CN108159146A - A kind of Chinese medicine composition and preparation method for reducing blood lipid - Google Patents

A kind of Chinese medicine composition and preparation method for reducing blood lipid Download PDF

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CN108159146A
CN108159146A CN201810104820.3A CN201810104820A CN108159146A CN 108159146 A CN108159146 A CN 108159146A CN 201810104820 A CN201810104820 A CN 201810104820A CN 108159146 A CN108159146 A CN 108159146A
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extraction process
chinese medicine
group
extraction
medicine composition
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CN108159146B (en
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徐建
白冰
徐云
许艳茹
张显涛
李志宝
徐艳霞
何帆
陈德峰
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Xiuzheng Pharmaceutical Group Changchun High-new Pharmaceutical Co.,Ltd.
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JILIN XIUZHENG PHARMACEUTICAL NEW MEDICINE DEVELOPMENT Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/73Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/734Crataegus (hawthorn)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/482Cassia, e.g. golden shower tree
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/62Nymphaeaceae (Water-lily family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/70Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704Polygonum, e.g. knotweed
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation 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
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

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  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

The present invention relates to drug fields, more particularly to drug and its extraction process.Water is selected to avoid a large amount of uses of organic solvent, Environmental Safety as solvent in the extraction process.In addition, being extracted using cryogenic high pressure difference, active ingredient is made to extract to the greatest extent, improve production efficiency.Pharmacological experiments show, mouse high cholesterol caused by Chinese medicine composition can be substantially reduced egg-nog made from extraction process provided by the invention, it improves significantly to experimental atherosclerosis rats hemorheology tool, whole blood viscosity can be reduced, cholesterol, triglyceride and the low-density lipoprotein content in serum are reduced, there is apparent effect for reducing blood fat.Effect for reducing fat with Chinese medicine composition of the present invention under dosage is apparent compared with JIANGZHINING KELI.

Description

A kind of Chinese medicine composition and preparation method for reducing blood lipid
Technical field
The present invention relates to drug field, more particularly to a kind of Chinese medicine compositions and preparation method for reducing blood lipid.
Background technology
Due to the raising of quality of life, hyperglycemia, hyperlipidemia, hypertension, which are increasingly becoming, threatens the three of human health to kill greatly Hand, and the trend of rejuvenation is presented, seriously affect people’s lives quality.And most of hyperlipemic patients have simultaneously Hypertension symptom is easy to cause the generation of apoplexy, angiocardiopathy, if cannot prevent and treat early, consequence is very serious.
Hyperlipemia can be divided into primary and secondary two class.In Patients With Primary Hyperlipoidemia is related with congenital and heredity, is Due to single-gene defect or polygenes defect, portable, the enzyme activity apolipoprotein caused by abnormal that participation lipoprotein is made to transport and be metabolized, Or it is caused due to environmental factor (diet, nutrition, drug) and by unknown mechanism.1. inherent cause:Heredity can be by a variety of Mechanism causes hyperlipidemia, certain possible lists be happened at cellular level it is famous on, want to buy and be mainly shown as cell surface fat egg The defects of polymeric immunoglobulin receptor defect and intracellular certain enzymes (the defects of such as lipoprotein lipase or shortage), may also occur at lipoprotein or On the molecule of apolipoprotein, mostly and to be caused due to gene defect.2. dietary factor:Dietary factor effect checks more eternal abdomen Chamber is complicated, and patients with hyperlipoproteinemia has sizable ratio in being hospitalized be closely related with dietary factor.Secondary high blood Fat disease is since those caused by other intermediate primary diseases, these diseases include:Diabetes, hepatopathy, thyroid disease, kidney disease Disease, pancreas, obesity, glycogenic thesaurismosis, gout, Addision's disease, Cushing's syndrome, dysglobulinemia etc..1. diabetes Have between glycometabolism and fat metabolism in human body with hyperlipoprotememia it is close contact, only clinical research is found, about 40% diabetic secondary can cause hyperlipidemia.2. hepatopathy and hyperlipoprotememia:The confirmation of modern medicine study data, The many substances of fatigue are processed, produce and decompose, drain in liver including lipid and lipoprotein etc..Once liver is ill Medical insurance, then lipid and lipoprotein metabolism will also get muddled.3. obesity and hyperlipoprotememia:Clinic study data Show that obesity most Chang Jifa causes blood triglyceride content to increase, some patientss cholesterolemia content first may also can increase Height is mainly shown as iv type hyperlipoprotememias too much, is secondly iib type hyperlipoprotememias.Secondary hyperlipemia may be used also Can with other factors such as the age, gender, season, drink, smoke, diet, physical exertion, stress, have emotional activity It closes.
Clinically the drug of common reducing blood lipid has Statins, is inhibitor of cholesterol biosynthetic enzyme, is clinical at present Most widely used one kind lipid-regulation medicine and the at present key agents for the treatment of hypercholesterolemia, there are stomach and intestine for such drug Reaction, headache, musclar toxicity is likely to occur when being shared with other fat-reducing medicaments;Fibrates are mainly used for hypertriglyceridemia Or triglycerides raising based on mixed type hyperlipidemia mass formed by blood stasis, the common adverse reaction of the medicine be gastrointestinal reaction, nausea, diarrhea, Severe patient can lead to hepatic lesion.Therefore, although these medicines have the effect of certain, but side effect is larger, for fitness compared with For weak crowd, be not suitable for using.
For Western medicine, Chinese medicine have safety, few side effects, it is not damaged to gastrointestinal tract, liver kidney is stimulated it is small excellent Point, has been to be concerned by more and more people.
JIANGZHINING KELI is made of hawthorn, prepared fleece flower root, cassia seed, four taste Chinese medicine of lotus leaf.Its major function is reducing blood lipid, Soften blood vessel.For enhancing coronary flow cycle.Arrhythmia and hyperlipemia.Its prescription, which records, at present issues mark in portion Quasi- WS3-B-2549-97.
In current preparation process, hawthorn is more containing sugar after water decocts, and is not easy to filter after concentration, is not easy drying, causes The moisture absorption repeatedly influences production efficiency.And largely using organic solvent in extraction process, a large amount of waste liquor contamination environment are unfavorable for work Industry metaplasia is produced.
Invention content
In view of this, the present invention provides a kind of Chinese medicine compositions and preparation method for reducing blood lipid.In extraction process Water is selected to avoid a large amount of uses of organic solvent, Environmental Safety as solvent.In addition, extracting using cryogenic high pressure difference, make to have Effect ingredient extracts to the greatest extent, improves production efficiency.Pharmacological experiments show extraction process system provided by the invention Mouse high cholesterol caused by the Chinese medicine composition obtained can be substantially reduced egg-nog, to experimental atherosclerosis rats blood stream Become learning aid to improve significantly, whole blood viscosity can be reduced, reduce cholesterol, triglyceride and low density lipoprotein in serum Protein content has apparent effect for reducing blood fat.Effect for reducing fat with Chinese medicine composition of the present invention under dosage is compared with JIANGZHINING KELI Significantly.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme:
A kind of extraction process of drug of the present invention, includes the following steps:
Bulk pharmaceutical chemicals include 500~600 parts by weight of hawthorn, 10~35 parts by weight cassia seed of prepared fleece flower root, 10~35 parts by weight, 50~100 parts by weight of lotus leaf;
Step 1:Bulk pharmaceutical chemicals is taken to be mixed after pre-processing with water;
Step 2:In 20~30Mpa, 30~60min of extraction for the first time, 30 are extracted then at 40~50Mpa second~ 60min;
Step 3:The extract that step 2 obtains is taken to collect filtrate through separation of solid and liquid.
In some specific embodiments of the present invention, the mass ratio of the bulk pharmaceutical chemicals and water is 1:(10~20).
The present invention some specific embodiments in, the bulk pharmaceutical chemicals mixed with water the time be 50~70min.
In some specific embodiments of the present invention, the temperature of the first time extraction is 0~10 DEG C.
In some specific embodiments of the present invention, the temperature of second of extraction is 0~10 DEG C.
In some specific embodiments of the present invention, separation of solid and liquid described in step 3 is centrifugation or filtering;The centrifugation Rotating speed for 8000~12000rpm, the time of the centrifugation is 10~30min.
In some specific embodiments of the present invention, the step of filtrate is taken to repeat step 2, step 3, institute are further included The number for stating repetition is at least 1 time.
The present invention some specific embodiments in, repeat step 2, step 3 the step of after further include merging filtrate, The step of filtering;It is described to be filtered into micro-filtration;
The aperture for the film that the micro-filtration uses is 0.45~1.0 μm.
In some specific embodiments of the present invention, the micro-filtration is specially that the filtrate after merging is taken to cross microfiltration membranes, is added Water makes to be no less than 2 times of the volume of the filtrate after the merging through liquid measure, and the content for filtering into dope solid content is no less than 20% (w/w);Microfiltration membranes are rinsed with water, cleaning solution is collected and is mixed with the dope.
In some specific embodiments of the present invention, the time of the filtering is no more than 6h, and the flow of the filtering drops Low amplitude is no less than 50%.
The present invention some specific embodiments in, in the filtering content of solid content be 10~20% (w/w), 50 The relative density measured at~80 DEG C is 1.05~1.20.
The present invention also provides drugs made from the extraction process.
Water is selected to avoid a large amount of uses of organic solvent, environmental protection peace as solvent in extraction process provided by the invention Entirely.In addition, being extracted using cryogenic high pressure difference, active ingredient is made to extract to the greatest extent, improve production efficiency.Pharmacological research The result shows that the high courage of mouse caused by Chinese medicine composition can be substantially reduced egg-nog made from extraction process provided by the invention Sterol improves significantly to experimental atherosclerosis rats hemorheology tool, can reduce whole blood viscosity, reduces blood Cholesterol, triglyceride and low-density lipoprotein content in clear have apparent effect for reducing blood fat.With in the present invention under dosage The effect for reducing fat of drug composition is apparent compared with JIANGZHINING KELI.
Specific embodiment
The invention discloses a kind of Chinese medicine composition and preparation method for reducing blood lipid, those skilled in the art can borrow Reflect present disclosure, is suitably modified technological parameter realization.In particular, it should be pointed out that all similar substitutions and modifications are to this field It is it will be apparent that they are considered as being included in the present invention for technical staff.The method of the present invention and application have passed through Preferred embodiment is described, related personnel significantly can not depart from the content of present invention, in spirit and scope to described herein Methods and applications be modified or suitably change with combining, to realize and using the technology of the present invention.
1. experiment material
1.1 test sample:1~3 Chinese medicine composition of the embodiment of the present invention, is carried by Jilin Revision Medicine New Medicine Development Co., Ltd For.
Control group 1:Chinese medicine composition made from comparative example 1;
Control group 2:Chinese medicine composition made from comparative example 2;
1.2 reagent
Yolk emulsion:75% yolk normal saline suspension;High lipoprotein emulsion:20% cholesterol, 1% propylthiouracil (PTU), 40% lard, 20% pig gall acid sodium solution (a concentration of l0%), 1% tween, 2% propylene glycol add distilled water to 100mL compositions;
Atorvastatin calcium:Pfizer inc, specification:20mg/ pieces, lot number:M97466;
Serum total cholesterol (TC);Triglyceride (TG);High-density lipoprotein cholesterol (HDL-cho) and low-density lipoprotein White cholesterol (LDL-cho) assay kit, is purchased from Nanjing and builds up Bioengineering Research Institute.
2. experimental animal
Wistar rats, male, 240-260g;ICR mouse, half male and half female, 18-22g, quality certification number:SCXK (Ji) 2014-0003.Source:This experimental animal technology Co., Ltd of Changchun hundred million, experimental animal production licence number:SCXK (Ji) 2014-0003.Licence issuing authority:Jilin Department of Science and Technology of Shanxi Province, the certification of fitness number:37009200005847.
3. instrument
Electronic balance, Minqiao Precision Scientific Instruments Co., Ltd., Shanghai, JA1103N;LBY-N6 automatic blood rheologic meters, Pulisheng Instruments Co., Ltd., Beijing;Microplate reader (SMP500-18272-LSIO, Manufactured in China Designed in California USA);LBY-NJ4 platelet aggregation instruments, thyrite health letter.
Raw materials used and reagent can be bought by market in drug provided by the invention and its extraction process.
With reference to embodiment, the present invention is further explained:
Embodiment 1
Formula:Hawthorn 55kg prepared fleece flower root 2.5kg cassia seed 1kg lotus leaves 5kg
(1) it is sieved after taking the pulverizing medicinal materials of formula ratio by No.1 (10 mesh)~No. tetra- (65 mesh);
(2) above-mentioned weight medicinal powder is taken to mix, 10 times of amount water is added to be stirred 60min, make fully to soak;
(3) it extracts for the first time:It sets low in warm High Pressure Difference extractor, in 5 DEG C of cycle extractions 2 times, first time 30Mpa, extraction 60min, second of 40Mpa extract 45min;
(4) separation of solid and liquid:By the slurry of extraction through centrifugation (rotating speed 8000rpm, the time of centrifugation is 20min) or filtering Make separation of solid and liquid, the solid content that control is transferred in extracting solution is no more than the 20% of medicinal material total amount, the extracting solution meter of separation It measures spare.
(5) it extracts for second:The solid dregs of a decoction of separation of solid and liquid are repeated into step 3~4, extraction fluid metering and first time The extracting solution of extraction is combined into step 6;
(6) micro-filtration:By the extracting solution of merging through 0.45 μm of inorganic membrane filtration to clarification;6.1 filtering to close to microstrainer most During partial circulating, add extraction that filter liquor is diluted with water, make to be no less than 2 times of extracting solution through liquid measure, continue filtering to dope and consolidate More than 20% shape object content.Filtered solution and dope are collected respectively.
6.2 are recycled 15 minutes with the water of microstrainer minimal circulation amounts and rinse inorganic membrane filter, by cleaning solution with 6.1 it is dense Liquid merges.
The filtration time of 6.3 every microstrainers is no more than 6 hours or flow drop is more than 50%.
(7) micro-filtrate is concentrated into solid content about 15%, relative density is the Chinese medical concrete of 1.05 (70 DEG C).
(8) above-mentioned medicinal extract adds proper auxiliary materials to be spray-dried, and obtains Chinese medicine composition of the present invention.
A kind of Chinese medicine composition for reducing blood lipid prepared by the present invention can use existing Chinese drug preparation technique and technique Any solid dosage forms is made in method, including capsule, tablet, powder or pill etc..Piece agent or particle are prepared in the present embodiment Agent, but dosage form is not limited.
Embodiment 2
Formula:Hawthorn 50kg prepared fleece flower root 3.5kg cassia seed 3.5kg lotus leaves 10kg.
(1) it is sieved after taking the pulverizing medicinal materials of formula ratio by No.1 (10 mesh)~No. tetra- (65 mesh);
(2) above-mentioned weight medicinal powder is taken to mix, 20 times of amount water is added to be stirred 70min, make fully to soak;
(3) it extracts for the first time:It sets low in warm High Pressure Difference extractor, in 10 DEG C of cycle extractions 2 times, first time 20Mpa, extraction 40min, second of 50Mpa extract 30min;
(4) separation of solid and liquid:By the slurry of extraction through centrifugation (rotating speed 10000rpm, the time of centrifugation is 15min) or mistake Filter makes separation of solid and liquid, and the solid content that control is transferred in extracting solution is no more than the 20% of medicinal material total amount, the extracting solution of separation It measures spare.
(5) it extracts for second:The solid dregs of a decoction of separation of solid and liquid are repeated into step 3~4, extraction fluid metering and first time The extracting solution of extraction is combined into step 6;
(6) micro-filtration:By the extracting solution of merging through 1.0 μm of inorganic membrane filtrations to clarification;
When 6.1 filterings are to close to microstrainer minimal circulation, add extraction that filter liquor is diluted with water, make to be no less than through liquid measure 2 times of extracting solution continue filtering to more than 20% dope solid content.Filtered solution and dope are collected respectively.
6.2 are recycled 15 minutes with the water of microstrainer minimal circulation amounts and rinse inorganic membrane filter, by cleaning solution with 6.1 it is dense Liquid merges.
The filtration time of 6.3 every microstrainers is no more than 6 hours or flow drop is more than 50%.
(7) micro-filtrate is concentrated into solid content about 20%, relative density is the Chinese medical concrete of 1.20 (50 DEG C).
(8) above-mentioned medicinal extract adds proper auxiliary materials to be spray-dried, and obtains Chinese medicine composition of the present invention.
A kind of Chinese medicine composition for reducing blood lipid prepared by the present invention can use existing Chinese drug preparation technique and technique Any solid dosage forms is made in method, including capsule, tablet, powder or pill etc..Piece agent or particle are prepared in the present embodiment Agent, but dosage form is not limited.
Embodiment 3
Formula:Hawthorn 60kg, prepared fleece flower root 1kg, cassia seed 2.5kg, lotus leaf 8kg.
(1) it is sieved after taking the pulverizing medicinal materials of formula ratio by No.1 (10 mesh)~No. tetra- (65 mesh);
(2) above-mentioned weight medicinal powder is taken to mix, 15 times of amount water is added to be stirred 50min, make fully to soak;
(3) it extracts for the first time:It sets low in warm High Pressure Difference extractor, in 0 DEG C of cycle extraction 2 times, first time 25Mpa, extraction 30min, second of 45Mpa extract 60min;
(4) separation of solid and liquid:By the slurry of extraction through centrifugation (rotating speed 12000rpm, the time of centrifugation is 10min) or mistake Filter makes separation of solid and liquid, and the solid content that control is transferred in extracting solution is no more than the 20% of medicinal material total amount, the extracting solution of separation It measures spare.
(5) it extracts for second:The solid dregs of a decoction of separation of solid and liquid are repeated into step 3~4, extraction fluid metering and first time The extracting solution of extraction is combined into step 6;
(6) micro-filtration:By the extracting solution of merging through 0.8 μm of inorganic membrane filtration to clarification;
When 6.1 filterings are to close to microstrainer minimal circulation, add extraction that filter liquor is diluted with water, make to be no less than through liquid measure 2 times of extracting solution continue filtering to more than 20% dope solid content.Filtered solution and dope are collected respectively.
6.2 are recycled 15 minutes with the water of microstrainer minimal circulation amounts and rinse inorganic membrane filter, by cleaning solution with 6.1 it is dense Liquid merges.
The filtration time of 6.3 every microstrainers is no more than 6 hours or flow drop is more than 50%.
(7) micro-filtrate is concentrated into solid content about 10%, relative density is the Chinese medical concrete of 1.1 (80 DEG C).
(8) above-mentioned medicinal extract adds proper auxiliary materials to be spray-dried, and obtains Chinese medicine composition of the present invention.
A kind of Chinese medicine composition for reducing blood lipid prepared by the present invention can use existing Chinese drug preparation technique and technique Any solid dosage forms is made in method, including capsule, tablet, powder or pill etc..Piece agent or particle are prepared in the present embodiment Agent, but dosage form is not limited.
Comparative example 1
Formula:Hawthorn (stoning) 500g;Prepared fleece flower root 25g;Cassia seed 25g;Lotus leaf 75g.
(1) raw material is placed:The raw material of formula ratio is crushed, it is 180 μm to make grain size;
(2) it vacuumizes:Under the conditions of -10 DEG C of reaction system temperature, make to be formed in High Pressure Difference continuous low-temperature extractor true Sky, vacuum degree are maintained at -100pa, add in water or 70% (v/v) ethanol water, keep 5min, wherein, the raw material and water Or 5% (v/v) ethanol water weight ratio be 1:6;
(3) subtract vacuum:Purification of compressed air is passed through, the pressure in High Pressure Difference continuous low-temperature extractor is made to rise to 0Mpa, Keep 1min;
(4) it pressurizes:Continue to be passed through compressed air, the pressure in High Pressure Difference continuous low-temperature extractor is made to reach 8Mpa, protect Hold 20min;
(5) it depressurizes:Stop pressurization, vacuumize, the pressure in High Pressure Difference continuous low-temperature extractor is made to be down to 0Mpa;
(6) cycle extraction:Step (2)-(5) are recycled, are recycled 10 times.
Tablet or granule is made in above-mentioned composition.
Comparative example 2
Formula:Hawthorn 500g;Prepared fleece flower root 25g;Cassia seed 25g;Lotus leaf 60g.
(1) raw material is placed:The raw material of formula ratio is crushed, it is 850 μm to make grain size;
(2) it vacuumizes:Under the conditions of 0 DEG C of reaction system temperature, make to form vacuum in High Pressure Difference continuous low-temperature extractor, Vacuum degree is maintained at 20pa, adds in water or 5% (v/v) ethanol water, keeps 30min, wherein, the raw material and water or 70% (v/v) weight ratio of ethanol water is 1:20;
(3) subtract vacuum:Purification of compressed air is passed through, the pressure in High Pressure Difference continuous low-temperature extractor is made to rise to 0Mpa, Keep 10min;
(4) it pressurizes:Continue to be passed through compressed air, the pressure in High Pressure Difference continuous low-temperature extractor is made to reach 12Mpa, protect Hold 1min;
(5) it depressurizes:Stop pressurization, vacuumize, the pressure in High Pressure Difference continuous low-temperature extractor is made to be down to 0Mpa;
(6) cycle extraction:Step (2)-(5) are recycled, are recycled 10 times.
Tablet or granule is made in above-mentioned composition.
Influence of the embodiment 4 to hyperlipidemic mice caused by egg-nog
Healthy male ICR kinds mouse 80 is selected, 8 groups is randomly divided by weight, is blank control group, model comparison respectively Group, atorvastatin calcium group (3mgkg-1), the basic, normal, high dosage group of Chinese medicine composition group made from the embodiment of the present invention 1~3 (2、4、8g·kg-1), 1 group of (4gkg of comparative example-1), 2 groups of (4gkg of comparative example-1).Except blank group daily gavage such as gives at the appearances Measure distilled water, remaining each group morning gavage gives yolk emulsion 0.5ml/ only, afternoon gastric infusion, administered volume 10ml kg-1, continuous 11d.Mouse is deprived of food but not water 12h before last dose, and 1h mouse pluck eyeball blood is taken (to test after the last administration 11d), 3000rmin-110min is centrifuged, detaches serum, serum triglyceride (TC), total courage are measured according to kit specification Sterol (TG) content.
Experimental result:
Model group mice serum TG, TC content significantly increases, and relatively has pole significant difference (p with blank control group< 0.001), atorvastatin calcium group, the basic, normal, high dosage group of Chinese medicine composition group and comparison made from the embodiment of the present invention 1~3 Example 1,2 each groups can obviously reduce hyperlipemia in mice serum TG, TC contents, with significant difference (p compared with model group< 0.05, p<0.01, p<0.001), while the middle and high dosage group of Chinese medicine composition group made from the embodiment of the present invention 1~3 is with comparing When 1,2 group of example is respectively compared, find that TG, TC content raising effect is inhibited to be substantially better than 1,2 group of comparative example, compare has significantly therewith Difference (p<0.05, p<0.01) it is, suitable with atorvastatin calcium group effect, it the results are shown in Table 1.
Table 1 to hyperlipemia model mice serum TC, TG caused by egg-nog influence (N=10)
Compared with blank control group△△△p<0.001;The * p compared with model control group<0.05, * * p<0.01,
***p<0.001;Compared with comparative example 1p<0.05,★★p<0.01;Compared with comparative example 2#p<0.05,##p< 0.01。
Influence of the embodiment 5 to experimental atherosclerosis rats
Model foundation:
By 90 rats in addition to 10 blank control group normal diets, remaining rat gives high lipid food nursing, feeds 8 weeks Extraction 5 cuts tail and takes whether TG content detection models in blood survey serum succeed afterwards.High lipid food formula:78.8% basal feed, 10% lard, 10% yolk powder, 1% cholesterol, 0.2% cholate.This experimental animal technology Co., Ltd of Changchun hundred million, it is low Temperature preserves.
Grouping and administration:
By 70 7 groups of modeling successful rats point:That is model control group, atorvastatin calcium group (1mgkg-1), this hair The basic, normal, high dosage group of Chinese medicine composition group made from bright Examples 1 to 3 (1.5,3,6gkg-1), 1 group of (3gkg of comparative example-1), 2 groups of (3gkg of comparative example-1).Remaining each group continues feeding high fat diet in addition to blank control group normal diet is fed, Blank control group and the isometric distilled water of model control group gavage, remaining each group gastric infusion, 10mlkg-1, it is administered 4 weeks.
Index:
It is deprived of food but not water 12h after the last administration, rat anaesthetizes (45mgkg with yellow Jackets-1), abdominal aorta blood sampling, Be put into containing heparin sodium, sodium citrate anticoagulant vacuum blood collection tube in, believe blood with Beijing Puli's green blood viscosity apparatus and thyrite health Platelet aggregation instrument measures whole blood contrast viscosity and platelet aggregation rate.A pipe blood, 3500rmin are acquired again-1Centrifuge 15min separation Serum measures T-CHOL (TG), triglyceride (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein in serum (LDL-C) it is horizontal, superoxides gasification enzyme (SOD) vigor is measured, measures malonaldehyde (MDA) content, kit is pressed in concrete operations Specification carries out.
Experimental result:
Influence to hemorheology of rat:
Whole blood viscosity under model control group rat blood difference shear rate is significantly raised, relatively has with blank control group Significant difference (p<0.05, p<0.01, p<0.001), atorvastatin calcium group, Chinese traditional medicine composition made from the embodiment of the present invention 1~3 1,2 group of whole blood viscosity and model control group ratio that can significantly inhibit under each shear rate of the basic, normal, high dosage group of object group and comparative example More significant difference (p<0.05, p<0.01, p<0.001;).Chinese medicine composition group made from the embodiment of the present invention 1~3 simultaneously Middle and high dosage group is significantly better than that the inhibiting effect of each point whole blood viscosity 1,2 group of comparative example, there is apparent advantage function (p< 0.05, p<0.01) 2, be the results are shown in Table.
Table 2 to hemorheology of rat influence (N=10)
Compared with blank control group△△p<0.01,△△△p<0.001;The * p compared with model control group<0.05, * * p< 0.01, * * * p<0.001;Compared with comparative example 1p<0.05,★★p<0.01;Compared with comparative example 2#p<0.05,##p<0.01。
Influence to Rat Erythrocytes aggregation rate and platelet aggregation rate:
Model control group rat blood erythrocyte aggregation rate and maximum platelet aggregation rate also significantly increase, with blank control Group compares that there were significant differences (p<0.05, p<0.01, p<0.001), atorvastatin calcium group, made from the embodiment of the present invention 1~3 1,2 group of the basic, normal, high dosage group of Chinese medicine composition group and comparative example can significantly inhibit erythrocyte aggregation rate and the big aggregation of blood platelet Rate increases, with the more significant difference (p of model control group<0.05, p<0.01, p<0.001;).The embodiment of the present invention 1 simultaneously The middle and high dosage group of Chinese medicine composition group made from~3 is bright to erythrocyte aggregation rate, the inhibiting effect of maximum platelet aggregation rate It is aobvious to be better than 1,2 group of comparative example, there is apparent advantage function (p<0.05, p<0.01) 3, be the results are shown in Table.
Table 3 to Rat Erythrocytes aggregation rate and maximum platelet aggregation rate influence (N=10)
Compared with blank control group△△p<0.01,△△△p<0.001;The * p compared with model control group<0.05, * * p< 0.01, * * * p<0.001;Compared with comparative example 1p<0.05,★★p<0.01;Compared with comparative example 2#p<0.05,##p<0.01。
Influence to rat blood serum TG, TC, HDL-C, LDL-C:
Model control group rat blood serum TG, TC, LDL-C content significantly increases, and HDL-C contents are substantially reduced, with blank pair Compare according to group and there were significant differences (p<0.001), atorvastatin calcium group, Chinese medicine composition made from the embodiment of the present invention 1~3 1,2 group of the basic, normal, high dosage group of group and comparative example can inhibit rat blood serum TG, TC, LDL-C content to increase in various degree, promote Rat blood serum HDL-C discharges, there were significant differences compared with model control group (p<0.05、p<0.01).Chinese medicine group of the present invention simultaneously The middle and high dosage group of object is closed compared with 1,2 group of comparative example, reduces TG, TC, LDL-C effect significantly, promotes HDL-C raisings effect Significantly (p<0.05、p<0.01), show Chinese medicine composition made from the embodiment of the present invention 1~3 and 1,2 group of reduction blood fat of comparative example The advantage of effect, the results are shown in Table 4.
Table 4 to rat blood serum TG, TC, HDL-C, LDL-C influence (N=10)
Compared with blank control group△△p<0.01,△△△p<0.001;The * p compared with model control group<0.05, * * p< 0.01, * * * p<0.001;Compared with comparative example 1p<0.05,★★p<0.01;Compared with comparative example 2#p<0.05,##p<0.01。
Influence to rat blood serum SOD, MDA:
Model control group rat blood serum SOD vigor reduces, and MDA contents significantly increase, and relatively has with blank control group significantly Difference (p<0.001), atorvastatin calcium group, the basic, normal, high dosage group of Chinese medicine composition group made from the embodiment of the present invention 1~3 And 1,2 group of comparative example can significantly increase rat blood serum SOD vigour changes, inhibit the release of MDA contents, compared with model control group There were significant differences (p<0.05、p<0.01、p<0.001).Chinese medicine composition group made from the embodiment of the present invention 1~3 is middle and high simultaneously Dosage group improves the effect of SOD vigor there were significant differences (p compared with 1,2 group of comparative example<0.05、p<0.01), middle and high dosage Group inhibits MDA contents release actions there were significant differences (p<0.05), show that Chinese medicine composition of the present invention improves antioxidation, suppression It makes the effect of its peroxidatic reaction of lipid to have a clear superiority, the results are shown in Table 5.
Table 5 to rat blood serum SOD, MDA influence (N=10)
Compared with blank control group△△p<0.01,△△△p<0.001;The * p compared with model control group<0.05, * * p< 0.01, * * * p<0.001;Compared with comparative example 1p<0.05,★★p<0.01;Compared with comparative example 2#p<0.05,##p<0.01。
Embodiment 6
Tablet prepared by tablet and comparative example 1, comparative example 2 made of the Chinese medicine composition provided embodiment 1 to 3 into The detection of row hardness, disintegration time limited, friability, active ingredient etc., testing result is as shown in 6~table of table 8:
The testing result of 6 production target of table
Note:Compared with comparative example 1,*Show with significant difference (P < 0.05),**Show with pole significant difference (P < 0.01);
Compared with comparative example 2,#Show with significant difference (P < 0.05),##Show with pole significant difference (P < 0.01).
Volatile oil extracting:
Composition made from composition made from Example 1~3 and comparative example 1, comparative example 2, according to《Middle traditional Chinese medicines Allusion quotation》Four essential oil extraction methods of version in 2015 continuously extract 8h, and with ether dissolution, volatile oil is obtained after anhydrous sodium sulfate drying. Recovery rate is as shown in table 7.
Influence of the table 7 to volatile oil extracting rate
Group Volatile oil extracting rate (%)
The composition that embodiment 1 provides 30*#
The composition that embodiment 2 provides 35**##
The composition that embodiment 3 provides 32*##
The composition that comparative example 1 provides 23
The composition that comparative example 2 provides 20
Note:Compared with comparative example 1,*Show with significant difference (P < 0.05),**Show with pole significant difference (P < 0.01);
Compared with comparative example 2,#Show with significant difference (P < 0.05),##Show with pole significant difference (P < 0.01).
Chromatographic condition:
Agilent 19091M-436 types quartz capillary column (0.25mm × 30m, 0.25 μm);Carrier gas is height Purity helium, volume flow 1mL/min, split ratio 50.2:1;280 DEG C of injector temperature;Temperature programming:60 DEG C (3min), 10 DEG C/min rises to 280 DEG C, keep 12min.1 μ L of sample size;Solvent delay 1.5min;Gasify 280 DEG C of room temperature;Multiplier voltage 1 952.9V。
Mass Spectrometry Conditions:
Electron bombardment (EI) ion source, ionization voltage 70eV;230 DEG C of ion source temperature;20~500amu of scanning range.
Under these experimental conditions, GC-MS analyses, inspection are carried out to the ingredient of the volatile oil in product made from embodiment 1 Go out 10 peaks.To each peak in total ion current figure after scanning of the mass spectrum mass spectrogram, through NIST08.L spectrograms library automatically retrieval and Verification standard mass spectrogram with reference to related standard mass spectrum document, is identified 10 kinds of volatile oil component, is measured with areas of peak normalization method Volatile oil each component percentage contents, the ingredient identified account for the 100% of complete oily total amount, the results are shown in Table 8.
The chemical composition and its relative amount of 8 volatile oil of table identification
Above-mentioned experiment, result of the test and the result of product made from embodiment 1 are carried out to product made from embodiment 2~3 Without significant difference (P > 0.05).Show that offer technique provided by the invention is extracted using cryogenic high pressure difference, make active ingredient maximum Degree extracts, and improves production efficiency.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications also should It is considered as protection scope of the present invention.

Claims (10)

1. a kind of extraction process of drug, which is characterized in that include the following steps:
Bulk pharmaceutical chemicals include 500~600 parts by weight of hawthorn, 10~35 parts by weight of prepared fleece flower root, 10~35 parts by weight of cassia seed, lotus leaf 50~100 parts by weight;
Step 1:Bulk pharmaceutical chemicals is taken to be mixed after pre-processing with water;
Step 2:30~60min is extracted for the first time in 20~30Mpa, and 30~60min is extracted second then at 40~50Mpa;
Step 3:The extract that step 2 obtains is taken to collect filtrate through separation of solid and liquid.
2. extraction process according to claim 1, which is characterized in that the temperature of the first time extraction is 0~10 DEG C.
3. extraction process according to claim 1 or 2, which is characterized in that the temperature of second of extraction is 0~10 ℃。
4. extraction process according to any one of claims 1 to 3, which is characterized in that separation of solid and liquid described in step 3 be from The heart or filtering;The rotating speed of the centrifugation is 8000~12000rpm, and the time of the centrifugation is 10~30min.
5. extraction process according to any one of claims 1 to 4, which is characterized in that further include and the filtrate is taken to repeat to walk Rapid 2, the step of step 3, the number of the repetition are at least 1 time.
6. extraction process according to claim 5, which is characterized in that further included after the step of repeating step 2, step 3 The step of merging filtrate, filtering;It is described to be filtered into micro-filtration;
The aperture for the film that the micro-filtration uses is 0.45~1.0 μm.
7. extraction process according to claim 6, which is characterized in that the micro-filtration is specially to take the filtrate after merging excessively micro- Filter membrane adds water to make to be no less than 2 times of the volume of the filtrate after the merging through liquid measure, filters into dope the content of solid content No less than 20% (w/w);Microfiltration membranes are rinsed with water, cleaning solution is collected and is mixed with the dope.
8. the extraction process described according to claim 6 or 7, which is characterized in that the time of the filtering is no more than 6h, the mistake The flow-reduction amplitude of filter is no less than 50%.
9. according to claim 6 to 8 any one of them extraction process, which is characterized in that the content of solid content in the filtering For 10~20% (w/w), the relative density that 50~80 DEG C of whens measure is 1.05~1.20.
10. according to drug made from 1 to 9 any one of them extraction process.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109350659A (en) * 2018-12-10 2019-02-19 成都大学 A kind of blood lipid-reducing blood sugar-decreasing composition and preparation method thereof, application

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
中华人民共和国***药典委员会编: "《中华人民共和国***药品标准.中药成方制剂》", 31 December 1997 *
刘超等: ""降脂宁颗粒质量标准的研究"", 《中国实验方剂学杂志》 *
黄裕等: ""低温高压差提取抗敏中药复方的工艺研究"", 《中国药物经济学》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109350659A (en) * 2018-12-10 2019-02-19 成都大学 A kind of blood lipid-reducing blood sugar-decreasing composition and preparation method thereof, application
CN109350659B (en) * 2018-12-10 2021-09-14 成都大学 Lipid-lowering and blood-sugar-reducing composition, and preparation method and application thereof

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