CN114652511A

CN114652511A - Medicine-carrying degradable lacrimal passage suppository

Info

Publication number: CN114652511A
Application number: CN202210543517.XA
Authority: CN
Inventors: 吴小李; 黄金波; 杨毅彬; 黄运矗
Original assignee: MAOMING PEOPLE'S HOSPITAL
Current assignee: MAOMING PEOPLE'S HOSPITAL
Priority date: 2022-05-19
Filing date: 2022-05-19
Publication date: 2022-06-24
Anticipated expiration: 2042-05-19
Also published as: CN114652511B

Abstract

The invention aims to provide a drug-loaded degradable lacrimal passage suppository, which aims to solve the problems that intraocular administration concentration is gradually reduced, efficiency is low, and dry eye treatment needs administration and secondary taking out, and the drug-loaded degradable lacrimal passage suppository comprises: skeleton, degradable layer, the skeleton with degradable layer link to each other, degradable layer contain the medicine, the medicine contain degradable layer surface coated medicine layer in or with carrying medicine microballon random distribution be in degradable in situ portion, lacrimal passage bolt do the skeleton with the cylindrical structure that degradable layer formed.

Description

Medicine-carrying degradable lacrimal passage suppository

Technical Field

The invention relates to the technical field of implants, in particular to a drug-loaded degradable lacrimal passage suppository.

Background

Dry eye, also known as keratoconjunctivitis sicca, is a general term for a variety of diseases characterized by multiple factors and complex causes of abnormal tear quality or quantity or hydrodynamics, resulting in decreased tear film stability, and associated ocular discomfort and/or ocular surface tissue pathology, which can lead to severe ocular surface immunoinflammation and other ocular surface diseases. At present, the treatment of the xerophthalmia is mainly an oral medicament and an external medicament, and is mainly based on the problem that inflammation exists due to the occurrence of the xerophthalmia.

The current intraocular administration is mainly an eye drop method, but the greatest problem of the administration method is low efficiency, and when one drop of eye drop is dropped into eyes, conjunctival sac (sac between eyes and eyelids) is filled, so that a large part of the eye drop is lost because the eye drop overflows to cheeks from the edge of eyelids. In addition, a significant portion of the eye drop remaining on the ocular surface can enter the punctum, thereby diluting the drug concentration. Currently, administration is also accomplished in the form of a drug-loaded punctal implant, but the problem is that the initial drug concentration is sufficient, and over time, the drug concentration becomes insufficient and the therapeutic effect is not achieved.

Therefore, the lacrimal passage suppository which can ensure the slow release and the continuous effectiveness of the medicine and can be used for treating the xerophthalmia is a good product with two advantages.

Disclosure of Invention

The invention aims to provide a drug-loaded degradable lacrimal passage suppository, which aims to solve the problems that the concentration of the concentrated intraocular drug administration is gradually reduced, the efficiency is low, and the drug administration and the secondary extraction are needed for the treatment of xerophthalmia.

The above object of the present invention is achieved by the following technical solutions:

a drug-loaded degradable lacrimal suppository comprising: skeleton, degradable layer, the skeleton with degradable layer link to each other, degradable layer contain the medicine, the medicine contain degradable layer surface coating in the medicine layer or with carrying medicine microballon random distribution in the degradable in situ portion, lacrimal passage bolt do the skeleton with the cylindrical structure that degradable layer formed.

Further, the framework is a cylindrical structure made of PHEMA materials, and the degradable layer is formed on the surface of the framework by spinning polylactic acid materials through electrostatic spinning.

Further, the diameter of the framework is 0.2-0.3mm, the thickness of the degradable layer is 0.05-0.1mm, the degradable layer is wound on the framework for 2-5 layers, and the diameter of the expanded framework is 0.5-1.2 mm.

Furthermore, the degradable layer is degraded for 3 to 5 days, and the framework is degraded for 6 to 25 days.

Further, the skeleton with the degradable layer form by PHEMA material through 3D printing, the skeleton be located the compact layer of lower part, the degradable layer be located the loose structure of skeleton upper portion.

Further, the skeleton is a membrane-shaped structure, and the skeleton and the degradable layer rotate the lacrimal passage suppository along the diagonal direction together.

Furthermore, the framework and the degradable layer are integrally printed by adopting PHEMA material.

Furthermore, the framework and the degradable layer contain at least two points of fracture.

Furthermore, a lead is fixed at one end of the framework.

Further, the medicine comprises: xerophthalmia medicine, glaucoma therapeutic medicine, anti-infective medicine, antiviral medicine, and analgesic medicine.

In conclusion, the beneficial technical effects of the invention are as follows:

(1) the continuous and stable concentration of the eye medicine can be realized by the gradual exertion of the function of the multilayer medicine layers and the function of the medicine carrying microspheres;

(2) the lead is reserved in the nasal cavity, so that the nasal cavity can be taken out conveniently and automatically without secondary taking out in an operation;

(3) through the design of the point-off part, the implant can be taken out in a segmented way, and the inflammatory reaction caused by individual large degradation products when all the implants are retained in the lacrimal passage and degraded is avoided.

Drawings

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described in detail with reference to the accompanying drawings, in which:

FIG. 1 is a schematic view of a lacrimal passage plug in an expanded state, according to an embodiment of the present invention;

fig. 2 is a schematic view of a lacrimal passage plug according to an embodiment of the present invention;

FIG. 3 is a schematic diagram of the second embodiment of the invention showing the deployed state of a lacrimal passage plug containing drug-loaded microspheres;

fig. 4 is a schematic view of a triple lacrimal passage peg configuration according to an embodiment of the present invention;

fig. 5 is a schematic view of a lacrimal peg with a guidewire according to an embodiment of the present invention;

fig. 6 is a schematic diagram of a five-way plug configuration in accordance with an embodiment of the present invention;

fig. 7 is a schematic view of the extended state of the lacrimal passage plug with a point-break in accordance with an embodiment of the present invention.

The specific symbols are:

a degradable layer-1; a first framework-2; carrying medicine microspheres-3; a lead-4; a second framework-5; point break-6.

Detailed Description

In order to more clearly illustrate the embodiments or technical solutions in the prior art of the present invention, the drawings and technical solutions required to be used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

At present, lacrimal passage plugs can be used for relieving and treating xerophthalmia and can be used as carriers for intraocular drug delivery. It is also a factor in inflammation in view of the current accepted recognition of the cause of dry eye.

Considering the drug loading of the lacrimal passage suppository, a multi-level gradual drug delivery mode is adopted, the next layer of drug delivery is carried out after the outer layer of drug delivery is finished, the drug delivery process is continuous and uniform, the assumption is that the film is formed by rotating and overlapping a layer of degradable film, and in order to better realize the continuous and uniform drug delivery effect, the drug is added into the degradable material in the form of slow release microspheres.

Meanwhile, in order to consider the fixation of the lacrimal passage suppository, a framework is added, the degradation time of the framework is far longer than the time of the complete degradation of the degradable layer, the degradation time of the degradable layer is set to be 3-5 days, the degradable layer is overlapped to form 2-5 layers, and the total degradation time, namely the administration time is 6-25 days.

In view of the fixation of the lacrimal plug, the thickness of the degradable layer is 0.05-0.1mm and the diameter or thickness of the skeleton is 0.2-0.3 mm. The framework is prepared from a self-expanding material PHEMA, the expansion of the PHEMA has a certain range, the framework gradually expands along with the gradual degradation of the degradable layer to realize the fixation of the lacrimal passage suppository, and the adjustable range of the framework is 0.5-1.2 mm.

The shape of the skeleton is based on the curling mode of the degradable layer, and the skeleton is cylindrical in a mode of rotating around the skeleton. For the structure formed by the framework and the degradable layer through co-rotation, the framework adopts a membrane-shaped structure.

Considering the design that the lacrimal passage suppository is convenient to take out and does not need to go to a hospital for secondary taking out, a lead is reserved at the lower end of the framework and is placed in the nasal cavity, and when treatment is completed or a product fails, the active framework is completely degraded and then is discharged automatically, or the lacrimal passage suppository is directly taken out by being directly pulled by the lead.

Still further, to the structure that skeleton and degradable layer slant curl jointly and form, can set up the skeleton into the point structure of breaking, every interval apart from skeleton can draw out a section skeleton under the tractive of lead wire, such lacrimal passage bolt can shorten gradually, finally draw out completely. The lead wire of the last section of framework is reserved in the nasal cavity, the lead wires of other sections of frameworks are reserved in the grooves at the point fracture positions, and when the first section of framework is broken after being drawn out, the lead wire connected with the new section of framework is automatically retained in the nasal cavity.

The first embodiment is as follows:

a lacrimal passage suppository is composed of a degradable layer 1, a first framework 2 and a drug coating, as shown in figure 1, the first framework 2 is a cylinder with the diameter of 0.3mm, the first framework 2 is made of PHEMA material, the degradable layer 1 is made of polylactic acid material, and is formed by spinning directly on the first framework 2 through rotation by using an electrostatic spinning machine, the structure is as shown in figure 2, the thickness of the degradable layer 1 is 0.05mm, a drug film is coated on the surface of one side of the degradable layer in the embodiment in advance, cyclosporin A with the concentration of 0.05% of the drug for treating xerophthalmia is selected, and one side with the drug film is positioned on the outer side.

Example two:

different from the first embodiment, the drug-loading mode of the degradable layer is drug-loaded microspheres 3, as shown in fig. 3, the drug is prepared into microspheres with a size of 30um by a microsphere technology in advance, and the drug used in the embodiment is the anti-infective tobramycin. Dissolving 5 wt% of drug-loaded microspheres 3 and polylactic acid in a solvent for electrostatic spinning.

Example three:

the difference between the second embodiment and the second embodiment is that the used materials, the preparation method and the rotational molding manner are as shown in fig. 4, in the second embodiment, the integrally molded degradable layer 1 and the first framework 2 are crimped to drive the degradable layer 1 to rotate by the first framework 2, the materials of the degradable layer 1 and the first framework 2 adopted in the second embodiment are PHEMA materials, the second embodiment is molded by a 3D printing manner, the printed first framework 2 is a compact structure, and the printed degradable layer 1 is a porous structure.

Example four:

in this embodiment, a lead 4 is added on the basis of the first to third embodiments, and as shown in fig. 5, the lead 4 is connected to one end of the framework.

Example five:

a lacrimal passage suppository comprises a second framework 5, a degradable layer 1 and a drug-carrying microsphere 3, wherein the preparation method of the drug-carrying microsphere 3 is the same as that of the second framework, the second framework 5 is of a membrane-shaped structure, the preparation method of the second framework is the same as that of the degradable layer 1, the second framework 5 and the degradable layer 1 rotate together along the diagonal direction to form a spiral second framework 5 structure, and as shown in figure 6, a lead 4 is fixed at one end of the second framework 5.

Example six:

on the basis of the fifth embodiment, the second framework 5 and the degradable layer 1 are integrally provided with three point fractures, as shown in fig. 7, the design can realize the sectional taking out of the lacrimal duct suppository, reduce inflammatory complications caused by the retention of degradation products in the lacrimal duct, in addition, a lead is fixed at each point fracture, and after one section of the tail end is pulled out, a new lead is unfolded and kept in the nasal cavity, thereby facilitating the subsequent operation.

The above description is only an embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that are not thought of through the inventive work should be included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope defined by the claims.

Claims

1. A drug-loaded degradable lacrimal suppository, comprising: skeleton, degradable layer, the skeleton with degradable layer link to each other, degradable layer contain the medicine, the medicine contain degradable layer surface coating in the medicine layer or with carrying medicine microballon random distribution in the degradable in situ portion, lacrimal passage bolt do the skeleton with the cylindrical structure that degradable layer formed.

2. The drug-loaded degradable lacrimal passage suppository of claim 1, wherein the skeleton is a cylindrical structure made of PHEMA material, and the degradable layer is formed on the surface of the skeleton by electrospinning and spinning polylactic acid material.

3. The drug-loaded degradable lacrimal suppository of claim 2, wherein the diameter of the scaffold is 0.2-0.3mm, the thickness of the degradable layer is 0.05-0.1mm, the degradable layer is wound on the scaffold for 2-5 layers, and the diameter of the scaffold after expansion is 0.5-1.2 mm.

4. The drug-loaded degradable lacrimal plug of claim 3, wherein the degradable layer degrades for 3-5 days and the scaffold degrades for 6-25 days.

5. The drug-loaded degradable lacrimal passage suppository of claim 1, wherein the skeleton and the degradable layer are formed by 3D printing of PHEMA material, the skeleton is a dense layer located at a lower portion, and the degradable layer is a loose structure located at an upper portion of the skeleton.

6. The drug-loaded degradable lacrimal plug of claim 1, wherein the scaffold is a membrane-like structure, and the scaffold and the degradable layer rotate together along a diagonal direction.

7. The drug-loaded degradable lacrimal plug of claim 6, wherein the skeleton and the degradable layer are integrally printed from PHEMA material.

8. The drug-loaded degradable lacrimal plug of claim 6, wherein the scaffold and the degradable layer comprise at least two point discontinuities.

9. The drug-loaded degradable lacrimal suppository of any of claims 1-8, wherein a lead is fixed to one end of the scaffold.

10. The drug-loaded degradable lacrimal plug of any of claims 1-8, wherein the drug comprises: xerophthalmia medicine, glaucoma therapeutic medicine, anti-infective medicine, antiviral medicine, and analgesic medicine.