 function of promoting blood circulation to disperse blood clots
The research sanchi flower total saponine impact on hemorheology of rat, finds high, medium and low dose of the total saponins extracted in flower of Radix Notoginseng
Amount group all can substantially reduce the whole blood contrast viscosity of rat's blood stasis model, reduces its packed cell volume, extends the time of thrombinogen, reduces
Fibrinous quantity, can effectively prevent hematoblastic gathering, prevent blood viscosity from increasing, thus play pre-preventing thrombosis
Effect.Illustrate that flower of Radix Notoginseng has the clinical efficacy of blood circulation promoting and blood stasis dispelling.
3.5 treatment Arrhythmias
Radix Notoginseng total arasaponins all has obvious antagonism to several Experimental arrhythmia models, and panasadiol saponio also has similar effect
Should, point out its antiarrhythmic effect to block epinephrine U-receptor or excited M-cholinoceptor institute not by competitiveness
Cause, but relevant with the direct suppression of cardiac muscle;Panasadiol saponio can reduce the spontaneous frequency of isolated rat right atrium, to rat
With rabbit experiment of electrocardiogram, it was demonstrated that panasadiol saponio has negative chronotropic action, negativity conduction, its result illustrates Radix Notoginseng
The antiarrhythmic effect of glycol glycosides.Flower of Radix Notoginseng treatment arrhythmia experiment also demonstrates it to be had preferably diseases such as cardiopalmus are uncomfortable in chest
Curative effect.
3.6 effects of clearing and nourishing throat
Utilizing buccal lozenge of notoginseng flower to carry out the human feeding trial of cleaning throat and moistening larynx, the total effective rate of moistening and cleaning throat effect is 80.0%, shows three
Seven flower buccal tablets to pharyngalgia, itching throat, pharynx is scorching hot, dry cough, polylogia increase the weight of, foreign body in pharynx sense, dry pharynx are puckery and expectoration is not well etc., and symptom is equal
There is improvement result, the symptoms such as pharyngeal congestion, edema and pharynx rear wall follicle hypertrophy are also had certain curative effect.
3.7 liver protection effect
Carrying out the buccal lozenge of notoginseng flower experimentation to alcoholic liver injury protective effect, result of study shows, buccal lozenge of notoginseng flower can
Significantly reduce the malonaldehyde (MDA) in the liver tissues of rats of alcoholic liver damage model and triglyceride (TG) content, improve liver group
Knit reduced glutathion (GSH) content, the hepatic tissue steatosis of alcoholic liver injury in rats can be alleviated, show that flower of Radix Notoginseng contains
Sheet has protective effect to alcoholic liver injury.
3.8 suppression cel l proliferations
The human aorta vascular smooth muscle cell proliferation induced with norepinephrine and calcium overload, as model, find sanchi flower total
Saponin each dosage group all can improve the cell viability of the human aorta vascular smooth muscle cell proliferation of norepinephrine induction,
This has also pointed out sanchi flower total saponine that vascular smooth muscle cell proliferation is had inhibitory action, and this effect may be intracellular with reduction
Calcium ion concentration is relevant.
4 conclusions
The chemical composition of flower of Radix Notoginseng and pharmacologically active, also in continuous exploratory development, need research to its analysis method.With
Time for the research of monomeric compound preparation of flower of Radix Notoginseng, and the metabolism research of flower of Radix Notoginseng metabolite especially arasaponin
All should give the attention of height.The research of flower of Radix Notoginseng goods should be in line with non agricultural chemical residuum, the principle of heavy metal free residual,
Chinese medicine can be pushed to international market.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of flower of Radix Notoginseng and Radix Notoginseng.
It is a further object of the present invention to provide the preparation method of this pharmaceutical composition.
Present invention also offers the quality determining method of this pharmaceutical composition.
Present invention also offers the pharmaceutical applications of this pharmaceutical composition.
A kind of pharmaceutical composition is made up of the raw material of following weight portion: flower of Radix Notoginseng 0.5~10 weight portion, Radix Notoginseng 0.5
~10 weight portions.
This pharmaceutical composition is preferably made up of the raw material of following weight portion: flower of Radix Notoginseng 0.5 weight portion, Radix Notoginseng 10 weight
Part.
This pharmaceutical composition is preferably made up of the raw material of following weight portion: flower of Radix Notoginseng 10 weight portion, Radix Notoginseng 0.5 weight
Part.
This pharmaceutical composition is preferably made up of the raw material of following weight portion: flower of Radix Notoginseng 5 weight portion, Radix Notoginseng 5 weight portion.
This pharmaceutical composition is preferably made up of the raw material of following weight portion: flower of Radix Notoginseng 3 weight portion, Radix Notoginseng 7 weight portion.
In described pharmaceutical composition, flower of Radix Notoginseng is 3 years raw sangqi ginseng flowers, and Radix Notoginseng is 3 years raw sangqi ginseng main roots or life three in 3 years
Seven clips.
3 years raw sangqi ginseng flowers after 3 years raw sangqi ginseng flowers are micronizing in described pharmaceutical composition or after breaking cellular wall, 3 years
3 years raw sangqi ginseng main roots after raw sangqi ginseng main root is micronizing or after breaking cellular wall, after within 3 years, raw sangqi ginseng clip is micronizing or broken
3 years raw sangqi ginseng clips after wall.
Described pharmaceutical composition can be prepared as tablet, pill, powder, hard capsule, soft capsule, granule,
Oral liquid, drop pill, injection.
The preparation method of described pharmaceutical composition is as follows:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate-30 DEG C~-
At 40 DEG C freezing, after maintaining 5h~10h, carry out lyophilization, lyophilization controls to carry out at-30 DEG C~-40 DEG C, and the time is
30h~120h;Radix Notoginseng after lyophilization is pulverized, is sieved by 100 eye mesh screens, obtain Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-30 DEG C
~freezing at-40 DEG C, after maintaining 5h~10h, carry out lyophilization, lyophilization controls to carry out at-30 DEG C~-40 DEG C, time
Between be 30h~120h;Flower of Radix Notoginseng after lyophilization is pulverized, is sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization thin
Powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder step (2) prepared and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, adopts
With the conventional method preparations shaping in Chinese materia medica.
In the preparation method of described pharmaceutical composition, in step (1), Radix Notoginseng and flower of Radix Notoginseng cryodesiccated time are 60h
~80h.
In the preparation method of described pharmaceutical composition, superfine notoginseng powder and flower of Radix Notoginseng superfine powder are mixed by step (3),
Carry out full pressed powder, make tablet.
In the preparation method of described pharmaceutical composition, superfine notoginseng powder and flower of Radix Notoginseng superfine powder are mixed by step (3),
Carry out full powder and fill enteric coated capsule, make enteric hard wafer.
Described pharmaceutical composition is adopted and is detected with the following method: employing high effective liquid chromatography for measuring:
(1) chromatographic condition: Kromasil C18Chromatographic column;Flowing is 70~90:10~30 acetonitrile-waters for ratio mutually;Detection ripple
Long 200~210nm;Flow velocity 0.5~2.0mL min-1;Column temperature 20~40 DEG C;Sample size 5~20 μ L.Theoretical cam curve presses Radix Ginseng
Saponin Rg1Peak calculates should be not less than 4000;
(2) prepared by need testing solution: take drug powder of the present invention, accurately weighed, accurate addition methanol, and weighed weight was placed
At night, put and in water-bath, keep micro-boiling, let cool, more weighed weight, supply the weight of less loss with methanol, shake up, filter, take subsequent filtrate,
Obtain;
(3) preparation of reference substance solution is mixed: precision weighs ginsenoside Rg1, ginsenoside Rb1, Panax Notoginseng saponin R1Reference substance and
Ginsenoside Re is appropriate, adds methanol and makes mixed solution, to obtain final product;
(4) measure: take reference substance solution and need testing solution each 5~20 μ L sample introduction respectively, measure.
Described pharmaceutical composition preferably employs following method and detects: employing high effective liquid chromatography for measuring:
(1) chromatographic condition: Kromasil C18Chromatographic column;Flowing is 82:18 acetonitrile-water for ratio mutually;Detection wavelength 203nm;
Flow velocity 1mL min-1;Column temperature 30 DEG C;Sample size 10 μ L.Theoretical cam curve presses ginsenoside Rg1Peak calculates should be not less than 4000;
(2) prepared by need testing solution: take drug powder 0.5g of the present invention, accurately weighed, the accurate methanol 50mL that adds, weighed heavy
Amount, stands overnight, puts and keep micro-boiling 2h to let cool in 80 DEG C of water-baths, more weighed weight, supplies the weight of less loss with methanol, shakes up,
Filter, take subsequent filtrate, to obtain final product;
(3) preparation of reference substance solution is mixed: precision weighs ginsenoside Rg1, ginsenoside Rb1, Panax Notoginseng saponin R1Reference substance and
Ginsenoside Re is appropriate, adds methanol and makes every 1mL containing ginsenoside Rg10.4mg, ginsenoside Rb10.4mg, ginsenoside
Re0.1mg, Panax Notoginseng saponin R1The mixed solution of 0.1mg, to obtain final product;
(4) measure: take reference substance solution and each 10 μ L sample introductions of need testing solution respectively, measure.
Described pharmaceutical composition can be used for preparation improve immunity, antitumor, treatment hypertension, treatment cardiovascular diseases,
Treatment cerebrovascular, treatment diabetes, treatment hyperlipidemia, treatment metabolism syndrome, treatment cyclomastopathy, treatment depression, anti-
Application in aging, the medicine of looks improving and the skin nourishing or health product.
Experiment one: medicine enhancing immunity experimentation of the present invention
1 experiment material
1.1 tested material
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
1.2 experimental animal feeding cleaning grade Male Kunming strain mice 240, weight 18~21g, by Nanjing Chinese medicine
University Experimental Animal Center provides, temperature 18~24 DEG C, humidity 40%~70% environment in raise.
1.3 main agents sheep red blood cell (SRBC)s (SRBC), HanK liquid (pH value 7.2~7.4), RPMI1640 culture fluid.Little
Ox blood serum, mycillin, concanavalin A, Con A (ConA), MTT, complement (guinea pig serum), SA buffer, india ink, Dou Shi tries
Agent, YAC-1 cell etc..
1.4 key instrument clean benches, carbon dioxide (CO2) incubator, centrifuge, TU-1901 dual-beam ultraviolet
Visible spectrophotometer (the general analysis in Beijing), microplate reader, microscope, slide gauge etc..
2 experimental techniques
2.1 animals packet and medication reference literature (1. Ministry of Health of the People's Republic of China. function of health food evaluation
Program and the method for inspection [S] .2003.;2. the tertiary cloud of Xu, Bian Rulian, Chen Xiu. pharmacological experimental methodology [M] .3 version. Beijing: the people
Health publishing house, 2002:1420-1460).Experiment point 3 big groups, 80 mices of every big group.It is abnormal anti-that immunity 1 group measures delayed
Should (DTH) and antibody-producting cell number;Immunity 2 groups carries out the mouse lymphocyte transformation experiment of ConA induction, NK cytoactive
Measure;Immunity 3 groups carries out carbonic clearance experiment.80 mices of every big group are randomly divided into 8 groups, respectively negative control group, positive right
According to group, medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, right
Ratio medicine second group, often group 10.Negative control group gives purified water, and positive controls is configured to 15.0mg mL-1Ganoderma
Full powder solution, medicine A group of the present invention is configured to 66.0mg mL-1Medicine solution A of the present invention, medicine B group of the present invention give
It is configured to 66.0mg mL-1Medicine B solution of the present invention, medicine C group of the present invention are configured to 66.0mg mL-1Medicine of the present invention
Thing C solution, medicine D group of the present invention are configured to 66.0mg mL-1Medicine solution D of the present invention, drugs compared first group are joined
Make 66.0mg mL-1Drugs compared first solution, drugs compared second group are configured to 66.0mg mL-1Drugs compared second is molten
Liquid.Each group gavage volume is 20mL kg-1, qd, continuous gavage 15d.
The situation of mice delayed allergy (DTH) is respectively organized in 2.2 cellular immune function assay detections after being administered, use
The foot sole of the foot thickens method.Every Mus lumbar injection 2%(V/V) SRBC suspension 0.2mL.4d after sensitization, measures left back sufficient sole of the foot thickness.Measuring
Position subcutaneous injection 20%SRBC.Every Mus 20 μ L, measures left back pedal swelling thickness after 24h, survey 3 times continuously, take average.In the past
Metapedes sole of the foot thickness difference represents DTH degree.
The mouse lymphocyte transformation experiment of ConA induction, uses mtt assay detection mouse lymphocyte to convert and propagation feelings
Condition.Aseptic taking spleen, make cell suspension in aseptic HanK liquid, 200 eye mesh screens filter, and HanK liquid washes 3 times.Train with RPmL1640
It is 3 × 106 mL that nutrient solution adjusts cell concentration-1.Then a point holes adds 24 well culture plates, every hole 1.0mL, and a hole adds ConA
Liquid 50 μ L, a hole compares, and puts 5%CO2, 37 DEG C cultivate 72h.Cultivation terminates front 4h, and every hole sucks supernatant 0.7mL, adds not
RPMI1640 culture fluid containing calf serum and MTT(5mg mL-1, every hole 50 μ L).After cultivation terminates, every hole adds acid different
Propanol 1mL, piping and druming mixing, measure absorbance (A value) by microplate reader at wavelength 570nm.The multiplication capacity of lymphocyte is with adding
The A value in ConA hole subtracts the A value expression being not added with ConA hole.
2.3 humoral immune functions measure with the antibody-producting cell detection assay medicine shadow to mouse humoral immune function
Ring, use Jeme to improve slide method.Every Mus lumbar injection 2%SRBC suspension 0.2mL, 4d after immunity, put to death mice, take spleen, uses
HanK liquid makes cell suspension, sieve aperture internal diameter (75.0 ± 4.1) μm (200 mesh) screen filtration, washs, is centrifuged 2 times, finally will be thin
Born of the same parents are suspended in HanK liquid 5mL.HanK liquid with 7.4,2 times of concentration of equivalent pH value after the culture medium heating for dissolving of top layer is mixed,
Subpackage small test tube, often pipe 0.5mL.10%SRBC suspension 50 μ L, splenocyte suspension 20 μ with the preparation of HanK liquid is added again in pipe
L, is poured on the slide of brush thin layer agarose after mixing rapidly, after solidification, puts into incubation 1.5h in CO2 gas incubator,
Add the complement (1:10) of HanK liquid dilution, after continuing incubation 1.5h, count hemolysis plaque number.
2.4 monocytes/macrophages detection of phagocytic functions use mice carbonic clearance experiment detection mouse monokaryon-macrophage
Phagocytic function.Mouse tail vein injection 10mL kg-1The india ink of 4 times, timing immediately, note is diluted with 0.9% sodium chloride solution
Enter after prepared Chinese ink the 2nd, 10 minute, take blood 20 μ L from angular vein clump, be added in 0.1% sodium carbonate liquor 2mL, shake up, 600nm ripple
Strong point surveys A value.Put to death mice, take liver, spleen is weighed, be calculated as follows phagocytic index: phagocytic index (α)=K1/3× body weight/(liver
Weight+spleen weight).K=(1gA in formula1-1gA2)/(t2-t1).A1For absorbance during 2min, A2For absorbance during 10min, t1t2It is respectively
2,10min.
2.5 NK cytoactive detections use lactic acid dehydrogenase (LDH) algoscopy detection NK cytoactive.24h before experiment
YAC-1 cell is carried out Secondary Culture, and adjusting cell concentration with RPMI1640 complete culture solution is 4 × 105Individual mL-1.Animal
Aseptic after giving medicine take spleen, be placed in the little plate filling appropriate aseptic HanK liquid, gently spleen ground with tweezers, make slender
Born of the same parents' suspension.Through sieve aperture internal diameter (75.0 ± 4.1) μm (200 mesh) screen filtration, add 0.5mL aquesterilisa 20s splitting erythrocyte, use
It is 2 × 10 that RPMI1640 complete culture solution adjusts cell concentration7Individual mL-1.Take YAC-1 cell and each 100 μ L of splenocyte, add
In 96 well culture plates;Target cell Spontaneous release hole adds target cell and each 100 μ L of culture fluid, and target cell maximum release aperture adds target cell
100 μ Ls each with 2.5%Triton;Above-mentioned every it is all provided with 3 multiple holes, in 37 DEG C, 5%CO2Incubator is cultivated 4h, then by 96 holes
Culture plate is with 1500r min-1Centrifugal 5min, in 96 well culture plates at the bottom of the Aspirate supernatant 100 μ L horizontalization of every hole, is simultaneously introduced LDH
Matrix liquid 100 μ L, reacts 3min, and every hole adds 1mol L-1Hydrochloric acid solution 30 μ L, measures A value at microplate reader 490nm.NK
Cytoactive (%)=(reaction A value-Spontaneous release hole A value)/(maximum release aperture A value-Spontaneous release hole A value) × 100%.
2.6 statistical method Excel, SPSS10.0 softwares carry out data conversion and statistical analysis.Homogeneity of variance is examined
Test qualified after, use dunnet single factor test multiple comparisons statistical analysis.
3 results
3.1 medicines of the present invention to mouse cell immune function experiment mice delayed allergy test in, medicine of the present invention
Thing A group thickens value compare to D group and the positive controls foot sole of the foot with negative control group, and difference has pole significance.Show medicine of the present invention
Thing liquid can increase mice delayed allergy.Mouse spleen lymphocyte transformation experiment to ConA induction, medicine A group of the present invention
A value difference value to D group and positive controls is higher than negative control group, and difference has significance.Show that medicine of the present invention can improve little
The ability of Mus Splenic vein hemodynamics.The results are shown in Table 1-1.
3.2 are shown in Table 1-1 on the impact of mouse humoral immune function to the impact of mouse antibodies cellulation.Medicine of the present invention
Thing A group is above negative control group to D group and positive controls mice hemolysis plaque number;Drugs compared first group, drugs compared second
Group is inconspicuous on the impact of mouse humoral immune function.Show that medicine of the present invention can improve the antibody-producting cell number of mice,
Medicine of the present invention is pointed out to have the effect strengthening mouse humoral immune function.
Table 1-1 respectively organize mice delayed allergy and Splenic vein hemodynamics and
Antibody-producting cell number result (± s)
Note: compare with negative control group, * P < 0.01, * * P < 0.05
3.3 medicines of the present invention on mouse monokaryon-macrophage phagocytic function affect Analysis of variance and statistics two-by-two than
Relatively, find that medicine A group of the present invention is above negative control group to the carbonic clearance phagocytic index (α) of D group and positive controls mice,
Difference has pole significance (P < 0.01), shows that medicine of the present invention has the effect of enhancing mouse monokaryon-macrophage phagocytic function,
Drugs compared first group, drugs compared second group effect inconspicuous, be shown in Table 1-2.
3.4 medicines of the present invention on NK cells in mice activity affect Analysis of variance and statistics compares two-by-two, find
Medicine A group of the present invention is above negative control group to the NK cytoactive of D group and positive controls mice, and difference has significance.
Show that medicine of the present invention has the effect strengthening NK cells in mice activity.The results are shown in Table 1-2.
Table 1-2 respectively organize mouse monokaryon-macrophage carbonic clearance and NK cytoactive testing result (± s)
Note: compare with negative control group, * P < 0.01, * * P < 0.05
4 discuss and conclusion
Experimental studies results shows, medicine of the present invention can increase mice delayed allergy, can strengthen the mice of ConA induction
Splenic vein hemodynamics multiplication capacity, has enhancing cellular immune function effect;Improve the antibody-producting cell number of mice, have enhancing
Humoral immune function effect;There is enhancing mouse monokaryon-macrophage phagocytic function and strengthen the effect of NK cells in mice activity.Table
Bright medicine of the present invention has enhancing mouse cell and humoral immune function and nonspecific effect.
And, experimental studies results is it is also shown that be used alone flower of Radix Notoginseng or be used alone the contrast medicine that Radix Notoginseng clip is made
The drug effectiveness of thing first and drugs compared second is the most inconspicuous, it can be seen that, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip
It is applied in combination, creates the obvious one-plus-one synergistic function more than two.
Experiment two: the experimentation of drugs against tumor of the present invention
1 material
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
Cyclophosphamide for injection, Jiangsu Sheng Di Pharmaceuticals Ltd, traditional Chinese medicines quasi-word H20023036;
Healthy Kunming mouse, male and female dual-purpose, weight 18~22g;Rat liver cancer H22Cell strain is purchased from Nanjing University of Traditional Chinese Medicine
Experimental Animal Center, sarcoma S180Cell strain, is purchased from by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center.
2 methods
2.1 prepare tumor cell suspension takes tumor mass under sterile working, weighs, with glass tissue homogenizer grind, grind even after put
Entering in sterile chamber, add normal saline dilution and become the cell suspension of 1:3, container is put on ice cube, fully mixes.
2.2 medicines of the present invention are to H22The inhibitory action of transplanted solid tumor takes mice 80, and every mice is all before the right side
Oxter inoculation H22Oncocyte liquid 0.2ml.Claim weight next day, and be randomly divided into 8 groups, be i.e. normal saline group, cyclophosphamide group, basis
Invention medicine A group, medicine B group of the present invention, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second
Group, often 10 mices of group.Gastric infusion after inoculation 24h, gavage volume is 20ml/kg weight, 1 time/d, successive administration 10d,
Cyclophosphamide group intraperitoneal injection, the next day 1 time.After drug withdrawal, next day puts to death mouse weights, and carefully peel off tumor tissue, thymus and
Spleen, weighs respectively, and calculates tumour inhibiting rate, index and spleen index, thymus index.
2.3 medicines of the present invention are to S180The impact of ascites tumor mouse storaging current takes mice 70, and every equal abdominal cavity of mice connects
Plant S180Oncocyte liquid 0.2ml.Be randomly divided into 7 groups, i.e. normal saline group, medicine A group of the present invention, medicine B group of the present invention, this
Bright medicine C group, medicine D group of the present invention, drugs compared first group, drugs compared second group, often 10 mices of group.Gavage after inoculation 24h
Being administered, gavage volume is 20ml/kg weight, 1 time/d, successive administration 10d.Count with the day of inoculated tumour, when record is dead
Between, calculate increase in life span.
2.4 statistical procedures respectively organize data with mean ± standard deviation (± s) represent, use F inspection to carry out adding up credit
Analysis.
3 results
3.1 couples of H22The inhibitory action medicine of the present invention A group of transplanted solid tumor to D group to H22The suppression of transplanted solid tumor
Compared with normal saline group, medicine A group of the present invention significantly inhibits H to D group22Transplanted solid tumor growth effect (P <
, and medicine A group of the present invention does not has obvious inhibitory action to D group to the increase of Mice Body quality 0.01).Although cyclophosphamide
Tumor killing effect is best, inhibitory rate to 68.71%, but it has obvious inhibitory action to the growth of mice.Drugs compared first group
And the action effect of drugs compared second group is the most inconspicuous.It is shown in Table 2-1, table 2-2.
Table 2-1 medicine of the present invention is to H22The inhibitory action of transplanted solid tumor (± s, 10 examples)
Note: compare with normal saline group, * * P < 0.01
3.2 are shown in Table 2-2 to the impact of tumor-bearing mice immune organ.
Table 2-2 medicine of the present invention is to lotus tumor (H22) Mus immune organ impact (± s, 10 examples)
Note: compare with normal saline group, * P < 0.05
3.3 couples of S180The impact of ascites tumor mouse storaging current is shown in Table 2-3.
Table 2-3 medicine of the present invention is to S180The impact of ascites tumor mouse storaging current (± s, 10 examples)
Note: compare with normal saline group, * * P < 0.01
4 discuss and conclusion
In the clinical treatment of tumor, that mainly applies remains traditional cell toxicant based chemotherapy medicine.Such medicine is playing
While curative effect, obvious to the toxic and side effects of body, especially immunity is had bigger destruction.Experimental result tentatively illustrates,
Enhancing immunologic function is one of possible approaches of drugs against tumor of the present invention.Medicine of the present invention except enhancing human body immunity function it
Outward, still there is antioxidation, improve the various active such as physical stress ability.
And, experimental studies results is it is also shown that be used alone flower of Radix Notoginseng or be used alone the contrast medicine that Radix Notoginseng clip is made
The drug effectiveness of thing first and drugs compared second is the most inconspicuous, it can be seen that, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip
It is applied in combination, creates the obvious one-plus-one synergistic function more than two.
Experiment three: the medicine of the present invention impact on spontaneous hypertensive rat blood pressure
1 experiment material
1.1 laboratory animal
Bull spontaneous hypertensive rat (SHR) 40, body weight 225 ± 30g.Wistar rat 90, male and female are held concurrently
With, 12 weeks ages of Mus, body weight 245g~310g.
1.2 experimental drug
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
Positive Chinese medicine: mountain chrysanthemum hypertension pill, Hengli Group Pharmaceutical Co., Ltd., Hebei produces, and Chinese medicine is made into concentration is
0.0288g/ml.By the volume gastric infusion of 1ml/100g.
1.3 experimental apparatus
Conscious Rat blood pressure heart rate analyzer, HX-III type
2 experimental techniques
2.1 packet
Laboratory animal being divided into 9 groups, often group 10, packet situation is as follows:
(1) blank group, Wistar rat;(2) model control group, SHR model comparison;(3) positive controls, gavage mountain chrysanthemum
Hypertension pill;(4) medicine A group of the present invention, gavage medicine of the present invention A;(5) medicine B group of the present invention, gavage medicine of the present invention B;(6)
Medicine C group of the present invention, gavage medicine of the present invention C;(7) medicine D group of the present invention, gavage medicine of the present invention D;(8) drugs compared first
Group, gavage drugs compared first;(9) drugs compared second group, gavage drugs compared second.
2.2 be administered
Before formal experiment, pressure measurement every day is trained 1 time, continuous 7 days, is randomly divided into by SHR after rat adapts to environment, blood pressure stabilization
9 groups, often group 10, i.e. blank group, SHR model control group, mountain chrysanthemum hypertension pill positive controls, medicine A group of the present invention, basis
Invention medicine B group, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second group, gavage is given respectively
Medicine, mountain chrysanthemum hypertension pill positive controls, medicine A of the present invention, medicine B of the present invention, medicine C of the present invention, medicine D of the present invention, contrast
Medicine first, drugs compared second, blank group, model control group give the distilled water of same volume.Administration time is every morning.Even
Continuous administration 28 days, the blood pressure measured after being administered in the 29th day.
2.3 experimental procedure
Before pressure measurement, SHR is put into 37 ± 1 DEG C of electrothermostats, heats and make rat-tail tremulous pulse fully expand, use Conscious Rat blood pressure
The contraction pressure of rat tail artery surveyed indirectly by heart rate measurement instrument, takes continuous 3 pressure values and makees less than the meansigma methods of 5mmHg difference
For answering measuring blood pressure value, use before and after self and between group, F inspection carries out statistical disposition, blood pressure difference in means before and after comparing administration and between group
Different significance.
3 experimental results
It is shown in Table 3-1 and table 3-2.
Table 3-1 surveys SBP(mmHg after being administered the course for the treatment of)
Note: with model control group than △ P < 0.05, with positive controls than * P < 0.05
Table 3-2 surveys DBP(mmHg after being administered the course for the treatment of)
Note: compare with model control group, △ P < 0.05;Compare with positive controls, * P < 0.05;With medicine ratio of the present invention
Relatively, # P < 0.05.
From table 3-1,3-2, model group rats is blood pressure no significant difference (P > compared with before treatment during testing
0.05).Gavage medicine A group of the present invention continuously slowly to decline to D group blood pressure, the drop-out value of SBP, DBP and model group phase after 28 days
Than there being notable difference, (△ P < 0.05 also has notable difference (* P < 0.05 compared with positive controls;Give mountain chrysanthemum hypertension pill
Blood pressure is also decreased obviously, and after 28 days, SBP, DBP drop-out value is substantially better than model group (△ P < 0.05).And drugs compared first and right
More inconspicuous than the action effect of medicine second.
Result above shows, medicine of the present invention has obvious antihypertensive effect, and its hypotensive effect is relatively lasting, and is substantially better than
Drugs compared first group, drugs compared second group, be also significantly better than positive control drug mountain chrysanthemum hypertension pill.As can be seen here, medicine of the present invention
Flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination, create the obvious one-plus-one synergistic function more than two.
Experiment four: the experimentation of medicine effect for reducing blood fat of the present invention
1 experiment material
1.1 medicine
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
XUEZHIKANG JIAONANG: Wei Xin bio tech ltd of Beijing University, traditional Chinese medicines quasi-word Z10950029.
1.2 reagent triglyceride determination test kits, T-CHOL measures test kit, low-density LP determination reagent
Box, high-density LP determination reagent box.
1.3 animal Kunming mouses, male and female half and half, body weight 18~22g.
1.4 instrument B-260 type thermostat water baths, TDL80-2B type low speed centrifuge, DG5033A type enzyme linked immunosorbent detection
Instrument.
2 experimental techniques
Egg yolk liquid 75mL is drawn in the preparation of 2.1 egg-nog solution, puts in the graduated cylinder of 100mL, with normal saline dilution to 100mL,
It is made into the egg-nog homogeneous solution of 75%.
2.2 packets take 70 Kunming mouses, male and female half and half with administration, and body weight, in the range of 18~22g, is randomly divided into 9
Group, often group 10, is respectively as follows: Normal group, hyperlipidemia model group, positive controls, medicine A group of the present invention, medicine B of the present invention
Group, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second group, gastric infusion.Normal group
Giving concentration every day with hyperlipidemia model group is 0.5% CMC-Na solution, and giving volume is 0.2mL/10g;Positive controls, this
Bright medicine A group, medicine B group of the present invention, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second
Group, gives relative medicine respectively, and dosage is 1g/kg.Being administered 14 days, last two hours after administration, except Normal group
Outward, remaining respectively organizes equal lumbar injection 75% egg-nog solution 0.02mL/g modeling, after modeling 20 hours, takes blood from eyeball, by blood
Sample is in 3000rpm min-1, centrifugal 10min, isolated serum, according to T-CHOL, triglyceride, low density lipoprotein, LDL
Operate with high density lipoprotein test kit description, measure T-CHOL (TC), triglyceride (TG), low density lipoprotein, LDL
And the concentration of high density lipoprotein (HDL-C) (LDL-C).
2.4 statistical procedures the data obtained SPSS10.0 statistical softwares carry out statistical analysis, analysis result with±s
Represent, statistically significant with P < 0.05.
3 experimental results
After being administered 14 days, measure the T-CHOL (TC) in each group of experiment mice serum, triglyceride (TG), low density lipoprotein respectively
Albumen (LDL-C) and the concentration of high density lipoprotein (HDL-C), experiment and analysis result are shown in Table 4-1.
The impact of table 4-1 drug administration of the present invention group blood lipids index corresponding on mice (± s)
Note: compare with normal blank matched group, ##P < 0.01;Compare with hyperlipidemia model group, * * P < 0.01, * P < 0.05
Experimental result shows, the water average specific normal blank matched group of TC, TG, LDL-C of hyperlipidemia model group significantly raise (P <
0.01), the level of HDL-C decreases than Normal group (P < 0.01), shows induced Hyperlipidemia in Mice model modeling success;With
Model group is compared, and medicine A group of the present invention all can significantly reduce TC, TG, LDL-C level (P < 0.01) of mice to D group, can raise
The level (P < 0.05) of HDL-C, and it is substantially better than drugs compared first group and drugs compared second group.As can be seen here, medicine of the present invention
Flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination, create the obvious one-plus-one synergistic function more than two.
4 conclusions
This experimentation shows that medicine of the present invention has obvious effect to the reduction of TC, TG, LDL-C, has significantly rising to HDL-C
Effect, medicine of the present invention has the definite effect reducing laboratory animal blood fat, and it has the exploitation prospect for blood lipid-lowering medicine.
Experiment five: the experimentation of Drug therapy coronary heart disease of the present invention
1.1 material
90 (180 ± 10) g of SPF level male SD rat, are purchased from Nanjing University of Traditional Chinese Medicine's Experimental Animal Center;
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
Simvastatin Tablets (trade name: simvastatin) is Hangzhou Mo Shadong pharmaceutical Co. Ltd product.
High lipid food entrusts the processing of Shanghai Slac Experimental Animal Co., Ltd. of the Chinese Academy of Sciences.Monocyte chemotactic
Albumen-1 polyclonal antibody, palatelet-selectin polyclonal antibody, Matrix Metalloproteinase-9 polyclonal antibody, matrix metalloproteinase
Inhibitive factor-1 is purchased from Tian Hong bio tech ltd, Shanghai.
1.2 method
90 male SD rats are randomly divided into 9 groups, often group 10, are respectively blank group, model group, medicine A group of the present invention, basis
Invention medicine B group, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second group, simvastatin group is (right
According to group), expose zero difference between group.Model of experimental atherosclerosis in rats preparation method is 150g vitamin D3(VitD3, every gram contains
VitD310 ten thousand IU) it is dissolved in 375mL distilled water, it is configured to 0.4g/mL, the solution of i.e. 40,000 IU/mL.High lipid food formula
For: 82.3% Rat Standard feedstuff, 2% cholesterol, 0.5% sodium cholate, 10% Adeps Sus domestica, 0.2% propylthiouracil, 5% white sugar.Remove
Outside blank group, other each group gives VitD3 by the accumulated dose gavage of 700,000 IU/kg, divides and gives for 3 days, feeds high fat afterwards every day and raises
Material 15g, feeds 57 days.Blank group and model group all gavage distilled water 5mL/(kg d);Treatment group 1 gavages medicine A of the present invention;
Treatment group 2 gavages medicine B of the present invention;Treatment group 3 gavages medicine C of the present invention;Treatment group 4 gavages medicine D of the present invention;Treatment group 5
Gavage drugs compared first;Treatment group 6 gavages drugs compared second;Simvastatin group gavages simvastatin 1.7mg/(kg d), above respectively
Medicine is all configured to solution by 5mL/(kg d with distilled water) dosage gavages.After VitD3 gavage terminates for 3 days, within the 4th day, start treatment,
The course for the treatment of is 57 days.After medication 57 days, with 100mg/kg ketamine intraperitoneal injection of anesthesia rat, open abdominal cavity, abdominal aortic blood
After be instantly separable from thoracic aorta, every treated animal takes 6 at random.Thoracic aorta formaldehyde is fixed, specimens paraffin embedding slices, and conventional line HE contaminates
Color, the form (including patch structure, inner membrance bowing, foam cell, calcification) of optical microphotograph Microscopic observation aorta, with-,
+, ++, +++, indicate respectively without pathological changes, slight, moderate, severe.Utilize IMS cell image analyze system detection inner film thickness and
Foam cell area percentage.MMP-9 albumen, the expression of MMP-9/TMP-1 protein ratio in SABC detection thoracic aorta.
Using the section of paraffin embedding routine, SP method, MMP-9mAb dilutes with 1:50;TMP-1mAb dilutes with 1:50;Dilution DAB colour developing,
Haematoxylin is redyed.Basis of microscopic observation, negative in hyacinthine, positive in brown color.Under high power lens, (× 400 times) observe often group
Section aorta, randomly selects 3 visuals field, surveys its positive staining occupied area in the whole visual field (full filed is set to 351000)
Percentage ratio, takes its meansigma methods and represents every positive area ratio cut into slices, statistics often group SABC positive area percentage ratio.
1.3 result
(1) Aortic Morphology change: each treated animal thoracic aorta observes discovery through HE dyeing at microscope: in seen from model group
The AS early lesions such as the physaliphore of theca cell hypertrophy and the interior light dye of subcutaneous appearance, seen from some position in film smooth muscle cell increase
Raw obvious, cell arrangement disorder or protuberance are in speckle block structure, and in some position, film has obvious calcification to be formed, around calcification district
Foam like cell occurs.Each treatment group, matched group are improved in varying degrees compared with model group, are shown in Table 5-1.
The pathological analysis of table 5-1 difference group rat chest aorta
(2) aortic tunica intima thickness: with the thoracic aorta wall inner film thickness of image analyzer detection, model group, matched group, treatment
Group inner film thickness has and thickens in various degree, all has significant difference (P < 0.01) compared with blank group.Each treatment group, matched group
Inner film thickness relatively model group is compared, and all has the most thinning, and difference is the most statistically significant.It is shown in Table 5-2.
Table 5-2 difference group rat chest aorta inner film thickness (40 × 10)
Note: compare between group: each group compares with blank group, * * P < 0.01;Model group compares with treatment group, matched group, △ P < 0.05,
△△P<0.01;Matched group compares with treatment group, #P > 0.05.
(3) aorta foam cell area percentage: with the thoracic aorta foam cell area hundred of image analyzer detection
Proportion by subtraction, each group all has showed increased, significant difference (P < 0.01) compared with blank group.Treatment group, matched group compared with model group,
Foam cell area percentage all has and reduces in various degree, statistically significant (P < 0.05).Each treatment group compared with matched group,
Treatment group 1 and treatment group 4 foam cell area percentage not statistically significant (P > 0.05).It is shown in Table 5-3.
Table 5-3 difference group rat chest aorta inner membrance foam cell area and foam cell percentage ratio (40 × 10)
Note: compare between group: each group compares with blank group, * * P < 0.01;Model group compares with treatment group, matched group, △ P < 0.05,
△△P<0.01;Matched group compares with treatment group, ☆ P<0.01, #P>0.05.
(4) aorta MMP-9 protein expression: blank group MMP-9 positive area compared with model group, treatment group, matched group
Percentage ratio is remarkably decreased (P < 0.01);Model group is compared with treatment group, matched group, and the positive area percentage ratio of MMP-9 substantially rises
Height, the most statistically significant (P < 0.01).Matched group is compared with treatment group 1 to treatment group 4, and the expression of MMP-9 is anticipated without statistics
Justice (P > 0.05).It is shown in Table 5-4.
Table 5-4 difference group rat chest aorta inner membrance MMP-9 expresses
Note: compare between group: each group compares with blank group, * * P < 0.01;Model group compares with treatment group, matched group, △ △ P <
0.01;Matched group compares with treatment group, #P > 0.05.
3 conclusions
Experimentation shows: medicine of the present invention has the rat for the treatment of Atherosclerosis Model and there is blood vessel lining cells hypertrophy
And the interior subcutaneous AS early lesion such as physaliphore occurring infecting, occur rising the unbalance shape of MMP-9/TMP-1 of a height of master with MMP-9
State.
And, experimental studies results is it is also shown that be used alone flower of Radix Notoginseng or be used alone the contrast medicine that Radix Notoginseng clip is made
The drug effectiveness of thing first and drugs compared second is the most inconspicuous, it can be seen that, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip
It is applied in combination, creates the obvious one-plus-one synergistic function more than two.
Experiment six: medicine blood sugar lowering experimentation of the present invention
1 materials and methods
1.1 laboratory animal
NIH kind white mice, weight 22g ± 2g, Nanjing University of Traditional Chinese Medicine's experimental animal center provide.
1.2 medicines and reagent
Alloxan (ALX) (Sigma chemical company of U.S. product), Glibenclamide Tablets (the raw pharmaceutical Co. Ltd in the Pacific Ocean, Tianjin,
Traditional Chinese medicines quasi-word H12020790), blood sugar test paper and tester are produced by Johnson Co., and full-automatic micropartical chemiluminescence is exempted from
Epidemic disease analyzes system.
The preparation of 1.3 given the test agent
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
1.4 laboratory animals and packet
1.4.1 diabetic mice modeling
With reference to Chen Jianguo etc. (Chen Jianguo, Mei Song, Fu Ying grind [J] etc. what. alloxan caused mice hyperglycemia model. sanitary toxicology
Learn magazine, 2004,18 (2): 98~100) method that alloxan causes mice hyperglycemia model, and it is suitably modified.Take little
After Mus 100 (male and female half and half) fasting (can't help water) 12h, the fresh ALX solution (220mg/kg) of lumbar injection 2% 2 times respectively
(the 1st injection volume is the 70% of total amount, and the 2nd time is the 30% of total amount, two minor tick 12h).After 3 days, after fasting 12h, docking takes
Blood, measures mouse blood sugar with blood sugar test paper and tester, and measures body weight.FPG > 11.1mmol/L, it is determined as diabetes model is little
Mus.
1.4.2 packet is tested
Model mice 80 being only randomly divided into 8 groups, often group 10, experiment periods respectively organizes gavage every day respectively.
(1) model group: distilled water 0.3~0.4ml/ is only;(2) glibenclamide group: gavage glibenclamide 10mg/kg;(3) originally
Invention medicine A group: gavage medicine of the present invention A 400mg/kg;(4) medicine B group of the present invention: gavage medicine of the present invention B 400mg/
kg;(5) medicine C group of the present invention: gavage medicine of the present invention C 400mg/kg;(6) medicine D group of the present invention: gavage medicine of the present invention D
400mg/kg;(7) drugs compared first group: gavage drugs compared first 400mg/kg;(8) drugs compared second group: gavage drugs compared
Second 400mg/kg.Experiment periods 14 days.
1.4.3 Testing index
Experiment periods observe the searching for food of mice, drink water, the situation such as weight, the mental status, hair color;Respectively 2h the most upon administration,
3d, 14d docking takes the blood glucose value after hematometry mice fasting 12h, measures the serum islet after mice fasting 12h at the end of experiment
Element.
1.5 statistical procedures
Carry out data analysis with SPSS10.0 statistical software, between group significance test use independent samples t test, all data with± s represents.
2 results
The hypoglycemic activity of 2.1 medicines of the present invention
Occur in that polydipsia, polyphagia, polyuria with the mice after alloxan modeling, lose weight, and respond blunt, mixed and disorderly by hair
The symptom such as unglazed, after medication, the medicine above symptom of group mice of the present invention all has improvement in various degree, and reaction is relatively flexible, Mao Ping
Lie prostrate and glossy.From table 6-l: to alloxan diabetes mice after gavage medicine of the present invention after 2h and 14d with model
Group compares, and energy is significantly and pole significantly decreases the blood glucose value (P < 0.05 and P < 0.01) of mice).
Table 6-1 medicine of the present invention on the impact of alloxan diabetes mice fasting glucose (± s)
Note: compare with model group, * P < 0.05, * * P < 0.01
2. the 2 medicines of the present invention impact on diabetic mice serum insulin levels
After gavaging medicine 14d of the present invention continuously, comparing mice serum insulin levels with model group has notable rising, is shown in Table 6-
2。
Table 6-2 medicine of the present invention on the impact of alloxan diabetes mice serum insulin (± s)
Note: compare with model group, * P < 0.05, * * P < 0.01
3 discuss and conclusion
This experiment with medicine of the present invention to alloxan diabetes mice with 400mg/kg d-12h after medicine gavage of the present invention,
3d and 14d, finds by measuring mice fasting plasma glucose concentration, compares the medicine of the present invention fall blood when 2h, 3d, 14d with model group
Sugar effect is substantially;Serum insulin is all significantly higher than model group when 14d.Illustrate that medicine of the present invention has and alleviate alloxan
To the degree of injury of beta Cell of islet or this damage being had a certain degree of protection and repair, this effect is with medication
Its effect of the prolongation of time is more significantly.
And, experimental studies results is it is also shown that be used alone flower of Radix Notoginseng or be used alone the contrast medicine that Radix Notoginseng clip is made
The drug effectiveness of thing first and drugs compared second is the most inconspicuous, it can be seen that, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip
It is applied in combination, creates the obvious one-plus-one synergistic function more than two.
Experiment seven: the experimentation of Drug therapy metabolism syndrome of the present invention
One, material and method
1. experiment material
1.1 instrument reagent
Blood sugar test paper and fast blood glucose meter are purchased from Abbott of the U.S., and biological skill opened up purchased from Beijing world by four items of blood lipid tests reagent in examining
Art company limited, micro-injection pump uses Novolin R, hand held FEJ-1000B electronics purchased from Bei Lang company of Germany, insulin
Scale, purchased from Foochow Electronics Co., Ltd. of Furistock.
1.2 laboratory animal
The male 6 week old SD rat of cleaning grade 90, feedstuff, experimental site are carried by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center
Confession, every cage 4-5 only, freely drinks drinking water, and the 12h daily cycle feeds.
1.3 Experimental agents
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
The composition of Avandia is Rosiglitazone Maleate Tablets (RM), and 4mg/ sheet is limited by U.S.'s GlaxoSmithKline PLC (Tianjin)
Company produces, traditional Chinese medicines quasi-word H20020475.
2. the foundation of model
Rats in normal control group is fed with common standard feedstuff (carbohydrate 60%, fat 11%, protein 29%);Model group
Rat feeds 8 Zhou Houcheng with high lipid food (78.8% normal feedstuff, 1% cholesterol, 10% yolk powder, 10% Adeps Sus domestica, 0.2% cholate)
Mould, weight and visceral fat mass significantly raise.
3. packet and administration
At random rat is divided into 9 groups, Normal group, metabolism syndrome group, Avandia group, medicine A group of the present invention, medicine of the present invention
Thing B group, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second group, often organize each 10 rats;Just
Often matched group feed common standard feedstuff, remaining rat feeding high lipid food.Throw something and feed medicine: after Cheng Mo, model group rats is random
It is divided into metabolism syndrome group, Avandia group, medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention, medicine of the present invention
Thing D group, drugs compared first group, drugs compared second group;Start Avandia group from the 9th week and press 2mg kg-1·d-1, feed Wen Di
Refined, medicine A group of the present invention presses 60mg kg-1·d-1Feed medicine of the present invention A, medicine B group of the present invention presses 60mg kg-1·d-1
Feed medicine of the present invention B, medicine C group of the present invention presses 60mg kg-1·d-1Feed medicine of the present invention C, medicine D group of the present invention is pressed
60mg·kg-1·d-1Feed medicine of the present invention D, drugs compared first group presses 60mg kg-1·d-1Feed drugs compared first, contrast
Medicine second group presses 60mg kg-1·d-1Feed drugs compared second, medicine is all with physiological saline solution;Normal group, metabolism are combined
Simulator sickness group is thrown something and fed the normal saline of same ratio volume, after persistently feeding 4 weeks, row clamp procedure.
4. experimental index measures
Taking blood under waking state, use EDAT anticoagulant, TG, TC, HDL-C, LDL-C biochemical process measures.Fasting insulin (IFNS)
Measure with putting the method for exempting from.All rats, in process of the test, measure weekly 1 weight.With RBP-l type rat blood pressure meter, use
Rat-tail cuff pressurization blocked method measures blood pressure, measures 1 time every two weeks.
5. visceral fat mass weighs method
By at rat after death, cut abdominal cavity open, take that right side is attached starts other fatty wet quality and replace visceral fat mass.
6. measure insulin sensitivity
The sensitivity of insulin is evaluated by euglycemic-hyperinsulinemic glucose clamps (GC) method.Each group rat (is pressed with the chloral hydrate of 10%
Every 300g rat weight 1ml) through intraperitoneal anesthesia, insert people's conduit (PE-50) the 2nd day to right carotid and left jugular vein, clearly
After measuring fasting glucose (FBS) under the state of waking up, respectively with initial concentration and the 4mU kg of 25mU/kg-1·min-1Maintain concentration,
Continue 150min intravenous drip insulin;The every 7min of blood glucose value measures 1 time, simultaneously with 12.5% Glucose Liquid continuous intravenous dripping;
For maintaining fasting blood glucose level, suitably adjust;Its infusion velocity.After blood glucose value is stable, with GC method (Fructus Vitis viniferae in last 35min
The meansigma methods of sugar infusion velocity, M value) evaluate insulin sensitivity.
7. data analysis
All data with± s represents;More all add up with SPSS between each group elementary statistics amount and homogeneity test of variance and two groups
Learn software analysis.
Two, result
1. each group weight and interior fat be relatively shown in Table 7-1, table 7-2.
Table 7-l respectively organize rat weight change (± s, g)
Note: compare with Normal group, * P < 0.05.
When table 7-2 respectively organizes rat 12 weeks weight and interior fat comparison (n=10,± s)
Note: compare with Normal group, * P < 0.05.
Metabolism syndrome group compared with normal matched group weight and interior fat increase substantially (P < 0.05);Table 7-2 can see
Go out Avandia and medicine group of the present invention relatively metabolism syndrome group, weight and interior fat all have downward trend, nothing between two groups
Difference.
Respectively organize the comparison of FBS, FINS, M value
It is shown in Table 7-3.Metabolism syndrome group compared with normal matched group M value substantially reduces (P < 0.01), FINS significantly raised (P < 0.01);
Medicine group of the present invention significantly raised compared with metabolism syndrome group M value (P < 0.05), FINS substantially reduces (P < 0.05).
Table 7-3 respectively organize FBS, FINS and M value comparison (± s)
Note: compare with Normal group, * P < 0.05, * * P < 0.01;Compare with metabolism syndrome group, △ P < 0.05.
3. each comparison organizing blood lipid level
It is shown in Table 7-4.Metabolism syndrome group compared with normal matched group TC, TG, LDL-C substantially increase, HDL-C zero difference;Medicine of the present invention
Thing group relatively metabolism syndrome group TC, TG, LDL-C substantially reduce, and improve inconspicuous to HDL-C.
Table 7-4 respectively organize comparison between TC, TG, LDL-C, HDL-C (± s, mmol/L)
Note: compare with Normal group, * P < 0.05, * * P < 0.01;Compare with metabolism syndrome group, △ P < 0.05.
Three, conclusion and discussion
Experimental data shows, after modeling 8 weeks, model group compared with normal matched group Insulin Sensitivity Index (M value) substantially reduces, body
Quality and interior fat substantially increase, and blood lipid level is significantly raised, and serum insulin also has rising trend simultaneously;Prompting is with center
Property fat and insulin resistant centered by, merge that blood pressure increases, the Metabolic Syndrome of blood fat disorder, hyperinsulinemia becomes
Merit is set up.Clinical research and epidemiological survey find that fat, super severe one is often accompanied by insulin resistant and abnormalities of sugar/lipid metabolism, fat
It is organized in the pathogenesis of insulin resistant and plays an important role.
Experimental result shows, medicine of the present invention can be obviously improved the insulin sensitivity of metabolism syndrome group has reduction interior
Dirty fat and the trend of serum insulin levels, it will be apparent that improve serum TC, TG, LDL-C level.Medicine of the present invention can have
Effect treatment Comprehensive Treatment metabolism syndrome.
And, experimental studies results is it is also shown that be used alone flower of Radix Notoginseng or be used alone the contrast medicine that Radix Notoginseng clip is made
The drug effectiveness of thing first and drugs compared second is the most inconspicuous, it can be seen that, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip
It is applied in combination, creates the obvious one-plus-one synergistic function more than two.
Experiment eight: the experimentation of Drug therapy cyclomastopathy of the present invention
1 materials and methods
1.1 laboratory animals and feedstuff are grown up the SD health ♀ rat 90 of unpregnancy, body weight 180~220g;Primary vegetative feedstuff
80kg, is provided by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center.
1.2 key instruments and medicine
ACS:I80SE type chemical illumination immunity analysis instrument, U.S.'s CHIRON Products;XX3 type blood viscosity electronics self-clocking
Instrument, Beijing Zhong Qinshidi scientific instrument company limited provides;
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
Estradiol benzoate (Estradiol, E2, hereinafter referred to as E2) injection, pharmaceutical factory, Shanghai the 9th produces, specification:
2mg·mL-1.Progesterone (Pro-gesterone, Pt, hereinafter referred to as Pt) injection, pharmaceutical factory, Shanghai the 9th produces, specification:
20mg·mL-1.Estradiol and Progesterone measure test kit, for CHIRON company of U.S. auxiliary products;Estradiol (E2), progesterone
(Pt) radioimmunoassay determination box, is provided Dako Products by Depew, Tianjin biotechnology and medical product company limited.
1.3 animal packets and process are normal after laboratory animal being bought back raises 2 weeks, is randomly divided into 8 groups of (models by body weight
Organizing 20, remaining often organizes 10): blank group (hereinafter referred to as matched group), model group, medicine A group of the present invention, medicine of the present invention
Thing B group, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second group.Model group every intramuscular injection E2
(0.5mg kg) d-1, continuous 40d, then use intramuscular injection Pt(4mg kg instead) d-1, continuous 10d, observe nipple occur red,
Swell and increase, and when having part mammary areola to occur, putting to death 5, confirming that hyperplasia of mammary gland model replicates successfully by pathological section.Comparison
The capacity normal saline such as group intramuscular injection every day, terminate to experiment.Medicine A group of the present invention, medicine B group of the present invention, medicine C of the present invention
Group, medicine D group of the present invention, drugs compared first group, drugs compared second group after modeling terminates by 400mg kg-1Gavage this respectively
Invention medicine A, medicine B of the present invention, medicine C of the present invention, medicine D of the present invention, drugs compared first, drugs compared second, dosage is
400mg·kg-1, terminate to experiment.Whole experimental period is 80d.
After 1.4 Indexs measure are administered 24h last with observation 1 time, animal fasting 12h, perusal each rat mammiform
State changes.Etherization, aorta sacrificed by exsanguination, leave and take blood and bilateral breast on request, automatic with XX3 type blood viscosity electronics
Chronograph detection blood viscosity, detects packed cell volume by hematocrit tube method;Extract blood plasma, CH-IRON company of application U.S. ACS:
I80SE type chemical illumination immunity analysis instrument and matched reagent detection detection blood plasma E thereof2And Pt;Every rat selects maximum mammary gland
Organizing 2, through nipple basad portion, maximum tangent plane is drawn materials, and routine paraffin wax is cut into slices, and HE dyes, and low power lens counts each lobule acinus
Number, seeks its meansigma methods, and high power lens observes Epithelial hyperplasia number, acinus number in lobule;ER and PR is observed by immunohistochemical ABC method
Change, ER, PR, working concentration 1:200, and set the positive and negative control.
1.5 statistical procedures data represent with mean ± standard deviation, and each group significance test uses Dunnett'sT inspection
Test.
2 results
2.1 PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM control rats breast ductal epithelial cells queueing disciplines, tube chamber is without expansion, and lobule is relatively
Few, acinus number 3~4 in lobule, kernel is inconspicuous.Intramuscular injection E2, rat nipple occurs red, swollen and increases after Pt modeling, and have
Mammary areola occurs, dissection can see below 3 pairs of breast mammary gland tissues and connect in flakes, demarcates unclear.Rat mammary gland is respectively organized seen from pathological section
Ductal epithelial cell hypertrophy is obvious, and local is in mamillary or fit shape the number of plies increase, and kernel is obvious, and tube chamber is substantially expanded, interior
Having Exfoliative cells and secretions, lobule showed increased, in lobule, acinus number hypertrophy is obvious, interstitial hemorrhage, edema and fiber
Hamartoplasia, it was demonstrated that cyclomastopathy modeling success, hypertrophy type is based on cystic hyperplasia.Compare with model group, medicine of the present invention
The nipple of suspension group gross examination of skeletal muscle is red and swollen, mammary gland increases and the hypertrophy of microexamination lobule, acinus and conduit, is the most substantially lighter than
Modeling group.In each group breast duct epithelial proliferation and lobule, acinus number compares.(being shown in Table 8-1)
Table 8-1 respectively organizes acinus number in breast duct epithelial proliferation and lobule and compares (n=10)
Note: ##P < 0.01, #P < 0.05 compared with matched group;* * P < 0.01, * P < 0.05 compared with model group.
2.2 impacts (being shown in Table 8-2) on hemorheology of rat
Model group whole blood viscosity (ratio), plasma viscosity (ratio), packed cell volume are significantly higher than matched group.Medicine group blood of the present invention
Hemorheological Indexes makes moderate progress, and majority parameters, close to normal level, is better than drugs compared first group and drugs compared second group.
The impact (n=10) on hemorheology of rat of the table 8-2 medicine of the present invention
Note: compared with matched group, * * P < 0.01;Compared with model group, ##P < 0.01, #P < 0.05.
2.3 couples of rat plasma E2, the impact (being shown in Table 8-3) of Pt
2.4 positive criterions that affect expressing rat breast tissue ER, PR are breast duct and lobule epithelial nucleus
And/or be positive during cytoplasm coloring.< 20% is (-) to positive cell rate;Positive cell rate is less than 20%, but regional area has
The positive cell person of the strongest a small amount of coloring be (±);Positive cell rate > 20% and positive cell number by few the most at most, coloring is by shallow
To being deeply+, ++, +++, ++++, and count 1,2,3,4,5,6 points respectively, integration is the highest shows that ER, PR content is the highest.(being shown in Table 8-3)
Compare with matched group, model group animal blood slurry estradiol (E2) content dramatically increases, progesterone (Pt) content significantly reduces,
There were significant differences for ER, PR integrated value, and after Drug therapy of the present invention, high dose group estradiol content substantially reduces, progesterone content
Significantly raised;ER, PR integrated value has notable and pole significant difference, and medicine effect of the present invention effect compared with model group the most respectively
Fruit is better than drugs compared first group and drugs compared second group.
Table 8-3 respectively organizes rat plasma E2, Pt and mammary gland tissue ER, PR integral contrast (n=10)
Note: compare * * P < 0.01, * P < 0.05 with matched group;Compare with model group, ##P < 0.01, #P < 0.05.
3 discuss and conclusion
Cyclomastopathy has obvious sex hormone dependent, model group blood plasma E2Level is significantly higher than matched group, medicine of the present invention
Group blood plasma E2Level is substantially less than model group, and Pt level is significantly higher than model group, and mammary gland tissue ER, PR content is significantly lower than model
Group, shows the therapeutical effect of medicine of the present invention and improves organism endocrine environment, reduces rat breast tissue ER, PR simultaneously and contains
Amount, thus weaken E2Relevant to the biological effect of target cell.
And, experimental studies results is it is also shown that be used alone flower of Radix Notoginseng or be used alone the contrast medicine that Radix Notoginseng clip is made
The drug effectiveness of thing first and drugs compared second is the most inconspicuous, it can be seen that, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip
It is applied in combination, creates the obvious one-plus-one synergistic function more than two.
Experiment nine: medicine antidepressant effect experimentation of the present invention
1 materials and methods
1.1 medicine
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
1.2 animal
Healthy SD rat, male, body weight 180~200g, healthy ICR mice, male and female do not limit, body weight 18~22g, Nanjing Chinese medicine
University's Experimental Animal Center provides.
1.3 medicines and reagent
VENLAFAXINE HCL sheet (Pharmaceutical Co Ltd, Changzhou Pharmaceutical Factory No.4, traditional Chinese medicines quasi-word H20110150), dosage 6.25mg/Kg,
5 times of behaviour quantity 1.25mg/Kg;Reserpine In Tablets (Shanghai Sine Pharmaceutical Co., Ltd., traditional Chinese medicines quasi-word H31021148).
1.4 instrument
Lucite swimming groove, high 40cm, long 60cm, wide 30cm, Nanjing University of Traditional Chinese Medicine's Experimental Animal Center provides;XZ-4 is little
Mus ambulatory activity count device, Nanjing University of Traditional Chinese Medicine's Experimental Animal Center provides.
1.5 method
1.5.1 rat forced swimming test: healthy SD rat 80, male, it is randomly divided into 8 groups by body weight, often group 10, i.e. mould
Type matched group, positive control VENLAFAXINE HCL sheet 6.25mg/Kg dosage group, medicine A 20.00 crude drugs/Kg dosage of the present invention
Group, medicine B 20.00 crude drugs of the present invention/Kg dosage group, medicine C 20.00 crude drugs of the present invention/Kg dosage group, medicine D of the present invention
20.00 crude drugs/Kg dosage group, drugs compared first 20.00 crude drugs/Kg dosage group, drugs compared second 20.00 crude drugs/Kg dosage
Group, model control group gives same volume deionized water.Rat oral gavage is administered, and is administered once/sky, continuous 10 days.9th day, in administration
Rear 30min puts into single for rat in lucite swimming groove, and the depth of water is 15cm, water temperature 25 DEG C, forces it to swim, after 15min
Take out animal, dry, then put back in cage.After last is administered 30min, rat is put in swimming groove, big in record 5min
Mus remains stationary as the time of state, i.e. rat micro-body of curling up, but keeps vertical position, the time surfaced in nostril.
1.5.2 tail suspension test experiment: healthy ICR mice 80, female, male half and half, it is randomly divided into 8 groups by body weight, often group
10, i.e. model control group, positive control VENLAFAXINE HCL sheet 6.25mg/Kg dosage group, medicine A 20.00 of the present invention life
Medicine/Kg dosage group, medicine B 20.00 crude drugs of the present invention/Kg dosage group, medicine C 20.00 crude drugs of the present invention/Kg dosage group, basis
Invention medicine D 20.00 crude drugs/Kg dosage group, drugs compared first 20.00 crude drugs/Kg dosage group, drugs compared second 20.00 are raw
Medicine/Kg dosage group, model control group gives same volume deionized water.Mouse stomach is administered, every day 1 time, continuous 10 days.In last
After being administered 30min, mouse tail (at tail point 1cm) is bonded on the batten exceeding desktop 3cm with adhesive plaster, animal in record 5min
Dead time.
1.5.3 Reserpine antagonistic test: healthy mice 160, female, male half and half, it is randomly divided into 8 groups by body weight, often organizes 20
Only, packet and dosage ibid, after last is administered 30min, mouse tail vein injection reserpine 2mg/Kg, observe after injection 1h
The number of animals of mice blepharoptosis, body rigidity keep the number of animals that flesh contraction state is motionless, and calculate its incidence rate, observe and remember
Temperature changing before and after record injection reserpine.
1.5.4 autonomic activities experiment: healthy mice 80, male and female half and half, is randomly divided into 8 groups by body weight, often group 10, i.e.
Model control group, VENLAFAXINE HCL sheet group, medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention, the present invention
Medicine D group, drugs compared first group, drugs compared second group, dosage is the same.Mouse stomach is administered, every day 1 time, and continuous 10
My god.30min after last is administered, respectively organizes the autonomic activities situation of mice, record with XZ-4 mice ambulatory activity count device record
5min, measures 2 times, takes its meansigma methods.
1.6 statistical method
Application SPSS10.0 statistical software carry out data process, all measurement datas with mean ± standard (± s) difference expression, group
Between compare employing t inspection, enumeration data use χ2Inspection.
2 results
2.1 rat forced swimming test
The motionless state occurred in forced swimming model also reflects the desperate behavior of animal, can be with the depressed shape of simulating human
State.Comparing with model control group, medicine A group of the present invention can substantially be resisted " disappointed " to D group, shortening non-swimming time (P <
0.05), the action effect of drugs compared first group and drugs compared second group is the most inconspicuous.As can be seen here, medicine of the present invention is by three
Seven flowers and Radix Notoginseng clip are applied in combination, and create the obvious one-plus-one synergistic function more than two.It is shown in Table 9-1.
Table 9-1 medicine of the present invention on the impact of rat forced swimming test (± s)
Note: compare with model control group, * P < 0.05
2.2 tail suspension test experiments
The motionless state that mice occurs in outstanding tail model reflects the desperate behavior of animal.Compare with model control group, this
Bright medicine A group to D group can shorten the dead time (P < 0.05) of mouse tail suspension, and drugs compared first group and drugs compared second group
Action effect is the most inconspicuous.As can be seen here, flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination by medicine of the present invention, create obvious one
The synergistic function adding one more than two.Point out medicine of the present invention to have and alleviate mice despair behavior, antidepressant effect.It is shown in Table 9-
2。
Table 9-2 medicine of the present invention to the effect of Tail suspension test (± s)
Note: compare with model control group, * P < 0.05, * * P < 0.01
2.3 Reserpine antagonistic test
Comparing with model control group, medicine A group of the present invention can obviously reduce reserpine to D group and causes mice blepharoptosis and mice
Motion can not incidence rate (P < 0.05), the degree (P < 0.05) of hypothermia after injection reserpine can be alleviated;And drugs compared first
The action effect of group and drugs compared second group is the most inconspicuous.As can be seen here, flower of Radix Notoginseng and Radix Notoginseng clip are combined by medicine of the present invention
Use, create the obvious one-plus-one synergistic function more than two.It is shown in Table 9-3~table 9-5.
Table 9-3 medicine of the present invention reserpine is caused mice blepharoptosis effect impact (± s)
Note: compare with model control group, * P < 0.05, * * P < 0.01
Table 9-4 medicine of the present invention reserpine is caused mouse movement can not impact (± s)
Note: compare with model control group, * P < 0.05, * * P < 0.01
Table 9-5 medicine of the present invention reserpine is caused impact that mouse temperature reduces (± s)
Note: compare with model control group, * P < 0.05
2.4 autonomic activities experiments
Have no that mice autonomic activities is had a significant impact by medicine of the present invention each dosage group.It is shown in Table 9-6.
Table 9-6 medicine of the present invention on the impact of mice autonomic activities (± s)
Note: compare with model control group, * * P < 0.01
3. conclusion
In terms of results of animal, medicine of the present invention can substantially resist " disappointed ", shortens non-swimming time;Mice can be shortened hang
The dead time of tail;Reserpine can be reduced and cause mice blepharoptosis and mice spasticity incidence rate, alleviate injection reserpine
The degree of rear hypothermia;On normal mouse autonomic activities without impact.As can be seen here, medicine of the present invention to behavior Stress model and
Drug-induced depression model has certain antidepressant effect, has no significant effect the autonomic activities of normal mouse simultaneously, this
Put to compare with positive drug and there is certain difference.
To sum up, medicine of the present invention has obvious antidepressant effect, and is better than drugs compared first and drugs compared second, says
In bright medicine of the present invention, the compatibility between each flavour of a drug is superior, indispensable, and the combination between each flavour of a drug creates the most collaborative
Potentiation.
Experiment ten: the experimentation of medicine defying age of the present invention
1 experiment material
1.1 laboratory animals: pure lines Kunming mouse, body weight 20 ± 2g, are provided by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center.
1.2 Experimental agents
1.2.1 medicine
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
Positive drug: LIUWEI DIHUANG WAN, Beijing Tongrentang produces.
1.2.2 D-galactose (D-galactose Shanghai reagent two factory): be made into, with deionized water, the D-gal that concentration is 5% molten
Liquid, after putting into air-tight bottle inner high voltage sterilizing, 4 DEG C of Refrigerator stores, standby.
1.3 main agents malonaldehyde (MDA) test kits, lipofuscin (LF) test kit, superoxide dismutase (SOD) try
Agent box, catalase (CAT) test kit, all originate in Nanjing and build up Bioengineering Research Institute.
1.4 key instrument refrigerated centrifugers, water bath with thermostatic control crucible, 722 type spectrophotometers, electric driven glass homogenizer, trace
Sample injector, ultra cold storage freezer, timer, autoclave, electric heating dry baking box.
2 experimental techniques
2.1 grouping experiments Kunming mouse 108, is randomly divided into 9 groups, i.e. blank group, model control group, medicine A of the present invention
Group, medicine B group of the present invention, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, drugs compared second group, positive drug
Medication group, each group 12.
While 2.2 make film administration, model group and administration group mice neck every day dorsal sc injection 5%D-galactose, continuously
Inject 6 weeks, the injection saline of blank group subcutaneous injection equivalent.Injection is all operated by sterility requirements.
2.3 are administered employing administration by gavage is administered 6 weeks.Medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention,
Medicine D group of the present invention, drugs compared first group, drugs compared second group give medicine A of the present invention, medicine B of the present invention, the present invention respectively
Medicine C, medicine D of the present invention, the decocting liquid of drugs compared first, drugs compared second, its concentration is 0.2g/ml, and medicine liquid volume is every
It 0.2ml/20g, positive drug medication group gives LIUWEI DIHUANG WAN.
2.4 draw materials and measure will be administered 6 weeks after respectively organize mice, eye socket take whole blood process after standby, and put to death animal take out
Liver, takes whole blood and illustrates that calligraphy carries out SOD, CAT vigor, MDA assay according to test kit;Take liver to illustrate according to test kit
Calligraphy carries out LF assay.
2.5 these experimental datas of statistical method all use (± s) represent, the data between each group compare employing t inspection.
3 experimental results
3.1 outward appearances and behavior observation aging model group, medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention, basis
Invention medicine D group, drugs compared first group, drugs compared second group, after being administered 12 days, start occur that mouse hair is withered and yellow, independently live
The aging phenomenons such as dynamic minimizing, is slow in action, lethargy.
The impact on mouse aging SOD in serum content of 3.2 medicines of the present invention
From table 10-1, comparing with blank group, aging model group SOD in serum content substantially reduces (P < 0.05), with mould
Type group compares, although drugs compared first group and drugs compared second group SOD content raise, but DeGrain (P > 0.05), this
Bright medicine A group is to D group SOD content significantly raised (P < 0.05).As can be seen here, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip group
Close and use, create the obvious one-plus-one synergistic function more than two.
Table 10-1 medicine of the present invention on the impact of mouse aging SOD in serum content (± s)
Note: compare with blank group, △ P < 0.05;Compare with aging model group, * P < 0.05.
The impact on mouse aging erythrocyte CAT activity of 3.3 medicines of the present invention
From table 10-2, comparing with blank group, aging model group erythrocyte CAT activity substantially reduces (P < 0.05), with
Model group compares, and LIUWEI DIHUANG WAN group, medicine A group of the present invention are to D group erythrocyte CAT activity the most significantly raised (P < 0.05), right
There is rising than medicine first group and drugs compared second group erythrocyte CAT activity, but compare with blank group, there was no significant difference (P
> 0.05).As can be seen here, flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination by medicine of the present invention, create obvious one-plus-one more than two
Synergistic function.
Table 10-2 medicine of the present invention on mouse aging erythrocyte CAT activity impact (± s)
Note: compare with blank group, △ P < 0.05;Compare with model group, * P < 0.05.
The impact on mouse aging Content of MDA of 3.4 medicines of the present invention
From table 10-3, comparing with blank group, aging model group Content of MDA significantly raised (P < 0.05), with mould
Type group compares, and LIUWEI DIHUANG WAN group, medicine A group of the present invention the most substantially reduce (P < 0.05) to D group Content of MDA, contrasts medicine
Thing first group and drugs compared second group Content of MDA decrease, but compare with model group, there was no significant difference (P > 0.05).
As can be seen here, flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination by medicine of the present invention, create obvious one-plus-one working in coordination with more than two
Potentiation.
Table 10-3 medicine of the present invention on the impact of mouse aging serum MDA content (± s)
Note: compare with blank group, △ P < 0.05;Compare with model group, * P < 0.05.
The impact on mouse aging liver LF content of 3.5 medicines of the present invention
From table 10-4, comparing with blank group, aging model group liver LF content significantly raised (P < 0.05), with model group
Relatively, LIUWEI DIHUANG WAN group, the liver LF content of medicine A group of the present invention to D group the most substantially reduce (P < 0.05), drugs compared first group
Decrease with the liver LF content of drugs compared second group, but compare with aging model group, there was no significant difference (P > 0.05).Thus
Visible, flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination by medicine of the present invention, create the obvious one-plus-one Synergistic more than two
Effect.
Table 10-4 medicine of the present invention on the impact of mouse aging liver LF content (± s)
Note: compare with blank group, △ P < 0.05;Compare with model group, * P < 0.05.
4 conclusions
Originally test result indicate that: medicine of the present invention can reduce exhausted mining areas serum MDA, LF content, makes SOD in serum, CAT
Activity improves (P < 0.05);Drugs compared first and drugs compared second action effect are inconspicuous.As can be seen here, medicine of the present invention is by three
Seven flowers and Radix Notoginseng clip are applied in combination, and create the obvious one-plus-one synergistic function more than two.
Test 11: the experimentation of drug cosmetics skin care of the present invention
1 experiment material
1.1 animal
Male golden yellow gopher, weighs 100 ± 20g, Nanjing University of Traditional Chinese Medicine's Experimental Animal Center provide, and control of microorganisms is cleaning
Level.
1.2 medicine
Medicine A of the present invention: prepare with reference to the embodiment 1 in description of the invention detailed description of the invention.
Medicine B of the present invention: prepare with reference to the embodiment 2 in description of the invention detailed description of the invention.
Medicine C of the present invention: prepare with reference to the embodiment 11 in description of the invention detailed description of the invention.
Medicine D of the present invention: prepare with reference to the embodiment 12 in description of the invention detailed description of the invention.
Drugs compared first: prepare with reference to the embodiment 3 in description of the invention detailed description of the invention.
Drugs compared second: prepare with reference to the embodiment 4 in description of the invention detailed description of the invention.
Matched group: QINGRE ANCHUANG PIAN (Wanglaoji Pharmaceutical Co., Ltd., Guangzhou City, traditional Chinese medicines quasi-word Z44020578), mainly
Composition: creat extract, artificial Calculus Bovis, Flos Lonicerae, extract of taraxacum, extractum rhei, root of Cymbidium goeringii extractum, Fructus Gardeniae extractum, Margarita
Layer powder, Radix Glycyrrhizae.
Model group: normal saline.
1.3 key instruments and reagent
(Chinese science technology is big for LD4-2 type high speed centrifuge (Beijing Medical Centrifugal Machine Factory), GC-1200C radiation immunity arithmometer
Subject skill industry head office Zhong Jia photoelectric instrument branch company), dewaterer, the automatic embedding machine of biological tissue, stand sheet machine, microtome.
Testosterone (T), estradiol (E2) test kit by sino-america joint-venture Tianjin Jiuding Medical Biological Engineering Co., Ltd provide.
2 experimental techniques
2.1 animal packets
Male golden yellow gopher is raised 3 days, has no adverse reaction, and diet, drinking-water, movable normal person include experiment in.It is randomly divided into 8 groups,
Model group, QINGRE ANCHUANG PIAN group, medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention, medicine D group of the present invention,
Drugs compared first group, drugs compared second group, often organize each 10.
2.2 animals are administered
Starting gastric infusion, continuous gavage 30 days after raising 3 days, each group Golden Hamster is administered by below scheme respectively: model group:
With normal saline gavage, 2mL/ days;QINGRE ANCHUANG PIAN group: with the QINGRE ANCHUANG PIAN solution gavage of 0.200g/mL concentration, 2mL/
My god;Medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention, medicine D group of the present invention, drugs compared first group, contrast
Medicine second group respectively with the medicine A of the present invention of 0.800g/mL concentration, medicine B of the present invention, medicine C of the present invention, medicine D of the present invention,
The solution gavage of drugs compared first, drugs compared second, 2mL/ days.
2.3 model
Using Golden Hamster flank portion Flank organs as experimental model.
2.4 collection of specimens
Within 34th day, draw materials in experiment, fasting before drawing materials, freely drink water, after 24h, with extracing eyeball method blood sampling 3~5mL instillation examination
Pipe, separates serum censorship.After blood sampling, de-cervical vertebra puts to death animal, under strong illumination, with speckle on the right side of vernier caliper measurement
Big transverse diameter and maximum indulge footpath.Take off Golden Hamster flank portion Flank organs tissue immediately, cut about 1cm × 1cm piece of tissue with 10%
Fixing in formaldehyde fixative, paraffin embedding, section, HE dyes, in the Histological change of light Microscopic observation Flank organs.
2.5 index observation and methods
2.5.1 diet, drinking-water, defecation, mental status and the mobility of ordinary circumstance observed and recorded every day Golden Hamster.
First most Golden Hamster back wool is shaved with electric shaver when 2.5.2 measuring the size experiment beginning of Flank organs, will
After suslik is anesthetized with ether, under strong illumination, indulge footpath by maximum transverse diameter and the maximum of speckle on the right side of vernier caliper measurement.Experiment
At the end of again Mus hair is shaved to the greatest extent, by same method, on the right side of same position is measured, maximum transverse diameter and the maximum of speckle is vertical
Footpath.
2.5.3 taken Mus blood 4 DEG C, 3000r/min are centrifuged 10min by the mensuration of serum testosterone (T), separate serum censorship,
Using double antibody radioimmune method to detect, concrete operations are carried out by test kit description.Attached by Nanjing University of Traditional Chinese Medicine
Hospital's Isotope Lab has been assisted.
2.5.4 serum estradiol (E2) mensuration taken Mus blood 4 DEG C, 3000r/min are centrifuged 10min, separate serum and send
Inspection, uses liquid equilibrium competition radio immunoassay to detect, and concrete operations are carried out by test kit description.By in Nanjing
Medical pharmaceutical university Affiliated Hospital Isotope Lab has been assisted.
2.5.5 the microstructural change of Flank organs is observed by fixing for the Flank organs tissue in 10% formaldehyde fixative de-
After water, routine paraffin wax embeds, section, after HE dyeing, and the microstructure of light Microscopic observation sebaceous gland class.By Nanjing University of Traditional Chinese Medicine
Pathology Deparment of Affiliated Hospital has assisted.
3 experimental results
3.1 impacts on Golden Hamster Flank organs size
Before experimental result display medication, each treated animal Flank organs size through statistical disposition, difference not statistically significant (P >
0.05), there is comparability between each group;After medication, medicine A group of the present invention, medicine B group of the present invention, medicine C group of the present invention, basis
Invention medicine D group, drugs compared first group, there is significant difference (P < 0.05), especially between drugs compared second group and model group
It it is difference highly significant (P < 0.01) between medicine A to D group of the present invention and model group and matched group.As can be seen here, medicine of the present invention
Flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination by thing, create the obvious one-plus-one synergistic function more than two.It is shown in Table 11-1.
The table 11-1 impact (mm on Golden Hamster Flank organs size2,± s)
Note: compare with model group, * P < 0.05;**P<0.01;Compare with matched group, #P < 0.05, ##P < 0.01.
3.2 impacts on Hamster serum testosterone levels
Experimental result shows: after medication, testosterone levels compares, medicine A group of the present invention to D group, drugs compared first group, drugs compared
Having significant difference (P < 0.05, P < 0.01) between second group and model group, medicine A group the most of the present invention is to D group and model
Difference highly significant (P < 0.01) between group.As can be seen here, flower of Radix Notoginseng and Radix Notoginseng clip are applied in combination by medicine of the present invention, produce
The obvious one-plus-one synergistic function more than two.It is shown in Table 11-2.
After table 11-2 treatment each group Hamster serum testosterone (T) level comparison (± s)
Note: compare with model group, * P < 0.05, * * P < 0.01.
The impact on Hamster serum estradiol level of 3.3 medicines of the present invention
After medication, estradiol level compares, and has significant difference (P < 0.05) between medicine group of the present invention and model group.It is shown in Table
11-3。
Each group Hamster serum estradiol (E after table 11-3 treatment2) level comparison (± s)
Note: compare with model group, * P < 0.05.
4 conclusions
Using Golden Hamster flank portion Flank organs as experimental model, observe medicine of the present invention to Flank organs, serum hormone
Impact, result shows, medicine of the present invention can reduce Flank organs, make sebaceous gland thinning, and quality is loosened earlier above, reduces serum simultaneously
Testosterone, raising serum estradiol level.The modern medicine mechanism of Drug therapy acne of the present invention is understood by this Preliminary Experiment, from
Zooscopy angle demonstrates the effectiveness of its treatment acne.
And, experimental studies results is it is also shown that be used alone flower of Radix Notoginseng or be used alone the contrast medicine that Radix Notoginseng clip is made
The drug effectiveness of thing first and drugs compared second is the most inconspicuous, it can be seen that, medicine of the present invention is by flower of Radix Notoginseng and Radix Notoginseng clip
It is applied in combination, creates the obvious one-plus-one synergistic function more than two.
Test 12: the quality determining method of medicine of the present invention is studied
1 instrument and reagent
1.1 instrument
LC-20AT high performance liquid chromatograph (Shimadzu Corporation of Japan), SPD-20AVWD detector, LCSolution chromatograph works
Stand;Phenomenex-NH2 chromatographic column (4.6mm × 250mm, 5.0 μm, Guangzhou Féraud door scientific instrument company limited);UV-
2000 ultraviolet-visible spectrophotometers (FDAC);METTLERAE240 type electronic analytical balance (Shanghai prunus mume (sieb.) sieb.et zucc. Teller-Tuo Li
Multiple instruments company limited);YP10002 type electronic balance (Shanghai Yue Ping scientific instrument company limited).
1.2 reagent
Medicine of the present invention, prepares with reference to the embodiment 1 in description of the invention detailed description of the invention;Ginsenoside Rg1's reference substance,
Ginsenoside Rb1's reference substance, ginsenoside Re's reference substance, arasaponin R1 reference substance are purchased from China's pharmaceutical biological product calibrating
Institute's (for assay);Acetonitrile (Caledon company, chromatographically pure);Pure water (Watson distilled water);Methanol (Beijing chemical industry
Factory, analytical pure).
2 methods and result
2.1 chromatographic condition
Kromasil C18Chromatographic column (4.6mm × 250mm, 5 μm);Flowing is 82:18 acetonitrile-water for ratio mutually;Detection wavelength
203nm;Flow velocity 1mL min-1;Column temperature 30 DEG C;Sample size 10 μ L.Theoretical cam curve is calculated should be not less than by ginsenoside Rg1 peak
4000,
2.2 the preparation of mixing reference substance solution
Precision weighs ginsenoside Rg1, ginsenoside Rb1, Panax Notoginseng saponin R1Reference substance and ginsenoside Re are appropriate, add methanol system
Become every 1mL containing ginsenoside Rg10.4mg, ginsenoside Rb10.4mg, ginsenoside Re 0.1mg, Panax Notoginseng saponin R10.1mg's is mixed
Close solution, to obtain final product.
The preparation of 2.3 need testing solutions
Take drug powder 0.5g of the present invention, accurately weighed, accurate addition methanol 50mL, weighed weight, stand overnight, put 80 DEG C of water
Micro-boiling 2h is kept to let cool in bath, more weighed weight, supply the weight of less loss with methanol, shake up, filter, take subsequent filtrate, to obtain final product.
2.4 linear relationships are investigated
Accurate mixing reference substance solution 2,6,10,14,18,22,26, the 30 μ L that draws, injection high performance liquid chromatograph measures, record
Peak area.With reference substance peak area as vertical coordinate (Y), with sample introduction quality as abscissa (X), draw standard curve, obtain the side of recurrence
Journey.Result shows, ginsenoside Rg1At 0.804~12.060 μ g, ginsenoside Re is 0.200~3.000 μ g, ginsenoside
Rb1At 0.820~12.300 μ g, Panax Notoginseng saponin R1In 0.218~3.264 μ g range, its sample introduction quality is all good with peak area
Good linear relationship, the results are shown in Table 12-1.
4 kinds of saponin linear relationship measurement results of table 12-1
2.5 precision are investigated
The accurate mixing reference substance solution 10 μ L that draws, repetition sample introduction 6 times, measure peak area, calculate relative standard deviation RSD.Knot
Really, ginsenoside Rg1RSD=0.21%, the RSD=0.46% of ginsenoside Re, ginsenoside Rb1RSD=1.83%, Radix Notoginseng soap
Glycosides R1RSD=0.22%, show that method precision is good.
2.6 stability test
Need testing solution under accurate absorption " 2.3 " item, 0,1,2,4,8,12,24h sample introduction measures after the production, result ginsenoside
Rg1, ginsenoside Re, ginsenoside Rb1, Panax Notoginseng saponin R1The RSD of peak area is respectively 1.98%, and 1.73%, 2.06%, 2.43%;
Show that need testing solution is stable in 24h.
2.7 replica test
Precision weighs same batch drug powder of the present invention 6 parts, by legal system available test sample solution below " 2.3 " item, according to above-mentioned color
Spectral condition sample introduction measures, and records peak area, result ginsenoside Rg respectively1, ginsenoside Re, ginsenoside Rb1, arasaponin
R1The RSD of content is respectively 2.12%, and 0.49%, 0.90%, 1.22%, show that method repeatability is good.
2.8 average recovery tests
Precision weighs the drug powder of the present invention 6 parts of 0.2g known content, and precision adds reference substance ginsenoside Rg respectively1
4mg, ginsenoside Re 1mg, ginsenoside Rb1 4mg, Panax Notoginseng saponin R11mg, more accurate addition 50mL methanol, by " 2.3 " item
Lower section legal system available test sample solution.Measure according to above-mentioned chromatographic condition sample introduction.Result each composition mean sample recovery rate all conforms to
Ask, show that this assay method is reliable and stable.
Detailed description of the invention:
Embodiment 1: medicine A of the present invention
Prescription: flower of Radix Notoginseng 50g, Radix Notoginseng clip 50g
Preparation method:
(1) lyophilization:
1. the preparation of Radix Notoginseng clip lyophilization fine powder: take fresh Radix Notoginseng clip, remove impurity, clean, smash homogenate, by homogenate-
Freezing at 35 DEG C, after maintaining 8h, carries out lyophilization, and lyophilization controls to carry out at-35 DEG C, and the time is 70h;Freezing is done
Radix Notoginseng clip after dry is pulverized, and is sieved by 100 eye mesh screens, obtains Radix Notoginseng clip lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-35 DEG C
Lower freezing, after maintaining 8h, carries out lyophilization, and lyophilization controls to carry out at-35 DEG C, and the time is 70h;After lyophilization
Flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng clip breaking cellular wall superfine powder: use the Radix Notoginseng clip lyophilization that step (1) is obtained by jet mill
Fine powder carries out micronizing, obtains the Radix Notoginseng clip breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng clip breaking cellular wall superfine powder step (2) prepared and flower of Radix Notoginseng breaking cellular wall superfine powder mix
Close, obtain medicine of the present invention.
Embodiment 2: medicine B of the present invention
Prescription: flower of Radix Notoginseng 50g, Radix Notoginseng clip 50g
Preparation method: Radix Notoginseng clip and notogenseng pollen are broken into fine powder, mixing, obtain medicine B of the present invention.
Embodiment 3: drugs compared first
Prescription: flower of Radix Notoginseng 100g
Preparation method:
(1) preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-35 DEG C
Lower freezing, after maintaining 8h, carries out lyophilization, and lyophilization controls to carry out at-35 DEG C, and the time is 70h;After lyophilization
Flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm, i.e. drugs compared first.
Embodiment 4: drugs compared second
Prescription: Radix Notoginseng clip 100g
(1) preparation of Radix Notoginseng clip lyophilization fine powder: take fresh Radix Notoginseng clip, remove impurity, clean, smash homogenate, by homogenate-
Freezing at 35 DEG C, after maintaining 8h, carries out lyophilization, and lyophilization controls to carry out at-35 DEG C, and the time is 70h;Freezing is done
Radix Notoginseng clip after dry is pulverized, and is sieved by 100 eye mesh screens, obtains Radix Notoginseng clip lyophilization fine powder;
(2) preparation of Radix Notoginseng clip breaking cellular wall superfine powder: use the Radix Notoginseng clip lyophilization that step (1) is obtained by jet mill
Fine powder carries out micronizing, obtains the Radix Notoginseng clip breaking cellular wall superfine powder of below particle diameter 30 μm, i.e. drugs compared second.
Embodiment 5: medicine capsule of the present invention
Prescription: flower of Radix Notoginseng 950g, Radix Notoginseng clip 50g
Preparation method:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-40 DEG C cold
Freezing, after maintaining 5h, carry out lyophilization, lyophilization controls to carry out at-40 DEG C, and the time is 30h;By three after lyophilization
Seven pulverize, and are sieved by 100 eye mesh screens, obtain Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-30 DEG C
Lower freezing, after maintaining 10h, carries out lyophilization, and lyophilization controls to carry out at-30 DEG C, and the time is 120h;By lyophilization
After flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder step (2) prepared and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, adds
Enter starch, pelletize, granulate, load capsule, make capsule 1000.
Indication: improve immunity, antitumor, treatment hypertension, cardiovascular diseases, cerebrovascular, diabetes, hyperlipidemia,
Metabolism syndrome, cyclomastopathy, depression, defying age, looks improving and the skin nourishing.
Usage and dosage: oral, each 1~2, every day 2~3 times.
Embodiment 6: medicine capsule of the present invention
Prescription: flower of Radix Notoginseng 500g, Radix Notoginseng clip 500g
Preparation method:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-35 DEG C cold
Freezing, after maintaining 8h, carry out lyophilization, lyophilization controls to carry out at-35 DEG C, and the time is 75h;By three after lyophilization
Seven pulverize, and are sieved by 100 eye mesh screens, obtain Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-35 DEG C
Lower freezing, after maintaining 7h, carries out lyophilization, and lyophilization controls to carry out at-35 DEG C, and the time is 75h;After lyophilization
Flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder step (2) prepared and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, adds
Enter starch or dextrin, pelletize, granulate, load capsule, make capsule 1000.
Indication: improve immunity, antitumor, treatment hypertension, cardiovascular diseases, cerebrovascular, diabetes, hyperlipidemia,
Metabolism syndrome, cyclomastopathy, depression, defying age, looks improving and the skin nourishing.
Usage and dosage: oral, each 1~2, every day 2~3 times.
Embodiment 7: bolus of drug of the present invention
Prescription: 3 years raw sangqi ginsengs flower 100g, 3 years raw sangqi ginseng clip 900g
Preparation method:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-35 DEG C cold
Freezing, after maintaining 7h, carry out lyophilization, lyophilization controls to carry out at-35 DEG C, and the time is 70h;By three after lyophilization
Seven pulverize, and are sieved by 100 eye mesh screens, obtain Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-38 DEG C
Lower freezing, after maintaining 8h, carries out lyophilization, and lyophilization controls to carry out at-35 DEG C, and the time is 80h;After lyophilization
Flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder step (2) prepared and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, uses
Water pill, is dried, makes 10000 balls.
Indication: improve immunity, antitumor, treatment hypertension, cardiovascular diseases, cerebrovascular, diabetes, hyperlipidemia,
Metabolism syndrome, cyclomastopathy, depression, defying age, looks improving and the skin nourishing.
Usage and dosage: oral, each 10~20 balls, every day 2~3 times.
Embodiment 8: medicinal granule of the present invention
Prescription: 3 years raw sangqi ginsengs flower 900g, 3 years raw sangqi ginseng clip 100g
Preparation method:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-30 DEG C cold
Freezing, after maintaining 5h, carry out lyophilization, lyophilization controls to carry out at-30 DEG C, and the time is 30h;By three after lyophilization
Seven pulverize, and are sieved by 100 eye mesh screens, obtain Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-30 DEG C
Lower freezing, after maintaining 5h, carries out lyophilization, and lyophilization controls to carry out at-30 DEG C, and the time is 30h;After lyophilization
Flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder step (2) prepared and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, adds
Suitable amount of sucrose, dextrin, ethanol, make granule, is dried, granulate, makes granule 10000g.
Indication: improve immunity, antitumor, treatment hypertension, cardiovascular diseases, cerebrovascular, diabetes, hyperlipidemia, metabolism
Syndrome, cyclomastopathy, depression, defying age, looks improving and the skin nourishing.
Usage and dosage: oral, each 10~20g, every day 2~3 times.
Embodiment 9: medicine capsule of the present invention
Prescription: flower of Radix Notoginseng 800g, Radix Notoginseng clip 200g
Preparation method:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-40 DEG C cold
Freezing, after maintaining 10h, carry out lyophilization, lyophilization controls to carry out at-40 DEG C, and the time is 120h;After lyophilization
Radix Notoginseng is pulverized, and is sieved by 100 eye mesh screens, obtains Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-40 DEG C
Lower freezing, after maintaining 10h, carries out lyophilization, and lyophilization controls to carry out at-40 DEG C, and the time is 120h;By lyophilization
After flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder step (2) prepared and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, adds
Enter starch or dextrin, pelletize, granulate, load capsule, make capsule 1000.
Indication: improve immunity, antitumor, treatment hypertension, cardiovascular diseases, cerebrovascular, diabetes, hyperlipidemia,
Metabolism syndrome, cyclomastopathy, depression, defying age, looks improving and the skin nourishing.
Usage and dosage: oral, each 1~2, every day 2~3 times.
Embodiment 10: medicinal tablet of the present invention
Prescription: 3 years raw sangqi ginsengs flower 50g, 3 years raw sangqi ginseng clip 950g
Preparation method:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-30 DEG C cold
Freezing, after maintaining 10h, carry out lyophilization, lyophilization controls to carry out at-30 DEG C, and the time is 120h;After lyophilization
Radix Notoginseng is pulverized, and is sieved by 100 eye mesh screens, obtains Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-40 DEG C
Lower freezing, after maintaining 5h, carries out lyophilization, and lyophilization controls to carry out at-40 DEG C, and the time is 30h;After lyophilization
Flower of Radix Notoginseng pulverize, sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization fine powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder prepared by step (2) and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, pressure
Sheet, makes 1000, tablet.
Indication: improve immunity, antitumor, treatment hypertension, cardiovascular diseases, cerebrovascular, diabetes, hyperlipidemia,
Metabolism syndrome, cyclomastopathy, depression, defying age, looks improving and the skin nourishing.
Usage and dosage: oral, each 1~2, every day 2~3 times.
Embodiment 11: medicine C of the present invention
Prescription: flower of Radix Notoginseng 4.8g, Radix Notoginseng clip 96g
Preparation method: Radix Notoginseng clip and notogenseng pollen are broken into fine powder, mixing, obtain medicine C of the present invention.
Embodiment 12: medicine D of the present invention
Prescription: flower of Radix Notoginseng 96g, Radix Notoginseng clip 4.8g
Preparation method: Radix Notoginseng clip and notogenseng pollen are broken into fine powder, mixing, obtain medicine D of the present invention.
Embodiment 13: medicinal dropping ball of the present invention
Prescription: flower of Radix Notoginseng 50g, Radix Notoginseng clip 50g
Preparation method: taking flower of Radix Notoginseng 50g, Radix Notoginseng clip 50g pulverized 120 eye mesh screens, and obtained mixing fine powders, standby;Take 250g to gather
Ethylene glycol 4000, is heated to melting, and adds mixing fine powders under 80 DEG C of keeping warm modes, and stirring makes suspendible;Employing machinery will
Spice is gradient cooling in water dropper is added dropwise to the dimethicone 100 of 2 DEG C, and molding i.e. obtains drop pill.
Embodiment 14: drug injection of the present invention
Prescription: flower of Radix Notoginseng 50g, Radix Notoginseng clip 50g
Preparation method: flower of Radix Notoginseng 50g, Radix Notoginseng clip 50g, adds 800mL 50% alcohol heating reflux secondary, each 2 hours, merges
Alcohol extract, decompression recycling ethanol is also concentrated into relative density 1.04~1.05, adjusts pH 2~3 with 0.5mol/L phosphoric acid, stands, from
The heart, filtrate is adjusted pH 9~10 with 30% sodium hydroxide solution, with chloroform extraction 3 times, combined chloroform liquid, is reclaimed chloroform to without substantially
The thick paste of chloroform layer, chloroform concentrated solution is with 1%(V/V) aqueous hydrochloric acid solution regulation pH value, continuing to be concentrated into relative density is 1.25
~the extractum of 1.35, vacuum drying, obtain mixing dry extract;Mixing dry extract adds 8 times amount 1% hydrochloric acid solutions and boils 2 times, cold
But, filter, divide and take sour water, be evaporated to the extractum of density 1.25~1.35, be dried, obtain mixed extract;To mixed extraction
Injecting in thing and use water, regulation pH value, to 1.5~2.0, is stirred to dissolve, cold preservation, filters, and filtrate merges, and boils, and cold preservation is filtered
Crossing, filtrate adds activated carbon adsorption, decarburization, with 30% sodium hydroxide solution regulation pH value to 4.0~5.0, boils, cold preservation, filter
Cross, ultrafiltration, obtain medicinal liquid;Adding tween 80 2ml, benzyl alcohol 2ml, mixing to medicinal liquid, regulation pH value, to 3.0~4.0, injects
With water to 100ml, microfiltration, nitrogen charging embedding, in 2ml ampoule, i.e. obtains injection in 30 minutes in 100 DEG C of flowing steam sterilizations.
Claims (15)
1. a pharmaceutical composition, it is characterised in that this pharmaceutical composition is made up of the raw material of following weight portion: flower of Radix Notoginseng
0.5~10 weight portions, Radix Notoginseng 0.5~10 weight portion.
2. pharmaceutical composition as claimed in claim 1, it is characterised in that this pharmaceutical composition is by the raw material system of following weight portion
Become: flower of Radix Notoginseng 0.5 weight portion, Radix Notoginseng 10 weight portion.
3. pharmaceutical composition as claimed in claim 1, it is characterised in that this pharmaceutical composition is by the raw material system of following weight portion
Become: flower of Radix Notoginseng 10 weight portion, Radix Notoginseng 0.5 weight portion.
4. such as claim 1 pharmaceutical composition, it is characterised in that this pharmaceutical composition is made up of the raw material of following weight portion
: flower of Radix Notoginseng 5 weight portion, Radix Notoginseng 5 weight portion.
5. such as claim 1 pharmaceutical composition, it is characterised in that this pharmaceutical composition is made up of the raw material of following weight portion
: flower of Radix Notoginseng 3 weight portion, Radix Notoginseng 7 weight portion.
6. the pharmaceutical composition as described in any one in Claims 1 to 5, it is characterised in that flower of Radix Notoginseng is 3 years raw sangqi ginsengs
Flower, Radix Notoginseng is 3 years raw sangqi ginseng main roots or 3 years raw sangqi ginseng clips.
7. pharmaceutical composition as claimed in claim 6, it is characterised in that raw sangqi ginseng flower was for after micronizing or after breaking cellular wall in 3 years
3 years raw sangqi ginsengs flower, 3 years raw sangqi ginseng main roots after raw sangqi ginseng main root was micronizing in 3 years or after breaking cellular wall, 3 years raw sangqi ginsengs
3 years raw sangqi ginseng clips after clip is micronizing or after breaking cellular wall.
8. the pharmaceutical composition as described in any one in Claims 1 to 5, it is characterised in that this pharmaceutical composition is prepared as
Tablet, pill, powder, hard capsule, soft capsule, granule, oral liquid, drop pill, injection.
9. the pharmaceutical composition as described in any one in Claims 1 to 5, it is characterised in that the preparation of this pharmaceutical composition
Method is as follows:
(1) lyophilization:
1. the preparation of Radix Notoginseng lyophilization fine powder: take fresh Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate-30 DEG C~-
At 40 DEG C freezing, after maintaining 5h~10h, carry out lyophilization, lyophilization controls to carry out at-30 DEG C~-40 DEG C, and the time is
30h~120h;Radix Notoginseng after lyophilization is pulverized, is sieved by 100 eye mesh screens, obtain Radix Notoginseng lyophilization fine powder;
2. the preparation of flower of Radix Notoginseng lyophilization fine powder: take fresh flower of Radix Notoginseng, remove impurity, clean, smash homogenate, by homogenate at-30 DEG C
~freezing at-40 DEG C, after maintaining 5h~10h, carry out lyophilization, lyophilization controls to carry out at-30 DEG C~-40 DEG C, time
Between be 30h~120h;Flower of Radix Notoginseng after lyophilization is pulverized, is sieved by 100 eye mesh screens, obtain flower of Radix Notoginseng lyophilization thin
Powder;
(2) micronizing breaking cellular wall:
1. the preparation of Radix Notoginseng breaking cellular wall superfine powder: the Radix Notoginseng lyophilization fine powder using jet mill to obtain step (1) is carried out
Micronizing, obtains the Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
2. the preparation of flower of Radix Notoginseng breaking cellular wall superfine powder: use the flower of Radix Notoginseng lyophilization fine powder that step (1) is obtained by jet mill
Carry out micronizing, obtain the flower of Radix Notoginseng breaking cellular wall superfine powder of below particle diameter 30 μm;
(3) preparation of pharmaceutical preparation: Radix Notoginseng breaking cellular wall superfine powder step (2) prepared and the mixing of flower of Radix Notoginseng breaking cellular wall superfine powder, adopts
With the conventional method preparations shaping in Chinese materia medica.
10. pharmaceutical composition as claimed in claim 9, it is characterised in that in step (1), Radix Notoginseng is cryodesiccated with flower of Radix Notoginseng
Time is 60h~80h.
11. pharmaceutical compositions as claimed in claim 9, it is characterised in that superfine notoginseng powder and flower of Radix Notoginseng are surpassed in (3) by step
Micropowder mixes, and carries out full pressed powder, makes tablet.
12. pharmaceutical compositions as claimed in claim 9, it is characterised in that superfine notoginseng powder and flower of Radix Notoginseng are surpassed in (3) by step
Micropowder mixes, and carries out full powder and fills enteric coated capsule, makes enteric hard wafer.
The quality determining method of 13. 1 kinds of pharmaceutical compositions, this pharmaceutical composition is made up of the raw material of following weight portion: three
Seven spend 0.5~10 weight portions, Radix Notoginseng 0.5~10 weight portion, it is characterised in that this pharmaceutical composition is adopted and detected with the following method:
Employing high effective liquid chromatography for measuring:
(1) chromatographic condition: Kromasil C18Chromatographic column;Flowing is 70~90:10~30 acetonitrile-waters for ratio mutually;Detection wavelength
200~210nm;Flow velocity 0.5~2.0mL min-1;Column temperature 20~40 DEG C;Sample size 5~20 μ L;Theoretical cam curve presses Radix Ginseng soap
Glycosides Rg1Peak calculates should be not less than 4000;
(2) prepared by need testing solution: take drug powder of the present invention, accurately weighed, accurate addition methanol, and weighed weight was placed
At night, put and in water-bath, keep micro-boiling, let cool, more weighed weight, supply the weight of less loss with methanol, shake up, filter, take subsequent filtrate,
Obtain;
(3) preparation of reference substance solution is mixed: precision weighs ginsenoside Rg1, ginsenoside Rb1, Panax Notoginseng saponin R1Reference substance and
Ginsenoside Re is appropriate, adds methanol and makes mixed solution, to obtain final product;
(4) measure: take reference substance solution and need testing solution each 5~20 μ L sample introduction respectively, measure.
The quality determining method of 14. pharmaceutical compositions as claimed in claim 13, it is characterised in that this pharmaceutical composition uses
Following method detection: employing high effective liquid chromatography for measuring:
(1) chromatographic condition: Kromasil C18Chromatographic column;Flowing is 82:18 acetonitrile-water for ratio mutually;Detection wavelength 203nm;Stream
Speed 1mL min-1;Column temperature 30 DEG C;Sample size 10 μ L;Theoretical cam curve presses ginsenoside Rg1Peak calculates should be not less than 4000;
(2) prepared by need testing solution: take drug powder 0.5g of the present invention, accurately weighed, the accurate methanol 50mL that adds, weighed heavy
Amount, stands overnight, puts and keep micro-boiling 2h to let cool in 80 DEG C of water-baths, more weighed weight, supplies the weight of less loss with methanol, shakes up,
Filter, take subsequent filtrate, to obtain final product;
(3) preparation of reference substance solution is mixed: precision weighs ginsenoside Rg1, ginsenoside Rb1, Panax Notoginseng saponin R1Reference substance and
Ginsenoside Re is appropriate, adds methanol and makes every 1mL containing ginsenoside Rg10.4mg, ginsenoside Rb10.4mg, ginsenoside
Re0.1mg, Panax Notoginseng saponin R1The mixed solution of 0.1mg, to obtain final product;
(4) measure: take reference substance solution and each 10 μ L sample introductions of need testing solution respectively, measure.
15. pharmaceutical compositions as described in any one in Claims 1 to 5, it is characterised in that this pharmaceutical composition is in preparation
Improve immunity, antitumor, treatment hypertension, treatment cardiovascular diseases, treatment cerebrovascular, treatment diabetes, treatment hyperlipidemia,
Application in treatment metabolism syndrome, treatment cyclomastopathy, treatment depression, defying age, the medicine of looks improving and the skin nourishing or health product.
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CN107629106A (en) * | 2017-11-17 | 2018-01-26 | 钦州学院 | A kind of method that notoginsenoside is extracted from pseudo-ginseng |
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CN107629106A (en) * | 2017-11-17 | 2018-01-26 | 钦州学院 | A kind of method that notoginsenoside is extracted from pseudo-ginseng |
CN108065393A (en) * | 2017-12-08 | 2018-05-25 | 云南白药集团股份有限公司 | A kind of food or health food prevented and treat cardiovascular and cerebrovascular disease |
CN115671152A (en) * | 2021-07-30 | 2023-02-03 | 上海中医药大学附属龙华医院 | Application of panax notoginseng flower saponins in preparation of medicine for preventing and treating acute cerebral infarction |
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