Multifunctional contact lens with passive release and active controllable drug delivery

Abstract

The application discloses a multifunctional drug delivery contact lens with passive release and active controllability, which is composed of a spherical cap contact lens body and a drug delivery additive layer on the inner surface of the contact lens body; the drug delivery additive layer is used for direct contact with the cornea and storage and control of drug release; the drug delivery additive layer has a plurality of radial drug delivery components in a radial pattern; the radial drug delivery component is composed of a deformable substrate and a plurality of deformable units; the plurality of deformable units are arranged at intervals on one side of the substrate away from the contact lens body; gaps are formed between adjacent deformable units; the contact lens body, the substrate and the deformable units are all subjected to hydrophilization treatment; and liquid medicine is stored in the gaps between the deformable units by capillary action. The multifunctional drug delivery contact lens solves the problem that the existing eye drug delivery contact lens cannot simultaneously consider active adjustment of the drug delivery amount and long-term continuous drug use of the eye.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a multifunctional contact lens with passive release and active controllable drug delivery. BACKGROUND

[0002] Glaucoma is the second leading cause of blindness worldwide, and can lead to irreversible blindness in severe cases. So far, drug treatment is essential for the recovery of most glaucoma patients, and the main means of drug treatment is eye drops. For ordinary eye drops, after the eye drops are dropped on the surface of the eyeball, the drug concentration on the surface of the eyeball will immediately increase to a high concentration, and then the drug is slowly absorbed by the eyeball, and the tear dilution leads to a short residence time of the eye drops on the surface of the eyeball. When the concentration of the eye drops is lower than the effective concentration, the eye drops will not work.

[0003] The conventional eye drug delivery method has many defects: the eye drops dropped on the eye will be diluted by tears, normal physiological behaviors such as blinking, and drug barriers such as corneal tissue, resulting in less than 5% of the total amount of drug actually absorbed by the eye, low bioavailability, and difficulty in producing good therapeutic effect. The pulsed drug delivery method once a day leads to a short residence time of the drug on the surface of the eyeball, and also causes a dramatic change in drug concentration, and even harmful side effects to the human body when the drug molecules enter the blood. The conventional eye drop drug delivery method requires high initiative of the patient, and some patients cannot achieve the expected therapeutic effect due to forgetfulness. In addition, for acute angle-closure glaucoma with sudden rise in intraocular pressure, usually accompanied by headache, nausea and vomiting, hindering the patient from manually self-administering, and the delay in reducing intraocular pressure will inevitably cause optic nerve damage.

[0004] Contact lenses are an ideal platform for intimate contact with the human eye, and eye drops can be administered through contact lenses. Embedding microtubes in contact lenses as drug containers can provide sustained drug release, and the deformation of contact lenses triggered by the rise in intraocular pressure can also increase drug release, but the amount of drug release increased by the deformation of the eyeball is limited and cannot be actively adjusted according to the physiological conditions of different patients. Embedding a micro-pump driven by an external magnetic field in a contact lens can achieve on-demand unidirectional drug delivery without a battery, and in addition, embedding a coil and a capacitor in a contact lens can achieve electrically triggered on-demand drug delivery using LC resonance.

[0005] The existing passive diffusion type contact lenses cannot actively adjust the drug action rate and the drug size according to the physiological conditions of different patients, the adaptive deformation of the drug size is limited, and the needs of patients with acute angle-closure glaucoma with sudden rise of intraocular pressure, usually accompanied by headache, nausea and vomiting, cannot be met, and the patients cannot manually self-administer, and the delay of intraocular pressure reduction will inevitably cause optic nerve damage. The drug-loaded contact lenses with active stimulation triggering drug release in the current research can actively control the drug release through external stimulation, but they cannot be used for continuous drug administration of patients, and cannot overcome the problem of poor patient compliance.

[0006] In summary, the present application solves the problem that the existing eye drug delivery contact lenses cannot simultaneously consider active adjustment of the drug size and long-term continuous drug administration of the eye. SUMMARY

[0007] Therefore, the present application provides a multifunctional drug delivery contact lens with passive release and active control, which can directly deliver drugs to the surface of the eyeball, greatly reduce drug loss, prolong the action time of drugs on the surface of the eyeball, improve the bioavailability of drugs, and can control the release amount of drugs by deformation, change the release rate of drugs, quickly release a large amount of drugs through a simple control method when the patient's eye disease is severe, reduce the harm of high intraocular pressure to the patient, and improve the treatment effect; solve the problem that the existing eye drug delivery contact lenses cannot simultaneously consider active adjustment of the drug size and long-term continuous drug administration of the eye.

[0008] The present application adopts the following specific technical solutions:

[0009] A multifunctional drug delivery contact lens with passive release and active control, which is composed of a spherical cap-shaped contact lens body and a drug delivery additive layer located on the inner surface of the contact lens body;

[0010] The drug delivery additive layer is used to directly contact the cornea and store and control drug release;

[0011] The drug delivery additive layer has a plurality of radial drug delivery components in a radial pattern; the radial drug delivery component is composed of a deformable substrate and a plurality of deformable units, and a plurality of deformable units are arranged on one side of the substrate away from the contact lens body; gaps are formed between adjacent deformable units;

[0012] The contact lens body, the substrate and the deformable units are subjected to hydrophilization treatment;

[0013] The liquid drug is stored in the gap between the deformable units by capillary action.

[0014] Further, the drug delivery additive layer is made of a mixture of magnetic nanoparticles and PDMS (polydimethylsiloxane).

[0015] The substrate and the variable shape unit are capable of being deformed under the action of a magnetic field.

[0016] Further, the radial drug delivery components constitute a ring structure and are coaxially arranged with the contact lens body.

[0017] The inner diameter of the ring structure formed by the radial drug delivery components is greater than the diameter of the pupil, and the outer diameter does not exceed the diameter of the contact lens body.

[0018] Further, the substrate is in the shape of a rectangle or a sector.

[0019] Further, the variable shape unit is in the shape of a circular arc or a rectangle extending circumferentially along the contact lens body.

[0020] Further, the top of the variable shape unit does not exceed the inner surface of the contact lens body.

[0021] Further, the contact lens body is provided with a groove corresponding to the substrate in shape.

[0022] The substrate is embedded in the corresponding groove.

[0023] Further, the contact lens body is made of a flexible and highly transparent material.

[0024] Further, the contact lens body is made of PDMS.

[0025] Further, the variable shape units are arranged radially.

[0026] Beneficial effects:

[0027] 1. The multifunctional drug delivery contact lens of the present application is provided with a plurality of variable units in the drug delivery additive layer, and gaps are formed between the variable units, the contact lens body, the substrate and the variable units are treated by hydrophilization process, so that the liquid medicine is stored in the gaps between the variable units by capillary action; in the process of normal drug delivery during daily wearing of the patient, the liquid medicine is stored between the variable units of the drug delivery additive layer, which reduces the contact area of the liquid medicine with the eyeball, and the drug molecules are slowly released to the corneal surface by diffusion, which realizes sustained drug delivery and drug release, prolongs the drug delivery time, and overcomes the poor patient compliance; when the intraocular pressure of the patient increases, the cornea is deformed and extruded on the variable units in the drug delivery additive layer, the distance between the variable units changes, forcing the drug molecules between the variable units to be released, realizing self-adaptive drug delivery, improving the drug concentration on the ocular surface, and achieving good therapeutic effect; when the intraocular pressure returns to normal, the variable units of the drug delivery additive layer return to the original shape; therefore, the multifunctional drug delivery contact lens of the present application has the functions of passive diffusion drug delivery and self-adaptive drug delivery driven by intraocular pressure, can directly deliver the drug to the surface of the eyeball, greatly reduces the loss of the drug, prolongs the action time of the drug on the surface of the eyeball, and improves the bioavailability of the drug.

[0028] 2. Since the drug delivery additive layer is made of a mixture of magnetic nanoparticles and PDMS, the substrate and the variable units can be deformed under the action of a magnetic field, accelerating drug release, meeting the function of active accelerated drug delivery controlled by an external magnetic field, and realizing remote control of the release amount of the drug; when the intraocular pressure of the patient increases sharply, the deformation degree of the variable units caused by the intraocular pressure is limited, at this time, the variable units are actively controlled by an external magnetic field to quickly deflect and accelerate the rapid discharge of a large amount of drug, so as to rapidly increase the drug concentration on the corneal surface. Therefore, when the patient's eye disease is in a severe attack and it is difficult to self-administer, a large amount of drug can be quickly released by a simple control method, the harm of high intraocular pressure to the patient is reduced, the treatment effect is improved, and the problem that the existing ocular drug delivery contact lens cannot simultaneously meet the functions of active adjustment of drug delivery amount and long-term continuous drug delivery on the eye is solved. The multifunctional drug delivery contact lens has the functions of passive diffusion drug delivery, self-adaptive drug delivery driven by intraocular pressure and active accelerated drug delivery controlled by an external magnetic field. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 It is a front view of the multifunctional drug delivery contact lens of the present application;

[0030] Figure 2 It is a front view of the multifunctional drug delivery contact lens of the present application; Figure 1 It is a sectional view of the multifunctional drug delivery contact lens in A1-A2 section;

[0031] Figure 3 It is a schematic diagram showing the state change of the radial drug delivery component in the drug delivery additive layer when the intraocular pressure increases;

[0032] Figure 4 A schematic diagram of the state change of the radial drug delivery component in the drug delivery additive layer under the action of an external magnetic field under high intraocular pressure.

[0033] Wherein, 1-Contact lens body, 2-Drug delivery additive layer, 3-Radial drug delivery component, 4-Variable unit, 5-Liquid drug, 6-Substrate DETAILED DESCRIPTION

[0034] The present application will be described in detail below with reference to the accompanying drawings and examples.

[0035] The present embodiment provides a multifunctional drug delivery contact lens with passive release and active controllable functions, as shown in the structure, the multifunctional drug delivery contact lens is composed of a spherical cap contact lens body 1 and a drug delivery additive layer 2 located on the inner surface of the contact lens body 1; the contact lens body 1 is made of a high-transparency material with good biocompatibility and soft elasticity, such as PDMS; Figure 1 Figure 2 The drug delivery additive layer 2 is used to directly contact the cornea and store and control drug release;

[0036] The drug delivery additive layer 2 is used to directly contact the cornea and store and control drug release;

[0037] As shown in the structure, the drug delivery additive layer 2 has a plurality of radial drug delivery components 3 in a radial pattern; in this embodiment, a ring structure composed of a plurality of radial drug delivery components 3 is taken as an example for illustration, and the plurality of radial drug delivery components 3 are arranged coaxially with the contact lens body 1; the inner diameter of the ring structure formed by the radial drug delivery components 3 is greater than the diameter of the pupil, and the outer diameter does not exceed the diameter of the contact lens body 1; since the inner diameter of the ring structure formed by the radial drug delivery components 3 is greater than the diameter of the pupil, the radial drug delivery components 3 can be prevented from being within the pupil of the patient, thereby ensuring that the drug delivery additive layer 2 does not affect the patient's vision field; Figure 1 As shown in the structure, the radial drug delivery component 3 is composed of a deformable substrate 6 and a plurality of variable units 4, and the shape of the substrate 6 can be rectangular or sector-shaped; the plurality of variable units 4 are arranged at intervals on the side of the substrate 6 away from the contact lens body 1, and the plurality of variable units 4 can be arranged radially along the contact lens body 1; gaps are formed between adjacent variable units 4;

[0038] Figure 3 As shown in the structure, the radial drug delivery component 3 is composed of a deformable substrate 6 and a plurality of variable units 4, and the shape of the substrate 6 can be rectangular or sector-shaped; the plurality of variable units 4 are arranged at intervals on the side of the substrate 6 away from the contact lens body 1, and the plurality of variable units 4 can be arranged radially along the contact lens body 1; gaps are formed between adjacent variable units 4; Figure 4

[0039] ​​​In order to improve the storage of the liquid medicine 5, the contact lens body 1, the substrate 6 and the variable unit 4 are all treated with hydrophilization, and more liquid medicine 5 can be stored between the substrate 6 and the variable unit 4 after the hydrophilization treatment; the liquid medicine 5 is stored in the gap between the variable units 4 by capillary action. The top of the variable unit 4 does not exceed the inner surface of the contact lens body 1, that is, as shown in Figure 2 , the side surface of the variable unit 4 facing the eyeball is flush with or located within the inner surface of the contact lens body 1; in order to prevent the top of the variable unit 4 from protruding from the inner surface of the contact lens body 1, as shown in Figure 2 , the contact lens body 1 is provided with a groove corresponding to the substrate 6 and matching in shape; the substrate 6 is embedded in the corresponding groove; the variable unit 4 has a circular arc structure or a rectangular structure extending circumferentially along the contact lens body 1.

[0040] When the patient wears the above multifunctional drug delivery contact lens in daily life and in the normal drug delivery process, the liquid medicine 5 is stored between the variable units 4 after the hydrophilization treatment, reducing the contact area of the liquid medicine 5 with the eyeball, and the drug molecules are slowly released to the corneal surface by diffusion, achieving sustained drug delivery and drug release, prolonging the drug delivery time, and overcoming the poor patient compliance; when the intraocular pressure of the patient increases, as shown in Figure 3 , the cornea is deformed and swells and extrudes the variable units 4 in the drug delivery additive layer 2, the spacing between the variable units 4 changes, forcing the drug molecules between the variable units 4 to be released, achieving self-adaptive drug delivery and improving the drug concentration on the surface of the cornea, achieving good therapeutic effect; when the intraocular pressure returns to normal, the variable units 4 of the drug delivery additive layer 2 return to the original shape; therefore, the multifunctional drug delivery contact lens has the functions of passive diffusion drug delivery and intraocular pressure driven self-adaptive drug delivery, can directly deliver the drug to the surface of the eyeball, greatly reduces the loss of the drug, prolongs the action time of the drug on the surface of the eyeball, promotes the penetration of the drug molecules through the corneal tissue, the eyeball wall and other parts to reach the inside of the eyeball through the chemical potential, and improves the bioavailability of the drug.

[0041] The contact lens body 1 is made of PDMS with low Young's modulus, and when the intraocular pressure increases, the whole contact lens body 1 will deform, changing the gap between the variable units 4 and promoting the discharge of the drug, further improving the self-adaptive drug delivery performance.

[0042] Since the substrate 6 is embedded in the groove of the contact lens body 1, the drug delivery additive layer 2 is conveniently positioned through the groove, so that the combination and assembly between the drug delivery additive layer 2 and the contact lens body 1, and the recycling and liquid supplementing of the drug delivery additive layer 2 are facilitated.

[0043] In a specific embodiment, the drug delivery additive layer 2 is made of a mixture of magnetic nanoparticles and PDMS; the substrate 6 and the variable shape unit 4 can be deformed under the action of a magnetic field.

[0044] Since the drug delivery additive layer 2 is made of a mixture of magnetic nanoparticles and PDMS; the substrate 6 and the variable shape unit 4 can be deformed under the action of a magnetic field, so the drug delivery amount can be controlled by an external magnetic field. For example, in the case of acute angle-closure glaucoma with sudden increase of intraocular pressure, which is usually accompanied by headache, nausea and vomiting, it is difficult for the patient to manually self-administer the drug. In this case, the variable shape unit 4 is deflected to one side by the magnetic field generated by the magnet, and the rotating magnetic field can make all the variable shape units 4 deflect, thereby rapidly releasing the stored drug, increasing the concentration of drug molecules in the ocular surface, and achieving better therapeutic effect. Figure 4

[0045] Therefore, the deformation of the substrate 6 and the variable shape unit 4 by the external magnetic field can also accelerate drug release, meet the active acceleration of drug delivery function controlled by the external magnetic field, and thus the release amount of the drug can also be remotely controlled by controlling the magnetic field. When the patient's intraocular pressure rises sharply, the deformation of the variable shape unit 4 caused by the intraocular pressure is limited, and at this time the variable shape unit 4 is actively controlled by the external magnetic field to quickly deflect, accelerate the rapid discharge of a large amount of drug, and rapidly increase the drug concentration on the corneal surface. Therefore, when the patient's eye disease is severe and it is difficult to self-administer the drug, a large amount of drug can be quickly released by a simple control method, the damage to the optic nerve caused by high intraocular pressure is reduced, the therapeutic effect is improved, and the above multifunctional drug delivery contact lens simultaneously has the functions of passive diffusion drug delivery, intraocular pressure driven self-adaptive drug delivery and external magnetic field controlled active acceleration drug delivery.

[0046] In summary, the above is only a preferred embodiment of the present application, and is not used to limit the protection scope of the present application. Any modification, equivalent replacement, improvement, etc. within the spirit and principles of the present application shall be included in the protection scope of the present application.​

Claims

1. A multifunctional drug delivery contact lens with both passive release and active controllability, characterized in that: A contact lens body in the shape of a spherical cap and a drug delivery additive layer on the inner surface of the contact lens body; The drug delivery additive layer is used to directly contact with the cornea and store and control the release of drugs; The drug delivery additive layer has a plurality of radial drug delivery components in the shape of a spoke; the radial drug delivery components are composed of a deformable substrate and a plurality of deformable units; the deformable units are arranged on the side of the substrate away from the contact lens body; the deformable units are arranged in a radial direction; gaps are formed between adjacent deformable units; The contact lens body, the substrate and the deformable units are all subjected to hydrophilic treatment; Liquid drugs are stored in the gaps between the deformable units by capillary action; the drug delivery additive layer is made of a mixture of magnetic nanoparticles and PDMS; The substrate and the deformable units can be deformed under the action of a magnetic field; the deformable units are deflected to one side by a magnetic field generated by a magnet to achieve active drug delivery; The deformable units are in the shape of a circular arc or a rectangle extending along the circumference of the contact lens body; The top of the deformable units does not exceed the inner surface of the contact lens body.

2. The multifunctional dosing contact lens of claim 1, wherein, The radial drug delivery components form a ring structure and are coaxial with the contact lens body; The inner diameter of the ring structure formed by the radial drug delivery components is greater than the diameter of the pupil and the outer diameter does not exceed the diameter of the contact lens body.

3. The multifunctional dosing contact lens of claim 1, wherein, The substrate is in the shape of a rectangle or a sector.

4. The multifunctional dosing contact lens of claim 1, wherein, The contact lens body is provided with grooves corresponding to the substrates in shape; The substrates are embedded in the corresponding grooves.

5. The multifunctional medicated contact lens of claim 1, wherein, The contact lens body is made of a flexible and highly transparent material.

6. The multifunctional dosing contact lens of claim 5, wherein, The contact lens body is made of PDMS.

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