CN101984958A - Nanoscale albendazole micropowder and preparation method thereof - Google Patents
Nanoscale albendazole micropowder and preparation method thereof Download PDFInfo
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Abstract
The invention relates to the technical field of medicinal materials, in particular to nanoscale albendazole micropowder and a preparation method thereof. The method comprises the following steps: 1. dissolving albendazole into a good solvent to obtain a first solution; 2. adding a surfactant, a polymeric substance and sodium hydroxide to a poor solvent to obtain a second solution; 3. fully mixing the first solution with the second solution to obtain an albendazole slurry; and 4. carrying out centrifugal separation on the albendazole slurry obtained in step 3 to obtain a centrifugal precipitate, and then freeze-drying the centrifugal precipitate to obtain the nanoscale albendazole micropowder. The invention has the advantages that the particle size of the albendazole raw material is obviously reduced and the solubility and dissolving-out speed of a drug are effectively improved, thus improving the absorption and bioavailability of the albendazole well, overcoming a series of defects of low bioavailability, poor absorption and the like of the traditional albendazole non-nanometer raw material or preparation, and effectively giving play to therapeutic effect of the albendazole in resisting parasites in tissues and organs.
Description
Technical field
The present invention relates to the medicinal raw material technical field, is a kind of nanoscale albendazole micropowder and preparation method thereof.
Background technology
Endoparasite is that a class colonizes in host or host (host) body, to obtain the biology of keeping its existence, growing or breed required nutrition or protection, this type of biology not only parasitizes in human digestive road, lung, liver, the blood conduit, even all can parasitic tissue and organ also to parasitize cerebral tissue and eyeball etc.
(Albendazole ABZ), has another name called albendazole to albendazole, is benzimidazoles derivative, is to be applied to clinical a kind of broad-spectrum anti-parasite medicine.Chemical constituent is [(5-rosickyite base)-1H-benzimidazolyl-2 radicals-yl] methyl carbamate.Since listing in 1977, be widely used in parasitic disease such as clinical treatment ancylostomiasis, ascariasis, trichuriasis, enterobiasis, trichonematosis, taeniasis, cysticercosis, clinical efficacy is good.Clinically in recent years be used for the treatment of echinococcus and alveolar hydatid disease has obtained certain curative effect, it is the anti-Enterozoa medicine of wide spectrum that uses clinically now, and is recommended as the choice drug of anti-echinococcosis by WHO.
Albendazole is white or off-white powder, and odorless is tasteless.Studies show that: albendazole was both water insoluble, also was insoluble to most organic solvents, belonged to insoluble drug.Existingly be used for antiparasitic preparation and Albenza arranged, albendazole capsule, albendazole granule, and Albendazole emulsion and dry suspension.These dosage form oral administration absorb the back has good anthelmintic action to gastrointestinal parasite (for example ascarid, ancylostome, cestode) really in body, yet the characteristic of albendazole dissolubility has determined its oral rear intestinal absorption difference, bioavailability is low, especially cause albendazole lower at each organ, tissue local drug level, therefore [liver entozoa for example is as Liver fluke, echinococcus (Echinococcus hydatid cyst) to the parasite of histoorgan; The lung entozoa is as bronchial fluke (being called for short Paragonismus westermani); The cerebral tissue parasite is as cysticercus cellulosae (pork measles); The blood vessel entozoa is as schistosomicide; The intralymphatic parasite is as filaricide; The muscular tissue parasite is as trichinella larvae; The osseous tissue parasite is as Echinococcus hydatid cyst; Ophthalmic parasite, as suck nematicide, pork measles etc.] effect is very little, and cause its toxic and side effects to increase during long-term prescription, as cerebral nervous system, cardiovascular system are produced serious adverse drug reaction.These have all influenced albendazole to a certain extent and brought into play good parasiticide effect in each organ-tissues.
Improve this defective of bringing owing to the albendazole characteristic, need be from improving its dissolubility, the absorption of enhancing body, improving bioavailability sets out, if the medicine albendazole is realized nanorize, will significantly improve its dissolubility so, the absorption of enhancing body, thereby the bioavailability of raising albendazole.
Nineteen fifty-nine, Nobel laureate Richard is taken graceful (RichardFeynman) and has at first been proposed this brand-new scientific concept of nanotechnology.Since 20th century six the seventies, the countries in the world scientist has carried out the research work of a large amount of relevant nano sciences in fields such as information industry, quasiconductor, engineering science and materialogies, and the 21 century nanotechnology is considered to the generation of a series of new and high technologies and development are had the focus subject of material impact.Nanotechnology now has been widely used in a plurality of fields such as materialogy, electronics, biology, micrology.And acquisition breakthrough.The implication of nanometer is promptly: handle atom and molecule in 0.1 to 100 nanometer space scale, material is processed, make and have the product of specific function or certain material is studied, grasp the new and high technology subject of the characteristics of motion and the characteristic of its atom, molecule.Continuous development along with nanotechnology now, nanotechnology is penetrated into field of medicaments gradually, Nano medication improve the oral absorption of insoluble drug, improve highlight aspect bioavailability, targeting and positioning release medicine and the medicine control conventional formulation incomparable advantage, nanotechnology has also shown the great potential that it promotes pharmaceutical development in the application of pharmaceutical field.
The size of nanoparticle is defined between 1 to 1000 nanometer in pharmaceutics.The nano-grade medicine particle can be divided into two classes: nano-carrier system and nanocrystal medicine.The nano-carrier system is meant the drug-polymer carrier system that makes by some physico-chemical process, as nanosphere, nanocapsule, nano-micelle, nanometer liposome, nano-emulsion and nanogel etc.; The nanocrystal medicine then is meant by the nano-powder technology material medicine is processed into the population of Nano grade, or claims nano powder, and this is actually the development again of micronization technology, micropowder technology.Being fit to micronized medicine also is not only chemical synthetic drug, and some protein or polypeptide drug as insulin, interferon, erythropoietin etc., can utilize lyophilized powder fluid energy mill new technique to be processed into nanoscale even thinner micropowder too.The content of surfactant seldom and has been avoided the use of organic solvent in the prescription, and particle diameter is enough little and can not block blood capillary, thereby is widely used in low solubility drugs.
For the insoluble drug albendazole, the research of countries in the world is all being carried out always, and some patent documentations about the albendazole conventional formulation have been arranged.In these relevant patent documentations, the patent documentation [number of patent application: 99113446] that the preparation Albendazole emulsion is arranged, the patent documentation [number of patent application: 200510098951] that the agent of preparation autoemulsified albendazole is arranged, patent documentation [the number of patent application: 200410078469 that the preparation Albendazole jelly is also arranged, 2000410078466], or the patent documentation [number of patent application: 200410078471] of preparation albendazole powder spray, spray, aerosol
But the various albendazole preparations of describing in these patent documentation reports, the perhaps general because inherent slightly solubility of traditional albendazole raw material makes that drug loading is low and can't carry out suitability for industrialized production, perhaps because medicine to enter body artifact availability lower and can not well bring into play whole body, especially bring into play the parasiticide effect in the histoorgan, again or because variation (powder spray, spray, aerosol as albendazole are used for the treatment of adenoid vegetation) has also taken place the change therapeutical effect of its dosage form.Secondly, for the Emulsion of albendazole, from Emulsion, its disperse particles is generally 0.1 to 100 micron, and the drip gauge area is big, and the surface free energy height so the destruction of Emulsion is its inevitable outcome, is mode and temporal difference.In addition, the selection of suitable emulsifying agent is very difficult.For suspensoid, its unstability more on thermodynamics, granule is big, and the selection of cosolvent still do not have clear and definite rule and can follow, and generally can only select for use expection can form the material of water soluble complex, double salt or associated complex according to pharmaceutical properties.For gel, it is an external preparation, when acting on body the time of staying short, easily lose most of drug effect, and do not bring into play the parasiticide effect during as medicine for external use.Equally, the powder spray of albendazole, spray and gel have similar deficiency, and the microgranule of powder spray, spray is bigger simultaneously, and meansigma methods is about 5 microns to 10 microns, and bioavailability is also lower, and production cost is higher, complex process.
Except the patent documentation of above-mentioned albendazole conventional formulation, pharmaceutics is also being carried out the research of albendazole Nano medication at present, and the ABZ nano-carrier system of success exploitation comprises; Kates (Kata) etc. with the albendazole enclose, make suspension with DM-(CD), have successfully increased the solubility property and the bioavailability of albendazole.Lid Si Teer (Gastillo) screens with the enclose of albendazole dissimilar CD (beta-schardinger dextrin-, HP-and methyl-beta-schardinger dextrin-) again, the water solublity of the clathrate that discovery is made is relevant with the type of employed cyclodextrin, and a high proportion of cyclodextrin derivative can increase the dissolubility of albendazole etc. to a greater degree.Zhang Xuenong etc. adopt the positive fourth vinegar of alpha-cyanoacrylate, and (btltylcyanocate BAC) is polymerization single polymerization monomer, and emulsion polymerization method prepares the positive fourth vinegar of biodegradable albendazole paracyanogen base acrylic acid nanosphere (ABZ-PBCA～NP).Animal experiment shows that nanosphere can improve albendazole bioavailability and hepatic targeting significantly.This novel targeted preparation itself has the sick effect of parasiticide, and higher at the drug level of target site.Luo Peisi (Lopez) makes solid dispersion with polyvinylpyrrolidone (PVP) with albendazole (ABZ), albendazole-sulfoxide (ABZSX), its corresponding carboxymethyl cellulose suspension compares, and the anti-intestinal precocious stage trichinella effect of solid dispersion significantly increases; Savios (Savio) etc. use the albendazole preparation of polymer phosphoric acid ester [Gelucires (44/14 and 35/02, a kind of synthetic resin gum)] and Polyethylene Glycol development oleaginous base.Studies show that this dosage form is a kind of whole body parasiticide novel form likely.In order to improve the hepatic targeting and the curative effect of albendazole treatment hepatic echinococcosis, Wen Hao etc. utilize liposome as targeting vector, adopt neutralisation to prepare ABZ liposome (granted patent ZL02152519.6).
Yet, these adopt the non-nano raw material to obtain the pharmaceutical preparation of nanometer through nano-carrier and nanometer formulation technology, though compare with conventional formulation, improve that albendazole absorbs and slightly solubility on played positive effect, on essential, source, really do not deal with problems.The slightly solubility of albendazole raw material makes that the general drug loading of present nanometer formulation is low, and this has limited the exploitation and the research of albendazole nano-carrier preparation greatly.Meanwhile, also there is very important problem in existing nano-carrier preparation.At first, for cyclodextrin inclusion technique, the dissolubility of cyclodextrin itself is just little, and to the poor stability of soda acid, drug loading is little, and inorganic drug scarcely should use.For example, cyclodextrin inclusion compound adopts surfactant, cyclodextrin inclusion compound usually or improves the dissolubility of the medicine of poorly water-soluble by cosolvent when preparation normal injection agent.But part surface activating agent such as polyoxyethylene castor oil etc. all have side effect, and haemolysis and anaphylaxis etc. easily take place.And cyclodextrin inclusion compound is not all effective to the medicine of all poorly water-solubles; Cosolvent then because of containing organic solvent, also can cause the anaphylaxis of human body etc., and injection the time can cause intensive pain, patient's poor compliance.Its general problem such as aging easily in addition.Secondly, for liposome, fat-soluble and all very poor medicine of water solublity should not prepare liposome, there are a lot of problems equally when being prepared into liposome, not good enough as physical and chemical stability in the body, and for example the liposome bin stability is not good enough, and especially liposome is easy to occur medicine in external seepage or the phenomenon of liposome seepage before the no show target tissue in vivo of taking place from liposome, and these all will limit the application of albendazole liposomes greatly.
Summary of the invention
The invention provides a kind of nanoscale albendazole micropowder and preparation method thereof, overcome the deficiency of prior art, solved the problem of albendazole slightly solubility, its process stabilizing, prepare various informative, easy and simple to handle, gained nanoscale albendazole micropowder granularity is less and controlled, have dissolubility preferably.
One of technical scheme of the present invention realizes by following measure: a kind of nanoscale albendazole micropowder, and it obtains by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is a kind of in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is a kind of in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is a kind of in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is a kind of in water, the ethanol;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
Two of technical scheme of the present invention realizes by following measure: a kind of nanoscale albendazole micropowder, and it obtains by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is two or more the mixture in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is two or more the mixture in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is two or more the mixture in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is water, alcoholic acid mixture;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
Three of technical scheme of the present invention realizes by following measure: a kind of nanoscale albendazole micropowder preparing process, and it is undertaken by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is a kind of in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is a kind of in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is a kind of in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is a kind of in water, the ethanol;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
Four of technical scheme of the present invention realizes by following measure: a kind of nanoscale albendazole micropowder preparing process, and it is undertaken by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is two or more the mixture in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is two or more the mixture in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is two or more the mixture in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is water, alcoholic acid mixture;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
Can do further to select or/and optimize to technique scheme according to actual needs:
Well-mixed condition is in above-mentioned the 3rd step: adopt alr mode fully to mix, its mixing time is that 10 minutes to 30 minutes, mixing speed are 500 rev/mins to 3000 rev/mins; Or/and, adopt ultrasonic power fully to mix, its ultrasonic time is 10 minutes to 30 minutes.
Stating the rotating speed of centrifugalize in the 4th step is that 10000 rev/mins to 20000 rev/mins, centrifugation time are 10 minutes
Technique effect of the present invention: the dissolubility of gained nanoscale albendazole micropowder of the present invention is apparently higher than the dissolubility of albendazole crude drug, nanoscale albendazole micropowder of the present invention dissolubility in ethanol is about 187% to 264% of raw material, and other solvents also all have clear improvement.Of the present invention method is simple, technology is simple.The present invention has significantly reduced the particle diameter of albendazole raw material, and the dissolubility and the dissolution rate of medicine have effectively been improved, so just can well improve the absorption and the bioavailability of albendazole, overcome traditional albendazole non-nano raw material or preparation and existed bioavailability low, a series of shortcomings such as absorption difference.Bring into play the parasitic therapeutical effect of the anti-histoorgan of albendazole effectively.
Description of drawings
Below accompanying drawing be respectively to without albendazole (ABZ) raw material of any processing and the Electronic Speculum figure of embodiment of the invention gained nanoscale albendazole micropowder under the same measured condition.
Accompanying drawing 1 is the sem photograph (* 20000) of albendazole crude drug.
Accompanying drawing 2 is the sem photograph (* 20000) of stochastic sampling 1 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 3 is the sem photograph (* 60000) of stochastic sampling 2 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 4 is the sem photograph (* 20000) of stochastic sampling 3 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 5 is an albendazole crude drug transmission electron microscope picture (* 25000).
Accompanying drawing 6 is the transmission electron microscope picture (* 25000) of stochastic sampling 4 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 7 is the transmission electron microscope picture (* 25000) of stochastic sampling 5 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 8 is the transmission electron microscope picture (* 25000) of stochastic sampling 6 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 9 is albendazole crude drug particle size distribution figure.
Accompanying drawing 10 is the particle size distribution figure of stochastic sampling 7 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 11 is the particle size distribution figure of stochastic sampling 8 in the embodiment of the invention gained nanoscale albendazole micropowder.
Accompanying drawing 12 is the particle size distribution figure of stochastic sampling 9 in the embodiment of the invention gained nanoscale albendazole micropowder.
The specific embodiment
The present invention is not subjected to the restriction of following embodiment, can determine concrete embodiment according to technical scheme of the present invention and practical situation.
Below in conjunction with embodiment the present invention is further described.
The first step takes by weighing 290 milligrams of albendazole raw materials, adds 2 milliliters of formic acid it is dissolved fully, the solution of winning.Second step, the cofabrication 2.75 gram Tween 80s that contain, 100 milliliters of 0.74 gram sodium hydroxide and the polyacrylic alcoholic solution of 0.10 gram are second solution.The 3rd step was that 40 ℃, mixing speed are that 3000 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution in temperature, albendazole slurry that must PH=4.50.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 270 nanometers.
Embodiment 2
The first step takes by weighing 290 milligrams of albendazole raw materials, adds 2 milliliters of formic acid it is dissolved fully, the solution of winning.Second step, the cofabrication 0.10 gram poloxamer-188 that contains, 100 milliliters of the aqueous solutions of 1.60 gram sodium hydroxide and 0.10 gram Polymeric sodium metaphosphate. are second solution.The 3rd step was that 0 ℃, mixing speed are that 500 rev/mins, mixing time are under 30 minutes the condition first solution fully to be mixed with second solution in temperature, made the albendazole slurry of PH=10.98.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 300 nanometers.
Embodiment 3
The first step takes by weighing 290 milligrams of albendazole raw materials, adds 2 milliliters of formic acid it is dissolved fully, the solution of winning.Second step, the cofabrication 0.20 gram poloxamer-188 that contains, 100 milliliters of the alcoholic solution of 0.78 gram sodium hydroxide and 40.0 gram polyvinylpyrrolidones are second solution.The 3rd step was that 25 ℃, mixing speed are that 1000 rev/mins, mixing time are under 20 minutes the condition first solution fully to be mixed with second solution in temperature, made the albendazole slurry of PH=4.60.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 280 nanometers.
Embodiment 4
The first step takes by weighing 6.0 milligrams of albendazole raw materials, adds 2 milliliters of acetone it is dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram sodium lauryl sulphate that contains, 100 milliliters of the aqueous solutions of 0.82 gram sodium hydroxide and 20.0 gram Polyethylene Glycol are second solution.The 3rd step was under 25 ℃, ultrasonic 30 minutes condition first solution and second solution fully to be mixed, makes the albendazole slurry of PH=6.50 in temperature.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 300 nanometers.
The first step takes by weighing 6.0 milligrams of albendazole raw materials, adds 2 milliliters of acetone it is dissolved fully, the solution of winning.Second step, the cofabrication 1.80 gram Tween 80s that contain, 100 milliliters of 0.76 gram sodium hydroxide and the polyacrylic alcoholic solution of 0.10 gram are second solution.The 3rd step was under 40 ℃, ultrasonic 20 minutes condition first solution and second solution fully to be mixed, makes the albendazole slurry of PH=4.85 in temperature.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 240 nanometers.
Embodiment 6
The first step takes by weighing 6.0 milligrams of albendazole raw materials, adds 2 milliliters of acetone it is dissolved fully, the solution of winning.Second step, the cofabrication 0.10 gram poloxamer-188 that contains, 100 milliliters of the aqueous solutions of 1.60 gram sodium hydroxide and 4.40 gram polyvinyl alcohol are second solution.The 3rd step was that 25 ℃, mixing speed are that 1000 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution in temperature, albendazole slurry that must PH=11.00.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 400 nanometers.
Embodiment 7
The first step takes by weighing 332 milligrams of albendazole raw materials, adds 2 milliliters of glacial acetic acids it is dissolved fully, the solution of winning.Second step, the cofabrication 0.20 gram poloxamer-188 that contains, 100 milliliters of the aqueous solutions of 0.74 gram sodium hydroxide and 2.00 gram sodium polyacrylate are second solution.The 3rd step was that 40 ℃, mixing speed are that 500 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution in temperature, albendazole slurry that must PH=4.60.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 200 nanometers.
Embodiment 8
The first step takes by weighing 332 milligrams of albendazole raw materials, adds 2 milliliters of glacial acetic acids it is dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram poloxamer-188 that contains, 100 milliliters of the aqueous solutions of 1.60 gram sodium hydroxide and 0.10 gram Polymeric sodium metaphosphate. are second solution.The 3rd step was that 0 ℃, mixing speed are that 1000 rev/mins, mixing time are under 10 minutes the condition in temperature, according to mode one in the step (four) first solution was fully mixed with second solution, made the albendazole slurry of PH=11.00.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 300 nanometers.
Embodiment 9
The first step takes by weighing 332 milligrams of albendazole raw materials, adds 2 milliliters of glacial acetic acids it is dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram poloxamer-188 that contains, 100 milliliters of the aqueous solutions of 0.76 gram sodium hydroxide and 4.40 gram polyvinyl alcohol are second solution.The 3rd step was that 25 ℃, mixing speed are that 1000 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution in temperature, made the albendazole slurry of PH=4.60.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 280 nanometers.
The first step takes by weighing 332 milligrams of albendazole raw materials, adds 2 milliliters of glacial acetic acids it is dissolved fully, the solution of winning.Second step, the cofabrication 1.80 gram Tween 80s that contain, 100 milliliters of the aqueous solutions of 1.10 gram sodium hydroxide and 0.10 gram sodium polyacrylate are second solution.The 3rd step, under temperature is 25 ℃, ultrasonic 10 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=6.50.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 220 nanometers.
Embodiment 11
The first step takes by weighing 332 milligrams of albendazole raw materials, adds 2 milliliters of glacial acetic acids it is dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram sodium lauryl sulphate that contains, 100 milliliters of the aqueous solutions of 0.76 gram sodium hydroxide and 0.10 gram sodium polyacrylate are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 20 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=4.85.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 240 nanometers.
Embodiment 12
The first step takes by weighing 332 milligrams of albendazole raw materials, adds 2 milliliters of glacial acetic acids it is dissolved fully, the solution of winning.Second step, the cofabrication 1.80 gram Tween 80s that contain, 100 milliliters of the aqueous solutions of 1.42 gram sodium hydroxide and 0.10 gram Polymeric sodium metaphosphate. are second solution.The 3rd step was that 25 ℃, mixing speed are that 1000 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution in temperature, made the albendazole slurry of PH=6.30.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 290 nanometers.
Embodiment 13
The first step takes by weighing 332 milligrams of albendazole raw materials, adds 2 milliliters of glacial acetic acids it is dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram sodium lauryl sulphate that contains, 100 milliliters of 0.76 gram sodium hydroxide and 2.50 gram Polymeric sodium metaphosphate ies and aqueous solutions are second solution.The 3rd step was that 25 ℃, mixing speed are that 1000 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution in temperature, made the albendazole slurry of PH=4.95.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 300 nanometers.
Embodiment 14
The first step takes by weighing 300 milligrams of albendazole raw materials, adds 2.20 gram lactic acid it is dissolved fully, the solution of winning.In second step, cofabrication 100 milliliters of alcoholic solution that contain 0.30 gram Tween 80 and 0.10 gram polymine are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 10 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=2.50.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 350 nanometers.
Embodiment 15
The first step takes by weighing 300 milligrams of albendazole raw materials, adds 2.20 gram lactic acid it is dissolved fully, the solution of winning.Second step, the cofabrication 0.20 gram poloxamer-188 that contains, 100 milliliters of 0.76 gram sodium hydroxide and the polyacrylic alcoholic solution of 0.10 gram are second solution.The 3rd step was 25 ℃ in temperature, and mixing speed is that 500 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution, makes the albendazole slurry of PH=4.56.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 320 nanometers.
Embodiment 16
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 0.20 gram poloxamer-188 that contains, 100 milliliters of the aqueous solutions of 0.80 gram sodium hydroxide and 0.10 gram sodium polyacrylate are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 20 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=5.65.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 200 nanometers.
Embodiment 17
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 0.90 gram Tween 80 that contains, 100 milliliters of the aqueous solutions of 0.84 gram sodium hydroxide and 3.00 gram Polymeric sodium metaphosphate ies are second solution.The 3rd step was that 40 ℃, mixing speed are that 500 rev/mins, mixing time are under 10 minutes the condition first solution fully to be mixed with second solution in temperature, made the albendazole slurry of PH=9.00.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 250 nanometers.
Embodiment 18
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 2.00 gram Tween 80s that contain, 100 milliliters of 0.75 gram sodium hydroxide and the polyacrylic alcoholic solution of 0.10 gram are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 10 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=4.95.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 220 nanometers.
Embodiment 19
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram sodium lauryl sulphate that contains, 100 milliliters of the aqueous solutions of 0.75 gram sodium hydroxide and 0.20 gram sodium polyacrylate are second solution.The 3rd step was that 40 ℃, mixing speed are under 500 rev/mins the condition first solution fully to be mixed with second solution in temperature, made the albendazole slurry of PH=4.60.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 290 nanometers.
Embodiment 20
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram sodium lauryl sulphate that contains, 100 milliliters of the aqueous solutions of 0.84 gram sodium hydroxide and 0.10 gram Polymeric sodium metaphosphate. are second solution.The 3rd step, under temperature is 25 ℃, ultrasonic 10 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=8.85.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 320 nanometers.
Embodiment 21
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram sodium lauryl sulphate that contains, 100 milliliters of 0.76 gram sodium hydroxide and the polyacrylic aqueous solutions of 0.1 gram are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 10 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=4.85.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 350 nanometers.
Embodiment 22
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 0.30 gram poloxamer-188 that contains, 100 milliliters of the chloroformic solutions of 0.70 gram sodium hydroxide and 5.00 gram polyvinylpyrrolidones are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 10 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=4.30.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 350 nanometers.
Embodiment 23
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 2.75 gram Tween 80s that contain, 100 milliliters of the alcoholic solution of 0.75 gram sodium hydroxide and 0.10 gram polymine are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 10 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=4.80.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 350 nanometers.
The first step, 300 milligrams of albendazole raw materials add 2.20 gram lactic acid it are dissolved fully, the solution of winning.Second step, the cofabrication 0.20 gram poloxamer-188 that contains, 100 milliliters of the aqueous solutions of 1.46 gram sodium hydroxide and 0.10 gram Polymeric sodium metaphosphate. are second solution.The 3rd step, under temperature is 40 ℃, ultrasonic 20 minutes condition, first solution is fully mixed with second solution, make the albendazole slurry of PH=6.50.The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 220 nanometers.
Embodiment 25
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is a kind of in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is a kind of in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is a kind of in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is a kind of in water, the ethanol;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 200 nanometer to 400 nanometers.
Embodiment 26
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is two or more the mixture in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is two or more the mixture in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is two or more the mixture in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is water, alcoholic acid mixture;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
The 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder, detect through particle diameter and learn that its particle diameter is 200 nanometer to 400 nanometers.
In the above-described embodiments: the rotating speed of centrifugalize in the 4th step is preferably 10000 rev/mins to 20000 rev/mins, centrifugation time and is preferably 10 minutes to 30 minutes.
From Figure of description 1 to 4 as can be known: the preparation of contrast albendazole crude drug and embodiments of the invention the sem photograph of albendazole nanoscale albendazole micropowder, can obviously observe: crude drug is a coarse powder, about mean diameter 1200 nanometers, its outward appearance is an irregular polyhedrons, lamellar, skewness; And the albendazole nanoscale albendazole micropowder of embodiments of the invention preparation is a micropowder, and particle diameter is about 200 nanometers, and its outward appearance is irregular granular, and it is comparatively even to distribute.
From Figure of description 4 to 8 as can be known: the preparation of contrast albendazole crude drug and embodiments of the invention the transmission electron microscope picture of albendazole nanoscale albendazole micropowder, further can find: the transmission plot outward appearance of crude drug is irregular lamellar, the big or small skewness of area; And the albendazole nanoscale albendazole micropowder transmission plot outward appearance of embodiments of the invention preparation is regular lamellar, and all less size distribution of area is more even.
From Figure of description 9 to 12 as can be known: the preparation of contrast albendazole crude drug and embodiments of the invention the particle size distribution figure of albendazole nanoscale albendazole micropowder.Can find out: the particle size distribution of albendazole crude drug is bimodal, and particle size distribution is very wide, and particle diameter does not wait in 300 to 2000 nanometers, and mean diameter is about 1200 nanometers, skewness; The albendazole nanoscale albendazole grain size of micropowder distribution of embodiments of the invention preparation is unimodal, and particle size distribution is very narrow, and particle diameter is between 80 to 700 nanometers, and mean diameter is about 200 nanometers, and is evenly distributed.
The contrast experiment that albendazole (ABZ) raw material and embodiments of the invention gained micropowder without any processing have been carried out dissolubility, for details see attached table data in.
Table one albendazole crude drug and nanoscale albendazole micropowder of the present invention dissolubility contrast table in dehydrated alcohol
| Dissolubility (mcg/ml) | |
| The alcoholic solution of albendazole raw material | 4.697? |
| The alcoholic solution of the |
8.783? |
| The alcoholic solution of the sampling 2 of nanoscale albendazole micropowder of the present invention | 12.40? |
By contrast, as can be known: the dissolubility of gained nanoscale albendazole micropowder of the present invention is apparently higher than the dissolubility of albendazole crude drug, nanoscale albendazole micropowder of the present invention dissolubility in ethanol is about the 187%-264% of raw material, and other solvents also all have clear improvement!
The present invention is not limited only to above embodiment, also can determine the specific embodiment according to the technical scheme and the practical situation of the invention described above.The technical solution used in the present invention combines the characteristic of albendazole, and specific implementation process is promptly selected suitable solvent, and albendazole is made solution.By changing solution environmental the albendazole dissolubility is reduced, from solution, separate out, the strict controlled condition of albendazole crystal precipitation process, it is dry to select suitable drying means to precipitate, and obtains the controlled albendazole nano-powder of particle diameter.
With regard to the various embodiments described above result, undressed crude drug is a coarse powder, and particle diameter is the 300-2000 nanometer, and particle size distribution is wide, and its outward appearance is an irregular polyhedrons, and skewness; Adopt the technical solution of the present invention preparation nanoscale albendazole micropowder of the present invention be sampled to micropowder, particle diameter is about 200 nanometers, particle size distribution is concentrated, it is irregular granular that outward appearance is, and be evenly distributed.The implementation method of technical solution of the present invention is by control slurry mixing temperature, mixing speed, ultrasonic time, (pH value is very wide in range for pH value, between 2.50 to 11.00) obtain the controlled micropowder of particle diameter, application is very strong, can be suitable for different commercial production to ingredient requirement.
The present invention prepares the process stabilizing of nanorize albendazole micropowder, prepare various informative, easy and simple to handle, controllable granularity, can realize the mixing of molecular atoms yardstick level, favorable reproducibility, meanwhile, the present invention realizes nanorize with the albendazole raw material, it is prepared into micropowder, to fundamentally solve albendazole slightly solubility problem, and, also will drive albendazole dosage form aspect deep research and invention simultaneously for the research of the various dosage forms of subsequent preparation albendazole, production lay the foundation.Have more vast potential for future development and using value, have a far reaching influence, have good application prospects.
Claims (10)
1. nanoscale albendazole micropowder is characterized in that obtaining by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is a kind of in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is a kind of in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is a kind of in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is a kind of in water, the ethanol;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
2. nanoscale albendazole micropowder is characterized in that obtaining by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is two or more the mixture in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is two or more the mixture in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is two or more the mixture in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is water, alcoholic acid mixture;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
3. nanoscale albendazole micropowder according to claim 1 and 2, it is characterized in that well-mixed condition is in the 3rd step: adopt alr mode fully to mix, its mixing time is that 10 minutes to 30 minutes, mixing speed are 500 rev/mins to 3000 rev/mins; Or/and, adopt ultrasonic power fully to mix, its ultrasonic time is 10 minutes to 30 minutes.
4. nanoscale albendazole micropowder according to claim 1 and 2 is characterized in that the rotating speed of centrifugalize in the 4th step is that 10000 rev/mins to 20000 rev/mins, centrifugation time are 10 minutes to 30 minutes.
5. nanoscale albendazole micropowder according to claim 3 is characterized in that the rotating speed of centrifugalize in the 4th step is that 10000 rev/mins to 20000 rev/mins, centrifugation time are 10 minutes to 30 minutes.
6. nanoscale albendazole micropowder preparing process is characterized in that being undertaken by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is a kind of in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is a kind of in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is a kind of in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is a kind of in water, the ethanol;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
7. nanoscale albendazole micropowder preparing process is characterized in that being undertaken by following step:
The first step is dissolved in good solvent with albendazole and obtains first solution, and in this first solution: the content of albendazole is 3.0 mg/ml to 166 mg/ml; Wherein, good solvent is two or more the mixture in formic acid, glacial acetic acid, lactic acid, the acetone;
In second step, will obtain second solution in surfactant, polymer substance, the sodium hydroxide adding poor solvent; In this second solution: the content of surfactant is 0.001 grams per milliliter to 0.0275 grams per milliliter, and the content of polymer substance is 0.001 grams per milliliter to 0.40 grams per milliliter, and sodium hydroxide content by weight percentage is 0% to 1.6%; Wherein: surfactant is two or more the mixture in poloxamer-188, Tween 80, the sodium lauryl sulphate, polymer substance is two or more the mixture in sodium polyacrylate, polyacrylic acid, Polymeric sodium metaphosphate., polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone, the polymine, and poor solvent is water, alcoholic acid mixture;
The 3rd step, under 0 ℃ to 40 ℃ temperature, first solution and second solution fully mixed obtaining the albendazole slurry, the pH value of this albendazole slurry is controlled at 2.50 to 11.00;
In the 4th step, earlier resulting albendazole slurry of the 3rd step is carried out centrifugalize and obtain centrifugal sediment, and then the centrifugal sediment lyophilization is obtained nanoscale albendazole micropowder.
8. according to claim 6 or 7 described nanoscale albendazole micropowder preparing process, it is characterized in that well-mixed condition is in the 3rd step: adopt alr mode fully to mix, its mixing time is that 10 minutes to 30 minutes, mixing speed are 500 rev/mins to 3000 rev/mins; Or/and, adopt ultrasonic power fully to mix, its ultrasonic time is 10 minutes to 30 minutes.
9. according to claim 6 or 7 described nanoscale albendazole micropowder preparing process, the rotating speed that it is characterized in that the centrifugalize in the 4th step is that 10000 rev/mins to 20000 rev/mins, centrifugation time are 10 minutes to 30 minutes.
10. nanoscale albendazole micropowder according to claim 8 is characterized in that the rotating speed of centrifugalize in the 4th step is that 10000 rev/mins to 20000 rev/mins, centrifugation time are 10 minutes to 30 minutes.
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| CN102973505A (en) * | 2012-11-07 | 2013-03-20 | 河南牧翔动物药业有限公司 | Albendazole nanoemulsion and preparation method thereof |
| CN103126782A (en) * | 2013-02-26 | 2013-06-05 | 内蒙古农牧业科学院 | Method for treating parasitic disease |
| CN104324009A (en) * | 2014-10-27 | 2015-02-04 | 郑州后羿制药有限公司 | Micro powder containing fenbendazole and preparation method thereof |
| US20150314004A1 (en) * | 2012-12-26 | 2015-11-05 | Hewei Li | Freeze-dried excipient and preparation method thereof |
| CN114224834A (en) * | 2021-12-24 | 2022-03-25 | 沈阳伟嘉生物技术有限公司 | Albendazole nano suspension with high bioavailability and preparation method thereof |
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| CN1457886A (en) * | 2003-06-06 | 2003-11-26 | 天津大学 | Process for preparing poly lactic acid super microball carrying medicine |
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| CN1457886A (en) * | 2003-06-06 | 2003-11-26 | 天津大学 | Process for preparing poly lactic acid super microball carrying medicine |
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| CN102973505A (en) * | 2012-11-07 | 2013-03-20 | 河南牧翔动物药业有限公司 | Albendazole nanoemulsion and preparation method thereof |
| US20150314004A1 (en) * | 2012-12-26 | 2015-11-05 | Hewei Li | Freeze-dried excipient and preparation method thereof |
| CN103126782A (en) * | 2013-02-26 | 2013-06-05 | 内蒙古农牧业科学院 | Method for treating parasitic disease |
| CN104324009A (en) * | 2014-10-27 | 2015-02-04 | 郑州后羿制药有限公司 | Micro powder containing fenbendazole and preparation method thereof |
| WO2022077087A1 (en) * | 2020-10-16 | 2022-04-21 | Ipanema Industria De Produtos Veterinarios Ltda | Microsuspension against parasites and method for obtaining same |
| CN114224834A (en) * | 2021-12-24 | 2022-03-25 | 沈阳伟嘉生物技术有限公司 | Albendazole nano suspension with high bioavailability and preparation method thereof |
| CN114224834B (en) * | 2021-12-24 | 2022-11-11 | 沈阳伟嘉生物技术有限公司 | Albendazole nano suspension with high bioavailability and preparation method thereof |
| CN115381793A (en) * | 2022-08-22 | 2022-11-25 | 吉林大学 | Albumin-loaded albendazole nano medicine and preparation method thereof |
| CN115381793B (en) * | 2022-08-22 | 2023-11-21 | 吉林大学 | Albumin-loaded albendazole nano-drug and preparation method thereof |
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