CN103039970B - A kind of active component and preparation method thereof of nutrient and healthcare products with resist oxygen lack, antifatigue - Google Patents
A kind of active component and preparation method thereof of nutrient and healthcare products with resist oxygen lack, antifatigue Download PDFInfo
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Abstract
The invention provides a kind of have resist oxygen lack, antifatigue its active component of nutrient and healthcare products by Chinese medicine material rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng forms, also comprise the fruit of Chinese magnoliavine, matrimony vine, ginseng, Radix Angelicae Sinensis, cultivated land, the Radix Astragali, Radix Glycyrrhizae and edible meal material and pharmaceutically customary adjuvant form.Through mouse functional experiment, display has resist oxygen lack, antifatigue, improve memory, develop immunitypty, improving water flood, improve microcirculation, anti-oxidant, the effect delayed senility, is applicable to heavy muscle power and brain worker, the person that needs Improving memory, fatiguability, hypoimmunity, poor sleep, the easy anoxic crowd that cardio-cerebrovascular obstacle or Respiratory Disturbances cause.
Description
[technical field]
The present invention relates to important health food, be specifically related to a kind of active component and preparation method thereof of nutrient and healthcare products with resist oxygen lack, antifatigue.
[background technology]
Oxygen participates in human metabolism, is the indispensable material of normal activities.Adult is under quiescent condition, and oxygen demand per minute is about 250ml; Time movable, oxygen demand increases.But oxygen reserve is few in human body, the supply of external environment oxygen must be depended on and constantly completed picked-up and the transport of oxygen by breathing, blood circulation, to ensure the needs of cell.
When tissue can not get sufficient oxygen, when maybe can not make full use of oxygen, all may there is ANOMALOUS VARIATIONS in metabolism, the function, even morphosis of cell, tissue, organ, this pathologic process is just called anoxic.Anoxic is a kind of pessimal stimulation to body, affects the various metabolism of body, particularly affects the oxidative function of body, finally can cause the major organs anoxic undersupplies such as the heart of body, brain and dead.
The conventional Chinese and western drugs sold on the market at present has side effect in various degree.
[summary of the invention]
The deficiency of invention for overcoming prior art, what provide a kind of safe, effective, integration of drinking and medicinal herbs has resist oxygen lack, antifatigue, improve memory, develop immunitypty, improving water flood, improve microcirculation, anti-oxidant, health products that the Chinese herbal medicine of the health care delayed senility is made and preparation method thereof.
The present invention is by the following technical solutions for achieving the above object:
Have the active component of nutrient and healthcare products for resist oxygen lack, antifatigue, its active component comprises the mixture of the meal of 50 ~ 75 parts of rhodiola roots and 10 ~ 40 parts of Ligusticum wallichii water extracts and 10 ~ 40 parts of rhizoma Gastrodiaes and 5 ~ 20 portions of pseudo-ginseng;
Or 50 ~ 75 parts of rhodiola roots, 10 ~ 40 parts of Ligusticum wallichiis, 10 ~ 40 parts of rhizoma Gastrodiaes, the mixture of the water extract of 5 ~ 20 portions of pseudo-ginseng;
Or the mixture of the meal of 50 ~ 75 parts of rhodiola roots and 10 ~ 40 parts of Ligusticum wallichii water extracting alcohol hypostasis and 10 ~ 40 parts of rhizoma Gastrodiaes and 5 ~ 20 portions of pseudo-ginseng;
Or 50 ~ 75 parts of rhodiola roots, 10 ~ 40 parts of Ligusticum wallichiis, 10 ~ 40 parts of rhizoma Gastrodiaes, the mixture of the water extracting alcohol hypostasis of 5 ~ 20 portions of pseudo-ginseng;
Or the mixture of the meal of 50 ~ 75 parts of rhodiola roots and 10 ~ 40 parts of Ligusticum wallichii alcohol extracts and 10 ~ 40 parts of rhizoma Gastrodiaes and 5 ~ 20 portions of pseudo-ginseng;
Or 50 ~ 75 parts of rhodiola roots, 10 ~ 40 parts of Ligusticum wallichiis, 10 ~ 40 parts of rhizoma Gastrodiaes, the mixture of the alcohol extract of 5 ~ 20 portions of pseudo-ginseng;
Or 50 ~ 75 parts of rhodiola roots, 10 ~ 40 parts of Ligusticum wallichiis, 10 ~ 40 parts of rhizoma Gastrodiaes, the mixture of the distillation extract of 5 ~ 20 portions of pseudo-ginseng.
A kind of active component of nutrient and healthcare products with resist oxygen lack, antifatigue of the present invention, wherein, the weight proportion of each raw material of active component is:
10 ~ 30 parts, rhodiola root 50 ~ 70 parts of Ligusticum wallichiis 10 ~ 30 parts of rhizoma Gastrodiaes
Pseudo-ginseng 8 ~ 15 parts.
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, the preparation method of active component comprises the steps:
A) water extraction: get rhodiola root and Ligusticum wallichii, adds the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
B) described rhizoma Gastrodiae and pseudo-ginseng being pulverized altogether is 80 ~ 200 orders, mixes, low temperature drying, be ground into fine powder with above-mentioned medicinal extract.
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, active component is prepared according to following step:
Get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng, add the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filter, merging filtrate, filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65.
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, the preparation method of active component comprises the steps:
C) water extraction: get rhodiola root, Ligusticum wallichii, adds the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
D) alcohol precipitation: be dissolved in water by above-mentioned medicinal extract, then add absolute ethyl alcohol, makes alcohol content reach 60% ~ 90%, gets supernatant after placing 12 ~ 24h, and 20 ~ 30 DEG C of survey relative densities made by recovery ethanol is the medicinal extract of 1.20 ~ 1.25;
E) described rhizoma Gastrodiae, pseudo-ginseng being pulverized altogether is 80 ~ 200 orders, mixes, low temperature drying, be ground into fine powder with the medicinal extract obtained by step d).
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, the preparation method of active component comprises the steps:
F) water extraction: get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng, adds the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.20 ~ 1.25;
G) alcohol precipitation: be dissolved in water by above-mentioned medicinal extract, then add absolute ethyl alcohol, makes alcohol content reach 60% ~ 90%, gets supernatant after placing 12 ~ 24h, and 20 ~ 30 DEG C of survey relative densities made by recovery ethanol is the medicinal extract of 1.10 ~ 1.65.
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, the preparation method of active component comprises the steps:
H) alcohol extracting: get rhodiola root, Ligusticum wallichii, adds 40% ~ 95% ethanol of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
I) described rhizoma Gastrodiae, pseudo-ginseng being pulverized altogether is 80 ~ 200 orders, mixes, low temperature drying, be ground into fine powder with above-mentioned medicinal extract.
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, the preparation method of active component carries out according to following step:
Alcohol extracting: get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng, adds 40% ~ 95% ethanol of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65.
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, the preparation method of active component comprises the steps:
J) get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng be broken into meal jointly, with the volatile oil in the total medicinal material of extraction by steam distillation after immersion, the another device of the aqueous solution after distillation is collected;
K) by step j) in distillation after the dregs of a decoction decoct 1 ~ 3 time, add 8 ~ 15 times amount soak by water 2 ~ 4h, collecting decoction at every turn, filter;
L) by step k) filtrate that obtains and step j) aqueous solution after the distillation that obtains merges, and adds step j) and in the volatile oil that obtains, being concentrated into and surveying relative densities at 20 ~ 30 DEG C is the medicinal extract of 1.10 ~ 1.65.
Prepare a method for the active component of nutrient and healthcare products of the present invention, wherein, the preparation method of active component comprises the steps:
Get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng is pulverized jointly, puts into microwave extraction tank, add respectively 6 ~ 20 times of water gagings, 6 ~ 20 times amount 40% ~ 95% ethanol, Microwave Extraction 1 ~ 4 time, filter, merging filtrate, being evaporated to and surveying relative density at 20 ~ 30 DEG C is the medicinal extract of 1.10 ~ 1.65.
A kind of active component of nutrient and healthcare products with resist oxygen lack, antifatigue of the present invention, wherein, active component comprises one or more any combination in following raw material:
Matrimony vine 1 ~ 70 part of ginseng 1 ~ 70 part of Radix Angelicae Sinensis 1 ~ 70 part
1 ~ 70 part, cultivated land 1 ~ 70 part of Radix Astragali 1 ~ 70 portion of Radix Glycyrrhizae
1 ~ 70 part, the fruit of Chinese magnoliavine.
Nutrient and healthcare products provided by the invention, wherein, the formulation of health products is capsule, tablet, pill, pulvis, particle electuary or oral liquid.
Nutrient and healthcare products provided by the invention, wherein, carrier is selected from excipient, lubricant, disintegrant or antioxidant.
Raw material selected by active component of the present invention all can adopt following methods to be prepared:
1, water extraction method:
Required medicinal material takes in prescription ratio by 1.1, and add the water of ormal weight, heating is boiled, and keeps micro-and boils, and decocts 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
The rhizoma Gastrodiae of described weight portion, pseudo-ginseng are pulverized by 1.2 altogether, cross 200 orders, mix with above-mentioned medicinal extract.
2, water extract-alcohol precipitation
Required medicinal material takes in prescription ratio by 2.1, and add the water of ormal weight, heating is boiled, and keeps micro-and boils, and decocts 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65, for subsequent use;
2.2, by above-mentioned obtained medicinal extract, are dissolved in water, then add absolute ethyl alcohol, make alcohol content reach 60% ~ 90%, place 24h, filter, and 20 ~ 30 DEG C of survey relative densities made by recovery ethanol is the medicinal extract of 1.10 ~ 1.65;
The rhizoma Gastrodiae of described weight portion, pseudo-ginseng are pulverized by 2.3 altogether, cross 200 orders, with step 2.2) obtained medicinal extract mixing.
3, alcohol extract:
3.1 all medicinal materials take in prescription ratio, take in prescription ratio, add 40% ~ 95% ethanol, keep micro-and boil, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filter, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
The rhizoma Gastrodiae of described weight portion, pseudo-ginseng are pulverized by 3.2 altogether, cross 200 orders, mix with above-mentioned medicinal extract.
4, two extraction method
4.1 all medicinal materials are ground into meal altogether, and with volatile oil total in steam distillation medicinal material after soaking, the another device of the aqueous solution after distillation is collected;
The dregs of a decoction after above-mentioned distillation are decocted 2 times by 4.2, and first time, for the second time with 6 ~ 10 times amount soak by water 1 ~ 2h, collecting decoction, filtered with 8 ~ 15 times amount soak by water 2 ~ 4h;
The aqueous solution after the filtrate decocted and distillation merges by 4.3, and adds the volatile oil obtained, and being concentrated into and surveying relative densities at 20 ~ 30 DEG C is the medicinal extract of 1.10 ~ 1.65.
5, ultrasonic extraction
Medicinal material is pulverized jointly, puts into microwave extraction tank, adds water respectively, the ethanol of normal concentration, and ultrasonic extraction 1 ~ 4 time, filters, merging filtrate, and being evaporated to and surveying relative densities at 20 ~ 30 DEG C is the medicinal extract of 1.10 ~ 1.65.
6, Microwave Extraction
All medicinal material heating using microwave certain hours, take out to be cooled to room temperature, filter, and repeat abovementioned steps, merging filtrate, reduced pressure concentration obtains medicinal extract.
Auxiliary material or carrier will be added in final medicinal extract/meal obtained by the preparation method of above-mentioned arbitrary active component prepare the formulation of any one or the upper accreditation of numerous food, comprise capsule, tablet, pill, pulvis, particle electuary or oral liquid.
Carrier comprises wetting agent, disintegrant, filler, flavouring, adhesive, lubricant, and auxiliary material comprises starch, dextrin, Icing Sugar, ethanol, dolomol etc.
1. prepare tablet
By the final medicinal extract that the preparation method of the active component of above-mentioned arbitrary proportioning extracts, add the starch of 5% of its total amount, mixing, compressing tablet after granulating, makes the tablet of 0.5g/ sheet.
2. prepare capsule
Is added the starch of 3% of its total amount in the final medicinal extract that the preparation method of the active component of above-mentioned arbitrary proportioning is extracted, mixing, dry, pulverize after granulation, filled capsules, makes the capsule of 0.5g/ grain.
3. prepare granule
Is added its total amount 50% dextrin and 20% sucrose in the final medicinal extract that the preparation method of the active component of above-mentioned arbitrary proportioning is extracted, granulate, dry, dress up the granule of 10g/ bag.
4. prepare pill
The refined honey being added its total amount 80% in the final medicinal extract that the preparation method of the active component of above-mentioned arbitrary proportioning is extracted as adhesive and 20% starch, mixing, pill, dry, make honeyed bolus.
5. prepare oral liquid
Being added water to 60 DEG C of relative densities in the final medicinal extract that the preparation method of the active component of above-mentioned arbitrary proportioning is extracted is 1.05 ~ 1.10, and mixing, pours in oral stable medicinal polythene bottle with high density, obtain oral liquid.
This product is with rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng 4 taste medicinal material or the interpolation fruit of Chinese magnoliavine, matrimony vine, ginseng, Radix Angelicae Sinensis, cultivated land, the Radix Astragali, a kind of in Radix Glycyrrhizae 7 taste or 2 kinds and above medicinal material are the health food that primary raw material is made, prove that there is resist oxygen lack through animal function test, antifatigue, improve memory, develop immunitypty, improving water flood, improve microcirculation, anti-oxidant, the effect delayed senility, be applicable to heavy muscle power and brain worker, the person that needs Improving memory, fatiguability person, hypoimmunity, poor sleep, the easy anoxic crowd that cardio-cerebrovascular obstacle or Respiratory Disturbances cause.
Prescription: rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng, the fruit of Chinese magnoliavine, matrimony vine, ginseng, Radix Angelicae Sinensis, cultivated land, the Radix Astragali, Radix Glycyrrhizae, Fang Zhong, rhodiola root taste is sweet, cold in nature.Return spleen, lung channel." Chinese herbal medicine is commonly used in Tibet " carries it: " promoting blood circulation and hemostasis "." China's book on Chinese herbal medicine " calls it: " tonifying Qi clearing lung-heat, intelligence development is nourished heart ", therefore rhodiola root has " strengthen the body resistance to consolidate the constitution, beneficial gas is capable stagnant " of similar ginseng to act on.Rhodiola root is top grade in medicine, has beneficial gas of making light of one's life by commiting suicide, does not always prolong life, and nontoxic many clothes, take inoffensive feature for a long time.Qi and activate blood circulation in this side, effectively can improve blood circulation, for qi deficiency to blood stasis, and wind headache during brain arteries and veins stasis blocking is caused, dispute
tiltedly, the card of dysphasia has good qi and activate blood circulation, the merit of disperse blood stasis and dredge collateral.Ligusticum wallichii taste is pungent, warm in nature.Return liver, courage, pericardium channel.Shennong's Herbal carries it: " main apoplexy enters brain headache, arthritis, muscle contraction emergency." " property of medicine opinion " call it: " control waist pin weak, hemiplegia." " Japan hanako materia medica " cloud its: " control a wind cutting, all gas, all strains, all blood, mend the exhaustion or lesion of the five internal organs, strengthen the bone, adjust many arteries and veins, and broken crux place blood, supports new blood." Compendium of Material Medica cloud its: " this medicine is up, specially controls all diseases of brains." " book on Chinese herbal medicine converge with speech " call it: " the up head, lower menstruation regulating water, middle relieving stagnation, gas medicine in blood." through cloud " control wind and first control blood, blood wind is from going out ", therefore Ligusticum wallichii merit is apt to the promoting flow of qi and blood circulation, dispelling wind and removing obstruction in the meridians.The pungent perfume (or spice) of Ligusticum wallichii is kind to be risen, and walks Liver Channel again, can top, up head mountain peak, not only can soothing the liver promoting the circulation of qi, and have invigorate blood circulation, wind-expelling pain-stopping effect; Rhodiola root and Ligusticum wallichii share can the promoting flow of qi and blood circulation, promotion of blood circulation, enlightened clear key, plays breath wind altogether and stops convulsion, qi and activate blood circulation, the effect of eleminating phlegm and freeing channels, is monarch drug in a prescription in side altogether.Be aided with
my godfiber crops, pseudo-ginseng, the fruit of Chinese magnoliavine, matrimony vine, ginseng, Radix Angelicae Sinensis, cultivated land, the Radix Astragali, Radix Glycyrrhizae, many raw material phases 5, qi and activate blood circulation, grows spleen and supports lung, strengthening vital QI to eliminate pathogenic factors, thus reach resist oxygen lack, antifatigue, improve memory, develop immunitypty, improving water flood, improves microcirculation, anti-oxidant, the effect delayed senility.
One, anti anoxia experiment
Material: KM mouse, SPF level, Male adult mice, 18 ~ 22g, Inst. of Hygienics and Environmental Medical Science, Academy of Military Medici's animal experimental center provides, credit number: SCXK-(army) 2009-003;
American Ginseng Rhodiola rosea capsules: the safe biotechnology development corporation, Ltd. of Sichuan Province Jia Hui, strong word G20100696, the specification 0.45g/ grain of lot number state food;
Glossy ganoderma Oral Liquid Radix Panacis Quinquefolii: Beijing Tongrentang Health Pharmaceutical Co., Ltd., the strong word G20090270 of lot number state food, specification 10ml/ props up;
1.1 oxygen deficit tolerance experiments
Experimental technique: mouse is divided into 6 groups, often organize 10, inventive samples 1, sample 2, sample 3 establish 3 dosage groups through gavage successive administration 30 days respectively, once a day, gavage volume is 0.1ml/10g body weight, negative control group gives equivalent distilled water, positive controls gavage American Ginseng Rhodiola rosea capsules 500mg/kg, glossy ganoderma Oral Liquid Radix Panacis Quinquefolii 500mg/kg, after last gavage 1h, each mouse puts into the 250ml port grinding bottle (every bottle) filling 5g soda lime respectively, sealing, stop as dead indication to breathe, the record mouse survival time.Result SPSS statistical software carries out t inspection, in table 1.
Table 1 is on the impact of mouse oxygen deficit tolerance time-to-live
Compare with model group, * P < 0.05
Show inventive samples 1 respectively group and control group comparing difference all have conspicuousness, inventive samples 1,2 and 3 each groups all can significantly improve the mouse survival time, have obvious resist oxygen lack effect.
The poisoning survival experiment of 1.2 natrium nitrosum
Experimental technique: mouse is divided into 6 groups, often organize 10, inventive samples 1, sample 2, sample 3 were set to 3 dosage groups respectively, through gavage successive administration 30 days, once a day, negative control group gives equivalent distilled water, positive controls gavage American Ginseng Rhodiola rosea capsules 500mg/kg, glossy ganoderma Oral Liquid Radix Panacis Quinquefolii 500mg/kg, after last gavage 1h, every treated animal is by 200 ~ 240mg/kg dosage injection natrium nitrosum, and ID is 0.1ml/10g body weight, record animal survival time.Result SPSS statistical software carries out t inspection, in table 2.
Table 2 is on the impact of mouse natrium nitrosum moderate time-to-live
Given the test agent 1,2 and 3 compares with control group, and all there is prolongation the time-to-live, and has statistical significance, and judged result is positive.
1.3 acute cerebral hypoxia experiments
Experimental technique: mouse is divided into 6 groups, often organize 10, inventive samples 1(200,500,1000mg/kg), sample 2(200,500,1000mg/kg), sample 3(200,500,1000mg/kg), through gavage successive administration 30 days, once a day, negative control group gives equivalent distilled water, positive controls gavage American ginseng Rhodiola rosea capsules 500mg/kg, glossy ganoderma Oral Liquid Radix Panacis Quinquefolii 500mg/kg, after last gavage 1h, each treated animal by only breaking end from neck, demonstrates to dehiscing after record mouse broken end and dehisces regularly, with the time of panting for index.Result SPSS statistical software carries out t inspection, in table 3.
Table 3 is on the impact of chmice acute cerebral anoxia time
Given the test agent 1,2 and 3 compares with control group, all can extend breathing time, and have statistical significance, and Observable medicine is to the protective effect of cerebral ischemia anoxic.
Two, anti-oxidant experiment
Instrument: RS9901 type light-emitting appearance (Shanghai Rong Sheng bioelectronics Co., Ltd)
Reagent: luminol (Aldrich company) pyrogallol (Shenyang City's reagent one factory) Phen (Shenyang City's reagent three factory) experimental technique:
2.1 non-oxidizabilitys measuring extract in hydroxyl radical free radical system
Adopt chemoluminescence method, utilize Fenton to react and produce hydroxyl radical free radical.Measuring the FeCl adding 40 μ L, 1mmol/L in pipe successively
2, the Phen of 60 μ L, 1mmol/L, 1.6ml carbonate buffer solution (CBSS, pH=10.2) and different sample add sample cell respectively, finally add 100 μ L, 0.6% H
2o
2.Mixing fast before surveying, start immediately to measure, every 10s records data once, separately does blank assay, replaces sample solution with CBSS.Result SPSS statistical software carries out t inspection, in table 4.
Clearance rate with following formulae discovery extract:
Clearance rate S (%)=[1-(A
i/ A
0)] × 100%
In formula: A
i: add the luminous value after Chinese medicine extract; A
0: blank luminous value.
Table 4 affects clearance rate (%) to Scavenging action to hydroxyl free radical
2.2 non-oxidizabilitys measuring extract in ultra-oxygen anion free radical system
Adopt chemoluminescence method, utilize mouse thymus cells system to produce ultra-oxygen anion free radical.Measuring the pyrogallol adding 50 μ L, 1mmol/L in pipe successively, 700 μ LCBSS (pH=10.2), luminol and a series of variable concentrations sample of 200 μ L, 1mmol/L add sample cell respectively, mixing fast before surveying, start immediately to measure, every 10s records data once, separately does blank assay, replaces sample solution with CBSS.Result SPSS statistical software carries out t inspection, in table 5.
Clearance rate with following formulae discovery rhodiola extract:
Clearance rate S (%)=[1-(A
i/ A
0)] × 100%
In formula: A
i: add the luminous value after Chinese medicine extract; A
0: blank luminous value.
Table 5 affects clearance rate (%) to superoxide anion clearance rate
Result shows, shows that each sample of the present invention all has obvious antioxidation activity.
Three, Antisenility Experiment
Material: 21 ~ 22 monthly age senile rats, body weight 360 ~ 510g; 5 months old rats, body weight 180 ~ 220g; Wistar rat, SPF level, is provided by Inst. of Hygienics and Environmental Medical Science, Academy of Military Medici's animal experimental center, credit number: SCXK-(army) 2009-003;
American Ginseng Rhodiola rosea capsules: the safe biotechnology development corporation, Ltd. of Sichuan Province Jia Hui, strong word G20100696, the specification 0.45g/ grain of lot number state food;
Glossy ganoderma Oral Liquid Radix Panacis Quinquefolii: Beijing Tongrentang Health Pharmaceutical Co., Ltd., the strong word G20090270 of lot number state food, specification 10ml/ props up;
5L/10 low-temperature cooling fluid circulating pump (Gongyi Yu Hua Instrument Ltd.);
R1002B constant speed stirred reactor (rotary evaporator) (Shanghai Shen Sheng Bioisystech Co., Ltd);
SHZ-D circulating water type vavuum pump (Gongyi Yu Hua Instrument Ltd.);
HK-16B800 gram of swing high speed medicinal herb grinder (Guangzhou Xu Lang plant equipment Co., Ltd);
CH-10 trough-type mixture machine (Chinese Taizhou City Tian Tai pharmaceutical machine factory);
YK-60 oscillating granulator (Chinese Taizhou City Tian Tai pharmaceutical machine factory).
Experimental technique:
Select 21 ~ 22 monthly age senile rats, be divided into 4 groups and aged control at random by body weight, often organize 12, select 5 months old rats 10 else, as young control, the equal male and female half and half of every treated animal.Administration group presses 500mg/kg gavage every day 1 time, continuous 30d, and control group gives normal saline, all places conventional in animal housing raising.Often organized 10 rats by intraperitoneal injection yellow Jackets 30mg/kg anaesthetize in the 31st day, abdominal aortic blood, surveys Content of MDA and SOD, CAT and GSH-Px by kit measurement method active, gets tissue survey brain and liver L f content and skin and liver Hyp content.Result SPSS statistical software carries out t inspection, in table 6 ~ 8.
Table 6 is on the impact of senile rat serum MDA, SOD and GSH-Px
As seen from table, senile rat Content of MDA is apparently higher than young control, and SOD, CAT and GSH-Px are active in young control, show that senile rat free radical metabolism is abnormal.Each sample of the present invention all can obviously reduce senile rat Content of MDA, and it is active to improve SOD, CAT and GSH-Px, compares tool significance with aged control.
Table 7 is on the impact of senile rat brain and hepatic tissue Lf content
As seen from table, each sample of the present invention all can make senile rat brain and hepatic tissue Lf content obviously reduce.
Table 8 is on the impact of senile rat skin and liver Hyp content
As seen from table, each sample of the present invention all can make senile rat brain and hepatic tissue Hyp content significantly improve.
Four, antifatigue experiment
Each compound composition 2% cmc soln is mixed with suspension.Body weight is selected to be the male Wistar rat 80 of 150 ± 7.5g, be divided into 8 groups, often organize 10, freely ingest and drink water, test group gavages each compound composition (once a day through stomach tube respectively, gavage during early morning), dosage is 1g/kg body weight, and control group gavages equal-volume starch cmc soln.Continuous gavage and raising 3 weeks.After gavage, half an hour carries out swimming test and pole-jump test according to a conventional method the last time.The results are shown in Table 9.
Table 9 is formula anti-fatigue test result respectively
Result of the test shows, each sample compared with negative control group, difference significance (P < 0.05); With the effect of each concentration of sample 2 for the best.
Five, toxicity test
5.1 acute toxicity test
Kunming mouse 100, body weight 18 ~ 22g, wistar rat 20, body weight 180 ~ 220g, male and female half and half, grouping, gavages the present composition with following dosage: mouse dose group is 2g/kg, 4g/kg, 6g/kg, 8g/kg and 10g/kg respectively; Rat dosage group is 1g/kg, 2.5g/kg, 4.5g/kg and 10g/kg.Observe 2 weeks after gavage, rat and mouse is showed no abnormal response, and freely, none is dead in activity.Result shows, the LD of rat and mouse
50value is all greater than 10g/kg.
5.2 chronic toxicity test
Wistar rat 80, body weight 180 ~ 200g, is divided into 4 groups, and often organize 20, male and female half and half, test group dosage is respectively 0.10g/kg, 0.75g/kg and 1.5g/kg, mixes feed, feed group based on control group.Observe and put to death after 30 days, do postmortem.Result: freely, hair luster, feed, stool and urine are normal for animal activity.Between each group in body weight growth, physiochemical indice, biochemical measurement index etc. all without significant difference.Autopsy findings is there are no the pathological change of significant difference.
5.3 mutagenesis and tertogenicity test
Kunming mouse, 25 ~ 28g, in mutagenicity test, test group dosage is respectively 1.25g/kg, 2.5g/kg and 5.0g/kg, and in tertogenicity test, test group dosage is respectively 2.5g/kg, 5.0g/kg and 7.5g/kg.Be all negative control group with distilled water, endoxan 40mg/kg is positive controls.Marrow nuclear test and testis chromosomal aberration test is made respectively by " foodsafety poison lithium assessment process and method ".Result: each test group micronuclear rates and negative control group are without significant difference (p > 0.05), and micronuclear rates is significantly higher than each test group and negative control group (p < 0.01).Each test group chromosome aberrations rate and negative control group, without significant difference (p > 0.05), are significantly higher than each test group and negative control group (p < 0.01).
The preparation of sample 1: 1) rhodiola root 55 parts, Ligusticum wallichii 18 parts add 70% ethanol of its gross weight 8 times amount, refluxing extraction 2 times, each 1h, filters, merging filtrate, and filtrate being concentrated into 60 DEG C, to survey relative densities be the medicinal extract of 1.10 ~ 1.65;
2) by 12 parts, rhizoma Gastrodiae, pseudo-ginseng 10 parts altogether pulverizing be 120 orders, mix with above-mentioned medicinal extract, add the auxiliary material (starch, Icing Sugar, dextrin, maltose) of 5% of its total amount, mixing, compressing tablet after granulating, makes the tablet of 0.6g/ sheet.
The preparation of sample 2: 70% alcohol reflux that 1) rhodiola root 65 parts, Ligusticum wallichii 25 parts, 5 parts, the fruit of Chinese magnoliavine, Radix Angelicae Sinensis 8 parts, the Radix Astragali 9 parts add its gross weight 10 times amount extracts 1h, after use instead 6 times amount 70% alcohol refluxs extract 1h, merging filtrate, filtrate being concentrated into 60 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
2) by 15 parts, rhizoma Gastrodiae, pseudo-ginseng 10 parts, ginseng 8 parts altogether pulverizing be 120 orders, mix with above-mentioned medicinal extract, the refined honey adding its total amount 80% as adhesive and 20% starch, mixing, pill, dry, make honeyed bolus.
The preparation of sample 3: 70% alcohol reflux that 1) rhodiola root 70 parts, Ligusticum wallichii 30 parts, 15 parts, the fruit of Chinese magnoliavine, Radix Angelicae Sinensis 10 parts, the Radix Astragali 12 parts, matrimony vine 9 parts, 12 parts, cultivated land, 5 parts, Radix Glycyrrhizae add its gross weight 6 times amount extracts 2 times, each 1h, filter, merging filtrate, filtrate being concentrated into 60 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
2) by 20 parts, rhizoma Gastrodiae, pseudo-ginseng 15 parts, ginseng 3 parts altogether pulverizing be 120 orders, mix with above-mentioned medicinal extract, add 5 auxiliary materials (starch, Icing Sugar, dextrin, maltose) and be prepared into granule.
[detailed description of the invention]
The proportioning of embodiment 1 active component
In table 10.
Embodiment 2 prepares active component
Formula 1 ~ 14 active component is prepared as follows:
1) water extraction: all the other medicinal materials got except rhizoma Gastrodiae, pseudo-ginseng, ginseng add the water of its gross weight 8 times amount, refluxing extraction 2 times, each 2h, filters, merging filtrate, and filtrate being concentrated into 25 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
2) rhizoma Gastrodiae, pseudo-ginseng, ginseng being pulverized altogether is 120 orders, mixes, low temperature drying, be ground into fine powder with above-mentioned medicinal extract.
Embodiment 3 prepares active component
Formula 1 ~ 14 active component is prepared as follows:
Get the water that all medicinal materials add its gross weight 10 times amount, refluxing extraction 3 times, each 2.5h, filter, merging filtrate, filtrate being concentrated into 25 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65.
Embodiment 4 prepares active component
Formula 1 ~ 14 active component is prepared as follows: all the other medicinal materials 1) got except rhizoma Gastrodiae, pseudo-ginseng, ginseng add the water of its gross weight 9 times amount, refluxing extraction 3 times, each 3h, filters, merging filtrate, filtrate being concentrated into 25 DEG C of survey relative densities is the medicinal extract of 1.20 ~ 1.25;
2) be dissolved in water by above-mentioned medicinal extract, then add absolute ethyl alcohol, make alcohol content reach 80%, get supernatant after placing 24h, 25 DEG C of survey relative densities made by recovery ethanol is the medicinal extract of 1.10 ~ 1.65;
3) rhizoma Gastrodiae, pseudo-ginseng, ginseng being pulverized altogether is 100 orders, with step 2) obtained by medicinal extract mixing, low temperature drying, is ground into fine powder.
Embodiment 5 prepares active component
Formula 1 ~ 14 active component is prepared as follows:
1) get all water adding its gross weight 12 times amount, refluxing extraction 2 times, each 4h, filter, merging filtrate, filtrate being concentrated into 25 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
2) be dissolved in water by above-mentioned medicinal extract, then add absolute ethyl alcohol, make alcohol content reach 80%, get supernatant after placing 24h, 25 DEG C of survey relative densities made by recovery ethanol is the medicinal extract of 1.10 ~ 1.65.
Embodiment 6 prepares active component
Formula 1 ~ 14 active component is prepared as follows: all the other medicinal materials 1) got except rhizoma Gastrodiae, pseudo-ginseng, ginseng add 70% ethanol of its gross weight 6 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filter, merging filtrate, filtrate being concentrated into 25 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
2) rhizoma Gastrodiae, pseudo-ginseng, ginseng being pulverized altogether is 80 ~ 200 orders, mixes, low temperature drying, be ground into fine powder with above-mentioned medicinal extract.
Embodiment 7 prepares active component
Be prepared as follows by formula 1 ~ 14 active component: get 70% ethanol that all medicinal materials add its gross weight 10 times amount, refluxing extraction 3 times, each 2h, filter, merging filtrate, filtrate being concentrated into 25 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65.
Embodiment 8 prepares active component
Formula 1 ~ 14 active component is prepared as follows:
1) get all medicinal materials and be jointly broken into meal, with the volatile oil in the total medicinal material of extraction by steam distillation after immersion, the another device of the aqueous solution after distillation is collected;
2) dregs of a decoction after distillation in step 1) are decocted 2 times, add 8 times amount soak by water 2h, collecting decoction at every turn, filter;
3) by step 2) aqueous solution after the distillation that obtains of the filtrate that obtains and step 1) merges, and adds the volatile oil obtained in step 1), and being concentrated into and surveying relative densities at 25 DEG C is the medicinal extract of 1.10 ~ 1.65.
Embodiment 9 prepares active component
Formula 1 ~ 14 active component is prepared as follows:
Get all common pulverizing, put into microwave extraction tank, add respectively 10 times of water gagings, 12 times amount 75% ethanol, Microwave Extraction 3 times, filter, merging filtrate, be evaporated to 25 DEG C survey relative densities be the medicinal extract of 1.10 ~ 1.65.
Embodiment 10 is prepared in final medicinal extract/meal that the preparation method of active component arbitrary in embodiment 2 ~ 9 extracts by health products and is added auxiliary material or carrier prepares the formulation that any one bromatology is approved, comprises capsule, tablet, pill, pulvis, particle electuary or oral liquid.
Embodiment 11
Formula 1 ~ 14 active component is prepared as follows:
Rhodiola root, Ligusticum wallichii are added 70% ethanol of its gross weight 8 times amount, refluxing extraction 2 times, each 1h, filter, merging filtrate, filtrate being concentrated into 60 DEG C, to survey relative densities be the medicinal extract of 1.10 ~ 1.65;
2) being pulverized altogether by surplus stock is 120 orders, mixes with above-mentioned medicinal extract, adds the auxiliary material (starch, Icing Sugar, dextrin, maltose) of 5% of its total amount, mixing, and compressing tablet after granulating, makes the tablet of 0.6g/ sheet.
Embodiment 12
Formula 1 ~ 14 active component is prepared as follows:
All raw materials except rhizoma Gastrodiae, pseudo-ginseng, ginseng are added its gross weight 10 times amount 70% alcohol reflux extract 1h, after use instead 6 times amount 70% alcohol refluxs extract 1h, merging filtrate, filtrate is concentrated into 60 DEG C survey relative densities be the medicinal extract of 1.10 ~ 1.65;
2) rhizoma Gastrodiae, pseudo-ginseng, ginseng being pulverized altogether is 120 orders, mixes with above-mentioned medicinal extract, the refined honey adding its total amount 80% as adhesive and 20% starch, mixing, pill, dry, make honeyed bolus.
Embodiment 13
Formula 1 ~ 14 active component is prepared as follows:
70% alcohol reflux that all raw materials except rhizoma Gastrodiae, pseudo-ginseng, ginseng add its gross weight 6 times amount is extracted 2 times, each 1h, filters, merging filtrate, filtrate being concentrated into 60 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
2) rhizoma Gastrodiae, pseudo-ginseng, ginseng being pulverized altogether is 120 orders, mixes with above-mentioned medicinal extract, adds 5 auxiliary materials (starch, Icing Sugar, dextrin, maltose) and is prepared into granule.
Table 10 active component proportioning
| Formula 1 | Formula 2 | Formula 3 | Formula 4 | Formula 5 | Formula 6 | Formula 7 | Formula 8 | Formula 9 | Formula 10 | Formula 11 | Formula 12 | Formula 13 | Formula 13 | Formula 14 | |
| Rhodiola root | 50 | 55 | 60 | 65 | 70 | 75 | 50 | 55 | 60 | 65 | 70 | 75 | 50 | 55 | 60 |
| Ligusticum wallichii | 10 | 15 | 20 | 25 | 30 | 35 | 40 | 40 | 35 | 30 | 25 | 20 | 10 | 15 | 20 |
| Rhizoma Gastrodiae | 40 | 35 | 30 | 25 | 20 | 15 | 10 | 15 | 20 | 25 | 30 | 35 | 40 | 35 | 30 |
| Pseudo-ginseng | 5 | 10 | 15 | 20 | 15 | 10 | 5 | 10 | 15 | 20 | 15 | 10 | 5 | 10 | 15 |
| The fruit of Chinese magnoliavine | 0 | 0 | 0 | 20 | 25 | 30 | 15 | 0 | 10 | 0 | 9 | 0 | 20 | 0 | 12 |
| Matrimony vine | 0 | 0 | 9 | 0 | 12 | 15 | 10 | 8 | 19 | 0 | 20 | 8 | 0 | 0 | 0 |
| Ginseng | 0 | 0 | 8 | 10 | 0 | 14 | 13 | 10 | 20 | 0 | 0 | 25 | 8 | 19 | 15 |
| Radix Angelicae Sinensis | 0 | 0 | 7 | 10 | 8 | 0 | 12 | 9 | 8 | 0 | 12 | 0 | 20 | 10 | 12 |
| Cultivated land | 0 | 0 | 10 | 7 | 15 | 6 | 0 | 19 | 9 | 0 | 20 | 10 | 0 | 0 | 0 |
| The Radix Astragali | 0 | 0 | 5 | 6 | 6 | 7 | 9 | 0 | 12 | 0 | 8 | 9 | 10 | 9 | 7 |
| Radix Glycyrrhizae | 0 | 0 | 5 | 3 | 5 | 9 | 9 | 8 | 0 | 0 | 3 | 4 | 0 | 5 | 0 |
Claims (8)
1. have the active component of nutrient and healthcare products for resist oxygen lack, antifatigue, its active component is made up of the mixture of the meal of 50 ~ 70 parts of rhodiola roots and 10 ~ 30 parts of Ligusticum wallichii water extracts and 10 ~ 30 parts of rhizoma Gastrodiaes and 8 ~ 15 portions of pseudo-ginseng;
Or by 50 ~ 70 parts of rhodiola roots, 10 ~ 30 parts of Ligusticum wallichiis, 10 ~ 30 parts of rhizoma Gastrodiaes, the mixture composition of the water extract of 8 ~ 15 portions of pseudo-ginseng;
Or be made up of the mixture of the meal of 50 ~ 70 parts of rhodiola roots and 10 ~ 30 parts of Ligusticum wallichii water extracting alcohol hypostasis and 10 ~ 30 parts of rhizoma Gastrodiaes and 8 ~ 15 portions of pseudo-ginseng;
Or by 50 ~ 70 parts of rhodiola roots, 10 ~ 30 parts of Ligusticum wallichiis, 10 ~ 30 parts of rhizoma Gastrodiaes, the mixture composition of the water extracting alcohol hypostasis of 8 ~ 15 portions of pseudo-ginseng;
Or be made up of the mixture of the meal of 50 ~ 70 parts of rhodiola roots and 10 ~ 30 parts of Ligusticum wallichii alcohol extracts and 10 ~ 30 parts of rhizoma Gastrodiaes and 8 ~ 15 portions of pseudo-ginseng;
Or by 50 ~ 70 parts of rhodiola roots, 10 ~ 30 parts of Ligusticum wallichiis, 10 ~ 30 parts of rhizoma Gastrodiaes, the mixture composition of the alcohol extract of 8 ~ 15 portions of pseudo-ginseng;
Or by 50 ~ 70 parts of rhodiola roots, 10 ~ 30 parts of Ligusticum wallichiis, 10 ~ 30 parts of rhizoma Gastrodiaes, the mixture composition of the distillation extract of 8 ~ 15 portions of pseudo-ginseng.
2. prepare a kind of method of active component of nutrient and healthcare products with resist oxygen lack, antifatigue as claimed in claim 1, it is characterized in that the preparation method of described active component comprises the steps:
A) water extraction: get rhodiola root and Ligusticum wallichii, adds the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
B) described rhizoma Gastrodiae and pseudo-ginseng being pulverized altogether is 80 ~ 200 orders, mixes, low temperature drying, be ground into fine powder with above-mentioned medicinal extract.
3. prepare a kind of method of active component of nutrient and healthcare products with resist oxygen lack, antifatigue as claimed in claim 1, it is characterized in that described active component is prepared according to following step:
Get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng, add the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filter, merging filtrate, filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65.
4. prepare a kind of method of active component of nutrient and healthcare products with resist oxygen lack, antifatigue as claimed in claim 1, it is characterized in that the preparation method of described active component comprises the steps:
C) water extraction: get rhodiola root, Ligusticum wallichii, adds the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
D) alcohol precipitation: be dissolved in water by above-mentioned medicinal extract, then add absolute ethyl alcohol, makes alcohol content reach 60% ~ 90%, gets supernatant after placing 12 ~ 24h, and 20 ~ 30 DEG C of survey relative densities made by recovery ethanol is the medicinal extract of 1.10 ~ 1.65;
E) described rhizoma Gastrodiae, pseudo-ginseng being pulverized altogether is 80 ~ 200 orders, mixes, low temperature drying, be ground into fine powder with the medicinal extract obtained by step d).
5. prepare a kind of method of active component of nutrient and healthcare products with resist oxygen lack, antifatigue as claimed in claim 1, it is characterized in that the preparation method of described active component comprises the steps:
F) water extraction: get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng, adds the water of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65;
G) alcohol precipitation: be dissolved in water by above-mentioned medicinal extract, then add absolute ethyl alcohol, makes alcohol content reach 60% ~ 90%, gets supernatant after placing 12 ~ 24h, and 20 ~ 30 DEG C of survey relative densities made by recovery ethanol is the medicinal extract of 1.10 ~ 1.65.
6. prepare a kind of method of active component of nutrient and healthcare products with resist oxygen lack, antifatigue as claimed in claim 1, it is characterized in that the preparation method of described active component comprises the steps:
H) alcohol extracting: get rhodiola root, Ligusticum wallichii, adds 40% ~ 95% ethanol of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.20 ~ 1.25;
I) described rhizoma Gastrodiae, pseudo-ginseng being pulverized altogether is 80 ~ 200 orders, mixes, low temperature drying, be ground into fine powder with above-mentioned medicinal extract.
7. prepare a kind of method of active component of nutrient and healthcare products with resist oxygen lack, antifatigue as claimed in claim 1, it is characterized in that the preparation method of described active component carries out according to following step:
Alcohol extracting: get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng, adds 40% ~ 95% ethanol of its gross weight 6 ~ 20 times amount, refluxing extraction 1 ~ 3 time, each 1 ~ 4h, filters, merging filtrate, and filtrate being concentrated into 20 ~ 30 DEG C of survey relative densities is the medicinal extract of 1.10 ~ 1.65.
8. prepare a kind of method of active component of nutrient and healthcare products with resist oxygen lack, antifatigue as claimed in claim 1, it is characterized in that the preparation method of described active component comprises the steps:
J) get rhodiola root, Ligusticum wallichii, rhizoma Gastrodiae, pseudo-ginseng be broken into meal jointly, with the volatile oil in the total medicinal material of extraction by steam distillation after immersion, the another device of the aqueous solution after distillation is collected;
K) by step j) in distillation after the dregs of a decoction decoct 1 ~ 3 time, add 8 ~ 15 times amount soak by water 2 ~ 4h, collecting decoction at every turn, filter;
L) by step k) filtrate that obtains and step j) aqueous solution after the distillation that obtains merges, and adds step j) and in the volatile oil that obtains, being concentrated into and surveying relative densities at 20 ~ 30 DEG C is the medicinal extract of 1.10 ~ 1.65.
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