CN102718254A - Mesoporous titanium dioxide and preparation method thereof and application thereof - Google Patents
Mesoporous titanium dioxide and preparation method thereof and application thereof Download PDFInfo
- Publication number
- CN102718254A CN102718254A CN2012101119485A CN201210111948A CN102718254A CN 102718254 A CN102718254 A CN 102718254A CN 2012101119485 A CN2012101119485 A CN 2012101119485A CN 201210111948 A CN201210111948 A CN 201210111948A CN 102718254 A CN102718254 A CN 102718254A
- Authority
- CN
- China
- Prior art keywords
- mesoporous tio
- preparation
- medicine
- mesoporous
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of medicine technology, and relates to a preparation method of mesoporous titanium dioxide with high biological compatibility and a controllable structure and application of the mesoporous titanium dioxide as a hard soluble drug carrier. The method adopts a soft template method, namely, adopts a surfactant as a structure guiding agent, isopropyl titanate as titanium source, and double distilled water as a reaction rate modifier to prepare the mesoporous titanium dioxide having different mesoporous passage structures. The prepared mesoporous titanium dioxide is of large specific surface area, chemical stability, non-toxic effect, no side effect and good biocompatibility, and is suitable for being used as the hard soluble drug carrier. The application of the titanium dioxide as the hard soluble drug carrier can lay a theoretical foundation for uses of multivariant functional carriers. The method adopts a solvent method and a fusion method to perform embedding and adsorption on a drug so as to uniformly disperse the drug inside the mesoporous or on surface of the carrier. The drug carrier system can assist in significantly enhancing water solubility of a hard soluble drug and improving dissolution rate in vitro and oral bioavailability.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of mesoporous TiO 2 with height bio-compatibility and controllable structure, preparation method and as the application of insoluble drug carrier.
Background technology
Oral prepns is the first-selected route of administration of present most drug because advantages such as conformability is strong, safety, convenience are prone to accepted and employing by patient.Yet it is the medicine of slightly water-soluble that the medicine more than 1/3 is arranged in including the maximum USP of medicine; In original new drug research, it is poorly water soluble drugs that 40% medicine is arranged approximately simultaneously, and these medicines are owing to poorly water-soluble, and gi tract stripping difficulty has influenced its oral administration biaavailability greatly.Especially the II class medicine during biopharmacy is classified, promptly indissoluble is separated the medicine that is prone to absorption, and dissolution rate just becomes the principal element that influences its oral administration biaavailability during oral application.Therefore will make insoluble drug bring into play drug effect to greatest extent, the solubleness and the bioavailability of how to employ new technology and improving such medicine are the new drug initiatives and have the great problem in science that solution is needed in the efficacy of drugs improvement badly now.
Titanium oxide is widely used in every field such as medicine, environment and photochemistry because it has the bio-compatibility, chemicalstability of height, the characteristics such as valence-band level of nontoxic and broad.Titanium oxide is mainly as opalizer and embedding dose and be used in pharmaceutics.Yet as the insoluble drug carrier, be used to improve the dissulution of insoluble drug and relevant report is not seen in the research of bioavailability, mesoporous TiO 2 has profound significance as the research of pharmaceutical carrier for the excipient substance of development of new.
Summary of the invention
The objective of the invention is:
1, a kind of mesoporous TiO 2 with height bio-compatibility and controllable structure is provided;
2, a kind of novel method for preparing mesoporous TiO 2 is provided;
3, the application of mesoporous TiO 2 as insoluble drug carrier aspect is provided;
4, a kind of mesoporous TiO 2 drug delivery system that is applicable to insoluble drug is provided.
Get a certain amount of mass concentration and be 95% isopropyl titanate and distilled water, be added drop-wise in an amount of absolute ethyl alcohol, stir and solution was fully reacted in 1-2 hour.Leave standstill 24-48h, centrifugal collecting precipitate, drying promptly gets mesoporous TiO 2.
Preferred pluronic F127 of described tensio-active agent or hexadecylamine HAD, the consumption of F127 are between 12～20 grams, preferred 16g, and between hexadecylamine HAD consumption 2～6 grams, preferred 4g; The method of said Centrifugical extraction preferably adopts 60 ℃ of absolute ethyl alcohols to clean repeatedly 6～9 times.
More than among two kinds of preparing methods: the volume ratio of isopropyl titanate and distilled water is 2.5:1～3.5:1, and preferred isopropyl titanate and distilled water volume ratio are 2.9:1.
In order to control the diameter of titania nanoparticles, also can add a spot of 0.1mol/L Klorvess Liquid, the volume ratio 5:1 of isopropyl titanate and Repone K～6:1; The volume ratio of preferred isopropyl titanate and Repone K is 5.8:1.
The mesoporous TiO 2 that the present invention prepares has the aperture structure of lower density, higher specific surface area and homogeneous, and can obtain having the mesoporous TiO 2 in different specific surface areas and aperture through control prescription and processing condition.Concrete pattern is seen Fig. 1 and Fig. 2 in the description of drawings.
The advantage of this kind structure is: (1) nano pore can be controlled drug particle at nano-scale; Improve the specific surface area and the dispersiveness of medicine; Can make medicine change amorphous or amorphous into behind the medicine carrying, thereby improve its solubleness and dissolution rate from crystal form; (2) titanium dioxide nano granule of preparation has the pore passage structure that is connected with each other, thereby this structure can effectively reduce the dissolution rate of the duct resistance raising medicine of medicine when discharging from the duct; (3) mesoporous TiO 2 of the present invention not only contains bigger specific surface area has good spherical pattern again simultaneously, and this has increased the drug loading of this material greatly; (4) titanium oxide has good chemically stable and physiological compatibility, can not kept original pattern and pore passage structure in the digestive process in vivo by GI enzyme liberating in vivo; (5) controllability of the inner pore passage structure of titanium oxide and surface modificability can effectively be controlled medicine at a year intravital form and the release behavior of existing.The mesoporous TiO 2 of the present invention's preparation is suitable for as the insoluble drug carrier.
The present invention also provides a kind of mesoporous TiO 2 drug delivery system that is applicable to insoluble drug, at the drug delivery system Chinese traditional medicine all with amorphous or mainly exist with unbodied form.
Said insoluble drug is meant to have than low water solubility and higher fat-soluble biologically active substance; Belong to biopharmacy categorizing system (biopharmaceutics classification system; BCS)
type medicine; It is characterized in that, poorly water-soluble, dissolution rate is low; Transmembrane transport is good, and oral administration biaavailability is low.
The medicine-carrying method for preparing said drug delivery system employing has solvent method and scorification, and specific embodiments is following:
(1) solvent method medicine carrying: medicine dissolution is processed certain concentration solution in volatile solvent, adds a certain amount of mesoporous TiO 2, ultrasonic its homodisperse that makes; The room temperature air tight condition stirs more than the balance 8h down; Centrifugal, the collecting precipitation thing is drying to obtain medicine-carried system.
(2) scorification medicine carrying: it is even that medicine and carrier are measured physical mixed in proportion, places temperature in the oil bath more than drug melting point 5-15 ℃, places ice bath or liquid nitrogen quenching after making the medicine fusion.
The drug delivery system that the present invention is constructed in the dissolution medium of medicine regulation, has the characteristic of snap-out release, and external dissolution test result shows that cumulative leaching rate is not less than 75% in 20min or the shorter time.
This drug delivery system realizes that medicine exists with amorphous or unbodied form, reduces the particle diameter of medicine, increases its wetting ability, thereby improves the dissolution rate and the oral administration biaavailability of insoluble drug.When being used for oral administration, gained pressed powder or particle can directly use, and are perhaps guaranteeing to carry out capsular filling, compressing tablet or dressing under the constant prerequisite of medicine snap-out release characteristic, if desired can be enteric coated.
The invention has the beneficial effects as follows: the present invention is directed to poorly water soluble drugs; The characteristics that bioavailability is low; Developed the novel vector of a kind of novel mesoporous TiO 2 targetedly, prepared the preparation that is fit to oral administration through solvent method and scorification as insoluble drug.The carrier of preparing has that structure height is controlled, even particle size, specific surface area are big, good fluidity, have no side effect, physiological compatibility is good and advantage such as non-degradable, this makes mesoporous TiO 2 become the ideal carrier of oral insoluble drug.Technological operation simultaneously is simple, easy to implement.The present invention is used to solve the insoluble drug poorly water-soluble with porous inorganic carrier as the stronger carrier of a kind of versatility; The difficult problem that oral administration biaavailability is low; Expand the application of new inorganic material, for the development of pharmaceutics provides a new way in the pharmaceutics field.
Description of drawings
Below in conjunction with accompanying drawing and embodiment the present invention is further specified.
Fig. 1 A is the electron scanning micrograph of the mesoporous TiO 2 of embodiment 1 preparation; Fig. 1 B is the transmission electron microscope photo of the mesoporous TiO 2 of embodiment 1 preparation, can find out that the mesoporous TiO 2 of embodiment 1 preparation contains the duct that vermiform is connected with each other.Fig. 1 C is the electron scanning micrograph of the mesoporous TiO 2 of embodiment 5 preparations; Fig. 1 D is the transmission electron microscope photo of the mesoporous TiO 2 of embodiment 5 preparations, can find out that slitlike duct is contained on the mesoporous TiO 2 surface of embodiment 5 preparations.
Fig. 2 A and B are the electron scanning micrographs of the mesoporous TiO 2 of embodiment 2 preparations, and Fig. 2 C and D are the transmission electron microscope photos of the mesoporous TiO 2 of embodiment 2 preparations, and visible mesoporous TiO 2 is the globosity of loose cotton shape.
Fig. 3 A and B are the electron scanning micrographs of the mesoporous TiO 2 of embodiment 3 preparations; Fig. 3 C and D are the transmission electron microscope photos of the mesoporous TiO 2 of embodiment 3 preparations, and visible mesoporous TiO 2 is globosity of uniform size and duct distribution homogeneous.Can find out through Fig. 1, Fig. 2 and Fig. 3,, can well control the pore passage structure of mesoporous TiO 2 through the control reaction conditions.
Fig. 4 is the adsorption isothermal line of the mesoporous TiO 2 nitrogen absorption of embodiment 1, embodiment 2 and embodiment 3 preparations.Wherein carrier 1 is the mesoporous TiO 2 of preparing among the embodiment 1; Carrier 2 is mesoporous TiO 2s of preparing among the embodiment 2; Carrier 3 is mesoporous TiO 2s of embodiment 3 preparations, can find out that the CONTROL PROCESS condition can prepare Jie's titanium oxide of different pore sizes and different specific surface areas.
Fig. 5 be carvedilol bulk drug, mesoporous TiO 2 and carvedilol bulk drug according to embodiment 8 medicine carryings after the differential calorimetric scanning spectra of system.The result shows when the ratio of carrier 2 (embodiment 2 preparations) and carrier 3 (embodiment 3 preparations) and carvedilol bulk drug is 2:1; Still contain a spot of drug crystallization in the sample; When the ratio of carrier 2 and carrier 3 and carvedilol bulk drug was 3:1, bulk drug then was present in the carrier with unbodied form fully, thereby can find out; The maximum effectively medicine carrying ratio of the mesoporous TiO 2 of embodiment 2 and embodiment 3 preparations is 3:1 (25% carrier/drug, a mass percent).And the ratio of carrier 1 (embodiment 1 preparation) and carvedilol bulk drug still contains a spot of drug crystallization in the sample when being 1:2 (mass percent); When the ratio of carrier 1 and bulk drug is 1:1 (mass percent); Bulk drug then is present in the carrier with unbodied form fully; Thereby can find out that the maximum effectively medicine carrying ratio of the mesoporous TiO 2 of embodiment 1 preparation is 1:1 (50% carrier/drug, a mass percent).The result shows that bigger specific surface area can improve the drug loading of carrier.
Fig. 6 be physical mixture and mesoporous TiO 2 and the carvedilol bulk drug of mesoporous TiO 2 bare, carvedilol bulk drug and carrier according to embodiment 8 medicine carryings after the X ray diffracting spectrum of system.Wherein carrier 1 is the mesoporous TiO 2 that embodiment 1 prepares; Carrier 2 is mesoporous TiO 2s that embodiment 2 prepares; Carrier 3 is mesoporous TiO 2s that embodiment 3 prepares, and can find out with bulk drug and compare, and the system drug main will exist with unbodied form behind the medicine carrying.Show that carrier can effectively change the crystal formation of medicine, makes it be present in the carrier with unbodied state.
Fig. 7 is the carvedilol bulk drug, according to the carvedilol/mesoporous TiO 2 medicine-carried system of embodiment 8 methods preparations, the external stripping curve in pH 1.2 hydrochloric acid solns (SGF).The result shows, compares with bulk drug, and the system release rate of drugs is obviously accelerated behind the medicine carrying.
Fig. 8 is the carvedilol bulk drug, according to the external stripping curve of carvedilol/mesoporous TiO 2 medicine-carried system in pH 6.8 hydrochloric acid solns (simulated intestinal fluid) of embodiment 8 methods preparations.The result shows, compares with bulk drug, and the system release rate of drugs is obviously accelerated behind the medicine carrying.
Fig. 9 is the oral carvedilol commercial tablets of beagle dog and according to the Plasma Concentration-time plot of the preparation of embodiment 15 preparation.With respect to commercial tablets, preparation preparation (embodiment 15) bioavailability obviously improves.(dosage: 3.2 mg/kg), the oral administration peak time of preparation group obviously shifts to an earlier date (being advanced to 0.45h by 1h), and oral administration biaavailability significantly improves (being increased to 2.394 mg/L h by 1.875 mg/L h).
Embodiment
Embodiment 1
Accurately get 15.8g F127 and join in the 400ml absolute ethyl alcohol, it is dissolved fully, add 9.25ml isopropyl titanate and 3.2ml distilled water; Static 24h behind the at room temperature lasting stirring 40min, centrifugal collecting precipitate stirs throw out after adding an amount of absolute ethyl alcohol in the centrifuge tube gently; Centrifugal collecting precipitate, 3 times repeatedly, with throw out as for 50 ℃ of oven drying 24h; Dried sample adds the 200ml absolute ethyl alcohol as in the Erlenmeyer flask, under the condition of 70 ℃ of water-baths, stirs 2h; Centrifugal collection throw out, throw out add in the Erlenmeyer flask, after the repetition aforesaid operations amounts to 3 times; With throw out as for 50 ℃ of oven drying 24h; The dry sample that obtains adds and continues in the Erlenmeyer flask to clean 2 times, after the cleaning with throw out as for 50 ℃ of oven drying 24h, clean so repeatedly and remove tensio-active agent F127 for three times and promptly obtain mesoporous spherical titanium dioxide.
Accurately getting 9.25ml isopropyl titanate and 1.6ml Klorvess Liquid joins in the 400ml absolute ethyl alcohol; Static 24h behind the at room temperature lasting stirring 40min, centrifugal collecting precipitate stirs throw out after adding an amount of absolute ethyl alcohol in the centrifuge tube gently; Centrifugal collecting precipitate; 3 times repeatedly, throw out as for 50 ℃ of oven drying 24h, is promptly obtained mesoporous loose spherical titanium dioxide after the drying.
Embodiment 3
Accurately getting 15.8g F127 joins in the 400ml absolute ethyl alcohol; It is dissolved fully, add 9.25ml isopropyl titanate and 3.2ml distilled water, static 24h behind the at room temperature lasting stirring 40min; Centrifugal collecting precipitate; Throw out is stirred centrifugal collecting precipitate, 3 times repeatedly gently after adding an amount of absolute ethyl alcohol in the centrifuge tube; Throw out is removed tensio-active agent F127 with dried sample in 400 ℃ of high-temperature calcination 4h and is obtained spherical mesoporous titanium oxide as for 50 ℃ of oven drying 24h the most at last.
Accurately getting 15.8g F127 joins in the 400ml absolute ethyl alcohol; It is dissolved fully, add 9.25ml isopropyl titanate and 1.6ml distilled water, static 24h behind the at room temperature lasting stirring 40min; Centrifugal collecting precipitate; Throw out is stirred centrifugal collecting precipitate, 3 times repeatedly gently after adding an amount of absolute ethyl alcohol in the centrifuge tube; Throw out is removed tensio-active agent F127 with dried sample in 400 ℃ of high-temperature calcination 4h and is obtained ball-type mesoporous sphere titanium oxide as for 50 ℃ of oven drying 24h the most at last.
Embodiment 5
Accurately get 4g HDA and join in the 400ml absolute ethyl alcohol, it is dissolved fully, add 9.25ml isopropyl titanate and 2.2ml Klorvess Liquid; Static 24h behind the at room temperature lasting stirring 40min, centrifugal collecting precipitate stirs throw out after adding an amount of absolute ethyl alcohol in the centrifuge tube gently; Centrifugal collecting precipitate, 3 times repeatedly, throw out is as for 50 ℃ of oven drying 24h the most at last; Dried sample is got 1.6g as in the autoclave, add 20ml absolute ethyl alcohol and 10ml ammoniacal liquor (0.45M), 160 ℃ of reacting by heating 16h; With sample filtering; Absolute ethyl alcohol cleans 3 times, and sample is as for 50 ℃ of oven drying 24h the most at last, and dried sample is removed tensio-active agent F127 in 400 ℃ of high-temperature calcination 4h and obtained mesoporous sphere titanium oxide.
Embodiment 6
Accurately get 2.4g HDA and join in the 240ml absolute ethyl alcohol, it is dissolved fully, add 5.55ml isopropyl titanate and 0.96ml Klorvess Liquid; Add distilled water 1.92ml simultaneously, static 24h behind the at room temperature lasting stirring 40min, centrifugal collecting precipitate; Throw out is stirred centrifugal collecting precipitate, 3 times repeatedly gently after adding an amount of absolute ethyl alcohol in the centrifuge tube; Throw out is got 1.6g as in the autoclave as for 50 ℃ of oven drying 24h with dried sample the most at last, adds 20ml absolute ethyl alcohol and 10ml ammoniacal liquor (0.45M); 160 ℃ of reacting by heating 16h, with sample filtering, absolute ethyl alcohol cleans 3 times; Sample is as for 50 ℃ of oven drying 24h the most at last, and dried sample is removed tensio-active agent F127 in 500 ℃ of high-temperature calcination 4h and obtained mesoporous cotton-shaped titanium oxide.
Embodiment 7
Accurately get 2.4g HDA and join in the 240ml absolute ethyl alcohol, it is dissolved fully, add 5.55ml isopropyl titanate and 0.96ml Klorvess Liquid; Add distilled water 1.92ml simultaneously; Static 24h behind the at room temperature lasting stirring 40min, centrifugal collecting precipitate stirs throw out after adding an amount of absolute ethyl alcohol in the centrifuge tube gently; Centrifugal collecting precipitate, dried sample is removed tensio-active agent F127 in 400 ℃ of high-temperature calcination 4h and is obtained mesoporous cotton-shaped titanium oxide.
Embodiment 7
With embodiment 1, embodiment 2 does specific surface area analysis mensuration with the meso-porous titanium dioxide titanium carrier that embodiment 4 prepares, and sees accompanying drawing 4.
Adopt the solvent evaporation method medicine carrying.Precision takes by weighing about 30mg carvedilol, is dissolved in the 3ml chloroform, obtains the chloroformic solution of medicine.Take by weighing 30mg respectively, 60mg, 90mg mesoporous TiO 2; Join 3ml and contain the chloroformic solution of medicine, make medicine: the carrier ratio is respectively 0.5:1,1:1; 1:2,1:3 mixes balance 8h; Be heated to 50 ℃ of volatilizations and remove organic solvent, vacuum-drying obtains the titanium oxide drug delivery system of medicine carrying.
Adopt the scorification medicine carrying.The meso-porous titanium dioxide titanium carrier that precision takes by weighing about 50mg model drug (carvedilol) and 150mg with the mortar uniform mixing after; Insert in the aluminium ware; Be placed in 130 ℃ of oil baths; Heat about 10min, put into quenching in the mixture of ice and water after waiting the whole fusions of medicine, obtain the poriferous titanium dioxide drug delivery system of medicine carrying.
Confirm maximum effectively drug loading.Get embodiment 1; Embodiment 2 is a carrier with the mesoporous TiO 2 of embodiment 4 preparations; Adopt the medicine-carrying method of embodiment 8; Wherein embodiment 1 is the ratio sample of 2:1 and 3:1 with the ratio of embodiment 4 carriers and bulk drug carvedilol, and other gets carrier and bulk drug ratio is that ratio physical mixed, the bulk drug of 3:1 done the differential scanning calorimetric in order to the definite existence of bulk drug in carrier.The ratio of embodiment 2 carriers and bulk drug is 1:1 and 0.5:1.Detailed data is seen accompanying drawing 5.
Embodiment 11
Confirming of drug loading; Get embodiment 1 respectively, embodiment 2 is a carrier with the mesoporous TiO 2 that embodiment 4 makes, and presses embodiment 8 method medicine carryings; The ratio of thing and carrier of getting it filled is done thermogravimetic analysis (TGA) for optimum proportion preparation, bulk drug, bare that embodiment 10 confirms; Because titanium oxide has thermostability, high temperature does not change, and medicine is at 600 ℃ of following complete agravities.Detailed data is seen accompanying drawing 6.
The sign of medicine existence in carrier; Get embodiment 1 respectively, embodiment 2 is a carrier with the titanium oxide that embodiment 4 makes, and presses embodiment 8 method medicine carryings; What get that embodiment confirms is most that medicine carrying sample, physical mixture and the bare of ratio done powder x-ray diffraction; After investigating the carrier drug loading, the variation of drug crystallization degree, detailed data is seen accompanying drawing 7.
Embodiment 13
The mensuration of mesoporous TiO 2 drug delivery system SGF dissolution in vitro is got embodiment 1 respectively, and embodiment 2 is a carrier with the titanium oxide that embodiment 4 makes; Press embodiment 8 method medicine carryings, get the sample of the best medicine carrying ratio that embodiment 10 confirms, carrying out external dissolution test: pH 1.2 hydrochloric acid soln 900ml according to two appendix second methods of version in 2010 is dissolution medium; 37.5 ± 0.5 ℃ of temperature; Rotating speed of agitator is 100rpm, measures absorbance at wavelength 241 nm places, calculates the dissolution in vitro of carvedilol medicine; Compare with bulk drug; With the mesoporous TiO 2 is the preparation of preparing carriers, and the dissolution rate in vitro of medicine is obviously accelerated, and detailed data is seen accompanying drawing 8.
Embodiment 14
The mensuration of mesoporous TiO 2 drug delivery system simulated intestinal fluid dissolution in vitro is got embodiment 1 respectively, and embodiment 2 is a carrier with the titanium oxide that embodiment 4 makes; Press embodiment 8 method medicine carryings, get the sample of the best medicine carrying ratio that embodiment 10 confirms, carrying out external dissolution test: pH 6.8 buffering salt 900ml according to two appendix second methods of version in 2010 is dissolution medium; 37.5 ± 0.5 ℃ of temperature, rotating speed of agitator are 100rpm, measure absorbance at wavelength 241 nm places; Calculate the dissolution in vitro of carvedilol medicine; Comparing with bulk drug, is the preparation of preparing carriers with the mesoporous TiO 2, and the dissolution rate in vitro of medicine is obviously accelerated.
Embodiment 15
Lactose (weighting agent), Sodium Croscarmellose (disintegrating agent), Magnesium Stearate (lubricant) and mesoporous TiO 2 medicine carrying sample in the ratio thorough mixing of 40:49:10:1 after compressing tablet, sheet heavily is 100mg, wherein every contains carvedilol 10mg.
6 of beasle dogs are divided into 2 groups at random, adopt commercially available of dicycle dual crossing method oral administration and mesoporous TiO 2 sheet (wherein mesoporous TiO 2 is the carrier 1 of embodiment 2 preparations, and dosage is every beagle dog 50mg carvedilol).Specified time point 0.25,0.5,0.75,1,1.5; 2,2.5,3,4,6; 8,12 h, the 24h vein is got blood 4ml, puts in the heparinization centrifuge tube high speed centrifugation; Separate obtaining blood plasma, press plasma sample disposal methods sample, measure each time point carvedilol Plasma Concentration, draw concentration-time curve figure, calculate pharmacokinetic parameters with DAS 2.1.Detailed data is seen accompanying drawing 9.
Claims (15)
1. a mesoporous TiO 2 is characterized by the size homogeneous, and size is at Nano grade, and the aperture is at 2-30nm, and particle radius is at 50-150nm, and specific surface area is at 100-500m
2Between/the g, has good structural controllability and physiology compatibility.
2. the preparation method of mesoporous TiO 2 as claimed in claim 1 is characterized in that:
Get a certain amount of mass concentration and be 95% isopropyl titanate and distilled water, be added drop-wise in an amount of absolute ethyl alcohol, stir and solution was fully reacted in 1-2 hour, left standstill 24-48 hour, centrifugal collecting precipitate, drying promptly gets.
3. the preparation method of mesoporous TiO 2 as claimed in claim 1 is characterized in that:
Getting an amount of tensio-active agent adds in the absolute ethyl alcohol; Being stirred to tensio-active agent dissolves fully; Get a certain amount of mass concentration and be 95% isopropyl titanate and distilled water, be added drop-wise in tensio-active agent and the ethanol solution, stir and solution fully reacted in 1-2 hour; Left standstill 24-48 hour, centrifugal collecting precipitate, drying was removed tensio-active agent in high-temperature calcination 4-6 hour for 400-500 ℃ and is obtained mesoporous TiO 2, perhaps taked the method for Centrifugical extraction to remove tensio-active agent and promptly got.
4. like claim 2 or 3 described preparing methods, the volume ratio that it is characterized in that isopropyl titanate and distilled water is 2.5:1～3.5:1.
5. like claim 2 or 3 described preparing methods, the volume ratio that it is characterized in that isopropyl titanate and distilled water is 2.9:1.
6. like claim 2 or 3 described preparing methods, it is characterized in that also can adding a spot of 0.1mol/L Klorvess Liquid, the volume ratio 5:1 of isopropyl titanate and Repone K～6:1.
7. preparation method as claimed in claim 6, the volume ratio that it is characterized in that isopropyl titanate and Repone K is 5.8:1.
8. preparation method as claimed in claim 3 is characterized in that said tensio-active agent is pluronic F127 or hexadecylamine HAD.
9. preparation method as claimed in claim 3, the consumption that it is characterized in that F127 is between 12～20 grams, between hexadecylamine HAD consumption 2～6 grams.
10. preparation method as claimed in claim 9, the consumption that it is characterized in that F127 is 16g, hexadecylamine HAD consumption is 4g.
11. preparation method as claimed in claim 3 is characterized in that the method for said Centrifugical extraction preferably adopts 60 ℃ of absolute ethyl alcohols to clean repeatedly 6～9 times.
12. mesoporous TiO 2 drug delivery system that is applicable to insoluble drug; Constitute by mesoporous TiO 2 and two kinds of components of insoluble drug; It is characterized in that medicine is by mesoporous TiO 2 Bao Zaihou, medicine is all with amorphous or mainly exist with unbodied form; And the duct that is dispersed in mesoporous TiO 2 is inner and surperficial, and preparation is flowability powder or a particle preferably behind the medicine carrying.
13. the preparation method of drug delivery system as claimed in claim 12 is characterized in that passing through solvent method or scorification medicine carrying, and insoluble drug is embedded in inside, mesoporous TiO 2 duct or evenly is adsorbed on carrier surface.
14. a kind of mesoporous TiO 2 drug delivery system that is applicable to insoluble drug as claimed in claim 12 is characterized in that said insoluble drug belongs to biopharmacy categorizing system II class medicine.
15. a kind of drug delivery system as claimed in claim 12 is characterized by and can combine pharmaceutical excipient to be prepared into to be suitable for oral various preparations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101119485A CN102718254A (en) | 2011-12-31 | 2012-04-17 | Mesoporous titanium dioxide and preparation method thereof and application thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110456484.7 | 2011-12-31 | ||
| CN201110456484 | 2011-12-31 | ||
| CN2012101119485A CN102718254A (en) | 2011-12-31 | 2012-04-17 | Mesoporous titanium dioxide and preparation method thereof and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102718254A true CN102718254A (en) | 2012-10-10 |
Family
ID=46944163
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101119485A Pending CN102718254A (en) | 2011-12-31 | 2012-04-17 | Mesoporous titanium dioxide and preparation method thereof and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102718254A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103723764A (en) * | 2013-12-30 | 2014-04-16 | 中国科学院上海硅酸盐研究所 | Preparation methods of nanocrystalline titanium dioxide polymerized spherical particles and titanium dioxide film photoanode |
| CN104192902A (en) * | 2014-08-28 | 2014-12-10 | 云南大学 | Preparation method of modified mesoporous TiO2 for removing fluorinion in lead and zinc smelting waste water |
| CN105800684A (en) * | 2016-04-05 | 2016-07-27 | 复旦大学 | Monodispersive porous crystal titanium oxide nanosphere with size smaller than 100 nm and preparation method thereof |
| CN108511664A (en) * | 2018-03-30 | 2018-09-07 | 吉林师范大学 | A kind of lithium-sulfur cell diaphragm and preparation method thereof |
| CN109052468A (en) * | 2018-08-29 | 2018-12-21 | 湖北工业大学 | A kind of mesoporous TiO 2 microballoon and preparation method thereof |
| CN111704161A (en) * | 2020-06-15 | 2020-09-25 | 闽江学院 | Hierarchical titanium dioxide microspheres and preparation method and application thereof |
| RU2792145C2 (en) * | 2021-01-13 | 2023-03-17 | Общество с ограниченной ответственностью "Фарматитан СПбГУ" | Application of nanocomposite titanium sorbents in medical technologies |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101792178A (en) * | 2010-03-08 | 2010-08-04 | 厦门大学 | Ordered mesoporous titanium dioxide film with three-dimensionally communicated vertical open pores and preparation method thereof |
| US20110171097A1 (en) * | 2008-05-21 | 2011-07-14 | Korea Research Institute Of Bioscience And Biotechnology | Fullerene-silica nanoparticles with improved fluorescence, preparation method thereof and use thereof |
-
2012
- 2012-04-17 CN CN2012101119485A patent/CN102718254A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110171097A1 (en) * | 2008-05-21 | 2011-07-14 | Korea Research Institute Of Bioscience And Biotechnology | Fullerene-silica nanoparticles with improved fluorescence, preparation method thereof and use thereof |
| CN101792178A (en) * | 2010-03-08 | 2010-08-04 | 厦门大学 | Ordered mesoporous titanium dioxide film with three-dimensionally communicated vertical open pores and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 《Microporous and Mesoporous Materials》 20111213 Haitao Jiang etc Development of an amorphous mesoporous TiO2 nanosphere as a novel carrier for poorly water-soluble drugs: Effect of different crystal forms of TiO2 carriers on drug loading and release behaviors 124-130 , * |
| DEHONG，CHEN.ETC.: "Mesoporous Anatase TiO2 Beads with High Surface Areas and Controllable Pore Sizes: A Superior Candidate for High-Performance Dye-Sensitized Solar Cells", 《ADVANCED MATERIALS》 * |
| HAITAO JIANG ETC.: "Development of an amorphous mesoporous TiO2 nanosphere as a novel carrier for poorly water-soluble drugs: Effect of different crystal forms of TiO2 carriers on drug loading and release behaviors", 《MICROPOROUS AND MESOPOROUS MATERIALS》 * |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103723764A (en) * | 2013-12-30 | 2014-04-16 | 中国科学院上海硅酸盐研究所 | Preparation methods of nanocrystalline titanium dioxide polymerized spherical particles and titanium dioxide film photoanode |
| CN103723764B (en) * | 2013-12-30 | 2015-04-15 | 中国科学院上海硅酸盐研究所 | Preparation methods of nanocrystalline titanium dioxide polymerized spherical particles and titanium dioxide film photoanode |
| CN104192902A (en) * | 2014-08-28 | 2014-12-10 | 云南大学 | Preparation method of modified mesoporous TiO2 for removing fluorinion in lead and zinc smelting waste water |
| CN105800684A (en) * | 2016-04-05 | 2016-07-27 | 复旦大学 | Monodispersive porous crystal titanium oxide nanosphere with size smaller than 100 nm and preparation method thereof |
| CN105800684B (en) * | 2016-04-05 | 2018-10-16 | 复旦大学 | Monodisperse of the size less than 100 nm, porous crystalline TiOx nano ball and preparation method thereof |
| CN108511664A (en) * | 2018-03-30 | 2018-09-07 | 吉林师范大学 | A kind of lithium-sulfur cell diaphragm and preparation method thereof |
| CN108511664B (en) * | 2018-03-30 | 2021-05-18 | 吉林师范大学 | Lithium-sulfur battery diaphragm and preparation method thereof |
| CN109052468A (en) * | 2018-08-29 | 2018-12-21 | 湖北工业大学 | A kind of mesoporous TiO 2 microballoon and preparation method thereof |
| CN109052468B (en) * | 2018-08-29 | 2020-10-13 | 湖北工业大学 | Mesoporous titanium dioxide microsphere and preparation method thereof |
| CN111704161A (en) * | 2020-06-15 | 2020-09-25 | 闽江学院 | Hierarchical titanium dioxide microspheres and preparation method and application thereof |
| CN111704161B (en) * | 2020-06-15 | 2022-09-13 | 闽江学院 | Hierarchical titanium dioxide microspheres and preparation method and application thereof |
| RU2792145C2 (en) * | 2021-01-13 | 2023-03-17 | Общество с ограниченной ответственностью "Фарматитан СПбГУ" | Application of nanocomposite titanium sorbents in medical technologies |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103086346B (en) | A kind of preparation method of mesoporous carbon and application | |
| JP6938425B2 (en) | Lanthanum carbonate hydroxide, lanthanum oxycarbonate and its production and usage | |
| CN102718254A (en) | Mesoporous titanium dioxide and preparation method thereof and application thereof | |
| CN109078006B (en) | Medicinal preparation of palbociclib and preparation method thereof | |
| CN105031671B (en) | Based on Prussian blue synergic nano diagnosis and treatment agent of intelligent pH triggering MRI monitoring insoluble drug releases and preparation method thereof | |
| CN101084880B (en) | Biological solid dispersion of vitamin E esters derivatives and preparation method thereof | |
| CN108653226A (en) | The daily single administration sustained release preparation of Mosapride of pharmacology and clinical effect is provided | |
| CN105121434A (en) | Canagliflozin monohydrate and crystal form thereof, preparation method and use thereof | |
| CN101816639B (en) | Tablets of mosapride citrate and preparation method thereof | |
| CN103893139B (en) | A kind of asenapine composition and preparation method thereof | |
| CN102583286B (en) | Porous hydroxyapatite and preparation method and application thereof | |
| CN102716090B (en) | Sustained-release metformin hydrochloride pellets and preparation method thereof | |
| CN109662949A (en) | A kind of fludrocortisone acetate oral disnitegration tablet and preparation method thereof | |
| CN102949377B (en) | Acetazolamide sustained-release capsule and preparation method thereof | |
| CN109044977A (en) | A kind of pleasure is cut down for Buddhist nun's solid dispersions and preparation method thereof and preparation | |
| CN102552164B (en) | Potassium citrate slow-release micro pill and preparation method thereof | |
| CN102552165B (en) | Sarpogrelate hydrochloride sustained release pellet and preparation method thereof | |
| CN108785268B (en) | Sotalol hydrochloride preparation and preparation method thereof | |
| CN111557920A (en) | Lipoic acid-containing tablet and preparation method thereof | |
| CN114796133B (en) | Injection pharmaceutical preparation and preparation method thereof | |
| CN105732517A (en) | Medicine preparation containing 5-fluorouracil drug eutectic with nicotinamide as precursor and preparation method of medicine preparation | |
| CN106880611A (en) | A kind of tolvaptan preparation of tolvaptan and water soluble adjuvant containing micronizing | |
| CN102485278A (en) | Preparation of polycaprolactone embolism microballoon | |
| CN104622828B (en) | A kind of preparation method of puerarin sustained-release dropping pills | |
| CN103772378B (en) | Meloxicam compound and tablet thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121010 |