CN101530532A - Oral pharmaceutical preparation of yam total sapogenin and preparation method and application thereof - Google Patents
Oral pharmaceutical preparation of yam total sapogenin and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses an oral pharmaceutical preparation of yam total sapogenin and a preparation method and application thereof, pertaining to the field of traditional Chinese medicine. In respect of the pharmaceutical preparation, sapogenin compositions in yam are hydrolyzed into sapogenin, then the sapogenin is matched with high-efficiency medical auxiliary materials and mixed evenly by the method of micronization, and then the high-efficiency oral pharmaceutical preparation is produced. The pharmaceutical preparation can greatly enhance the dispersibility, wettability and solubility of the sapogenin compositions, increase the absorption and utilization degree of the sapogenin and improve the biological utilization degree of the sapogenin. The pharmaceutical preparation has outstanding effects in treating diseases such as gout affection, hyperlipemia, diabetes, coronary heart disease, angina, rheumatism and depressive illness.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation that contains Rhizoma Dioscoreae Nippponicae total sapogenins, it is oral drug preparation of main effective ingredient and uses thereof that the saponin component in particularly a kind of Rhizoma Dioscoreae Nipponicae is hydrolyzed into sapogenin.Belong to the field of Chinese medicines.
Background technology
Rhizoma Dioscoreae Nipponicae is the dry rhizome of Dioscoreaceae yam Dioscorea nipponica Mak. Ningpo Yam Rhizome Dioscorea nipponica Makino, have the effect that expelling wind and removing dampness, relaxing muscles and tendons and activating QI and blood in the collateral, relieving cough and asthma eliminate the phlegm, cure mainly arthritis, lumbago and skelalgia pain, numb limbs and tense tendons, big arthrosis, injury from falling down, chronic bronchitis etc.Main component is the steroidal saponin constituents in the Rhizoma Dioscoreae Nipponicae, and total saponin extracts has better curative effect to coronary heart disease, atherosclerosis, hyperlipidemia, asthma, inflammation and tumor.Mainly contain tens kinds of steroidal saponin constituents such as dioscin, gracillin in the Rhizoma Dioscoreae Nipponicae, diosgenin (diosgenin, Dio) be wherein a kind of steroid sapogenin, be also referred to as diosgenin or diosgenin, it is by the product (article of Huang Yahui, Sheng Xiaobang " progress of diosgenin ", " the Chinese wild plant resource " 24th that be published in 2005 year October roll up 5th phase 20th page) of dioscin (dioscin) after hydrolysis is sloughed glycosyl.
Though the saponin component in the Rhizoma Dioscoreae Nipponicae always by as medical substance by clinical practice, discovering in recent years, real in human body the performance drug effect, be the sapogenin that saponin is obtained by the flora decomposition and inversion in people's intestinal.Experimental results demonstrate, Dio all shows very strong biological activity (Wang Xiao roc survey article " new development of dioscin bioactivity research " is published in the 138th page of " foreign medical science Chinese medicine fascicle " 2004 the 26th the 3rd phase of volume) in methods such as antitumor, immunomodulating, antiinflammatory, blood fat reducing, anti-AIDS.
Many pharmacokinetics prove, saponin component is difficult to absorb in intestinal, mostly need to be decomposed into sapogenin through intestinal bacteria, enzyme and could see through mucosa and be absorbed into blood and bring into play curative effect.So for reducing the step that saponin component absorbs in vivo in the Rhizoma Dioscoreae Nipponicae, saponin component is hydrolyzed with the method for acid hydrolysis, enzyme hydrolysis or microbial hydrolysis in external elder generation, with its aglycon medication, it is rapid then to bring into play curative effect, relatively rationally.Glycosides is made up of aglycon and sugar, and its hydrophilic is strong, and molecular weight is big, and the lipotropy of aglycon is strong, and molecular weight is little.Aglycon has been sloughed glycosyl with respect to glycosides, and its polarity reduces, fat-soluble enhancing.Can learn that from biopharmaceutical research though fat-soluble strong material can be easier to be absorbed by the body, but just because of it is fat-soluble strong, cause it to be difficult for by the body fluid moistening, so in fact be difficult to enter the process of absorption, its bioavailability is lower.This problem is not that conventional formulation technology can solve, and never draws attention for many years, so just the phenomenon that sapogenin is not made into preparation can occur yet.There is such problem equally in saponin component in the Rhizoma Dioscoreae Nipponicae, and therefore the research to Rhizoma Dioscoreae Nippponicae total sapogenins has great significance.But existing technology has all been ignored the research to Rhizoma Dioscoreae Nippponicae total sapogenins, and its effect and applicable cases are in space state always.
Summary of the invention
It is the oral drugs of active component with the Rhizoma Dioscoreae Nippponicae total sapogenins that first purpose of the present invention is to provide a kind of;
Second purpose provides the dosage form of this medicine, particularly a kind of high-efficiency preparation;
The 3rd purpose provides the preparation method of this medicine high-efficiency preparation.
Provide the application of this medicine in the medicine of treatment goat, hyperlipemia, diabetes, coronary heart disease, angina pectoris, rheumatism or depressive illness at last.
The object of the invention first purpose is achieved in that
The inventor provides a kind of oral medicine, and this medicine is active component with the Rhizoma Dioscoreae Nippponicae total sapogenins.
Although what people took is the preparation that contains the Yam total saponin in the past, must wait until that saponin is become aglycon by the intestinal microbial population decomposition and inversion after, could real onset.And the many defectives that exist in this conversion process cause the drug effect shakiness: medicine long operational time, transformation efficiency in vivo is low; Conversion process is uncertain, decomposes the aglycon of being not only that obtains, and also may be other inert matters; Individual variation is big, and everyone transformation efficiency height is different, can not give full play to drug effect or the like.In view of above reason, have only and Rhizoma Dioscoreae Nippponicae total sapogenins is directly made pharmaceutical preparation be applied to human body, when could guarantee to reduce dosage, improve drug effect.
Medical value at Rhizoma Dioscoreae Nipponicae, the inventor extracts from the Rhizoma Dioscoreae Nipponicae medical material by prior art and obtains the Yam total saponin, and it is hydrolyzed, make saponin component wherein slough glycosyl, generation has more bioactive sapogenin, promptly becomes Rhizoma Dioscoreae Nippponicae total sapogenins provided by the present invention, the inventor confirms after deliberation, glycoside material gained aglycon after hydrolysis has not had glycosyl, and its lipotropy strengthens greatly, thereby aglycon is absorbed than the easier intestinal mucosa that sees through of glycosides; Simultaneously, the molecule of medicine is more little also easy more to be absorbed, the glycosides hydrolysis fall with glycan molecule become aglycon after, molecular change gets littler, also can easier absorption.In addition, directly as medical substance, overcome in the past glycoside material long operational time, factor such as transformation efficiency is low, conversion results is uncertain in vivo, improved the bioavailability of medicine greatly, saved drug resource with aglycon.
In medicine provided by the invention, Rhizoma Dioscoreae Nippponicae total sapogenins can use separately, also can unite use with the other drug composition, that is: in active constituents of medicine, can have only the pure product of Rhizoma Dioscoreae Nippponicae total sapogenins, also can be the Rhizoma Dioscoreae Nippponicae total sapogenins crude product, can also be the mixture of Rhizoma Dioscoreae Nippponicae total sapogenins and other drug, reaches the purpose of partner treatment, auxiliary treatment.The present invention preferably uses the Rhizoma Dioscoreae Nippponicae total sapogenins crude product, promptly extracts the Yam total saponin from medical material, hydrolysis in a suitable manner again, and make with extra care as required, obtain required purity.Except mainly containing the Rhizoma Dioscoreae Nippponicae total sapogenins, also contain inevitable accessory substance and impurity in other extractions and the hydrolytic process in extract obtained, comprise a small amount of unhydrolysed glycosides and secondary glycosides etc.
Above-mentioned method for hydrolysis has comprised acid hydrolysis, enzyme hydrolysis or microbial hydrolysis, and the inventor is through screening, and following several concrete method for hydrolysis is provided respectively: acid hydrolysis can be hydrolyzed with hydrochloric acid, sulphuric acid, acetic acid and the formic acid etc. of 1～10mol/L; Enzyme hydrolysis can be hydrolyzed with emulsin, maltase, conversion carbohydrase, hesperidinase etc.; Microorganism can be hydrolyzed with escherichia coli, enterococcus, lactobacillus, clostridium, lopsided thalline, bifidus bacillus and human body intestinal canal normal flora etc.
Second purpose of the present invention provides the pharmaceutical preparation of above-mentioned Rhizoma Dioscoreae Nippponicae total sapogenins, especially a kind of high-efficiency preparation.Those skilled in the art can cooperate Rhizoma Dioscoreae Nippponicae total sapogenins of the present invention with suitable adjuvant easily, are prepared into various conventional formulations.But the inventor is also noted that another problem, and promptly because aglycon fat-soluble stronger relatively, thereby after its preparation was applied to human body, aglycon composition wherein was difficult for wetted and stripping, if can not address this problem, also can influence the absorption of aglycon.So at this problem, the inventor provides a kind of new solution, can guarantee Rhizoma Dioscoreae Nippponicae total sapogenins is made high-efficiency preparation, this technical scheme is:
Scheme one: a kind of is the efficient pharmaceutical preparation of active component with Rhizoma Dioscoreae Nippponicae total sapogenins of the present invention, contain bio-adhesive agent and wetting agent in its adjuvant, can also contain the conventional adjuvant on dispersant and other pharmaceuticss, and be made into oral formulations such as tablet, capsule, granule, pill.
The core of this technical scheme is Rhizoma Dioscoreae Nippponicae total sapogenins is used for pharmaceutical preparation, and guarantees the efficient utilization of Rhizoma Dioscoreae Nippponicae total sapogenins by special adjuvant.Thereby; embody in the concrete pharmaceutical preparation; can have only Rhizoma Dioscoreae Nippponicae total sapogenins of the present invention in its active constituents of medicine; also can be used with other medicinal or non-medical substances; as long as its objective is contained Rhizoma Dioscoreae Nippponicae total sapogenins is utilized bio-adhesive agent and wetting agent, can also utilize dispersant, carry out moistening, dispersion; to make oral high-efficiency preparation, all should be in the scope of the present patent application protection.In like manner, technical solution of the present invention is selected bio-adhesive agent and wetting agent for use, can also be with dispersant as main adjuvant, and purpose is to make Rhizoma Dioscoreae Nippponicae total sapogenins to be able to fully, to disperse uniformly, is beneficial to absorption; In actual applications; can also add other conventional adjuvants and molding adjuvant as required; as starch, microcrystalline Cellulose, carboxymethylstach sodium, citric acid, sodium bicarbonate, low-substituted hydroxypropyl methylcellulose, lactose, mannitol, citric acid, Aspartane, dextrin, magnesium stearate etc.; these all should be considered as the work finished on the basis of the technology of the present invention, also should be subjected to the protection of the present patent application.
In this technical scheme, the bio-adhesive agent is preferably chitosan, carbomer, polyvinylpyrrolidone or the mixture between them; Wetting agent is preferably lecithin, poloxamer or its mixture; Dispersant is preferably micropowder silica gel, cyclodextrin, Polyethylene Glycol or the mixture between them.
Wherein, chitosan, carbomer have the bio-adhesive performance as the bio-adhesive agent, but prolong drug significantly improves bioavailability of medicament in the gastrointestinal holdup time.Surfactant such as lecithin, poloxamer has the effect of moistened surface to Rhizoma Dioscoreae Nippponicae total sapogenins, reduces surface tension, increases the dissolubility of fat-soluble Rhizoma Dioscoreae Nippponicae total sapogenins, promotes it to absorb rapidly, is beneficial to rapid performance curative effect.Micropowder silica gel, cyclodextrin, Polyethylene Glycol be as dispersant, and itself possess hydrophilic property is beneficial to moistening, the dispersion of aglycon, strengthens stability of drug.Rhizoma Dioscoreae Nippponicae total sapogenins of the present invention and above-mentioned adjuvant are used, and fully mix homogeneously can strengthen wherein dispersibility, the wettability of Rhizoma Dioscoreae Nippponicae total sapogenins, improves its bioavailability.
In the preferred case, each composition proportion is preferably active component 20～60% in the medicine of the present invention, bio-adhesive agent 1～10%, wetting agent 5～20%, dispersant 0～30%, other adjuvants 0～50%.Other adjuvants wherein are meant other adjuvants of preparation some in forming process, as: starch, microcrystalline Cellulose, carboxymethylstach sodium, citric acid, sodium bicarbonate, low-substituted hydroxypropyl methylcellulose, lactose, mannitol, citric acid, Aspartane, dextrin, magnesium stearate etc.
Technique scheme is mainly used in oral formulations, and optimum dosage form is tablet, capsule, granule, powder and pill.
Scheme two: a kind of is the efficient pharmaceutical preparation of active component with Rhizoma Dioscoreae Nippponicae total sapogenins of the present invention, contain dispersant and wetting agent in its adjuvant, can also contain the conventional adjuvant on bio-adhesive agent and other pharmaceuticss, and oral formulations such as the soft capsule that is made into, liquid hard capsule, drop pill.
The core of this technical scheme is Rhizoma Dioscoreae Nippponicae total sapogenins is used for pharmaceutical preparation, and guarantees the efficient utilization of Rhizoma Dioscoreae Nippponicae total sapogenins by special adjuvant.Thereby; embody in the concrete pharmaceutical preparation; can have only Rhizoma Dioscoreae Nippponicae total sapogenins of the present invention in its active constituents of medicine; also can be used with other medicinal or non-medical substances; as long as its objective is contained Rhizoma Dioscoreae Nippponicae total sapogenins is utilized dispersant and wetting agent, can also utilize the bio-adhesive agent, carry out moistening, dispersion; to make oral high-efficiency preparation, all should be in the scope of the present patent application protection.In like manner, technical solution of the present invention is selected dispersant and wetting agent for use, can also be with the bio-adhesive agent as main adjuvant, and purpose is to make Rhizoma Dioscoreae Nippponicae total sapogenins to be able to fully, to disperse uniformly, is beneficial to absorption; In actual applications; can also add other conventional adjuvants and molding adjuvant as required; as glycerol, glycine, citric acid, ethyl hydroxybenzoate, Cera Flava etc., these all should be considered as the work finished on the basis of the technology of the present invention, also should be subjected to the protection of the present patent application.
In this technical scheme, dispersant is preferably vegetable oil or Polyethylene Glycol; Wetting agent is preferably lecithin, poloxamer, propylene glycol or the mixture between them; The bio-adhesive agent is preferably chitosan, carbomer or its mixture.Sapogenin and above-mentioned adjuvant are used, and fully mix homogeneously can strengthen aglycon dispersibility, wettability, improves its bioavailability.
Wherein, surfactants such as lecithin, poloxamer, propylene glycol have the effect of moistened surface to Rhizoma Dioscoreae Nippponicae total sapogenins, reduce surface tension, increase the dissolubility of fat-soluble Rhizoma Dioscoreae Nippponicae total sapogenins, promote it to absorb rapidly, are beneficial to rapid performance curative effect.Vegetable oil, Polyethylene Glycol can be uniformly dispersed Rhizoma Dioscoreae Nippponicae total sapogenins as dispersant.Chitosan, carbomer have the bio-adhesive performance as the bio-adhesive agent, but prolong drug significantly improves bioavailability of medicament in the gastrointestinal holdup time.Rhizoma Dioscoreae Nippponicae total sapogenins of the present invention and above-mentioned adjuvant are used, and fully mix homogeneously can strengthen wherein dispersibility, the wettability of Rhizoma Dioscoreae Nippponicae total sapogenins, improves its bioavailability.
In the preferred case, each composition proportion is preferably active component 10～40% in the medicine of the present invention, bio-adhesive agent 0～10%, wetting agent 5～20%, dispersant 50～80%, other adjuvants 0～20%.Other adjuvants wherein are meant other adjuvants of preparation some in forming process, as: glycerol, glycine, citric acid, ethyl hydroxybenzoate, Cera Flava etc.
Technique scheme is mainly used in oral formulations, and optimum dosage form is liquid hard capsule, soft capsule and drop pill.
The 3rd purpose of the present invention provides the preparation method of above-mentioned high-efficiency preparation, core technology wherein is with behind Rhizoma Dioscoreae Nippponicae total sapogenins and any method mix homogeneously during required adjuvant mixes by fusion, dissolving, stirring, grinding or micronizing, add required conventional formulation adjuvant again, technology is made preparation routinely.And the blended method of the preferred vibromill micronizing of the mixed method here.
Have only by effective hybrid mode, could guarantee that contained Rhizoma Dioscoreae Nippponicae total sapogenins and special adjuvant fully are uniformly dispersed in the extract, moistening rapidly, stripping, absorption when being applied to human body, performance is effect efficiently.Through inventor's checking, modes such as fusion, dissolving, stirring, grinding or micronizing mixing can both realize the object of the invention, and micronizing mode effect wherein are the most outstanding.
Though superfine communication technique occurs already, the application in technical field of Chinese medicines stays in the conceptive of " pulverizing " always, do not break through all the time, thereby its scope is limited to very much.The inventor finds in practice, superfine communication technique has been not only crushing technology, a kind of especially high efficient mixed technology, it can make aglycon be subjected to intensive forward extrusion power and the tangentially effect of shearing force with adjuvant, utilization high speed, high-energy are pulverized, are mixed, and resulting powder medium particle diameter is reduced to 10 by 75 original μ m
Below the μ m, granularity exquisiteness, even, surface area increases, porosity increases, make drug particle fully contact, mix, both improved the dispersion of drug particle, guaranteed its rapid moistening and stripping again with the adjuvant particle, improved the absorbance and the bioavailability of medicine greatly, its advantage is that present conventional mixed method is incomparable.At this wherein, vibromill micronizing mode is to realize the best approach of the object of the invention.
Medicine of the present invention can be used in preparation is used for the treatment of the medicine of goat, hyperlipemia, diabetes, coronary heart disease, angina pectoris, rheumatism or depressive illness.
Beneficial effect
Technical scheme of the present invention considers that from practical angle in conjunction with the needs of preparation, after the saponin component hydrolysis in the Rhizoma Dioscoreae Nipponicae, the Rhizoma Dioscoreae Nippponicae total sapogenins of gained adds proper auxiliary materials, pulverizes by the method height of micronizing and mixes, and makes required preparation.Can make the maximum moistening of active component, dissolving and absorption, can prolong the holdup time of aglycon again, further promote absorbing of aglycon, improve bioavailability.Specifically, this patent method has following advantage:
1, improves bioavailability: adopt this patent invention preparation method, can obviously improve the deficiency of additive method, it has following clear superiority: the poorly water-soluble of aglycon, lipotropy is strong, being difficult for moistening absorbs, and the present invention has added hydrophilic high-molecular biologic binder and wetting agent, dispersant before the preparation micropowder mixes, strengthened the wettability of aglycon, being beneficial to it absorbs, and the rest parts saponin component is beneficial to moistening after the hydrolysis, also can certain wettability be arranged to lipophilic aglycon; Micronization itself can strengthen the performance of sticking of medicine greatly, improves wettability, and the present invention added the high-performance bio binder, can prolong the holdup time of micropowder, strengthens the absorption of effective ingredient.
2, conservation, increase operation rate: the inventive method can maximally utilise crude drug, uses the curative effect that can obtain former prescription less than the dose of general preparation, economizes in raw materials, and improves the utilization rate of crude drug, can reduce the waste of resource again.
So the present invention has obtained outstanding technique effect, has reached goal of the invention.For further checking the present invention in order to prove that pharmaceutical preparation of the present invention improves the effect of bioavailability, the inventor cures mainly according to its function, has carried out animal contrast pharmacodynamic experiment:
One, animal body intracellular metabolite test
1, material
1.1 experimental animal
Large ear rabbit, body weight (2.0 ± 0.2) kg, male and female half and half.Provide by Shandong University's Experimental Animal Center.
1.2 test drug and instrument
The saponin preparation: get Yam total saponin 58g (being equivalent to Rhizoma Dioscoreae Nipponicae medical material 1kg), add carbomer 10g, lecithin 10g, and add micropowder silica gel to 100g, micronizing was mixed 60 minutes, and getting wherein, 50g is suspended to 100ml with water;
The general preparation of sapogenin: get Rhizoma Dioscoreae Nippponicae total sapogenins 46g (being equivalent to Rhizoma Dioscoreae Nipponicae medical material 1kg), add starch to 100g, mixing, getting wherein, 50g is suspended to 100ml with water;
The sapogenin high-efficiency preparation: get Rhizoma Dioscoreae Nippponicae total sapogenins 46g (being equivalent to Rhizoma Dioscoreae Nipponicae medical material 1kg), add carbomer 10g, lecithin 10g, and add micropowder silica gel to 100g, micronizing was mixed 60 minutes, and getting wherein, 50g is suspended to 100ml with water.
Instrument: TGL-20B centrifuge; Tianjin, island LC-10A high performance liquid chromatograph.
2, test method is got fasting 12h, 6 of the large ear rabbits of freely drinking water, and body weight is (2.0 ± 0.2) kg, is divided into 3 groups at random, 2 every group.The 1st group is sapogenin high-efficiency preparation group (experimental group); The 2nd group is the general preparation group of sapogenin (reference group 1); The 3rd group is saponin preparation group (reference group 2).Every group of gastric infusion dosage only is 8ml/, respectively at after the administration the 5th, 10,20,30,60,90,120,180, the about 2ml of 240min ear edge vein exploitating blood, place the heparinization test tube, with the centrifugal 20min of 4000r/min, blood plasma is preserved stand-by in-20 ℃ of refrigerators.Get the 1ml plasma sample, 100 ℃ of water-bath 10min get supernatant and detect diosgenin concentration with the HPLC method with the centrifugal 20min of 15000r/min.The peak area of each time is the meansigma methods of 2 same time points of white rabbit.Calculate blood drug level, curve when drawing medicine.
3, result of the test sapogenin high-efficiency preparation the results are shown in following table to the determination of plasma concentration of normal white rabbit.
Table dialogue Sanguis Leporis seu oryctolagi concentration measurement result (ug/ml)
According to above-mentioned time and blood drug level data, curve when drawing medicine sees accompanying drawing for details.
Above result of the test shows that the diosgenin in the sapogenin high-efficiency preparation is absorbed into blood concentration than general preparation of sapogenin and saponin preparation height, and effect is obvious.
Two, to the influence of hyperuricemia rat serum uric acid level
1, material
1.1 animal Wister rat, male and female half and half, body weight 200 ± 20g.Provide by Shandong University's Experimental Animal Center.
1.2 medicine and reagent
The saponin preparation: get Yam total saponin 58g (being equivalent to Rhizoma Dioscoreae Nipponicae medical material 1kg), add chitosan 5g, lecithin 5g, micropowder silica gel 25g, and add microcrystalline Cellulose to 100g, micronizing was mixed 50 minutes, and getting wherein, 20g is suspended to 100ml with water;
The general preparation of sapogenin: get Rhizoma Dioscoreae Nippponicae total sapogenins 46g (being equivalent to Rhizoma Dioscoreae Nipponicae medical material 1kg), add starch to 100g, mixing, getting wherein, 20g is suspended to 100ml with water;
The sapogenin high-efficiency preparation: get Rhizoma Dioscoreae Nippponicae total sapogenins 46g (being equivalent to Rhizoma Dioscoreae Nipponicae medical material 1kg), add chitosan 5g, lecithin 5g, micropowder silica gel 25g, and add microcrystalline Cellulose to 100g, micronizing was mixed 50 minutes.Getting wherein, 20g is suspended to 100ml with water.
Positive control drug: get colchicine 6g, add the solution that water is made 100ml.
Reagent: hypoxanthine, nicotinic acid, blood uric acid test kits.
1.3 instrument ultraviolet-visible spectrophotometer: UV1100 (Shanghai Techcomp Instrument Ltd.).
2, method and result
2.1 test method is divided into six groups at random with 60 rats, every group 10: blank group, model group, positive drug control group, aglycon high-efficiency preparation group, the general preparation group of aglycon, saponin preparation group, every day, gastric infusion was 1 time, successive administration 4d, dosage is respectively 10ml/kg, and blank group, model group are irritated stomach with the volume normal saline.Behind each treated animal last administration 1h, all the other 4 treated animal Intraperitoneal injection of hypoxanthine 100mg/kg irritate stomach simultaneously and give nicotinic acid 80mg/kg except that the blank group; Blank treated animal lumbar injection is also irritated stomach and is given isopyknic normal saline.Injection back 30min, each treated animal is through abdominal aortic blood, and the centrifugal 15min of 3000r/min gets serum, presses the operation of blood uric acid testing cassete description, surveys the hematuria acid number.
2.2 result of the test sees the following form.
Table is to the influence of hyperuricemia rat serum uric acid level (X ± S)
Annotate: compare with model group:
*P＜0.05,
*P＜0.01.
Above result of the test shows, compares with the blank group, and model group animal hematuria acid number obviously raises, prompting modeling success.Positive drug control group, sapogenin high-efficiency preparation group and model group compare, and the hematuria acid number obviously reduces, and has utmost point significant difference; The general preparation group of aglycon, glycoside preparation group and model group compare, and the hematuria acid number reduces, and has significant difference, and the general preparation group of aglycon is effective than glycoside preparation group.
Three, the effect of Rhizoma Dioscoreae Nippponicae total sapogenins Chinese People's Anti-Japanese Military and Political College Mus venous thrombosis
1, material
1.1 animal Wister rat, male and female half and half, body weight 200 ± 20g.Provide by Shandong University's Experimental Animal Center.
1.2 medicine
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
2, method and result
2.1 test method is got 40 of Wistar rats, male and female half and half, body weight 200 ± 20g, be divided into 4 groups at random, every group 10: sapogenin high-efficiency preparation group, the general preparation group of sapogenin, saponin preparation group, blank group, gastric infusion every day 1 time, dosage is respectively 10ml/kg, the blank group is irritated stomach and is given with the volume normal saline continuous 7 days.Behind the last administration 6h, be that the capillary glass tube of 1mm inserts Mus angular vein clump and gets blood, reach 5cm to the capillary blood post with internal diameter, every fracture one section in capillary tube of 30s, inspection has or not and clotting strands occurs, and the calculating capillary tube is taken a blood sample to and the blood clotting silk time occurred, is clotting time.
2.2 result of the test the results are shown in following table.
Table is to the thrombotic influence of rat vein (X ± S)
Compare (t check) with the blank group,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Above result of the test shows that Rhizoma Dioscoreae Nippponicae total sapogenins high-efficiency preparation group all can obviously prolong clotting time, relatively has significant difference with the blank group, and is all effective than the general preparation group of sapogenin, saponin preparation group.
Four, Rhizoma Dioscoreae Nippponicae total sapogenins is to the influence of depressed mice
1, material
1.1 the animal Kunming mouse, (20 ± 2) g, male and female half and half are provided by Shandong University's Experimental Animal Center.Raising is stablized 3d before the experiment under 25 ℃ of conditions, ad lib drinking-water.
1.2 medicine
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Positive control drug: get fluoxetine 3g, add the solution that water is made 100ml.
2, method and result
2.1 test method: mice forced swimming experiment.
Get 50 of mices, male and female half and half, body weight (20 ± 2) g is divided into 5 groups at random, 10 every group: blank group, positive drug group, sapogenin high-efficiency preparation group, the general preparation group of sapogenin, saponin preparation group.Dosage is 0.2ml/10g, and blank group filling stomach gives the normal saline with volume, each treated animal gastric infusion every day 1 time, successive administration 7d.Behind the last administration 30min, mice is put into high 20cm, in the cylindrical glass cylinder of diameter 14cm, one in every cylinder, depth of water 10cm in the cylinder, water temperature (25 ± 1) ℃.Behind the mice swimming 2min, begin immediately to observe, observe and continue 4min, motionless (mice stops to struggle in water, or animal is floating state, and tiny the limb motion is only arranged) time in this 4min of accumulative total.
2.2 result of the test: the results are shown in following table.
Table to the influence of mice forced swimming dead time (X ± S, n=10)
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01.
Above result of the test shows that the high-efficiency preparation group of sapogenin, positive drug group all can obviously shorten the mice dead time, relatively has utmost point significant difference with the blank group, and is all effective than saponin preparation group; The general preparation group of sapogenin, saponin preparation group relatively have significant difference with the blank group, and the general preparation group of sapogenin is better than saponin preparation group.
Five, Rhizoma Dioscoreae Nippponicae total sapogenins paratartaric acid antimony potassium causes the influence of mouse writhing reaction
1, material
1.1 the animal Kunming mouse is provided by Shandong University's Experimental Animal Center.
1.2 medicine and reagent
Medicine: the preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Reagent: antimony potassium tartrate.
2, method and result
2.1 test method
Get 40 of mices, male and female half and half, body weight 20 ± 2g, evenly be divided into 4 groups at random, every group 10, promptly blank group, sapogenin high-efficiency preparation group, the general preparation group of sapogenin, saponin preparation group, gastric infusion dosage is 0.25ml/10g, blank group filling stomach gives the normal saline with volume, administration every day 1 time, successive administration 5 days, 1h after last 1 administration, the antimony potassium tartrate liquid of the new preparation of every Mus lumbar injection is observed incubation period and the interior mouse writhing generation number of 10min that writhing response appears in mice first immediately.
2.2 result of the test the results are shown in following table.
Table is to the influence of antimony potassium tartrate induced mice writhing response (X ± S)
Annotate: with blank group ratio,
*P＜0.05,
*P＜0.01.
Above result of the test shows that the high-efficiency preparation group of sapogenin can obviously prolong the incubation period that mice is turned round body first, reduces the mouse writhing number of times, relatively has utmost point significant difference with the blank group, and is effective than saponin preparation group; The general preparation group of sapogenin, saponin preparation group and blank group relatively have significant difference, and the general preparation group of sapogenin is better than saponin preparation group.
Six, Rhizoma Dioscoreae Nippponicae total sapogenins is to the influence of hyperlipidemia rats serum TC, TG, HDL-C
1, material
1.1 animal Wistar rat is provided by Shandong University's Experimental Animal Center.
1.2 medicine and reagent
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Positive control drug: get lovastatin 2g, be suspended to 100ml with water.
Reagent: HDL-C (HDL-C) testing cassete, T-CHOL (TC) testing cassete, triglyceride (TG) testing cassete.
1.3 instrument ZS-3 type semiautomatic biochemistry analyzer.
2, method and result
2.1 the foundation of animal model 1% cholesterol, 0.2% methylthiouracil, 0.3% cholate, 7.5% Adeps Sus domestica, 10% yolk powder, 81% normal feedstuff is made high lipid food, the feed rat.
2.2 test method rat adaptability was raised 5 days, fasting 12h, detect serum TC and TG, by body weight and blood lipid level rat is divided into 6 groups at random, 10 every group: i.e. blank group, model control group, aglycon high-efficiency preparation group, the general preparation group of aglycon, saponin preparation group, lovastatin group.Except that blank group feed normal feedstuff, all the other each groups are all fed high lipid food, average every Mus 18g every day, and deficiency gives normal diet and replenishes.When giving high lipid food, gastric infusion dosage is 10ml/kg, and blank group and model group filling stomach give the normal saline with volume, administration every day 1 time, successive administration 30 days is after the last administration, fasting 12h, postcava is got blood, enzymatic assays TC, TG, HDL-C.
2.3 result of the test sees the following form to the influence of hyperlipidemia rats serum TC, TG, HDL-C.
Table to the influence of hyperlipidemia rats serum TC, TG, HDL-C (mmol/L, X ± S, n=10)
Annotate: compare with model control group,
*P＜0.05,
*P＜0.01.
Above result of the test shows that TC, TG level are significantly higher than blank group (P＜0.01) in the model control group rat serum, and HDL-C significantly is lower than blank group (P＜0.01), prompting modeling success; Compare with model control group, aglycon high-efficiency preparation group and lovastatin group all can significantly reduce TC, TG, and rising blood HDL-C level; The general preparation group of aglycon, glycosides formulation group and model control group relatively can reduce TC, TG, rising blood HDL-C level.
Seven, Rhizoma Dioscoreae Nippponicae total sapogenins is to the influence of diabetes rat model hyperglycemia
1, material
1.1 animal Wistar rat is provided by Shandong University's Experimental Animal Center.
1.2 medicine and reagent
The preparation method of saponin preparation, the general preparation of sapogenin, sapogenin high-efficiency preparation is the same.
Positive control drug: get glyburide 3g, be suspended to 100ml with water.
1.3 instrument blood sugar analyzer.
2, method and result
2.1 test method is chosen 100 of healthy rats, body weight 200 ± 20g, and male and female half and half, adaptability raised for 1 week, 18 ℃～24 ℃ of room temperatures.Make before the diabetes model behind the fasting 12h, get blood, use blood sugar analyzer to survey blood glucose value from rat tail vein, choose blood glucose value in 5.0mmol/L～6.0mmol/L scope rat with 55mg/kg streptozotocin lumbar injection; Fasting 12h and get blood and survey blood glucose behind the 72h selects 50 of the close rats of blood glucose value, is divided into 5 groups at random: model group, glyburide group, aglycon high-efficiency preparation group, the general preparation group of aglycon, glycoside preparation group; Other gets blood glucose value 10 of healthy rats in 5.0mmol/L～6.0mmol/L scope, male and female half and half, as the blank group, each is organized gastric infusion dosage and is 10ml/kg, blank group and model group filling stomach give the normal saline with volume, administration every day 1 time, 14d continuously, get blood respectively at the 3rd day, the 7th day, the 14th day fasting 12h during the administration, survey blood glucose value.
2.2 test results test the results are shown in following table.
Table to the influence of diabetes rat model hyperglycemia (X ± S, n=10)
Annotate: compare with model group,
*P＜0.05,
*P＜0.01.
Above result of the test shows, behind the 55mg/kg streptozotocin lumbar injection rat blood sugar is obviously raise, gavages aglycon high-efficiency preparation and glyburide continuously, and blood glucose obviously reduced in the 7th day, and its blood sugar reducing function was more obvious in the 14th day; The general preparation of aglycon, the 14th day blood sugar reducing function of saponin preparation are comparatively obvious.
Description of drawings:
Curve when accompanying drawing is a medicine under the different dosage forms of Rhizoma Dioscoreae Nipponicae saponin and aglycon thereof
The specific embodiment
Enumerate embodiment below, further specify the present invention, each embodiment only is used to illustrate the present invention, does not limit the present invention:
Embodiment 1
Get Rhizoma Dioscoreae Nippponicae total sapogenins 100g, add chitosan 20g, carbomer 10g, poloxamer 50g, lecithin 50g, micropowder silica gel 30g, betacyclodextrin 80g, and add starch to 450g, the vibromill micronizing was mixed 30 minutes, granulated drying, granulate is made capsule.
Embodiment 2
Get Rhizoma Dioscoreae Nippponicae total sapogenins 80g, Rhizoma Dioscoreae Zingiberensis total sapogenins 10g, add chitosan 20g, poloxamer 30g, lecithin 10g, micropowder silica gel 30g, betacyclodextrin 20g, microcrystalline Cellulose 50g, and add starch to 300g, vibromill micronizing 30 minutes, adding 70% ethanol closes and sticks together 10 minutes, pill bar, gradation and round, drying, pill is made in polishing.
Embodiment 3
Get Rhizoma Dioscoreae Nippponicae total sapogenins 120g, add chitosan 2g, lecithin 10g, Aspartane 1g, and add dextrin to 200g, stir, dry-pressing is granulated, and granule is made in packing.
Embodiment 4
Get Rhizoma Dioscoreae Nippponicae total sapogenins 60g, add chitosan 10g, polyvinylpyrrolidone 2g, poloxamer 8g, betacyclodextrin 20g, and add starch to 200g, the mix homogeneously that sieves is granulated, and the dress enteric coated capsule is made capsule.
Embodiment 5
Get Rhizoma Dioscoreae Nippponicae total sapogenins 100g, add polyvinylpyrrolidone 10g, poloxamer 20g, lecithin 10g, micropowder silica gel 10g, betacyclodextrin 50g, the vibromill micronizing was mixed 50 minutes, granulates, tabletting, coating is made tablet.
Embodiment 6
Get Rhizoma Dioscoreae Nippponicae total sapogenins 20g, add propylene glycol 10g, poloxamer 10g, lecithin 20g, chitosan 10g, carbomer 10g, add PEG400 to 200g, vibromill micronizing 20 minutes makes mix homogeneously, makes liquid hard capsule, promptly.
Embodiment 7
Get Rhizoma Dioscoreae Nippponicae total sapogenins 30g, add lecithin 10g, glycine 10g, glycerol 30g adds Macrogol 600 again to 200g, and vibromill micronizing 30 minutes makes mix homogeneously, is pressed into soft capsule, promptly.
Embodiment 8
Get Rhizoma Dioscoreae Nippponicae total sapogenins 50g, add chitosan 10g, lecithin 20g, poloxamer 4g, ethyl hydroxybenzoate 1g, Cera Flava 5g, and add soybean oil to 200g, and stirring evenly, colloid mill ground 5 minutes, was pressed into soft capsule, promptly.
Embodiment 9
Get Rhizoma Dioscoreae Nippponicae total sapogenins 40g, propylene glycol 10g, glycerol 5g, polyethylene glycol 6000 50g, Macrogol 4000 50g, heating and melting, mix homogeneously drips and makes drop pill, promptly.
Embodiment 10
Get Rhizoma Dioscoreae Nippponicae total sapogenins 100g, lecithin 25g, ethyl hydroxybenzoate 2.5g, Cera Flava 47.5g, and add soybean oil to 500g, vibromill ultra micro 40 minutes makes mix homogeneously, is pressed into soft capsule, promptly.
Embodiment 11
Get Rhizoma Dioscoreae Nipponicae medical material 4.5kg, pulverize, add 70% ethanol percolation and extract, percolate reclaims ethanol, and water liquid adds 0.5% activated carbon decolorizing, filter, filtrate is crossed the D101 macroporous resin column, respectively water, 20% ethanol, 60% ethanol elution is collected 60% ethanol elution, reclaim ethanol, surplus water liquid emulsin hydrolysis 72 hours, hydrolyzed solution concentrating under reduced pressure, drying under reduced pressure, get Rhizoma Dioscoreae Nippponicae total sapogenins (crude product) 205g, add carbomer 40g, lecithin 40g, micropowder silica gel 40g, and add starch to 400g, micronizing was mixed 60 minutes, granulate, drying, granulate is loaded capsule.
Embodiment 12
Get Rhizoma Dioscoreae Nipponicae 4kg, coarse pulverization adds 60% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid are added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 70% ethanol elution, collect 70% ethanol elution, decompression recycling ethanol, surplus water liquid was with 2mol/L sulphuric acid hydrolysis 2 hours, and it is an amount of that hydrolyzed solution adds calcium oxide, filter, and with an amount of washing with alcohol precipitation, filter, merge water liquid and ethanol washing liquid, decompression recycling ethanol, drying under reduced pressure gets Rhizoma Dioscoreae Nippponicae total sapogenins (crude product) 178g, adds chitosan 20g, lecithin 20g, micropowder silica gel 100g, and add microcrystalline Cellulose to 400g, micronizing was mixed 50 minutes, granulated drying, granulate is pressed into 1000.
Embodiment 13
Get Rhizoma Dioscoreae Nipponicae 4kg, coarse pulverization adds 70% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, and dry thing is dissolved in water, 115 ℃ of sterilization 20min, with lactic acid bacteria culturers hydrolysis 72 hours, hydrolyzed solution concentrating under reduced pressure, drying under reduced pressure, get Rhizoma Dioscoreae Nippponicae total sapogenins (crude product) 186g, add carbomer 40g, lecithin 20g, polyethylene glycol 6000 40g, and add dextrin to 400g, micronizing was mixed 80 minutes, granulate, drying, granulate makes granule.
Embodiment 14
Get Rhizoma Dioscoreae Nipponicae 5kg, coarse pulverization adds 70% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, dry thing is dissolved in water, and is added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 80% ethanol elution, collect 80% ethanol elution, decompression recycling ethanol adds hydrochloric acid and makes acid content reach 5mol/L, hydrolysis 6 hours, hydrolyzed solution hydro-oxidation sodium is regulated pH to 7.0, concentrate, drying with the dehydrated alcohol reflux, extract,, reclaims ethanol, drying under reduced pressure, get Rhizoma Dioscoreae Nippponicae total sapogenins 178g, add chitosan 10g, poloxamer 50g, cyclodextrin 180g, carboxymethyl starch sodium 20g, and add starch to 500g, micronizing was mixed 30 minutes, with water is adhesive, and the system soft material is pressed into ball.
Embodiment 15
Get Rhizoma Dioscoreae Nipponicae medical material 3kg, pulverize, add 70% ethanol percolation and extract, percolate reclaims ethanol, water liquid adds 0.5% activated carbon decolorizing, filter, filtrate is crossed the D101 macroporous resin column, respectively water, 20% ethanol, 60% ethanol elution, collect 60% ethanol elution, reclaim ethanol, surplus water liquid concentrates with emulsin hydrolysis 72 hours, hydrolyzed solution, dry, get Rhizoma Dioscoreae Nippponicae total sapogenins (crude product) 156g, add carbomer 20g, lecithin 20g, and add Polyethylene Glycol 400 to 400g, micronizing was mixed 60 minutes, the compacting soft capsule.
Embodiment 16
Get Rhizoma Dioscoreae Nipponicae 3kg, coarse pulverization adds 60% alcohol reflux three times, each 1.5 hours, filter, merging filtrate, decompression recycling ethanol, water liquid are added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 70% ethanol elution, collect 70% ethanol elution, decompression recycling ethanol, surplus water liquid was with 2mol/L sulphuric acid hydrolysis 2 hours, it is an amount of that hydrolyzed solution adds calcium oxide, filter, and, filter with an amount of washing with alcohol precipitation, merge water liquid and ethanol washing liquid, decompression recycling ethanol, drying under reduced pressure gets Rhizoma Dioscoreae Nippponicae total sapogenins 127g, add propylene glycol 45g, ethyl hydroxybenzoate 6g, and add Polyethylene Glycol 400 to 600g, and micronizing was mixed 30 minutes, and fill becomes liquid hard capsule.
Embodiment 17
Get Rhizoma Dioscoreae Nipponicae 4.5kg, coarse pulverization decocts with water three times, each 2 hours, filter merging filtrate, being evaporated to relative density is 1.10～1.15 (60 ℃), adds ethanol and makes and contain alcohol amount and reach 70%, leaves standstill 12 hours, filter, filtrate recycling ethanol extracts three times with water-saturated n-butanol, merges n-butyl alcohol liquid, water bath method, residue is dissolved in water, and is added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 70% ethanol elution, collect 70% ethanol elution, decompression recycling ethanol, surplus water liquid was with 5mol/L hydrochloric acid hydrolysis 3 hours, and hydrolyzed solution hydro-oxidation sodium is adjusted to neutrality in right amount, concentrate, dry, with an amount of ethanol extraction, filter, reclaim ethanol, drying under reduced pressure, get Rhizoma Dioscoreae Nippponicae total sapogenins 184g, add carbomer 7.5g, poloxamer 30g, propylene glycol 50g, glycine 3g, and add Polyethylene Glycol 400 to 600g, micronizing was mixed 40 minutes, 1000 of compacting soft capsules.
Embodiment 18
Get Rhizoma Dioscoreae Nipponicae 5kg, coarse pulverization, add 70% alcohol reflux three times, each 1.5 hours, filter, merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, dry thing is dissolved in water, 115 ℃ of sterilization 20min are with bifidus bacillus strain fermentation hydrolysis 72 hours, hydrolyzed solution concentrating under reduced pressure, drying under reduced pressure, Rhizoma Dioscoreae Nippponicae total sapogenins 198g, add chitosan 10g, lecithin 20g, and with soybean oil to 500g, micronizing was mixed 30 minutes, and fill becomes liquid hard capsule.
Embodiment 19
Get Rhizoma Dioscoreae Nipponicae 3kg, coarse pulverization adds 70% alcohol reflux three times, each 1.5 hours, filter merging filtrate, decompression recycling ethanol, water liquid extracts three times with water-saturated n-butanol, n-butyl alcohol liquid evaporate to dryness, and dry thing is dissolved in water, be added on the D101 macroporous adsorptive resins, respectively with water, 30% ethanol, 80% ethanol elution is collected 80% ethanol elution, decompression recycling ethanol, adding hydrochloric acid makes acid content reach 5mol/L, hydrolysis 3 hours, hydrolyzed solution hydro-oxidation sodium is regulated pH to 7.0, concentrates, dry, with the dry thing of dehydrated alcohol reflux, extract,, reclaim ethanol, drying under reduced pressure gets Rhizoma Dioscoreae Nippponicae total sapogenins 132g, add chitosan 10g, poloxamer 20g, and adding Polyethylene Glycol 6000 to 400g, heating and melting drips and makes drop pill.
Get embodiment 12 made tablet in treatment rheumatic arthritis patient 40 examples.Therapeutic scheme: every day 3 times, each 3, use after 20 days, cure rate is 41.7%, obvious effective rate is 50.8%.
Embodiment 21
Get embodiment 17 made soft capsule treatment tumor patient 52 examples.Therapeutic scheme: every day 3 times, each 2,2 weeks were a course of treatment, added up therapeutic outcome after 2 courses of treatment, and obvious effective rate is 25.8%, and total effective rate is 82.4%.
Claims (18)
1, a kind of is the oral drugs of active component with the Rhizoma Dioscoreae Nippponicae total sapogenins.
2, medicine according to claim 1 is characterized in that described active component can have only Rhizoma Dioscoreae Nippponicae total sapogenins, also can be that Rhizoma Dioscoreae Nippponicae total sapogenins and other drug composition are united use.
3, medicine according to claim 2 is characterized in that described Rhizoma Dioscoreae Nippponicae total sapogenins obtains by hydrolysis Yam total saponin.
4, medicine according to claim 3 is characterized in that method for hydrolysis is acid hydrolysis, enzyme hydrolysis or microbial hydrolysis.
5, according to each described medicine in the claim 1 to 4, it is characterized in that acceptable auxiliary is used on active constituents of medicine and the pharmaceutics.
6, medicine according to claim 5 is characterized in that containing in the adjuvant bio-adhesive agent and wetting agent.
7, medicine according to claim 6 is characterized in that also can containing dispersant in the adjuvant.
8, medicine according to claim 7 is characterized in that the bio-adhesive agent in the adjuvant is meant chitosan and/or carbomer; Wetting agent is meant lecithin and/or poloxamer; Dispersant is meant any or the compositions more than two kinds in micropowder silica gel, cyclodextrin, the Polyethylene Glycol.
9, medicine according to claim 8 is characterized in that the medicine proportion of composing is:
Active component 20～60%,
Bio-adhesive agent 1～10%,
Wetting agent 5～20%,
Dispersant 0～30%,
Other adjuvants 0～50%.
10, medicine according to claim 9 is characterized in that being made into tablet, capsule, granule or pill.
11, medicine according to claim 5 is characterized in that containing in the adjuvant wetting agent and dispersant.
12, medicine according to claim 11 is characterized in that also can containing the bio-adhesive agent in the adjuvant.
13, medicine according to claim 12 is characterized in that bio-adhesive agent in the adjuvant is meant any or the compositions more than two kinds in chitosan, carbomer, the polyvinylpyrrolidone; Wetting agent is meant any or the compositions more than two kinds in propylene glycol, lecithin, the poloxamer; Dispersant is meant Polyethylene Glycol or vegetable oil.
14, medicine according to claim 13 is characterized in that the medicine proportion of composing is:
Active component 10～40%,
Bio-adhesive agent 0～10%,
Wetting agent 5～20%,
Dispersant 50～80%,
Other adjuvants 0～20%.
15, medicine according to claim 14 is characterized in that being made into soft capsule, liquid hard capsule or drop pill.
16, the method for preparing each described medicine in the claim 6 to 15, it is characterized in that behind active constituents of medicine and any method mix homogeneously during required adjuvant mixes by fusion, dissolving, stirring, grinding or micronizing, add required conventional formulation adjuvant again, technology is made preparation routinely.
17, preparation method according to claim 16 is characterized in that using the vibromill superfine grinding method to mix.
18, each described medicine is used for the treatment of application in the medicine of goat, hyperlipemia, diabetes, coronary heart disease, angina pectoris, rheumatism or depressive illness in preparation in the claim 1 to 4.
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| CN200810101723A CN101530532A (en) | 2008-03-11 | 2008-03-11 | Oral pharmaceutical preparation of yam total sapogenin and preparation method and application thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585402A (en) * | 2013-08-15 | 2014-02-19 | 大连医科大学 | Application of Dioscorea nipponica total saponins in preparation of medicines for treatment of diabetes mellitus and complications of diabetes mellitus |
| CN104667255A (en) * | 2015-02-15 | 2015-06-03 | 高长庚 | Traditional Chinese medicinal preparation used for treating diabetes mellitus |
| WO2020256243A1 (en) * | 2019-06-17 | 2020-12-24 | 한국한의학연구원 | Composition for preventing or treating depression comprising mixed extract of dioscorea nipponica makino and prickly pear |
-
2008
- 2008-03-11 CN CN200810101723A patent/CN101530532A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585402A (en) * | 2013-08-15 | 2014-02-19 | 大连医科大学 | Application of Dioscorea nipponica total saponins in preparation of medicines for treatment of diabetes mellitus and complications of diabetes mellitus |
| CN104667255A (en) * | 2015-02-15 | 2015-06-03 | 高长庚 | Traditional Chinese medicinal preparation used for treating diabetes mellitus |
| WO2020256243A1 (en) * | 2019-06-17 | 2020-12-24 | 한국한의학연구원 | Composition for preventing or treating depression comprising mixed extract of dioscorea nipponica makino and prickly pear |
| KR20200144042A (en) * | 2019-06-17 | 2020-12-28 | 한국 한의학 연구원 | Composition for preventing or treating depression comprising mixed extract of Dioscorea nipponica Makino and Prickly Pear |
| KR102323577B1 (en) | 2019-06-17 | 2021-11-09 | 한국한의학연구원 | Composition for preventing or treating depression comprising mixed extract of Dioscorea nipponica Makino and Prickly Pear |
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