CN112439063A - Preparation method of far infrared magnetic therapy body nano robot - Google Patents

Preparation method of far infrared magnetic therapy body nano robot Download PDF

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CN112439063A
CN112439063A CN201910739921.2A CN201910739921A CN112439063A CN 112439063 A CN112439063 A CN 112439063A CN 201910739921 A CN201910739921 A CN 201910739921A CN 112439063 A CN112439063 A CN 112439063A
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far infrared
infrared magnetic
magnetic film
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porous
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张伯伦
杨志
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Hunan Zaochen Nano Robot Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0042Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K47/02Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

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Abstract

The invention discloses a preparation method of a far infrared magnetic therapy body nano robot, which is characterized in that far infrared ceramic particles with the mass fraction of 28-33% are added into far infrared magnetic film precursor slurry for preparing a porous far infrared magnetic film, and the far infrared ceramic particles can effectively increase the porosity of the porous far infrared magnetic film, namely increase the number of holes in the porous far infrared magnetic film; the nano robot prepared by the porous far infrared magnetic film can release heat energy when being irradiated by infrared rays, so that the drug release can be realized in a short time, namely the release speed of the nano robot is effectively increased, and the treatment effect is better; and the far infrared ceramic particles can directly release heat energy at the focus, so that the thermotherapy can be directly carried out at the focus, and the thermotherapy efficiency is effectively improved.

Description

Preparation method of far infrared magnetic therapy body nano robot
Technical Field
The invention relates to the field of nano robots, in particular to a preparation method of a far infrared magnetic therapy nano robot.
Background
With the continuous progress of science and technology in recent years, the application of the nano robot is more and more extensive. The nano robot refers to a small robot with the size of several nanometers to hundreds of micrometers and the maximum size of centimeter, and has very important potential application in the fields of biomedicine, environmental protection and the like, such as targeted therapy in the biomedicine field and the like.
In the prior art, the material constituting the nano-robot is generally a magnetic material, and the movement of the nano-robot is controlled during use or by an applied external magnetic field. For example, in a targeted therapy process, the nanocrobes may carry drugs. After the patient takes the medicine, the nanometer robot in the human body can be controlled to move to the focus through the magnetic field outside the human body, and then the carried medicine is released for treatment.
However, in the prior art, the drug release speed of the nano robot is generally slow, and the treatment effect is poor. Therefore, how to increase the drug release speed of the nano robot is an urgent problem to be solved by those skilled in the art.
Disclosure of Invention
The invention aims to provide a preparation method of a far infrared magnetic therapy body nano robot, and the prepared nano robot can have higher drug release speed.
In order to solve the technical problems, the invention provides a preparation method of a far infrared magnetic therapy body nano robot, which comprises the following steps:
arranging a layer of chitosan film on the surface of the substrate;
coating a layer of far infrared magnetic film precursor slurry on the surface of the chitosan film; the far infrared magnetic film precursor slurry comprises the following components in parts by mass: 28-33% of far infrared ceramic particles, 32-48% of magnetic materials, 10-15% of surface active molecules and 14-20% of additives;
heating the far infrared magnetic film precursor slurry at a preset temperature for a preset time to solidify the far infrared magnetic film precursor slurry into a porous far infrared magnetic film;
immersing the substrate provided with the porous far-infrared magnetic film into dilute hydrochloric acid to dissolve the chitosan film, so that the porous far-infrared magnetic film is separated from the substrate;
adsorbing a preset drug in the porous far infrared magnetic film;
and cutting the porous far infrared magnetic film to a preset size to prepare the far infrared magnetic therapy body nano robot.
Optionally, the step of disposing a layer of chitosan film on the surface of the substrate includes:
extruding chitosan gel onto the surface of the substrate to form a chitosan gel layer;
rolling and extruding the chitosan gel layer to a preset thickness by using an OSP (organic solderability preservative) wire rod to prepare a chitosan wet film;
and air-drying the chitosan wet film to prepare the chitosan thin film.
Optionally, the immersing the substrate provided with the porous far-infrared magnetic film into dilute hydrochloric acid to dissolve the chitosan film, so that the separating the porous far-infrared magnetic film from the substrate includes:
immersing the substrate provided with the porous far-infrared magnetic film into dilute hydrochloric acid to dissolve the chitosan film;
and adding ultra-pure water into the dilute hydrochloric acid to separate the porous far infrared magnetic film from the substrate.
Optionally, heating the far infrared magnetic film precursor slurry at a preset temperature for a preset time includes:
heating the far infrared magnetic film precursor slurry at a preset temperature for a preset time; the preset temperature ranges from 350 ℃ to 450 ℃, inclusive; the preset time ranges from 120min to 360min, inclusive.
Optionally, the step of adsorbing preset drugs in the porous far-infrared magnetic film comprises:
immersing the porous far-infrared magnetic film into a preset medicine solution;
stirring the preset drug solution soaked with the porous far-infrared magnetic film;
and (3) applying ultrasonic waves to the porous far-infrared magnetic film immersed in the preset medicine solution.
Optionally, the additive comprises polyethylene and polyvinylpyrrolidone;
the far-infrared magnetic thin film precursor slurry comprises: 8-10% of the polyethylene and 6-10% of the polyvinylpyrrolidone.
Optionally, the surface active molecule comprises any one or any combination of the following:
carboxamides, carboxylates, carboxylic chlorides, diketones, alkylsilanes.
Optionally, the magnetic material includes any one or any combination of the following:
ferroferric oxide, ferric oxide and titanium dioxide.
Optionally, the cutting the porous far infrared magnetic film to a preset size includes:
and grinding the porous far infrared magnetic film to a preset size by using a grinder.
Optionally, before disposing a layer of chitosan film on the surface of the substrate, the method further includes:
and cleaning the surface of the substrate.
The preparation method of the far infrared magnetic therapy body nano robot provided by the invention is characterized in that the far infrared ceramic particles with the mass fraction of 28-33% are added into the far infrared magnetic film precursor slurry for preparing the porous far infrared magnetic film, and the far infrared ceramic particles can effectively increase the porosity of the porous far infrared magnetic film, namely increase the number of holes in the porous far infrared magnetic film; the nano robot prepared by the porous far infrared magnetic film can release heat energy when being irradiated by infrared rays, so that the drug release can be realized in a short time, namely the release speed of the nano robot is effectively increased, and the treatment effect is better; and the far infrared ceramic particles can directly release heat energy at the focus, so that the thermotherapy can be directly carried out at the focus, and the thermotherapy efficiency is effectively improved.
Drawings
In order to more clearly illustrate the embodiments or technical solutions of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained based on these drawings without creative efforts.
Fig. 1 to 4 are process flow charts of a method for preparing a far infrared magnetic therapy nano robot according to an embodiment of the present invention;
fig. 5 is a flow chart of a specific method for preparing a far infrared magnetic therapy nano robot provided by the embodiment of the invention.
In the figure: 1. the substrate, 2, chitosan film, 3, porous far infrared magnetic film.
Detailed Description
The core of the invention is to provide a preparation method of a far infrared magnetic therapy body nanometer robot. In the prior art, a nano robot can only directionally move a medicine to a focus for natural release, but the speed of the natural release of the medicine is generally slow, and the treatment effect is poor.
The preparation method of the far infrared magnetic therapy body nano robot provided by the invention is characterized in that the far infrared ceramic particles with the mass fraction of 28-33% are added into the far infrared magnetic film precursor slurry for preparing the porous far infrared magnetic film, and the far infrared ceramic particles can effectively increase the porosity of the porous far infrared magnetic film, namely increase the number of holes in the porous far infrared magnetic film; the nano robot prepared by the porous far infrared magnetic film can release heat energy when being irradiated by infrared rays, so that the drug release can be realized in a short time, namely the release speed of the nano robot is effectively increased, and the treatment effect is better; and the far infrared ceramic particles can directly release heat energy at the focus, so that the thermotherapy can be directly carried out at the focus, and the thermotherapy efficiency is effectively improved.
In order that those skilled in the art will better understand the disclosure, the invention will be described in further detail with reference to the accompanying drawings and specific embodiments. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Referring to fig. 1 to 4, fig. 1 to 4 are process flow charts of a method for preparing a far infrared magnetic therapy body nano robot according to an embodiment of the present invention.
Referring to fig. 1, in the embodiment of the present invention, a method for preparing a far infrared magnetic therapy body nano robot generally includes:
s101: a layer of chitosan film is arranged on the surface of the substrate.
Referring to fig. 2, the above-described chitosan film 2 is used as a layer to be separated in the embodiment of the present invention, so as to separate the porous far-infrared magnetic film 3 and the substrate 1 from each other in a subsequent step. Specifically, the chitosan film 2 is made of chitosan, and the chitosan can react with dilute hydrochloric acid to be decomposed. The specific process for preparing the chitosan film 2 will be described in detail in the following embodiments of the invention, and will not be described herein.
The substrate 1 may be a glass substrate, a stainless steel plate, a high temperature resistant PET (poly-p-phenylene terephthalate plastic), or the like in the embodiment of the present invention, and is not particularly limited in the embodiment of the present invention, as the case may be. In the embodiment of the present invention, a glass substrate is preferably used as the substrate 1. Accordingly, the size and shape of the substrate 1 are not particularly limited in the embodiment of the present invention, depending on the process requirements. Specifically, the size of the substrate 1 in the embodiment of the present invention may range from 1mm × 1mm to 10cm × 10cm, inclusive.
S102: coating a layer of far infrared magnetic film precursor slurry on the surface of the chitosan film.
In an embodiment of the present invention, the far-infrared magnetic thin film precursor paste includes the following components by mass: 28-33% of far infrared ceramic particles, 32-48% of magnetic materials, 10-15% of surface active molecules and 14-20% of additives.
In this step, a layer of far infrared magnetic film precursor slurry is coated on the surface of the chitosan film 2 prepared in step S101, so that the porous far infrared magnetic film 3 is prepared in the subsequent step by using the far infrared magnetic film precursor slurry as a raw material. Far infrared ceramic particles and magnetic materials are required to be added into the far infrared magnetic film precursor slurry, wherein the far infrared ceramic particles can generate heat energy when being irradiated by infrared rays, and the magnetic materials can enable the porous far infrared magnetic film 3 to have magnetism, so that the movement of the porous far infrared magnetic film 3 can be controlled conveniently through a magnetic field. Specifically, the far infrared ceramic particles and the magnetic material are usually present in the form of particles in the far infrared magnetic film precursor slurry, and the particle diameters of the far infrared ceramic particles and the magnetic material are usually between 1nm and 100nm, inclusive; preferably, the particle size of the far infrared ceramic particles and the magnetic material is generally between 10nm and 20nm, inclusive. For the specific components of the far infrared ceramic particles, reference may be made to the prior art, and further description thereof is omitted.
In the embodiment of the present invention, the above additives are generally used as a binder, an activator, and a leveling agent in the far infrared magnetic film precursor slurry, and the additives are also generally used as a polymer matrix of the far infrared magnetic film precursor slurry, so as to form a far infrared magnetic film with a porous structure in a subsequent step. Specifically, in the embodiment of the present invention, the additive may include polyethylene and polyvinylpyrrolidone; the far infrared magnetic film precursor slurry comprises 8-10% of polyethylene by mass and 6-10% of polyvinylpyrrolidone (PVP) by mass.
The surface active molecules are bridges connected between the far infrared ceramic particles and the polymer matrix, and are used for generating required compatibility between the far infrared ceramic particles and the polymer matrix so as to ensure that the far infrared ceramic particles can be fixed in the far infrared magnetic film precursor slurry. Specifically, the surface active molecules described above need to have a bifunctional structure so that a part of the surface active molecules can be bound to the surface of the far-infrared ceramic particle and another part of the surface active molecules can be bound to the polymer matrix described above to achieve the desired compatibility between the far-infrared ceramic particle and the polymer matrix.
Specifically, in the embodiment of the present invention, the surface active molecule may include any one or any combination of the following: carboxamides, carboxylates, carboxylic chlorides, diketones, alkylsilanes. Carboxamides are preferred as surface active molecules required for the far infrared magnetic film precursor slurry in the embodiments of the present invention.
The magnetic material is used for providing the porous far infrared magnetic film 3, namely the magnetism required by the nano robot, so that the directional movement of the nano robot is controlled by an external magnetic field during the use process. Specifically, in the embodiment of the present invention, the magnetic material may include any one or any combination of the following: ferroferric oxide, ferric oxide and titanium dioxide. Of course, other magnetic materials can be selected from the slurry of the far infrared magnetic film precursor, and the specific material of the magnetic material is not particularly limited in the embodiment of the present invention, as the case may be.
S103: and heating the far infrared magnetic film precursor slurry at a preset temperature for a preset time so as to solidify the far infrared magnetic film precursor slurry into the porous far infrared magnetic film.
Referring to fig. 3, in this step, the far infrared magnetic film precursor slurry is usually baked at a predetermined temperature for a predetermined time, and the baked far infrared magnetic film precursor slurry is naturally cooled to a normal temperature to form the porous far infrared magnetic film 3. Specifically, it is generally required that the far-infrared magnetic thin film precursor paste be in an inert gas atmosphere at the time of baking.
Specifically, in this step, the preset temperature ranges from 350 ℃ to 450 ℃, inclusive; the preset time ranges from 120min to 360min inclusive. That is, in this step, the far infrared magnetic film precursor slurry is heated at a temperature of 350 ℃ to 450 ℃ for a period of 120min to 360min to form the porous far infrared magnetic film 3.
S104: and (3) immersing the substrate provided with the porous far-infrared magnetic film into dilute hydrochloric acid to dissolve the chitosan film, so that the porous far-infrared magnetic film is separated from the substrate.
Referring to fig. 4, in this step, the substrate 1 provided with the porous far-infrared magnetic film 3 is immersed in dilute hydrochloric acid to dissolve the chitosan film 2, depending on the property of the chitosan film 2 to be dissolved in the dilute hydrochloric acid. At this time, the substrate 1 and the porous far-infrared magnetic film 3 respectively positioned at the opposite sides of the chitosan film 2 are separated from each other, thereby realizing the peeling of the porous far-infrared magnetic film 3 from the surface of the substrate 1. The details of this step will be described in detail in the following embodiments of the invention, and will not be described herein again.
After this step, it is usually necessary to dry the separated porous far-infrared magnetic film 3 in order to carry out drug loading using the porous far-infrared magnetic film 3 in a subsequent step. Specifically, when the porous far-infrared magnetic film 3 is dried, the porous far-infrared magnetic film 3 is usually heated at 100 to 120 ℃ for 30 to 60 minutes to be dried.
S105: adsorbing preset medicines in the porous far infrared magnetic film.
In this step, a predetermined drug is adsorbed in the porous far-infrared magnetic film 3, so that the nano robot provided by the embodiment of the present invention carries the drug. The specific type of the predetermined drug is not particularly limited in the embodiments of the present invention, and is determined according to the specific situation. The porous far-infrared magnetic film 3 prepared in S104 can adsorb tumor drugs, and the specific types of the tumor drugs in the embodiment of the present invention are not specifically limited, and may be Paclitaxel (PTX), Dexamethasone (DXM), or ranolon. The details of this step will be described in detail in the following embodiments of the invention, and will not be described herein again.
S106: the porous far infrared magnetic film is cut to a preset size to prepare the far infrared magnetic therapy body nano robot.
In the step, the porous far infrared magnetic film 3 is cut to a preset size, so that the far infrared magnetic therapy body nano robot provided by the embodiment of the invention can enter the focus of a human body in the using process. The details of this step will be described in detail in the following embodiments of the invention, and will not be described herein again.
The preparation method of the far infrared magnetic therapy body nano robot provided by the embodiment of the invention is characterized in that far infrared ceramic particles with the mass fraction of 28-33% are added into far infrared magnetic film precursor slurry used for preparing the porous far infrared magnetic film 3, and the far infrared ceramic particles can effectively increase the porosity of the porous far infrared magnetic film 3, namely increase the number of holes in the porous far infrared magnetic film 3; the nano robot prepared by the porous far infrared magnetic film 3 can release heat energy when being irradiated by infrared rays, so that the drug release can be realized in a short time, namely the release speed of the nano robot is effectively increased, and the treatment effect is better; and the far infrared ceramic particles can directly release heat energy at the focus, so that the thermotherapy can be directly carried out at the focus, and the thermotherapy efficiency is effectively improved.
The details of the preparation method of the far infrared magnetic therapy nano robot provided by the invention will be described in detail in the following invention embodiments.
Referring to fig. 5, fig. 5 is a flowchart of a specific method for preparing a nano robot for far infrared magnetic therapy.
Referring to fig. 5, in an embodiment of the present invention, a method for preparing a far infrared magnetic therapy body nano robot generally includes:
s201: and cleaning the surface of the substrate.
In this step, the surface of the substrate 1 needs to be cleaned to avoid the impurities carried on the surface of the substrate 1 from interfering with each film layer prepared in the subsequent step. Specifically, in this step, the substrate 1 is usually wiped with alcohol, then the substrate 1 is placed in an ultrasonic cleaning machine, the substrate 1 is ultrasonically cleaned with deionized water and alcohol in sequence, and finally the substrate 1 is placed in alcohol vapor to be dried, and when the substrate 1 is taken out of the alcohol vapor, the condensed vapor evaporates from the surface, so that the substrate 1 can be dried quickly. The ultrasonic power of the ultrasonic cleaning machine during operation is usually between 75W and 300W, inclusive.
S202: the chitosan gel is extruded onto the substrate surface to form a chitosan gel layer.
In this step, the chitosan gel is diluted by 10 times, and then the diluted chitosan gel is extruded onto the surface of the substrate 1, and the temperature of the surface of the substrate 1 is usually controlled to be 45 ℃ to 65 ℃ to form a chitosan gel layer on the surface of the substrate 1.
S203: and rolling and extruding the chitosan gel layer to a preset thickness by using an OSP wire rod to prepare the chitosan wet film.
In this step, the chitosan gel layer is rolled using an OSP wire rod having a diameter of 6.5mm to 9.4mm at a speed of about 0.5m/min, a weight of about 0.6kg, to a preset thickness, which in the present embodiment is typically 10 μm to 30 μm, to form a chitosan wet film, i.e., the preset thickness, i.e., 10 μm to 30 μm, inclusive.
S204: and air-drying the chitosan wet film to prepare the chitosan film.
In this step, usually in a hundred-grade dust-free plant, the temperature in the plant needs to be controlled at 25 ± 3 ℃ and the humidity needs to be controlled at 45% to 75%, the chitosan wet film is naturally dried for 30min to 60min to form the chitosan film 2, and after drying, the thickness of the chitosan film 2 is usually 5 μm to 15 μm, and the uniformity is usually 3%.
S205: coating a layer of far infrared magnetic film precursor slurry on the surface of the chitosan film.
This step is substantially the same as S102 in the above embodiment of the present invention, and for details, reference is made to the above embodiment of the present invention, which is not repeated herein.
In this step, the substrate 1 provided with the chitosan film 2 can be placed on the working table of an automatic knife-scraping and rotary-spreading machine by a manipulator, and after automatic positioning, a layer of far-infrared magnetic film precursor slurry is scraped on the surface of the chitosan film 2 by a centrifugal law so as to prepare the porous far-infrared magnetic film 3 in the subsequent step. In the rotary scraping process, the rotary scraping speed is usually adjustable between 1000rpm and 3000rpm, the rotary scraping time is usually between 10s and 15s, the uniformity is usually required to be controlled within +/-3%, and the thickness of a layer of far infrared magnetic thin film precursor slurry obtained by rotary scraping is usually between 1000nm and 100000 nm. And then, naturally drying the substrate 1 which is scraped with the far infrared magnetic film precursor slurry in a natural air way for 3 to 5 minutes in an operating environment, and then baking the substrate in a dust-free oven for 20 to 30 minutes for shaping. The temperature of the dust-free oven in operation is usually about 60 ℃, and the heating uniformity of the dust-free oven is usually within +/-3 ℃. The operating environment for the rotary scraping far infrared magnetic film precursor slurry generally needs a hundred-grade dust-free workshop, the temperature in the workshop needs to be controlled at 22 +/-3 ℃, and the humidity needs to be controlled at 45-75%.
S206: and heating the far infrared magnetic film precursor slurry at a preset temperature for a preset time so as to solidify the far infrared magnetic film precursor slurry into the porous far infrared magnetic film.
This step is substantially the same as S103 in the above embodiment of the present invention, and for details, reference is made to the above embodiment of the present invention, which is not repeated herein.
S207: and immersing the substrate provided with the porous far-infrared magnetic film into dilute hydrochloric acid to dissolve the chitosan film.
In this step, the substrate 1 provided with the chitosan film 2 and the porous far-infrared magnetic film 3 is immersed in dilute hydrochloric acid, and the chitosan film 2 is dissolved by the reaction of the dilute hydrochloric acid and chitosan. For the specific reaction between hydrochloric acid and chitosan, reference may be made to the prior art, which is not described herein. Specifically, in this step, the substrate 1 is immersed in dilute hydrochloric acid for about 10 to 15 minutes.
S208: adding ultra-pure water into the dilute hydrochloric acid to separate the porous far infrared magnetic film and the substrate.
In this step, ultra-pure water is added to the dilute hydrochloric acid to make the dilute hydrochloric acid flow for about 30 minutes, and the chitosan film 2 is dissolved in the dilute hydrochloric acid and flows out along with the ultra-pure water, so that the substrate 1 and the porous far infrared magnetic film 3 are separated. The rest of the steps have been described in detail in the above embodiments of the present invention, and are not described herein again.
S209: the porous far infrared magnetic film is immersed in a preset medicinal solution.
Before this step, the predetermined drug may be dissolved to prepare a predetermined drug solution. Specifically, if the predetermined drug is a tumor drug, the tumor drug is usually dissolved in acetone to prepare a predetermined drug solution. In this step, the porous far-infrared magnetic film 3 is immersed in a predetermined drug solution so as to adsorb a predetermined drug in the porous far-infrared magnetic film 3 in a subsequent step.
S210: stirring the preset medicine solution soaked with the porous far infrared magnetic film.
In this step, the preset drug solution soaked with the porous far-infrared magnetic film 3 is usually stirred at a stirring speed of 50r/min to 100r/min for about 10min, so that the preset drug solution is fully covered on the surface of the porous far-infrared magnetic film 3.
S211: ultrasonic waves are applied to a porous far-infrared magnetic film immersed in a predetermined drug solution.
In this step, the ultrasonic wave generated by the ultrasonic transducer is usually applied to the porous far-infrared magnetic film 3 immersed in the preset drug solution, so that the porous far-infrared magnetic film 3 oscillates and the preset drug solution can more sufficiently enter the pores of the porous far-infrared magnetic film 3. Specifically, this step usually lasts for 15min to 30 min.
After this step, the predetermined drug solution impregnated with the porous far-infrared magnetic thin film 3 is left standing for 30 to 60 minutes, usually at 20 to 30 ℃, so that the porous far-infrared magnetic thin film 3 and the predetermined drug are precipitated.
S212: and grinding the porous far infrared magnetic film to a preset size by using a grinder.
In this step, the porous far-infrared magnetic film 3 is ground using a grinder, specifically, a CMSD2000 type grinder. The shear rate of the above-mentioned mills is generally between 8000rpm and 10000rpm, and the speed of the rotor thereof is generally between 20m/s and 30 m/s. In this step, the particle size of the grinded porous far-infrared magnetic particles is usually adjustable between 10nm and 1000 nm.
The preparation method of the far infrared magnetic therapy body nano robot provided by the embodiment of the invention specifically provides the specific details of each step, and simultaneously, the ultrasonic wave is used for acting on the porous far infrared magnetic film 3 immersed in the preset medicine solution, so that the preset medicine can more fully enter the pores of the porous far infrared magnetic film 3.
In the embodiment of the invention, a test is carried out to verify the specific efficacy of the far infrared magnetic therapy body nano robot provided by the embodiment of the invention.
Specifically, in the embodiment of the invention, the peak area is measured by an HPLC method and is compared with a standard solution, so that the slow release time and the slow release concentration of the drug in the far infrared magnetic therapy body nano robot are obtained. Three groups of data are needed for determining the drug concentration in the blood plasma by the HPLC method, which are respectively as follows: firstly, blank plasma; secondly, a chromatogram of a reference substance; and thirdly, a plasma sample chromatogram. The HPLC measuring instrument used in the examples of the present invention is a high performance liquid chromatograph (Watet515 pump, ELSD detector). Among the above required data:
first, blank plasma: the peak area is measured by HPLC method with the blood not injected into the far infrared magnetic therapy body nanometer robot provided by the embodiment of the invention.
Secondly, chromatogram of a reference substance: precisely weighing 1mg of the far infrared magnetic therapy body nano robot standard substance provided by the embodiment of the invention, putting the far infrared magnetic therapy body nano robot standard substance into a 10mL volumetric flask, adding methanol to dissolve and dilute the far infrared magnetic therapy body nano robot standard substance to a scale, shaking up, and measuring the peak area by an HPLC method.
And thirdly, a plasma sample chromatogram map, namely 1mg of the far infrared magnetic therapy body nano robot provided by the embodiment of the invention is dispersed in physiological saline and then injected into a mouse body through a tail edge vein. Taking 0.1mL of blood plasma at different time periods, adding a proper amount of 2% hydrochloric acid and 3mL of ethyl acetate, carrying out vortex oscillation for 5min, carrying out ultrasonic treatment for 10min, centrifuging for 10min at 12000r/min, drying at 60 ℃ by using nitrogen, fully dissolving residues by using 1mL of methanol, limiting the sample injection to 20uL, and observing the concentration of the medicine.
In the embodiment of the invention, the far infrared magnetic therapy body nano robot is loaded with the tumor drug, 1mg of the far infrared magnetic therapy body nano robot is dispersed in physiological saline, the physiological saline is injected into a mouse body through a tail edge vein, the far infrared magnetic therapy body nano robot is pushed to a tumor area through a magnetic control system, and the drug slow release time and the drug slow release concentration are observed.
The following table 1 shows the results of the experimental data, and the specific contents of each example in table 1 are as follows:
example 1, a common magnetic drug-loaded nano-robot is adopted, and the rest contents are as same as those of the far infrared magnetic therapy body nano-robot provided by the embodiment of the invention; increasing infrared radiation at 4 hours; wherein, the common magnetic nano robot has about 10% of the far infrared magnetic therapy nano robot provided by the embodiment of the invention, the drug loading capacity is poor, and the far infrared magnetic therapy nano robot can not generate heat after absorbing infrared rays.
Example 2, consistent with the far infrared magnetic therapy body nanometer robot provided by the embodiment of the invention, the drug is normally slowly released.
Example 3, consistent with the far infrared magnetotherapy body nano robot provided by the above invention embodiment, infrared irradiation was increased at 4 th hour.
Example 4 the far infrared magnetic therapy body nano robot provided by the embodiment of the invention is loaded with fluorescent powder (without carrying medicine), so that X-ray and fluorescence are respectively photographed and tracked, and a thermal imager is used for sensing temperature change.
TABLE 1 results of experimental data
Figure BDA0002163588840000121
Figure BDA0002163588840000131
As can be seen from the above table, the far infrared magnetic therapy nano robot prepared by the preparation method of the far infrared magnetic therapy nano robot provided by the embodiment of the invention can release heat energy when being irradiated by infrared rays, so that the drug release can be realized in a short time, that is, the release speed of the nano robot is effectively increased, and the treatment effect is better; and the far infrared ceramic particles can directly release heat energy at the focus, so that the thermotherapy can be directly carried out at the focus, and the thermotherapy efficiency is effectively improved.
The embodiments are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same or similar parts among the embodiments are referred to each other.
Those of skill would further appreciate that the various illustrative elements and algorithm steps described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or combinations of both, and that the various illustrative components and steps have been described above generally in terms of their functionality in order to clearly illustrate this interchangeability of hardware and software. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the implementation. Skilled artisans may implement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the present invention.
The steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in a software module executed by a processor, or in a combination of the two. A software module may reside in Random Access Memory (RAM), memory, Read Only Memory (ROM), electrically programmable ROM, electrically erasable programmable ROM, registers, hard disk, a removable disk, a CD-ROM, or any other form of storage medium known in the art.
Finally, it should also be noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other identical elements in a process, method, article, or apparatus that comprises the element.
The preparation method of the far infrared magnetic therapy nano robot provided by the invention is described in detail above. The principles and embodiments of the present invention are explained herein using specific examples, which are presented only to assist in understanding the method and its core concepts. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.

Claims (10)

1. A preparation method of a far infrared magnetic therapy nano robot is characterized by comprising the following steps:
arranging a layer of chitosan film on the surface of the substrate;
coating a layer of far infrared magnetic film precursor slurry on the surface of the chitosan film; the far infrared magnetic film precursor slurry comprises the following components in parts by mass: 28-33% of far infrared ceramic particles, 32-48% of magnetic materials, 10-15% of surface active molecules and 14-20% of additives;
heating the far infrared magnetic film precursor slurry at a preset temperature for a preset time to solidify the far infrared magnetic film precursor slurry into a porous far infrared magnetic film;
immersing the substrate provided with the porous far-infrared magnetic film into dilute hydrochloric acid to dissolve the chitosan film, so that the porous far-infrared magnetic film is separated from the substrate;
adsorbing a preset drug in the porous far infrared magnetic film;
and cutting the porous far infrared magnetic film to a preset size to prepare the far infrared magnetic therapy body nano robot.
2. The method of claim 1, wherein disposing a chitosan film on the surface of the substrate comprises:
extruding chitosan gel onto the surface of the substrate to form a chitosan gel layer;
rolling and extruding the chitosan gel layer to a preset thickness by using an OSP (organic solderability preservative) wire rod to prepare a chitosan wet film;
and air-drying the chitosan wet film to prepare the chitosan thin film.
3. The method as claimed in claim 2, wherein the immersing the substrate provided with the porous far-infrared magnetic film in dilute hydrochloric acid to dissolve the chitosan film, and the separating the porous far-infrared magnetic film from the substrate comprises:
immersing the substrate provided with the porous far-infrared magnetic film into dilute hydrochloric acid to dissolve the chitosan film;
and adding ultra-pure water into the dilute hydrochloric acid to separate the porous far infrared magnetic film from the substrate.
4. The method according to claim 1, wherein the heating the far infrared magnetic thin film precursor paste at a preset temperature for a preset time comprises:
heating the far infrared magnetic film precursor slurry at a preset temperature for a preset time; the preset temperature ranges from 350 ℃ to 450 ℃, inclusive; the preset time ranges from 120min to 360min, inclusive.
5. The method as claimed in claim 1, wherein the adsorbing the predetermined medicine in the porous far infrared magnetic film comprises:
immersing the porous far-infrared magnetic film into a preset medicine solution;
stirring the preset drug solution soaked with the porous far-infrared magnetic film;
and (3) applying ultrasonic waves to the porous far-infrared magnetic film immersed in the preset medicine solution.
6. The method according to any one of claims 1 to 5, wherein the additives comprise polyethylene and polyvinylpyrrolidone;
the far-infrared magnetic thin film precursor slurry comprises: 8-10% of the polyethylene and 6-10% of the polyvinylpyrrolidone.
7. The method of claim 6, wherein the surface active molecules comprise any one or any combination of:
carboxamides, carboxylates, carboxylic chlorides, diketones, alkylsilanes.
8. The method of claim 7, wherein the magnetic material comprises any one or any combination of:
ferroferric oxide, ferric oxide and titanium dioxide.
9. The method according to claim 1, wherein the cutting the porous far infrared magnetic thin film to a predetermined size comprises:
and grinding the porous far infrared magnetic film to a preset size by using a grinder.
10. The method of claim 9, wherein prior to disposing a layer of chitosan film on the surface of the substrate, the method further comprises:
and cleaning the surface of the substrate.
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CN107007551A (en) * 2017-03-30 2017-08-04 南昌大学 A kind of preparation method of the nanometer formulation of temperature controlled release thrombolytic drug

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CN102302473A (en) * 2011-07-23 2012-01-04 兰州大学第二医院 Matrine magnetic slow-releasing capsule and preparation method
CN104940958A (en) * 2015-05-19 2015-09-30 中南大学 Fluorescent magnetic nano targeted medicine and preparation method thereof
CN107007551A (en) * 2017-03-30 2017-08-04 南昌大学 A kind of preparation method of the nanometer formulation of temperature controlled release thrombolytic drug

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