CN101695501B - Chitosan entrapment body of nano-scale arsenous acid and manufacturing method thereof - Google Patents
Chitosan entrapment body of nano-scale arsenous acid and manufacturing method thereof Download PDFInfo
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Abstract
The invention provides a chitosan entrapment body of nano-scale arsenous acid, which comprises the following components in part by weight: 0.2 to 0.4 part of nano chitosan, 0.001 to 0.002 part of nano arsenous acid, 0.00024 to 0.02 part of ion shift variant agent, 0.005 to 0.03 part of surface active agent, 0.2 to 0.4 part of lactic acid or acetic acid, 0.1 to 0.3 part of fatty alcohol polyethenoxy ether, and the balance of deionized water. An integration process of three highly difficult reactions including the preparation of an arsenous acid pre-dispersed intermediate, the preparation of an active nano chitosan three-dimensional network colloid and the entrapment to the nano arsenous acid by the active nano chitosan three-dimensional network colloid is achieved by a 'one-step method', and nano arsenous acid particles in the manufactured chitosan entrapment body have the main area particle size distribution of between 20 and 50 nanometers and show the characteristics of the arsenous acid. The chitosan entrapment body of the nano-scale arsenous acid has the advantages of high bioavailability, enhanced slow-release property, reduced dosage, low toxic or side effect and enhanced anti-cancer curative effect, and provides a selection path with high-tech synthesis for arsenic medicaments.
Description
Technical field
The invention belongs to the novel drugs preparation field, definitely say chitosan package carrier and the manufacture method thereof that relates to a kind of nano-scale arsenious acid.
Background technology
Arsenic class medicine applicating history in China's traditional medicine is long.In recent years, clinical practice widely and basic research show, arsenic trioxide class preparation is all effective in cure to acute promyelocytic leukemia (APL) and multiple malignant hematologic disease and solid tumor, arsenic class medicine has demonstrated important, wide application prospect in tumor treatment, become global antitumor research field hot of research and development.Now, the problem that faces is that arsenic class preparation has problems such as bioavailability is low, toxic and side effects is big anxious to be solved in clinical practice.
When modern nanotechnology was based on material particle and is machined into nano-scale, because small-size effect, the surface and interface effect of material particle, nanoparticle can present novel physics, chemistry and biology characteristic.Nano medication is compared with conventional medicine, granule is little, surface reaction activity is high, the active center is many, high adsorption capacity owing to having, therefore it has the advantage that many conventional medicines do not possess, mainly show: can improve bioavailability, present new pharmacodynamic properties, reduce dosage, strengthen slow-releasing and curative effect, widen former medicine indication, reduce toxic and side effects, have important clinical significance, can be arsenic class medicament provides high-tech synthetic selection approach.The micro encapsulation of Nano medication and biopharmaceutical macromolecular drug carrier can be realized targeting drug release and medicament slow release etc.The basic research aspect has also obtained the progress that attracts people's attention, confirm as experiment in vitro, ultramicronising arsenic trioxide preparation is to cervical cancer, hepatocarcinoma, gastric cancer, the esophageal carcinoma, colon cancer, ovarian cancer, breast cancer cell etc. all have obvious growth to suppress and apoptosis-induced effect, have shown obvious superiority in anticancer experimentation.
Summary of the invention
The purpose of this invention is to provide a kind of bioavailability height, slow release, intensifier target tropism, widen former medicine indication, reduce the chitosan package carrier that dosage, toxic and side effects are low, strengthen the nano-scale arsenious acid of anticancer therapeutic; For arsenic class medicament provides high-tech synthetic selection approach.
Another purpose of the present invention provides the method for the chitosan package carrier of making this nano-scale arsenious acid.
The objective of the invention is to realize by the enforcement following technical proposals:
A kind of chitosan package carrier of nano-scale arsenious acid, by 100 parts by weight, its composition has:
The chitosan 0.2-0.4 weight portion of nano-scale
The arsenious acid 0.001-0.002 weight portion of nano-scale
Ionotropy agent 0.00024-0.02 weight portion
Surfactant 0.005-0.03 weight portion
Lactic acid or acetic acid 0.2-0.4 weight portion
Fatty alcohol-polyoxyethylene ether 0.1-0.3 weight portion
Surplus is deionized water.
80,000 times of transmission electron microscope detect and show: the primary area particle size distribution of nanometer arsenious acid particle is 20-50nm in this package carrier; Infrared spectrum analysis (IR) shows, at 795cm
2, 946-950cm
2Show as strong arsenious acid characteristic absorpting spectrum; At 774cm
2, 854cm
2, 1131cm
2, 1517-1596cm
2Show as strong chitosan characteristic absorpting spectrum;
Above-mentioned detection confirms:
1. there is the arsenious acid feature in this chitosan package carrier, has tangible arsenious acid characteristic;
2. in this chitosan package carrier class ball shaped nano arsenious acid distribution of particles in the three-dimensional network of Nano chitosan and realized that Nano chitosan three-dimensional network colloid carries the bag of nanometer arsenious acid.
Described ionotropy agent is in sodium sulfate, sodium tripolyphosphate, the sodium citrate any; Described surfactant, in tween 80, Si Ban-80, the castor oil polyoxyethylene ether any.
Make the method for the chitosan package carrier of described nano-scale arsenious acid, comprise in regular turn: the preparation technology of the preparation technology of the pre-dispersed intermediate of arsenious acid, active nano chitosan three-dimensional network colloid, active nano chitosan three-dimensional network colloid are to Bao Zaisan integral process of nanometer arsenious acid, and its step is as follows:
(1) preparation technology of the pre-dispersed intermediate of arsenious acid:
1), get described surfactant 0.005-0.03 weight portion, deionized water 200-1000 weight portion places the reactor of being furnished with widely different flow condenser, and mixing speed is adjusted to 1200-2000 rev/min, stirs 30 minutes earlier under 40 ℃ of-60 ℃ of bars companion;
2), then, the arsenious acid with the 0.001-0.002 weight portion in 50 minutes progressively adds wherein, after arsenious acid adds, under identical mixing speed and temperature conditions, continue to keep 40-60 minute, obtaining product is the pre-dispersed intermediate of water white arsenious acid, and called after A material is standby;
(2) preparation technology of active nano chitosan three-dimensional network colloid:
1., get chitosan 10 weight portions, deionized water 250 weight portions, lactic acid or acetic acid 10 weight portions, place the reactor of being furnished with widely different flow condenser, under 1000-2000 rev/min of stirring, 40 ℃ of-60 ℃ of conditions, gave molten 2 hours or standing over night; After treating oneself big portion dissolving of chitosan, progressively with still temperature rise to 60 ℃-65 ℃, add fatty alcohol-polyoxyethylene ether 8 weight portions, and then with still temperature rise to 85 ℃-95 ℃ and kept 0.5-1.5 hour, follow filtered while hot, obtaining pH value is the light salmon viscous solution of 5-5.5, is the chitosan dispersion liquid, below abbreviates it as B material;
2., get B material 50-100 weight portion, use the 300-700 parts by weight of deionized water, under 40 ℃-60 ℃, 1200-2000 rev/min stirring condition pre-molten 1-2 hour, make the diluent of chitosan dispersion liquid, abbreviate C as and expect;
3., the ionotropy agent of getting the 0.1-10 weight portion, with the 100-1500 parts by weight of deionized water it is dissolved, be called the D material, standby;
4., get 100-300 weight portion C material and place reactor, under 40 ℃ of-60 ℃ of temperature and 1000-2000 rev/min of stirring redispersion 30-50 minute, make redispersion C material;
5., the reactor of 100-300 weight portion redispersion C material will be housed, its speed of agitator degree is adjusted into 10-20 rev/min, under 40 ℃ of-60 ℃ of conditions, D material with the 1-12 weight portion in 30-90 minute progressively adds in it, under same temperature and mixing speed, continue to keep 30-60 minute, make activation Nano chitosan three-dimensional network colloid, abbreviate the E material as;
(3) active nano chitosan three-dimensional network colloid carries technology to the bag of nanometer arsenious acid:
6., in being furnished with the reactor of widely different flow condenser, give and add 100-300 weight portion E material earlier, 40 ℃-60 ℃, 1000-2000 rev/min stir and 40-100W ultrasonic cavitation condition under, in 20-60 minute, 60-100 weight portion A material is added, the reinforced back that finishes of A material continues to keep 30-60 minute under identical temperature, mixing speed and ultrasonic cavitation condition, the bag process of carrying is namely accused and is finished, and makes little brown transparent liquid, is the chitosan package carrier of nano-scale arsenious acid.
Show through 80,000 times of transmission electron microscope detections: the primary area particle size distribution of nanometer arsenious acid particle is 20-50nm in this package carrier; Infrared spectrum analysis (IR) shows, at 795cm
2, 946-950cm
2Show as strong arsenious acid characteristic absorpting spectrum, at 774cm
2, 854cm
2, 1131cm
2, 1517--1596cm
2Show as strong chitosan characteristic absorpting spectrum; Above-mentioned detection confirms:
1. there is the arsenious acid feature in this chitosan package carrier, has tangible arsenious acid characteristic;
2. in this chitosan package carrier class ball shaped nano arsenious acid distribution of particles in the three-dimensional network of Nano chitosan and realized that Nano chitosan three-dimensional network colloid carries the bag of nanometer arsenious acid.
The outstanding advantage of the chitosan package carrier of nano-scale arsenious acid of the present invention is:
The arsenious acid chitosan package carrier of the present invention that the applying nano technology produces, it is the micro encapsulation package carrier, compare with conventional medicine, granule is little, surface reaction activity is high, the active center is many, high adsorption capacity owing to having, it has the advantage that many conventional medicines do not possess, mainly show bioavailability height, slow release, intensifier target tropism, widen former medicine indication, reduce toxic and side effects, reduce dosage, strengthen anticancer therapeutic, have the important clinical meaning and provide high-tech synthetic selection approach for arsenic class medicament.
The manufacture method of the chitosan package carrier of nano-scale arsenious acid of the present invention, its innovation place is to adopt " one-step method " to realize that preparation, the preparation of active nano chitosan three-dimensional network colloid, the active nano chitosan three-dimensional network colloid of the pre-dispersed intermediate of arsenious acid carry the integrated innovation combination of these three highly difficult synthesis techniques to the bag of nanometer arsenious acid.Have that method is simple, the outstanding advantages such as excellent biomedical feature of processing ease, product tool nano material.
Embodiment 1:
1) the chitosan package carrier of A type nano-scale arsenious acid, by 100 weight portions, its composition has:
Chitosan 0.361 weight portion of nano-scale
Arsenious acid 0.0018 weight portion of nano-scale
Sodium sulfate (ionotropy agent) 0.0024 weight portion
Si Ban-80 (surfactant) 0.0188 weight portion
Acetic acid 0.361 weight portion
Fatty alcohol-polyoxyethylene ether 0.289 weight portion
Surplus is deionized water 98.966 weight portions
2) manufacture method of the chitosan package carrier of this A type nano-scale arsenious acid, step is as follows:
(1) preparation technology of the pre-dispersed intermediate of arsenious acid:
1, get Si Ban-80 (surfactant) 0.1 weight portion, deionized water 200 weight portions place the reactor of being furnished with widely different flow condenser, and mixing speed is adjusted to 2000 rev/mins, stir 30 minutes earlier under 60 ℃ of bar companions;
2, then, the arsenious acid with 0.01 weight portion in 50 minutes progressively adds wherein, after arsenious acid adds, under identical mixing speed and temperature conditions, continue to keep 40 minutes, obtaining product is the pre-dispersed intermediate of water white arsenious acid, and called after A material is standby;
(2) preparation technology of active nano chitosan three-dimensional network colloid:
1., get chitosan 10 weight portions, deionized water 250 weight portions, lactic acid or acetic acid 10 weight portions, place the reactor of being furnished with widely different flow condenser, under 1000 rev/mins of stirrings, 60 ℃ of conditions, gave molten 2 hours or standing over night; After treating oneself big portion dissolving of chitosan, progressively with still temperature rise to 65 ℃, add fatty alcohol-polyoxyethylene ether 8 weight portions, and then with still temperature rise to 85 ℃-90 ℃ and kept 1.5 hours, follow filtered while hot, obtaining pH value is the light salmon viscous solution of 5-5.5, is the chitosan dispersion liquid, below abbreviates it as B material;
2., get B and expect 60 weight portions, use 300 parts by weight of deionized water, under 40 ℃, 1200 rev/mins stirring conditions pre-molten 1.5 hours, make the diluent of chitosan dispersion liquid, abbreviate the C material as;
3., get the sodium sulfate (ionotropy agent) of 0.1 weight portion, with 100 parts by weight of deionized water it is dissolved, be called the D material, standby;
4., get 100 weight portion C material and place reactor, redispersion is 50 minutes under 40 ℃ of temperature and 1000 rev/mins of stirrings, makes redispersion C material;
5., the reactor of 100 weight portion redispersion C material will be housed, its speed of agitator degree is adjusted into 10-20 rev/min, under 60 ℃ of conditions, D material with 4 weight portions in 90 minutes progressively adds in it, under same temperature and mixing speed, continue to keep 60 minutes, make activation Nano chitosan three-dimensional network colloid, abbreviate the E material as;
(3) activation Nano chitosan three-dimensional network colloid carries technology to the bag of nanometer arsenious acid:
6., in being furnished with the reactor of widely different flow condenser, give and add 100 weight portion E material earlier, under 60 ℃, 1500 rev/mins stirrings and 40W ultrasonic cavitation condition, in 60 minutes, 60 weight portion A material is added, the reinforced back that finishes of A material continues to keep 60 minutes under identical temperature, mixing speed and ultrasonic cavitation condition, the bag process of carrying is namely accused and is finished, and makes little brown transparent liquid, is the chitosan package carrier of A type nano-scale arsenious acid.
Show through 80,000 times of transmission electron microscope detections: nanometer arsenious acid distribution of particles is in the three-dimensional network colloid of active nano chitosan in this package carrier, and the primary area particle size distribution of nanometer arsenious acid particle is 20-50nm in this package carrier;
Infrared spectrum analysis (IR) shows, at 795cm
2, 946-950cm
2Show as strong arsenious acid characteristic absorpting spectrum, at 774cm
2, 854cm
2, 1131cm
2, 1517--1596cm
2Show as strong chitosan characteristic absorpting spectrum, so this chitosan package carrier has the feature of tangible arsenious acid.
Embodiment 2:
1) the chitosan package carrier of Type B nano-scale arsenious acid, by 100 weight portions, its composition has:
Chitosan 0.238 weight portion of nano-scale
Arsenious acid 0.00115 weight portion of nano-scale
Sodium tripolyphosphate (ionotropy agent) 0.00024 weight portion
Tween 80 (surfactant) 0.006 weight portion
Lactic acid 0.238 weight portion
Fatty alcohol-polyoxyethylene ether 0.19 weight portion
Surplus is deionized water 99.088 weight portions
2) manufacture method of the chitosan package carrier of this Type B nano-scale arsenious acid, step is as follows:
(1) preparation technology of the pre-dispersed intermediate of arsenious acid:
1), get tween 80 (surfactant) 0.12 weight portion, deionized water 500 weight portions place the reactor of being furnished with widely different flow condenser, and mixing speed is adjusted to 2000 rev/mins, stir 30 minutes earlier under 55 ℃ of bars companion;
2), then, the arsenious acid with 0.03 weight portion in 50 minutes progressively adds wherein, after arsenious acid adds, under identical mixing speed and temperature conditions, continue to keep 40 minutes, obtaining product is the pre-dispersed intermediate of water white arsenious acid, and called after A material is standby;
(2) preparation technology of active nano chitosan three-dimensional network colloid:
1., get chitosan 10 weight portions, deionized water 250 weight portions, lactic acid 10 weight portions, place the reactor of being furnished with widely different flow condenser, under 1000 rev/mins of stirrings, 60 ℃ of conditions, gave molten 2 hours or standing over night; After treating oneself big portion dissolving of chitosan, progressively with still temperature rise to 65 ℃, add fatty alcohol-polyoxyethylene ether 8 weight portions, and then with still temperature rise to 85 ℃-90 ℃ and kept 1.5 hours, follow filtered while hot, obtaining pH value is the light salmon viscous solution of 5-5.5, is the chitosan dispersion liquid, below abbreviates it as B material;
2., get B and expect 50 weight portions, use 500 parts by weight of deionized water, under 50 ℃, 1200 rev/mins stirring conditions pre-molten 1.5 hours, make the diluent of chitosan dispersion liquid, abbreviate the C material as;
3., get the sodium tripolyphosphate (ionotropy agent) of 0.5 weight portion, with 1500 parts by weight of deionized water it is dissolved, be called the D material, standby;
4., get 200 weight portion C material and place reactor, redispersion is 50 minutes under 60 ℃ of temperature and 1000 rev/mins of stirrings, makes redispersion C material;
5., the reactor of 300 weight portion redispersion C material will be housed, its speed of agitator degree is adjusted into 10-20 rev/min, under 60 ℃ of conditions, D material with 1 weight portion in 90 minutes progressively adds in it, under same temperature and mixing speed, continue to keep 40 minutes, make activation Nano chitosan three-dimensional network colloid, abbreviate the E material as;
(3) activation Nano chitosan three-dimensional network colloid carries technology to the bag of nanometer arsenious acid:
6., in being furnished with the reactor of widely different flow condenser, give and add 300 weight portion E material earlier, under 60 ℃, 1500 rev/mins stirrings and 100W ultrasonic cavitation condition, in 30 minutes, 100 weight portion A material is added, the reinforced back that finishes of A material continues to keep 60 minutes under identical temperature, mixing speed and ultrasonic cavitation condition, the bag process of carrying is namely accused and is finished, and makes little brown transparent liquid, is the chitosan package carrier of Type B nano-scale arsenious acid.
Show through 80,000 times of transmission electron microscope detections: in this package carrier product, nanometer arsenious acid distribution of particles is in the three-dimensional network colloid of active nano chitosan; The primary area particle size distribution of nanometer arsenious acid particle is 20-50nm in this package carrier;
Infrared spectrum analysis (IR) shows, at 795cm
2, 946-950cm
2Show as strong arsenious acid characteristic absorpting spectrum, at 774cm
2, 854cm
2, 1131cm
2, 1517--1596cm
2Show as strong chitosan characteristic absorpting spectrum, so this chitosan package carrier has the feature of tangible arsenious acid.
Embodiment 3:
1) the chitosan package carrier of C type nano-scale arsenious acid, by 100 weight portions, its composition has:
Chitosan 0.322 weight portion of nano-scale
Arsenious acid 0.00125 weight portion of nano-scale
Sodium citrate (ionotropy agent) 0.02 weight portion
Castor oil polyoxyethylene ether (surfactant) 0.025 weight portion
Acetic acid 0.322 weight portion
Fatty alcohol-polyoxyethylene ether 0.258 weight portion
Surplus is deionized water.99.052 weight portion
2) manufacture method of the chitosan package carrier of this C type nano-scale arsenious acid, step is as follows:
(1) preparation technology of the pre-dispersed intermediate of arsenious acid:
1), get castor oil polyoxyethylene ether (surfactant) 1.0 weight portions, deionized water 1000 weight portions place the reactor of being furnished with widely different flow condenser, and mixing speed is adjusted to 2000 rev/mins, stir 30 minutes earlier under 50 ℃ of conditions;
2), then, the arsenious acid with 0.05 weight portion in 50 minutes progressively adds wherein, after arsenious acid adds, under identical mixing speed and temperature conditions, continue to keep 40 minutes, obtaining product is the pre-dispersed intermediate of water white arsenious acid, and called after A material is standby;
(2) preparation technology of active nano chitosan three-dimensional network colloid:
1., get chitosan 10 weight portions, deionized water 250 weight portions, acetic acid 10 weight portions, place the reactor of being furnished with widely different flow condenser, under 1000 rev/mins of stirrings, 60 ℃ of conditions, gave molten 2 hours or standing over night; After treating oneself big portion dissolving of chitosan, progressively with still temperature rise to 65 ℃, add fatty alcohol-polyoxyethylene ether 8 weight portions, and then with still temperature rise to 85 ℃-90 ℃ and kept 1.5 hours, follow filtered while hot, obtaining pH value is the light salmon viscous solution of 5-5.5, is the chitosan dispersion liquid, below abbreviates it as B material;
2., get B and expect 100 weight portions, use 700 parts by weight of deionized water, under 60 ℃, 1500 rev/mins stirring conditions pre-molten 1.5 hours, make the diluent of chitosan dispersion liquid, abbreviate the C material as;
3., get the sodium citrate (ionotropy agent) of 10 weight portions, with 1500 parts by weight of deionized water it is dissolved, be called the D material, standby;
4., get 250 weight portion C material and place reactor, redispersion is 50 minutes under 50 ℃ of temperature and 1500 rev/mins of stirrings, makes redispersion C material;
5., the reactor of 250 weight portion redispersion C material will be housed, its speed of agitator degree is adjusted into 10-20 rev/min, under 50 ℃ of conditions, D material with 12 weight portions in 90 minutes progressively adds in it, under same temperature and mixing speed, continue to keep 60 minutes, make activation Nano chitosan three-dimensional network colloid, abbreviate the E material as;
(3) activation Nano chitosan three-dimensional network colloid carries technology to the bag of nanometer arsenious acid:
6., in being furnished with the reactor of widely different flow condenser, give and add 300 weight portion E material earlier, under 40 ℃, 1500 rev/mins stirrings and 100W ultrasonic cavitation condition, in 60 minutes, 100 weight portion A material is added, the reinforced back that finishes of A material continues to keep 50 minutes under identical temperature, mixing speed and ultrasonic cavitation condition, the bag process of carrying is namely accused and is finished, and makes little brown transparent liquid, is the chitosan package carrier of C type nano-scale arsenious acid.
Show through 80,000 times of transmission electron microscope detections: in this package carrier product, nanometer arsenious acid distribution of particles is in the three-dimensional network colloid of active nano chitosan, and the primary area particle size distribution of nanometer arsenious acid particle is 20-50nm in this package carrier;
Infrared spectrum analysis (IR) shows, at 795cm
2, 946-950cm
2Show as strong arsenious acid characteristic absorpting spectrum, at 774cm
2, 854cm
2, 1131cm
2, 1517--1596cm
2Show as strong chitosan characteristic absorpting spectrum, so this chitosan package carrier has the feature of tangible arsenious acid.
Claims (3)
1. the chitosan package carrier of a nano-scale arsenious acid, by 100 weight portions, its composition has:
80,000 times of transmission electron microscope detect and show: the primary area particle size distribution of nanometer arsenious acid particle is 20-50nm in this package carrier; Infrared spectrum analysis shows, at 795cm
2, 946-950cm
2Show as strong arsenious acid characteristic absorpting spectrum; At 774cm
2, 854cm
2, 1131cm
2, 1517--1596cm
2Show as strong chitosan characteristic absorpting spectrum;
Above-mentioned detection confirms:
1. there is the arsenious acid feature in this chitosan package carrier, has tangible arsenious acid characteristic;
2. class ball shaped nano arsenious acid particle in this chitosan package carrier is distributed in the three-dimensional network of Nano chitosan, and has realized that Nano chitosan three-dimensional network colloid carries the bag of nanometer arsenious acid;
Nano-scale arsenious acid chitosan package carrier with described feature, by following process manufacturing: include the preparation technology, active nano chitosan three-dimensional network colloid of preparation technology, the active nano chitosan three-dimensional network colloid of the pre-dispersed intermediate of arsenious acid in regular turn to Bao Zaisan integrated technology of nanometer arsenious acid, its step is as follows:
(1) preparation technology of the pre-dispersed intermediate of arsenious acid:
1), get described surfactant 0.005-0.03 weight portion, deionized water 200-1000 weight portion places the reactor of being furnished with widely different flow condenser, and mixing speed is adjusted to 1200-2000 rev/min, stirs 30 minutes earlier under 40 ℃ of-60 ℃ of conditions;
2), then, the arsenious acid with the 0.001-0.002 weight portion in 50 minutes progressively adds wherein, after arsenious acid adds, under identical mixing speed and temperature conditions, continue to keep 40-60 minute, obtaining product is the pre-dispersed intermediate of water white arsenious acid, and called after A material is standby;
(2) preparation technology of active nano chitosan three-dimensional network colloid:
1., get chitosan 10 weight portions, deionized water 250 weight portions, lactic acid or acetic acid 10 weight portions, place the reactor of being furnished with widely different flow condenser, under 1000-2000 rev/min of stirring, 40 ℃ of-60 ℃ of conditions, gave molten 2 hours or standing over night; After treating the big dissolving of chitosan, progressively with still temperature rise to 60 ℃-65 ℃, add fatty alcohol-polyoxyethylene ether 8 weight portions, and then with still temperature rise to 85 ℃-95 ℃ and kept 0.5-1.5 hour, follow filtered while hot, obtaining pH value is the light salmon viscous solution of 5-5.5, is the chitosan dispersion liquid, below abbreviates it as B material;
2., get B material 50-100 weight portion, use the 300-700 parts by weight of deionized water, under 40 ℃-60 ℃, 1200-2000 rev/min stirring condition pre-molten 1-2 hour, make the diluent of chitosan dispersion liquid, abbreviate C as and expect;
3., the ionotropy agent of getting the 0.1-10 weight portion, with the 100-1500 parts by weight of deionized water it is dissolved, be called the D material, standby;
4. get 100-300 weight portion C material and place reactor, under 40 ℃ of-60 ℃ of temperature and 1000-2000 rev/min of stirring redispersion 30-50 minute, make redispersion C material;
5., the reactor of 100-300 weight portion redispersion C material will be housed, its speed of agitator is adjusted into 10-20 rev/min, under 40 ℃ of-60 ℃ of conditions, D material with the 1-12 weight portion in 30-90 minute progressively adds in it, under same temperature and mixing speed, continue to keep 30-60 minute, make activation Nano chitosan three-dimensional network colloid, abbreviate the E material as;
(3) active nano chitosan three-dimensional network colloid carries technology to the bag of nanometer arsenious acid:
6., in being furnished with the reactor of widely different flow condenser, give and add 100-300 weight portion E material earlier, 40 ℃-60 ℃, 1000-2000 rev/min stir and 40-100W ultrasonic cavitation condition under, in 20-60 minute, 60-100 weight portion A material is added, the reinforced back that finishes of A material continues to keep 30-60 minute under identical temperature, mixing speed and ultrasonic cavitation condition, the bag process of carrying is namely accused and is finished, and makes little brown transparent liquid, is the chitosan package carrier of described nano-scale arsenious acid.
2. according to the chitosan package carrier of the described nano-scale arsenious acid of claim 1, it is characterized in that: described ionotropy agent is in sodium sulfate, sodium tripolyphosphate, the sodium citrate any.
3. according to the chitosan package carrier of the described nano-scale arsenious acid of claim 1, it is characterized in that: described surfactant is in tween 80, Si Ban-80, the castor oil polyoxyethylene ether any.
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