KR101969594B1 - Implant for intraocular drug delivery - Google Patents

Abstract

The present invention relates to intraocular drug delivery implants that continuously release drugs in a desired direction in the eye and methods of making the same.
The implant according to the present invention is economical and efficient because the drug released in an undesired direction in the eye can be controlled by the impermeable part. In addition, since the implant according to the present invention is formed by coating an infiltration layer and an impermeable layer on a medicament, a desired shape can be easily manufactured.

Description

IMPLANT FOR INTRAOCULAR DRUG DELIVERY < RTI ID = 0.0 >

The present invention relates to intraocular drug delivery implants and methods of making the same. More particularly, the present invention relates to intraocular drug delivery implants that continuously release the drug in a desired direction and methods of making the same.

The primary problem in treating diseases or conditions of the eye is the introduction of active ingredients, such as drugs or other therapeutic agents, into the eye with therapeutically effective guinea pigs for the required period of time. Systemic administration can not be an ideal solution because the incidence of unacceptable side effects of the active ingredient increases and an often unacceptably high systemic dose is often required to achieve effective guide concentrations. A simple eye drop or application can not, in many cases, be an acceptable alternative, since the tear-action can cause the active ingredient to quickly wash away or be released into the general circulatory system in the eye.

Intravitreal injection of a drug solution is also performed, but drug efficacy is also transient. It is still difficult to maintain therapeutic levels of the drug for a reasonable period of time without re-administration.

Efforts to address these problems have resulted in the development of implants that can release a controlled amount of the desired active ingredient for a number of days, weeks, or months and can be inserted into the eye. Many of these devices have already been reported. For example, U.S. Patent No. 5,164,188 discloses a method of implanting a bioerodable implant containing a drug into a choroidal space or a pars plana of an eye to treat an eye condition. Also, U.S. Patent No. 7658364 uses a dual mode to regulate drug release. However, although the conventional technologies release the drug into the eyeball, the amount and the direction of the release of the drug are still not controlled, and development of an implant that effectively transfers the drug to the anterior segment is still effective.

The present invention provides an implant capable of continuously releasing a drug in a desired direction in the eyeball.

An object of the present invention is to provide an implant manufacturing method capable of freely controlling an implant shape and a discharge direction.

One aspect of the present invention is an implant comprising: a penetration layer containing a therapeutic agent therein; And a non-transmissive portion formed on a part of the outer surface of the penetrating layer to control the direction of emission of the therapeutic agent, wherein the therapeutic agent is released into the eye through the outer surface of the penetrating layer on which the non-transmissive portion is not formed, (intraocular) drug delivery implants.

One aspect of the present invention is an intraocular drug delivery implant for the treatment of ocular disease, the implant comprising a therapeutic agent of a predetermined shape; A penetration layer formed on all or part of the outer surface of the therapeutic agent; And a non-permeable portion formed on or coated on a portion of the outer surface of the permeable layer on which the penetrating layer is not formed, wherein the therapeutic agent is dissolved so that the non-permeable portion is released into the eye through the non- (intraocular) drug delivery implants.

In another aspect, the invention is an intraocular drug delivery implant for the treatment of ocular disease, the implant comprising a therapeutic agent of a predetermined shape located on the opaque portion; And an intraocular drug delivery implant comprising an impermeable layer or an impermeable layer formed on the outer surface of the therapeutic agent in a predetermined shape, wherein the therapeutic agent is dissolved and released into the eye through the impermeable layer without coating the impermeable portion.

In another aspect, the present invention provides a method of preparing an intraocular drug delivery implant for the treatment of eye diseases,

Forming a non-transparent layer by spin coating; placing a therapeutic agent of a predetermined shape on the opaque layer; And coating an impermeable layer on the impermeable layer and the therapeutic agent, wherein the therapeutic agent is dissolved and released into the eye through the impermeable layer, wherein the impermeable portion is not coated, to produce an intraocular drug delivery implant Method.

The implant according to the present invention is economical and efficient because the drug released in an undesired direction in the eye can be controlled by the impermeable part.

The implant according to the present invention is formed by coating an infiltration layer and an impermeable layer on a drug, so that a desired shape can be easily manufactured.

1 is a cross-sectional view of an intraocular drug delivery implant according to one embodiment of the present invention.
2 is a cross-sectional view of a guide drug implant of the present invention having a therapeutic agent of a predetermined shape.
3 is a cross-sectional view of another guided drug implant of the present invention having a therapeutic agent of a predetermined shape.
4 is a cross-sectional view of a guide drug implant according to another embodiment of the present invention.
5 shows the hydrophobic polymer formed on the implant of Fig.
Figure 6 shows a method of manufacturing an intraocular drug delivery implant of the present invention.
7 shows a method of manufacturing a drug delivery implant according to another embodiment of the present invention.

The present invention can be all accomplished by the following description. The following description should be understood to describe preferred embodiments of the present invention, but the present invention is not necessarily limited thereto.

In addition, the accompanying drawings may be exaggeratedly expressed relative to the actual layer thickness (or height) or the ratio with respect to other layers in order to facilitate understanding, and the meaning thereof may be properly understood in view of the specific purpose of the related description to be described later .

The lamination structure referred to in the present specification should be understood in an exemplary sense, and the present invention is not limited to such a specific lamination structure.

As used herein, the terms " on " or " on " may be used to refer to the relative position concept, as well as where other elements or layers are directly present in the stated layer, It should be understood that the layer (interlayer) or component may be interposed or present, and also includes the case where the surface of the layer mentioned above (particularly the surface having a three-dimensional shape) is not completely covered, . Therefore, unless otherwise expressly referred to as " directly " is used, it can be understood as a relative concept as described above. Similarly, the expression "underneath", "underneath" or "underneath" may also be understood as a relative concept of the position between a particular layer (element) and another layer (element).

1 is a cross-sectional view of an intraocular drug delivery implant according to one embodiment of the present invention. 2 is a cross-sectional view of a guide drug implant of the present invention having a therapeutic agent of a predetermined shape. 3 is a cross-sectional view of a guide drug implant provided with a therapeutic agent of a predetermined shape. 4 is a cross-sectional view of a guide drug implant according to another embodiment of the present invention. 5 is a cross-sectional view of a guide drug implant according to another embodiment of the present invention. 1 to 5, the guiding drug delivery implant of the present invention includes a therapeutic agent 10, a non-permeable portion 20 and a permeable layer 30 in a predetermined shape.

First, referring to FIG. 1, a guide implant includes a non-opaque portion 20 and a penetration layer 30. FIG. The permeable layer 30 contains a therapeutic agent therein. The penetration layer 30 is formed by coating a mixture containing a therapeutic agent and a permeable polymer. The therapeutic agent present in the penetration layer 30 may dissolve in the eyeball and may be continuously released in a desired direction in the eyeball through the outer surface where the opaque portion is not formed.

The implant of FIG. 1 can form the penetrating layer and the non-penetrating portion in the form of a thin film of a bilayer. In addition, in the present invention, the implant of FIG. 1 can be manufactured by variously modifying it. For example, the implant may be formed by coating an impermeable portion except for a part of the outer surface of the permeable layer. More specifically, the implant of the present invention may include an implant of a structure that surrounds the remaining area of the permeable layer with the impermeable portion, except for the upper portion of the permeable layer.

The opaque portion 20 and the penetrating layer 30 will be described later.

In FIG. 1, the therapeutic agent is present in the penetration layer rather than in a predetermined shape, whereas the implant in FIGS. 2 to 5 further comprises a therapeutic agent 10 of a predetermined shape. Here, the term " predetermined shape " is used as a term indicating that the therapeutic agent has a certain size and shape and is solidified, not in a liquid or powder state. The therapeutic agent contained in the permeation layer of Fig. 1 or the therapeutic agent of the above-mentioned shape need not necessarily be the same component. The therapeutic agent of the predetermined shape may have a cylindrical shape, a square pillar, or a stripe shape. In the present invention, the therapeutic agent may have a predetermined shape by compressing a powdery therapeutic agent, for example, a pellet press, but is not limited thereto. As the therapeutic agent is compressed and formed into a predetermined shape, the volume can be minimized.

Although the size (diameter) and thickness of the therapeutic agent 10 are not limited, it is preferable that the diameter is 30 mm or less, preferably 5 to 15 mm, and the thickness is 0.1 to 1 mm, preferably 0.3 to 1 mm, Preferably about 0.5 mm.

As the therapeutic agent, a non-aqueous drug, for example, a drug which can be injected into the steroid-based drug eye can be used without limitation.

Preferably, timolol and latanoprost, which are glaucoma therapeutic agents, can be used.

Referring to FIG. 2, the therapeutic agent 10 is located on the permeable layer 30. The penetration layer 30 is formed on all or part of the outer surface of the therapeutic agent 10. [ Preferably, the permeable layer 30 is coated on the upper surface or the lower surface of the therapeutic agent, but not on the entire outer surface of the therapeutic agent 10. Referring to FIG. 2, the opaque portion 20 may be formed on the therapeutic agent 10 on which the penetrating layer 30 is not formed, or may be coated on a part of the outer surface of the penetrating layer. The opaque portion 20 is formed of a material which takes a long period of time even though the drug hardly passes or passes through, and substantially does not have a drug release effect.

3, the implant according to the present invention is characterized in that the therapeutic agent 10 is located on the opaque portion 20 and includes a permeable layer 30 formed on the opaque portion 20 or the outer surface of the therapeutic agent 10. In FIG. 3, the impermeable portion may be formed by first coating and then coating the penetration layer with the therapeutic agent 10 thereon.

Referring to FIG. 4, the implant of the present invention includes the penetration layer 30 formed on the therapeutic agent 10, the therapeutic agent 10 being positioned on the opaque portion 20 protruded on both sides. The implant of FIG. 4 can be formed by placing the therapeutic agent 10 on the cast portion 20 and coating the permeable layer 30 thereon.

Referring to Figs. 2 to 4, the penetration layer is coated on one side of the therapeutic agent, and the opaque part can be coated on at least one of the side and the side of the therapeutic agent.

2 to 4, since the therapeutic agent 10 hardly transmits the opaque portion 20, the therapeutic agent can be released into the eye through only the penetrating layer 30.

In the present invention, the release direction of the therapeutic agent can be controlled by forming the opaque portion 20 in a specific region on the therapeutic agent 10 or the penetrating layer 30.

The opaque portion 20 may be formed on the therapeutic agent 10 on which the penetrating layer 30 is not formed, or may be coated on a part of the outer surface of the penetrating layer. The opaque portion 20 is formed of a material which takes a long period of time even though the drug hardly passes or passes through, and substantially does not have a drug release effect.

Since the therapeutic agent 10 hardly transmits the opaque portion 20, the therapeutic agent can be released into the eye through only the penetrating layer 30.

The opaque portion 20 can be a biocompatible material and can maintain its shape even after a long period of time. For example, the opaque portion 20 may be at least one selected from silicon, polysulfone, polyether imide, polyimide, polymethyl methacrylate, polyether ether ketone, and copolymers of these compounds. The opaque portion may preferably be made of silicon, and more preferably, a medical grade silicon is used.

The penetration layer 30 is formed by coating a mixture containing a therapeutic agent and a permeable polymer. In the permeable layer (30), a therapeutic agent is contained in the permeable polymer. The therapeutic agent contained in the penetration layer 30 is preferably the same as the therapeutic agent 10 of the predetermined shape. That is, a permeation layer in which a therapeutic agent in a powdery or liquid state is mixed with a permeable polymer at a predetermined ratio and then coated on the surface of the therapeutic agent 10, or a powder or liquid therapeutic agent is mixed with the permeable polymer in a predetermined ratio is formed first, The therapeutic agent 10 can be placed.

The therapeutic agent of the permeable layer 20 is firstly released into the eyeball prior to the therapeutic agent 10 of the predetermined shape and the therapeutic agent 10 is secondarily discharged through the space where the therapeutic agent of the permeable layer 20 is released, Lt; / RTI >

The permeable polymer used in the permeable layer is preferably a biocompatible material and a material capable of retaining its shape even after a long period of time and capable of functioning as a binder capable of supporting a therapeutic agent. As the permeable polymer, silicone or polyvinyl alcohol can be used, and silicon is preferable.

The weight ratio of the permeable polymer forming the permeable layer to the therapeutic agent may be 1: 0.5 to 0.01, preferably 1: 0.3 to 0.1.

The content of the therapeutic agent contained in the penetrating layer can be controlled to control the amount of the substance released into the eyeball. However, when the content of the therapeutic agent contained in the permeable layer exceeds 50% of the permeable polymer, it is difficult to form the skeleton of the permeable layer.

The permeable layer and the opaque portion are not limited in thickness. For example, the permeable layer may be about 0.5 to 1.5 mm, preferably 1 to 1.2 mm, the opaque layer may have a thickness of 0.1 to 1 mm, preferably 0.2 to 0.5 mm Lt; / RTI > According to the present invention, since the impregnated layer and the impermeable portion are coated, the total thickness of the implants can be made relatively thin. Further, since the impermeable portion or the shape of the impregnated layer is not formed using the template, It is efficient.

5 shows the hydrophobic polymer formed on the implant of Fig. Referring to FIG. 5, the implant may include a hydrophobic polymer layer 40 between the opaque portion 20 and the therapeutic agent 10. The therapeutic agent can not penetrate the hydrophobic polymer layer. Therefore, the hydrophobic polymer layer can be formed to increase the unidirectionality, and the release direction of the therapeutic agent can be controlled similarly to the opaque layer.

The hydrophobic polymer layer is a biocompatible material that is not toxic to the human body, chemically inert, and free of immunogens. Materials that should not be dissolved or dissolved in water even after prolonged use can be used.

Illustratively, the hydrophobic polymer layer may be a silicone, polysulfone, polyetherimide, polyimide, polymethylmethacrylate, polyetheretherketone, polyorthoester, polyetherester, polyurethane, Polyacrylates, ethylene-vinyl acetate polymers, and the like.

Figure 6 shows a method of manufacturing an intraocular drug delivery implant of the present invention. 7 shows a method of manufacturing a drug delivery implant according to another embodiment of the present invention.

Referring to FIG. 6, the method includes forming the opaque portion 20 by spin coating, placing a therapeutic agent 10 of a predetermined shape on the opaque portion, (30). ≪ / RTI >

7, the method includes spin coating a permeable layer 30, placing a therapeutic agent 10 of a predetermined shape on the permeable layer, and depositing a therapeutic agent 10 on the permeable layer 30 and the therapeutic agent 10 Coating the impermeable portion 20 on the substrate. Referring to FIG. 7, continuing the coating of the impermeable portion 20 may cover the impermeable portion to the side of the therapeutic agent 10 and the penetrating layer 30. In this case, the therapeutic agent can not be released sideways but can be released only to the lower part where the penetration layer 30 is present.

The permeability layer may be formed by coating a mixture containing a therapeutic agent and a permeable polymer, wherein the weight ratio of the therapeutic agent to the permeable polymer is 1: 0.5 to 0.01, preferably 1: 0.3 to 0.1.

As for the therapeutic agent 10, the impermeable portion 20, and the permeable layer 30, the above description can be referred to.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following embodiments are provided for the purpose of easier understanding of the present invention, but the present invention is not limited thereto.

Example

First, timolol, a therapeutic agent for glaucoma, was compressed using a pellet press (parr instrument, 2811) to prepare a circular therapeutic agent having a diameter of 1/4 inch and a thickness of 0.5 mm.

Then, 0.21 g of 100% silicone (Nusil technology) was mixed with 0.07 g of thymolol, and the mixture was spin-coated on the bottom to form a penetration layer having a thickness of 0.5 mm. The circular therapeutic agent prepared on the permeation layer was placed, and then 100% silicone (Nusil technology) was spin-coated on the therapeutic agent to form an impermeable portion with a thickness of 0.2 mm. After drying for two days, an implant of the present invention was obtained.

It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the appended claims.

10: Therapeutic agent 20: Impermeable part
30: Penetrating layer 40: hydrophobic polymer layer

Claims (15)

An intraocular drug delivery implant for the treatment of eye diseases, said implant comprising:
A solid therapeutic agent (10) solidified into a predetermined size and shape;
A non-opaque portion (20) which contacts at least one surface of the solid therapeutic agent (10) or surrounds at least one surface thereof to inhibit permeation of the solid therapeutic agent;
And an impermeable layer (30) formed on at least one surface of the solid therapeutic agent,
Wherein the permeable layer is coated with a mixture comprising a therapeutic agent and a permeable polymer, the weight ratio of the permeable polymer to the therapeutic agent is 1: 0.3-0.1,
The therapeutic agent for the solid therapeutic agent 10 and the permeable layer 30 may be the same or different,
The therapeutic agent of the penetration layer 30 is released into the eyeball before the solid therapeutic agent 10 and the solid therapeutic agent is released into the eye through the space generated by disappearance of the therapeutic agent of the permeable layer,
The permeable polymer is silicone or polyvinyl alcohol,
Wherein the impermeable portion is at least one selected from silicone, polysulfone, polyetherimide, polyimide, polymethylmethacrylate, polyetheretherketone, and copolymers of these compounds. delete delete delete delete The guide drug delivery implant according to claim 1, wherein the solid therapeutic agent has a thickness of 0.1 to 1 mm. The guiding drug delivery implant according to claim 1, wherein the thickness of the penetration layer is 0.5 to 1.5 mm and the thickness of the opaque layer is 0.1 to 1 mm. delete delete delete 2. The guiding drug delivery implant of claim 1, wherein the implant comprises a hydrophobic polymer layer between the opaque portion and the solid therapeutic agent. The guiding drug delivery implant according to claim 1, wherein the solid therapeutic agent or the therapeutic agent for the penetration layer is a steroid-based drug or timolol or latanoprost which is a glaucoma therapeutic agent.

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