CN1593504A - Microencapsulation method of Chinese traditional medicine - Google Patents
Microencapsulation method of Chinese traditional medicine Download PDFInfo
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- CN1593504A CN1593504A CN 200410019984 CN200410019984A CN1593504A CN 1593504 A CN1593504 A CN 1593504A CN 200410019984 CN200410019984 CN 200410019984 CN 200410019984 A CN200410019984 A CN 200410019984A CN 1593504 A CN1593504 A CN 1593504A
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Abstract
The invention relates to a coated medicine-carrying process for volatile medicament or oil form traditional Chinese medicine with mucosity such as borneol, which consists of dissolving the medicinal components and capsule material in organic solvent, stirring and charging into the aqueous phase of surface active agent, then performing cross-linking, aging, filtering and drying, thus obtaining coated medicine-carrying microcapsule or microsphere.
Description
Technical field
The invention belongs to Chinese medicine parcel drug delivery technologies.Relate to traditional medicine volatile oil, volatile medicine, and the extractum that obtains of various extracting method and dispersion, the parcel drug delivery technologies of oil; Provide that a kind of drug loading is big, the Chinese medicine medicine carrying practice of pharmacy of parcel medicine carrying stable performance.
Background technology
The Chinese medicine ingredients complexity, Chinese patent medicine is formed by plurality of Chinese.Volatile oil and volatility Borneolum Syntheticum, Herba Menthae etc. are conventional Chinese medicines.In existing preparation production technique, all with direct pulverizing or spray into group medicine, refabrication becomes corresponding preparations at present.Borneolum Syntheticum, Herba Menthae are in existing preparation production technique, and being used as medicine exists two big technical problems.First production process is because its volatility, the technical process pollution production environment that runs off in a large number.Its two be since its distillation characteristic is arranged, all exist the storage period medicine ceaselessly to distil a moment from preparation problem that composition loses such as the tablet of present domestic traditional handicraft preparation, capsule, pill, powder, in accelerated test proves Borneolum Syntheticum effective ingredient year in some preparations, can run off about 30%, affect the treatment.It three is that the Borneolum Syntheticum pharmaceutical pack that constantly distils be difficult to be selected, particularly modern tablet, and the plastic packaging of pill etc. " bubble eye " transparent wrapper then often because of Borneolum Syntheticum distillation, " frost mist " pollute, and can not use the transparent modern packaging thing that waits.The Chinese medicine volatile ingredient is mostly by tens complex mixtures of forming to hundreds of kind chemical compound.They occupy critical positions in Chinese medicine.Existing Chinese medicine preparation technology, most of volatile oil component is many to be used as medicine with direct spirt group medicine, and a lot of volatile ingredients not only affect the treatment, influence outward appearance in medicine storage phase instability, particularly can not formulate the quality standard of content of drug, lack competitiveness in the world.For this reason, to the Chinese medicine ingredients of physical property distillation, use that modern medicinal agents learns a skill, to change its production status be the task of top priority to modern medicinal novel adjuvant.
The ethereal oil of Chinese medicine in Effective Components of Chinese Herb, is the active component that occupies important proportion.Storax oil, Fructus Xanthii oil, Rhizoma Atractylodis wet goods owing to it is thickness liquid state or liquid drug, carry not to be one of its shortcoming in existing Chinese medicine production technology; Another shortcoming be in conventional formulation is produced Chang Yinqi thickness, liquid state, cause in the preparation process mobile poor, the preparation resistance is big, poor compressibility, obstacle the process of modernization of Chinese medicine production.To make some kind still can not serialization, mechanization production, also continuing to use the backward technology of manual powder charge.
In sum, adopting modern medicinal agents technology and novel medicinal auxiliary material, seek to be suitable for the parcel drug delivery technologies of volatile, distillation, thickness, oily medicine, is the key of the modernization of Chinese medicine, is the task of top priority.
Summary of the invention
The problem that solves:
At above-mentioned situation, the invention provides the toughness that traditional medicine volatile oil, volatile medicine Borneolum Syntheticum, Herba Menthae etc. and various Chinese medicine extraction and preparation method obtain and dispersion, the parcel medicine-carrying method of oily Chinese medicine ingredients.The Chinese medicine microencapsulation method has solved volatilization, distillation problems such as Borneolum Syntheticum, Herba Menthae and has caused content of drug instability, the abominable problem of production environment, solved Storax oil, Fructus Xanthii oil, Rhizoma Atractylodis oil, etc. the toughness medicine, it is used as medicine, and the preparation resistance is big, the problem of difficult forming.The Chinese medicine that the present invention is stable for preparation, content is controlled, enrich the Chinese patent medicine novel form and lay a good foundation.
Technical scheme:
The Chinese medicine microencapsulation method is to adopt coacervation or interfacial polymerization, medicinal ingredient and capsule material is dissolved in the pharmacopeia regulation can be used in the organic solvent of pharmacy, the formation organic facies; Water intaking in addition, the surfactant of adding 2～3% disperses, and forms water; Water is stirred or ultransonic condition under, organic facies is at the uniform velocity splashed into above-mentioned aqueous phase, it is fully disperseed, regulate pH value to 4～10, through crosslinked and solidify, obtain medicinal parcel medicine carrying microcapsule or microsphere; With excessive water extraction organic solvent, more after filtration, drying, can obtain discharging medicinal ingredient, runny parcel medicine carrying microcapsule or microsphere; Above-mentioned stirring or ultrasonic time are 0.5～2 hour; Be not less than 2 hours crosslinked and hardening time.
Wherein the capsule material is selected from natural or synthetic medical high-molecular additive, and natural polymer medical adjuvant comprises gelatin, arabic gum, sodium alginate, cellulose and cellulosic derivant, chitosan; The synthetic high polymer pharmaceutic adjuvant comprises the copolymer of poly-methyl-prop diluted acid, polymethyl acrylate, poly-methyl-prop diluted acid and poly-methyl-prop diluted acid ester, Youteqi E-100, Youteqi EPO, polyvinyl alcohol, in polyvinylpyrrolidone and the Polyethylene Glycol 1～3 kind.
Need to prove:
Above-mentioned in preparation parcel medicine carrying microcapsule, capsule material concentration is 1～10% in the organic facies.
Used medicinal ingredient can be the solid ground product of Chinese medicine; Also can be Borneolum Syntheticum, Herba Menthae of volatile, easy distillation etc.; Or thick or buttery Chinese medicine Storax oil, Rhizoma Atractylodis oil, Fructus Xanthii wet goods; Or the water of Rhizoma Chuanxiong, steam is carried or alcohol extraction, ether is carried, supercritical extraction obtains volatile oil and extractum or exsiccant solid medicine.
Used organic solvent is selected from the organic solvent that approval is used in the pharmacopeia, as ethanol, ethyl acetate, Ethyl formate and chloroform.
Used surfactant is selected from tween, class of department, sodium lauryl sulphate, polyvinyl alcohol, polyvinylpyrrolidone, Polyethylene Glycol.
Plasticizer is selected from citric acid, triethyl citrate, Polyethylene Glycol etc.In cross-linking agent such as formaldehyde and the glutaraldehyde one or both.Be not less than 2 hours crosslinked and hardening time.
Beneficial effect:
The present invention uses modern solid dispersion technology and novel medicinal auxiliary material, use the strongly hydrophilic carrier, increase dissolubility and the dissolution rate of insoluble medicine Borneolum Syntheticum, Herba Menthae, improved bioavailability, improved volatility, overcome because of distillation, the medicine content storage period instability that is caused, affected the treatment, influenced outward appearance, the abominable problem of production environment; Dispersion, parcel drug delivery technologies to toughness and oily Chinese medicine Storax oil, Rhizoma Atractylodis oil, Fructus Xanthii oil, make the liquid Chinese medicine solid state of oily, and having solved Storax oil, Fructus Xanthii oil, Rhizoma Atractylodis wet goods toughness medicine, not portable, the difficult storage of its liquid state, flowability differ from and the big problem of preparation resistance of being used as medicine.Thereby improve the drug flow and the compressibility of Chinese medicine preparation production process.The Rhizoma Chuanxiong extract microencapsulation is given the medicine controlled releasing system.The parcel medicine carrying microcapsule made from the Chinese medicine microencapsulation method, be to make various pharmaceutical dosage forms, the ideal material of oral cavity disintegration tablet particularly, so present technique horn of plenty Chinese patent medicine novel form,, Chinese medicine, control Chinese medicine content that content controlled stable, formulate the controlled standard of Chinese patent medicine content and improved the preparation level of Chinese patent medicine production process, lay a good foundation for preparation.The invention process has been optimized production environment, has been covered the bad smell of Chinese medicine, has improved drug quality, has improved the compliance of patient's medication, both has an economic benefit, and social benefit is arranged again.
Description of drawings
Fig. 1: the distillation amount and the time curve comparison diagram of Borneolum Syntheticum, Borneolum Syntheticum parcel medicine carrying microcapsule;
Fig. 2: the distillation amount and the temperature relation curve comparison diagram of Borneolum Syntheticum, Borneolum Syntheticum parcel medicine carrying microcapsule;
The specific embodiment
Only preparation process of the present invention is done to specify below in conjunction with embodiment, but not any way limits the scope of the invention.
Embodiment 1:
Get Borneolum Syntheticum 10g, be dissolved in the 100ml ethanol, add polyvinylpyrrolidone 3g.Microcrystalline Cellulose 1g, ultrasonic mixing is added drop-wise in the 500ml aqueous solution that contains gelatin and each 0.5g of arabic gum.Will stir water during dropping, it is fully mixed, ultra-sonic dispersion 30 minutes is transferred pH value to 4, react 1 hour, adds cross-linking agent, and promptly 20% formalin and 5% glutaraldehyde solution 5ml altogether transfers to 8 with pH value, and is crosslinked, solidified 2 hours, gets the Borneolum Syntheticum microcapsule.Filtration product washes with water, with 5% citric acid solution 20ml post processing 10 hours, gets the Borneolum Syntheticum microcapsule, mean diameter 50-60um.
The usefulness of parcel medicine carrying microcapsule as depicted in figs. 1 and 2.Fig. 1 is the distillation amount and the time curve comparison diagram of Borneolum Syntheticum, Borneolum Syntheticum parcel medicine carrying microcapsule.Fig. 2 is the distillation amount and the temperature relation curve comparison diagram of Borneolum Syntheticum, Borneolum Syntheticum parcel medicine carrying microcapsule.In Fig. 1, A is the distillation discharge curve of Borneolum Syntheticum, and B is the distillation discharge curve of Borneolum Syntheticum parcel medicine carrying microcapsule, as can be seen, prolongs in time, and the distillation amount of Borneolum Syntheticum increases, and the distillation quantitative changeization of Borneolum Syntheticum parcel medicine carrying microcapsule is little.In Fig. 2, A is the distillation discharge curve of Borneolum Syntheticum, and B is the distillation discharge curve of Borneolum Syntheticum parcel medicine carrying microcapsule, as can be seen, raises with temperature, and the distillation amount of Borneolum Syntheticum increases, and the distillation quantitative changeization of Borneolum Syntheticum parcel medicine carrying microcapsule is little.In sum, under the same conditions, Borneolum Syntheticum is more much bigger than Borneolum Syntheticum parcel medicine carrying microcapsule distillation amount, illustrates that Borneolum Syntheticum is dispersed in the carrier, and content is more stable, has reduced its sublimability.
Embodiment 2-4:
Get oil-containing (or Rhizoma Atractylodis oil or Fructus Xanthii oil) 10g of Soviet Union and 1g ethyl cellulose, be dissolved in the 50ml ethyl acetate, be prepared into oil phase.The 1g sodium lauryl sulphate is dissolved in the 100ml water, adds ethyl acetate 1ml again, be prepared into by the saturated aqueous solution of ethyl acetate, with this as water.Water is being carried out under the stirring condition oil phase is at the uniform velocity splashed into water,, adding 500ml water again, removing solvent, can form Soviet Union's oil-containing (or Rhizoma Atractylodis oil or Fructus Xanthii oil) microcapsule through crosslinked and solidified 2 hours.Again after filtration, drying obtains microcapsule.The microcapsule mean diameter is 50-60um.Envelop rate 99%.
Embodiment 5:
Get Rhizoma Chuanxiong oil 10g, polypropylene acid resin 1g, be dissolved in the 50ml ethyl acetate, prepare oil phase.Get 100ml water, add the 2g Polyethylene Glycol, ultrasonic 30 minutes, preparation became water.Water is being carried out under the stirring condition organic facies is at the uniform velocity splashed into above-mentioned aqueous phase, solidifying 3 hours, removing solvent, more after filtration, drying can obtain the microcapsule of medicine carrying Rhizoma Chuanxiong.Other is with embodiment 2-4.Mean diameter 50-60um.Envelop rate 90%.
Embodiment 6:
Get Herba Menthae 10g,, add gelatin 0.1g with ethanol 20ml dissolving.Microcrystalline Cellulose 0.1g, ultrasonic mixing is prepared into oil phase, get 200ml water adding sodium alginate 1.5g it is fully mixed, ultra-sonic dispersion was prepared into water in 30 minutes, and water is being carried out under the ultrasound condition, organic facies is at the uniform velocity splashed into above-mentioned aqueous phase, reacted 1 hour, pH value is transferred to 8, crosslinked, solidified 2 hours, obtain microcapsule, filtration product washes with water, again drying, make the Herba Menthae microcapsule, mean diameter 50-60um.
Embodiment 7:
Get 1 kilogram of Rhizoma Chuanxiong, ethanol 10 rises up in the retort, heats back gold-plating, extracts 10 hours, concentrating under reduced pressure reclaims ethanol and volatile oil, merges volatile oil and concentrate, makes medicinal ingredient, and is standby.Get above-mentioned medicinal ingredient 10g, join among the alcoholic solution 10ml that contains 5% the strange E-100 of You Te, make oil phase.Other 100ml that fetches water adds the 3g citric acid, forms water; Water is being carried out under the stirring condition organic facies is at the uniform velocity splashed into aqueous phase, through crosslinked, solidified 4 hours, obtain medicinal Rhizoma Chuanxiong parcel medicine carrying microcapsule; With excessive water extraction organic solvent, more after filtration, drying, just obtain discharging medicinal ingredient, runny parcel Rhizoma Chuanxiong medicine carrying microcapsule, its mean diameter is 80um.
Embodiment 8:
Get Borneolum Syntheticum 1g, be dissolved in 10ml ethanol, add polyvinylpyrrolidone and each 0.5g of ethyl cellulose, form oil phase, other 500ml that fetches water adds the sodium lauryl sulphate and the Polyethylene Glycol of 1g of 5g, disperses the formation water; Water is being carried out under the stirring condition organic facies is at the uniform velocity splashed into above-mentioned aqueous phase, through crosslinked, solidified 3 hours, obtain medicinal Borneolum Syntheticum parcel medicine carrying microcapsule; Again after filtration, drying, obtain discharging medicinal ingredient, runny parcel Borneolum Syntheticum medicine carrying microcapsule.Borneolum Syntheticum is handled through said method, promptly gets drug loading and be 40% medicine carrying microcapsule, and its particle diameter is 50～100um.
Claims (9)
1. the Chinese medicine microencapsulation method is characterized in that adopting coacervation or interfacial polymerization; Medicinal ingredient and capsule material are dissolved in pharmacopeia organic solvent regulation, that can be used for pharmacy, form organic facies; Water intaking in addition, the surfactant of adding 2～3% disperses, and forms water; Water is stirred or ultrasound condition under, organic facies at the uniform velocity is added drop-wise to aqueous phase, make its dispersion, regulate pH value to 4～10, add plasticizer or cross-linking agent, through crosslinked and solidify, obtain medicinal parcel medicine carrying microcapsule or microsphere; With excessive water extraction organic solvent, more after filtration, drying, obtain discharging medicinal ingredient, runny parcel medicine carrying microcapsule or microsphere;
Above-mentioned capsule material is selected from natural and the synthetic high polymer pharmaceutic adjuvant, and natural polymer medical adjuvant comprises gelatin, arabic gum, sodium alginate, cellulose and cellulosic derivant, chitosan; The synthetic high polymer pharmaceutic adjuvant comprises the copolymer of poly-methyl-prop diluted acid, polymethyl acrylate, poly-methyl-prop diluted acid and poly-methyl-prop diluted acid ester, Youteqi E-100, Youteqi EPO, polyvinyl alcohol, in polyvinylpyrrolidone and the Polyethylene Glycol 1～3 kind.
2. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that medicinal ingredient is the Chinese medicine solid ground product that obtains by the pharmacopeia conventional method, extractive of volatile oil, also can is the medicine of volatile, easy distillation such as Borneolum Syntheticum, Herba Menthae; Or thick, buttery Chinese medicine Storax oil, Rhizoma Atractylodis oil, Fructus Xanthii oil; Or the water of Rhizoma Chuanxiong, steam is carried or alcohol extraction, ether is carried, supercritical extraction obtains volatile oil and extractum or exsiccant solid medicine.
3. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that organic solvent is selected from the organic solvent that approval is used in the pharmacopeia, as ethanol, ethyl acetate, Ethyl formate and chloroform.
4. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that surfactant is selected from tween, class of department, sodium lauryl sulphate, polyvinyl alcohol, polyvinylpyrrolidone or Polyethylene Glycol.
5. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that stirring or ultrasonic time are 0.5～2 hour.
6. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that crosslinked and be not less than 2 hours hardening time.
7. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that plasticizer is selected from citric acid, triethyl citrate, Polyethylene Glycol etc.
8. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that in cross-linking agent such as formaldehyde and the glutaraldehyde one or both.
9. according to the described Chinese medicine microencapsulation method of claim 1, it is characterized in that capsule material concentration is 1～10% in the organic facies in preparation parcel medicine carrying microcapsule.
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100381568C (en) * | 2005-04-27 | 2008-04-16 | 中国科学院沈阳应用生态研究所 | Biological microcapsulation |
| CN100427145C (en) * | 2006-09-06 | 2008-10-22 | 魏郁梦 | Method for preparing carrier of hollow microsphere for medication in use for treating gastrointestinal tract |
| CN101972038A (en) * | 2010-10-28 | 2011-02-16 | 上海理工大学 | Slowly-released filter stick essence microcapsule and preparation method thereof |
| CN103565902A (en) * | 2013-11-13 | 2014-02-12 | 中国科学院青海盐湖研究所 | Slow release agent as well as preparation method and application thereof |
| CN106138212A (en) * | 2016-08-31 | 2016-11-23 | 天津中新药业研究中心 | A kind of compositions treating headache and preparation method thereof |
| CN106309527A (en) * | 2016-10-14 | 2017-01-11 | 广西放心源生物科技有限公司 | Method for preparing panax notoginseng microcapsules |
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| CN106333975A (en) * | 2016-10-14 | 2017-01-18 | 广西放心源生物科技有限公司 | Method for producing brucea javanica micro-capsule particles |
| CN106727387A (en) * | 2017-03-22 | 2017-05-31 | 上海市第八人民医院 | Rhizoma chuanxiong volatile oil oral instant microencapsule tablet and preparation method thereof |
| CN107468668A (en) * | 2017-08-31 | 2017-12-15 | 清华大学 | Utilize a large amount of methods for preparing natural polymer microcapsules of positive and negative charge effect |
| CN108437128A (en) * | 2018-04-23 | 2018-08-24 | 中国热带农业科学院橡胶研究所 | A kind of preparation method of the load iodo- 2-propynyl butylamino butyl formate microcapsule-type mildew preventing agent for wood of 3- |
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- 2004-07-15 CN CN 200410019984 patent/CN1299671C/en not_active Expired - Fee Related
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100381568C (en) * | 2005-04-27 | 2008-04-16 | 中国科学院沈阳应用生态研究所 | Biological microcapsulation |
| CN100427145C (en) * | 2006-09-06 | 2008-10-22 | 魏郁梦 | Method for preparing carrier of hollow microsphere for medication in use for treating gastrointestinal tract |
| CN101972038A (en) * | 2010-10-28 | 2011-02-16 | 上海理工大学 | Slowly-released filter stick essence microcapsule and preparation method thereof |
| CN103565902A (en) * | 2013-11-13 | 2014-02-12 | 中国科学院青海盐湖研究所 | Slow release agent as well as preparation method and application thereof |
| CN103565902B (en) * | 2013-11-13 | 2016-01-20 | 中国科学院青海盐湖研究所 | Slow releasing agent and its preparation method and application |
| CN106138212A (en) * | 2016-08-31 | 2016-11-23 | 天津中新药业研究中心 | A kind of compositions treating headache and preparation method thereof |
| CN106309527A (en) * | 2016-10-14 | 2017-01-11 | 广西放心源生物科技有限公司 | Method for preparing panax notoginseng microcapsules |
| CN106309881A (en) * | 2016-10-14 | 2017-01-11 | 广西放心源生物科技有限公司 | Method for microencapsulating radix asparagi |
| CN106333975A (en) * | 2016-10-14 | 2017-01-18 | 广西放心源生物科技有限公司 | Method for producing brucea javanica micro-capsule particles |
| CN106727387A (en) * | 2017-03-22 | 2017-05-31 | 上海市第八人民医院 | Rhizoma chuanxiong volatile oil oral instant microencapsule tablet and preparation method thereof |
| CN107468668A (en) * | 2017-08-31 | 2017-12-15 | 清华大学 | Utilize a large amount of methods for preparing natural polymer microcapsules of positive and negative charge effect |
| CN109745298A (en) * | 2017-11-02 | 2019-05-14 | 中国医学科学院药物研究所 | A kind of oral jamaicin micro-capsule nanoparticle is fitted into preparation and dosage regimen |
| CN109745298B (en) * | 2017-11-02 | 2022-04-15 | 中国医学科学院药物研究所 | Oral berberine microcapsule nanoparticle chimeric preparation and administration scheme |
| CN108437128A (en) * | 2018-04-23 | 2018-08-24 | 中国热带农业科学院橡胶研究所 | A kind of preparation method of the load iodo- 2-propynyl butylamino butyl formate microcapsule-type mildew preventing agent for wood of 3- |
| CN112675793A (en) * | 2020-12-10 | 2021-04-20 | 广州中国科学院先进技术研究所 | Preparation method of ganoderma lucidum spore oil nano microcapsule |
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| CN1299671C (en) | 2007-02-14 |
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