CN102961340A - Nanoscale insulin and preparation method thereof - Google Patents
Nanoscale insulin and preparation method thereof Download PDFInfo
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- CN102961340A CN102961340A CN2012105370839A CN201210537083A CN102961340A CN 102961340 A CN102961340 A CN 102961340A CN 2012105370839 A CN2012105370839 A CN 2012105370839A CN 201210537083 A CN201210537083 A CN 201210537083A CN 102961340 A CN102961340 A CN 102961340A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
Abstract
The invention discloses nanoscale insulin and a preparation method thereof, relating to specific medicine insulin for treating diabetes mellitus. In allusion to the defects that the insulin is low in bioavailability for oral administration and the existing insulin injections are severe in toxic and side effects and inconvenient in use, the invention firstly aims at providing a nanoscale insulin particle which can be prepared into an oral preparation; the nanoscale insulin particle is characterized by taking silicon dioxide aerogel as a carrier of the insulin; the invention secondly aims at providing a preparation method of the nanoscale insulin particle; and the preparation method is characterized by comprising the steps of: dissolving the insulin in a 0.01mol/L hydrochloric acid solution, adding the silicon dioxide aerogel, drying for later use after complete adsorption, dissolving PEG (Polyethylene Glycol) in absolute ethyl alcohol, adding the solid obtained via drying and sending into an emulsifying machine for emulsification, drying the obtained emulsified liquid in a constant-temperature drying box, grinding and sieving via a 200-mesh sieve to obtain the nanoscale insulin particle. The nanoscale insulin is especially suitable for oral administration.
Description
Technical field
The present invention relates to treat the specific drug insulin of diabetes, be specifically related to a kind of nanoscale insulin that can be oral and preparation method thereof.
Background technology
Diabetes are to be positioned at a large disease that threatens human health after cardiovascular disease and the cancer.According to pointing out in 1998 ADA's annual reports that diabetics is about 1.35 hundred million people in the world wide at present, by 2025, estimate that diabetics will rise to 300,000,000 people, wherein developed country is increased to 7,200 ten thousand by 5,100 ten thousand, increases by 42%; And developing country is by 8,400 ten thousand 2.28 hundred million people that make a leapleap forward, and amplification reaches 170%.In developed country, U.S.'s diabetics accounts for 5.9% of U.S.'s total population near 1,600 ten thousand, and the U.S. spends 1,000 hundred million dollars every year approximately on prevention and treatment diabetes for this reason.The patient of diabetes Prevalence of China also allows of no optimist.Statistics in 1998 shows that there are more than 2,000 ten thousand diabeticss in China, and sickness rate is 2.5% among 25 years old to 64 years old the crowd.Along with the live change of mode of the day by day aging of China's population and modern, prevention and treatment diabetes have caused widely to be paid close attention to.
Insulin is found at first by the Banting of Canadian that in nineteen twenty-one nineteen twenty-two begins for clinical, is one of the most effective medicine for the treatment of at present diabetes.For a long time, insulin is always take drug administration by injection as main, and insulin is indispensable medicine during I type and middle severe type ii diabetes patient treat every day.Because the insulin biological half-life is short, diabetics needs lifelong every day of subcutaneous injection insulin, frequently be administered to for a long time the patient and bring very large misery and inconvenience, and the long term injections insulin also may produce lipoatrophy, edema etc. occur, and the overdose administration also can cause the multiple untoward reaction such as hypoglycemia shock.Therefore, the insulin preparation of development non-injection administration is the focus of recent domestic research.
Oral administration is the optimal administering mode of insulin, and its main advantage is: (1) simulates the physiological patterns of human pancreas's nature excreting insulin easily; (2) through the metabolism of normal hepatocytes metabolic pathway, the generation that can lower diabetic complication; (3) taking convenience, good patient compliance.
But the regular insulin oral formulations bioavailability without special technical finesse only has 0.1%～0.2%, without clinical meaning.Its main cause have following some: (1) insulin is a kind of peptide hormone, its under the effect of gastric juice sour environment and the various protease of digestive tract, the inactivation of very easily degrading; (2) the insulin molecule amount is about 6000, and intermolecular very strong polymerization trend is arranged, thereby makes it be difficult to be absorbed by the epithelium layer of gastrointestinal wall by diffusion; (3) have liver first-pass effect, bioavailability is low; (4) the insulin conformation problem in the preparation process.The oral administration of insulin is a global difficult problem always.
Nano medication is with medicine dissolution, seals or be adsorbed on the carrier and the microgranule of the nano-scale of making is made nano particle preparations with insulin, can greatly improve the absorption of insulin.Though the research of at present relevant this direction report is many, but still fail fundamentally to solve the low problem of oral administration biaavailability of insulin, after oral, nanoparticle is not absorbed and directly excretes greatly, only has the sub-fraction nanoparticle to be absorbed, if drug absorption is in low-level fluctuation, the percent error of its absorbed dose will be significant so, for a given dose, if the picked-up of microgranule has surpassed desired value, toxicity will produce so; And if the amount that absorbs is less or make drug level be lower than the dosage range for the treatment of, cause treating unsuccessfully.
Summary of the invention
Low for the oral insulin bioavailability, and serious, the awkward defective of existing injection of insulin agent toxic and side effects, first purpose of the present invention provides a kind of nanoscale insulin granule that can be made into oral formulations.
For achieving the above object, the invention provides a kind of nanoscale insulin granule, it is characterized in that: with the carrier of aerosil as insulin.
Further, the mass ratio of described insulin and described aerosil is 1:0.5～20.
In order further to improve the slow releasing function of this nanoscale insulin granule, preferably in granule, add PEG.
Further, the molecular weight of described PEG is 400～20000.
Further, the mass ratio of described PEG and described insulin is 1:05～20.
Above-mentioned nanoscale insulin granule can be made into pharmaceutically acceptable oral formulations.
Further, described oral formulations is tablet, pill, powder, capsule, granule or suspensoid.
Above-mentioned nanoscale insulin granule can be made into pharmaceutically acceptable injection or suppository.
Another object of the present invention provides the preparation method of above-mentioned nanoscale insulin granule, it is characterized in that, said method comprising the steps of:
(1) insulin is dissolved in the hydrochloric acid solution of 0.01mol/L;
(2) in above-mentioned hydrochloric acid solution, add aerosil;
(3) after absorption fully after insulin and the aerosil absorption fully, drying;
(4) PEG is dissolved in the dehydrated alcohol;
(5) solid with the dry gained of step (3) adds in the alcoholic solution of step (4);
(6) alcoholic solution of step (5) is sent into emulsifying in the mulser;
(7) step (6) gained emulsion is dry in thermostatic drying chamber;
(8) solid of the dry gained of grinding steps (7), and cross 200 mesh sieves, namely get the nanoscale insulin granule.
When the aerosil described in the step (2) has hydrophobicity, before adding hydrochloric acid solution, need to make its surperficial alkyl disappearance and have hydrophilic through 300～1000 ℃ of heat treatments first.
Further, the drying described in the step (3) is natural drying or lyophilization.
Aerosil used in the present invention preferably has the aerosil of following characteristic: porosity is 95～99%, the aperture is that 10～50nm, specific surface area are 200～1000m
2/ g, density are 3～300kg/m
3, network consisting colloidal particle diameter be 1～50nm.
Beneficial effect:
1, the present invention has successfully prepared the nanoscale insulin first take aerosil as carrier, different from existing nanoscale insulin, the diameter of this nanoscale insulin has reached the Nano grade of materialogy category below 100nm, be nanoscale insulin truly.Therefore although diameter all is called as nanoparticle less than the particle of 1 μ m, yet people tend to develop particle diameter less than the particle of 100nm, because these particles can show some unique physical propertys, and demonstrate potential different and useful biological characteristics.As, limit by the microcirculation of body blood capillary and barrier cell, can enter blood circulation and then the optimum grain-diameter of the drug particle that absorbed by body is 10～100nm.Therefore, nanoscale insulin of the present invention has had qualitative leap aspect bioavailability.
2, the drug loading of nanoscale insulin granule of the present invention can reach more than 90%, that existing liposome nano granule, polymer nanoparticle etc. are too far behind to catch up, its drug loading can compare favourably with nanometer crystal formation pharmaceutical suspension, but manufacture method is simpler, and cost is cheaper.
3, in the nanoscale insulin granule of the present invention, insulin is loaded in the countless nanoscale hole of aerosil, form the independence " Nanodispersion " that can not reunite, structure is extremely stable, and directly having cracked in the micro-nano drug research can not patent medicine because reuniting, insoluble medicine is difficult to improve the galenic pharmacy international headaches such as bioavailability.
4, oral insulin is regarded as the most significant end technology of pharmaceutical field always, and many decades is attacked for a long time and is unable to.Nanoscale insulin provided by the invention, realized the brand-new oral mechanism take the nanometer picked-up as main absorption pattern, again with the brand new of " nano-solid dispersion " so that the drug effect of insulin increases greatly, be able to oral absorption, broken through the international forbidden zone that oral insulin can't absorb.Directly realized first the bioavailability of oral replacement injection in the material aspect.The appearance that the oral insulin dosage form replaces injection type brings the revolutionary advancement for the treatment of diabetes medicament.Peroral dosage form has overcome injection type complicate fabrication process, workshop appliance and packing instructions height, the high defective of production cost simultaneously.
5, in the nanoscale insulin of the present invention as the precursor of the employed aerosil of carrier for cheap, be easy to get and extensive use in medicine and food, use silica-based medicine edible adjuvant for many years with country and international standard, it also is that " one of adjuvant of putting down in writing in the pharmaceutic adjuvant handbook is so the safety of nanoscale insulin of the present invention is reliable.
Test to illustrate that below by the treatment of diabetic mice nanoscale insulin of the present invention is to the therapeutic effect of diabetes:
1 materials and methods
1.1 instrument and material
Insulin (27.8u/mg, Jiangsu Wan Bang Biomedics Inc.), aerosil, PEG 600, and PEG 4000, and PEG 6000, PEG10000, hydrochloric acid, dehydrated alcohol are the AR level;
Mice, BALB/c, the SPF level, male, body weight 16 ± 2g, Guangdong Medical Lab Animal Center provides, the quality certification number: SCXK(Guangdong) 2008-0002;
Freezer dryer, Beijing rich doctor health experimental apparatus company limited; Constant Temp. Oven; The ultrasonic emulsification machine; Blood glucose meter, Roche Holding Ag; Blood sugar test paper, Roche Holding Ag; The Semilente Insulin injection, Jiangsu Wan Bang Biomedics Inc.; The Novolin 30R injection, Denmark Novo Nordisk Co.,Ltd.
1.2 method
1.2.1 get 50 of mices, male, fasting 12h, precision takes by weighing STZ 200mg, with the citric acid solution dissolving, respectively to the mouse peritoneal injection, then normally raises mice 6 days with 200mg/kg dosage, mouse blood sugar is raise form the diabetes pathological model.
1.2.2 with 27 of the diabetic mices of above-mentioned injection STZ, fasting is divided into 9 groups at random after 8 hours, every group 3, the A group is Normal group, the B group is subcutaneous injection Semilente Insulin (3U/kg), the C group is subcutaneous injection Novolin 30R (3U/kg), D group is subcutaneous injection Nanometer Insulin-PEG600(3U/kg), E group is oral administration nanometer insulin-PEG600(1000U/kg), F group is subcutaneous injection Nanometer Insulin-PEG4000(3U/kg), the G group is oral administration nanometer insulin PEG-4000(1000U/g), H group is subcutaneous injection Nanometer Insulin-PEG6000(3U/kg), and the I group is oral administration nanometer insulin-6000(1000U/kg), respectively at before the administration with administration after 0.5h, 1h, 2h, 3h, 4h, 6h, 8h, mice is cut tail and gets blood, with the variation of blood glucose meter measuring blood.
2 experimental results
2.1 experimental result data adopts blood glucose value to represent that measurement result sees Table 1.
Table 1 Nanometer Insulin is to the therapeutic effect of diabetic mice
2.2 take administration time as abscissa, blood glucose value sees Fig. 4 and Fig. 5 as vertical coordinate is depicted as chart with the data in the table 1.
3 discussion of results
3.1 the subcutaneous injection Nanometer Insulin is compared with two kinds of commodity insulin injections, nano injection Insulin 3 u/kg(PEG600, PEG4000, PEG6000) obvious blood sugar decreasing effect is all arranged, wherein PEG600 and two kinds of commodity insulins more all have goodish hypoglycemic effect;
3.2 the oral administration nanometer insulin is compared with two kinds of commodity insulin injections, and obvious hypoglycemic effect is arranged, linear blood sugar lowering behavior in front 3 hours, but hypoglycemic effect is lower than injection commodity group.After 3 hours, hypoglycemic effect is better than two kinds of commodity insulin injections, and drug effect steadily keeps more than 5 hours, and having pointed out oral administration nanometer insulin of the present invention is the good long-acting hypoglycemic medicine of curative effect.
Description of drawings
Fig. 1 is the Electronic Speculum picture that the present invention uses aerosil;
Fig. 2 is the Electronic Speculum picture of insulin raw material medicine;
Fig. 3 is the Electronic Speculum picture of nanoscale insulin of the present invention;
Fig. 4 is the treatment contrast of nano injection insulin of the present invention and commodity injection;
Fig. 5 is the treatment contrast of nano oral insulin of the present invention and commodity injection.
The specific embodiment
The present invention is described in further detail below in conjunction with accompanying drawing, and following examples are explanation of the invention, and the present invention is not limited to following examples.
Embodiment 1
The nanoscale insulin of present embodiment prepares by the following method:
1, insulin raw material medicine (Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.) 1g, the AR grade hydrochloric acid 50ml that adds 0.01mol/L dissolves;
2, the aerosil 5g behind 800 ℃ of heat treatments of adding adsorbs;
3, after adsorbing fully, with the dry 4h of freezer dryer;
4, the PEG-600 that gets in addition 5g adds in the dehydrated alcohol of 1000ml and dissolves;
5, the solid after step 3 lyophilizing is added in the alcoholic solution of above-mentioned PEG-600 ultrasonic emulsification machine emulsifying 3min;
6, with emulsion dry 12h in 60 ℃ of Constant Temp. Ovens of step 5;
7, grinding steps 6 dried solids, and cross 200 mesh sieves, obtain the nanoscale insulin granule.
Embodiment 2
The nanoscale insulin of present embodiment prepares by the following method:
1, insulin raw material medicine (Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.) 1g, the AR grade hydrochloric acid 100ml that adds 0.01mol/L dissolves;
2, the aerosil 10g behind 500 ℃ of heat treatments of adding adsorbs;
3, after adsorbing fully, natural drying 24h;
4, the PEG-400 that gets in addition 10g adds in the dehydrated alcohol of 2000ml and dissolves;
5, the dried solid of step 3 is added in the alcoholic solution of above-mentioned PEG-400 ultrasonic emulsification machine emulsifying 3min;
6, with emulsion dry 12h in 60 ℃ of Constant Temp. Ovens of step 5;
7, grinding steps 6 dried solids, and cross 200 mesh sieves, obtain the nanoscale insulin granule.
Embodiment 3
The nanoscale insulin of present embodiment prepares by the following method:
1, insulin raw material medicine (Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.) 1g, the AR grade hydrochloric acid 5ml that adds 0.01mol/L dissolves;
2, the aerosil 0.5g behind 1000 ℃ of heat treatments of adding adsorbs;
3, after adsorbing fully, with the dry 3h of freezer dryer;
4, the PEG-6000 that gets in addition 0.5g adds in the dehydrated alcohol of 800ml and dissolves;
5, the dried solid of step 3 is added in the alcoholic solution of above-mentioned PEG-6000 ultrasonic emulsification machine emulsifying 3min;
6, with emulsion dry 12h in 60 ℃ of Constant Temp. Ovens of step 5;
7, grinding steps 6 dried solids, and cross 200 mesh sieves, obtain the nanoscale insulin granule.
Embodiment 4
The nanoscale insulin of present embodiment prepares by the following method:
1, insulin raw material medicine (Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.) 1g, the AR grade hydrochloric acid 200ml that adds 0.01mol/L dissolves;
2, the aerosil 20g behind 300 ℃ of heat treatments of adding adsorbs;
3, after adsorbing fully, natural drying 24h;
4, the PEG-10000 that gets in addition 20g adds in the dehydrated alcohol of 1500ml and dissolves;
5, the dried solid of step 3 is added in the alcoholic solution of above-mentioned PEG-10000 ultrasonic emulsification machine emulsifying 3min;
6, with emulsion dry 12h in 60 ℃ of Constant Temp. Ovens of step 5;
7, grinding steps 6 dried solids, and cross 200 mesh sieves, obtain the nanoscale insulin granule.
Embodiment 5
The nanoscale insulin of present embodiment prepares by the following method:
1, insulin raw material medicine (Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.) 1g, the AR grade hydrochloric acid 150ml that adds 0.01mol/L dissolves;
2, the aerosil 15g behind 400 ℃ of heat treatments of adding adsorbs;
3, after adsorbing fully, dry 10h in 60 ℃ of Constant Temp. Ovens;
4, the PEG-20000 that gets in addition 15g adds in the dehydrated alcohol of 1500ml and dissolves;
5, the dried solid of step 3 is added in the alcoholic solution of above-mentioned PEG-10000 ultrasonic emulsification machine emulsifying 3min;
6, with emulsion dry 12h in 60 ℃ of Constant Temp. Ovens of step 5;
7, grinding steps 6 dried solids, and cross 200 mesh sieves, obtain the nanoscale insulin granule.
Embodiment 6
The nanoscale insulin of present embodiment prepares by the following method:
1, insulin raw material medicine (Jiangsu Wanbang Biological Pharmaceutical Co., Ltd.) 1g, the AR grade hydrochloric acid 50ml that adds 0.01mol/L dissolves;
2, adding hydrophilic aerosil 5g adsorbs;
3, after adsorbing fully, with the dry 4h of freezer dryer;
4, the PEG-4000 that gets in addition 5g adds in the dehydrated alcohol of 1000ml and dissolves;
5, the solid after step 3 lyophilizing is added in the alcoholic solution of above-mentioned PEG-600 ultrasonic emulsification machine emulsifying 3min;
6, with emulsion dry 12h in 60 ℃ of Constant Temp. Ovens of step 5;
7, grinding steps 6 dried solids, and cross 200 mesh sieves, obtain the nanoscale insulin granule.
Embodiment 7
Behind the nanoscale insulin granule that embodiment 1 to 6 obtains and an amount of microcrystalline Cellulose, starch and the magnesium stearate mix homogeneously, use the tablet machine tabletting, obtain nanoscale insulin tablet of the present invention.
Embodiment 8
The nanoscale insulin granule that embodiment 1 to 6 is obtained directly is packed in the hard capsule case, obtains nanoscale insulin capsule of the present invention.
Embodiment 9
The nanoscale insulin granule that embodiment 1 to 6 obtains adds in the aqueous solution, stirs, and obtains nanoscale insulin suspension of the present invention.This suspension can be directly oral, also can make injection according to the preparation standard of injection.
Embodiment 10
The nanoscale insulin granule that embodiment 1 to 6 obtains and an amount of Witepsol adopt hot melt to prepare nanoscale insulin suppository of the present invention.
Claims (10)
1. a nanoscale insulin granule is characterized in that: with the carrier of aerosil as insulin.
2. nanoscale insulin granule according to claim 1, it is characterized in that: the mass ratio of described insulin and described aerosil is 1:0.5～20.
3. nanoscale insulin granule according to claim 1, it is characterized in that: described nanoscale insulin granule also comprises PEG.
4. nanoscale insulin granule according to claim 3, it is characterized in that: the molecular weight of described PEG is 400～20000.
5. according to claim 3 or 4 described nanoscale insulin granules, it is characterized in that: the mass ratio of described PEG and described insulin is 1:0.5～20.
6. the pharmaceutically acceptable oral formulations of making to the described nanoscale insulin granule of 5 any one according to claim 1.
7. oral formulations according to claim 6, it is characterized in that: described oral formulations is tablet, pill, powder, capsule, granule or suspensoid.
8. pharmaceutically acceptable injection or the suppository made to the described nanoscale insulin granule of 5 any one according to claim 1.
9. the preparation method of claim 3,4 or 5 described nanoscale insulin granules is characterized in that, said method comprising the steps of:
(1) insulin is dissolved in the hydrochloric acid solution of 0.01mol/L;
(2) in above-mentioned hydrochloric acid solution, add aerosil;
(3) after insulin and aerosil absorption fully, drying;
(4) PEG is dissolved in the dehydrated alcohol;
(5) solid with the dry gained of step (3) adds in the alcoholic solution of step (4);
(6) alcoholic solution of step (5) is sent into emulsifying in the mulser;
(7) step (6) gained emulsion is dry in thermostatic drying chamber;
(8) solid of the dry gained of grinding steps (7), and cross 200 mesh sieves, namely get the nanoscale insulin granule.
10. the preparation method of nanoscale insulin granule claimed in claim 9, it is characterized in that: when the aerosil described in the step (2) has hydrophobicity, before adding hydrochloric acid solution, need to make it have hydrophilic through 300～1000 ℃ of heat treatments first.
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| CN201210537083.9A CN102961340B (en) | 2012-12-13 | 2012-12-13 | Nanoscale insulin and preparation method thereof |
| PCT/CN2013/089150 WO2014090167A1 (en) | 2012-12-13 | 2013-12-11 | Nanoscale insulin and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014090185A1 (en) * | 2012-12-13 | 2014-06-19 | 清华大学深圳研究生院 | Application of silicon dioxide aerogel in pharmacy |
| WO2017075777A1 (en) * | 2015-11-05 | 2017-05-11 | 清华大学深圳研究生院 | Method for preparing nanoscale pesticide preparation by using silica aerogel |
| CN107375244A (en) * | 2017-09-12 | 2017-11-24 | 吉林大学珠海学院 | A kind of nanoscale docetaxel and preparation method thereof |
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| CN101829331A (en) * | 2010-05-28 | 2010-09-15 | 沈阳药科大学 | Three-dimensionally ordered macroporous silicon dioxide medicament administration system suitable for slightly soluble medicament |
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| US9125872B2 (en) * | 2009-10-13 | 2015-09-08 | Yosry A. Attia | Polyethylene glycol aerogels for targeted delivery of pharmaceutical drubs |
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| CN101111225A (en) * | 2005-02-03 | 2008-01-23 | 金文申有限公司 | Drug delivery materials made by sol/gel technology |
| CN101829331A (en) * | 2010-05-28 | 2010-09-15 | 沈阳药科大学 | Three-dimensionally ordered macroporous silicon dioxide medicament administration system suitable for slightly soluble medicament |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014090185A1 (en) * | 2012-12-13 | 2014-06-19 | 清华大学深圳研究生院 | Application of silicon dioxide aerogel in pharmacy |
| WO2017075777A1 (en) * | 2015-11-05 | 2017-05-11 | 清华大学深圳研究生院 | Method for preparing nanoscale pesticide preparation by using silica aerogel |
| CN107375244A (en) * | 2017-09-12 | 2017-11-24 | 吉林大学珠海学院 | A kind of nanoscale docetaxel and preparation method thereof |
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| CN102961340B (en) | 2014-08-13 |
| WO2014090167A1 (en) | 2014-06-19 |
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