CN101890164A - Method for laser preparation of nano-drug preparation - Google Patents
Method for laser preparation of nano-drug preparation Download PDFInfo
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- CN101890164A CN101890164A CN 201010108804 CN201010108804A CN101890164A CN 101890164 A CN101890164 A CN 101890164A CN 201010108804 CN201010108804 CN 201010108804 CN 201010108804 A CN201010108804 A CN 201010108804A CN 101890164 A CN101890164 A CN 101890164A
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Images
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The invention discloses a method for laser preparation of a nano-drug preparation, which comprises the following steps: carrying out laser radiation on water-based suspension of an insoluble drug and excipients, and obtaining the suspension containing nano-particles. The method adopts the laser nanocrystallization technology, a laser beam with the specific wavelength is utilized for treating the solution of the insoluble drug, and the insoluble drug is produced into micro-particles in the water-based solution through the laser radiation principle, thereby becoming a pre-nano-preparation. The method can completely avoid the pollution of an organic solvent and the impacts of the high-pressure and high-shearing process on the temperature of the drug. Furthermore, devices used in the operation are not in any physical contact with the drug solution during the whole nanocrystallization process, thereby well ensuring the sterile state of the drug solution and eliminating the complex sterilization step. More importantly, the particle size of the nano-particles formed by laser radiation is 30-300nm and can be precisely controlled, the particle size is uniform, and the passive targeting effect can be well achieved in an injection preparation.
Description
Technical field
The present invention relates to the preparation method of indissoluble medicament nano granule.
Background technology
The insoluble drug preparation is the pharmacy work always person's research focus because such medicine is poorly soluble in aqueous medium, causes its valid density in body fluid low, not only be difficult to see through biomembrane and influence curative effect of medication, simultaneously also to medicament preparation make troubles.
Use present situation: for a lot of dissolubility are low but the medicine that curative effect is good, preparation preparation technology commonly used comprises solubilising, liposome enclose, (little) emulsifying, cyclodextrin parcel, block copolymer micelle parcel, water-soluble prodrug, natural polymer enclose and " pure medicine " nanoparticle etc.
At present, the nanoparticle technology of preparing can be divided into 3 classes: mechanical crushing method, physics dispersion method and chemical synthesis.Remove the improvement of some traditional mechanical crushing equipments, outside vibromill, jet mill, ultrasonic nebulizer etc., some new mechanical activation comminution technology also are used to the medicament nano granule preparation gradually, as supercritical fluid technology, supercritical fluid-liquid film ultrasonic technique, high pressure homogenization method-advanced technology and relevant devices such as air pocket blasting technique.Above-mentioned in recent years most of pharmaceutical preparation method for making Nano has all had significant progress, but much still rests on breadboard conceptual phase, and suitability for industrialized production still is unrealized.Main cause is some limitation of prior art.
Liposome: liposome is to be to combine and the drug-supplying system that produces by Van der Waals force by lipophilic drugs and liposome internal layer.Its stable temperature influence is bigger, if also exist instability as drug administration by injection, easily leaks, and the cost height is produced problems such as difficulty greatly.Quality problems take place in present domestic taxusol-lipid body injection again and again, make the clinical practice of this class preparation be subjected to significant limitation.
(little) emulsifying drug-supplying system:
Be lower than the nanoscale microemulsion of 100nm for particle diameter, its preparation prescription is still needed and will be used a large amount of emulsifying agents, co-emulsifier except water and oil phase.A large amount of emulsifying agents are to the zest or the toxicity problem noticeable [2] of body in pharmaceutical preparation especially injection.Particle diameter is at the submicron emulsion of 100-1000nm, and material often needs impouring high pressure dispersing emulsification machine internal emulsification during preparation, and this process is prone to the system temperature that is caused by high pressure and raises, and there is hidden danger in the stability to sensitive medicaments thus.
The cyclodextrin clathrate preparation:
Structure-outside is hydrophilic, inner hydrophobic enjoys medicament educational circles to attract attention for medicinal " cage " shape because of its uniqueness of cyclodextrin.Wherein hydroxypropyl is most widely used because water solublity is big, toxicity is little.But as class pharmaceutic adjuvant newly developed, its preparation especially long-term safety of intravenous formulation is worth The effect.Interrelated data shows that the untoward reaction of intravenous injection hydroxypropyl mainly shows as nephrotoxicity and hemolytic.The sudden change of antibacterial and mammalian genes measure and chromosomal aberration test as can be known, hydroxypropyl may have certain teratogenesis and carcinogenecity.As can be known, hydroxypropyl is mainly at renal metabolism under the warning item of the Itraconazole injection description of FDA approval, and particularly the nephrotoxicity of the major impurity beta-schardinger dextrin-of this adjuvant is bigger, so the patient Ying Shenyong of renal insufficiency.Hydroxypropyl can cause the generation of pancreas in rat cancer in addition, but does not see discovery at the carcinogenicity test of mice
[3]The 45% aqueous solution 0.1mL that studies show that homemade hydroxypropyl promptly causes rabbit 2% red cell suspension haemolysis, proves that its haemolysis is not sneezed at.Johson ﹠ Johnson's itraconazole intravenous fluid contains hydroxypropyl 40%, drips speed to the method for 1mL/min with control during clinic trial and alleviates this problem.
The block copolymer micelle drug-supplying system:
Block copolymer is meant and has the different segment of two or more structure in the single linear molecule, can synthesize the copolymer with particular chemical structure, molecular weight as required.The tool amphipathic block can independently be dressed up specific supramolecular ordered aggregation-micelle in solution.Its preparation method mainly contains physics method and chemical method.Such macromolecule micelle possess hydrophilic property shell and lipotropy kernel are finished solubilising and parcel to medicine with this structure.
As a kind of novel drug-supplying system, block copolymer micelle has great potentiality at pharmaceutical field, but the problem that exists at present is also a lot.Aspect synthetic, factors such as the purity of copolymer and range of molecular weight distributions have all limited its application in pharmaceutical preparation.Moreover the size of the crystal formation of segmental consumption of hydrophilic and molecular weight, medicine and molecular weight, micelle particle diameter and environment pH value etc. all can influence the drug release feature of block copolymer micelle in the macromolecule.Configuration aspect in vivo after the medication, macromolecular material degradation time commonly used is long, can accumulate in vivo, causes the preparation toxicity that adjuvant causes.In addition, also there is the prominent problem of releasing of medicine in the micelle of physical method preparation; The micelle of chemical method preparation may influence the structure and the pharmacologically active of medicine itself owing to experience chemical reaction; There is the problem of release accuracy in the temperature-sensitive micelle; Copolymer micelle is also remaining conclusive evidence aspect the subcellular targeting.
Water-soluble prodrug:
The new derivative compound that activity is high in water solublity group and the insoluble drug position is generated by chemical reaction, such compound water soluble obviously increases, does not possess the pharmacologically active of former medicine than active parent drug, but discharges active parent drug in body after transforming.This conversion can be spontaneous, also can cause because of hydrolysis or enzyme catalysis.The modification of prodrug roughly is divided into micromolecule derives, and as inorganic acid alkali, organic acids and base, and water soluble polymer props up and carries.The exploitation of prodrug has two basic demands: one, after the administration, in body, take place can be converted into active parent drug rapidly before the cometabolism.Two, prodrug must possess suitable physical and chemical stability.Otherwise may cause two kinds of consequences: will cause after the degraded of the prodrug moiety of poor stability active parent drug before administration just precipitation separate out, this problem seems for the former medicine of water solublity extreme difference and is even more important; Or stability is strong excessively, and the ratio that prodrug carries out biotransformation in vivo is low excessively, can not reach treatment level in the active parent drug concentration of therapentic part.This shows that the design of water-soluble prodrug needs to consider simultaneously at least two above contradictory elements.
Natural polymer parcel: by means such as the high pressure breast are even, select especially human body endogenous macromolecule of natural polymer for use,, insoluble drug is carried out the nanometer coating, become a new focus of insoluble drug preparation research as the human albumin.The injection paclitaxel albumin microparticle of drugs approved by FDA in 2005 (paclitaxel protein-bound particles, ABI-007/ trade name Abraxane) is wherein representative successful illustration.
Abraxane belongs to albumin coating nanometer formulation, be a kind of new, with the pacilitaxel nano granule lyophilized preparation of human albumin as carrier, the preparation of this medicine by earlier with medicine dissolution in organic solvent, utilize high-pressure homogenization that paclitaxel and human albumin are made paclitaxel albumin nanometer particle suspension liquid (mean particle dia 130～150nm) again.The more former medicine of dissolubility improves greatly, and cause strong anaphylactoid adjuvant in the former medicine injection because of not using, need not in advance that administration prevents its anaphylaxis, can adopt the standard infusion catheter, and can the angular vein administration of high dose short time, bring tangible facility and safety to doctor and patient.
Yet, research worker finds that again Abraxane exists in preparation not enough: because the intermolecular disulfide bond of the simple human serum albumin of dependence is reset under high pressure and high shear but be crosslinked between protein molecule, the time of high pressure homogenization is longer, medicine stability is affected on the one hand, particularly thermal instability medicine such as paclitaxel is easily degraded, and the loss of high pressure homogenization apparatus is also very big; Disulfide bond number in the albumin is limited on the other hand, so it is less to receive the crosslinked ratio of brilliant peripheral protein matter intermolecular rearrangement at medicine, the shell of formation built on the sand, (as 24 hours) still can assemble in the certain hour, are unfavorable for stable production.Propose novel protein stabilized nano preparation thus, by adopting the material that contains sulfydryl or disulfide bond safely and effectively, the disulfide bond between the help protein molecule is reset under the high pressure high shear but is quickened crosslinked between protein molecule and the crosslinked ratio of raising.
" pure medicine " nanoparticle: owing to all to adopt the high pressure homogenization apparatus in the above-mentioned multiple nanometer method, thereby be difficult to avoid exothermal process.For the challenge greatly beyond doubt of slightly solubility temperature-sensitive medicine, do not arise at the historic moment so do not contain " naked medicine " nanoparticle of any excipient.This dosage form is the stable colloidal dispersion system that adds the nanoscale " pure medicine " of appropriate surfactant, is otherwise known as " nano suspension " (nanosuspensions).This class preparation and traditional nanoparticle have notional difference, and the latter belongs to matrix scaffold type nanosystems.Said method is mostly taked in the preparation of " nanometer suspension liquid ".The new technology of Chinese patent report by solvent method preparation " pure medicine " nanoparticle arranged recently.Concrete technical scheme is as follows: 1) medicine is dissolved in formation solution in first solvent (good solvent), 2) the solution and the second solvent (poor solvent, be generally water) the pre-suspensoid of mixing formation, 3) pre-suspension is applied energy and forms the nanoparticle of average effective particle diameter less than 2 μ m, 4) to the further preparation processing of this nanoparticle.It is said that the preparation of this nano suspension has that technology is simple, the characteristics of better stability of preparation, nanoparticle has passive target and slow-releasing and controlled-releasing action.The particle diameter of its final products is along with medicine and post-processing approach is different roughly at 100-1000nm, 50-200nm, and 70-600nm fluctuates between the 80-800nm.
Summary of the invention
The method that the purpose of this invention is to provide a kind of laser preparation of nano-drug preparation is to overcome the above-mentioned defective that prior art exists.
Method of the present invention comprises the steps:
With the aqueous suspension of insoluble drug and adjuvant, through laser emission, obtain to contain the suspension of nanoparticle, the particle diameter of wherein said nanoparticle is 30-300nm;
Described nanoparticle is crystalline solid or amorphous compound, or both mixture;
Described insoluble drug includes, but are not limited to paclitaxel, etoposide, itraconazole or curcumin;
Described adjuvant includes but not limited to more than one in organic acid, weak base, sugar alcohols, polysaccharide, polyalcohols, surfactant or the cellulose family;
Described organic acid is selected from more than one in citric acid, citric acid, alginic acid, tartaric acid, oxalic acid, malic acid, ascorbic acid, benzoic acid, salicylic acid or the caffeic acid etc.;
Described weak base is selected from more than one in sodium bicarbonate, sodium alginate or the triethanolamine etc.;
Described sugar alcohols is selected from more than one in D-trehalose, D one sorbitol, sodium alginate, dextran 40, D-galactose, lactose, glucose, mannitol or the xylitol;
Described polysaccharide is selected from more than one in arabic gum, glycogen, starch, glucosan or chitosan and the derivant thereof;
Described cellulose family is selected from more than one in methylcellulose (MC), ethyl cellulose (EC), propyl cellulose (PC), hydroxy methocel (HMC), hydroxyethyl-cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) or the carboxymethyl cellulose (CMC) etc.;
Described polyalcohols is selected from more than one in Polyethylene Glycol (PEG), polypropylene glycol (PPG), methoxypolyethylene glycol (MPEG), poly-para Toluic Acid (PBG) or the ethylene glycol copolymer etc.;
Described surfactant is selected from more than one in phospholipid, cholic acid salt, Tween 80 or the poloxamer 188 etc.;
The quality of described adjuvant and insoluble drug is 10 than scope: 1-1: 10;
Described in aqueous suspension can include but not limited to distilled water and aqueous buffer, as phosphate buffer, carbonate buffer solution or acetate buffer etc.;
The used wavelength of described laser emission is 21nm～700 μ m;
The used radiation witdth of described laser emission is 10fs～100ns;
The used energy density of described laser emission is 5 μ J/cm
2～2000mJ/cm
2
The used repetitive rate of described laser emission is 0.001Hz～1000Hz;
Laser emission is undertaken by laser light irradiation apparatus, and described laser light irradiation apparatus can adopt the commercially available prod, as the Nd:YAG frequency tripling ultraviolet solid state laser SpitLight2100-10 of German InnoLas company;
The present invention adopts a kind of laser nano technology, utilizes the laser beam treatment insoluble drug solution of specific wavelength, and the principle by laser emission becomes " pre-nanometer formulation " with insoluble drug micronize in aqueous solution.Should " pre-nanometer formulation " can be according to physical and chemical properties of drugs through further preparation process, preparation becomes through injection, oral, mucosal drug delivery or local skin drug-supplying system.This laser nano technology has been avoided the pollution of organic solvent and the high pressure high shear process temperature effect to medicine fully.And in whole nanorize process, operate between used apparatus and the drug solution contacting, can guarantee the aseptic condition of medicinal liquid well, save complicated sterilization steps without any physics.The more important thing is that the formed nano particle diameter of laser emission can accurately be controlled between 30-300nm, epigranular can reach the effect of passive target well in ejection preparation.
Description of drawings
Fig. 1 is the sem photograph of the nano particle diameter of embodiment 1.
Fig. 2 is that the particle diameter of the nanoparticle of embodiment 1 is schemed respectively.
Fig. 3 is a particle size distribution behind embodiment 1 redispersion.
Fig. 4 is that the particle diameter of the nanoparticle of embodiment 2 is schemed respectively.
Fig. 5 is a particle size distribution behind embodiment 2 redispersion.
Fig. 6 is that the particle diameter of the nanoparticle of embodiment 3 is schemed respectively.
Particle size distribution behind Fig. 7 embodiment 3 redispersion.
The specific embodiment
Embodiment 1
The preparation of paclitaxel nano grain lyophilized powder:
The paclitaxel of 600mg is placed the 50mL sterile water solution, obtain suspension 1.
Other prepares the citric acid saturated aqueous solution, and 0.22 μ m membrane filtration obtains 1000mL solution 2.
1g mannitol is dissolved in the 10mL aqueous solution, 0.22 μ m membrane filtration obtains solution 3 again.
In sterilizing room,, obtain suspension 4, again solution 2 is splashed into suspension 4, regulate its pH value, subsequently this suspension is settled to 100mL with sterile purified water to 3.0-5.0 with solution 3 impouring suspensions 1.
Dividing in the brown ampoule of 10mL of packing into then, ampoule is placed in the laser nano instrument again, is light source with Nd:YAG frequency multiplication green glow solid state laser, and radiation wavelength is 532nm, and energy density is 80mJ/cm
2, radiation witdth is 15ns, and repetitive rate is 10Hz, and making particle diameter is the medicament nano suspension of 46nm, and the sem photograph of nano particle diameter is seen Fig. 1, its particle size distribution situation is seen Fig. 2.
At last ampoule is inserted-80 ℃ of following pre-freeze 30min in the ultra cold storage freezer, take out back-10 ℃ of lyophilizing 48hr in the lyophilizing instrument.This nano freeze-dried powder adds 100mL
WeightConcentration is that 0.9% sodium-chloride water solution redispersibility is good, and particle size distribution is seen Fig. 3 behind the redispersion.This is heavily disperseed to the results are shown in following " sensitivity test " content partly after back nanometer formulation, commercially available paclitaxel injection and the administration of reference substance mouse vein.
Embodiment 2
The preparation of etoposide nanometer lyophilized preparation:
The etoposide of 2.0g is placed about 50mL sterile water solution, obtain suspension 1.
Other prepares weight concentration is 30% acid solution, and 0.22 μ m membrane filtration obtains 1000mL solution 2.
0.5g D-trehalose is dissolved in the 10mL aqueous solution, 0.22 μ m membrane filtration obtains solution 3 again.
In sterilizing room,, obtain suspension 4, again solution 2 is splashed into suspension 4, regulate its pH value, subsequently this suspension is settled to 100mL with sterile purified water to 3.5-5.5 with solution 3 impouring suspensions 1.Divide in the brown ampoule of 10mL of packing into then, again ampoule is placed radiation in the laser nano instrument, divide then in the brown ampoule of 10mL of packing into, ampoule is placed in the laser nano instrument again, with ultraviolet XeCl excimer laser is light source, and radiation wavelength is 351nm, and energy density is 30mJ/cm
2, radiation witdth is 35ns, and repetitive rate is 10Hz, and making particle diameter is the medicament nano suspension of 190nm, and its particle size distribution situation is seen Fig. 4.At last ampoule is inserted-80 ℃ of pre-freeze 90min in the ultra cold storage freezer, take out back-10 ℃ of lyophilizing 36hr in the lyophilizing instrument.This nano freeze-dried powder adds 100mL
WeightConcentration is that 5% D/W redispersibility is good, and particle size distribution is seen Fig. 5 behind the redispersion.
Embodiment 3
The preparation of Itraconazole nanometer grain lyophilized preparation:
The aseptic itraconazole of 1.0g is placed about 50mL sterile water solution, obtain suspension 1.
In addition 1.0g D-sorbitol is dissolved in the 10mL aqueous solution, 0.22 μ m membrane filtration obtains 9.5mL solution 2.
In sterilizing room,, obtain suspension 3 with solution 2 impouring suspensions 1.
Subsequently this suspension is settled to 100mL with sterile purified water.Dividing in the brown ampoule of 10mL of packing into then, ampoule is placed radiation in the laser nano instrument again, is light source with Nd:YAG frequency tripling ultraviolet solid state laser, and radiation wavelength is 355nm, and energy density is 80mJ/cm
2, radiation witdth is 10ns, and repetitive rate is 10Hz, and making particle diameter is the medicament nano suspension of 100nm, and its particle size distribution situation is seen Fig. 6.At last ampoule is inserted-80 ℃ of pre-freeze 90min in the ultra cold storage freezer, take out back-10 ℃ of lyophilizing 36hr in the lyophilizing instrument.This nano freeze-dried powder adds 100mL
WeightConcentration 5% D/W redispersibility is good, and particle size distribution is seen Fig. 7 behind the redispersion.
Embodiment 4
The preparation of curcumin nano dry powder:
The aseptic curcumin of 1.5g is placed about 50mL aqueous solution, obtain suspension 1.
In addition 1.0g D-galactose is dissolved in the 10mL aqueous solution, obtains solution 2.
With solution 2 impouring suspensions 1, obtain suspension 3.
Subsequently this suspension is settled to 100mL with distilled water.Dividing in the brown ampoule of 20mL of packing into then, ampoule is placed radiation in the laser nano instrument again, is light source with the semiconductor laser, and radiation wavelength is 580nm, and energy density is 50mJ/cm
2, radiation witdth is 10ns, and repetitive rate is 10Hz, and making particle diameter is the medicament nano suspension of 200nm.
Add the 3.6g lactose in this suspension, mixing is granulated, and 55 ℃ are dry down, the granulate packing, promptly.
Embodiment 5
Pharmacology's check
Whole body is hypersensitive test (ASA) initiatively
Be subjected to the paclitaxel nano preparation (specification 30mg/ml) of reagent thing: embodiment 1
Reagent: bovine serum albumin (positive reference substance); 0.9% sodium chloride injection (blank product)
24 of animal: Hartley white healthy guinea pigs, about body weight 350g, the male and female dual-purpose
Method:
Choose 24 of healthy guinea pigs, be equally divided into 4 groups at random: blank group, positive controls, be subjected to reagent thing low dose group and be subjected to reagent object height dosage group.The dosage of blank group and positive controls is 3mg/, and being subjected to reagent thing low dose group is 2.7g/m
2, being subjected to reagent thing low dose group is 5.4g/m
2, the next day 1 time, totally 3 lumbar injections carry out sensitization.Above corresponding each reagent set of the 12nd day abdominal cavity fast injection two multiple doses excites after the last sensitization, observes in the 30min anaphylaxis whether occurs.During the sensitization, observe the symptom of animal every day, and in first sensitization and excite the body weight of measuring each animal the same day.After exciting, intravenous injection, has or not corresponding symptom according to table 1 observed and recorded animal at once to 30min, and appearance of record symptom and extinction time, and associative list 2 carries out the evaluation of sensitization degree.
Table 1. symptoms of allergic
| 0 is normal | 7 rapid breathing | 14 instability of gait |
| 1 is restless | 8 urinate | 15 jump |
| 2 perpendicular hairs | 9 defecation | 16 pant |
| 3 |
10 shed tears | 17 spasm |
| 4 scratch nose | 11 dyspnea | 18 rotations |
| 5 sneezes | 12 wheezing sounds | 19 Cheyne-Stokes respiration |
| 6 coughs | 13 |
20 death |
Table 2. whole body sensitization evaluation criterion
| 0 | - | The anaphylaxis feminine gender |
| The 1-4 symptom | + | Anaphylaxis is weak positive |
| The 5-10 symptom | ++ | The anaphylaxis positive |
| The 11-19 symptom | +++ | The anaphylaxis strong positive |
| 20 symptoms | ++++ | The extremely strong positive of anaphylaxis |
The result:
Any abnormal response does not all appear in each test group Cavia porcellus during sensitization, movable, ingest, drink water normal, not influential to the Cavia porcellus body weight gain.After giving booster dose, tried low dose group, negative control group and obvious abnormal response all do not occurred, 1～20 order reaction symptom do not occurred, the death of Cavia porcellus do not occurred, judged that thus the anaphylaxis of self-control paclitaxel nano preparation is negative.Tried restless except that appearance, the perpendicular hair of high dose group, tremble, scratch the weak positive (+) anaphylaxis of nose, all the other obvious abnormal response all do not occur.The positive controls Cavia porcellus cough occurred, scratched nose, has shed tears, dyspnea, tic, tide are significantly anaphylaxis such as to breathe but strong positive (++ the+) anaphylaxis of not seeing animal dead, symptoms of allergic disappears in exciting back 30min substantially, and anaphylaxis is positive.
Table 3. anaphylaxis level numerical table
Conclusion
Low dose group is subjected to the test preparation anaphylaxis negative, and in the time of can determining the dosage of clinical practice, the experimenter anaphylaxis can not occur.High dose group is subjected to the test preparation anaphylaxis to be mainly feminine gender, and only a few occurs weak positive, and is may excessive with drug dose (2-4 of conventional amount used doubly) relevant.This result of the test shows, is subjected to reagent thing safety in routine administration dosage, and its safety range is bigger.
Tumor control rate is measured:
Measured among the embodiment one the paclitaxel nano preparation to the external fragmentation effect of melanoma cell A375 by mtt assay, as shown in table 4.
Table 4 inhibition rate of tumor cell %
This shows that laser emission nanometer suspension liquid is compared with commercially available formulation for paclitaxel the suppression ratio of melanoma cell A375, toxic and side effects obviously alleviates.And suitable with the inhibitory action to tumor cell under the concentration.
Claims (9)
1. the method for laser preparation of nano-drug preparation is characterized in that, comprises the steps: the aqueous suspension with insoluble drug and adjuvant, through laser emission, obtains to contain the suspension of nanoparticle.
2. method according to claim 1 is characterized in that, contains in the suspension of nanoparticle, and the particle diameter of nanoparticle is 30-300nm.
3. method according to claim 1 is characterized in that, described nanoparticle is crystalline solid or amorphous compound, or both mixture.
4. method according to claim 1 is characterized in that described adjuvant includes but not limited to more than one in organic acid, weak base, sugar alcohols, polysaccharide, polyalcohols, surfactant or the cellulose family;
Described organic acid is selected from more than one in citric acid, citric acid, alginic acid, tartaric acid, oxalic acid, malic acid, ascorbic acid, benzoic acid, salicylic acid or the caffeic acid etc.;
Described weak base is selected from more than one in sodium bicarbonate, sodium alginate or the triethanolamine etc.;
Described sugar alcohols is selected from more than one in D-trehalose, D one sorbitol, sodium alginate, dextran 40, D-galactose, lactose, glucose, mannitol or the xylitol;
Described polysaccharide is selected from more than one in arabic gum, glycogen, starch, glucosan or chitosan and the derivant thereof;
Described cellulose family is selected from more than one in methylcellulose (MC), ethyl cellulose (EC), propyl cellulose (PC), hydroxy methocel (HMC), hydroxyethyl-cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) or the carboxymethyl cellulose (CMC) etc.;
Described polyalcohols is selected from more than one in Polyethylene Glycol (PEG), polypropylene glycol (PPG), methoxypolyethylene glycol (MPEG), poly-para Toluic Acid (PBG) or the ethylene glycol copolymer etc.;
Described surfactant is selected from more than one in phospholipid, cholic acid salt, Tween 80 or the poloxamer 188.
5. method according to claim 4 is characterized in that described aqueous suspension includes but not limited to distilled water and aqueous buffer.
6. method according to claim 1 is characterized in that, the used wavelength of described laser emission is 21nm～700 μ m; The used radiation witdth of described laser emission is 10fs～100ns; The used energy density of described laser emission is 5 μ J/cm
2～2000mJ/cm
2The used repetitive rate of described laser emission is 0.001Hz～1000Hz.
7. according to each described method of claim 1～6, it is characterized in that the quality of described adjuvant and insoluble drug is 10 than scope: 1-1: 10.
8. according to each described method of claim 1～6, it is characterized in that described insoluble drug includes, but are not limited to paclitaxel, etoposide, itraconazole or curcumin.
9. method according to claim 7 is characterized in that described insoluble drug includes, but are not limited to paclitaxel, etoposide, itraconazole or curcumin.
Priority Applications (1)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102337296A (en) * | 2011-07-05 | 2012-02-01 | 天津大学 | Glucan-agmatine polycation transgenic vector, and preparation method and application thereof |
| CN108057406A (en) * | 2017-12-14 | 2018-05-22 | 中国科学院长春光学精密机械与物理研究所 | A kind of phthalocyanin nano material and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1422666A (en) * | 2001-10-09 | 2003-06-11 | 黑龙江省光电技术研究所 | Method for preparing Chinese medicine and difficult-to-dissolve western medicine anao-powder by ultraviolet laser |
| CN101528181A (en) * | 2006-05-15 | 2009-09-09 | 国立大学法人大阪大学 | Method of producing nanoparticle dispersion of medicinal component |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1422666A (en) * | 2001-10-09 | 2003-06-11 | 黑龙江省光电技术研究所 | Method for preparing Chinese medicine and difficult-to-dissolve western medicine anao-powder by ultraviolet laser |
| CN101528181A (en) * | 2006-05-15 | 2009-09-09 | 国立大学法人大阪大学 | Method of producing nanoparticle dispersion of medicinal component |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102337296A (en) * | 2011-07-05 | 2012-02-01 | 天津大学 | Glucan-agmatine polycation transgenic vector, and preparation method and application thereof |
| CN108057406A (en) * | 2017-12-14 | 2018-05-22 | 中国科学院长春光学精密机械与物理研究所 | A kind of phthalocyanin nano material and preparation method thereof |
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