CN104548114B - Preparation method of inorganic-organic compound aerogel drug carrier - Google Patents
Preparation method of inorganic-organic compound aerogel drug carrier Download PDFInfo
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- CN104548114B CN104548114B CN201410816687.6A CN201410816687A CN104548114B CN 104548114 B CN104548114 B CN 104548114B CN 201410816687 A CN201410816687 A CN 201410816687A CN 104548114 B CN104548114 B CN 104548114B
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Abstract
The invention discloses a preparation method of an inorganic-organic compound aerogel drug carrier. The preparation method comprises the following steps: in mass percent, adding 8.1-9.1% of beta-cyclodextrin hydrosol, 90.4-91.5% of SiO2 alcosol and 0.2-0.5% of drying control chemical additive into a reactor to stir and disperse uniformly to obtain a gel compound; aging the gel compound by a mixed solution of absolute ethyl alcohol and water at a constant temperature to obtain an aged product; soaking the aged product in an ethanol solution of a silane coupling agent, replacing by a replacing solvent after the soaking, and carrying out vacuum drying at the room temperature to obtain the inorganic-organic compound aerogel drug carrier. The inorganic-organic compound aerogel drug carrier synthesized by the method can be applied to the entrapment and release of anti-inflammation and analgesia drugs, has better drug release performance under the synergistic effect of the beta-cyclodextrin and silicon dioxide, and provides a new thought for the design and research of novel drug carriers.
Description
Technical field
The invention belongs to technical field of polymer, and in particular to a kind of system of inorganic-organic hybrid aeroge pharmaceutical carrier
Preparation Method.
Background technology
Aeroge (aerogel) by its good biocompatibility, higher porosity, larger specific surface area and compared with
Good stability, its internal gutter structure for opening, high porosity, big specific surface area and physiological-toxicity-free make silicon dioxide
Aeroge becomes the excellent carrier of medicine, has broad application prospects in terms of pharmaceutical carrier.Due to the expensive system of aeroge
The shortcomings of standby cost, material are difficult in itself the low-intensity, the high fragility that overcome becomes restriction its wide variety of bottleneck.
The content of the invention
It is an object of the invention to provide a kind of preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier, solves
SiO2Aeroge is used as the low problem of drug carrier material low intensity, fragility height, poor biocompatibility, drug loading.
In order to achieve the above object, the technical solution used in the present invention, by mass percentage, by 8.1～9.1% β-ring
The dextrin hydrosol, 90.4～91.5% SiO2Alcosol and 0.2～0.5% drying control chemical additive add reaction
Dispersed with stirring is uniform in device, obtains gel composite；The mixed solution constant temperature of gel composite dehydrated alcohol and water is aged,
Obtain being aged product；Then ageing product is soaked in the ethanol solution of silane coupler, is entered with replacement solvent after having soaked
Line replacement, last room temperature in vacuo is dried, that is, obtain inorganic-organic hybrid aeroge pharmaceutical carrier.
The preparation method of the described beta-schardinger dextrin-hydrosol is：By percentage to the quality, take respectively 9.2～9.7% β-
Cyclodextrin, 0.58～1.63% epoxychloropropane, 80.69～82.3% purified water, 7.87～7.91% sodium hydroxide
And 0.05～0.07% composite initiator being made up of benzoyl peroxide and azo-bis-iso-dimethyl；Then by β-ring
Dextrin is dissolved in purified water, and with sodium hydroxide pH value is adjusted, and in 80～85 DEG C of constant temperature 30～40min is stirred, and is subsequently added into epoxy
Chloropropane and composite initiator, in 60～65 DEG C of waters bath with thermostatic control 1～1.5h is reacted, that is, obtain the beta-schardinger dextrin-hydrosol.
Benzoyl peroxide accounts for the 25～35% of composite initiator quality, the isopropylformic acid. of azo two in described composite initiator
Dimethyl ester accounts for the 65～75% of composite initiator quality.
Described SiO2The preparation process of alcosol is：By percentage to the quality, 15.45～16.32% are weighed respectively
Alkaline silica sol, the hydrochloric acid that 0.07～0.11% mass concentration is 4～5% and 83.57～84.48% ethanol；Then to
Hydrochloric acid is added in alkaline silica sol, lower addition ethanol is followed by stirring for, that is, obtains SiO2Alcosol.
SiO in described alkaline silica sol2Mass content is 27～32%.
The speed of agitator that adopts is for 600～800r/min when ethanol is added under described stirring, a length of 3～5h during stirring,
Whipping temp is 35～45 DEG C.
Described drying control chemical additive adopts DMF, silicon in the ethanol solution of silane coupler
Alkane coupling agent adopts hexamethyldisiloxane.
Dehydrated alcohol and water volume ratio (1 in described dehydrated alcohol and the mixed solution of water:2)～(2:1) it is, silane coupled
Hexamethyldisiloxane and ethanol mass ratio are (1 in the ethanol solution of agent:7)～(1:6).
For 800～1000r/min, the temperature of constant temperature ageing is 55～65 to the mixing speed adopted during described dispersed with stirring
DEG C, when a length of 1～1.5d of constant temperature ageing, soaking temperature is 30～35 DEG C, a length of 2～3d during immersion.
Described replacement solvent is normal hexane, and displacement number of times is 2 times, every time 4～5h.
Compared with prior art, the beneficial effects of the present invention is：
The ring that beta-schardinger dextrin-is made up of 7 D (+)-glucopyranoses in the beta-schardinger dextrin-hydrosol that the present invention is adopted
Shape oligomer, it can be applied to biomedicine field as drug carrier material, by this beta-schardinger dextrin-hydrosol, SiO2Alcohol
Colloidal sol and drying control chemical additive mix, then constant temperature ageing, soak in the ethanol solution of silane coupler
Standby inorganic-organic hybrid aeroge pharmaceutical carrier is made, the test of Jing drug carrying abilities finds, this inorganic-organic hybrid aeroge
Pharmaceutical carrier has higher drug loading, realizes the controllable release of medicine, overcomes traditional aeroge as pharmaceutical carrier
Many disadvantages, while reducing cost, improve drug carrying capacity.In addition, addition drying control chemical additive is helped
In the control of sol-gel process, make the well-balanced even particle size distribution of colloidal particle, pore passage structure, pore-size distribution concentration, reduce
The cracking that come due to stress different band everywhere during gel drying and broken.
Further, the present invention passes through to control sol in the preparation process of inorganic-organic hybrid aeroge pharmaceutical carrier
The temperature and mixing speed of system, makes gelation time long enough, to ensure that pluralgel can be formed than more complete network knot
Structure.
Description of the drawings
Fig. 1 is curve drug accumulation release time of the present invention.
Specific embodiment
The preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier of the present invention is mainly obtained by following steps：Anti-
Answer and be proportionally added in device the beta-schardinger dextrin-hydrosol and SiO2Alcosol, is subsequently adding drying control chemical additive, after stirring
Decentralized processing, is aged with ethanol water constant temperature, (is soaked in HMDS and ethanol solution, is made in the ethanol solution of silane coupler
Enter line replacement with normal hexane, gained gel is put and is vacuum dried at room temperature, obtain inorganic-organic hybrid aeroge pharmaceutical carrier.
Specifically include following steps：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.2～9.7% beta-schardinger dextrin-is taken respectively, 0.58～1.63% epoxychloropropane,
80.69～82.3% purified water, 7.87～7.91% sodium hydroxide and 0.05～0.07% by benzoyl peroxide and
The composite initiator of azo-bis-iso-dimethyl composition；Then beta-schardinger dextrin-is dissolved in purified water, is adjusted with sodium hydroxide
PH value, in 80～85 DEG C of waters bath with thermostatic control 30～40min are stirred, be subsequently added into as cross-linking agent epoxychloropropane and compound draw
Agent is sent out, in 60～65 DEG C of waters bath with thermostatic control 1～1.5h is reacted, that is, obtain the beta-schardinger dextrin-hydrosol；Wherein, peroxide in composite initiator
Change benzoyl and account for the 25～35% of composite initiator quality, azo-bis-iso-dimethyl account for composite initiator quality 65～
75%；
2)SiO2The preparation of alcosol：
By percentage to the quality, 15.45～16.32%SiO is weighed respectively2Mass content be 27～32% alkaline silicon it is molten
Glue, the hydrochloric acid that 0.07～0.11% mass concentration is 4～5% and 83.57～84.48% ethanol；Then it is molten to alkaline silicon
Hydrochloric acid is added in glue, then the stirring addition ethanol under 35～45 DEG C, the mixing speed of 600～800r/min, stirring duration 3～
5h, that is, obtain SiO2Alcosol；
3) by mass percentage, by 8.3～9.1% beta-schardinger dextrin-hydrosol, 90.4～91.5% SiO2Alcosol
And 0.2～0.5% drying control chemical additive adds dispersed with stirring in reactor uniformly, to obtain gel composite；Will
The mixed solution constant temperature ageing of gel composite dehydrated alcohol and water, obtains being aged product；Then product will be aged in silane
Soak in the ethanol solution of coupling agent, replaced 2 times with normal hexane after soak, 4～5h every time, last room temperature in vacuo drying 12～
16h, that is, obtain inorganic-organic hybrid aeroge pharmaceutical carrier；Wherein, drying control chemical additive adopts N, N- dimethyl methyls
Amide；For 800～1000r/min, the temperature of constant temperature ageing is 55～65 DEG C to the mixing speed adopted during dispersed with stirring, and constant temperature is old
When a length of 1～1.5d of change, soaking temperature is 30～35 DEG C, a length of 2～3d during immersion；Wherein, drying control chemical additive
Using DMF, silane coupler adopts hexamethyldisiloxane in the ethanol solution of silane coupler；It is anhydrous
Dehydrated alcohol and water volume ratio are (1 in the mixed solution of second alcohol and water:2)～(2:1), six in the ethanol solution of silane coupler
Methyl disilazane is (1 with ethanol mass ratio:7)～(1:6).
The present invention is when inorganic-organic hybrid aeroge pharmaceutical carrier is prepared in SiO2Introduce in the preparation process of aeroge
The beta-schardinger dextrin-hydrosol, the inorganic-organic hybrid aeroge has a preferable biocompatibility, more stable internal structure and compared with
High drug loading, realizes the controllable release of medicine.Meanwhile, by controlling the temperature of sol system and stirring in preparation process
Speed is mixed, gelation time long enough is made, to ensure that pluralgel can be formed than more complete network structure.Addition N, N- bis-
Methylformamide contributes to the control of sol-gel process, makes that the even particle size distribution of colloidal particle, pore passage structure be well-balanced, hole
The cracking that come due to stress different band everywhere when footpath distribution is concentrated, reduces gel drying and broken, this is to preparing for loading medicine
The aeroge of thing is highly beneficial.
The present invention is described in further details with reference to embodiment, following examples are only explained, and are not lain in
Limit.
Embodiment 1：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.4% beta-schardinger dextrin-, 1.63% epoxychloropropane, 81.05% purification are taken respectively
Water, 7.87% sodium hydroxide and the 0.05% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 30min in 80 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 60 DEG C of water bath with thermostatic control reaction 1h, that is, the beta-schardinger dextrin-hydrosol is obtained；Wherein,
Benzoyl peroxide accounts for the 25% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for composite initiator
The 75% of quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 15.45%SiO is weighed respectively2Mass content is 27% alkaline silica sol, 0.07% matter
Amount concentration is 4% hydrochloric acid and 84.48% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 35 DEG C,
Stirring under the mixing speed of 800r/min adds ethanol, stirs duration 3h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 8.3% beta-schardinger dextrin-hydrosol, 91.5% SiO2Alcosol and 0.2%
DMF adds dispersed with stirring in reactor uniformly, to obtain gel composite；By the anhydrous second of gel composite
The mixed solution constant temperature ageing of alcohol and water, obtains being aged product；Then by ageing product in the ethanol solution of silane coupler
Immersion, is replaced 2 times after having soaked with normal hexane, and each 4h, last room temperature in vacuo is dried 12h, that is, obtain inorganic-organic hybrid gas
Gel drug carrier；Wherein, the mixing speed for adopting during dispersed with stirring is for 800r/min, and the temperature of constant temperature ageing is 55 DEG C, permanent
When a length of 1d of temperature ageing, soaking temperature is 30 DEG C, a length of 3d during immersion；Wherein, nothing in the mixed solution of dehydrated alcohol and water
Water-ethanol is 1 with water volume ratio:1；Silane coupler adopts hexamethyldisiloxane, silane in the ethanol solution of silane coupler
Silane coupler and ethanol mass ratio are 1 in the ethanol solution of coupling agent:7.
Embodiment 2：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.6% beta-schardinger dextrin-, 1.6% epoxychloropropane, 80.85% purification are taken respectively
Water, 7.89% sodium hydroxide and the 0.06% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 35min in 81 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 61 DEG C of water bath with thermostatic control reaction 1.25h, that is, the beta-schardinger dextrin-hydrosol is obtained；Its
In, benzoyl peroxide accounts for the 30% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for compound drawing
Send out the 70% of agent quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 16.32%SiO is weighed respectively2Mass content is 32% alkaline silica sol, 0.09% matter
Amount concentration is 4.5% hydrochloric acid and 83.59% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 40 DEG C,
Stirring under the mixing speed of 700r/min adds ethanol, stirs duration 4h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 8.7% beta-schardinger dextrin-hydrosol, 91% SiO2Alcosol and 0.3% N,
Dinethylformamide adds dispersed with stirring in reactor uniformly, to obtain gel composite；By gel composite dehydrated alcohol
It is aged with the mixed solution constant temperature of water, obtains being aged product；Then ageing product is soaked in the ethanol solution of silane coupler
Bubble, is replaced 2 times after having soaked with normal hexane, and each 4.5h, last room temperature in vacuo is dried 14h, that is, obtain inorganic-organic hybrid gas
Gel drug carrier；Wherein, the mixing speed for adopting during dispersed with stirring is for 900r/min, and the temperature of constant temperature ageing is 60 DEG C, permanent
When a length of 1.25d of temperature ageing, soaking temperature is 31 DEG C, a length of 2.5d during immersion；Wherein, the mixed solution of dehydrated alcohol and water
Middle dehydrated alcohol is 1 with water volume ratio:1；Silane coupler adopts hexamethyldisiloxane in the ethanol solution of silane coupler,
Silane coupler and ethanol mass ratio are 1 in the ethanol solution of silane coupler:6.
Embodiment 3：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.7% beta-schardinger dextrin-, 1.57% epoxychloropropane, 80.75% purification are taken respectively
Water, 7.91% sodium hydroxide and the 0.07% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 40min in 82 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 62 DEG C of water bath with thermostatic control reaction 1.5h, that is, the beta-schardinger dextrin-hydrosol is obtained；Its
In, benzoyl peroxide accounts for the 35% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for compound drawing
Send out the 65% of agent quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 15.85%SiO is weighed respectively2Mass content is 29% alkaline silica sol, 0.11% matter
Amount concentration is 5% hydrochloric acid and 84.04% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 45 DEG C,
Stirring under the mixing speed of 800r/min adds ethanol, stirs duration 5h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 9% beta-schardinger dextrin-hydrosol, 90.5% SiO2Alcosol and 0.5% N,
Dinethylformamide adds dispersed with stirring in reactor uniformly, to obtain gel composite；By gel composite dehydrated alcohol
It is aged with the mixed solution constant temperature of water, obtains being aged product；Then ageing product is soaked in the ethanol solution of silane coupler
Bubble, is replaced 2 times after having soaked with normal hexane, and each 5h, last room temperature in vacuo is dried 16h, that is, obtain inorganic-organic hybrid airsetting
Glue pharmaceutical carrier；Wherein, for 1000r/min, the temperature of constant temperature ageing is 65 DEG C to the mixing speed for adopting during dispersed with stirring, constant temperature
When a length of 1.5d of ageing, soaking temperature is 32 DEG C, a length of 3d during immersion；Wherein, nothing in the mixed solution of dehydrated alcohol and water
Water-ethanol is 1 with water volume ratio:1；Silane coupler adopts hexamethyldisiloxane, silane in the ethanol solution of silane coupler
Silane coupler and ethanol mass ratio are 1 in the ethanol solution of coupling agent:7.
Embodiment 4：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.2% beta-schardinger dextrin-, 1.63% epoxychloropropane, 81.25% purification are taken respectively
Water, 7.87% sodium hydroxide and the 0.05% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 30min in 83 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 63 DEG C of water bath with thermostatic control reaction 1h, that is, the beta-schardinger dextrin-hydrosol is obtained；Wherein,
Benzoyl peroxide accounts for the 25% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for composite initiator
The 75% of quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 16.05%SiO is weighed respectively2Mass content is 30% alkaline silica sol, 0.07% matter
Amount concentration is 4% hydrochloric acid and 83.88% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 35 DEG C,
Stirring under the mixing speed of 600r/min adds ethanol, stirs duration 3h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 8.5% beta-schardinger dextrin-hydrosol, 91.3% SiO2Alcosol and 0.2%
DMF adds dispersed with stirring in reactor uniformly, to obtain gel composite；By the anhydrous second of gel composite
The mixed solution constant temperature ageing of alcohol and water, obtains being aged product；Then by ageing product in the ethanol solution of silane coupler
Immersion, is replaced 2 times after having soaked with normal hexane, and each 4h, last room temperature in vacuo is dried 12h, that is, obtain inorganic-organic hybrid gas
Gel drug carrier；Wherein, the mixing speed for adopting during dispersed with stirring is for 800r/min, and the temperature of constant temperature ageing is 55 DEG C, permanent
When a length of 1d of temperature ageing, soaking temperature is 33 DEG C, a length of 2d during immersion；Wherein, nothing in the mixed solution of dehydrated alcohol and water
Water-ethanol is 1 with water volume ratio:1；Silane coupler adopts hexamethyldisiloxane, silane in the ethanol solution of silane coupler
Silane coupler and ethanol mass ratio are 1 in the ethanol solution of coupling agent:6.
Embodiment 5：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.3% beta-schardinger dextrin-, 1.6% epoxychloropropane, 81.15% purification are taken respectively
Water, 7.89% sodium hydroxide and the 0.06% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 35min in 84 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 64 DEG C of water bath with thermostatic control reaction 1.25h, that is, the beta-schardinger dextrin-hydrosol is obtained；Its
In, benzoyl peroxide accounts for the 30% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for compound drawing
Send out the 70% of agent quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 16.22%SiO is weighed respectively2Mass content is 30% alkaline silica sol, 0.08% matter
Amount concentration is 4.5% hydrochloric acid and 83.7% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 40 DEG C,
Stirring under the mixing speed of 700r/min adds ethanol, stirs duration 4h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 8.8% beta-schardinger dextrin-hydrosol, 90.8% SiO2Alcosol and 0.4%
DMF adds dispersed with stirring in reactor uniformly, to obtain gel composite；By the anhydrous second of gel composite
The mixed solution constant temperature ageing of alcohol and water, obtains being aged product；Then by ageing product in the ethanol solution of silane coupler
Immersion, is replaced 2 times after having soaked with normal hexane, and each 4.5h, last room temperature in vacuo is dried 14h, that is, obtain inorganic-organic hybrid
Aeroge pharmaceutical carrier；Wherein, for 900r/min, the temperature of constant temperature ageing is 60 DEG C to the mixing speed for adopting during dispersed with stirring,
When a length of 1.25d of constant temperature ageing, soaking temperature is 34 DEG C, a length of 2.5d during immersion；Wherein, the mixing of dehydrated alcohol and water is molten
Dehydrated alcohol and water volume ratio are 1 in liquid:1；Silane coupler adopts the silicon nitrogen of hexamethyl two in the ethanol solution of silane coupler
Alkane, silane coupler and ethanol mass ratio are 1 in the ethanol solution of silane coupler:7.
Embodiment 6：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.5% beta-schardinger dextrin-, 1.57% epoxychloropropane, 80.95% purification are taken respectively
Water, 7.91% sodium hydroxide and the 0.07% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 40min in 85 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 65 DEG C of water bath with thermostatic control reaction 1.5h, that is, the beta-schardinger dextrin-hydrosol is obtained；Its
In, benzoyl peroxide accounts for the 35% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for compound drawing
Send out the 65% of agent quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 15.65%SiO is weighed respectively2Mass content is 30% alkaline silica sol, 0.11% matter
Amount concentration is 5% hydrochloric acid and 84.24% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 45 DEG C,
Stirring under the mixing speed of 800r/min adds ethanol, stirs duration 5h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 8.1% beta-schardinger dextrin-hydrosol, 91.4% SiO2Alcosol and 0.5%
DMF adds dispersed with stirring in reactor uniformly, to obtain gel composite；By the anhydrous second of gel composite
The mixed solution constant temperature ageing of alcohol and water, obtains being aged product；Then by ageing product in the ethanol solution of silane coupler
Immersion, is replaced 2 times after having soaked with normal hexane, and each 5h, last room temperature in vacuo is dried 16h, that is, obtain inorganic-organic hybrid gas
Gel drug carrier；Wherein, the mixing speed for adopting during dispersed with stirring is for 1000r/min, and the temperature of constant temperature ageing is 65 DEG C, permanent
When a length of 1.5d of temperature ageing, soaking temperature is 35 DEG C, a length of 3d during immersion；Wherein, in the mixed solution of dehydrated alcohol and water
Dehydrated alcohol is 1 with water volume ratio:1；Silane coupler adopts hexamethyldisiloxane, silicon in the ethanol solution of silane coupler
Silane coupler and ethanol mass ratio are 1 in the ethanol solution of alkane coupling agent:6.
Embodiment 7：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.2% beta-schardinger dextrin-, 0.58% epoxychloropropane, 82.3% purification are taken respectively
Water, 7.87% sodium hydroxide and the 0.05% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 40min in 85 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 65 DEG C of water bath with thermostatic control reaction 1.5h, that is, the beta-schardinger dextrin-hydrosol is obtained；Its
In, benzoyl peroxide accounts for the 35% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for compound drawing
Send out the 65% of agent quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 16.32%SiO is weighed respectively2Mass content is 30% alkaline silica sol, 0.11% matter
Amount concentration is 5% hydrochloric acid and 83.57% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 45 DEG C,
Stirring under the mixing speed of 800r/min adds ethanol, stirs duration 5h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 8.1% beta-schardinger dextrin-hydrosol, 91.4% SiO2Alcosol and 0.5%
DMF adds dispersed with stirring in reactor uniformly, to obtain gel composite；By the anhydrous second of gel composite
The mixed solution constant temperature ageing of alcohol and water, obtains being aged product；Then by ageing product in the ethanol solution of silane coupler
Immersion, is replaced 2 times after having soaked with normal hexane, and each 5h, last room temperature in vacuo is dried 16h, that is, obtain inorganic-organic hybrid gas
Gel drug carrier；Wherein, the mixing speed for adopting during dispersed with stirring is for 1000r/min, and the temperature of constant temperature ageing is 65 DEG C, permanent
When a length of 1.5d of temperature ageing, soaking temperature is 35 DEG C, a length of 3d during immersion；Wherein, in the mixed solution of dehydrated alcohol and water
Dehydrated alcohol is 1 with water volume ratio:2；Silane coupler adopts hexamethyldisiloxane, silicon in the ethanol solution of silane coupler
Silane coupler and ethanol mass ratio are 1 in the ethanol solution of alkane coupling agent:6.5.
Embodiment 8：
1) preparation of the beta-schardinger dextrin-hydrosol：
By percentage to the quality, 9.7% beta-schardinger dextrin-, 1.63% epoxychloropropane, 80.69% purification are taken respectively
Water, 7.91% sodium hydroxide and the 0.07% compound initiation being made up of benzoyl peroxide and azo-bis-iso-dimethyl
Agent；Then beta-schardinger dextrin-is dissolved in purified water, with sodium hydroxide pH value is adjusted, stir 35min in 84 DEG C of waters bath with thermostatic control, then
Epoxychloropropane and composite initiator are added, in 64 DEG C of water bath with thermostatic control reaction 1.25h, that is, the beta-schardinger dextrin-hydrosol is obtained；Its
In, benzoyl peroxide accounts for the 30% of composite initiator quality in composite initiator, and azo-bis-iso-dimethyl accounts for compound drawing
Send out the 70% of agent quality；
2)SiO2The preparation of alcosol：
By percentage to the quality, 16.22%SiO is weighed respectively2Mass content is 30% alkaline silica sol, 0.08% matter
Amount concentration is 4.5% hydrochloric acid and 83.7% ethanol；Then hydrochloric acid is added in alkaline silica sol, then in 40 DEG C,
Stirring under the mixing speed of 700r/min adds ethanol, stirs duration 4h, that is, obtain SiO2Alcosol；
3) by mass percentage, by the 8.8% beta-schardinger dextrin-hydrosol, 90.8% SiO2Alcosol and 0.4%
DMF adds dispersed with stirring in reactor uniformly, to obtain gel composite；By gel composite silane idol
The ethanol solution constant temperature ageing of connection agent, obtains being aged product；Then ageing product is soaked in the ethanol solution of silane coupler
Bubble, is replaced 2 times after having soaked with normal hexane, and each 4.5h, last room temperature in vacuo is dried 14h, that is, obtain inorganic-organic hybrid gas
Gel drug carrier；Wherein, the mixing speed for adopting during dispersed with stirring is for 900r/min, and the temperature of constant temperature ageing is 60 DEG C, permanent
When a length of 1.25d of temperature ageing, soaking temperature is 34 DEG C, a length of 2.5d during immersion；Wherein, the mixed solution of dehydrated alcohol and water
Middle dehydrated alcohol is 2 with water volume ratio:1；Silane coupler adopts hexamethyldisiloxane in the ethanol solution of silane coupler,
Silane coupler and ethanol mass ratio are 1 in the ethanol solution of silane coupler:6.
Pharmaceutical carrier performance test：
1st, inorganic-organic hybrid aeroge pharmaceutical carrier is loaded with to medicine
Loaded with by model drug of ibuprofen, using the preparation method of above-described embodiment composite aerogel medicine is prepared
Thing carrier.
The composite aerogel pharmaceutical carrier 10mg for weighing is added in 10mL centrifuge tubes, 4mL concentration 3mmol/ is added
The ibuprofen ethanol solution of mL, lucifuge sealing preserve is positioned over shaken at room temperature 12h in agitator.Selected to be centrifuged with high speed centrifuge
20min is centrifuged under speed 12000rmp.Take supernatant ultraviolet spectroscopy in centrifuge tube and determine wherein ibuprofen concentration, precipitate
Ibuprofen composite aerogel is freeze-dried to obtain, drug loading is calculated and envelop rate is respectively 15.6% and 63.02%.
2nd, the extracorporeal releasing test of inorganic-organic hybrid aeroge pharmaceutical carrier
The drug release in vitro behavior of pharmaceutical carrier of this experiment using dialysis to preparing is investigated.Weigh embodiment
1st, the pharmaceutical carrier 8.6mg obtained by 3,5, is positioned over good seal in the bag filter that molecular cut off is 14000, parallel three parts,
Immersion is held in the beaker of phosphate buffer solution release medium 250mL of pH7.2, is placed on 37 DEG C of constant temperature oscillators, rotating speed choosing
Select 100rpm, pharmaceutical carrier parallel group respectively 0.5,1,1.5,2,4,8,16,32,64 and 128h, separately sampled 5mL.And it is same
When supplement 5mL release medium.Obtain sample and use ultraviolet spectrophotometry, in maximum absorption wave strong point mensuration absorbance, calculate
Cumulative release percentage rate, and curve is made with this data versus time, pharmaceutical carrier cumulative in vitro drug release profiles are shown in accompanying drawing 1.
As shown in Figure 1, the pharmaceutical carrier of embodiment 1,3,5 32 hours medicine cumulative percentage releases in PBS exceed
70%, medicine cumulative percentage release increase afterwards in 32 hours is slow, illustrates that medicine can pass freely through bag filter.Three embodiments
The pharmaceutical carrier tablets in vitro curve similarity of preparation is high, has obvious phenomenon of burst release in 16 hours for starting, real
The medicine cumulative percentage release for applying example 1,3,5 has respectively reached 57.2%, 61.8%, 65.7%.Reason is possibly adsorbed
From the pharmaceutical carrier table in the medicine short time on pharmaceutical carrier surface or weaker with the composite aerogel pharmaceutical carrier adhesion
Emaciated face falls, cause the quick rising of drug level, and medicine cumulative percentage release of the pharmaceutical carrier in PBS is over time
Increase and be slowly increased.All reach in the minimum medicine cumulative percentage release of 64 hours three embodiment pharmaceutical carriers
78.6%, it is 81.2% in the minimum medicine cumulative percentage release of 128 hours three embodiment pharmaceutical carriers, illustrate model drug
The drug release of thing carrier model medicine ibuprofen in PBS media is slow and release percentage ratio is higher.Result above shows
Prepared pharmaceutical carrier has certain sustained release performance, thus it is speculated that reason is probably the drug release process of model drug in pharmaceutical carrier
In addition to diffusion, the degraded of pharmaceutical carrier itself equally plays a role during drug release.
Claims (9)
1. a kind of preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier, it is characterised in that：By mass percentage, by 8.1
～9.1% beta-schardinger dextrin-hydrosol, 90.4～91.5% SiO2Alcosol and 0.2～0.5% drying control chemistry
Additive adds dispersed with stirring in reactor uniformly, to obtain gel composite；By the mixed of gel composite dehydrated alcohol and water
The ageing of solution constant temperature is closed, obtains being aged product；Then ageing product is soaked in the ethanol solution of silane coupler, has been soaked
Enter line replacement with replacement solvent afterwards, last room temperature in vacuo is dried, that is, obtain inorganic-organic hybrid aeroge pharmaceutical carrier；
Described drying control chemical additive adopts DMF, silane idol in the ethanol solution of silane coupler
Connection agent adopts hexamethyldisiloxane.
2. the preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 1, it is characterised in that institute
The preparation method of the beta-schardinger dextrin-hydrosol stated is：By percentage to the quality, 9.2～9.7% beta-schardinger dextrin-is taken respectively, 0.58
～1.63% epoxychloropropane, 80.69～82.3% purified water, 7.87～7.91% sodium hydroxide and 0.05～
0.07% composite initiator being made up of benzoyl peroxide and azo-bis-iso-dimethyl；Then beta-schardinger dextrin-is dissolved in pure
In changing water, with sodium hydroxide pH value is adjusted, in 80～85 DEG C of constant temperature 30～40min is stirred, be subsequently added into epoxychloropropane and
Composite initiator, in 60～65 DEG C of waters bath with thermostatic control 1～1.5h is reacted, that is, obtain the beta-schardinger dextrin-hydrosol.
3. the preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 2, it is characterised in that：Institute
Benzoyl peroxide accounts for the 25～35% of composite initiator quality in the composite initiator stated, and azo-bis-iso-dimethyl accounts for multiple
Close the 65～75% of initiator quality.
4. the preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 1, it is characterised in that institute
The SiO for stating2The preparation process of alcosol is：By percentage to the quality, weigh respectively 15.45～16.32% alkaline silica sol,
0.07～0.11% mass concentration is 4～5% hydrochloric acid and 83.57～84.48% ethanol；Then in alkaline silica sol
Hydrochloric acid is added, lower addition ethanol is followed by stirring for, that is, obtains SiO2Alcosol.
5. the preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 4, it is characterised in that：Institute
SiO in the alkaline silica sol stated2Mass content is 27～32%.
6. the preparation method of the inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 4 or 5, it is characterised in that：
The speed of agitator that adopts is for 600～800r/min when ethanol is added under described stirring, a length of 3～5h, whipping temp during stirring
For 35～45 DEG C.
7. the preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 1, it is characterised in that：Institute
Dehydrated alcohol and water volume ratio are (1 in the dehydrated alcohol stated and the mixed solution of water:2)～(2:1), the ethanol of silane coupler
Silane coupler and ethanol mass ratio are (1 in solution:7)～(1:6).
8. the preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 1, it is characterised in that：Institute
For 800～1000r/min, the temperature of constant temperature ageing is 55～65 DEG C to the mixing speed adopted during the dispersed with stirring stated, and constant temperature is old
When a length of 1～1.5d of change, soaking temperature is 30～35 DEG C, a length of 2～3d during immersion.
9. the preparation method of inorganic-organic hybrid aeroge pharmaceutical carrier according to claim 1, it is characterised in that：Institute
The replacement solvent stated is normal hexane, and displacement number of times is 2 times, every time 4～5h.
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