CN100374463C - Method for preparing nanometer realgar gel and nanometer realgar with biomacromolecule template to regulate shape and particle thereof - Google Patents
Method for preparing nanometer realgar gel and nanometer realgar with biomacromolecule template to regulate shape and particle thereof Download PDFInfo
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- CN100374463C CN100374463C CNB2005100204885A CN200510020488A CN100374463C CN 100374463 C CN100374463 C CN 100374463C CN B2005100204885 A CNB2005100204885 A CN B2005100204885A CN 200510020488 A CN200510020488 A CN 200510020488A CN 100374463 C CN100374463 C CN 100374463C
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Abstract
The present invention provides a method for preparing a nanometer realgar colloid and nanometer realgar by using a biomacromolecule template to regulate shape and particle diameter thereof, which is characterized in that a chemical method is utilized to remove white arsenic and impurity elements in natural realgar ore, the biomacromolecule is taken as a template to regulate and control the shape and the particle diameter to obtain a nanometer realgar colloid and nanometer realgar, and the nanometer realgar with different shapes and particle diameters can be obtained by changing the template kind and the aging condition. The present invention has wide used treating material. The manufactured nanometer realgar has high purity, uniform particle diameter and high water-solubility and is not easy to oxidize and aggregate. The nanometer realgar has positive synergistic effect with the molecule of the template and can obviously enhance the effects of realgar antibiotic drugs and anti-tumor drugs, improve the biological availability of realgar, reduce the side effects of the realgar and can expand the administration route of the realgar.
Description
(1) technical field:
The present invention relates to the preparation method of Chinese medicine nanometer-size realgar, particularly prepare the method for nanometer-size realgar colloid and nanometer-size realgar with biomacromolecule template to regulate shape and particle diameter.
(2) background technology:
Realgar is as a kind of mineral Chinese medicine, and is on the books in China's first medicine monograph Shennong's Herbal.Be used to control mange for a long time, dislike diseases such as sore and snake bite and insect sting.From nineteen fifties, Chinese scholar takes the lead in containing compound preparation or the former medicine realgar of realgar, is used for the cancer at clinical treatment blood system and other positions of human body, has higher safe remission rate.Yet, realgar is as a kind of arsenical compound, effect to body shows as two-phase, in kill cancer cell and bacterium, also show toxicity, can suppress to contain the activity of sulfenyl enzyme, stop cellular oxidation, breathing, interference tissue metabolism, make central nervous system disorder etc., serious also can carcinogenic teratogenesis.Studies show that, the toxic side effect of realgar and its using dosage, existence and with the antagonism of other materials or act synergistically relevant, there is the scholar to obtain satisfactory effect with the realgar treatment malignant hematologic disease of high purifying, also have the scholar to replace traditional realgar with nanometer-size realgar, discovery has tangible dimensional effect, and nanometer-size realgar can strengthen drug effect, reduces toxicity.At present, what the making method of nanometer-size realgar adopted usually is physical method, promptly uses external force such as air-flow, ball milling, makes between the material particles to bump, impact and rub and pulverize, and makes particle diameter reach micrometer/nanometer level level, and existing physics method has:
(1) comminution by gas stream: the realgar meal by micronizer mill, is controlled air pressure and flow rate regulation granularity under action of high-speed airflow;
(2) thin pearl polishing: the realgar meal ground about 2 hours with the thin pearl of zirconium white of diameter 1mm, and rotating speed is 500r/min;
(3) microjet method: water flies realgar and crosses 500 mesh sieves, suitably adds hot distilled water, stirs and makes;
(4) high-energy ball milling method: the realgar meal is placed the vacuum of being furnished with the deep cooling overcoat or the ball grinder of inert atmosphere, a certain proportion of abrading-ball of packing into, the rotating speed and the time of control high energy ball mill.
Adopt the prepared by physical method nanometer-size realgar to have that production process is continuous, throughput is big, the level of automation advantages of higher, but shortcoming is also arranged.Specifically:
(1) purity is low: physics method processing nanometer-size realgar is subjected to the restriction of raw material arsenic disulfide grade, unavoidably can bring orpiment (As into
2S
3), arsenic (As
2O
3), impurity such as metal ion, can not directly process the low-grade realgar that foreign matter content is high.
(2) particle diameter can't be regulated and control: the particle diameter of physics method processing nanometer-size realgar is difficult to obtain the particle that yardstick disperses homogeneous, obtains for the more difficult even processing of nanometer-size realgar of small particle size (＜1 μ m).
(3) poor stability: because the nanometer-size realgar specific surface area is big, not only oxidation easily, and reunite easily.
(4) poorly water-soluble: the nanometer-size realgar poorly water-soluble of physics method processing, reduced its bioavailability, often can only take administering mode oral, external application.
(5) drug effect is single: the nanometer-size realgar activeconstituents of physics method processing is single, so drug effect is single.
(3) summary of the invention:
The objective of the invention is to disclose and a kind ofly prepare nanometer-size realgar colloidal method with biomacromolecule template to regulate shape and particle diameter.With the nanometer-size realgar purity height of this method preparation, uniform particle diameter, size adjustable, pattern is variable, and good water solubility can solve the problem that existing nanometer-size realgar is insoluble in water, easily oxidation, easily reunites, toxicity is bigger.
Concrete processing step of the present invention is:
1, the arsenic disulfide raw material is pulverized, made the realgar meal;
2, with the realgar meal, with the salt acid soak of 0.1～3M 1～12 hour, and constantly stir, use distilled water flushing, filtration afterwards, abandon filtrate, arsenic (As has been removed
2O
3) the realgar powder;
3, with the above-mentioned realgar powder of the salt acid soak of 0.5～6M 1～24 hour, again with distilled water flushing to neutral, refilter, abandon filtrate, must remove the realgar powder of impurity elements such as Ca, Mg, Fe, Sb;
In the process of the 2nd, 3 processing steps, the chemical reaction that relates to has:
As
2O
3+H
2O＝2HAsO
2
HAsO
2+2HCl＝AsCl
3+2H
2O
FeS+2HCl＝FeCl
2+H
2S↑
Sb
2S
3+6HCl＝2SbCl
3+H
2S↑
CaCO
3+2HCl＝CaCl
2+CO
2↑+H
2O
MgCO
3+2HCl＝MgCl
2+CO
2↑+H
2O
4, with above-mentioned pretreated realgar powder, at rare gas element N
2Or CO
2Protection under, with the Na of 0.001～6M
2The solution soaking of S, keeping the pH value is 10～13, stirs, and filters, waste keeps filtrate;
5, with above-mentioned gained filtrate, 30～85 ℃ of constant temperature are at rare gas element N
2Or CO
2Protection under, the hydrochloric acid that adds 0.1～6M, regulate pH to 3～7, under vigorous stirring, the adding parts by weight are that the active bio macromole solution of 1～100 times of nanometer-size realgar parts by weight is made template, stir, and require ageing 1 hour to 60 days according to particle diameter, promptly making with this biomacromolecule is the nanometer-size realgar colloid of template to regulate shape and particle diameter, stores under sealing, lucifuge, the room temperature;
6, with the further vacuum-drying of nanometer-size realgar colloid, obtain nanometer-size realgar with biomacromolecule template to regulate shape and particle diameter.
Described active bio macromole solution template is three classes:
The first kind: protein comprises: serum albumin, (α-, β-, γ-) Interferon, rabbit, oxyphorase, immunoglobulin (Ig) etc.;
Second class, biological polyoses comprises: starch, chitosan, Xylo-Mucine etc.;
The 3rd class, macromolecular compound: comprising: polyvinylpyrrolidone etc.,
Prepared is that nanometer-size realgar is main active ingredient in the nanometer-size realgar colloid of template with the active bio macromole, and biological macromolecular template is a time active ingredient, and distilled water is solvent, and the weight part of each component is:
The nanometer-size realgar of main active ingredient 1 weight part
The biological macromolecular template of inferior active ingredient 1～100 weight part
The distilled water of solvent 1000～100000 weight parts
Control nanometer-size realgar pattern and particle diameter are to realize by the kind that changes used biological macromolecular template.
The size of control nanometer-size realgar is to realize by kind, consumption and the ageing condition that changes biomacromolecule.
The nanometer-size realgar that the present invention makes has following advantage:
(1) purity height: the present invention is a raw material with natural realgar mineral, adopts chemical method to remove impurity such as arsenic, metal ion, the nanometer-size realgar purity height that obtains.
(2) particle diameter and pattern can be regulated and control: the present invention is template with the biomacromolecule, pattern and the particle diameter of regulating and control nanometer-size realgar by the kind, consumption and the ageing condition that change template can prepare the nanometer-size realgar of size distribution homogeneous simply, and easily prepare ultra-fine grain diameter (1～10nm) nanometer-size realgar.
(3) stability is strong: the nanometer-size realgar of the present invention's preparation is dispersed in the biological macromolecular template, is difficult for reuniting, and is difficult for oxidation, and lucifuge can be stablized storage.
(4) good water solubility: the water miscible nanometer-size realgar colloidal sol of the present invention's preparation, solve not (difficulty) water-soluble difficult problem of realgar, can improve the realgar bioavailability, and can conveniently make injection, oral liquid, externally applied agent, the route of administration of expansion realgar.
(5) strong drug action: some biomacromolecules that the present invention adopts itself have the front physiologically active, can regulate the human immunologic function, and have the forward synergistic effect after the nanometer-size realgar effect, have strengthened the drug effect of nanometer-size realgar, reduce its toxic side effect.
Prove that through external anticancer cell experiment and antibacterial experiment it is remarkable with the biomacromolecule to be that the nanometer-size realgar of template preparation has cytotoxicity, the antibacterial effect obvious characteristics.With KB (human body nasopharyngeal carcinoma) cell is example, and during 50% inhibiting rate, nanometer-size realgar concentration is lower than 1.8 μ g/mL, and realgar concentration surpasses 9.0 μ g/mL, and drug effect improves 5 times.To golden grape MIC minimum inhibitory concentration, nanometer-size realgar is 62.5 μ g/mL, and realgar is 5mg/mL, and drug effect improves 80 times.
(4) description of drawings:
Fig. 1 is a process flow diagram of the present invention.
(5) specific embodiment:
Embodiment 1 is that biological macromolecular template prepares nanometer-size realgar colloid and nanometer-size realgar with the serum albumin:
Press Fig. 1 process flow steps, the filtrate that I～V makes, under the N2 protection, adding concentration is the hydrochloric acid of 0.1～1M, regulates pH3～7, under violent stirring, adding concentration is 10
-5MolL
-1Serum albumin (protein-based) solution, its weight part is heavy part 40～70 times of nanometer-size realgar, ageing 1～6 hour, making with the serum albumin is the nanometer-size realgar colloid of template.Wherein, the nanometer-size realgar almost spherical, particle diameter is 1～20nm, with the further vacuum-drying of above-mentioned nanometer-size realgar colloid, promptly obtaining with the serum albumin is the nanometer-size realgar of template.
Embodiment 2 is the nanometer-size realgar colloid and the nanometer-size realgar of biological macromolecular template preparation with the Xylo-Mucine:
Press example 1 described processing step, adding concentration is 0.1～0.5% cellulose sodium carboxymethyl (biological polyoses class), and its weight part is 30～50 times of nanometer-size realgar weight part, ageing, and making with the cellulose sodium carboxymethyl is the nanometer-size realgar colloid of template.By changing the nanometer-size realgar that digestion time can obtain different size, ageing 1 hour～10 days, obtaining particle diameter is the dendroid nanometer-size realgar of 10～100nm; Ageing 11～60 days, obtaining particle diameter is the dendroid nanometer-size realgar of 100nm～5 μ m, with the further vacuum-drying of above-mentioned nanometer-size realgar colloid, promptly obtaining with the Xylo-Mucine is the nanometer-size realgar of template.
Embodiment 3 is that biological macromolecular template prepares nanometer-size realgar colloid and nanometer-size realgar with the polyvinylpyrrolidone:
Press example 1 described processing step, adding concentration is 0.1～0.6% polyvinylpyrrolidone (macromolecular compound), and its heavy part is 10～40 times of heavy part of nanometer-size realgar, ageing 1～12 hour, and obtaining with the polyvinylpyrrolidone is the nanometer-size realgar colloid of template.Wherein, it is spherical that nanometer-size realgar is approximately, and particle diameter is 10～80nm, and with the further vacuum-drying of above-mentioned nanometer-size realgar colloid, promptly obtaining with the polyvinylpyrrolidone is the nanometer-size realgar of template.
Claims (1)
1. method for preparing nanometer-size realgar with biomacromolecule template to regulate shape and particle diameter, it is characterized in that: comprise the steps: that (1) realgar meal after will pulverizing was with the salt acid soak of 0.1M 1～12 hour, stir, use distilled water flushing, filter, abandon filtrate, obtain removing the realgar powder of arsenic; (2) the above-mentioned realgar powder of salt acid soak of usefulness 6.0M is 1～24 hour, and distilled water flushing filters to neutral, abandons filtrate, must remove the realgar powder of impurity element; (3) with above-mentioned pretreated realgar powder, at rare gas element N
2Or CO
2Protection under, with 0.001～6M Na
2The S solution soaking keeps pH 10～13, stirs, and filters, and waste keeps filtrate; (4) with 30～85 ℃ of filtrate constant temperature, rare gas element N
2Or CO
2Protection, the hydrochloric acid that adds 0.1～6M, regulate pH to 3～7, under violent stirring, add biological macromolecule solns and make template, described biomacromolecule is serum albumin or Xylo-Mucine or polyvinylpyrrolidone, the parts by weight of described biomacromolecule are 1-100 times of nanometer-size realgar parts by weight, stir, ageing makes the nanometer-size realgar colloid with this biomacromolecule template to regulate shape and particle diameter; (5) vacuum-drying of nanometer-size realgar colloid is obtained nanometer-size realgar with biomacromolecule template to regulate shape and particle diameter.
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| CN105079814B (en) * | 2014-05-12 | 2018-07-24 | 中国药科大学 | A kind of realgar of modified with folic acid-mesoporous monox nanometer combination drug |
| CN107320489A (en) * | 2017-04-15 | 2017-11-07 | 安徽天康(集团)股份有限公司 | The application of a kind of nanometer-size realgar medically and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1116028C (en) * | 2000-09-25 | 2003-07-30 | 华中科技大学 | Nanometer-size realgar and its preparation |
| CN1478486A (en) * | 2003-07-08 | 2004-03-03 | 华中科技大学 | Nanometer realgar solid dispersion and its preparation method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1116028C (en) * | 2000-09-25 | 2003-07-30 | 华中科技大学 | Nanometer-size realgar and its preparation |
| CN1478486A (en) * | 2003-07-08 | 2004-03-03 | 华中科技大学 | Nanometer realgar solid dispersion and its preparation method |
Non-Patent Citations (1)
| Title |
|---|
| 纳米雄黄的制备及其与牛血清白蛋白作用研究尼古丁与牛血清白蛋白相互作用的光谱研究. 陈韵.广西师范大学硕士研究生学位论文. 2004 * |
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