CN114106746B - Mesoporous silica modified pressure-sensitive adhesive and application thereof - Google Patents

Mesoporous silica modified pressure-sensitive adhesive and application thereof Download PDF

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CN114106746B
CN114106746B CN202111359416.9A CN202111359416A CN114106746B CN 114106746 B CN114106746 B CN 114106746B CN 202111359416 A CN202111359416 A CN 202111359416A CN 114106746 B CN114106746 B CN 114106746B
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mesoporous silica
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sensitive adhesive
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CN114106746A (en
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金明实
张�林
张嘉琪
申晨
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Yanbian University
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    • C—CHEMISTRY; METALLURGY
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    • C09J133/00—Adhesives based on homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Adhesives based on derivatives of such polymers
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    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
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Abstract

The invention discloses a mesoporous silica modified pressure-sensitive adhesive, which comprises the following components: 0.5-2.0 parts of mesoporous silica nanoparticles, 0.5-2.0 parts of modified mesoporous silica nanoparticles, 55-70 parts of soft monomers, 30-40 parts of hard monomers, 0-5 parts of functional monomers, 0.5 parts of initiator and 100 parts of solvent; the modified mesoporous silica nanoparticle is obtained by surface treatment of mesoporous silica nanoparticle with hexamethyldisilazane; a transdermal patch comprising: a backing layer, a drug-carrying layer and an anti-adhesive layer; the medicine carrying layer is prepared by doping 1.5wt% of indometacin into the mesoporous silica modified pressure-sensitive adhesive; the mesoporous silica modified pressure-sensitive adhesive has the advantages of improved adhesive property, good water resistance, high peel strength, low water absorption and high air permeability; the prepared transdermal patch releases indometacin 70% within 3 days and has good effect.

Description

Mesoporous silica modified pressure-sensitive adhesive and application thereof
Technical Field
The invention belongs to the technical field of pressure-sensitive adhesives, and particularly relates to a mesoporous silica modified pressure-sensitive adhesive and application thereof.
Background
Indomethacin is a non-steroidal anti-inflammatory drug, has the effects of diminishing inflammation and easing pain, is mainly used for treating acute rheumatic and rheumatoid arthritis, and has adverse reaction of central nervous system on gastrointestinal tract stimulation. Thus, to overcome the adverse effects of indomethacin, we selected a safer, more patient-compliant Transdermal Drug Delivery System (TDDS) administration. Transdermal drug delivery is a drug delivery technique in which the skin is used as a drug delivery channel, and drugs enter the body circulation at a constant speed and for a long time through the skin, and comprises a bath agent, a patch, a paste and the like. It has four advantages: the first pass effect is avoided, the medicine utilization rate is high, and meanwhile, the damage to the stomach and the liver is reduced; the medicine is convenient to take, and is especially suitable for old people, children and patients who cannot take medicine orally; the administration times are less, the medicine is stable in slow release and can be released continuously for a long time. Transdermal drug delivery systems include four types, framework type, depot type, multi-layer complex type, and gum mixture type, wherein the gum mixture type is simple in preparation method, and is also the most common Transdermal Drug Delivery System (TDDS). The structure comprises a backing layer, an adhesive and a release film, wherein the pressure-sensitive adhesive is a main auxiliary material in the transdermal patch. The pressure sensitive adhesive has the function of tightly attaching the drug delivery system to the skin, and can also be used as a carrier of the drug to regulate the drug release.
Aiming at the defects of poor adhesiveness and poor water resistance of the traditional patch matrix, the invention prepares the novel mesoporous silica nanoparticle modified polyacrylate pressure-sensitive adhesive carrier material. The invention selects inorganic nano material as cross-linking agent, and the polymer/inorganic nano composite material combines the characteristics of different materials, so that the material has the advantages of high rigidity of inorganic material, and the like, and also has the advantages of polymer material, such as viscoelasticity, and the like. And finally, modifying the pressure-sensitive adhesive by adopting mesoporous silica nanoparticles. The mesoporous silica has the advantages of no physiological toxicity, adjustable pore diameter, large specific surface area, good biocompatibility, rich chemical functional groups for modification on the surface and the like, is widely used in medical fields such as drug carriers, drug slow release and the like at present, is doped into pressure-sensitive adhesives, has molecular interaction between hydroxyl groups on the surface and polymer chains, can improve the crosslinking degree of the pressure-sensitive adhesives, can form a reticular structure in the crosslinking process, can obviously increase the molecular weight, thereby improving the cohesion of the system, leading to obviously improved holding power and improved adhesive property, and further enhancing the adhesive force to the skin surface. The original mesoporous silica nanoparticles tend to pass throughSecondary interactions between their surface-OH aggregate. While HMDS is used to prevent particle aggregation and to create hydrophobicity. During the reaction, part of the-OH groups on the particle surface are gradually replaced by-CH groups 3 Substitution due to the-CH of the particle surface 3 (substituted-OH) is not attracted to each other and the aggregates are broken down into small particles dispersed in the sol. By incorporating HMDS-modified silica in the pressure sensitive adhesive, the hydrophobicity of the subbing layer can be increased.
Disclosure of Invention
The invention aims to provide mesoporous silica modified pressure-sensitive adhesive and application thereof, aiming at solving the defects of poor adhesiveness and poor water resistance of the traditional patch matrix.
A mesoporous silica modified pressure sensitive adhesive comprising: 0.5-2.0 parts of mesoporous silica nanoparticles, 0.5-2.0 parts of modified mesoporous silica nanoparticles, 55-70 parts of soft monomers, 30-40 parts of hard monomers, 0-5 parts of functional monomers, 0.5 parts of initiator and 100 parts of solvent;
the modified mesoporous silica nanoparticle is obtained by surface treatment of mesoporous silica nanoparticle with hexamethyldisilazane;
1.5 parts of mesoporous silica nanoparticles and 1.5 parts of modified mesoporous silica nanoparticles;
the soft monomer is isooctyl acrylate, the hard monomer is methyl acrylate, the functional monomer is hydroxyethyl acrylate, the initiator is benzoyl peroxide, and the solvent is ethyl acetate;
the mesoporous silica nanoparticle is prepared by the following method:
1) Weighing 5-6 g of hexadecene-1-acetate, ultrasonically dissolving in 270-280 g of deionized water, adding 220-230 g of isopropanol, heating in a water bath, stirring, and heating to 60 ℃ for 0.5-1.5 h;
2) 8-9 g of ammonia water is added, and stirring is carried out for 0.8-1.5 h at the constant temperature of 60 ℃;
3) Rapidly adding 26-28 g of silicon source tetraethyl orthosilicate, and continuously stirring for 12-18 h in a constant-temperature water bath at 60 ℃; finishing the reaction, and cooling to room temperature;
4) Repeatedly centrifuging and washing for 6 times, and drying to obtain powder; calcining at a high temperature of 500-600 ℃ to obtain the mesoporous silica nanoparticle.
The hexadecene-1-acetate is 5.1, g, the deionized water is 275g, the isopropyl alcohol is 225g, the ammonia water is 8.7, g, and the silicon source tetraethyl orthosilicate is 27.057g;
the high-temperature calcination in the step 4) is carried out, and the temperature is 550 ℃;
the mesoporous silica modified pressure-sensitive adhesive is prepared by the following method:
1) Weighing 55-70 g of isooctyl acrylate, 30-40 g of methyl acrylate, 0-5 g of hydroxyethyl acrylate and 100g of ethyl acetate, heating in a water bath at 75-85 ℃, and continuously stirring at 100-150 rpm/min;
2) Adding 0.3-0.7 g of benzoyl peroxide and uniformly mixing;
3) Continuously reacting for 10-15 h under the protection of nitrogen;
4) Closing the water bath and the nitrogen, adding ethyl acetate for dilution, and uniformly stirring; cooling to room temperature to obtain polyacrylate pressure-sensitive adhesive;
5) Weighing 0.5-2.0 parts of mesoporous silica nano particles and 0.5-2.0 parts of modified mesoporous silica nano particles according to mass, mixing 100 parts of the modified mesoporous silica nano particles into the polyacrylate pressure-sensitive adhesive prepared in the step 4), and stirring until the mixture is uniform, thus obtaining the mesoporous silica modified pressure-sensitive adhesive;
55g of isooctyl acrylate, 40g of methyl acrylate, 5g of hydroxyethyl acrylate, 100g of ethyl acetate and 0.5g of benzoyl oxide.
A transdermal patch comprising: a backing layer, a drug-carrying layer and an anti-adhesive layer;
the medicine carrying layer is prepared by doping indometacin with the mass fraction of 1.5% into the mesoporous silica modified pressure-sensitive adhesive, stirring at the speed of 350-450 r/min for 1.5-2.5 h;
the transdermal patch is prepared by the following steps:
1) At room temperature, uniformly coating the drug carrying layer on the anti-sticking layer, and standing for 0.5-1.5 h; drying at 45-55 ℃ and placing for 10-20 min;
2) Taking out, solidifying, transferring to backing film, and obtaining transdermal patch.
The invention provides a mesoporous silica modified pressure-sensitive adhesive, which comprises the following components: 0.5-2.0 parts of mesoporous silica nanoparticles, 0.5-2.0 parts of modified mesoporous silica nanoparticles, 55-70 parts of soft monomers, 30-40 parts of hard monomers, 0-5 parts of functional monomers, 0.5 parts of initiator and 100 parts of solvent; the modified mesoporous silica nanoparticle is obtained by surface treatment of mesoporous silica nanoparticle with hexamethyldisilazane; a transdermal patch comprising: a backing layer, a drug-carrying layer and an anti-adhesive layer; the medicine carrying layer is prepared by doping 1.5wt% of indometacin into the mesoporous silica modified pressure-sensitive adhesive; the mesoporous silica modified pressure-sensitive adhesive has the advantages of improved adhesive property, good water resistance, high peel strength, low water absorption and high air permeability; the prepared transdermal patch releases indometacin 70% within 3 days and has good effect.
Drawings
FTIR spectra of the pressure sensitive adhesive of fig. 1 at different monomer ratios;
FIG. 2 effect of SMS content on pressure sensitive adhesive before and after soaking a) primary adhesion, b) hold adhesion, c) 180 peel strength;
FIG. 3 HP-effect of SMS content on pressure sensitive adhesive before and after soaking a) primary adhesion, b) hold adhesion, c) 180 peel strength;
FIG. 4 effect of SMS, HP-SMS content on pressure sensitive adhesive water absorption;
FIG. 5 effect of SMS, HP-SMS content on pressure sensitive adhesive moisture permeability;
figure 6 in vitro release percentage curves for different patches.
Detailed Description
Example 1 preparation of mesoporous silica modified pressure sensitive adhesive
A mesoporous silica modified pressure-sensitive adhesive composite material is prepared by the following steps:
1) Synthesis of mesoporous silica nanoparticles (SMS): a sol-gel method is adopted; accurately weighing hexadecene-1-acetate surfactant of 5.1 and g, ultrasonically dissolving in 275g of deionized water, then adding 225g of isopropanol, heating and stirring the mixed solution in a water bath, and heating to 60 ℃ and continuously maintaining at 1h; adding 8.7. 8.7 g ammonia water into the mixed solution, and stirring at a constant temperature of 60 ℃ for 1h; 27.057g of silicon source tetraethyl orthosilicate (TEOS) is added rapidly, and stirring is continued for 15h in a constant temperature water bath kettle at 60 ℃; ending the reaction; cooled to room temperature. The centrifugal washing was repeated 6 times, and dried overnight in an oven to obtain a powder. Finally calcining in a high-temperature furnace at 550 ℃ to obtain mesoporous silica nanoparticles (SMS) for standby;
2) HMDS (hexamethyldisilazane) hydrophobically modified SMS: accurately weighing 2.5g of SMS,0.3gHMDS,70g n-hexane, mixing completely, carrying out suction filtration on the mixture obtained after reacting for one hour under the condition of reflux and water bath at 100 ℃ and stirring speed of 7 rpm, and washing twice with n-hexane during the suction filtration to obtain a final product HP-SMS for later use;
3) Synthesizing polyacrylate pressure-sensitive adhesive: adopting a free radical polymerization method; 55g of isooctyl acrylate (2-EHA), 40g of Methyl Acrylate (MA), 5g of hydroxyethyl acrylate (HEA) and 100g of Ethyl Acetate (EA) are sequentially added into a four-necked flask according to the mass ratio, a condensation reflux device, a stirring device and a nitrogen blowing device are arranged on the four-necked flask, the four-necked flask is heated in a water bath at 80 ℃, the stirring is continuously carried out at 120 rpm/min, and 0.5g of Benzoyl Peroxide (BPO) serving as an initiator is added and mixed uniformly. The reaction time was continued for 12h under nitrogen protection, removing as much residual monomer as possible. Stopping the reaction, closing the water bath and the nitrogen, adding a proper amount of ethyl acetate for dilution according to the viscous state of the obtained pressure-sensitive adhesive, uniformly stirring, and cooling to room temperature to obtain the polyacrylate pressure-sensitive adhesive for later use;
4) And respectively mixing 0.5-2.0wt% of SMS and 0.5-2.0wt% of HP-SMS into the polyacrylate pressure-sensitive adhesive, and stirring at a speed of 400 r/min until the materials are uniformly mixed to obtain the mesoporous silica modified pressure-sensitive adhesive.
Example 2 preparation of mesoporous silica modified pressure sensitive adhesive
A mesoporous silica modified pressure-sensitive adhesive composite material is prepared by the following steps:
1) Synthesis of mesoporous silica nanoparticles (SMS): a sol-gel method is adopted; precisely weighing 5.0g of hexadecene-1-acetate surfactant, ultrasonically dissolving in 270g of deionized water, then adding 220g of isopropanol, heating the mixed solution in a water bath, stirring, and heating to 60 ℃ and continuously maintaining 1h; 8.0g of ammonia water is added into the mixed solution, and the mixture is stirred for 1h at the constant temperature of 60 ℃; 26g of silicon source tetraethyl orthosilicate (TEOS) is added rapidly, and stirring is continued for 15h in a constant temperature water bath kettle at 60 ℃; ending the reaction; cooled to room temperature. The centrifugal washing was repeated 6 times, and dried overnight in an oven to obtain a powder. Finally calcining in a high-temperature furnace at 550 ℃ to obtain mesoporous silica nanoparticles (SMS) for standby;
2) HMDS hydrophobically modified SMS: accurately weighing 2.5g of SMS,0.1gHMDS,70g n-hexane, mixing completely, carrying out suction filtration on the mixture obtained after reacting for one hour under the condition of reflux and water bath at 100 ℃ and stirring speed of 7 rpm, and washing twice with n-hexane during the suction filtration to obtain a final product HP-SMS for later use;
3) Synthesizing polyacrylate pressure-sensitive adhesive: adopting a free radical polymerization method; 65g of isooctyl acrylate (2-EHA), 30g of Methyl Acrylate (MA), 5g of hydroxyethyl acrylate (HEA) and 100g of Ethyl Acetate (EA) are sequentially added into a four-necked flask according to the mass ratio, a condensation reflux device, a stirring device and a nitrogen blowing device are arranged on the four-necked flask, the four-necked flask is heated in a water bath at 80 ℃, the stirring is continuously carried out at 120 rpm/min, and 0.5g of Benzoyl Peroxide (BPO) serving as an initiator is added and mixed uniformly. The reaction time was continued for 12h under nitrogen protection, removing as much residual monomer as possible. Stopping the reaction, closing the water bath and the nitrogen, adding a proper amount of ethyl acetate for dilution according to the viscous state of the obtained pressure-sensitive adhesive, uniformly stirring, and cooling to room temperature to obtain the polyacrylate pressure-sensitive adhesive for later use;
4) And respectively mixing 0.5-2.0wt% of SMS and 0.5-2.0wt% of HP-SMS into the polyacrylate pressure-sensitive adhesive, and stirring at a speed of 400 r/min until the materials are uniformly mixed to obtain the mesoporous silica modified pressure-sensitive adhesive.
Example 3 preparation of mesoporous silica modified pressure sensitive adhesive
A mesoporous silica modified pressure-sensitive adhesive composite material is prepared by the following steps:
1) Synthesis of mesoporous silica nanoparticles (SMS): a sol-gel method is adopted; accurately weighing 6.0g of hexadecene-1-acetate surfactant, ultrasonically dissolving in 280g of deionized water, then adding 230g of isopropanol, heating the mixed solution in a water bath, stirring, and heating to 60 ℃ and continuously maintaining for 1h; 9.0g of ammonia water is added into the mixed solution, and the mixture is stirred for 1h at the constant temperature of 60 ℃; rapidly adding 28.0g of silicon source tetraethyl orthosilicate (TEOS), and continuously stirring in a constant-temperature water bath kettle at 60 ℃ for 15 hours; ending the reaction; cooled to room temperature. The centrifugal washing was repeated 6 times, and dried overnight in an oven to obtain a powder. Finally calcining in a high-temperature furnace at 550 ℃ to obtain mesoporous silica nanoparticles (SMS) for standby;
2) HMDS hydrophobically modified SMS: accurately weighing 2.5g of SMS,0.5gHMDS,70g n-hexane, mixing completely, carrying out suction filtration on the mixture obtained after reacting for one hour under the condition of reflux and water bath at 100 ℃ and stirring speed of 7 rpm, and washing twice with n-hexane during the suction filtration to obtain a final product HP-SMS for later use;
3) Synthesizing polyacrylate pressure-sensitive adhesive: adopting a free radical polymerization method; 70g of isooctyl acrylate (2-EHA), 30g of Methyl Acrylate (MA) and 100g of Ethyl Acetate (EA) are sequentially added into a four-necked flask according to the mass ratio, a condensation reflux device, a stirring device and a nitrogen blowing device are arranged on the four-necked flask, water bath heating is carried out at 80 ℃, stirring is continuously carried out at 120 rpm/min, and 0.5g of Benzoyl Peroxide (BPO) serving as an initiator is added and mixed uniformly. The reaction time was continued for 12h under nitrogen protection, removing as much residual monomer as possible. Stopping the reaction, closing the water bath and the nitrogen, adding a proper amount of ethyl acetate for dilution according to the viscous state of the obtained pressure-sensitive adhesive, uniformly stirring, and cooling to room temperature to obtain the polyacrylate pressure-sensitive adhesive for later use;
4) And respectively mixing 0.5-2.0wt% of SMS and 0.5-2.0wt% of HP-SMS into the polyacrylate pressure-sensitive adhesive, and stirring at a speed of 400 r/min until the materials are uniformly mixed to obtain the mesoporous silica modified pressure-sensitive adhesive.
Example 4 preparation of Indometacin transdermal Patch
An indomethacin transdermal patch comprising: a backing layer, a drug-carrying layer and an anti-adhesive layer; the back lining layer is a polyurethane film, and the anti-sticking layer is a polyester film with the surface subjected to silicone oil anti-sticking treatment; and uniformly coating the medicine carrying layer on the anti-adhesive layer, and covering a backing film after the medicine carrying layer is dried to obtain the indometacin patch. The drug-carrying layer is enclosed between the backing layer and the release layer in the form of an adhesive. The medicine-carrying layer and the anti-adhesive layer are arranged in sequence from top to bottom.
The preparation method comprises the following steps:
1) Adding 1.5wt% of indometacin into the mesoporous silica modified pressure-sensitive adhesive prepared in the embodiment 1, 2 or 3, stirring at a stirring rate of 400 r/min for 2 hours to obtain a drug-carrying layer;
2) Placing the medicine carrying layer on the release film for 1h at room temperature, placing the medicine carrying layer in a baking oven at 50 ℃, and taking out the medicine carrying layer after 15 min of placing; and after curing, transferring the obtained product onto a backing film to obtain the indometacin transdermal patch.
EXAMPLE 5 Effect of SMS and HP-SMS content on the pressure sensitive adhesive Properties of polyacrylate before and after soaking
The mesoporous silica modified pressure-sensitive adhesive prepared in example 1 was taken out after being soaked in water for 12 hours, and the surface moisture was rapidly wiped off with filter paper, and then the test was performed. According to the regulations of Chinese pharmacopoeia (2005 edition), the initial tackiness test of the pressure-sensitive adhesive film is carried out by using an inclined plane rolling ball method according to the initial tackiness test method of the GB4852-84 pressure-sensitive adhesive tape. The holding viscosity test was carried out by using a hanging weight method according to the specification of the Chinese pharmacopoeia (2005 edition) and the holding viscosity test method of the pressure-sensitive adhesive tape of GB 4851-84. According to the specification of Chinese pharmacopoeia (2005 edition), 180 DEG peel strength test of the pressure-sensitive adhesive tape is carried out by using an electronic peel testing machine according to the 180 DEG peel strength test method of GB2972-81 pressure-sensitive adhesive tape.
Figure DEST_PATH_IMAGE001
As shown in fig. 2 and table 1, as the SMS content increases, the initial adhesion of the adhesive film slightly decreases, the holding adhesion increases greatly, and the 180 ° peel strength tends to increase first and then decrease. The result shows that the adhesive property of the pressure-sensitive adhesive after SMS modification is improved to a certain extent, and the adhesive property of the adhesive film after soaking is also within the applicable range; the pressure sensitive adhesive film added with 1.5wt% SMS works best.
Figure 718426DEST_PATH_IMAGE002
As shown in fig. 3 and table 2, with the increase of the content of HP-SMS, the holding power can be up to 53-h, which is 37-h higher than that of unmodified pressure-sensitive adhesive, the holding power after soaking is up to 69-h, the water resistance is good, the peel strength is high, and the initial adhesion is also in the application range; the pressure sensitive adhesive film with 1.5wt% HP-SMS added works best.
Example 6 Effect of SMS and HP-SMS1 content on Water absorption of polyacrylate pressure sensitive adhesive
The Water absorption (Water absorption) of the pressure-sensitive adhesive samples prepared in example 1 was determined according to HG/T3344-2015 paint film Water absorption assay. Cutting the adhesive film into standard samples with the length of 2cm multiplied by 2cm, putting the standard samples into an oven for drying at 50 ℃ until the weight is constant, accurately weighing the weight of the adhesive film and recording the weight as W 2 Then placing the dried adhesive film into a beaker filled with sufficient water, placing 24h in a 50 ℃ oven, taking out, rapidly sucking the water on the surface with filter paper, and weighing and marking as W 3 。
The water absorption of the pressure sensitive adhesive sample was measured as follows: water absorption (%) = (W) 3 -W 2 ）/W 2 ×100%
Wherein W is 2 Mass (g), W of the solvent-removed pressure-sensitive adhesive sample 3 Is the mass (g) after the pressure sensitive adhesive sample was placed in water for 24 hours and the surface moisture was removed. As shown in fig. 4, since SMS is a hydrophilic material, the water absorption of the pressure-sensitive adhesive film gradually increases as the content of SMS increases, and skin sweat can be effectively absorbed. At SMS contents of less than 1.5wt%, the water absorption of the sample is less than 10% and the stability in humid environments is high. Since the HP-SMS surface is hydrophobically modified, the water absorption of the sample is low, but the water resistance is good.
EXAMPLE 7 Effect of SMS and HP-SMS content on pressure sensitive adhesive moisture permeability
100 mL distilled water is filled into a 150mL beaker, and the weighing is recorded as W 1 . Sealing beaker with pressure sensitive adhesive prepared in example 1, placing in a dry oven at 37deg.C for 24h, taking out, removing film, and weighingW 2 . When the area S of the mouth of the beaker is measured, the water vapor transmission rate of the pressure-sensitive adhesive is (g.m) -2 ·h -1 )：P=(W 1 -W 2 )/24×S
As shown in FIG. 5, the conventional patch matrix has a vapor permeability of only 2.5 g.m due to poor vapor permeability -2 ·h -1 It is difficult for body fluid to permeate the patch. Body fluids accumulate on the skin surface and are difficult to volatilize, resulting in skin being soaked and whitish, and even causing allergies or inflammation. The water vapor transmittance of the pressure-sensitive adhesive modified by mesoporous silica is obviously improved, wherein the maximum of the SMS modified pressure-sensitive adhesive film can reach 20g m -2 ·h -1 Above, sweat that can normally absorb skin shows can not appear soaking phenomenon such as whitening in the use.
Example 8 in vitro Release of Indometacin transdermal Patches
The in vitro release profile of PSA1 (homemade) and PSA2 (commercially available) was examined using a thermostatted shaker. 1cm×1cm transdermal patch was added to the pretreated dialysis bag, the bag was fastened, placed in a centrifuge tube containing 4 ml of PBS solution pH7.4, and shaken at 37℃and a rotational speed of 100 r. Min-1. Samples 0.8 ml were taken at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, 72 h, respectively, and isothermal equal volumes of blank release medium were timely replenished. The solution was removed and filtered through a 0.45 μm microfiltration membrane, and the sample was tested in parallel for 3 runs. The cumulative release amount per unit area (Q) at different time points is calculated according to the formula:
Figure 966392DEST_PATH_IMAGE004
wherein V is 1 To release the medium volume, V 2 For each sample volume, C n For the drug concentration measured at the nth sampling, C i The concentration of the drug in the released solution at the ith sampling is designated as A, and A is the permeation area.
Calculating the in vitro release percentage (Pr) according to a formula, wherein Qt is the accumulated release amount at different times, and D is the marked amount. As shown in FIG. 6, it was reflected in the release of indomethacin 70% within 3 days, which is higher than that of the commercially available pressure-sensitive adhesive.
Figure DEST_PATH_IMAGE005
Fitting a zero-order kinetic equation, a first-order kinetic equation and a Higuchi equation respectively by using the in-vitro release cumulative release degree and time to obtain R 2 And according to R 2 Determining the equation of the in vitro release process complex, R 2 The larger the equation fit the better. As shown in Table 3, the first order kinetic equation fits well, R 2 Larger (R) 2 The larger the equation fit the better).

Claims (8)

1. A mesoporous silica modified pressure sensitive adhesive comprising: 0.5-2.0 parts of mesoporous silica nanoparticles, 0.5-2.0 parts of modified mesoporous silica nanoparticles, 55-70 parts of soft monomers, 30-40 parts of hard monomers, 0-5 parts of functional monomers, 0.5 parts of initiator and 100 parts of solvent;
the modified mesoporous silica nanoparticle is obtained by surface treatment of mesoporous silica nanoparticle with hexamethyldisilazane;
the soft monomer is isooctyl acrylate, the hard monomer is methyl acrylate, the functional monomer is hydroxyethyl acrylate, the initiator is benzoyl peroxide, and the solvent is ethyl acetate;
the preparation method comprises the following steps:
1) Isooctyl acrylate, methyl acrylate, hydroxyethyl acrylate and ethyl acetate are heated in a water bath at 75-85 ℃ and continuously stirred at 100-150 rpm/min;
2) Adding benzoyl peroxide and uniformly mixing;
3) Continuously reacting for 10-15 h under the protection of nitrogen;
4) Closing the water bath and the nitrogen, adding ethyl acetate for dilution, and uniformly stirring; cooling to room temperature to obtain polyacrylate pressure-sensitive adhesive;
5) Weighing 0.5-2.0 parts of mesoporous silica nano particles and 0.5-2.0 parts of modified mesoporous silica nano particles according to mass, mixing the nano particles with 100 parts of the polyacrylate pressure-sensitive adhesive prepared in the step 4), and stirring until the nano particles are uniformly mixed to obtain the mesoporous silica modified pressure-sensitive adhesive.
2. The mesoporous silica modified pressure-sensitive adhesive according to claim 1, wherein: 1.5 parts of mesoporous silica nanoparticle and 1.5 parts of modified mesoporous silica nanoparticle.
3. The mesoporous silica modified pressure-sensitive adhesive according to claim 1 or 2, wherein: the mesoporous silica nanoparticle is prepared by the following method:
1) Weighing 5-6 g of hexadecene-1-acetate, ultrasonically dissolving in 270-280 g of deionized water, adding 220-230 g of isopropanol, heating in a water bath, stirring, and heating to 60 ℃ for 0.5-1.5 h;
2) 8-9 g of ammonia water is added, and stirring is carried out for 0.8-1.5 h at the constant temperature of 60 ℃;
3) Rapidly adding 26-28 g of silicon source tetraethyl orthosilicate, and continuously stirring for 12-18 h in a constant-temperature water bath at 60 ℃; finishing the reaction, and cooling to room temperature;
4) Repeatedly centrifuging and washing for 6 times, and drying to obtain powder; calcining at a high temperature of 500-600 ℃ to obtain the mesoporous silica nanoparticle.
4. The mesoporous silica modified pressure-sensitive adhesive according to claim 3, wherein: the hexadecene-1-acetate 5.1-g, deionized water 275g, isopropanol 225g, ammonia water 8.7 g and silicon source tetraethyl orthosilicate 27.057g.
5. The mesoporous silica modified pressure-sensitive adhesive according to claim 4, wherein: and (3) calcining at a high temperature of 550 ℃ in the step (4).
6. The mesoporous silica modified pressure-sensitive adhesive according to claim 5, wherein: 55 parts of isooctyl acrylate, 40 parts of methyl acrylate, 5 parts of hydroxyethyl acrylate, 100 parts of ethyl acetate and 0.5 part of benzoyl oxide.
7. A transdermal patch comprising: the medicine-carrying layer is sequentially provided with a back lining layer, a medicine-carrying layer and an anti-sticking layer from top to bottom;
the back lining layer is a polyurethane film, and the anti-adhesion layer is a polyester film with the surface subjected to silicone oil anti-adhesion treatment; the medicine carrying layer is prepared by doping 1.5wt% of indometacin into the mesoporous silica modified pressure-sensitive adhesive of claim 1, and stirring at the speed of 350-450 r/min for 1.5-2.5 h.
8. A transdermal patch according to claim 7, prepared by the process of:
1) Uniformly coating the drug carrying layer on the anti-adhesive layer at room temperature, standing for 0.5-1.5 h, and drying;
2) Taking out, solidifying, transferring to backing film, and obtaining transdermal patch.
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