CN108465002A - A kind of pharmaceutical composition that treating atherosclerosis and its application - Google Patents
A kind of pharmaceutical composition that treating atherosclerosis and its application Download PDFInfo
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Abstract
The present invention provides a kind of pharmaceutical composition for treating atherosclerosis, including dihydroquercetin and Flos Trollii extract, and pharmaceutically acceptable adjuvant, wherein as the content of the dihydroquercetin of active constituent and Flos Trollii extract in terms of molal weight, dihydroquercetin is 20% 35%, and Flos Trollii extract is 15% 60%.A kind of composition provided by the present invention, including dihydroquercetin and Flos Trollii extract have the function of reducing inflammatory factor, and can have the function that prevent and treat atherosclerosis.And both compounds derive from a wealth of sources, readily available, so it is the Related products such as food additives, health food and drug to be developed, have very high potentiality to be exploited.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for treating atherosclerosis and its applications.
Background technology
Atherosclerosis (aherosclerosis, AS) is a kind of common disease seriously endangering human health, is coronary disease
The main pathological basis of the ischemic angiocardiopathy and cerebrovascular diseases such as disease, cerebrovascular disease and thrombotic disease.Up to the present, the hair of AS
Interpretation of the cause, onset and process of an illness system is not yet fully apparent from, and there are a variety of theories, are related to Other Risk Factors, so that clinical lack effectively preventing drug.
A large amount of basis and clinical research show that it includes hyperlipidemia, hypertension, hyperglycemia (diabetes), height to cause the risk factor of AS
Fibrinogenemia, Homocysteine, hyperuricemia, obesity, renin-angiotensin-aldosterone system
(RAAS) activation, smoking, coagulation function hyperfunction (tissue factor, fibrin ferment), metabolism of trace elements imbalance (such as iron, copper, zinc, selenium,
Chromium, manganese, germanium etc.), autologous organisms active material (such as serotonin, NO, endothelin -1) metabolic disorder, chronic stress etc., and
Explain that the theory of AS pathogenesis has lipid infiltration theory, retention reaction theory, vascular smooth muscle cells clonal theory, oxidation to answer
Swash theory, the hyperfunction theory of platelet function, thrombosis theory, Ca2+Excess load theory, immunologic dysfunction theory, shearing are answered
Mechanics says, injury response theory, inflammation theory etc..In recent years, the incidence of cardiovascular and cerebrovascular diseases increases year by year, wherein by artery congee
The case fatality rate that sample hardening causes disease rises year by year, and prevention atherosclerosis becomes research hotspot.
Dihydroquercetin is present in as a kind of important flavone compound in various plants, in larch content compared with
Height, especially pesudotsuga taxifolia.In recent years, the presence of dihydroquercetin, especially grape, orange and grapefruit are had also discovered in fruit
In.Dihydroquercetin has the function of many important biological activities, including：1, anticancer：It is active to mouse leukemia P388,
The increase in life span of 150 and 100mg/kg is respectively 40% and 37%.2, antibacterial：To staphylococcus aureus, Escherichia coli, dysentery
Shigella and typhoid bacillus have stronger bacteriostasis.3, inhibit and activate a variety of enzymes to generate different physiological effects, such as
Inhibit the proliferation of common lymphocyte.4, antioxidant activity protects damage of the mitochondria from peroxy radicals, and to enzymatic activity
Without influence.5, red blood cell is protected, oxidative hemolysis is prevented.
Trollflower：Alias：The cold lotus of non-irrigated lotus, common nasturtium herb, land lotus, nonirrigated farmland lotus, globe-flower, golden pimple；Latin name：
Trollius chinensis Bunge are Ranunculaceae Trollius.《A Supplement to the Compendium of Materia Medica》It is middle meaning its " bitter, it is cold in nature,
It is nontoxic ", " aphtha can be controlled, larynx is swollen, superficial heat pingival atrophy, ear pain, mesh pain ", there is the effect of " improving eyesight, solution haze miasma ".According to the literature,
Contain flavonoids, organic acid, alkaloid and volatile oil etc. in trollflower.Flavonoids include water soluble ingredient Vitexina, orientoside,
The ingredients such as Quercetin；Organic acid includes liposoluble constituent proglobeflowery acid, vanillic acid, veratric acid, Li Lu amides, palmitic acid etc..
According to the literature, total flavones of tropaeolum (water soluble ingredient) has analgesia, antipyretic, anti-inflammatory effect；Trollflower liposoluble
Property ingredient (liposoluble ingredient) have inhibiting effect to gram-positive cocci and negative bacillus, the antibacterial of Pseudomonas aeruginosa is made
With particularly evident.Therefore complex chemical composition in trollflower, dose-effect relationship are complicated, effective part group is multiple, each effective part group it
Between interact, play anti-inflammatory, liver protection and other effects jointly.And current Flos Trollii extract is extractive of general flavone, and carry
It is crude extract to take object, and general flavone content is low, and pharmacological activity is weak.
In addition, having no but being applied in artery congee after combining dihydroquercetin and Flos Trollii extract with rational proportion at present
Effect in the prevention and treatment of sample hardening, there is not yet relevant report.
Invention content
The technical problem to be solved by the present invention is to overcome the deficiencies of existing technologies, provides and a kind for the treatment of atherosclerosis
Pharmaceutical composition, with good prevention and treatment effect, raw material supply is sufficient.
In order to solve the above technical problems, the present invention provides a kind of pharmaceutical composition for treating atherosclerosis, including two
Hydrogen Quercetin and Flos Trollii extract and pharmaceutically acceptable adjuvant, wherein the dihydroquercetin as active constituent
Content with Flos Trollii extract is in terms of molal weight, dihydroquercetin 20%-35%, Flos Trollii extract 15%-
60%.
The content of the dihydroquercetin and Flos Trollii extract is in terms of molal weight, dihydroquercetin 30%-35%,
Flos Trollii extract is 40%-55%.
The preparation method of the Flos Trollii extract includes the following steps：Take the dry trollflower raw material to constant weight, cold water
Steeped overnight, the dosage of cold water are at least 30 times of raw material dry weight, take the dregs of a decoction after dipping, the dregs of a decoction with buck circumfluence distillation 1~
2h, extraction time are 2~4 times, and buck dosage is 8~20 times of raw material dry weight, and the pH value range of buck is 8~9, merges buck
Extracting solution is concentrated under reduced pressure after adjusting pH value to neutrality, and the temperature of reduced pressure is not higher than 60 DEG C, is concentrated into the 1/20 of raw material dry weight
~1/10 must extract concentrate, and after extraction concentrate filtering, filtrate crosses low pole macroporous absorbent resin, washed with impurities, and 5~10%
Ethanol elution cleans, and 30%~50% ethanol elution at least eight column volume simultaneously collects eluent, and eluent is concentrated into no alcohol taste
Afterwards, it filters, is added in filtrate and is equivalent to the drying of raw material dry weight 1%~5% to the activated carbon of constant weight, 50~70 DEG C of heat preservation is simultaneously stirred
4~8h is mixed, is filtered after stirring, extractive of general flavone I is obtained after filtrate drying；The dregs of a decoction that buck extracted are taken, add 10~20
The middle polarity organic solvent diafiltration extraction of amount again, the flow velocity for being percolated extraction is collection 5~15mL percolates per minute, in collection
Isopolarity organic solvent percolate, dry after concentration, dried object adds water ultrasound to redissolve, and amount of water is the 15~20 of dried object weight
It measures again, ultrasonic time is at least 30min, is filtered after dissolving, polyamide resin column on filtrate, washing at least six column volume, 30%
~50% column volume of ethanol elution 4~6,80%~95% column volume of ethanol elution 3~4 collect 80%~95% ethyl alcohol
Eluent obtains total phenolic acid extract II, is uniformly mixed to get 50 after extractive of general flavone I and total phenolic acid extract II are crushed:
1 Flos Trollii extract.
The low pole macroporous absorbent resin includes D101, AB-8, HPD-100, HP-20 or ADS-8.
The middle polarity organic solvent includes acetone, ethyl acetate or chloroform.
The dosage form of the composition is one or more of tablet, capsule and pill.
The adjuvant is one or more of emulsifier, solubilizer, excipient or stabilizer.
Application of the pharmaceutical composition in preventing and treating atherosclerosis.
The atherosclerotic blood that described pharmaceutical composition is used to prevent and treat oxidative stress and chronic inflammation induces
Pipe lesion.
The advantageous effect that the present invention is reached：
Composition provided by the present invention can reduce IL-6 and TNF-α content in Hyperlipemia model rat serum.
IL-6 is the important inflammatory factor for participating in cardiovascular pathology, and TNF-α participates in the inflammatory reaction process of AS patches, can also coup injury
Blood vessel endothelium increases its permeability, and Blood Cholesterol is made to penetrate readily through inner membrance and sink to accumulating in inner membrance, forms AS lesions.This
The composition of invention can be by reducing IL-6 in serum, and TNF-α content increases patch to reduce the inflammatory reaction during AS
Stability, play the role of reducing and atherogenesis and fall off, reduce acute coronary syndrome,
Also, composition provided by the present invention has the pathological change of High fat diet rats Atherosclerosis Model bright
Aobvious inhibiting effect, to lipopolysaccharides joint high lipid food cause the carotid artery intima of Corn Bract Decotion, medial thickening and
Pathological change has obvious inhibiting effect, i.e., the artery congee that composition Endothelial Injury provided by the present invention or inflammation cause
Sample hardening has inhibiting effect.
Therefore, a kind of composition provided by the present invention, including dihydroquercetin and Flos Trollii extract, having reduces inflammation
The effect of inflammation factor, and can have the function that prevent and treat atherosclerosis.And both compounds derive from a wealth of sources, just
In acquisition, so it is the Related products such as food additives, health food and drug to be developed, there is very high potentiality to be exploited.
Specific implementation mode
The following examples are only intended to illustrate the technical solution of the present invention more clearly, and cannot limit the present invention with this
Protection domain.
Embodiment one
A kind of pharmaceutical composition for treating atherosclerosis, including dihydroquercetin and Flos Trollii extract and medicine
Acceptable adjuvant on, wherein as the dihydroquercetin of active constituent and the content of Flos Trollii extract with molal weight
Meter, dihydroquercetin 20%, Flos Trollii extract 60%.
Dihydroquercetin is commercially available high-purity dihydroquercetin monomer.
The preparation method of the Flos Trollii extract includes the following steps：Take the dry trollflower raw material to constant weight, cold water
Steeped overnight, the dosage of cold water are 30 times of raw material dry weight, and the dregs of a decoction, dregs of a decoction buck circumfluence distillation 1h, extraction are taken after dipping
Number is 2 times, and buck dosage is 8 times of raw material dry weight, and the pH value of buck is 8, merges buck extracting solution, adjusts pH value to neutrality
After be concentrated under reduced pressure, the temperature of reduced pressure is 60 DEG C, and being concentrated into the 1/20 of raw material dry weight must extract concentrate, extraction concentrate mistake
After filter, filtrate crosses D101 macroporous absorbent resins, washed with impurities, the removal of impurities of 5~10% ethanol elutions, 30%~50% ethanol elution 8
A column volume simultaneously collects the eluent, after eluent is concentrated into no alcohol taste, filters, and is added in filtrate and is equivalent to raw material dry weight 1%
Drying to constant weight activated carbon, heat preservation 50 DEG C simultaneously stir 4h, filtered after stirring, filtrate drying after extractive of general flavone
Ⅰ；The dregs of a decoction that buck extracted are taken, adds the acetone diafiltration extraction of 10 times of amounts, is percolated the flow velocity of extraction and is percolated for collection 5mL per minute
Liquid collects acetone percolate, dry after concentration, and dried object adds water ultrasound to redissolve, and amount of water is 15 times of amounts of dried object weight, is surpassed
The sound time is 30min, is filtered after dissolving, polyamide resin column on filtrate, and at least six column volume, 30% ethanol elution 4 are washed
Column volume, 80% column volume of ethanol elution 3 collect 80% ethanol eluate, obtain total phenolic acid extract II, general flavone is extracted
Object I and total phenolic acid extract II are uniformly mixed after crushing to get 50:1 Flos Trollii extract.
The dosage form of the composition is one or more of tablet, capsule and pill.
The adjuvant is one or more of emulsifier, solubilizer, excipient or stabilizer.
Application of the pharmaceutical composition in preventing and treating atherosclerosis.
The atherosclerotic blood that described pharmaceutical composition is used to prevent and treat oxidative stress and chronic inflammation induces
Pipe lesion.
The ultraviolet content assaying method of extractive of general flavone I：
The selection of Detection wavelength：Quercetin contrast solution is taken, debita spissitudo is diluted to, 10% liquor alumini chloridi 2 is added
ML, it is 7 potassium acetate-acetic acid buffer solution 4mL to adjust pH value, is shaken up, and is scanned under 200-600 nm wavelength after placing 30 min.
Obtain a length of 374nm of maximum absorption wave.
Standard curve：In the corresponding range of linearity, the Quercetin contrast solution of each concentration is sat with absorbance (A) to be vertical
Mark, concentration (μ g/mL) are abscissa, draw standard curve, linear equation is：Y=0.0266X+0.0092, R2=0.9997.
Assay data：It takes I 1mg of extractive of general flavone to 5mL measuring bottles, is settled to scale after ethyl alcohol dissolving, obtains for examination
Product solution takes 1mL test solutions, and 10% liquor alumini chloridi, 2 mL is added, and it is 7 potassium acetate-acetic acid buffer solution to adjust pH value
4mL does blank with coordinative solvent, measures content.Specifically it is shown in Table 1.
1 extractive of general flavone of table, I assay data
The ultraviolet content assaying method of total phenolic acid extract II：
The selection of Detection wavelength：Veratric acid contrast solution is taken, debita spissitudo is diluted to, ferric trichloride-potassium ferricyanide is added
Reagent colour development 10min, shakes up, and is scanned under 200-800 nm wavelength after placing 30 min.Obtain a length of 680nm of maximum absorption wave.
Standard curve：In the corresponding range of linearity, the veratric acid contrast solution of each concentration is sat with absorbance (A) to be vertical
Mark, concentration (μ g/mL) are abscissa, draw standard curve, linear equation is：Y=0.0083X-0.0103, R2=0.9999.
Assay data：It takes II 4mg of total phenolic acid extract to 10mL measuring bottles, is settled to scale after ethyl alcohol dissolving, obtains confession
Test sample solution takes 2mL test solutions, and 1% potassium ferricyanide solution 3mL is added, and is taken out after heating 10min in boiling water bath, cold
But to after room temperature, with 0.1mol/L salt acid for adjusting pH value to 4,2% ferric chloride solution 3mL is added, after standing 10min, ethyl alcohol
It is settled to 10mL and shakes up, blank is done with coordinative solvent, measures content.Specifically it is shown in Table 2.
2 total phenolic acid extract of table, II assay data
Embodiment two
A kind of pharmaceutical composition for treating atherosclerosis, including dihydroquercetin and Flos Trollii extract and medicine
Acceptable adjuvant on, wherein as the dihydroquercetin of active constituent and the content of Flos Trollii extract with molal weight
Meter, dihydroquercetin 35%, Flos Trollii extract 15%.
Dihydroquercetin is commercially available high-purity dihydroquercetin monomer.
The preparation method of the Flos Trollii extract includes the following steps：Take the dry trollflower raw material to constant weight, cold water
Steeped overnight, the dosage of cold water are 40 times of raw material dry weight, and the dregs of a decoction, dregs of a decoction buck circumfluence distillation 2h, extraction are taken after dipping
Number is 4 times, and buck dosage is 20 times of raw material dry weight, and the pH value of buck is 9, merges buck extracting solution, adjusts pH value into
Property after be concentrated under reduced pressure, the temperature of reduced pressure is 50 DEG C, and being concentrated into the 1/10 of raw material dry weight must extract concentrate, extraction concentrate
After filtering, filtrate crosses AB-8 macroporous absorbent resins, washed with impurities, the removal of impurities of 10% ethanol elution, 50% cylinder of ethanol elution 10
Eluent is accumulated and collects, after eluent is concentrated into no alcohol taste, filtration is added in filtrate and is equivalent to the drying of raw material dry weight 5% extremely
The activated carbon of constant weight, 70 DEG C of heat preservation are simultaneously stirred 8h, are filtered after stirring, and extractive of general flavone I is obtained after filtrate drying；Take buck
The dregs of a decoction extracted add the ethyl acetate diafiltration extraction of 20 times of amounts, and the flow velocity for being percolated extraction is collection 15mL percolates per minute,
Ethyl acetate percolate is collected, dry after concentration, dried object adds water ultrasound to redissolve, and amount of water is 20 times of amounts of dried object weight,
Ultrasonic time is 40min, is filtered after dissolving, polyamide resin column on filtrate, washes 7 column volumes, 50% column of ethanol elution 6
Volume, 95% column volume of ethanol elution 4 collect 95% ethanol eluate, total phenolic acid extract II are obtained, by extractive of general flavone
I and total phenolic acid extract II crush after be uniformly mixed to get 50:1 Flos Trollii extract.
The dosage form of the composition is one or more of tablet, capsule and pill.
The adjuvant is one or more of emulsifier, solubilizer, excipient or stabilizer.
Application of the pharmaceutical composition in preventing and treating atherosclerosis.
The atherosclerotic blood that described pharmaceutical composition is used to prevent and treat oxidative stress and chronic inflammation induces
Pipe lesion.
I content of extractive of general flavone of the present embodiment is 45.19%.II content of total phenolic acid extract is 71.48%.
Embodiment three
The present embodiment is differed only in embodiment 1：A kind of pharmaceutical composition for treating atherosclerosis, feature
It is：Including dihydroquercetin and Flos Trollii extract and pharmaceutically acceptable adjuvant, wherein as active constituent
The content of dihydroquercetin and Flos Trollii extract is in terms of molal weight, dihydroquercetin 30%, and Flos Trollii extract is
40%.
Example IV
The present embodiment is differed only in embodiment 1：A kind of pharmaceutical composition for treating atherosclerosis, feature
It is：Including dihydroquercetin and Flos Trollii extract and pharmaceutically acceptable adjuvant, wherein as active constituent
The content of dihydroquercetin and Flos Trollii extract is in terms of molal weight, dihydroquercetin 33%, and Flos Trollii extract is
55%.
The present invention can also be prepared by the way that the dosage forms such as tablet, capsule and pill are made in the pharmaceutical composition
Its drug effect is verified at solution, and by the following test of pesticide effectiveness.
Effect experiment example：
One, influence of the composition to High fat diet rats Atherosclerosis Model
1. experimental method
SD rats 50 are lain on the back after anesthesia on operating table, detaching arteria carotis communis, and folder closes proximal part and distal end temporarily hinders
Clinopodium polycephalum.Seal wire is punctured into lumen of vessels, 3 times is twitched back and forth to damage inner membrance, extracts seal wire out, at biogum closing puncture.
Rat is randomly divided into model group, composition group after inner film injury is performed the operation, according to weight, daily oral medication 1 time, and volume is administered
For 10ml/kg, composition group gives the composition 0.5g/kg in embodiment one, and model group is given corresponding physiological saline, separately taken
10 normal rats, as blank control group.In addition to blank group, other each groups give high lipid food (3% cholesterol, 0.5% courage
Sour sodium, 10% lard, 0.2% propylthiouracil, 5% white sugar, 81.3% basal feed) it raises 12 weeks, give within every 4 weeks dimension life
Plain D3300,000 U/kg of injection im1 times.
Orbital venous plexus takes blood after the last administration, and serum is centrifuged after standing 30min.Blood is measured according to kit method
The content of TC, TG, LDL and HDL in clear；ELISA method measures IL-6 in serum, the content of TNF-α.Take rat right carotid
It organizes about 2cm, after the intravascular remaining blood of 4 DEG C of 0.9% normal saline flushing, sets and fix one week in 10% formalin solution
Afterwards, specimens paraffin embedding slices, HE dyeing.The histological change of light microscopic observation arterial wall (inner membrance, middle film).And according to lesion weight
Degree, sxemiquantitative successively is "+" (slight), and " ++ " (moderate), " +++ " (severe), no pathological tissues are then labeled as "-", and root
It scores according to semi-quantitative results statistical pathology.
2. result
TC in model group serum, TG, the content of HDL-C, LDL-C have significant difference (P ＜ compared with blank group
0.05 or P ＜ 0.01).TC in composition group animal blood serum, the content of TG, LDL-C reduce, and HDL-C contents increase, and and mould
Type group compares, and has significant difference (P ＜ 0.05), is shown in Table 3.
Influence (x ± s, n=10) of 3 composition of table to atherosclerotic rat blood fat
Compared with blank group, * P ＜ 0.05, * * P ＜ 0.01；Compared with model group,#P ＜ 0.05.
The content of IL-6 in model group serum, TNF-α increase, with significant difference (P ＜ compared with blank group
0.01).IL-6 in composition group animal blood serum, the content of TNF-α compared with model group, have significant difference (P ＜ 0.05 or
P ＜ 0.01), it is shown in Table 4.
4 composition of table is to IL-6 in atherosclerotic rat serum, the influence (x ± s, n=10) of TNF-α
Compared with blank group, * * P ＜ 0.01；Compared with model group,#P ＜ 0.05,##P ＜ 0.01.
Pathological examination is the results show that model group endotheliocytic swelling, deformation, missing are notable；Endarterium thickened degree is bright
It is aobvious；Foam cells and lipidosis are apparent；Inner membrance and middle film macrophage content obviously increase, and composition can improve artery congee
Sample hardens the endothelial function of rat artery blood vessel, hence it is evident that reduces the macrophage quantity in artery lesion；To atherosclerotic plaque
Formation and inflammation have apparent intervention effect, hence it is evident that reduce arteria carotis communis Histopathology detection in histological scores water
It is flat, with significant difference (P ＜ 0.05) compared with model group.Show that composition has centainly experimental atherosclerosis in rats
Therapeutic effect is shown in Table 5.
Influence (x ± s, n=10) of 5 composition of table to atherosclerotic rat arteria carotis communis Histopathology
Compared with blank group, * * P ＜ 0.01；Compared with model group,#P ＜ 0.05.
This result of study is shown, after giving composition, the content reduction of TC in modeling rat blood serum, TG, LDL-C are unknown
Aobvious, HDL-C contents increase, and IL-6 and TNF-α content reduce in serum, prompting combination object may by reducing IL-6 in serum,
TNF-α content increases the stability of patch to reduce the inflammatory reaction during AS, and it is comprehensive then to play reduction acute coronary
The effect that simulator sickness occurs.
Two, composition causes lipopolysaccharides (LPS) joint high lipid food the influence of Corn Bract Decotion
1. experimental method
New Zealand White Rabbit is randomly divided into 3 groups, single cage is raised, every group 6 after Animal Lab. adaptability is raised 1 week.It is empty
White control group：Basal feed is fed, 1 times a week auricular vein injecting normal saline 1mL, oral to give physiological saline；Model pair
According to group：High lipid food (79.5% basal feed, 15.0% yolk powder, 0.5% cholesterol, 5.0% lard) is fed, 1 times a week
Auricular vein injects 1 000ng/kg of LPS, oral to give physiological saline；Composition group：High lipid food is fed, 1 times a week ear edge
LPS 1000ng/kg are injected intravenously, and takes orally and gives composition 0.4g/kg.
It raised for 8 weekends, is fixed on operating table after being anaesthetized with 3% yellow Jackets of mass fraction, aorta is taken out in dissection,
It with normal saline flushing, is put into 10% neutral formalin of volume fraction and fixes 4h or more, cut off and modified along horizontal axis with eye scissors
Vascular tissue is put into embedded box dehydration, transparent, paraffin embedding, slice step by step, and HE is dyed, neutral gum mounting, under microscope
It observes and images, according to lesion light and heavy degree, sxemiquantitative successively is "+" (slight), and " ++ " (moderate), " +++ " (severe) is disease-free
Become tissue and be then labeled as "-", and is scored according to semi-quantitative results statistical pathology.Under 10 × 10 power microscopes, with 1/10 mesh
Mirror micrometer measures Intimamedia thickness at the arch of aorta.
2. experimental result
Blank control group rabbit endangium is thin and smooth, middle film smooth muscle cell marshalling, and outer membrane is loose knot
Tissue is formed, model group rabbit inner membrance obviously thickens, and has a large amount of foam cells and AS patches, has inflammatory cell infiltration around patch,
Middle film obviously thickens, and smooth muscle cell arrangement is mixed and disorderly at nearly inner membrance, and outer membrane is loose connective tissue, composition group rabbit endangium
It sexually revises and is substantially reduced with the pathology of middle film, pathology comprehensive score reduces.
Influence (x ± s, n=6) of 6 composition of table to Corn Bract Decotion arteria carotis communis histological scores
Compared with blank group, * * P ＜ 0.01；Compared with model group,#P ＜ 0.05.
Inner film thickness and media thickness increase at each model group rabbit aorta bow, more significant with blank control group
Difference (P ＜ 0.01), inner film thickness and media thickness are more substantially reduced with model group at composition group rabbit aorta bow, and
Significant difference (P ＜ 0.01, P ＜ 0.05).
Influence (x ± s, n=of 7 composition of table to Corn Bract Decotion arteria carotis communis inner membrance and media thickness
6)
Compared with blank group, * * P ＜ 0.01；Compared with model group,#P ＜ 0.05,##P ＜ 0.01.
Therefore, composition of the invention causes lipopolysaccharides joint high lipid food in the strength artery of Corn Bract Decotion
Film thickens and pathological change has obvious inhibiting effect.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the technical principles of the invention, several improvement and deformations can also be made, these improvement and deformations
Also it should be regarded as protection scope of the present invention.
Claims (9)
1. a kind of pharmaceutical composition for treating atherosclerosis, it is characterised in that：It is extracted including dihydroquercetin and trollflower
Object and pharmaceutically acceptable adjuvant, wherein as the dihydroquercetin of active constituent and the content of Flos Trollii extract
In terms of molal weight, dihydroquercetin 20%-35%, Flos Trollii extract 15%-60%.
2. the pharmaceutical composition for the treatment of atherosclerosis according to claim 1, it is characterised in that：The dihydro quercitrin
The content of element and Flos Trollii extract is in terms of molal weight, dihydroquercetin 30%-35%, Flos Trollii extract 40%-55%.
3. the pharmaceutical composition for the treatment of atherosclerosis according to claim 1, it is characterised in that：The trollflower carries
The preparation method of object is taken to include the following steps：The dry trollflower raw material to constant weight is taken, cold water steeped overnight, the dosage of cold water is extremely
It is 30 times of raw material dry weight less, it is 2 ~ 4 times that the dregs of a decoction, dregs of a decoction buck 1 ~ 2h of circumfluence distillation, extraction time are taken after dipping, buck
Dosage is 8 ~ 20 times of raw material dry weight, and the pH value range of buck is 8 ~ 9, merges buck extracting solution, subtracts after adjusting pH value to neutrality
The temperature of pressure concentration, reduced pressure is not higher than 60 DEG C, and concentrate must be extracted by being concentrated into the 1/20 ~ 1/10 of raw material dry weight, and extraction is dense
After the filtering of contracting liquid, filtrate crosses low pole macroporous absorbent resin, washed with impurities, and 5 ~ 10% ethanol elutions clean, and 30% ~ 50% ethyl alcohol is washed
De- at least eight column volume simultaneously collects eluent, and after eluent is concentrated into no alcohol taste, filtration is added that be equivalent to raw material dry in filtrate
1% ~ 5% drying is weighed to the activated carbon of constant weight, 50 ~ 70 DEG C of heat preservation is simultaneously stirred 4 ~ 8h, is filtered after stirring, after filtrate drying
Extractive of general flavone I；The dregs of a decoction that buck extracted are taken, the middle polarity organic solvent diafiltration extraction of 10 ~ 20 times of amounts, diafiltration is added to carry
The flow velocity taken is collection 5 ~ 15mL percolates per minute, collects middle polarity organic solvent percolate, dry after concentration, dried object
Water ultrasound is added to redissolve, amount of water is 15 ~ 20 times of amounts of dried object weight, and ultrasonic time is at least 30min, is filtered after dissolving, filter
Polyamide resin column on liquid washes at least six column volume, 30% ~ 50% column volume of ethanol elution 4 ~ 6,80% ~ 95% ethanol elution
3 ~ 4 column volumes collect 80% ~ 95% ethanol eluate, obtain total phenolic acid extract II, extractive of general flavone I and total phenolics are carried
It is uniformly mixed to get 50 after taking object II to crush:1 Flos Trollii extract.
4. the pharmaceutical composition for the treatment of atherosclerosis according to claim 3, it is characterised in that：The low pole is big
Macroporous adsorbent resin includes D101, AB-8, HPD-100, HP-20 or ADS-8.
5. the pharmaceutical composition for the treatment of atherosclerosis according to claim 3, it is characterised in that：The middle polarity
Organic solvent includes acetone, ethyl acetate or chloroform.
6. the pharmaceutical composition for the treatment of atherosclerosis according to claim 1, it is characterised in that：The composition
Dosage form is one or more of tablet, capsule and pill.
7. the pharmaceutical composition for the treatment of atherosclerosis according to claim 1, it is characterised in that：The adjuvant is
One or more of emulsifier, solubilizer, excipient or stabilizer.
8. application of the pharmaceutical composition according to claim 1 in preventing and treating atherosclerosis.
9. application according to claim 8, it is characterised in that：Described pharmaceutical composition is for preventing and treating oxidative stress
Become with the atherosclerotic vascular disease that chronic inflammation induces.
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| CN201810641755.8A CN108465002A (en) | 2018-06-21 | 2018-06-21 | A kind of pharmaceutical composition that treating atherosclerosis and its application |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810641755.8A CN108465002A (en) | 2018-06-21 | 2018-06-21 | A kind of pharmaceutical composition that treating atherosclerosis and its application |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010129138A2 (en) * | 2009-04-27 | 2010-11-11 | Limerick Biopharma | Phosphorylated and phosphonated pyrone analogs for therapeutic treatment |
| CN105263340A (en) * | 2012-04-10 | 2016-01-20 | 弗拉维特普雷有限公司 | Method of using nutritional compounds dihydroquercetin (taxifolin) and arabinogalactan in combination with dihydroquercetin (taxifolin) to reduce and control cardiometabolic risk factors associated with metabolic syndrome and hypercholesterolemia |
| WO2016096781A1 (en) * | 2014-12-15 | 2016-06-23 | Institut National De La Recherche Agronomique (Inra) | Process for obtaining a composition enriched with dihydroquercetin or with tannins |
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2018
- 2018-06-21 CN CN201810641755.8A patent/CN108465002A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010129138A2 (en) * | 2009-04-27 | 2010-11-11 | Limerick Biopharma | Phosphorylated and phosphonated pyrone analogs for therapeutic treatment |
| CN105263340A (en) * | 2012-04-10 | 2016-01-20 | 弗拉维特普雷有限公司 | Method of using nutritional compounds dihydroquercetin (taxifolin) and arabinogalactan in combination with dihydroquercetin (taxifolin) to reduce and control cardiometabolic risk factors associated with metabolic syndrome and hypercholesterolemia |
| WO2016096781A1 (en) * | 2014-12-15 | 2016-06-23 | Institut National De La Recherche Agronomique (Inra) | Process for obtaining a composition enriched with dihydroquercetin or with tannins |
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| VLADIMIR A等: "Myeloperoxidase/nitrite-mediated lipid peroxidation of low-density lipoprotein as modulated by flavonoids", 《FEBS LETTERS》 * |
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Application publication date: 20180831 |