The specific embodiment
Embodiment 1, compound recipe isoflavone soft capsule
Prescription (1000):
Soybean isoflavone 5g
Radix Notoginseng panoxadiol type saponin (contains Rb
155%) 5g
Rhizoma Cimicifugae extract 20g
Alpha-linolenic acid 160g
Gamma-Linolenic acid 60g
Linoleic acid 160g
Oleic acid 40g
Red pigment is an amount of.
Preparation technology: under nitrogen protection, liquid oiliness things such as the alpha-linolenic acid of formula ratio and gamma-Linolenic acid are mixed, add soybean isoflavone and Radix Notoginseng panoxadiol type saponin, Rhizoma Cimicifugae extract, fully stir, dissolving, filter, the degassing, deliver in the jar of filling machine top, stand-by; Be ready to the gelatin solution that the rubber in the soft capsule filling machine top insulation gelatin jar is used simultaneously, stand-by; Under 300,000 grades, 21 ℃~25 ℃, the condition of RH%:39~41%, start rotating mould press pelleting, the soft capsule of making is cleaned, [28 ± 2] ℃ dry 19-27 hour down, packing, packing promptly gets 1000 of the red soft capsule finished products of compound recipe isoflavone soft capsule 450mg (intragranular is tolerant heavy).
Embodiment 2, compound recipe isoflavone soft capsule
Prescription (1000):
Radix Puerariae isoflavone 45g
Saponin of Radix Notoginseng leaf 25g
Rhizoma Cimicifugae extract 38g
Alpha-linolenic acid 154g
Gamma-Linolenic acid 140g
Linoleic acid 60g
Oleic acid 50g
Gelatin is an amount of
Glycerol is an amount of
Amaranth is an amount of
Brilliant black is an amount of.
Preparation technology: with embodiment 1 (summary).1000 of the aubergine soft capsule finished products of 512mg content.
Embodiment 3, compound recipe isoflavone soft capsule
Prescription (1000):
Radix Puerariae isoflavone 100g
Radix Panacis Quinquefolii saponin 5g
Rhizoma Cimicifugae extract 12g
Alpha-linolenic acid 200g
Gamma-Linolenic acid 10g
Linoleic acid 100g
Oleic acid 100g
Gelatin is an amount of
Glycerol is an amount of
Edible titanium dioxide is an amount of.
Preparation technology: with embodiment 1 (summary).1000 of every white soft capsule finished products that contains the 519mg content.
Embodiment 4: compound recipe isoflavone liquid capsule
Prescription (1000):
Radix Puerariae isoflavone 8g
Panoxadiol's type saponin (contains Rb
180%) 10g
Rhizoma Cimicifugae extract 6g
Alpha-linolenic acid 50g
Gamma-Linolenic acid 50g
Linoleic acid 60g
Oleic acid 49g.
Preparation technology: under nitrogen protection, liquid oiliness things such as the alpha-linolenic acid of formula ratio and gamma-Linolenic acid are mixed, add Radix Puerariae isoflavone and panoxadiol's type saponin, Rhizoma Cimicifugae extract, fully stir, dissolving, filter, the degassing, deliver in the jar of capsule machine top, stand-by; Be ready to green liquid capsule simultaneously,, promptly get green compound recipe isoflavone liquid capsule with the packing of liquid capsule machine.
Embodiment 5: compound recipe isoflavone fat emulsion oral liquid
Prescription (1000)
Soybean isoflavone 10g
Radix Notoginseng panoxadiol type saponin (contains Rb
195%) 9g
Rhizoma Cimicifugae extract (containing triterpene 20%) 48g
Gamma-Linolenic acid 40g
Pinolenic acid 160g
Linoleic acid 60g
Oleic acid 9g
Glycerol 210g
Soybean phospholipid 100g.
Preparation technology: under 100 grades condition, under nitrogen protection, soybean phospholipid is added no saline 5000ml; add fluid, isoflavone, panoxadiol's type saponin, Rhizoma Cimicifugae extracts such as acid and gamma-linolenic again; be stirred to evenly, add glycerol, add no saline to 10000ml.In 70~80 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Send into racking machine, by every bottle of 10ml packing, Zha Gai, packing, check, qualified, finished product.Can make the compound recipe isoflavone fat emulsion oral liquid finished product of the specification of 1000 10ml.
For of the present invention may the combination clearly is described, above embodiment is provided, but never is in order to limit the present invention, and scope of the present invention is not subjected to the limitation of illustrated embodiment.
Product study of pharmacy and effect:
One, the stability of product
The lucifuge keeping at room temperature of 1,2,3,4,5 five samples of embodiment was placed 1,2,3,6,12 month, checked that on time it is constant substantially that every sample gets outward appearance, and effective ingredient does not change through check yet.Peroxide value is constant.Assay is measured the isoflavone method with ultraviolet method and is measured.Therefore, think that tentatively various products and various prescription all can reach the shelf-life about 1 year.
The stability test result:
The result shows the sample of this invention preparation, and through the preliminarily stabilised investigation, product quality is basicly stable, can reach more than 1 year.
1, product can replenish women's class estrogen, and then the serial disease cause because of estrogen descends of prevention
(1) bone density improving function
Test according to Ministry of Health of the People's Republic of China's middle bone density improving functional check method of version " health food check and assessment technique standard " in 2003.
The prepared sample emulsion of experimental drug: embodiment 5 prescriptions.Gastric infusion is by 25,50, the 100mg/kg.W administration.The result is as follows:
Each treated animal body weight gain situation is: middle dosage group is best, and model group is the poorest.Low dose group also is better than matched group.
Each organizes the retention of femur calcium: high dose group is best, and model group is the poorest.Low dose group also is better than matched group.
Each measurement result of organizing serum calcium is: high dose group is best, and model group is the poorest.Low dose group also is better than matched group.
Compbined test draws, and the compound recipe isoflavone has remarkable promotion animal weightening finish, raising calcium apparent digestibility, the retention of increase femur calcium both to improve effects such as serum calcium cancentration, and every index all is better than calcium carbonate control group.
(2) improve climacteric syndrome
Age, voluntary accepting embodiment 2 samples with each 1 sooner or later of every day, were taken 60 days continuously, observed 180 days, improved the clinical trial of climacteric syndrome 35 of 42~55 years old the volunteers who enters into the climacteric period.Several cardinal symptoms show as following table in the climacteric syndrome as a result:
The result shows that compound recipe isoflavone product improves significantly to the cardinal symptom of climacteric syndrome.
Two, effects such as defying age, antioxidation, removing interior free yl
(1) blood fat reducing
Material
1. animal: SD rat, body weight 180-230g, the quality certification number " the moving pipe of cloud B04 ".
2. medicine and reagent:
The sample code name FYH that compound recipe isoflavone soft capsule embodiment 1 makes
Cholesterol: Shanghai chemical reagent packing, lot number: 050517
Cholate: east, Suzhou medical biochemical product factory produces lot number: 050101
The propylthiouracil sheet: bridge pharmaceutical factory in Guangzhou produces, lot number: 900523
Adeps Sus domestica: commercially available
Fenofibrate: Taixing, Jiangsu pharmaceutical factory produces, lot number: 050816
3. instrument: Mooarch1000 type full automatic biochemical apparatus (U.S.'s product)
Method
1. high fat emulsifying agent preparation
With cholesterol, propylthiouracil sheet pulverize.Be mixed with lipomul (W/V) by 10% cholesterol, 2% cholate, 1% propylthiouracil, 20% Adeps Sus domestica amount with distilled water.Refrigerator is preserved, and the time spent places in the hot bath and melts.
2. the compound recipe isoflavone soft capsule is to the influence of rat hyperlipidemia model serum lipids
With 40 of above-mentioned SD rats, be divided into the heavy dose of group of (1) normal control group (2) model control group (3) FYH small dose group (4) FYH at random, every group of 10 rats, male and female half and half.Grouping back animal every morning (1) group ig give distilled water, and (2) (3) (4) group ig give isopyknic high lipoprotein emulsion; Hereinafter ig145mg/kg, 290mg/kg are respectively organized in (3) (4), and (1) (2) group is given distilled water, continuously 20d.After the last administration, animal fasting 16h, rat eye socket venous plexus is got blood, and separation of serum is with enzymatic assays serum cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein, LDL (LDL-C), ApoA (APOA), apolipoprotein B (APOB).
The results are shown in Table.
FLQ
Group |
TC (mmll/L) |
TG (mmll/L) |
HDL-C (mmll/L) |
LDL-C (mmll/L) |
APOA (mmll/L) |
APOB (mmll/L) |
The normal control group |
1.37±1.02 |
0.92±0.29 |
0.99±0.25 |
0.18±0.18 |
0.379±0.010 |
0.052±0.042 |
Model control group |
2.67±0.33 |
0.85±0.22 |
1.12±0.38 |
1.10±0.19 |
0.373±0.011 |
0.050±0.012 |
Fenofibrate |
2.62±0.25 |
0.74±0.13 |
1.14±0.21 |
1.30±0.31 |
0.384±0.016 |
0.049±0.017 |
Model+high dose group |
2.30±0.26
* |
0.51±0.23
** |
1.09±0.23 |
0.92±0.29 |
0.381±0.018 |
0.057±0.005 |
Group |
TC (mmll/L) |
TG (mmll/L) |
HDL-C (mmll/L) |
LDL-C (mmll/L) |
APOA (mmll/L) |
APOB (mmll/L) |
Model+low dose group |
2.45±0.28 |
0.54±0.20
** |
1.04±0.29 |
1.23±0.22 |
0.363±0.005 |
0.051±0.005 |
Model control group and normal control group compare: △ P<0.05 △ △ P<0.01
Administration group and model group matched group compare: * P<0.05**P<0.01
The result
By table as seen, the FYH high dose group can significantly reduce the TC (P<0.05) in the hyperlipidemia model rat serum, and low agent group also has reduction trend; Two groups of TG are reduced significantly (P<0.01); HDL-C, LDL-C, APOA, APOB are not made significant difference.
(2) FYH is to the nootropic effect research of aged animal model
1 material
1.1 laboratory animal ICR mice, body weight 20 ± 2g, male and female half and half are provided by Yunnan Province natural drug pharmacology key lab, and the animal quality certification is numbered: No. the 00205th, the real moving card in Yunnan.
1.1.2 medicine and reagent
1.1.2.1 the sample that test sample embodiment 2 makes (code name FYH).Face the time spent, be mixed with 5%, 10% and 20% suspension with 1% carmethose.
1.1.2.2 reference substance brain recovering capsule faces the time spent, the carboxylic first fiber sodium with 1% is mixed with 5% suspension.
1.2 experimental technique and result
Earlier mice is divided into blank group and aging model group.Aging model group mice retrobulbar injection every day D-galactose 0.12mg/g, January continuously
[1]Divide some groups after the mice moulding as required again.Mice does following grouping at random during experiment: (1) blank group (not moulding of animal), irritate stomach N.S.(2) moulding matched group (animal-shaped) is irritated stomach N.S.(3) positive drug control group, animal-shaped, filling stomach brain recovering capsule solution (0.5g/kg is clinical two times of adult's dosage).(4)-(6) group is the basic, normal, high dosage group of FYH, irritates the FYH solution (dosage is respectively clinical 2,5 and 10 times adult's dosage) of stomach 5%, 10% and 20% respectively.Each is organized the mouse stomach volume and is 10ml/kg, once a day, and continuous two weeks.After the last administration, make following index determining.
1.2.1FYH the influence that the learning and memory of aging model mice is kept
1.2.1.1 step down test is imitated literature method
[2], earlier mice was put into diving tower reaction chamber endoadaptation environment 3 minutes, pass to the 36V alternating current to the copper grid at the bottom of the reaction chamber then, after animal is shocked by electricity, tend to skip to platform, to keep away noxious stimulation.Because platform is narrow, inconvenience stops, and forces it to skip to the copper grid once more or repeatedly, but rebound platform promptly again after being shocked by electricity so trained 5 minutes, writes down the number of times that every Mus is shocked by electricity, with this school grade as this Mus.Recast test after 24 hours.During test, earlier mice is placed on the platform, time (incubation period) and the 3 minutes endogenous cause of ill that the record mice jumps off platform is for the first time jumped off platform and the number of times (being errors number) that shocked by electricity, with this index of keeping as memory.The results are shown in Table 1.
Table 1 FLQ is to influence (diving tower method) x ± SD of aging model learning and memory of little mouse, n=20
Annotate: compare with the moulding matched group:
*: P<0.05
*: P<0.01.
Compare with the blank group:
△: P<0.05;
△ △: P<0.01
Above result shows, FYH significant prolongation mice diving tower incubation period, obviously reduces the errors number (P<0.01) of diving tower simultaneously.
1.2.1.2 it is a collection of that square type maze test is got the qualified mice of moulding, divides into groups and administration (or N.S) by above-mentioned test.Be administered to the 11st day, fasting was got the food training as the labyrinth after 12 hours.Mice is put into the starting area, arrives the target area through the rectangle labyrinth.Go to the wrong way in the way, help its correction.Reach its feed of target area relief 5 minutes.So practise 10 times every day, continuous three days.The 4th day (being the fortnight of administration) formal experiment.Each group is chosen 20 of the consistent mices of motility, and the record mice arrives the time of target area and the number of times of going to the wrong way midway from the starting area
[3]Doing the merging of twice, two secondary data continuously averages as the school grade of mice.Animal continues administration, repeats above-mentioned test after the week, and what the gained data were promptly represented to remember keeps, and the results are shown in Table 2:
Table 2 FYH is to improvement effect (maze method) x ± SD n=20 of aging model learning and memory of little mouse
Annotate: compare with the moulding matched group:
*: P<0.05
*: P<0.01.
Compare with the blank group:
△: P<0.05;
△ △: P<0.01
Above result shows that FYH obviously improves the school grade that the aging model mice walks the labyrinth, reduces the memory phase of keeping and walks the errors number that the labyrinth takes place, and promptly strengthens the maintenance effect of mice to memory.
1.2.2FYH influence to monoamine neurotransmitters in aging model mice serum MDA and SOD content and the cerebral tissue
It is a collection of to get mice, grouping and dosage and method are tested with above-mentioned 1.2.1. but administration (or N.S) time be two courses of treatment (28 days), after the last administration, got blood and got the full brain of mice from femoral artery in one hour. measure the content of respectively organizing malonaldehyde the mice serum (MDA) and superoxide dismutase (SOD) respectively by the described method of testing cassete that Nanjing is built up bio-engineering research and provided
[4]Measure the content of monoamine neurotransmitter in the mouse brain tissue with fluorescence spectrophotometry.Operational approach and result are as follows:
The assay of serum malonaldehyde (MDA), the according to the form below operation
|
Standard pipe |
The blank pipe of standard |
Measure pipe |
Measure blank pipe |
10nmol/m standard substance (ml) |
0.1 |
|
|
|
Dehydrated alcohol (ml) |
|
0.1 |
|
|
Specimen (ml) |
|
|
0.1 |
0.1 |
Reagent one (ml) |
0.1 |
0.1 |
0.1 |
0.1 |
Mixing (shaking several test tube racks down)
Reagent two (ml) |
3 |
3 |
3 |
3 |
Reagent three (ml) |
1 |
1 |
1 |
|
50% glacial acetic acid (ml) |
|
|
|
1 |
Vortex vortex mixer mixing, the test tube mouth is tightened with antistaling film, sting an aperture,, take out back flowing water cooling in 95 ℃ of water-baths 40 minutes, centrifugal then (4000rpm) 10 minutes, get supernatant, the 1cm of 532nm place optical path, distilled water zeroing colorimetric, survey and respectively manage the absorbance value, press the content of MDA in the column count serum again:
The vitality test of serum superoxide dismutases (SOD), the according to the form below operation
Reagent |
Measure pipe |
Control tube |
No. 1 reagent (ml) |
1.00 |
1.0 |
Sample (ml) |
0.03 |
|
Distilled water (ml) |
0.50 |
0.5+0.03 |
No. 2 reagent (ml) |
0.1 |
0.1 |
No. 3 reagent (ml) |
0.1 |
0.1 |
Reagent |
Measure pipe |
Control tube |
No. 4 reagent (ml) |
0.1 |
0.1 |
With the abundant mixing of vortex vortex mixer, put 37 ℃ of waters bath with thermostatic control 40 minutes
Mixing is poured into after 10 minutes in the 1cm optical path cuvette, and the distilled water zeroing in wavelength 550nm place colorimetric, is calculated as follows SOD vigor (nu/ml)
The results are shown in Table 3:
Table 3 FYH is to the x ± SD that influences of mice plasma MDA and SOD
Annotate: compare with the moulding matched group:
*: P<0.05
*: P<0.01.
Compare with the blank group:
△: P<0.05;
△ △: P<0.01
Above result shows that FYH can obviously reduce the activity of blood plasma lipide peroxidating content of mda and raising blood plasma superoxide dismutase (SOD).
Three, improve the skin aging symptom
Have 45~56 years old women volunteer 45 example that skin is easily dry, canthus wrinkle, senile plaque, winter skin pruritus occurs, oral product of the present invention (the white soft capsules of embodiment 3 gained), in in October, 2005 to 2005 year December, after continuous 2 months, through paying a return visit the experimenter, the result is as follows in the statistics back:
The result shows that pharmaceutical composition of the present invention has tangible effect to beautifying skin, can comparatively fast increase the moisture and the elasticity of skin, improves the skin physical appearance.The mental status of observing user simultaneously obviously improves.