CN101716220B - Shielding alkaloid traditional Chinese medicine - Google Patents
Shielding alkaloid traditional Chinese medicine Download PDFInfo
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- CN101716220B CN101716220B CN2009102162692A CN200910216269A CN101716220B CN 101716220 B CN101716220 B CN 101716220B CN 2009102162692 A CN2009102162692 A CN 2009102162692A CN 200910216269 A CN200910216269 A CN 200910216269A CN 101716220 B CN101716220 B CN 101716220B
- Authority
- CN
- China
- Prior art keywords
- chinese medicine
- exchange resin
- ion exchange
- extract
- traditional chinese
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Abstract
The invention relates to a shielding alkaloid traditional Chinese medicine which solves the problems of bitter taste of a traditional Chinese medicine composition, complicated process of a traditional taste shielding method, unsuitability of the industrialized production and incomplete taste shielding.The shielding alkaloid traditional Chinese medicine is a composition of a traditional Chinese medicine extract and ion exchange resin, wherein the traditional Chinese medicine extract comprises at least one single-agent traditional Chinese medicine extract, the ion exchange resin is firstly transformed into ion exchange resin acid by acidification treatment, and then the ion exchange resin acid is mixed with the traditional Chinese medicine extract, or the ion exchange resin is subacid ion exchange resin which is directly mixed with the traditional Chinese medicine extract. The mixing weight ratio is as follows: the ratio of the weight of alkaloid in the traditional Chinese medicine extract to the weight of the ion exchange resin is 1:(0.2-10). After mixing, deionized water is added, the pH value of mixed liquid is regulated within a range of 3-10, the exchange rate of a reaction is controlled, the mixed liquid is stirred and concentrated into a thick paste, and the traditional Chinese medicine taste-shielding compound is obtained by pulverization after drying.
Description
Technical field:
The present invention is relevant with middle prescription agent or compound medicine, and is especially relevant with the Chinese medicine medicine of spent ion exchange resin shielding alkaloid.
Technical background:
Alkaloid is to be present in the organic compound that contains nitrogen-atoms in the biological intravital molecule.Alkaloid is distributed in plant kingdom widely; Mainly be present in the dicotyledon; There is the plant of more than 100 section to contain alkaloid; Wherein many common Chinese medicines are like Radix Sophorae Flavescentis, Rhizoma Coptidis, Rhizoma Menispermi, Rhizoma Corydalis, Flos Daturae, Semen daturae, hyoscyami, Radix stephaniae tetrandrae, Semen Papaveris, Radix Berberidis etc., and the medicinal organism alkali of clinical practice at present has kind more than 100.Alkaloid has complicated azacyclo-structure more, has alkalescence usually, ability and sour salify, and have significant physiologically active.Mainly comprise cardiovascular system, central nervous system, antiinflammatory, antiviral, protect the liver, various pharmacological activities such as anticancer.
Contain alkaloidal Chinese medicine, in Chinese medicinal formulae, be widely used, all contain alkaloids Chinese medicine or its agents area in most of Chinese medicinal formulaes.Rhizoma Coptidis is classified as in the medicine top grade in the Chinese medicine Rhizoma Coptidis for example, " legendary god of farming's wood grass through ".Name side with Rhizoma Coptidis is formed just has 12 in treatise on Febrile Diseases, account for 10% of this book prescription.In the Tang Dynasty Thousand Golden Prescriptions, " medical secrets of official " two books; Have the prescription of Rhizoma Coptidis reach 260 surplus the side; It is thus clear that Rhizoma Coptidis is cured the disease wide, contains multiple alkaloids such as berberine (also claiming berberine), coptisine, jateorhizine, palmatine in the Rhizoma Coptidis, wherein berberine is a main component.All extensive uses in Chinese medicinal formulae such as Radix Sophorae Flavescentis, Rhizoma Menispermi, hyoscyami, Rhizoma Corydalis in addition; The main chemical compositions of these Chinese medicines is matrine, oxymatrine; Dauricine (dauricine), Caulis menispermi are appointed alkali (menisperine), daurinoline (daurinoline) etc.; Hyoscyamine, Anisodamine, alkaloids such as Rhizoma Corydalis first element, second element.These alkaloids all have bitter taste.The oral formulations that contains alkaloids Chinese medicine or its agents area, like mixture, granule, tablet and powder, these preparation tastes are bitter, and patient's compliance is poor.Use traditional taste masking means, for example add sweeting agent, aromatic, these methods all are difficult to solve fully the bitter taste of drug problem.
Ion exchange resin combines with active constituents of medicine; The masking agents bitterness has been known; For example, patent IE990009A1 discloses a kind of ion exchange resin and has combined with ketone lactone medicine, forms taste-masking composite; In order to reach complete masking agents bitterness, also adopt Eudragit E udragit RD100 that ion exchange resin～medicinal composition is carried out coating in the above-mentioned patent.The ion exchange resin resin that adopts is Dowex 50wx2～400; The method for preparing of ion exchange resin～medicinal composition is: earlier the example exchanger resin is washed with purified water; Medicine and ion exchange resin are 8% with the ratio of 400mg/g in active constituents of medicine concentration, exchange in the 1mol/L aqueous hydrochloric acid solution medium.To change finishes filters exchange solution, and deionized water rinsing is dried under 40 ℃ of conditions.Dowex type ion exchange resin is usually used in separation and purification in this invention; Be used for pharmaceutical preparation hardly, ion exchange resin complexes described in the patent does not have complete masking agents bitterness, must solve bitter taste of drug by means of the coating means; Therefore preparation technology is immature, the improvement of still needing.Do not relate to ion exchange resin in the patent and be used for the Chinese medicine taste masking, its preparation method is also different with the method that this patent is proposed.
Patent CA2437266A1 discloses a kind of taste masking and has used resinate, wherein contains and the active substance that is insoluble in water that can reach the ion exchange resin complexes composition of effectively covering bitterness dosage.The pH that proposes exchange media in the patent is the principal element that influences exchange efficiency, and the ratio screening scope of risperidone and ion exchange resin was from 1: 4～1: 12.Risperidone and ion exchange resin reaction medium are citric acid～phosphate buffer solution and the 1.7% gelatin mixed liquor of deionized water, pH 5.93.The ion exchange resin of mentioning in the patent is cation exchange resin, mainly is porous methacrylic acid divinyl benzene copolymer and divinylbenzene crosslink polystyrolsulfon acid copolymer, comprises AMBERLITE
TMIRP64, IRP88 and IRP69.
Risperidone-drug-resin complex can be applied in the preparation of following dosage form: quickly disintegrating tablet, effervescent tablet, chewable tablet, gel, suspension, powder.
But do not relate to ion exchange resin in the patent and be used for the Chinese medicine taste masking, the taste masking effect differs widely in the proportion of risperidone and ion exchange resin.The exchange media of mentioning in the patent is a mixed solution, and operating procedure is complicated, is not suitable for the Chinese medicine taste masking, also is not suitable for industrialized great production simultaneously.
Summary of the invention:
It is simple to the purpose of this invention is to provide a kind of processing technology, easy to operate, is suitable for suitability for industrialized production, and the masking agents bitterness is shielding alkaloid Chinese medicine medicine completely.
The present invention is achieved in that
Shielding alkaloid Chinese medicine medicine of the present invention; Compositions for Chinese medicine extract and ion exchange resin; Chinese medicine extract is made up of at least a single agent Chinese medicine extract, and ion exchange resin acidified processing earlier is converted into the amberlite fat acid and mixes with Chinese medicine extract, and perhaps ion exchange resin is that weak-acid ion exchange resin directly mixes with Chinese medicine extract; The mixed weight ratio is: alkaloid weight in the Chinese medicine extract: ion exchange resin weight=1: (0.2～10); Mix the back and add deionized water, the pH value through regulating mixed liquor in 3～10, control reaction exchange rate; Mixed liquor stirs, is condensed into thick paste, and crushed after being dried promptly gets the Chinese medicine medicine.
The pH value of mixed liquor is 5～8.
Ion exchange resin is that the polystyrolsulfon acid copolymer is held in methacrylic acid divinyl benzene copolymer or divinylbenzene friendship, and alkaloid weight and ion exchange resin weight ratio are 1 in the Chinese medicine extract: (2～5).
The method for preparing of Chinese medicine extract is following: earlier each single agent Chinese medicine must be filtrated with ethanol extraction, filtration, recovery ethanol respectively, will extract the back medicinal residues more separately and merge, water decocts; Medicinal residues are crossed and are filtered filtrating; All filtratings are merged, and adjustment weight is 8～10 times of all single agent Chinese medicine gross weights, filters; Get the thick paste that supernatant is evaporated to proportion 1.30～1.35, crushed after being dried promptly gets the Chinese medicine extract powder.
All alkaloids content is measured by following method in the Chinese medicine extract: adopt the weight of matrine in the high effective liquid chromatography for measuring Chinese medicine extract, it is an amount of to get the Chinese medicine dry extract, porphyrize; The accurate title, decide; Put in the tool plug conical flask, adopt ammonia alkalization back chloroform supersound extraction matrine, dilute the back as need testing solution with mobile phase; It is an amount of that precision takes by weighing the matrine reference substance, adds mobile phase and process reference substance solution; Chromatographic system is following: reversed phase chromatographic column, mobile phase are the low phosphorus acid solution that contains acetonitrile, and the detection wavelength is 207nm; Flow velocity: 1mL/min injects high performance liquid chromatogram according to the said determination condition with need testing solution and reference substance solution, calculates matrine weight with external standard method.
Chinese medicine extract is made up of three kinds of single agent Chinese medicine extract: the prescription of three kinds of single agent Chinese medicines is following: Radix Astragali 1500g, Rhizoma Chuanxiong 750g, Radix Sophorae Flavescentis 750g.
Contain flavoring agent, be prepared into tablet or granule or powder or suspensoid or solution.
The principle of ion exchange resin taste masking mainly is that ion exchange, absorption or enclose take place in exchange media for active constituents of medicine and ion exchange resin, forms a kind of complex, stops the bitterness medicine to contact with taste bud, reaches the purpose of taste masking.
Contain alkaloidal middle pharmaceutically active ingredient or prescription and be prepared into oral formulations, bitterness is mainly from alkaloid.The lone electron of nitrogen-atoms is captured positive charge (like the hydrogen proton) positively charged easily in the alkaloid, can form complex through ion exchange with cation ion exchange resin, shelters bitterness.Ion exchange resin has the characteristic of macromonomer copolymer simultaneously, also can stop alkaloid to contact with taste bud through the form of absorption or complexation, reaches the purpose of taste masking.
Ion exchange resin described in the invention is methacrylic acid divinyl benzene copolymer or divinylbenzene crosslink polystyrolsulfon acid copolymer, comprises AMBERLITE
TMIRP64, IRP88 and TRP69.
Cation exchange resin AMBERLITE
TMIRP88 and IRP69 are respectively methacrylic acid potassium divinyl benzene copolymer and divinylbenzene crosslink kayexalate copolymer, are middle pharmaceutically active ingredient alkaloid or contain to want acidified processing before the alkaloid Chinese medicine extract combines.Ion exchange resin salt is converted into the amberlite fat acid, and through the conditioned reaction system pH, exchange rate is reacted in control when medicine～ion exchange resin combines.Cation exchange resin AMBERLITE
TMIRP88 and IRP69 handle through following mode:
Get AMBERLITE
TMIRP88 and IRP69 ion exchange resin are an amount of, add in the 1mol/L hydrochloric acid solution, stir 1～2 hour, take out filtration and drain, and reuse deionized water rinsing filter bed is till drain.Again gained ion exchange resin is added in the 1mol/L hydrochloric acid solution, continue to stir 1～2 hour, filter, use the deionized water rinsing filter bed.Ion exchange resin after handling is put 60 ℃ of drying under reduced pressure casees, dry for standby.
AMBERLITE
TMIRP64 is the methacrylic acid divinyl benzene copolymer; Weak-acid ion exchange resin; When exchange reaction, need not to carry out acidification; Directly add the effective ingredient alkaloid or contain in the reactant liquor of alkaloid Chinese medicine extract conditioned reaction system pH, preparation ion exchange resin～taste masking complex.
Chinese medicine medicine intermediate ion exchanger resin according to the invention and single agent Chinese medicine extract or Chinese medicine compound extract Chinese traditional medicine biology alkali weight 10: 1 to 1: 10, preferred 5: 1 to 1: 5.Confirm the inventory of ion exchange resin resin according to the content of alkaloid component.
Behind the dry thing proportional mixing of ion exchange resin according to the invention and Chinese medicine extract, be exchange media with the deionized water.According to alkaloidal existence (free or protonated), with the pH value of low concentration bronsted lowry acids and bases bronsted lowry solution adjusting exchange media, exchange media pH scope 3～10, preferred 5～8.
Can add suitable sweeting agent in the medicine ion exchanger resin complex of the present invention's preparation, like sucrose, fructose, stevioside, saccharin sodium, aspartame and sucralose, suitable aromatic, coolant agent.
The method for preparing of the medicine of Chinese medicine described in the invention can realize through following method:
With Chinese medicine extract, 60 ℃ of drying under reduced pressure are pulverized, and it is subsequent use to cross 100 mesh sieves, according to the weight percentage of alkaloid in extract, calculate the inventory of ion exchange resin.Take by weighing a certain amount of cation exchange resin AMBERLITE
TMIRP64 (trade name: polacrilin) or through acid-treated AMBERLITE
TMIRP88, IRP69.Chinese medicine extract fine powder and ion exchange resin are even by 10: 1 to 1: 10 mixed, add deionized water, regulate in pH to 5～8 scopes, under 25～80 ℃ of conditions, stir 8～12 hours.Be evaporated to thick paste, take out, vacuum drying is pulverized, and promptly gets the Chinese medicine medicine.
This medicine is a pressed powder, adds excipient, correctives, can be prepared into oral formulations such as granule, tablet, mixture and powder.This Chinese medicine medicine has been covered the bitterness that contains alkaloid Chinese medicine and preparation, have good mouthfeel, has improved the compliance that the patient takes medicine, has bigger economy and social value.Have stronger anti-hygroscopic effect in this Chinese medicine medicine simultaneously, obviously changed the bibulous characteristic of Chinese medicine preparation.
Methacrylic acid divinyl benzene copolymer or divinylbenzene crosslink polystyrolsulfon acid terpolymer ionomer exchanger resin used among the present invention are the pharmaceutical grade adjuvants, typically comprise AMBERLITE
TMIRP64, IRP88 and three kinds of cation exchange resiies of IRP69.AMBERLITE wherein
TMIRP64 is the methacrylic acid divinyl benzene copolymer, and every 1g exchange capacity is (with H
+) meter is no less than 10mEq (mM equivalent).
The medicine of Chinese medicine described in the invention can be prepared into above four kinds of peroral dosage forms, but be not limited to tablet, granule, powder and mixture, and the complex that alkaloid monomer forms can also be prepared into other oral formulations such as suspensoid, dry suspension, oral gel.The present invention proposes a kind of a kind of method of utilizing ion exchange resin shielding alkaloid extract monomer or containing alkaloid Chinese medicine compound extract bitterness.
The present invention proposes the Chinese medicine medicine, and to have preparation technology easy, and the advantage that taste masking is effective has reduced postprocessing working procedures simultaneously, is fit to suitability for industrialized production.
The specific embodiment:
The peaceful granule of the health heart has benefiting QI for activating blood circulation, promoting QI circulation for relieving depression, the function that coronary circulation-promoting pain-relieving, consolidating YIN are throbbed with fear surely.Cure mainly blood stasis-type thoracic obstruction caused by qi deficiency, cardiopalmus, angina pectoris, sexual type wit and arrhythmia etc. fast.In the side three flavor medical material is the Radix Astragali, Rhizoma Chuanxiong and Radix Sophorae Flavescentis.Radix Sophorae Flavescentis is the dry root of leguminous plant Radix Sophorae Flavescentis, has the effect of heat-clearing and toxic substances removing, dispeiling pathogenic wind and removing dampness, killing parasites for relieving itching.In recent years from Radix Sophorae Flavescentis extraction separation identify over one hundred kind of chemical constituent; And clear and definite its main effective ingredient is a total alkaloids; Wherein matrine and oxymatrine are again the main active in the total alkali; Modern pharmacological research shows that matrine and oxymatrine have experimental antiarrhythmic effect.
Radix Sophorae Flavescentis is the source of the peaceful granule bitterness of the health heart in the embodiment of the invention, and effective ingredient is for mainly being matrine.The extraction process of the Radix Astragali mainly is in order to obtain the effective ingredient astragalus polysaccharides, and the Rhizoma Chuanxiong extraction process mainly is in order to obtain effective ingredient ligustrazine and ferulic acid.
The peaceful granule prescription of the health heart is Radix Astragali 1500g, Rhizoma Chuanxiong 750g, Radix Sophorae Flavescentis 750g, and the extraction process of three flavor medical materials is following in the prescription: the Radix Astragali adds 70% ethanol, reflux, extract, 2 times; Adding for the first time 8 times of amounts extracted 1.5 hours; Add for the second time 6 times of amounts and extracted 1 hour, filter, filtrating merges; Decompression recycling ethanol, medicinal residues, medicinal liquid are subsequent use.Rhizoma Chuanxiong adds 8 times of amounts for the first time and extracted 2 hours with 90% alcohol reflux 2 times, adds 6 times of amounts for the second time and extracts 1 hour, filters, and filtrating merges, decompression recycling ethanol, and medicinal residues, medicinal liquid are subsequent use.Radix Sophorae Flavescentis extracted 1 hour with 8 times of amount 70% alcohol reflux 2 times at every turn, merged extracted twice liquid, filter, and decompression recycling ethanol, medicinal residues, medicinal liquid are subsequent use.Above medicinal residues are merged, and decocte with water 2 times adds 10 times of amounts of water for the first time, decocts 1 hour; For the second time add 8 times of amounts of water, decocted 0.5 hour, filter; Merge twice decocting liquid and above-mentioned medicinal liquid, adjustment volume to 1: 8-10 (medical material: medicinal liquid), filter; Get the thick paste that supernatant is evaporated to proportion 1.30～1.35 (60 ℃), drying under reduced pressure, it is subsequent use to be ground into fine powder.
Main bitter is to have matrine to introduce among the Kang Xinning, selects in the prescription design therefore that the inventory ratio of content of matrine and ion exchange resin is that 1: 1,1: 2,1: 3,1: 4,1: 5,1: 0.5,1: 0.33,1: 0.25,1: 0.2 amount is reacted in the peaceful dry extract of the health heart.
The determination of matrine method is following in the peaceful dry extract of the health heart: the chromatographic condition chromatographic column: Diamonsil C18 (2) 5 μ m, 250mm * 4.6mm, rustless steel packed column; Mobile phase: acetonitrile-0.2% phosphoric acid solution (5: 95); The detection wavelength is 207nm; Flow velocity: 1mL/min; Column temperature: room temperature.The preparation of reference substance solution: it is an amount of that precision takes by weighing the matrine reference substance, adds mobile phase and process the solution that every 1mL contains 5 μ g, shakes up, and promptly gets.The preparation of need testing solution: get the about 1g of the peaceful dry extract of the health heart, porphyrize, the accurate title, decide, and puts in the tool plug conical flask, accurate chloroform 25mL, strong ammonia solution 1mL, the close plug of adding; Claim decide weight, supersound process 30min is put coldly, and weight decided in title again, supplies the weight that subtracts mistake with chloroform; Shake up, filter, precision is measured subsequent filtrate 10mL, puts in the evaporating dish evaporate to dryness; Residue dissolves with mobile phase and is transferred in the 10mL volumetric flask, adds mobile phase and is diluted to scale, shakes up, and filters, and promptly gets.
According to the extraction process of confirming, record that content of matrine is respectively 0.08g/g in three batches of peaceful dry extracts of the health heart, 0.083g/g and 0.084g/g, containing matrine in the peaceful dry extract of promptly every gram health heart is 0.0823g.
The pH span of control is 3～10 in the reaction system, and being preferably the pH scope is 5～8.AMBERLITE
TMIRP64 (polacrilin) is a weak-type ion exchange resin, when system pH reaches 6, and AMBERLITE
TMAcrylic acid hydrogen proton is in free state among the IRP64, can ion exchange take place with positively charged medicine in the reaction system (contain the N electron withdraw group, obtain positive charge), forms ion exchange resin～medicinal composition.AMBERLITE
TMIRP88 acidified processing back and AMBERLITE
TMThe IRP64 structural formula is identical, so both are sisters' ion exchange resin.AMBERLITE
TMIRP69 is a divinylbenzene crosslink kayexalate terpolymer ionomer exchanger resin, after acidification, forms acid stronger sulfonated ion exchange resin and middle pharmaceutically active ingredient alkaloid or contains alkaloid Chinese medicine compound extract and carry out ion exchange.Exchanging mechanism is identical with IRP64, and high spot reviews IRP64 shelters the effect of the peaceful extract bitterness of the health heart among the embodiment.
Embodiment 1:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other takes by weighing cation exchange resin polacrilin 82.3g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
Above-mentioned complex and dextrin are pressed the prescription mixed, add aspartame, citric acid again, use 90% alcohol granulation, 60 ℃ dry, and granulate, packing promptly get the peaceful granule of the health heart.
Embodiment 2:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other takes by weighing cation exchange resin polacrilin 164.6g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Embodiment 3:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other takes by weighing cation exchange resin polacrilin 246.9g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 50 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Embodiment 4:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other takes by weighing cation exchange resin polacrilin 329.2g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Embodiment 5:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other adds cation exchange resin polacrilin 411.5g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Embodiment 6:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other adds cation exchange resin polacrilin 41.5g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Embodiment 7:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other adds cation exchange resin polacrilin 27.4g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Embodiment 8:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other adds cation exchange resin polacrilin 20.58g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Embodiment 9:
Take by weighing the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other adds cation exchange resin polacrilin 16.46g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
Bitterness is sheltered in alkaloid (mainly being matrine) generation ion exchange in cation exchange resin and the Radix Sophorae Flavescentis in the embodiment of the invention.Matrine and polacrilin (AMBERLITE
TMIRP64) structural formula is following:
(1) matrine structural formula (2) cation exchange resin polacrilin
N is in around the electron-donating group in the matrine, and cloud density is increased, and alkalescence strengthens, and the positive charge that is easy to get with hydrogen proton generation ion exchange in the polacrilin, forms the ion exchange resin alkaloid composite.Can use following reaction equation to describe:
RCOO
+H
～Represent the cation exchange resin polacrilin
BH
+Represent matrine
Simultaneously,, can combine with matrine, form taste-masking composite through the form of absorption and complexation because polacrilin is a kind of porous macromolecular compound.
Embodiment 10:
Get AMBERLITE
TMIRP69 ion exchange resin 1kg adds in the 1mol/L hydrochloric acid solution, stirs 1～2 hour, takes out filtration and drains, and reuse deionized water rinsing filter bed is till drain.Again gained ion exchange resin is added in the 1mol/L hydrochloric acid solution, continue to stir 1～2 hour, filter, use the deionized water rinsing filter bed.Ion exchange resin after handling is put 60 ℃ of drying under reduced pressure casees, dry for standby.
Get the peaceful extract dried powder of health heart 1kg (matrine content is 82.3g), other adds cation exchange resin AMBERLITE
TMIRP69164.6g, mix homogeneously.Add the 1L deionized water, using the 0.1mol/ML sodium hydroxide to regulate pH value is about 6, stirs 12h under 25 ℃ of conditions; 60 ℃ are evaporated to relative density (1.3～1.5) thick paste, and 60 ℃ of vacuum drying 24h take out; Pulverize, get yellowish-brown ion exchange resin complexes powder.
With above-mentioned complex and dextrin proportional mixing, adding aspartame, citric acid, use 90% alcohol granulation, 60 ℃ are dry, promptly get the peaceful granule of the health heart.
AMBERLITE
TMAfter the IRP88 acidification, the same AMBERLITE of structural formula
TMIRP64, so the same IRP64 of taste masking are not described further.
Find that in preliminary experiment reaction temperature is in 25～80 ℃ of scopes, the taste masking influential effect is little, and for saving cost, the exchange reaction temperature is selected 25 ℃ of room temperatures; Mixing time is investigated 8h, 12h, 16h and 24h respectively, and the result finds, stirs that the taste masking effect changes not quite after 12 hours, confirms mixing time 12 hours.Therefore, drug extract and ion exchange resin ratio is the key factor that influences the taste masking effect.The pH of system is controlled between 5～8 in the reaction, helps improving the reaction exchange efficiency, reaches satisfied taste masking effect.
Embodiment 11:
Bitterness is estimated
The power of bitterness does not have corresponding physiologic index to use, and can taste test to sample, and according to the strong and weak divided rank of bitterness, specifically be classified as follows: 0 grade for there not being bitterness; 1 grade for feeling bitterness; 2 grades for there being obvious bitterness; 3 grades awkward to swallow; 4 grades is that bitterness is strong, spues at once; 5 grades bitter for extremely, causes vomiting.Get the peaceful granule of the 10mg health heart during trial test at every turn and put into the about 10s of mouth, rinse the mouth with drinking water before each the trial test.
The peaceful ion exchange resin complexes craft screening of the table 1 health heart
Prepare the peaceful ion exchange resin complexes of the health heart according to embodiment; Prepare ion exchange resin complexes sample and matrine reference substance according to determination of matrine method among the Kang Xinning; Respectively according to chromatographic condition sample introduction under the assay item, investigate the disturbed condition that adds behind the ion exchange resin resin assay.
The peaceful ion exchange resin complexes craft screening of table 2 health heart result
Annotate: the contrast prescription is to prepare granule according to the peaceful preparation technology of the health heart, does not have ion exchange resin taste masking process.
Conclusion: the homo-ion exchanger resin of Chinese medicine extract is stirred through mixing, and concentrate drying makes medicine, can shelter the bitterness of matrine.In this example; Mixing time reaches 12 hours; Reaction temperature is 25 ℃ of room temperatures; Matrine and ion exchange resin mass ratio are that the bitterness that the medicine for preparing under 1: 2 the condition is sheltered matrine has splendid effect, and noiseless to the quality control of matrine, and this complex does not disturb other component content to measure simultaneously.IRP69 is according to the same IRP64 of optimum prescription preparation Chinese medicine taste masking effect.Therefore, ion exchange resin is used for the bitterness alkaloid or has effect preferably aspect the taste masking of alkaloid Chinese prescription extract containing.
In a word, the preparation technology of this Chinese medicine taste masking complex is simple, is convenient to operation, has huge marketing prospect.
Claims (3)
1. shielding alkaloid Chinese medicine medicine; It is characterized in that compositions for Chinese medicine extract and ion exchange resin; Ion exchange resin acidified processing earlier is converted into the amberlite fat acid and mixes with Chinese medicine extract; Perhaps ion exchange resin is that weak-acid ion exchange resin directly mixes with Chinese medicine extract, and Chinese medicine extract is processed by three kinds of single agent Chinese medicine extraction: the prescription of three kinds of single agent Chinese medicines is following: Radix Astragali 1500g, Rhizoma Chuanxiong 750g, Radix Sophorae Flavescentis 750g, ion exchange resin are methacrylic acid divinyl benzene copolymer or divinylbenzene crosslink polystyrolsulfon acid copolymer; The mixed weight ratio is: alkaloid weight and ion exchange resin weight ratio are 1 in the Chinese medicine extract: (2-5); Mix the back and add deionized water, the pH value through regulating mixed liquor is greater than 6 less than in 10, control reaction exchange rate; Mixed liquor stirs, is condensed into thick paste, and crushed after being dried promptly gets the Chinese medicine medicine.
2. Chinese medicine medicine according to claim 1; The method for preparing that it is characterized in that Chinese medicine extract is following: earlier each single agent Chinese medicine must be filtrated with ethanol extraction, filtration, recovery ethanol respectively; To extract the back medicinal residues more separately and merge, water decocts, and medicinal residues are crossed and filtered filtrating; All filtratings are merged, and adjustment weight is 8～10 times of all single agent Chinese medicine gross weights, filters, and gets the thick paste that supernatant is evaporated to proportion 1.30～1.35, and crushed after being dried promptly gets the Chinese medicine extract powder.
3. Chinese medicine medicine according to claim 1 is characterized in that alkaloids content is measured by following method in whole Chinese medicine extract: adopt the weight of matrine in the high effective liquid chromatography for measuring Chinese medicine extract, it is an amount of to get the Chinese medicine dry extract; Porphyrize, the accurate title, decide, and puts in the tool plug conical flask; Adopt ammonia alkalization back chloroform supersound extraction matrine; As need testing solution, it is an amount of that precision takes by weighing the matrine reference substance, adds mobile phase and process reference substance solution with mobile phase dilution back; Chromatographic system is following: reversed phase chromatographic column, mobile phase are the low phosphorus aqueous acid that contains acetonitrile, and the detection wavelength is 207nm; Flow velocity: 1mL/min injects high performance liquid chromatogram according to the said determination condition with need testing solution and reference substance solution, calculates matrine weight with external standard method.
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| CN1698838A (en) * | 2005-06-24 | 2005-11-23 | 殷昕 | Chinese medicine for treating cardiovascular disease and method for preparing same |
| CN101103978A (en) * | 2006-07-12 | 2008-01-16 | 梁伟 | Berberine resin composition and its preparation method and medicinal composition containing the same |
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| CN101103978A (en) * | 2006-07-12 | 2008-01-16 | 梁伟 | Berberine resin composition and its preparation method and medicinal composition containing the same |
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| 李大成.离子交换树脂法提取苦参总碱.《中成药研究》.1982,(第6期),第35-36页. * |
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