CN115381796A - Drug-loaded shape memory material, preparation method and application thereof - Google Patents
Drug-loaded shape memory material, preparation method and application thereof Download PDFInfo
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- CN115381796A CN115381796A CN202211016609.9A CN202211016609A CN115381796A CN 115381796 A CN115381796 A CN 115381796A CN 202211016609 A CN202211016609 A CN 202211016609A CN 115381796 A CN115381796 A CN 115381796A
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- 229940079593 drug Drugs 0.000 title claims abstract description 181
- 239000012781 shape memory material Substances 0.000 title claims abstract description 94
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000004005 microsphere Substances 0.000 claims abstract description 74
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 42
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 31
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- 238000000034 method Methods 0.000 claims abstract description 22
- 238000003756 stirring Methods 0.000 claims abstract description 15
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000012074 organic phase Substances 0.000 claims abstract description 12
- 229920000747 poly(lactic acid) Polymers 0.000 claims abstract description 9
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- 239000000696 magnetic material Substances 0.000 claims abstract description 7
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- 239000000463 material Substances 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
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- 239000003795 chemical substances by application Substances 0.000 claims description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 6
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 6
- -1 polyethylene Polymers 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 238000007747 plating Methods 0.000 claims description 4
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- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 229930182555 Penicillin Natural products 0.000 claims description 3
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- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 239000004793 Polystyrene Substances 0.000 claims description 3
- 229940124587 cephalosporin Drugs 0.000 claims description 3
- 150000001780 cephalosporins Chemical class 0.000 claims description 3
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 3
- 229940041033 macrolides Drugs 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
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- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000003298 dental enamel Anatomy 0.000 description 2
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- 208000024891 symptom Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
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- 230000003446 memory effect Effects 0.000 description 1
- CLASFMUIFVKHQI-UHFFFAOYSA-N n-[diethoxyphosphoryl-(2-fluorophenyl)methyl]-4-methyl-1,3-benzothiazol-2-amine Chemical compound N=1C2=C(C)C=CC=C2SC=1NC(P(=O)(OCC)OCC)C1=CC=CC=C1F CLASFMUIFVKHQI-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention provides a drug-loaded shape memory material, a preparation method and application thereof, and relates to the technical field of shape memory materials, wherein the method comprises the following steps: dissolving polylactic acid in a dichloromethane solution to obtain an organic phase solution; adding an organic phase solution, a magnetic material and a medicament into a continuous phase solution, stirring, heating, forming a film, and deep drawing to obtain a medicament-carrying shape memory material which is magnetically transported directionally and contains ellipsoidal medicament-carrying microspheres, and simultaneously accurately spraying platinum on the ellipsoidal medicament-carrying microspheres by using a silicon wafer as a mold to obtain the medicament-carrying shape memory material which is transported directionally by a micro-nano motor and contains the ellipsoidal medicament-carrying microspheres. The ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material subjected to magnetic directional delivery or micro-nano motor directional delivery are suitable for entering dentinal tubules in a micro-channel structure in a magnetic field or micro-nano motor directional delivery mode, and subjected to shape recovery under magnetic drive or thermal drive, so that the dentinal tubules are blocked and are not easy to fall off, and long-term curative effect can be maintained.
Description
Technical Field
The invention relates to the technical field of shape memory materials, in particular to a drug-loaded shape memory material, a preparation method and application thereof.
Background
Dentine hypersensitivity is a sore symptom caused by external stimulation such as temperature (cold and heat), chemical substances (sour and sweet), mechanical action (friction or hard biting) and the like, and is characterized by rapid onset, sharp pain and short time.
At present, the incidence of dentin sensitivity in China is high, and various methods for treating dentin sensitivity exist, for example, desensitization treatment can be carried out on teeth, for example, fluoride such as Dufulin or sodium fluoride is used and is smeared on an affected part, and thymol can also be used for desensitization, and the main purpose is to seal dentinal tubules and isolate external stimulation to dental nerves; or by filling of the teeth, it is possible to perform restoration of the shape using, for example, resin while isolating the external cold and hot stimuli. However, the above methods have a limited depth for the occlusion of dentinal tubules, generally only one layer or about 20 microns deep on the surface of the occlusion, when the leakage of dentinal tubules is mechanically stimulated (such as by brushing teeth), the surface insulator is easy to peel off, the dentinal tubules are opened again, and the long-term curative effect is difficult to maintain, and some irreversible methods, such as filling therapy and root canal therapy, are less clinically used due to great damage to the tooth body.
Disclosure of Invention
The invention solves the problems that the existing method for treating dentin hypersensitivity has limited depth for dentin tubule blockage, and the surface insulator is easy to peel off and difficult to maintain long-term curative effect.
In order to solve the problems, the invention provides a preparation method of a drug-loaded shape memory material, which comprises the following steps:
step S1, dissolving polylactic acid in a dichloromethane solution to obtain an organic phase solution;
s2, adding the organic phase solution, the magnetic material and the medicine into the continuous phase solution, and stirring to obtain emulsion;
s3, adding the emulsion into deionized water, continuously stirring and heating to evaporate dichloromethane to obtain a suspension containing spherical microspheres;
s4, washing and filtering the suspension, adding the suspension into a film forming agent, and heating to obtain a drug-loaded film material;
and S5, heating and stretching the drug-loaded membrane material, dissolving the drug-loaded membrane material in deionized water, standing and washing to obtain a drug-loaded shape memory material which is transported in a magnetic orientation mode or in a micro-nano motor orientation mode, wherein the drug-loaded shape memory material which is transported in the magnetic orientation mode or in the micro-nano motor orientation mode is a solution containing ellipsoidal drug-loaded microspheres.
Optionally, in step S5, the drug-loaded membrane material is heated and stretched, and then dissolved in deionized water, and after standing and washing, a drug-loaded shape memory material for magnetic directional delivery or micro-nano motor directional delivery is obtained, including:
s51, heating and stretching the drug-loaded membrane material, dissolving the drug-loaded membrane material in deionized water, standing and washing to obtain a drug-loaded shape memory material for magnetic directional delivery;
s52, dropping the magnetically-directionally-conveyed drug-loaded shape memory material on a silicon wafer or a sample manufactured by taking the silicon wafer as a mold, wherein the silicon wafer has a honeycomb-shaped porous structure;
step S53, arranging a magnet at the bottom of the silicon wafer, and moving the magnet at the bottom of the silicon wafer to enable the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material conveyed in the magnetic orientation to enter the honeycomb porous structure, wherein the tips of the ellipsoidal drug-loaded microspheres are exposed at the opening of the honeycomb porous structure;
and S54, plating platinum on the tips of the ellipsoidal drug-loaded microspheres to obtain the drug-loaded shape memory material directionally conveyed by the micro-nano motor.
Optionally, in step S53, the moving the magnet on the bottom of the silicon wafer includes: and enabling the magnet to move at the bottom of the silicon wafer from top to bottom and from left to right.
Optionally, in step S2, the drug comprises an anti-inflammatory drug, and the anti-inflammatory drug is selected from one of penicillins, cephalosporins, or macrolides.
Optionally, in step S4, the film forming agent includes one of polyvinyl alcohol, polymethyl methacrylate, polyethylene, polystyrene, polyethylene glycol, polyethylene oxide, or polyoxyethylene.
Optionally, in step S5, the drug-loaded film material is heated and stretched, and then dissolved in deionized water, including: the medicinal film material is heated and stretched by 2-3 times and then dissolved in deionized water.
Optionally, in step S2, the magnetic material is ferroferric oxide, nickel or CrO 2 To (3) is provided.
Compared with the prior art, the preparation method of the drug-loaded shape memory material has the advantages that the drug-loaded shape memory material prepared by the method can be subjected to shape recovery under magnetic drive or thermal drive, can be used for treating dentin sensitivity drugs, has the effects of avoiding inflammation of dental pulp cavities, reducing bacteria breeding and the like, has the magnetic directional delivery or micro-nano motor directional delivery characteristics, has a large depth of entering dentin tubules, and can reach 1.5-2mm, so that the drug-loaded shape memory material is not easy to strip when mechanical stimulation (such as tooth brushing) is applied again, and can maintain long-term curative effect. Compared with filling treatment and root canal treatment, the microsphere material is softer, so that the microsphere material has less damage to tooth bodies. The microspheres can be loaded with drugs to achieve the effects of avoiding inflammation of the pulp cavity, reducing bacterial growth and the like.
In order to solve the technical problems, the invention also provides a medicine-carrying shape memory material, which is prepared according to the preparation method of the medicine-carrying shape memory material.
Optionally, the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material can be subjected to shape recovery under magnetic drive or thermal drive, and the particle size of the ellipsoidal drug-loaded microspheres in the original spherical shape is 2-2.5 microns.
Compared with the prior art, the drug-loaded shape memory material and the preparation method thereof have the same advantages, and are not repeated herein.
In order to solve the technical problems, the invention also provides an application of the drug-loaded shape memory material, which comprises the application of the drug-loaded shape memory material in drugs for treating dentin hypersensitivity, and specifically comprises the following steps:
dropping the drug-loaded shape memory material at the inlet of the micro-channel structure, and aligning the outlet of the micro-channel structure to the leakage of dentinal tubules of teeth;
enabling the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material to enter the exposed part of the dentinal tubules in a magnetic directional delivery or micro-nano motor directional delivery mode;
the shape of the ellipsoidal drug-loaded microspheres is recovered by a magnetic drive or thermal drive mode and is changed into an original spherical shape to plug dentinal tubules.
The application of the drug-loaded shape memory material in the drugs for treating dentin hypersensitivity is the same as the advantages of the drug-loaded shape memory material compared with the prior art, and the detailed description is omitted.
Drawings
FIG. 1 is a flow chart of a method for preparing a drug-loaded shape memory material according to an embodiment of the present invention;
FIG. 2 is a schematic diagram showing the change of a drug-loaded film material before and after stretching in an embodiment of the present invention;
FIG. 3 is a top view of a silicon wafer in an embodiment of the present invention;
FIG. 4 is a side view of a silicon wafer in an embodiment of the present invention;
FIG. 5 is a schematic view of the location of a dentinal tubule and an enlarged view thereof in accordance with an embodiment of the present invention;
FIG. 6 is an electron micrograph of a dentinal tubule in position in accordance with an embodiment of the present invention;
FIG. 7 is a plan view of a micro flow channel structure according to an embodiment of the invention;
FIG. 8 is a side view of a micro flow channel structure in an embodiment of the invention;
FIG. 9 is a front view of a micro flow channel structure according to an embodiment of the invention;
FIG. 10 is a schematic diagram of the movement process of the ellipsoidal drug-loaded microspheres in the micro flow channel structure according to the embodiment of the present invention;
FIG. 11 is a flow chart illustrating the process of shape memory recovery after a drug loaded shape memory material is introduced into dentinal tubules as a drug for treating dentinal hypersensitivity in an embodiment of the present invention;
FIG. 12 is a schematic view of an application process of a drug loaded shape memory material in an embodiment of the present invention.
Description of the reference numerals
1-inlet of micro-channel structure, 2-micro-channel, 3-outlet of micro-channel structure, 4-tip of ellipsoid drug-carrying microsphere, 5-oxygen, 6-micro-channel filled with hydrogen peroxide, 7-dentin tubule, 8-enamel, 9-dentin, 10-dental pulp tissue.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and exhaustively described below with reference to the accompanying drawings.
The description of the term "some embodiments" means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same implementation or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
As shown in fig. 1, the invention provides a preparation method of a drug-loaded shape memory material, which comprises the following steps:
step S1, dissolving polylactic acid in a dichloromethane solution to obtain an organic phase solution;
s2, adding the organic phase solution, the magnetic material and the medicine into the continuous phase solution, and stirring to obtain emulsion;
s3, adding the emulsion into deionized water, continuously stirring, heating and evaporating dichloromethane to obtain a suspension containing spherical microspheres;
s4, washing and filtering the suspension, adding the suspension into a film forming agent, and heating and drying the suspension to obtain a drug-loaded film material;
and S5, heating and stretching the drug-loaded membrane material, dissolving the drug-loaded membrane material in deionized water, standing and washing to obtain a drug-loaded shape memory material which is transported in a magnetic orientation mode or in a micro-nano motor orientation mode, wherein the drug-loaded shape memory material which is transported in the magnetic orientation mode or in the micro-nano motor orientation mode is a solution containing ellipsoidal drug-loaded microspheres.
In a preferred embodiment, in step S1, the solution of polylactic acid and dichloromethane is stirred and dissolved on a magnetic stirrer, so as to accelerate the dissolution rate and dissolution effect.
In a preferred embodiment, in step S3, adding the emulsion into deionized water, and stirring and heating to evaporate dichloromethane to obtain a suspension containing spherical microspheres, the method includes: and adding the emulsion into deionized water, stirring for 2-3h, and heating for 1-2h to volatilize dichloromethane to obtain a suspension containing spherical microspheres.
Specifically, in step S2, the drug includes an anti-inflammatory drug, and the anti-inflammatory drug is selected from one of penicillins, cephalosporins, or macrolides. Therefore, the anti-inflammatory and antibacterial effects are good.
Specifically, in the step S2, the continuous phase solution is a polyvinyl alcohol aqueous solution, so that the cost is low.
Specifically, in step S4, the film forming agent includes one of polyvinyl alcohol, polymethyl methacrylate, polyethylene, polystyrene, polyethylene glycol, polyethylene oxide, or polyoxyethylene. Thus, the film forming property is good. Preferably, polyvinyl alcohol is used as the film forming agent, so that the cost is low.
Optionally, in step S5, the step of heating and stretching the drug-loaded film material and then dissolving the drug-loaded film material in deionized water includes: the medicinal film material is heated and stretched by 2-3 times and then dissolved in deionized water. Therefore, the shape of the drug-carrying microsphere in the drug-carrying membrane material is changed into an ellipsoid shape, which is convenient for implantation.
Optionally, in step S2, the magnetic material is ferroferric oxide, nickel or CrO 2 One kind of (1). So that the subsequent directional movement to the target position is facilitated in a magnetic driving mode.
In a specific embodiment, in step S5, the drug-loaded film material is heated and stretched, then dissolved in deionized water, and left to stand and washed to obtain a drug-loaded shape memory material for magnetic directional delivery or micro-nano motor directional delivery, including:
s51, heating and stretching the drug-loaded membrane material, dissolving the drug-loaded membrane material in deionized water, standing and washing to obtain a drug-loaded shape memory material for magnetic directional delivery;
s52, dropping the magnetically-directionally-conveyed drug-loaded shape memory material on a silicon wafer or a sample manufactured by taking the silicon wafer as a mold, wherein the silicon wafer has a honeycomb-shaped porous structure;
step S53, arranging a magnet at the bottom of the silicon wafer, and moving the magnet at the bottom of the silicon wafer to enable the ellipsoidal drug-loaded microspheres in the magnetically-driven drug-loaded shape memory material to enter the honeycomb-shaped porous structure, wherein the tips of the ellipsoidal drug-loaded microspheres are exposed at the opening of the honeycomb-shaped porous structure;
and S54, plating platinum on the tip 4 of the ellipsoidal drug-loaded microsphere to obtain the drug-loaded shape memory material directionally conveyed by the micro-nano motor.
Therefore, the tips 4 of the ellipsoidal drug carrying microspheres are plated with platinum to accurately enter the target position when the subsequent micro-nano motor is directionally conveyed and opened, so that the phenomenon that the ellipsoidal drug carrying microspheres rotate or do not move according to a preset route and cannot enter the target position is avoided.
In a preferred embodiment, the silicon wafer has a plurality of cylindrical pores in the shape of a honeycomb. The result is simple, and is suitable for the entry of the ellipsoidal drug-loaded microspheres.
In a preferred embodiment, the moving the magnet on the bottom of the silicon wafer in step S53 includes: and enabling the magnet to move at the bottom of the silicon wafer from top to bottom and from left to right. Therefore, the ellipsoidal drug-loaded microspheres on the whole silicon wafer completely enter the honeycomb-shaped porous structure under the action of magnetic force.
Therefore, the drug-loaded shape memory material in the method can recover the shape under the temperature stimulation, can be used for treating dentin sensitive drugs, and has the effects of avoiding the inflammation of a dental pulp cavity, reducing the breeding of bacteria and the like, compared with the traditional method for treating dentin sensitivity, the drug-loaded shape memory material has the characteristics of magnetic directional delivery or micro-nano motor directional delivery, the depth of entering a dentin tubule is larger and can reach 1.5-2mm, therefore, when mechanical stimulation (such as tooth brushing) is applied again, the drug-loaded shape memory material is not easy to strip off, and the long-term curative effect can be maintained. Compared with filling treatment and root canal treatment, the microsphere material is softer, so that the microsphere material has less damage to tooth bodies. The microspheres can be loaded with drugs to achieve the effects of avoiding inflammation of the pulp cavity, reducing bacterial growth and the like. The invention also provides a medicine-carrying shape memory material which is prepared according to the preparation method of the medicine-carrying shape memory material.
In the embodiment, the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material can be recovered in shape under external stimulation, and the particle size of the ellipsoidal drug-loaded microspheres in the original spherical shape is 2-2.5 micrometers.
In some preferred embodiments, the ellipsoidal drug-loaded microspheres are capable of shape recovery under magnetic or thermal actuation. The method is simple.
Compared with the prior art, the drug-loaded shape memory material and the preparation method thereof have the same advantages, and are not repeated herein.
As shown in fig. 5-6, the left drawing in fig. 5 is an enlarged schematic diagram at the circle in the right drawing. In the prior art, dentin sensitivity is caused by chewing hard food, enamel 8 at the outermost layer of a tooth is abraded to expose dentin 9 inside, a plurality of dentin tubules 7 of the dentin 9 lead to dental pulp tissues 10, and the dental pulp tissues 10 are also called dental nerves, so that the external cold, hot, sour and sweet stimulation can be sensed. After the enamel 8 is worn, cold, hot, sour and sweet allergies occur, and severe symptoms of pain may occur. The dentine sensitivity is also caused by bad tooth brushing habits, for example, transverse tooth brushing can cause wedge-shaped defects of teeth, long-term mechanical abrasion of bristles at the neck of the teeth can cause transverse sulcus, also called wedge-shaped defects. The defect reaches dentin 9 to cause cold-hot stimulation pain. Factors that induce dentin hypersensitivity include dentin 9 exposure, such as: because of the untimely tooth washing, the calculus is serious, even the periodontal disease occurs, and the gingival atrophy appears over time, which causes the dentin exposure. In addition, there are patients with gastroesophageal reflux, and the mouth is in an acidic environment for a long period of time and may be diseased.
Therefore, in order to treat dentin hypersensitivity, the invention also provides the application of the medicine-carrying shape memory material, wherein the application comprises the application of the medicine-carrying shape memory material in medicines for treating dentin hypersensitivity.
Specifically, as shown in fig. 11, the drug-loaded shape memory material in this embodiment is used as a drug for treating dentin hypersensitivity to perform shape memory recovery after entering dentin tubules as follows:
dropping the drug-loaded shape memory material at the inlet 1 of the micro-channel structure, and aligning the outlet 2 of the micro-channel structure to the exposed part of the dentin tubule 7 of the tooth;
the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material enter the exposed part of the dentin tubule 7 by utilizing a magnetic directional delivery or micro-nano motor directional delivery mode;
the ellipsoidal drug-loaded microspheres are restored to the original spherical shape by magnetic drive or thermal drive to plug dentinal tubules.
Specifically, as shown in fig. 7 to 9, in fig. 7, an inlet 1 of the micro flow channel structure is a concave groove, the micro flow channel 2 is used for providing the ellipsoidal drug-loaded microspheres to move directionally, and the diameter of the micro flow channel 2 is 1.5 micrometers, and in fig. 9, an outlet 3 of the micro flow channel structure is the end of the micro flow channel 2.
The application of the drug-loaded shape memory material in the drug for treating dentin hypersensitivity is the same as the advantages of the drug-loaded shape memory material compared with the prior art, and the details are not repeated herein.
Example 1
The invention provides a preparation method of a drug-loaded shape memory material for magnetic directional delivery, which comprises the following steps:
and 4, washing the suspension by using deionized water for three times, and filtering by using 2-micrometer filter paper. Adding the mixture into the water-soluble PVA solution again, pouring the mixture into a mould, heating and evaporating the mixture to form a film, and obtaining a drug-loaded film material;
and 5, heating and stretching the drug-loaded membrane material by 2 times, dissolving the drug-loaded membrane material in deionized water, standing for 1h to enable the stretched drug-loaded microspheres to be precipitated to the bottom, washing the drug-loaded microspheres with deionized water for three times to obtain the drug-loaded shape memory material for magnetic directional delivery, wherein the drug-loaded shape memory material for magnetic directional delivery is a solution containing ellipsoidal drug-loaded microspheres, and is shown in figure 2.
Fig. 7 to 9 and 12 (a) show, wherein fig. 12 (a) is a schematic view of an application process of the drug-loaded shape memory material for magnetic directional delivery in the embodiment of the present invention. The drug-loaded shape memory material which is transported in the magnetic orientation mode in the embodiment is dripped at the inlet 1 of the prepared micro-channel structure, the outlet 3 of the micro-channel structure is aligned to the exposed position of the dentinal tubule 7 of the tooth, a small magnet is arranged below the micro-channel structure, and the magnet slowly moves towards the position close to the tooth along the flow direction of the micro-channel structure, so that the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material which is transported in the magnetic orientation mode also move in the orientation mode. When the magnet is about to reach the outlet of the micro-channel structure (corresponding to the position of the tooth), the magnet is transferred to the back of the tooth (not entering the tooth, only staying at the outer side of the tooth), and at the moment, under the attraction effect of the magnetic field, the ellipsoidal drug-loaded microspheres can enter the designated position of the dentinal tubules 7.
After the ellipsoidal drug-loaded microspheres reach the designated positions, the microspheres can be restored to the original shape by applying temperature (for example, hot water is contained in the mouth or a hot water bag with the corresponding temperature is placed at the teeth) or applying an alternating magnetic field (the microspheres contain magnetic particles which can generate heat under the action of the alternating magnetic field, so that the shape memory effect can be realized), the ellipsoidal drug-loaded microspheres are changed into the spherical shape before being stretched, the plugging effect on dentinal tubules 7 is achieved, dentin is isolated from the outside, the sensitive effect of treating dentin is achieved, and meanwhile, the inflammation of dental pulp cavities can be avoided and the bacterial growth can be reduced due to the anti-inflammatory drugs on the surfaces of the drug-loaded microspheres.
Example 2
The invention provides a preparation method of a drug-loaded shape memory material directionally conveyed by a micro-nano motor, which comprises the following steps:
and 4, washing the suspension by using deionized water for four times, and filtering by using 2-micron filter paper. Adding the mixture into the water-soluble PVA solution again, pouring the mixture into a mould, heating and evaporating the mixture to form a film, and obtaining a drug-loaded film material;
and 8, plating platinum on the tips 4 of the ellipsoidal drug-loaded microspheres to obtain the drug-loaded shape memory material directionally conveyed by the micro-nano motor.
As shown in fig. 7 to 10 and 12 (b), fig. 12 (b) is a schematic diagram of an application process of the drug-loaded shape memory material directionally conveyed by the micro-nano motor in the embodiment of the present invention. The method comprises the following steps of dropping a drug-loaded shape memory material directionally conveyed by a micro-nano motor in an inlet 1 of a prepared micro-channel structure, aligning an outlet 2 of the micro-channel structure to a dentin tubule 7 explosion position of teeth, simultaneously, pre-injecting hydrogen peroxide into the micro-channel structure to form a micro-channel 6 filled with the hydrogen peroxide, dropping the drug-loaded shape memory material directionally conveyed by the micro-nano motor in the inlet 1 of the micro-channel structure, and after an ellipsoidal drug-loaded microsphere is contacted with the hydrogen peroxide, carrying Pt attached to the tip of the ellipsoidal drug-loaded microsphere and the hydrogen peroxide to generate oxygen 5 through a catalytic reaction, wherein the reaction formula is as follows:
wherein, the generated oxygen 5 can push the ellipsoidal drug-loaded microspheres to do directional motion similar to rocket launching, so that the ellipsoidal drug-loaded microspheres enter the designated position of the dentinal tubules 7.
After the ellipsoidal drug-loaded microspheres reach the designated positions, the ellipsoidal drug-loaded microspheres are changed into the spherical shape before being stretched by applying temperature (such as containing hot water in the mouth or placing a hot water bag at the position of the teeth with a corresponding temperature) or applying an alternating magnetic field, so that dentin is isolated from the outside, the sensitive effect of treating dentin is achieved, and meanwhile, because the drug-loaded microspheres have anti-inflammatory drugs on the surfaces, the inflammation of dental pulp cavities can be avoided, and the breeding of bacteria can be reduced.
Therefore, the drug-loaded shape memory material in the embodiment can recover the shape under the temperature stimulation, can be used for treating dentin sensitivity drugs, and has the effects of avoiding the inflammation of a dental pulp cavity, reducing the breeding of bacteria and the like, compared with the traditional method for treating dentin sensitivity, the drug-loaded shape memory material has the characteristics of magnetic directional delivery or micro-nano motor directional delivery, the depth of entering a dentin tubule is larger and can reach 1.5-2mm, therefore, when mechanical stimulation (such as tooth brushing) is applied again, the drug-loaded shape memory material is not easy to strip off, and the long-term curative effect can be maintained. Compared with filling treatment and root canal treatment, the microsphere material is softer, so that the microsphere material has less damage to tooth bodies. The microspheres can be loaded with drugs to achieve the effects of avoiding inflammation of the pulp cavity, reducing bacterial growth and the like.
Although the present disclosure has been described above, the scope of the present disclosure is not limited thereto. Various changes and modifications may be made by those skilled in the art without departing from the spirit and scope of the disclosure, and these changes and modifications are intended to fall within the scope of the invention.
Claims (10)
1. The preparation method of the drug-loaded shape memory material is characterized by comprising the following steps:
step S1, dissolving polylactic acid in a dichloromethane solution to obtain an organic phase solution;
s2, adding the organic phase solution, the magnetic material and the medicine into the continuous phase solution, and stirring to obtain emulsion;
s3, adding the emulsion into deionized water, continuously stirring and heating to evaporate dichloromethane to obtain a suspension containing spherical microspheres;
s4, washing and filtering the suspension, adding the suspension into a film forming agent, and heating to obtain a drug-loaded film material;
and S5, heating and stretching the drug-loaded membrane material, dissolving the drug-loaded membrane material in deionized water, standing and washing to obtain a drug-loaded shape memory material which is transported in a magnetic orientation mode or in a micro-nano motor orientation mode, wherein the drug-loaded shape memory material which is transported in the magnetic orientation mode or in the micro-nano motor orientation mode is a solution containing ellipsoidal drug-loaded microspheres.
2. The preparation method of the drug-loaded shape memory material according to claim 1, wherein in step S5, the drug-loaded film material is heated and stretched, then dissolved in deionized water, and then left to stand and washed to obtain the drug-loaded shape memory material for magnetic directional delivery or micro-nano motor directional delivery, comprising:
s51, heating and stretching the drug-loaded membrane material, dissolving the drug-loaded membrane material in deionized water, standing and washing to obtain a drug-loaded shape memory material for magnetic directional delivery;
step S52, dripping the drug-loaded shape memory material conveyed in the magnetic orientation on a silicon wafer or a sample manufactured by taking the silicon wafer as a mold, wherein the silicon wafer has a honeycomb-shaped structure;
step S53, arranging a magnet at the bottom of the silicon wafer, and moving the magnet at the bottom of the silicon wafer to enable the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material conveyed in the magnetic orientation to enter the honeycomb porous structure, wherein the tips of the ellipsoidal drug-loaded microspheres are exposed at the opening of the honeycomb porous structure;
and S54, plating platinum on the tip (4) of the ellipsoidal drug-loaded microsphere to obtain the drug-loaded shape memory material directionally conveyed by the micro-nano motor.
3. The method for preparing the drug-loaded shape memory material according to claim 2, wherein the moving the magnet at the bottom of the silicon wafer in step S53 comprises: and enabling the magnet to move at the bottom of the silicon wafer from top to bottom and from left to right.
4. The method for preparing a drug-loaded shape memory material according to claim 1 or 2, wherein in step S2, the drug comprises an anti-inflammatory drug, and the anti-inflammatory drug is selected from one of penicillins, cephalosporins, or macrolides.
5. The preparation method of the drug-loaded shape memory material according to claim 1 or 2, wherein in step S4, the film-forming agent comprises one of polyvinyl alcohol, polymethyl methacrylate, polyethylene, polystyrene, polyethylene glycol, polyethylene oxide, or polyoxyethylene.
6. The preparation method of the drug-loaded shape memory material according to claim 1 or 2, wherein in step S5, the drug-loaded film material is heated and stretched and then dissolved in deionized water, and the method comprises the following steps: the medicinal film material is heated and stretched by 2-3 times and then dissolved in deionized water.
7. The preparation method of the drug-loaded shape memory material according to claim 1, wherein in step S2, the magnetic material is ferroferric oxide, nickel or CrO 2 To (3) is provided.
8. A drug-loaded shape memory material, prepared according to the method of any one of claims 1-7.
9. The drug-loaded shape memory material of claim 8, wherein the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material can be shape-recovered under magnetic or thermal drive, and the particle size of the ellipsoidal drug-loaded microspheres under the shape of the original spheres is 2-2.5 microns.
10. Use of a drug-loaded shape memory material according to claim 8 or 9, comprising the use of a drug-loaded shape memory material in a medicament for the treatment of dentinal hypersensitivity, in particular comprising:
dropping the drug-loaded shape memory material at an inlet (1) of the micro-channel structure, and aligning an outlet (2) of the micro-channel structure to a leakage position of a dentin tubule (7) of a tooth;
enabling the ellipsoidal drug-loaded microspheres in the drug-loaded shape memory material to enter the exposed part of the dentinal tubule (7) by utilizing a magnetic directional conveying or micro-nano motor directional conveying mode;
the ellipsoidal drug-loaded microspheres are restored in shape by magnetic drive or thermal drive and changed into original spherical shape to plug dentinal tubules.
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