CN1448141A - Medicine with total dogwood glycosides as main component for treating chronic nephritis and its production process - Google Patents
Medicine with total dogwood glycosides as main component for treating chronic nephritis and its production process Download PDFInfo
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Abstract
The invention relates to a Chinese patent medicine for treating chronic nephritis, which is prepared by extracting total glycoside effective parts from a single traditional Chinese medicine dogwood and adding auxiliary materials. In particular to a medicine for treating chronic nephritis by taking the effective part of the total glycosides of the dogwood as the main component, an extraction method, a preparation method and a monitoring method thereof, and the toxicological and efficacy and clinical test results of the medicine. The preparation method comprises pulverizing Corni fructus, soaking in 70% ethanol, reflux-extracting, enriching total glycosides with macroporous resin, vacuum drying, and making into final product. The capillary electrophoresis Corni fructus fingerprint chromatogram is used for monitoring the production process of Corni fructus total glycoside extraction, preparation and final product. Animal experiments and drug effect experiments show that the medicine has low toxicity and has obvious treatment effect on chronic nephritis model animals; clinical observation shows that the medicine has obvious curative effect on chronic nephritis, the effective rate of clinical symptoms reaches 90 percent, and no toxic or side effect is seen. The invention has obvious social benefit and economic benefit.
Description
One. technical field
The present invention relates to Fructus Corni total glycosides is the Drug therapy chronic nephritis and the production technology thereof of Main Ingredients and Appearance, is specifically related to a kind of Chinese patent medicine for the treatment of chronic nephritis.
Two. background technology
Chronic glomerulonephritis means that the bilateral glomerule diffusivity of the different pathological types that a variety of causes causes or focal inflammation change, clinical onset concealment, and the course of disease is tediously long, and PD is the general name of one group of primary glomerulopathy slowly.Most scholars think that this disease may cause by immunologic mechanism, the inflammatory mediator factor and non-immunologic mechanism etc. owing to infection such as various antibacterials, virus or protozoons.This disease pathogeny can be summarized as: circulating immune complex deposition, the formation of original position immune complex, cellular immunization and glomerular injury, inflammatory mediator and effect of cytokines etc.Basic therapeutic scheme is: 1) general treatment: as lie up, restriction Sal is taken in, and regulates diet etc.; 2) hormone, immunosuppressant treatment etc.; 3) azotemia is handled.If now the drug main hormones that adopts clinically, cyclophosphamide, tripterygium glycosides etc., these medicine life-time service all produce serious toxic and side effects, and some patients can not use these medicines because of contraindication.Therefore, develop the natural Chinese medicine for the treatment of chronic nephritis safely, effectively and have its important society and economic worth.
Fructus Corni (Cornus officinalis Sieb.et Zucc.), another name another name for Sichuan Province Fructus Jujubae, Mus arrow, chicken foot, Fructus Corni, real Fructus Jujubae, Fructus Corni and Fructus Corni etc. are one of Chinese medicine common first names precious medicinal materials.All there are distribution and cultivation in ground such as China Zhejiang, Henan, Shandong, Anhui, Jiangsu, Shanxi, Shaanxi, Sichuan.Its sour in the mouth of Fructus Corni, puckery, slightly warm in nature is returned the Liver and kidney warp, and the effect of liver and kidney tonifying, essence astringing and desertion stemming is arranged.Cure mainly vertigo and tinnitus, soreness of waist and knee joint, impotence and seminal emission, enuresis frequent micturition, bleeding not during menses, profuse sweating collapse, interior-heat is quenched one's thirst.The medicinal record the earliest of Fructus Corni sees Shennong's Herbal, classifies middle product as; The Pharmacopoeia of the People's Republic of China (version in 2000) also records.In chief editors such as chief editors' such as Chen Keji " newly organized delay aging drug " and Zhou Jinhuang " Pharmacology and Clinics of Chinese Materia Medica progress " the Chinese materia medica to Fructus Corni carried out elaboration.Fructus Corni often becomes compound recipe with other drug matching clinically.
Modern pharmacology studies show that, Fructus Corni has effects such as regulating immune, antibiotic, shock, anticoagulant, anti-diabetic, anti-hepatic injury, and clinical effectiveness is good, and safety, toxic and side effects are low.Zhao Shiping etc. (China-Japan Friendship Hospital's journal, 1996,10 (4), 294-298) early studied anti inflammatory immunity inhibitory action in the body of Fructus Corni general glycoside; Zhao Wushu etc. (Chinese microbiology and Journal of Immunology, 1995,15 (5), 325-327) studied the Fructus Corni general glycoside to immunity in the mice body with to the influence of heart transplant survival; Guo Lili etc. (Chinese Journal of Immunology, 2002,18 (3), 197-199) preliminary study the arthritic immunization mechanism of Fructus Corni total glycosides resisting rheumatoid disease; (Shanghai Journal of Immunology such as Li Jianmin, 2001,21 (5), 298-299) reported the Fructus Corni general glycoside to HUVEC express alpha 4 and the plain influence of β 7 integration, think that it may be one of the main antiinflammatory of Fructus Corni total glycosides and immunosuppression mechanism that inhibition vascular endothelial cell express alpha 4 and β 7 integrate elements; (Chinese patent database CN:1310011) has been announced a kind of medicine that immune disease kidney that lupus erythematosus causes decreases for the treatment of to Ding Congli etc., wherein is made up of 16 flavor medicines such as Cortex Moutan, the Radix Astragali, Fructus Corni.
Zhao Shiping etc. (CN_1148968) introduce a kind of extraction process with Fructus Corni extract of immunosuppressive action and antiinflammatory action, use polarity or nonpolar macroporous adsorption resin, ethanol elution, vacuum drying.But the not mentioned composition that extracts is a Fructus Corni total glycosides, and the isolating sample of macroporous adsorbent resin that this patent adopts is the water decoction extract of Fructus Corni.
At present, Fructus Corni total glycosides yet there are no report as the Drug therapy chronic nephritis of Main Ingredients and Appearance and production technology thereof and economy quality-monitoring research efficiently.
Three, summary of the invention
The object of the invention is to provide a kind of medicine for the treatment of chronic nephritis.
Another object of the present invention provides the production technology of a kind of Fructus Corni total glycosides as the Drug therapy chronic nephritis of Main Ingredients and Appearance.
The technical scheme that realizes the object of the invention comprises following step: 1) extract Fructus Corni total glycosides effective site; 2) preparation; The capillary electrophoresis fingerprint monitoring of 3) Fructus Corni total glycosides extraction, preparation and finished product; 4) toxicity and drug effect; 5) clinical observation.A. extract Fructus Corni total glycosides effective site
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening is first with 8 times of soak with ethanol 6-12 hours of measuring 70% concentration, heated 65 ℃~75 ℃ reflux, extract, 2~4 hours, and filtered, medicinal residues continue to add the alcohol reflux 2~4 hours of 6 times of amount 70% concentration, filter, merge extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.05~1.10 (60 ℃) for 45 ℃~60 ℃ in temperature;
4). with concentrated solution stand at low temperature (4~10 ℃) 24 hours, get supernatant, cross macroporous resin D
101, the diameter 40cm of pillar and height 200cm, earlier with 5~7 times of amount pure water rinsing, eluent flow rate 20~25ml/min, the water lotion reject is used the alcohol flushing of 10~30% concentration instead, and eluent becomes clear by mixing, and eluent discards; Continue to collect 50%~80% ethanol elution with 5~6 times of amount 50~80% ethanol elutions; Each step of capillary electrophoresis (CE) the finger printing monitoring elution process that provides with the present invention.
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.B. preparation
With 60~90 parts of Fructus Corni total glycosides, 10~40 parts of mixing and stirring of yellow starch gum (or other excipient), be divided in the capsule or make tablet or make the pharmaceutically any dosage form of acceptable.Capillary zone electrophoresis (CZE) optimal conditions of the capillary electrophoresis fingerprint monitoring Fructus Corni alcohol extraction thing chemistry characteristic fingerprint pattern of c. Fructus Corni total glycosides extraction, preparation and finished product is: coating elasticity is not melted silicon capillary 54cm (internal diameter 50 μ m, effectively separation length 50cm); The 50mM borate buffer solution, pH9.5; Pressure sample introduction 5psi * sec, operating voltage 22kV (+) → (-), 200nm ultraviolet detection on the post, 30 ℃ of column temperatures.The optimal conditions of micellar electrokinetic capillary chromatography (MECC): 30mM SDS, 50mM borate buffer solution, pH9.5, the same CZE of other condition.D. toxicity and drug effect
1). toxicity
Acute toxicity testing studies show that, gives mouse stomach with 4 parts of Fructus Corni total glycosides effective sites and 3 parts of yellow starch gum preparations, measures maximum tolerated dose, LD
50>30g/kg (in Fructus Corni crude drug amount) illustrates that this poison of drug is less.
2). drug effect
The present invention is based on the immunology pathogenesis of chronic glomerulonephritis and Fructus Corni general glycoside pathology pharmacological research conclusion as immunosuppressant, can infer at first theoretically that the Fructus Corni general glycoside has good curative effect to chronic glomerulonephritis, this is a theoretical basis of the present invention.
Fructus Corni total glycosides is to the effect research of rat Heymann nephritis model.Press document (Zhang Jingbo etc., Chinese Journal of Nephrology, 1999,15 (3), 158-161) duplicate rat Heymann glomerulonephritis model, animal pattern is divided into model group, Fructus Corni total glycosides group, positive controls at random (selects dexamethasone for use, 0.1mg/kg), other establishes the blank group, and every treated animal is no less than 15.Gastric infusion 15 days is determined dosage by the frequency or the drug level of administration every day.Observation index comprises qualitative, quantitative urine protein, serum creatinine and blood urea nitrogen, immune globulin Pseudobulbus Bletillae (Rhizoma Bletillae) complement and pathological examination etc.Press t significance test deal with data, the result shows: the Fructus Corni total glycosides preparation can reduce serum creatinine content and the twenty-four-hour urine protein content of animal pattern and alleviate the glomerule lesion degree.
The laboratory observation Fructus Corni total glycosides is to the therapeutical effect of mice IgA nephritis.Press document (Mo Rong etc., Chinese Journal of Nephrology, 1989,5 (2), 123-127) use dextran (Dextran) as antigen, bring out mice IgA nephritis, the treatment of experimentizing property of medication, the content of observation urine protein content, serum urea nitrogen (BUN), creatinine (SCr).Get kidney and carry out perusal and histopathologic examination's discovery, behind the injected in mice antigen, albuminuria occurs, serum BUN raises.After the Fructus Corni total glycosides treatment, the mice body weight there is reduction trend, may be gently relevant with the model mice edema, and can significantly reduce urine protein (P<0.01); Fructus Corni total glycosides 10g/kg group can obviously reduce the content (P<0.05) of BUN in the blood; Fructus Corni total glycosides has certain mitigation to the glomerule pathological changes that Dextran causes.E. clinical observation
The medicine (capsule) that with the Fructus Corni total glycosides is Main Ingredients and Appearance is used for the treatment of chronic nephritis, Preliminary Clinical Observation 50 examples.Select case by chronic nephritis diagnostic criteria (new Chinese medicine clinical research guideline, version in 2002), wherein plain edition (30 example), hypertension type (10 example), acute attack type (10 example).Continuous oral 3 months, every day 3 times, each 4 (every amount that is equivalent to 2g Fructus Corni crude drug) is parameters for observation on effect with urine protein, renal function, edema, hypertension etc.The result shows, total effective rate 80%; Tcm symptom (soreness of waist and knee joint, abdominal distention, the tired power of body, oliguria, edema etc.) remission rate 95%, urine protein correction rate 30%.Menses, urine, just conventional, liver function (ALT, AST) and kidney function test, patient's no abnormal change in back of taking medicine; Do not see untoward reaction.This show this medicine can within a short period of time relieve chronic nephritis symptom, improve patient's whole body functional condition, delay nephridial tissue and effect such as further damage.And take nontoxic, safety and economy for a long time.
Four. description of drawings
Fig. 1 Fructus Corni alcohol extraction thing CZE characteristic fingerprint pattern;
Fig. 2 Fructus Corni alcohol extraction thing MECC characteristic fingerprint pattern;
Fig. 3 Fructus Corni total glycosides effective site CZE finger printing;
Fig. 4 Fructus Corni total glycosides effective site MECC finger printing.
Five. the specific embodiment
Below in conjunction with the embodiment that accompanying drawing and inventor provide, the present invention is described in further detail.
By optimization to conditions such as buffer kind, concentration, pH value, micellar concentration and column temperatures, same for test agent under same instrument, capillary column and close buffer conditions, two kinds of finger printing that separating mechanism is different of acquisition.Optimum Fructus Corni extract finger printing condition is seen (three c).
Shown in Figure 1, Fructus Corni alcohol extraction thing CZE characteristic fingerprint pattern, deposition condition comprises buffer: Borax 50mM, pH9.5; Voltage: 22kV (+) → (-); 30 ℃ of capillary tube column temperatures; Pressure sample introduction 5psi * sec; The 200nm ultraviolet detection;
Shown in Figure 2, Fructus Corni alcohol extraction thing MECC characteristic fingerprint pattern, the Borax 50mM of deposition condition buffer: pH9.5, SDS:30mM; Voltage: 22kV (+) → (-); 30 ℃ of capillary tube column temperatures; Pressure sample introduction 5psi * sec; The 200nm ultraviolet detection;
Shown in Figure 3, Fructus Corni total glycosides effective site CZE finger printing (the same Fig. 1 of deposition condition);
Shown in Figure 4, Fructus Corni total glycosides effective site MECC finger printing (the same Fig. 2 of deposition condition).
In sum, Fig. 1~4 are respectively Fructus Corni alcohol extraction thing and CZE and the MECC chemical feature finger printing of Fructus Corni total glycosides effective site under optimal conditions.And obtain the basic parameters such as migration time, peak area, relative migration time and area percentage of Fructus Corni CZE and each characteristic peak of MECC characteristic fingerprint pattern simultaneously.These finger printing data are the bases of formulating the Fructus Corni quality control standard.
Fructus Corni alcohol extraction thing is through ether defatting, water-saturated n-butanol extraction, and dehydration, obtains Fructus Corni total glycosides effective site.Fructus Corni total glycosides effective site is compared with Fructus Corni alcohol extraction thing, and its saponin content enlarges markedly, and other composition significantly reduces or disappear (as polysaccharide, esters etc.).The peak number of optimal conditions CZE and MECC Fructus Corni alcohol extraction thing characteristic fingerprint pattern (Fig. 1 and Fig. 2) is respectively 39 and 41, and Fructus Corni total glycosides finger printing (Fig. 3 and Fig. 4) peak number is 13 and 20.The CZE finger printing of contrast Fructus Corni alcohol extraction thing (Fig. 1) and Fructus Corni total glycosides effective site (Fig. 3) just can be found, the component of Fig. 1 migration time 19.63min (No. 1 peak), the component of migration time 19.66min in the corresponding diagram 3 (No. 1 peak), its relative peak area rises to 50.66% of Fig. 3 from 8.97% of Fig. 1.In MECC, the component of Fig. 2 migration time 20.48min (No. 7 peaks), the component of migration time 20.58min in the corresponding diagram 4 (No. 8 peaks), its relative peak area rises to 51.16% of Fig. 4 from 9.56% of Fig. 2.This and Fructus Corni alcohol extraction thing obtain Fructus Corni total glycosides effective site through n-butanol extraction, and it is consistent supplying the fact of the chemical compound proportion increase of test agent glycoside structure.In addition, borate buffer solution CE collection of illustrative plates migration time lags behind and supports from another point of view that also this peak is this inference of chemical compound of cornin class formation.
Two kinds of pattern finger printing of the CZE of Fructus Corni ethanol extract and Fructus Corni total glycosides effective site and MECC are stable under optimal conditions, meet the correlation technique requirement of finger printing.
Below be pharmaceutical composition, the Fructus Corni total glycosides effective site extracting method embodiment that the inventor provides.
1. pharmaceutical composition embodiment
Embodiment 1: contain 60~90 parts of Fructus Corni total glycosides in the medicine, 10~40 parts of yellow starch gums.
Embodiment 2: contain 65~85 parts of Fructus Corni total glycosides in the medicine, 15~35 parts of yellow starch gums.
Embodiment 3: contain 70~80 parts of Fructus Corni total glycosides in the medicine, 20~30 parts of yellow starch gums.
Embodiment 4: contain 65~70 parts of Fructus Corni total glycosides in the medicine, 25~35 parts of yellow starch gums.
Embodiment 5: contain 60~90 parts of Fructus Corni alcohol extraction things in the medicine, 10~40 parts of yellow starch gums.
2. Fructus Corni total glycosides effective site extracting method
Method 1:
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 6 hours, heat 70 ℃ of reflux, extract, 2 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.05 (60 ℃) for 50 ℃ in temperature;
4). concentrated solution low temperature (4 ℃) was left standstill 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 20% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 50% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.
Method 2:
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 8 hours, heat 70 ℃ of reflux, extract, 3 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.08 (60 ℃) for 50 ℃ in temperature;
4). concentrated solution low temperature (5 ℃) was left standstill 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 30% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 60% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.
Method 3:
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 10 hours, heat 70 ℃ of reflux, extract, 4 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.07 (60 ℃) for 60 ℃ in temperature;
4). concentrated solution low temperature (8 ℃) was left standstill 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 10% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 70% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.
Method 4:
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 8 hours, heat 72 ℃ of reflux, extract, 2 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.06 (60 ℃) for 55 ℃ in temperature;
4). with concentrated solution stand at low temperature (4 ℃) 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 20% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 80% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.
Claims (10)
1. one kind is the medicine of Main Ingredients and Appearance with the Fructus Corni total glycosides, comprises following step: 1) extract Fructus Corni total glycosides effective site; 2) preparation; The capillary electrophoresis fingerprint monitoring of 3) Fructus Corni total glycosides extraction, preparation and finished product; 4) toxicity and drug effect; 5) clinical observation is characterized in that containing in this medicine 60~90 parts of Fructus Corni total glycosides effective sites, 10~40 parts of excipient.
2. according to claim 1 is the medicine of Main Ingredients and Appearance with the Fructus Corni total glycosides, it is characterized in that containing in this medicine 65~85 parts of Fructus Corni total glycosides effective sites, 25~35 parts of excipient.
3. according to claim 1 is the medicine of Main Ingredients and Appearance with the Fructus Corni total glycosides, it is characterized in that containing in this medicine 70~80 parts of Fructus Corni total glycosides effective sites, 20~30 parts of excipient.
4. according to claim 1 is the medicine of Main Ingredients and Appearance with the Fructus Corni total glycosides, it is characterized in that containing in this medicine 75~85 parts of Fructus Corni total glycosides effective sites, 25~35 parts of excipient.
5. according to claim 1 is the medicine of Main Ingredients and Appearance with the Fructus Corni total glycosides, it is characterized in that containing in this medicine 80~90 parts of Fructus Corni total glycosides effective sites, 10~20 parts of excipient.
6. one kind is used the described medicine production technology of claim 1, and it is characterized in that production technology undertaken by following step: a. extracts Fructus Corni total glycosides effective site 1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved; 2). the powder of Fructus Corni of crushing screening is first with 8 times of soak with ethanol 6-12 hours of measuring 70% concentration, add
65 ℃~75 ℃ reflux, extract, of heat 2~4 hours filter, and medicinal residues continue to add 6 times of amount 70% concentration
Alcohol reflux 2~4 hours, filter, merge extracted twice liquid; 3). decompression and solvent recovery, be concentrated into the alcohol amount 20% that contains for 45 ℃~60 ℃ in temperature, relative density 1.05~
1.10, in the time of 60 ℃, measure; 4). concentrated solution 4~10 ℃ of stand at low temperature 24 hours, is got supernatant, cross macroporous resin D
101, post
The diameter 40cm of son and height 200cm are earlier with 5~7 times of amount pure water rinsing, eluent flow rate
20~25ml/min, the water lotion reject is used the alcohol flushing of 10~30% concentration instead, eluent by
It is clear to mix change, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, collection 50%~
80% ethanol elution; Each step with capillary electrophoresis fingerprint monitoring elution process.5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol,
The thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.B. preparation
With 60~90 parts of Fructus Corni total glycosides, 10~40 parts of mixing and stirring of excipient, be divided in the capsule or make tablet or make the pharmaceutically any dosage form of acceptable.The capillary zone electrophoresis optimal conditions of the capillary electrophoresis fingerprint monitoring Fructus Corni alcohol extraction thing chemistry characteristic fingerprint pattern of c. Fructus Corni total glycosides extraction, preparation and finished product is: coating elasticity is not melted silicon capillary 54cm: internal diameter 50 μ m, effectively separation length 50cm; The 50mM borate buffer solution, pH9.5; Pressure sample introduction 5psi * sec, operating voltage 22kV+ →-, 200nm ultraviolet detection on the post, 30 ℃ of column temperatures.The optimal conditions of micellar electrokinetic capillary chromatography: 30mM SDS, 50mM borate buffer solution, pH9.5, the same capillary zone electrophoresis of other condition.
7. one kind is used the described medicine production technology of claim 1, and it is characterized in that production technology undertaken by following step: a. extracts Fructus Corni total glycosides effective site
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 6 hours, heat 70 ℃ of reflux, extract, 2 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.05 (60 ℃) for 50 ℃ in temperature;
4). concentrated solution low temperature (4 ℃) was left standstill 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 20% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 50% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.B. preparation
With 65~85 parts of Fructus Corni total glycosides effective sites, 25~35 parts of mixing and stirring of excipient are divided in the capsule or make tablet or make the pharmaceutically any dosage form of acceptable.The capillary zone electrophoresis optimal conditions of the capillary electrophoresis fingerprint monitoring Fructus Corni alcohol extraction thing chemistry characteristic fingerprint pattern of c. Fructus Corni total glycosides extraction, preparation and finished product is: coating elasticity is not melted silicon capillary 54cm: internal diameter 50 μ m, effectively separation length 50cm; The 50mM borate buffer solution, pH9.5; Pressure sample introduction 5psi * sec, operating voltage 22kV+ →-, 200nm ultraviolet detection on the post, 30 ℃ of column temperatures.The optimal conditions of micellar electrokinetic capillary chromatography: 30mM SDS, 50mM borate buffer solution, pH9.5, the same capillary zone electrophoresis of other condition.
8. one kind is used the described medicine production technology of claim 1, and it is characterized in that production technology undertaken by following step: a. extracts Fructus Corni total glycosides effective site
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 8 hours, heat 70 ℃ of reflux, extract, 3 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.08 (60 ℃) for 50 ℃ in temperature;
4). concentrated solution low temperature (5 ℃) was left standstill 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 30% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 60% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.B. preparation
With 70~80 parts of Fructus Corni total glycosides effective sites, 20~30 parts of mixing and stirring of excipient are divided in the capsule or make tablet or make the pharmaceutically any dosage form of acceptable.The capillary zone electrophoresis optimal conditions of the capillary electrophoresis fingerprint monitoring Fructus Corni alcohol extraction thing chemistry characteristic fingerprint pattern of c. Fructus Corni total glycosides extraction, preparation and finished product is: coating elasticity is not melted silicon capillary 54cm: internal diameter 50 μ m, effectively separation length 50cm; The 50mM borate buffer solution, pH9.5; Pressure sample introduction 5psi * sec, operating voltage 22kV+ →-, 200nm ultraviolet detection on the post, 30 ℃ of column temperatures.The optimal conditions of micellar electrokinetic capillary chromatography: 30mM SDS, 50mM borate buffer solution, pH9.5, the same capillary zone electrophoresis of other condition.
9. one kind is used the described production technology of claim 6, and it is characterized in that production technology undertaken by following step: a. extracts Fructus Corni total glycosides effective site
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 10 hours, heat 70 ℃ of reflux, extract, 4 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.07 (60 ℃) for 60 ℃ in temperature;
4). concentrated solution low temperature (8 ℃) was left standstill 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 10% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 70% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.B. preparation
With 75~85 parts of Fructus Corni total glycosides effective sites, 25~35 parts of mixing and stirring of excipient are divided in the capsule or make tablet or make the pharmaceutically any dosage form of acceptable.The capillary zone electrophoresis optimal conditions of the capillary electrophoresis fingerprint monitoring Fructus Corni alcohol extraction thing chemistry characteristic fingerprint pattern of c. Fructus Corni total glycosides extraction, preparation and finished product is: coating elasticity is not melted silicon capillary 54cm: internal diameter 50 μ m, effectively separation length 50cm; The 50mM borate buffer solution, pH9.5; Pressure sample introduction 5psi * sec, operating voltage 22kV+ →-, 200nm ultraviolet detection on the post, 30 ℃ of column temperatures.The optimal conditions of micellar electrokinetic capillary chromatography: 30mM SDS, 50mM borate buffer solution, pH9.5, the same capillary zone electrophoresis of other condition.
10. one kind is used the described medicine production technology of claim 1, and it is characterized in that production technology undertaken by following step: a. extracts Fructus Corni total glycosides effective site
1). at first Fructus Corni sarcocarp is cleaned, dries, pulverizes, sieved;
2). the powder of Fructus Corni of crushing screening earlier with the soak with ethanol of 8 times of amount 70% concentration 8 hours, heat 72 ℃ of reflux, extract, 2 hours, filter, medicinal residues continue to add the alcohol reflux 2 hours of 6 times of amount 70% concentration, filtration, merging extracted twice liquid;
3). decompression and solvent recovery is concentrated into the alcohol amount of containing 20%, relative density 1.06 (60 ℃) for 55 ℃ in temperature;
4). with concentrated solution stand at low temperature (4 ℃) 24 hours, get supernatant, cross macroporous resin D
101Earlier with 5~7 times of amount pure water rinsing, diameter of pillar (40cm) and height 200cm), eluent flow rate 20~25ml/min, capillary electrophoresis (CE) the finger printing monitoring total glycosides index that provides with the present invention refers to the water lotion reject, use the alcohol flushing of 20% concentration instead, eluent becomes clear by mixing, and monitors relevant index with CE, and eluent discards; Continue with 5~6 times of amount 50~80% ethanol elutions, flow velocity 20~25ml/min, 80% ethanol elution is collected in the monitoring of CE finger printing;
5). collect eluent, 50 ℃~60 ℃ distilling under reduced pressure, vacuum is 0.088Mpa, reclaims ethanol, the thick paste of gained promptly gets Fructus Corni total glycosides behind vacuum drying.B. preparation
With 80~90 parts of Fructus Corni total glycosides effective sites, 10~20 parts of mixing and stirring of excipient are divided in the capsule or make tablet or make the pharmaceutically any dosage form of acceptable.The capillary zone electrophoresis optimal conditions of the capillary electrophoresis fingerprint monitoring Fructus Corni alcohol extraction thing chemistry characteristic fingerprint pattern of c. Fructus Corni total glycosides extraction, preparation and finished product is: coating elasticity is not melted silicon capillary 54cm: internal diameter 50 μ m, effectively separation length 50cm; The 50mM borate buffer solution, pH9.5; Pressure sample introduction 5psi * sec, operating voltage 22kV+ →-, 200nm ultraviolet detection on the post, 30 ℃ of column temperatures.The optimal conditions of micellar electrokinetic capillary chromatography: 30mM SDS, 50mM borate buffer solution, pH9.5, the same capillary zone electrophoresis of other condition.
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CN102389162A (en) * | 2011-08-04 | 2012-03-28 | 深圳烟草工业有限责任公司 | Method for preparing cornus officinalis extract, application in cigarettes and cigarette |
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