CN104983688A - Andrographolide nano crystal intermediate, preparation method and applications thereof - Google Patents
Andrographolide nano crystal intermediate, preparation method and applications thereof Download PDFInfo
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Abstract
The invention belongs to the field of medicinal preparation, and relates to an andrographolide nano crystal intermediate and a preparation method thereof. The provided andrographolide nano crystal intermediate can be immediately dispersed into a nano state after being contacted with water; the solubility, dissolving-out speed, and bioavailability of andrographolide are prominently improved; the intermediate can be made into different dosage forms containing the nano crystal intermediate; the intermediate can be disintegrated into nano crystals after being contacted with water; the drug stability is enhanced, and the drug function is reinforced. The preparation technology is simple, no toxic solvent is used, the cost is low, and the technology can be easily industrialized, and thus has a good application prospect.
Description
Technical field
The present invention relates to technical field of medicine, especially relate to a kind of andrographolide nanocrystal intermediate and preparation method thereof.
Background technology
Andrographolide has special efficacy to many infectious disease, clinically as antiviral drug of first choice, be called as " natural antibiotics ", there is antibacterial, antiinflammatory, antiviral, bring down a fever, immunity moderation function and antitumor action, prostaglandin can be suppressed to synthesize, discharge and cause scorching active, be mainly used in bacillary dysentery, viral pneumonia, viral upper respiratory tract infection, acute tonsillitis etc.But andrographolide water solubility difference (under 22 DEG C of conditions 69 μ g/ml), and poor stability (under pH>12 condition easy open loop, dehydration, isomerization etc.), under condition of neutral pH, Determination of oil-water partition coefficient (LogP) is 2.013, bioavailability low (oral administration biaavailability 0.98%) (Wei Cunfang. the pharmacokinetic of Herba Andrographis diterpene ginkgolide. Traditional Chinese Medicine University Of Guangzhou's master thesis, 2009), so the pharmacologically active of andrographolide is not not fully exerted.
At present, the potassium sodium dehydroandroan drographolide succinate injection of Clinical practice, Induced by Chuanhuning Injection, Xiyanping injection, Lian Bizhi injection are different salt or the derivative formulations of andrographolide, are applied to clinical with drug administration by injection.Although it is fast that andrographolide injection has distribution, the feature such as distribute wide, but increasingly extensive along with the clinical practice of andrographolide injection, clinical compliance is poor, Reporting of harms day by day increases, mainly contain Circulatory involvement, respiratory system damage, digestive system damage, hematological, nervous system damage, (the Zeng Congyan such as renal damage, Qiu Kaiyue .189 example Induced by Chuanhuning Injection untoward reaction document analysis [J]. Chinese pharmacovigilance .2011 (12): 759-762. He Jing is quick, Cheng Guoyin. the different salt injection analysis of adverse reactions of andrographolide. Chinese Pharmaceutical, 2011, 20 (19): 60. Wang Yan, Xu Yanjiao, Liu east .278 example andrographolide injection untoward reaction document analysis [J]. Journal of Chinese Hospital Pharmacy .2011, 31 (08): 701-703. Wei's armies, Li Ying moth, Zhu Liyang. potasium dehydroandrographolisuccinate succinate injection causes child's thrombocytopenia 5 example [J]. adverse effect magazine, 2002, 4 (6): 405).
In addition, the preparation that andrographolide has been developed and researched and developed also has tablet, capsule, dispersible tablet etc., and gone on the market the preparation such as andrographolide tablet, dripping pills of andrographolide.But existing oral conventional formulation technologies does not significantly improve saturation solubility or the dissolution rate of andrographolide, thus compares drug administration by injection approach, andrographolide bioavailability is improved still limited.Also have people to be prepared into cyclodextrin clathrate, although overcome the low problem of insoluble drug dissolubility, cyclodextrin clathrate internal metabolism is slow, has serious Toxicity of Kidney, and cost higher (CN 102343096A).Bibliographical information in addition andrographolide is made solid lipid nanoparticle (CN 102716080A); Make solid dispersion (CN 101433522A); Make nano-emulsion (CN1931130A); Make lipoid microsphere (CN 1686108A); Make the method for grinding suspension (CN 102614133A) to improve stripping and the absorption of andrographolide, but need to add a large amount of carrier materials, complicated process of preparation, and drug loading is low, poor stability, effect is all undesirable, successfully goes on the market there are no product development.
Above document and the method involved by patent improve the body absorption of andrographolide to a certain extent, but still there is a lot of problem, the bioavailability as preparation still adds a large amount of carrier materials or toxic solvent, complicated process of preparation, high in cost of production in lower, liquid preparation poor stability, preparation process.In order to give full play to the pharmacologically active of andrographolide, still need to overcome existing problem further.
Summary of the invention
One of object of this invention is to provide a kind of andrographolide nanocrystal intermediate, meets after water and can become nanocrystal suspension by redispersion fast, thus significantly improve the dissolubility of andrographolide, dissolution rate and bioavailability.Thus provide following invention:
Andrographolide nanocrystal intermediate according to any one of the present invention, it is made up of effective ingredient andrographolide and stabilizing agent.
Andrographolide nanocrystal intermediate according to any one of the present invention, is characterized in that the average particle size range of the andrographolide nanocrystal formed after redissolution dispersion in water is 10 ~ 1500nm, span 0.5 ~ 2.5; Preferably average particle size range 100-1000nm, span 1 ~ 2; Be more preferably average particle size range 500-700nm, span 1.2 ~ 1.6.
Andrographolide nanocrystal intermediate according to any one of the present invention, wherein, the content of andrographolide is 10%-90% (w/w); Preferably 20%-70% (w/w); Be more preferably 30%-50% (w/w).
Andrographolide nanocrystal intermediate according to any one of the present invention, wherein, the content of stabilizing agent is 0.5%-50% (w/w); Preferably 10%-45% (w/w); Be more preferably 15%-30% (w/w).
Andrographolide nanocrystal intermediate according to any one of the present invention, wherein, described stabilizing agent comprises stabilizing agent I, and preferably, described stabilizing agent also comprises stabilizing agent II, and more preferably, described stabilizing agent also comprises described stabilizing agent III.
According to andrographolide nanocrystal intermediate of the present invention, wherein, the content of stabilizing agent I is 1%-30% (w/w), and the content of stabilizing agent II is 1%-30% (w/w), and the content of stabilizing agent III is 10%-70% (w/w); Preferably, the content of stabilizing agent I is 2%-25% (w/w), and the content of stabilizing agent II is 2%-25% (w/w), and the content of stabilizing agent III is 30%-60% (w/w); More preferably for the content of stabilizing agent I is 5%-15% (w/w), the content of stabilizing agent II is 5%-15% (w/w), and the content of stabilizing agent III is 40%-60% (w/w);
Described stabilizing agent I can be lecithin, PLURONICS F87, poloxamer188, Tween 80, sodium deoxycholate, sodium lauryl sulphate, any one of D-alpha tocopherol cetomacrogol 1000 succinate or any multiple mixture;
Described stabilizing agent II can be PVP K30, arabic gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose, gelatin, tragakanta, polyvinyl alcohol, any one of sodium carboxymethyl cellulose and microcrystalline Cellulose or its any multiple mixture;
Described stabilizing agent III can be any one in sucrose, lactose, glucose, trehalose, maltose, mannitol, maltodextrin, sorbitol, Polyethylene Glycol, micropowder silica gel or its any multiple mixture;
Particularly preferably, described stabilizing agent I is D-alpha tocopherol cetomacrogol 1000 succinate, and stabilizing agent II is sodium carboxymethyl cellulose or microcrystalline Cellulose, and stabilizing agent III is mannitol.
Andrographolide nanocrystal intermediate according to any one of the present invention, it is pressed powder or particle, redispersible one-tenth nanocrystal suspension in water, and can realize the rapid stripping of andrographolide;
Get appropriate andrographolide nanocrystal intermediate powder, adhere on sample stage with two-sided conducting resinl respectively, plate the golden film of thick layer 1 ~ 3nm with LB-3 type particle sputter, observe form under scanning electron microscope, the results are shown in accompanying drawing 1.Be solid powder particles by accompanying drawing 1 known andrographolide nanocrystal intermediate, granular size is homogeneous, in spherical particle.
After andrographolide nanocrystal intermediate being added suitable quantity of water redissolution dispersion, get on the one after another drop of copper mesh in covering carbon film, drying at room temperature.The pattern of transmission electron microscope observation andrographolide nanocrystal, the results are shown in accompanying drawing 2.From accompanying drawing 2, creat lactone nanocrystal is oval or subsphaeroidal shape, and size is even.
The dsc analysis of andrographolide nanocrystal intermediate: contrast: blank aluminum dish; Heating and cooldown rate: 10 DEG C/min; Scanning temperature: 40 ~ 260 DEG C; Atmosphere: N
2, respectively to andrographolide crude drug, stabilizing agent and nanocrystal intermediate powder thereof carry out dsc analysis, the results are shown in accompanying drawing 3.
The DSC curve of andrographolide crude drug shown in accompanying drawing 3, andrographolide nanocrystal intermediate, stabilizing agent, result shows that andrographolide crude drug demonstrates obvious crystal melting feature 230 DEG C, occurs the strongest absworption peak; And andrographolide nanocrystal intermediate presents the crystal melting feature similar to andrographolide crude drug at 230 DEG C, illustrate that andrographolide nanocrystal and crude drug have identical crystal structure or crystalline structure, only because particle diameter reduces to cause endothermic peak intensity to diminish, andrographolide exists with nanocrystal state, instead of molecularity or unformed state.
Two of goal of the invention of the present invention is to provide the preparation method of above-mentioned andrographolide nanocrystal intermediate.
The technical scheme realizing above-mentioned purpose is as follows:
A preparation method for andrographolide nanocrystal intermediate, comprises the following steps:
(1) preparation just suspension: by stabilizing agent I water dissolution of formula ratio, adds the stabilizing agent II also mix homogeneously of formula ratio again, obtains stabiliser solution after mix homogeneously; Or by stabilizing agent II water dissolution of formula ratio, add the stabilizing agent I also mix homogeneously of formula ratio after mix homogeneously again, obtain stabiliser solution; Then, be scattered in stabiliser solution by the andrographolide of formula ratio, shear through high speed shear emulsion process, rotating speed is: 10000 ~ 25000rpm, and shear time is 2 ~ 15min; Obtained average particle size range is the first suspension of 20 ~ 150 μm;
(2) prepare nanocrystal suspension: adopt low temperature-high pressure classification homogenizing method, controlling homogenizing temperature is 4 ~ 25 DEG C, respectively circulates 5 ~ 30 times respectively at 200bar, 400bar, 600bar, 800bar; Then circulate 20-50 time under 1000bar ~ 1500bar condition, obtained nanocrystal suspension;
(3) nanocrystal intermediate is prepared: stabilizing agent III dispersing and dissolving adding formula ratio in the nanocrystal suspension of above-mentioned preparation, then spraying dry rapid solidification techniques is adopted, spraying dry hot blast temperature is 105 ~ 150 DEG C, leaving air temp 50-80 DEG C, the peristaltic velocity of pump is 1 ~ 20ml/min, and namely dry solidification obtains nanocrystal intermediate powder.
Three of goal of the invention of the present invention is to provide the andrographolide nanocrystal intermediate prepared by foregoing invention method for the preparation for the treatment of bacillary dysentery, viral pneumonia, viral upper respiratory tract infection, application in the medicines such as acute tonsillitis, namely make with the andrographolide nanocrystal intermediate of effective dose and pharmaceutically suitable carrier and/or excipient and be used for the treatment of bacillary dysentery, viral pneumonia, viral upper respiratory tract infection, the medicament of acute tonsillitis etc., made medicament can be dosage form described on any one pharmaceutics, tablet, dispersible tablet, capsule, granule, suspensoid, dry suspension, powder, inhalant, electuary or pill.
Above-mentioned andrographolide nanocrystal preparation bioavailability is high, compared with prior art (solid dispersion, microemulsion, micropill etc.), demonstrate following superiority: 1. drug entity nanorize, medicine is with nanocrystal state high degree of dispersion, specific surface area is large, improves the wettability of medicine, saturation solubility and dissolution rate; 2. can strengthen and biomembranous adhesion, extend adhesion time and holdup time, effectively improve drug bioavailability; 3. preparation technology is simple, and avoid complicated technology, cost is low, is easy to industrialized great production; 4. not containing other carrier materials, use adjuvant safety, toxicity is little.
Because the andrographolide nanocrystal in nanocrystal suspension belongs to thermodynamics and dynamics Unstable Systems, easy sedimentation, reunion or coalescent, and andrographolide easily decomposes, poor stability cannot reach the object improving its dissolubility and bioavailability.The present invention creatively uses low temperature-high pressure classification homogeneous technology and rapid solidification techniques to prepare the andrographolide nanocrystal of solidification form, and the bottleneck problem of andrographolide stability can be overcome, redispersible one-tenth nanocrystal suspension after the nanocrystal intermediate aquation of the form of solidification simultaneously, thus the object of nanorize administration can be realized, final its dissolubility of raising and bioavailability.
Accompanying drawing explanation
Fig. 1 is the scanning electron microscope pattern of andrographolide nanocrystal intermediate powder particle;
Fig. 2 is the transmission electron microscope pattern of the suspension after andrographolide nanocrystal intermediate redissolves;
Fig. 3 is the DSC phase change characteristics figure of andrographolide nanocrystal intermediate;
Fig. 4 is andrographolide nanocrystal suspension dissolution and the time curve of different-grain diameter scope in embodiment 2.
Detailed description of the invention
Below in conjunction with specific embodiment, embodiment of the present invention are described in detail, only for illustration of the present invention, and should as the restriction to interest field of the present invention.The person that do not mark actual conditions in embodiment, the condition of conveniently conditioned disjunction manufacturer suggestion is carried out.Agents useful for same or instrument do not mark production firm person, are and can buy by market the conventional products obtained.
Embodiment 1: the preparation of different average particle size range (500nm, 600nm, 700nm, 800nm, 900nm) andrographolide nanocrystal suspension
Polyvinylpyrrolidone-the K30 (stabilizing agent I) taking 0.15g adds 100ml water dissolution, add the D-alpha-tocofecol succinic acid macrogol ester (stabilizing agent II) of 0.15g after mix homogeneously again and mix homogeneously, obtain stabiliser solution; Then, be scattered in stabiliser solution by the andrographolide of 0.5g, shear through high speed shear emulsion process, rotating speed is: 13000rpm, and shear time is 5min; Obtained mean diameter is the first suspension of 45 μm; Then above-mentioned just suspension is carried out high pressure homogenize, controlling homogenizing temperature is 10 DEG C, prepares the nanocrystal suspension of different-grain diameter scope respectively by following homogenization:
Homogenization is 1.: first at 200bar, 400bar, 600bar, the each homogenizing of 800bar 5 times, then homogenizing 10 times under 1000bar pressure, finally under 1200bar, homogenizing, respectively at circulation 50 circulation, prepares andrographolide nanocrystal suspension, obtains the nanocrystal of average particle size range at 500nm.
Homogenization is 2.: first at 200bar, 400bar, 600bar, the each homogenizing of 800bar 5 times, then homogenizing 10 times under 1000bar pressure, finally under 1200bar homogenizing respectively at circulation 40 circulation, prepare andrographolide nanosuspension, obtain the nanocrystal of average particle size range at 600nm.
Homogenization is 3.: first at 200bar, 400bar, 600bar, the each homogenizing of 800bar 5 times, then homogenizing 10 times under 1000bar pressure, finally under 1200bar homogenizing respectively at after circulation 30 circulation, prepare andrographolide nanosuspension, obtain the nanocrystal of average particle size range at 700nm.
Homogenization is 4.: first each homogenizing of 200bar, 400bar, 600bar, 800bar 5 times, then after homogenizing 40 circulation, prepare andrographolide nanosuspension, obtain the nanocrystal of average particle size range at 800nm under 1000bar pressure.
Homogenization is 5.: first each homogenizing of 200bar, 400bar, 600bar 5 times, then after homogenizing 40 circulation, prepare andrographolide nanocrystal suspension, obtain the nanocrystal suspension of average particle size range at 900nm under 800bar pressure.
Embodiment 2: the mensuration of different-grain diameter andrographolide nanocrystal suspension saturation solubility
Dissolution determination adopts paddle method, with pH 7.4 phosphate buffered solution 900mL for dissolution medium, and rotating speed 100rmin
-1, bath temperature 37 DEG C, precision pipettes and gets the prepared mean diameter obtained of above-mentioned example 1 is 500nm, 600nm, 700nm, 800nm, the each 10ml of suspension of 900nm, suspension is placed in stripping rotor 0.5min, 1min, 1.5min, 4min, 6min, 1mL is sampled after 10min, 20min, 30min, filter through 0.22 μm of microporous filter membrane, adopting HPLC to measure, is A=29593C (R according to andrographolide standard curve
2=0.9994), the range of linearity 0.0456 ~ 0.0912mg/ml, calculates its dissolution, and its content is in table 1, and the andrographolide nanocrystal suspension dissolution of different-grain diameter scope and time curve are shown in accompanying drawing 4.
The andrographolide nanocrystal suspension dissolution of table 1 different-grain diameter scope compares
| Time (min) | 500nm | 600nm | 700nm | 800nm | 900nm | Crude drug |
| 0.5 | 94.06％ | 90.75％ | 70.66％ | 87.91％ | 76.43％ | 12.31％ |
| 1 | 100.15％ | 92.71％ | 89.58％ | 90.20％ | 79.85％ | 19.42％ |
| 1.5 | 103.06％ | 94.70％ | 91.52％ | 92.05％ | 81.40％ | 22.27％ |
| 4 | 105.26％ | 100.30％ | 93.64％ | 93.04％ | 80.51％ | 29.16％ |
| 6 | 106.95％ | 101.90％ | 98.57％ | 96.93％ | 88.05％ | 32.47％ |
| 10 | 107.13％ | 103.08％ | 97.28％ | 95.06％ | 91.83％ | 33.16％ |
| 20 | 108.21％ | 102.70％ | 99.48％ | 96.51％ | 94.19％ | 33.42％ |
| 30 | 107.64％ | 103.51％ | 99.86％ | 98.21％ | 96.49％ | 34.68％ |
From study in vitro dissolution experimental result, the dissolution of size on andrographolide has appreciable impact.As shown in table 1, only accumulative stripping 35% in crude drug andrographolide 30 minutes, and mean diameter be 900nm, 800nm, 700nm andrographolide nanocrystal suspension 30 minutes in accumulative stripping reach more than 95%.Mean diameter is that the andrographolide nanocrystal suspension of 500nm gets final product 100% complete stripping in 1min.Visible, the change of nanocrystal size can affect dissolution rate, and particle diameter is less, and dissolution rate is faster, and then is conducive to improving bioavailability.
Embodiment 3: the preparation of andrographolide nanocrystal intermediate powder
Experimental technique: get the nanocrystal suspension sample that the mean diameter obtained according to embodiment 1 experimental technique is 500nm, add 1.0g lactose (stabilizing agent III) dispersing and dissolving, then spraying dry rapid solidification techniques is adopted, spraying dry hot blast temperature is 120 DEG C, leaving air temp 60 DEG C, the peristaltic velocity of pump is 5ml/min, and namely dry solidification obtains andrographolide nanocrystal intermediate powder.
Embodiment 4: with andrographolide crude drug for matched group, has carried out the bioavailability study experiment in animal oral administration body, has investigated andrographolide nanocrystal intermediate powder bioavailability in vivo prepared by example 3.Method is by male SD rat 12, be divided into two groups at random, often organize 6, gavage gives the suspension after andrographolide crude drug and andrographolide nanocrystal intermediates diffuse respectively, timing gets blood from eye socket, after process, adopts LC-MS method to measure the blood drug level of andrographolide, calculate pharmacokinetic parameters, result is as shown in table 2:
Bioavailability experimental result in table 2 andrographolide nanocrystal intermediate rat body
Result shows, compared with connecting lactone crude drug with punching, the maximum plasma concentration of andrographolide nanocrystal intermediate powder group significantly increases, and peak time shortens, and area under the drug-time curve significantly increases, and oral administration biaavailability significantly improves.
Embodiment 5: the application of andrographolide nanocrystal intermediate in dispersible tablet formulation processing
Get according to the nanocrystal intermediate powder prepared by the method for embodiment 3, add the micropowder silica gel of 1g fluidizer, after mixing, cross 100 mesh sieves, direct powder compression is compressing obtains nanocrystal dispersible tablet, and hardness is 4.5kg, can disperse by Quick uniform in water, significantly can improve the dissolution in vitro of andrographolide, identical with the dissolution of andrographolide nanocrystal intermediate before tabletting.Recipe quantity is as follows:
Although the specific embodiment of the present invention has obtained detailed description, it will be understood to those of skill in the art that.According to disclosed all instructions, can carry out various amendment and replacement to those details, these change all within protection scope of the present invention.Four corner of the present invention is provided by appended patent requirements and any equivalent thereof.
Claims (8)
1. an andrographolide nanocrystal intermediate, is characterized in that: it is nanocrystal solids powder or particle, is made up of effective ingredient andrographolide and stabilizing agent; It meets the nanocrystal suspension that can form uniform particle diameter after water redissolves, and the average particle size range of andrographolide nanocrystal after disperseing of redissolving in water is 10 ~ 1500nm, span 0.5 ~ 2.5; Preferably 100 ~ 1000nm, span 1 ~ 2; Be more preferably 500 ~ 700nm, span 1.2 ~ 1.6.
2. andrographolide nanocrystal intermediate according to claim 1, is characterized in that: the mass content of andrographolide is 10%-90%; Preferably 20%-70%; Be more preferably 30%-50%; The mass content of stabilizing agent is 0.5%-50%; Preferably 10%-45%; Be more preferably 15%-30%.
3. andrographolide nanocrystal intermediate according to claim 1, is characterized in that: described stabilizing agent comprises stabilizing agent I, and preferably, described stabilizing agent also comprises stabilizing agent II, and more preferably, described stabilizing agent also comprises described stabilizing agent III; Described stabilizing agent I can be lecithin, PLURONICS F87, poloxamer188, Tween 80, sodium deoxycholate, sodium lauryl sulphate, any one of D-alpha tocopherol cetomacrogol 1000 succinate or any multiple mixture; Described stabilizing agent II can be PVP K30, arabic gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose, gelatin, tragakanta, polyvinyl alcohol, any one of sodium carboxymethyl cellulose and microcrystalline Cellulose or its any multiple mixture; Stabilizing agent III can be any one in sucrose, lactose, glucose, trehalose, maltose, mannitol, maltodextrin, sorbitol, Polyethylene Glycol, micropowder silica gel or its any multiple mixture; Particularly preferably, described stabilizing agent I is D-alpha tocopherol cetomacrogol 1000 succinate, and stabilizing agent II is sodium carboxymethyl cellulose/microcrystalline Cellulose, and stabilizing agent III is mannitol.
4. andrographolide nanocrystal intermediate according to claim 3, is characterized in that: the mass content of described stabilizing agent I is 1%-30%, and the mass content of stabilizing agent II is 1%-30%, and the mass content of stabilizing agent III is 10%-70%; Preferably, the mass content of stabilizing agent I is 2%-25%, and the mass content of stabilizing agent II is 2%-25%, and the mass content of stabilizing agent III is 30%-60%; More preferably for the mass content of stabilizing agent I is 5%-15%, the mass content of stabilizing agent II is 5%-15%, and the mass content of stabilizing agent III is 40%-60%.
5. andrographolide nanocrystal intermediate according to any one of Claims 1-4, is characterized in that: preparation method is:
(1) preparation just suspension: by stabilizing agent I water dissolution of formula ratio, adds the stabilizing agent II also mix homogeneously of formula ratio again, obtains stabiliser solution after mix homogeneously; Or by stabilizing agent II water dissolution of formula ratio, add the stabilizing agent I also mix homogeneously of formula ratio after mix homogeneously again, obtain stabiliser solution; Then, be scattered in stabiliser solution by the andrographolide of formula ratio, shear through high speed shear emulsion process, rotating speed is: 10000 ~ 25000rpm, and shear time is 2 ~ 15min; Obtained average particle size range is the first suspension of 20 ~ 150 μm;
(2) prepare nanocrystal suspension: adopt low temperature-high pressure classification homogenizing method, controlling homogenizing temperature is 4 ~ 25 DEG C, respectively circulates 5 ~ 30 times respectively at 200bar, 400bar, 600bar, 800bar; Then circulate 20-50 time under 1000bar ~ 1500bar condition, obtained nanocrystal suspension;
(3) nanocrystal intermediate is prepared: stabilizing agent III dispersing and dissolving adding formula ratio in the nanocrystal suspension of above-mentioned preparation, then spraying dry rapid solidification techniques is adopted, spraying dry hot blast temperature is 105 ~ 150 DEG C, leaving air temp 50-80 DEG C, the peristaltic velocity of pump is 1 ~ 20ml/min, and namely dry solidification obtains nanocrystal intermediate powder.
6. according to the andrographolide nanocrystal intermediate described in claim 5, it is characterized in that: can be applicable in the medicines such as treatment bacillary dysentery, viral pneumonia, viral upper respiratory tract infection, acute tonsillitis.
7. treat a medicine for bacillary dysentery, viral pneumonia, viral upper respiratory tract infection, acute tonsillitis etc., it is characterized in that: it is the dosage form of andrographolide nanocrystal intermediate according to claim 6 containing effective dose and pharmaceutically suitable carrier and/or excipient.
8. the medicine for the treatment of bacillary dysentery according to claim 7, viral pneumonia, viral upper respiratory tract infection, acute tonsillitis etc., it is characterized in that: described dosage form is tablet, dispersible tablet, capsule, granule, suspensoid, dry suspension, powder, inhalant, electuary or pill.
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| CN106038578A (en) * | 2016-05-30 | 2016-10-26 | 江西中医药大学 | Andrographolide and glycyrrhizin dual-drug nano-composite particles and preparation method and application thereof |
| CN106377500A (en) * | 2016-11-22 | 2017-02-08 | 南京中医药大学 | Andrographolide nano suspension and preparation method thereof |
| CN109568265A (en) * | 2017-09-28 | 2019-04-05 | 神威药业集团有限公司 | A kind of andrographolide nano suspension |
| CN109568266A (en) * | 2017-09-28 | 2019-04-05 | 神威药业集团有限公司 | A kind of andrographolide nano suspension |
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| CN115192530A (en) * | 2022-07-14 | 2022-10-18 | 深圳大学 | Diterpene lactone compound and preparation method thereof |
| CN115778907A (en) * | 2022-11-18 | 2023-03-14 | 江西中医药大学 | Andrographolide oral nanocrystal and preparation method and application thereof |
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