CN103301090A - Preparation method of genistein targeted nanometer particle - Google Patents
Preparation method of genistein targeted nanometer particle Download PDFInfo
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- CN103301090A CN103301090A CN2013102633589A CN201310263358A CN103301090A CN 103301090 A CN103301090 A CN 103301090A CN 2013102633589 A CN2013102633589 A CN 2013102633589A CN 201310263358 A CN201310263358 A CN 201310263358A CN 103301090 A CN103301090 A CN 103301090A
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Abstract
The invention discloses a preparation method of a genistein targeted nanometer particle, which belongs to the technical field of pharmacy. The preparation method comprises the following steps of: mixing trisodium citrate dehydrate, sodium hydroxide, ferrous sulfate heptahydrate, sodium tripolyphosphate and deionized water; adding a polyethylene glycol 400 solution of genistein; adding chitosan under stirring; centrifuging and separating after 2 hours to obtain the yellowish-brown genistein targeted nanometer particle. The product prepared by the preparation method disclosed by the invention can be used for changing the distribution of the drug in the human body and the dynamic characteristic of the drug, so that the drug is prevented from distributing broadly in the body and diffusing quickly; the targeted orientation of the drug can be used for reducing the drug exposure of the normal tissue, so that the side and toxic effect is lowered, and the treatment effect of the drug is improved.
Description
Technical field
The invention belongs to the pharmaceutical technology field.
Background technology
Nanochemistry (nanochemistry) is mainly studied the science of the various Chemical Problem in the Nanometer World that atom is above, 100nm is following, is the science of chemical preparation, chemical property and the application of research nanometer system.The main focus that various surprising complex steps that the life system runs into and process are nanochemistry is understood and is used in attempt.
Chitosan (chitosan writes a Chinese character in simplified form CS) is to be obtained through deacetylation by the chitin (chitin) that nature extensively exists, and chemical name is Chitosan (1-4)-2-amino-B-D glucose.Chitosan is not only the natural biologic material with good biocompatibility and degradability, also is the cationic polymer of the unique a large amount of existence of occurring in nature, because its distinctive character and cheap has become novel nano-medicament carrier.At present, utilize chitosan for the method that bag ancient piece of jade, round, flat and with a hole in its centre material prepares drug microcapsule covalent cross-linking method, ion induction method and self-assembly method etc. to be arranged, wherein, covalent cross-linking method is one of method of commonly using, it is to utilize the amino of chitosan molecule chain and chemical cross-linking agent to react, but because the cross-linking agent such as the Organic substances such as formaldehyde, glutaraldehyde that often use contain certain toxicity, therefore can't be applicable to vivo medicine-feeding; Though self-assembly method has certain advantage to the release of control macromolecular drug, its test method is comparatively loaded down with trivial details; And the ion induction method is to prepare the most general method of chitosan nano, it is by the intermolecular and intramolecular nanoparticle that is cross-linked to form of protonated amino generation positively charged on electronegative ion and the chitosan, this method mild condition, technique is simple, the condition controllability is higher, but this method generally is applicable to hydrophilic medicament, brings difficulty for the preparation of hydrophobic drug nanoparticle.
Genistein (Genistein) is the main component of soybean isoflavone, claims again genistein, genistein, is the isoflavonoid that comes from bean and dentation plant, its chemistry genistein by name.Genistein has multiple physiology or pharmacologically active, and Several Kinds of Malignancy such as breast carcinoma, gastric cancer, hepatocarcinoma, colon cancer, esophageal carcinoma etc. are had stronger inhibitory action.The structure of genistein and relative molecular mass and estradiol are similar.But genistein is not soluble in water, has therefore greatly limited its use at aqueous phase, and directly the oral bioavailability rate is lower.
Summary of the invention
The object of the invention is to propose a kind of easy and simple to handle, condition is easily controlled, be easy to the preparation method of industrialized genistein targeted nano-particle.
Technical solution of the present invention is: after two hydration trisodium citrates, sodium hydroxide, green vitriol, sodium tripolyphosphate and deionized water are mixed, add the PEG400 solution of genistein, under agitation add chitosan.After 2 hours, centrifugalize obtains yellowish-brown genistein targeted chitosan nanoparticle.
These 8 kinds of raw materials of two hydration trisodium citrates, sodium hydroxide, green vitriol, sodium tripolyphosphate, chitosan, genistein, PEG400 and deionized water account for respectively 0.20～0.36%, 0.3～0.7%, 0.7～1.1%, 0.2～0.6%, 1.6～2.0%, 4.0～8.0%, 20%～25% and 62.5～68.5% of the gross mass that feeds intake.
The present invention is with the standby genistein targeted nano-particle emulsion of chitosan ion induction legal system, take sodium tripolyphosphate as ion crosslinking agent it is carried out the physical crosslinking packaging medicine and form nanoparticle, improve hydrophobic drug by the penetrating rate of cell membrane with chitosan, take the magnetisable material ferriferrous oxide nano-particle as pharmaceutical carrier, the disposable genistein targeted nano-particle emulsion of making.This product changes the distribution of medicine in human body and the dynamics of medicine, avoids medicine to distribute in vivo extensively, spread soon, and the drug exposure of normal structure has been reduced in the targeting of medicine location, reduces toxic and side effects, improves curative effect of medication; Because the magnetisable material ferriferrous oxide nano-particle that wherein comprises adds under the magnetic navigation function of high frequency alternating magnetic field outside, arrive tumor locus again, by regulating the intensity of externally-applied magnetic field, the interior nano-particle temperature of body is risen come the kill tumor cell.
Description of drawings
Fig. 1 is the infrared spectrum evaluation figure of the genistein targeted nano-particle that adopts the present invention and make.
The specific embodiment
One, preparation technology: two hydration trisodium citrates, sodium hydroxide, green vitriol, sodium tripolyphosphate are joined in the deionized water.After each thing dissolving mixes, add the PEG400 solution of genistein, under agitation add chitosan.After 2 hours, under 5000～10000 r/min conditions, adopt centrifugal separation method, obtain yellowish-brown genistein targeted chitosan nanoparticle.
In kind, adopt following five kinds of different mix proportion schemes, can prepare respectively five parts of genistein targeted nano-particles:
1: two hydration trisodium citrate of scheme 0.2kg, sodium hydroxide 0.3 kg, green vitriol 0.8 kg, sodium tripolyphosphate 0.6 kg, chitosan 1.6 kg, genistein 5.0 kg, Polyethylene Glycol 23 kg, deionized water 68.5 kg.
Scheme 2: two hydration trisodium citrate 0.2 kg, sodium hydroxide 0.4 kg, green vitriol 0.8 kg, sodium tripolyphosphate 0.5 kg, chitosan 1.7 kg, genistein 6.0 kg, Polyethylene Glycol 23 kg, deionized water 67.4 kg.
Scheme 3: two hydration trisodium citrate 0.28 kg, sodium hydroxide 0.5 kg, green vitriol 0.9 kg, sodium tripolyphosphate 0.5 kg, chitosan 1.8 kg, genistein 7.5kg, Polyethylene Glycol 25 kg, deionized water 63.52kg.
Scheme 4: two hydration trisodium citrate 0.35 kg, sodium hydroxide 0.7 kg, green vitriol 1.0 kg, sodium tripolyphosphate 0.3 kg, chitosan 1.6 kg, genistein 8.0 kg, Polyethylene Glycol 21 kg, deionized water 67.05 kg.
Scheme 5: two hydration trisodium citrate 0.35 kg, sodium hydroxide 0.5 kg, green vitriol 1.1 kg, sodium tripolyphosphate 0.6 kg, chitosan 2.0 kg, genistein 7.0 kg, Polyethylene Glycol 22 kg, deionized water 66.54 kg.
Two, product is identified with infrared spectrum:
Infrared spectrum is recorded by Fourier infrared spectrograph (NEXUS-670F-IR).
As shown in Figure 1, wherein, curve 1 is the infrared spectrogram of the genistein targeted nano-particle of the present invention's preparation, curve 2 is the infrared spectrogram of genistein nanoparticle, curve 3 is the infrared spectrogram of magnetic ferroferric oxide, curve 4 is the infrared spectrogram of genistein, and curve 5 is the infrared spectrogram of chitosan.The genistein targeted nano-particle is the infared spectrum stack of chitosan, genistein and ferroso-ferric oxide, but peak intensity is again than strong a lot, this is because ferroso-ferric oxide and the less particle surface that is adsorbed on of genistein, and be wrapped in together chitosan inside, and relative amount is less, and the absworption peak of genistein targeted nano-particle has the stack than multimodal, and therefore, peak intensity is stronger.
Ferroso-ferric oxide is at 585cm
-1There is characteristic absorption peak at the place, also embodies in the infared spectrum of genistein targeted nano-particle; At 3350cm
-1Larger absworption peak has appearred in left and right sides genistein targeted nano-particle, and chitosan and genistein also have absorption herein; At 800cm
-1To 1750cm
-1Near comparatively many peaks have appearred, at 1600cm
-1And 1500cm
-1The similar peak of more genistein has appearred in place's medicament nano particle, and on the whole, the genistein targeted nano-particle is the infared spectrum stack of chitosan, genistein and ferroso-ferric oxide.Infared spectrum proves that to the sign of medicament nano particle, chitosan and genistein genistein and ferroso-ferric oxide are wrapped up by chitosan, contain the genistein effective ingredient in the genistein targeted nano-particle.
Three, the process of extracorporeal releasing test and result:
Adopt the dynamic dialysis method, in-vitro simulated releasing effect by contrast genistein reference substance, genistein chitin nanometer and the magnetic genistein targeted nano-particle of tool, almost all discharge in the genistein reference substance 7h, burst size is 96.07% behind the genistein chitin nanometer 60h, and the burst size behind the genistein targeted nano-particle 60h only reaches 78.35%, proves that the genistein targeted nano-particle has preferably slow releasing function.
Claims (2)
1. the preparation method of a genistein targeted nano-particle, it is characterized in that: after two hydration trisodium citrates, sodium hydroxide, green vitriol, sodium tripolyphosphate and deionized water are mixed, the PEG400 solution that adds genistein, under agitation add chitosan, after 2 hours, centrifugalize obtains genistein targeted chitosan nanoparticle.
2. described preparation method according to claim 1, it is characterized in that: when feeding intake, described two hydration trisodium citrates, sodium hydroxide, green vitriol, sodium tripolyphosphate, chitosan, genistein, PEG400 and deionized water account for respectively 0.20～0.36%, 0.3～0.7%, 0.7～1.1%, 0.2～0.6%, 1.6～2.0%, 4.0～8.0%, 20%～25% and 62.5～68.5% of the gross mass that feeds intake.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017133599A1 (en) * | 2016-02-04 | 2017-08-10 | 覃扬 | New use of tumour gene methylation modifier and anti-tumour drugs |
| CN110384684A (en) * | 2019-08-26 | 2019-10-29 | 安徽农业大学 | A kind of mono carboxylic chitosan/alkannin composite nanometer particle and preparation method thereof |
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2013
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Non-Patent Citations (2)
| Title |
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| 周孙英等: "5-氟尿嘧啶磁性壳聚糖纳米微囊的制备及特性", 《海峡药学》 * |
| 谢玄: "三羟基异黄酮壳聚糖纳米体的制备及其体内吸收、抗氧化研究", 《中国优秀硕士学位论文全文数据库工程科技I辑》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017133599A1 (en) * | 2016-02-04 | 2017-08-10 | 覃扬 | New use of tumour gene methylation modifier and anti-tumour drugs |
| US11179349B2 (en) | 2016-02-04 | 2021-11-23 | Yang Qin | Use of tumor gene methylation regulator and anti-tumor drugs |
| CN110384684A (en) * | 2019-08-26 | 2019-10-29 | 安徽农业大学 | A kind of mono carboxylic chitosan/alkannin composite nanometer particle and preparation method thereof |
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