KR101754959B1

KR101754959B1 - Antimicrobial punctum plug and manufacturing method thereof

Info

Publication number: KR101754959B1
Application number: KR1020150160994A
Authority: KR
Inventors: 김동관
Original assignee: 주식회사 유엠아이옵틱스
Priority date: 2015-11-17
Filing date: 2015-11-17
Publication date: 2017-07-06
Also published as: KR20170057644A

Abstract

The present invention relates to an antibacterial point plug and a method for producing the same, and more particularly to a biodegradable suture that constitutes a body of a plug with a missing point; And i) a PGLA polymer coated on the surface of the suture, and ii) a coating layer containing chlorhexidine or a salt thereof; To a point plug.
According to the present invention, when the punctal closure technique is performed, not only the symptom of dryness of the eye, which is the function of the punctal plug, but also the antimicrobial effect to the trauma after ophthalmic surgery is suppressed by suppressing the bacterial proliferation, Can be expected more.

Description

An antimicrobial punctum plug and a method of manufacturing the same,

More particularly, the present invention relates to an antibacterial plug which is useful for dry eye syndrome by using a suture coated with an antibacterial substance and is useful for inhibiting bacterial growth in the eye, and a method for producing the same .

Dry eye syndrome is a disease in which the tear is insufficient or excessively evaporated and the tear component is not balanced and the surface of the eye is damaged. It may be snowy or blurred, and in severe cases it can cause eye soreness and pain, such as sand in the eyes. Causes of dry eye syndrome include: 1) decreased amount of tears from the lacrimal gland, 2) incomplete formation of tear film due to abnormal tear component (caused by eyelid inflammation), 3) (Such as a computer or a book), 4) a lack of stimulation of the tear secretion due to the deterioration of the sensory nerve in the cornea (mainly occurring in patients wearing contact lenses) , And 5) those associated with eyelid inflammation, drug abuse, trauma, chronic conjunctivitis, eyelid abnormalities, and systemic disease.

As a method of treating dry eye syndrome, there is a method of supplementing the moisture of eyes by eye drop (artificial tear liquid) or ointment which is similar to tears in the outside as the tear is insufficient, and a method of closing the eye with a plug . The dots called "tear holes" are circular or elliptical holes with an average diameter of 0.25 mm, and they are the entrance portions of the umbilical cords with one on each side of the upper and lower eyelids. When tears are generated, they flow down along the surface of the eyeballs, flow into the dots, and flow down into the nostrils through the nasolas connected to the nose. The closure technique is a cure that keeps tears in the eye by keeping the tears flowing through the plugs. Unlike conventional artificial tears, there is no fear of exposure to preservatives, and the duration of effect is long. The point plug is disclosed, for example, in Japanese Patent Laid-Open No. 10-2007-0121555.

On the other hand, keratitis is a common eye disease. The cornea, which corresponds to the blackness of our eyes, is a glassy transparent tissue that serves as the window of the eye. Keratitis is inflammation of the cornea due to various causes. The causes of keratitis can be divided into infectious and non-infectious. Infectious keratitis is caused by various pathogens such as bacteria, viruses, fungi (fungus), etc. Staphylococcus and Pseudomonas aeruginosa are the bacteria causing the infection, herpes simplex virus ), And fungi include Fusarium. Currently, there is a continuing need for measures that can effectively inhibit such bacteria in the eyeballs.

It is an object of the present invention to provide an antibacterial plug having antibacterial effect after ocular related surgery or trauma by suppressing bacterial growth as well as alleviating symptoms of dry eyeball, and a method for producing the same.

According to an aspect of the present invention,

A biodegradable suture constituting the body of the plug; And

I) a PGLA polymer coated on the surface of the suture, and ii) a coating layer containing chlorhexidine or a salt thereof;

Of the plug.

Also,

a) preparing a solution of chlorhexidine or a salt thereof;

b) preparing a PGLA polymer solution;

c) mixing the chlorhexidine or salt solution thereof with the PGLA polymer solution to prepare a coating solution;

d) coating the biodegradable suture with the coating solution; And

e) drying the coated suture

And a method of manufacturing a leak plug including the plug.

According to the present invention, when the punctal closure technique is performed, not only the symptom of dryness of the eye, which is the function of the punctal plug, but also the antimicrobial effect to the trauma after ophthalmic surgery is suppressed by suppressing the bacterial proliferation, Can be expected more.

The present invention is also applicable to 1) inhibition of bacterial growth and relieving dry eye syndrome after LASIK and LASEK surgery, and 2) treatment of keratitis.

1 is a schematic view showing an antibacterial point plug according to an embodiment of the present invention.
Fig. 2 is an enlarged schematic view of an antimicrobial coating layer indicated by a dotted line in Fig. 1. Fig.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In order to clearly illustrate the present invention, parts not related to the description are omitted, and similar parts are denoted by like reference characters throughout the specification.

Throughout the specification, when an element is referred to as "comprising ", it means that it can include other elements as well, without excluding other elements unless specifically stated otherwise.

1 is a schematic view showing an antibacterial point plug according to an embodiment of the present invention.

2 is an enlarged schematic view of an antimicrobial coating layer indicated by a dotted line in Fig.

The plug 10 of the present invention is formed by coating a biodegradable suture 20 with a coating material containing an antibacterial substance chlorhexidine or its salt 31 and a PGLA polymer 32 to form a coating layer 30 And is an antibacterial plug with a predetermined length. The suture 20 may be a single yarn composed of one or more strands, or may be a twisted yarn composed of a plurality of strands twisted together.

Chlorhexidine has an antibacterial effect against the following bacteria.

Staphylococcus aureus (SA) - Staphylococcus aureus

· Methicillin-resistant Staphylococcus aureus (MRSA) - Methicillin-resistant Staphylococcus aureus

· Staphylococcus epidermidis (SE) - Staphylococcus epidermidis

· Methicillin-resistant Staphylococcus epidermidis (MRSE) - Methicillin-resistant Staphylococcus epidermidis

Genotoxicity studies in mice have shown that chlorhexidine can cause primary DNA damage to leukocytes, kidney cells, and oral mucosal cells, but there is no chromosome breakage or loss of red blood cells. Chlorhexidine has high cytotoxicity in vitro and can cause apoptosis and self-digestion / necrotic cell death, disruption of mitochondrial function, increased intracellular calcium and oxidative stress.

Specifically, PGLA (poly (lactic- co- glycolic acid)) may be used as the biodegradable suture 10. PGLA is a copolymer of glycolic acid and lactide, which is hydrolyzed in the body by lactic acid and glycolic acid. PGLA or poly (lactic-co-glycolic acid) is used in a number of Food and Drug Administration (FDA) approved therapeutic devices due to biodegradability and biocompatibility. PGLA has been successfully used as a biodegradable polymer because it is hydrolyzed in the body as the original monomers, lactic acid and glycolic acid. Under normal physiological conditions, these two monomers are by-products of various metabolic pathways in the body. Because the body effectively treats the two monomers, they have minimal human toxicity with respect to the use of PGLA for drug delivery and biomaterial applications. In addition, the possibility of adjusting the decomposition time of the polymer by changing the proportion of the monomers used in the synthesis can be achieved by using PGLA in various products of biomedical devices such as implants, sutures, implants, prosthetic devices, surgical sealants, micro- and nanoparticles .

As described above, PGLA is excellent in biocompatibility and biodegradability and is suitable as a suture applied to a sensitive eye such as the present invention. Specifically, PGLA is a polyglycolic acid and a polylactide of a suture used in the present invention. ) Can be applied in a weight ratio of 9: 1.

Also, the coating layer 30 coated on the suture 20 includes chlorhexidine or its salt 31 and an PGLA polymer 32, which are antimicrobial substances. Preferably, the coating layer 30 may further include silver (Ag) or silver salt.

Specifically, the chlorhexidine or its salt 31 may be contained in an amount capable of imparting an antibacterial function to the plug 10, for example, 0.02-0.5 wt% of the plug 10 And the content of the PGLA polymer (32) may be 5 to 40 parts by weight relative to 1 part by weight of chlorhexidine or its salt (31). When silver or silver salt is contained, silver or silver salt and antimicrobial substance To 1: 0.2 to 1: 5.

A leak plug according to the present invention comprises: a) preparing a solution of chlorhexidine or a salt thereof; b) preparing a PGLA polymer solution; c) mixing the chlorhexidine or salt solution thereof with the PGLA polymer solution to prepare a coating solution; d) coating the biodegradable suture with the coating solution; And e) drying the coated suture. The coating solution may further include silver (Ag) or silver salt.

a) Preparation of chlorhexidine or its salt solution may be carried out using methanol or ethanol as a solvent. Specific examples thereof include chlorhexidine or a salt thereof in an amount of 2 to 15% by weight based on the total weight of the solution Can be prepared.

b) In the step of preparing the PGLA polymer solution, ethyl acetate or methylene chloride may be used as a solvent, and the biodegradable PGLA polymer may be dispersed in a solvent. When the biodegradable PGLA polymer is dispersed, calcium stearate ) Can be used. Specifically, glycolide and lactide PGLA polymer (PGLA copolymer) and calcium stearate in a weight ratio of 3: 7 are dissolved in ethyl acetate or methylene chloride as a solvent and dispersed. In this case, the PGLA polymer may be used in an amount of 0.5-20% by weight, calcium stearate (1-10% by weight) and a residual solvent.

c) preparing a coating solution by mixing chlorhexidine or a salt solution thereof with a PGLA polymer solution, preparing a coating solution by mixing a solution of the antimicrobial agent prepared in a) and a polymer solution in b) Specifically, the antimicrobial agent solution and the polymer solution may be mixed in a ratio of 1: 5 to 1:40 based on the weight ratio.

The coating solution may further contain silver (Ag) or silver salt. Specifically, the silver or silver salt may be contained such that the molar ratio of the silver or silver salt to the antimicrobial agent is 1: 0.2 to 1: 5.

d) coating the biodegradable suture with the coating solution may include coating the biodegradable suture with the biodegradable suture using a coating method known in the art. For example, the biodegradable suture may be biodegradable It can be coated on suture.

Specifically, PGLA (poly (lactic- co- glycolic acid)) may be used as the biodegradable suture 10. PGLA is a copolymer of glycolic acid and lactide. More specifically, the weight ratio of poly glycolic acid to poly lactide in the suture used in the present invention is 9: 1 < / RTI >

As a specific example, the coating solution coated on the biodegradable suture may be coated to 20 to 35 parts by weight based on 100 parts by weight of the biodegradable suture.

e) In the step of drying the coated suture, the coated suture coated with the coating solution may be dried at 70 to 90 캜.

The biodegradable suture coated with the coating solution after the drying step is cut to a length of 1.9-2.1 mm, which is a length suitable for use in the occlusion, and is packaged in a package to be sterilized with EO (ethylene oxide gas).

In the above description, chlorhexidine is used as an antibacterial substance. However, the following antibacterial substances can also be used.

1. Triclosan or grapefruit seed extract, the content of which is 0.01-10 wt%

2. For the manufacture of antimicrobial coatings

18 kg of methylene chloride (MC), which is a solvent, was added to 1 g of a copolymer (PGLA) of glycolide and lactide having a weight ratio of 3: 7, 1 g of calcium stearate and 2,000 ppm of triclosan, Dissolve.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, Of the right.

10: Leakage plug
20: Suture
30: Antimicrobial coating layer
31: Antimicrobial agent
32: Polymer

Claims

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18 kg of methylene chloride (MC) as a solvent was added to 1 g of a copolymer of glycollide and lactide (PGLA) having a weight ratio of 3: 7, 1 g of calcium stearate and 2,000 ppm of triclosan in a coating bath to dissolve Preparing a coating solution,
Coating the biodegradable suture with the coating solution;
Drying the coated suture;
Cutting the dried suture to a predetermined length and packaging it in a package to sterilize EO (Ethylene Oxide Gas)
Of the plug.

5. The method of claim 4,
Wherein the coating solution further comprises a silver salt.

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