CN101091731A - Medication of reducing blood fat, preparation method, and application - Google Patents
Medication of reducing blood fat, preparation method, and application Download PDFInfo
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- CN101091731A CN101091731A CN 200610027869 CN200610027869A CN101091731A CN 101091731 A CN101091731 A CN 101091731A CN 200610027869 CN200610027869 CN 200610027869 CN 200610027869 A CN200610027869 A CN 200610027869A CN 101091731 A CN101091731 A CN 101091731A
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Abstract
The present invention discloses a medicine for reducing blood-fat. It is a medicine preparation made up by using water-insoluble portion in ethyl alcohol extract or aqueous ethyl alcohol extract of Chinese holly leaf. It can be mixed with pharmaceutically-acceptable carriers and can be made into various preparations. Said invention also provides its preparation method and medicinal application.
Description
Technical field
The present invention relates to a kind of blood lipid-lowering medicine, be specifically related to the effective site of extraction separation blood fat reducing from the Chinese medicine Folium Ilicis Cornutae; The invention still further relates to the preparation method of this blood lipid-lowering medicine; In addition, the present invention also relates to the medical usage of this blood lipid-lowering medicine.
Background technology
The Chinese medicine Folium Ilicis Cornutae is the dry leaf of Aquifoliaceae (Aquifoliaceae) Ilex (Ilex L.) plant Ilex cornuta Lindl. Ilexcornuta Lindl.ex Paxt..Mainly be distributed in Jiangsu, China south, the Hunan, Anhui, zhejiang and other places is one of main source plant of Folium Ilicis.Beginning is stated from supplement to the Herbal, and traditional Chinese medicine theory thinks that Folium Ilicis Cornutae has clearing away heat and nourishing YIN, suppressing the hyperactive liver kidney tonifying, effects such as dispelling wind and activating meridian; Modern age, pharmacological research showed, Folium Ilicis Cornutae has antifertility, coronary artery dilator, effect such as antibiotic grade.The modern plants chemical research shows that triterpene and glycoside thereof are the main components in the Folium Ilicis Cornutae.Modern medicine is thought atherosclerosis (Atherosclerosis, AS) be the main pathological basis of cardiovascular and cerebrovascular disease, perfect day by day along with what the atherosclerotic cause of disease, pathological change, epidemiology and harm situation were familiar with, the pathogenesis of AS is recognized that relatively it is the initiating link of AS that hyperlipemia causes endothelial cell damage.Blood lipid-lowering medicine has caused people's extensive concern.
In the prior art, Folium Ilicis Cornutae is usually used in making health tea or health beverage (Chinese patent CN1718056A, CN1709109A, CN1194864A, CN1112812A), also is used for preparation contraception Chinese patent drug (Chinese patent 1079389A, CN1090498A, CN1491676A).Do not see that as yet Folium Ilicis Cornutae has blood fat reducing, and be used to prepare the report of the cardiovascular diseases's that the treatment hyperlipemia causes medicine.
Summary of the invention
The technical issues that need to address of the present invention are: for suffering from the elderly patients of dyslipidemia, research is medicine more targetedly, so that symptomatic treatment more exactly, thereby improves therapeutic effect to dyslipidemia; Also provide a kind of medicine with good preventive effect for the sickness rate that is about to step into senile middle age prevention or reduce dyslipidemia.Because no matter prevent the morbidity of dyslipidemia or the patient that treatment has suffered from dyslipidemia, all need to take medicine for a long time, so on the basis that guarantees curative effect, should reduce dosage as far as possible, improve pharmaceutical dosage form, reduce medicine cost and price.
Another technical problem that the present invention need solve provides the preparation method of this blood lipid-lowering medicine.
The inventor utilizes the modern pharmacology laboratory facilities, finds that the Chinese medicine Folium Ilicis Cornutae has certain curative effect to the treatment cardiovascular disease, and its effective site is screened, and the extracting method of effective site is studied, and obtains a kind of brand-new blood lipid-lowering medicine.
For further guarantee curative effect stable, reduce dosage, improve pharmaceutical dosage form, just need analyze Folium Ilicis Cornutae, extraction separation has the effective site of curative effect, and the chemical constituent of effective site is studied, and extraction and separation process reasonable in design, obtain following technical solution:
A kind of blood lipid-lowering medicine, it is to be not dissolved in the medicament that the part of water is made in the ethanol of Folium Ilicis Cornutae or the aquiferous ethanol extract, the concentration of aquiferous ethanol is preferably more than 60%, and this medicament is a said dosage form on any pharmaceutics, but is preferably tablet or capsule.
The adjuvant of oral formulations commonly used can be selected for use: disintegrating agent, as: hydroxypropyl starch, hyprolose, carboxymethyl starch sodium, carboxymethylcellulose calcium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose etc.; Filler, as: lactose, sucrose, mannitol, microcrystalline Cellulose, dextrin, starch, calcium phosphate, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, cyclodextrin, micropowder cellulose etc.; Wetting agent and binding agent, as: ethanol, pregelatinized Starch, polyvidone, sodium carboxymethyl cellulose, hypromellose; Lubricant, as: Pulvis Talci, stearic acid, magnesium stearate, calcium stearate, micropowder silica gel, hydrogenated vegetable oil, Macrogol 4000 and polyethylene glycol 6000; Wetting agent, as: sodium lauryl sulphate, Tween 80.
The method of Folium Ilicis Cornutae being made blood lipid-lowering medicine of the present invention is: Folium Ilicis Cornutae is extracted with ethanol or aquiferous ethanol, the concentration of described aquiferous ethanol is more than 60%, be evaporated to and do not have alcohol flavor back water dissolution, the part that is not dissolved in water is added an amount of adjuvant commonly used, make said dosage form on any pharmaceutics.
Folium Ilicis Cornutae is made blood lipid-lowering medicine of the present invention can also adopt following method: Folium Ilicis Cornutae is extracted with ethanol or aquiferous ethanol, the concentration of described aquiferous ethanol is more than 60%, be evaporated to and do not have alcohol flavor back water dissolution, use ethyl acetate and n-butanol extraction respectively, merge ethyl acetate and butanol extraction liquid, add appropriate amount of auxiliary materials, make tablet or capsule.
The chemical constituent of drug effective region of the present invention is analyzed the back to be found:
Contain lupeol in the effective site, 11-ketone group-α-Amyrin cetylate, α-Amyrin cetylate, 3,28-maloic acid glycol, ursolic acid, 30-aldehyde radical lupeol, lupeol falls in the 30-ketone group, darutoside, tanacetene, cupreol, emodin, pomolic acid3-O-[β-D-glucuronic acid methyl ester (1 → 2)]-α-L-arabino-pyranoside, pomolic acid 3-O-α-L-arabinopyranosyl-28-O-β-D-glucopy-ranoside, pomolic acid 3-O-α-L-arabinopyranoside, pomolic acid 3-O-β-D-glucopyranosyl (1 → 2)-α-L-arabinopyranoside, quercetin3-O-β-D-glucopyranosyl-(1 → 2)-α-L-arabinopyranoside, quercetin3-O-β-D-glucopyranoside, rhamnetin 3-O-β-D-glucopyranosid, siaresinolic acid 3-O-β-D-glucopy-ranosyl (1 → 2)-α-L-arabinopyranoside, behenic acid, n-hexacosane.
Its chemical constitution is respectively:
Lupeol 11-ketone group-α-Amyrin cetylate α-Amyrin cetylate
3,28-maloic acid glycol ursolic acid (V) 30-aldehyde radical lupeol
Lupeol cupreol darutoside falls in the 30-ketone group
The emodin behenic acid
pomolic acid 3-O-methyl-β-D-glucopyranosyluronate(1→3)-α-L-arabinopyranoside(I)，pomolicacid 3-O-α-L-arabinopyranosyl-28-O-β-D-glucopyranoside(II)，pomolic acid 3-O-α-L-arabinopyranoside(III)，pomolic acid 3-O-β-D-glucopyranosyl(1→2)-α-L-arabinopyranoside(IV)，quercetin 3-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside(V)，quercetin 3-O-β-D-glucopyranoside(VI)，rhamnetin 3-O-β-D-glucopyranoside(VII)，siaresinolic acid3-O-β-D-glucopyranosyl(1→2)-α-L-arabinopyranoside(VIII)。
For sake of convenience, abbreviate ethanol or the aquiferous ethanol extract of Folium Ilicis Cornutae of the present invention as IL-1, non-water-soluble position abbreviates IL-9 as, and water soluble part abbreviates IL-10 as.
Adopt bait hyperlipemia model rat, with liver index (liver weight/rat body weight); Cholesterol in serum, triglyceride, HDL-C, LDL-C, and the cholesterol, the triglyceride that calculate in HDL-C/TC ratio and the liver be index, carried out activity research.Experimental result proof IL-1, IL-9, IL-10 all can obviously reduce the serum regulating liver-QI tissue T C of rising, reduce the serum regulating liver-QI tissue T G that raises; IL-1, IL-9 obviously reduce the serum LDL-C of rising, and low HDL-C/TC ratio is gone up; IL-9 obviously reduces the liver index of rising.
One, method
1. experiment material
Animal: regular grade male SD rat (150-190g) provides the quality certification number: SCXK (Soviet Union) 2002-0018 by animal reproduction field, Green Dragon mountain, Jiangning.
1.1 medicine and reagent
Simvastatin sheet (Simvastatin), Hangzhou Mo Shadong pharmaceutical Co. Ltd, lot number: 20030708; The zhibituo sheet, Chengdu Diao 9 Wang pharmaceutical factory, lot number: 20030715; The propylthiouracil sheet, Nantong Jinghua Pharmacy Co. Ltd provides, lot number: 20030502; Fel Sus domestica salt, Shanghai chemical reagents corporation of Chinese Medicine group, lot number: F20031029; Cholesterol, Shanghai pure heart biochemical reagents company, lot number: 20040210; T-CHOL (TC) is measured test kit, and Shanghai Rongsheng Bioisystech Co., Ltd provides; Triglyceride (TG), low density lipoprotein, LDL (LDL-C) and high density lipoprotein (HDL-C) are measured test kit: Eastern Europe, Zhejiang biological engineering company limited provides; Other reagent is commercially available analytical pure.
1.2 instrument
The FA1004 electronic balance, Shanghai balance equipment factory; The 80-2B desk centrifuge, Anting Scientific Instrument Factory, Shanghai; Sigma 1-15K type High speed refrigerated centrifuge; 721 type spectrophotometers, Shanghai the 3rd analytical tool factory.
2. experimental technique
100 of male SD rats, body weight 150～180g, normal diet fed for 1 week, after water 12h was can't help in the rat fasting, the eye socket rear vein beard was got blood (etherization), separation of serum, press kit method and measure serum total cholesterol, just be divided into 10 groups according to T-CHOL, 10 every group.Normal group is fed with normal diet, use high lipid food (2% cholesterol for all the other 9 groups, 0.5% Fel Sus domestica salt, 10% Adeps Sus domestica, 0.2% propylthiouracil, normal feedstuff 87.3%) feeds, fed for 4 weeks continuously, high fat gives IL-1300 by 10mL/kg body weight per os respectively when feeding, 600mg/kg, IL-9 150,300mg/kg, IL-10 300,600mg/kg, zhibituo 1000mg/kg, simvastatin 8mg/kg, model group and normal group give the distilled water of equivalent, and continuous 28 days, once a day, after administration the 14th, 21d is after water 12h is can't help in the rat fasting, the eye socket rear vein beard is got blood, and separation of serum is pressed kit method and measured serum cholesterol.The 28th, i.e. after water 12h was can't help in rat fasting, femoral artery was got blood, and rat is put to death in the cervical vertebra dislocation again, dissects rat, and liver is weighed, and calculates liver index (liver weight/rat body weight); Separation of serum is measured cholesterol, triglyceride, HDL-C, LDL-C, and calculates HDL-C/TC ratio; It is an amount of to get fresh liver, makes 10% liver tissue homogenate with isopropyl alcohol, and behind the 48h, 4000rpm is centrifugal, gets supernatant and measures cholesterol, triglyceride by kit method, represents content with μ mol/mg hepatic tissue.
Two, result
As table 1 and shown in Figure 1, to compare with normal group, the liver index of model group obviously raises, and compares with model group, and IL-9 150,300mg/kg, zhibituo 1000mg/kg and simvastatin 8mg/kg all make the liver index of rising obviously reduce.
Table 1. Folium Ilicis Cornutae is to the exponential influence of bait hyperlipidemia rats liver
| Group | Dosage (mg/kg) | Number of animals (only) | Liver index (* 10 -2) |
| |
10 | 3.48±0.22 | |
| |
10 | 4.00±0.63# | |
| IL-1 | 300 | 10 | 3.91 ±0.86 |
| 600 | 10 | 4.06±0.70 | |
| IL-9 | 150 | 9 | 3.19±0.77* |
| 300 | 9 | 3.47±0.38* | |
| IL-10 | 300 600 | 8 9 | 3.47±0.74 3.86±0.71 |
| Zhibituo | 1000 | 7 | 2.88±0.48** |
| Simvastatin | 8 | 8 | 3.28±0.51* |
#:P＜0.05vs normal group *: P＜0.05, * *: P＜0.01vs model group
As table 2 and shown in Figure 2, to compare with normal group, the serum total cholesterol of model group (TC) obviously raises, and compares with model group, and in the time of the 28th day, IL-1 300,600mg/kg all obviously reduce the serum TC that raises; IL-9 300mg/kg, IL-10 600mg/kg, zhibituo 1000mg/kg and simvastatin 8mg/kg all obviously reduced the serum TC that raises at the 21st and the 28th day.
Table 2. Folium Ilicis Cornutae is to the influence (mmol/L) of bait hyperlipidemia rats serum TC
| Group | Dosage (mg/kg) | Number of animals (only) | Before the test | After the test | ||
| The 14th day | The 21st day | The 28th day | ||||
| |
10 | 2.05±0.58 | 1.91±0.31 | 1.78±0.17 | 1.82±0.21 | |
| |
10 | 1.87±0.68 | 5.52±1.48 ### | 5.68±1.07 ### | 6.52±1.92 ### | |
| IL-1 | 300 | 10 | 1.92±0.53 | 5.69±1.52 | 5.11±1.09 | 3.51±0.56*** |
| 600 | 10 | 1.92±0.53 | 4.96±1.13 | 4.64±0.81 | 3.83±1.34** | |
| IL-9 | 150 | 9 | 1.92±0.53 | 4.68±1.14 | 4.73±1.19 | 6.00±1.51 |
| 300 | 9 | 1.94±0.48 | 4.72±2.15 | 4.61±1.28* | 4.71±0.79* | |
| IL-10 | 300 | 8 | 1.92±0.45 | 4.88±1.35 | 4.79±1.04 | 5.40±1.65 |
| 600 | 9 | 1.87±0.68 | 4.47±1.01 | 4.68±0.88* | 4.39±1.29* | |
| Zhibituo | 1000 | 7 | 2.05±0.44 | 4.23±1.59 | 4.08±1.21* | 3.78±1.40** |
| Simvastatin | 8 | 8 | 2.07±0.58 | 5.08±2.37 | 4.20±1.09* | 4.73±1.11* |
###:P＜0.001vs normal group *: P＜0.05, * *: P＜0.01, * * *: P＜0.001vs model group
As table 3 and shown in Figure 3, compare with normal group, the serum regulating liver-QI tissue triglycerides (TG) of model group and hepatic tissue TC all extremely obviously raise, and compare with model group, and IL-1 300,600mg/kg all extremely obviously reduce serum regulating liver-QI tissue T G and the hepatic tissue TC that raises; IL-9 150,300mg/kg and IL-10 300,600mg/kg all extremely obviously reduce the serum regulating liver-QI tissue T G that raises; IL-9 300mg/kg and IL-10 600mg/kg all obviously reduce the hepatic tissue TC that raises; Zhibituo 1000mg/kg and simvastatin 8mg/kg all obviously reduce serum regulating liver-QI tissue triglycerides and the hepatic tissue TC that raises.
Table 3. Folium Ilicis Cornutae is to the influence (mmol/L) of bait hyperlipidemia rats serum regulating liver-QI tissue T G
| Group | Dosage (mg/kg) | Number of animals (only) | Serum TG | Hepatic tissue TG | Hepatic tissue TC |
| (mmol/L) | (μmol/mg) | (μmol/mg) | |||
| |
10 | 0.35±0.13 | 2.99±1.07 | 2.87±0.72 | |
| |
10 | 1.36±0.31### | 5.68±0.76### | 7.11±1.21### | |
| IL-1 | 300 | 10 | 0.80±0.28*** | 4.42±0.59*** | 4.71±1.14*** |
| 600 | 10 | 0.58±0.21*** | 3.68±0.78*** | 5.04±1.06*** |
| IL-9 | 150 300 | 9 9 | 0.93±0.24** 0.75±0.22*** | 4.56±0.61** 4.25±0.88*** | 6.38±1.13 5.66±1.15* |
| IL-10 | 300 | 8 | 0.86±0.30** | 3.64±0.93*** | 6.60±1.29 |
| 600 | 9 | 0.91±0.17** | 3.81±1.24*** | 5.33±0.97** | |
| Zhibituo | 1000 | 7 | 0.83±0.25** | 4.62±0.69* | 5.80±0.90* |
| Simvastatin | 8 | 8 | 0.71±0.29*** | 4.16±1.02** | 5.69±0.86* |
###:P＜0.001vs normal group *: P＜0.05, * *: P＜0.01, * * *: P＜0.001vs model group
As table 4 and shown in Figure 4, to compare with normal group, the serum low-density LP-cholesterol of model group (LDL-C) obviously raises, and HDL-C/TC ratio is obviously low.Compare with model group, IL-1 300,600mg/kg, IL-9 300mg/kg all obviously reduce the serum LDL-C that raises, and low HDL-C/TC ratio is gone up.Zhibituo 1000mg/kg and simvastatin 8mg/kg all obviously reduce the LDL-C that raises, and make low HDL-C/TC ratio rebound significantly.
Table 4. Folium Ilicis Cornutae is to the influence of bait hyperlipidemia rats serum blood lipoprotein
| Group | Dosage (mg/kg) | Number of animals (only) | LDL-C | HDL-C | HDL-C/TC |
| (mmol/L) | (mmol/L) | ||||
| |
10 | 0.69±0.17 | 1.19±0.32 | 0.66±0.17 | |
| |
10 | 4.43±0.79### | 1.29±0.36 | 0.22±0.09### | |
| IL-1 | 300 | 10 | 2.46±0.27 *** | 1.31±0.38 | 0.38±0.13** |
| 600 | 2.71±0.42 *** | 1.52±0.34 | 0.43±0.13*** | ||
| IL-9 | 150 | 9 | 3.95±1.16 | 1.28±0.41 | 0.22±0.07 |
| 300 | 2.80±0.68*** | 1.51±0.58 | 0.32±0.12* | ||
| IL-10 | 150 | 8 | 3.86±0.51 | 1.47±0.52 | 0.29±0.13 |
| 300 | 3.66±1.05 | 1.23±0.32 | 0.29±0.08 | ||
| Zhibituo | 1000 | 7 | 1.05±0.27** | 1.38±0.39 | 0.42±0.22* |
| Simvastatin | 8 | 8 | 0.89±0.17*** | 1.46±0.49 | 0.31±0.07* |
###:P＜0.001vs normal group *: P＜0.05, * *: P＜0.01, * * *: P＜0.001vs model group
Description of drawings
Fig. 1 is that medicine of the present invention is to the exponential sketch map that influences of bait hyperlipidemia rats liver;
Fig. 2 is the influence sketch map of medicine of the present invention to bait hyperlipidemia rats serum TC;
Fig. 3 is influence (mmol/L) sketch map of medicine of the present invention to bait hyperlipidemia rats serum regulating liver-QI tissue T G;
Fig. 4 is the influence sketch map of medicine of the present invention to bait hyperlipidemia rats serum blood lipoprotein.
The specific embodiment
Below in conjunction with embodiment the present invention is described in further detail.
Get 20 kilograms of Folium Ilicis Cornutaes, pulverize, add 85% ethanol 20L reflux, extract 4h, filter; Repeat to extract 2 times, merge extractive liquid,, being evaporated to does not have the alcohol flavor, uses an amount of dissolved in distilled water, gets the insoluble position of water, after the insoluble position adding of water appropriate amount of auxiliary materials, is pressed into tablet.
Get 20 kilograms of Folium Ilicis Cornutaes, pulverize, add 85% ethanol 20L reflux, extract 4h, filter; Repeat to extract 2 times, merge extractive liquid,, being evaporated to does not have the alcohol flavor, uses an amount of dissolved in distilled water, gets the insoluble position of water, after the insoluble position adding of water appropriate amount of auxiliary materials, granulates, and records capsule.
Get 20 kilograms of Folium Ilicis Cornutaes, pulverize, add 85% ethanol 20L reflux, extract 4h, filter; Repeat to extract 2 times, merge extractive liquid,, being evaporated to does not have the alcohol flavor, uses an amount of dissolved in distilled water, uses ethyl acetate and n-butanol extraction respectively, merges ethyl acetate and butanol extraction liquid, after the adding appropriate amount of auxiliary materials, is pressed into tablet.
Get 20 kilograms of Folium Ilicis Cornutaes, pulverize, add 85% ethanol 20L reflux, extract 4h, filter; Repeat to extract 2 times, merge extractive liquid,, being evaporated to does not have the alcohol flavor, uses an amount of dissolved in distilled water, uses ethyl acetate and n-butanol extraction respectively, merges ethyl acetate and butanol extraction liquid, after the adding appropriate amount of auxiliary materials, granulates, and records capsule.
Claims (7)
1, a kind of blood lipid-lowering medicine is characterized in that, it is to be not dissolved in the medicament that the part of water is made in the ethanol of Folium Ilicis Cornutae or the aquiferous ethanol extract.
2,, blood lipid-lowering medicine as claimed in claim 1, it is characterized in that the concentration of aquiferous ethanol is more than 60%.
3, blood lipid-lowering medicine as claimed in claim 1 or 2 is characterized in that, described medicament is a said dosage form on any pharmaceutics.
4, blood lipid-lowering medicine as claimed in claim 3 is characterized in that, described medicament is tablet or capsule.
5, the preparation method of the described blood lipid-lowering medicine of claim 4, it is characterized in that, Folium Ilicis Cornutae is extracted with ethanol or aquiferous ethanol, the concentration of described aquiferous ethanol is more than 60%, be evaporated to and do not have alcohol flavor back water dissolution, the part that is not dissolved in water is added appropriate amount of auxiliary materials, make tablet or capsule.
6, the preparation method of the described blood lipid-lowering medicine of claim 4, it is characterized in that, Folium Ilicis Cornutae is extracted with ethanol or aquiferous ethanol, the concentration of described aquiferous ethanol is more than 60%, be evaporated to not have and use water dissolution after alcohol is distinguished the flavor of, use ethyl acetate and n-butanol extraction respectively, merge ethyl acetate and butanol extraction liquid, add appropriate amount of auxiliary materials, make tablet or capsule.
7, any one described medicine is used in the cardiovascular diseases's that preparation treatment hyperlipemia causes medicine among the claim 1-4.
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|---|---|---|---|
| CN 200610027869 CN101091731A (en) | 2006-06-20 | 2006-06-20 | Medication of reducing blood fat, preparation method, and application |
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|---|---|---|---|
| CN 200610027869 CN101091731A (en) | 2006-06-20 | 2006-06-20 | Medication of reducing blood fat, preparation method, and application |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070924A (en) * | 2011-10-25 | 2013-05-01 | 上海中医药大学 | Chinese traditional medicine composition for treating metabolic syndrome, and preparation method and application thereof |
| CN112646022A (en) * | 2020-12-16 | 2021-04-13 | 熊猫乳品集团股份有限公司 | Bioactive peptide PKCPKCDKEVYFAERV, and preparation method and application thereof |
-
2006
- 2006-06-20 CN CN 200610027869 patent/CN101091731A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070924A (en) * | 2011-10-25 | 2013-05-01 | 上海中医药大学 | Chinese traditional medicine composition for treating metabolic syndrome, and preparation method and application thereof |
| CN103070924B (en) * | 2011-10-25 | 2014-10-15 | 上海中医药大学 | Chinese traditional medicine composition for treating metabolic syndrome, and preparation method and application thereof |
| CN112646022A (en) * | 2020-12-16 | 2021-04-13 | 熊猫乳品集团股份有限公司 | Bioactive peptide PKCPKCDKEVYFAERV, and preparation method and application thereof |
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Open date: 20071226 |