KR20180045845A - Ophthalmic formulation for treating glaucoma - Google Patents

Abstract

The present invention relates to an eye drop formulation for treating glaucoma. More specifically, the present invention relates to an eye drop formulation for treating glaucoma, consisting of a glaucoma treatment drug, an albumin nanoparticle holding the drug, and a coating layer encapsulating the nanoparticle. As the coating layer is bio-degraded by enzymes present in the tears upon administration of the eye drop formulation, it is possible to extend a time that the drug takes effect through consistent release of the drug, and the drug is not released when stored.

Description

Ophthalmic formulation for treating glaucoma < RTI ID = 0.0 >

The present invention relates to an ophthalmic drug for treating glaucoma, and more particularly, to a medicament for treating glaucoma, an albumin nanoparticle carrying the drug, and a coating layer surrounding the nanoparticle, The present invention relates to an ophthalmic formulation for treating glaucoma which is biodegraded by an existing enzyme to increase the effective time through sustained release of the drug and does not release the drug during storage.

Glaucoma is a disease in which the optic nerve is damaged due to the elevation of the intraocular pressure and gradually becomes blind. Drugs are widely used to treat this disease. Conventional glaucoma treatment drugs treat glaucoma by lowering the pressure in the eye by increasing the flow rate of the drug through the cornea and the flow of water through the cornea when the drug is prescribed on the surface of the cornea .

<Patent Literature>

Patent Publication No. 10-2012-0047851 (2012. 95. 14. Open) "Pharmaceutical composition containing no phosphate added for the treatment of glaucoma"

However, conventional drugs for treating glaucoma are monomolecular, and only about 2 to 3% penetrate the cornea and enter the anterior chamber. Therefore, the drug efficacy is lower than the amount used, and the drug washed out from the surface of the cornea The drug is transferred to other organs of the body, which causes various side effects.

SUMMARY OF THE INVENTION The present invention has been made to solve the above problems,

It is an object of the present invention to provide an anti-glaucoma medicament for treating glaucoma in which the retention time at the surface of the cornea is increased to continuously release the drug to increase the effective time and reduce the amount of drug circulating throughout the body.

It is also an object of the present invention to provide an eye drop formulation for treating glaucoma which does not release a drug during storage.

It is another object of the present invention to provide an anti-glare agent for treating glaucoma in which a coating layer on the surface of nanoparticles is slowly decomposed by enzymes present in tears and drugs can be released in a sustained release form from nanoparticles.

The above-described incidence is implemented by an embodiment having the following configuration in order to achieve the above-mentioned object.

According to an embodiment of the present invention, the ophthalmic medicament for treating glaucoma according to the present invention comprises a drug for treating glaucoma, albumin nanoparticles carrying the drug, and a coating layer surrounding the nanoparticles, The coating layer is biodegraded.

According to another embodiment of the present invention, in the ophthalmic formulation for treating glaucoma according to the present invention, the coating layer is decomposed by an enzyme contained in the tears.

According to another embodiment of the present invention, in the ophthalmic medicament for treating glaucoma according to the present invention, the ophthalmic drug formulation has a spherical shape.

According to another embodiment of the present invention, in the eye drop formulation for treating glaucoma according to the present invention, the eye drop formulation has a diameter of 100 to 300 nm.

According to another embodiment of the present invention, in the ophthalmic formulation for treating glaucoma according to the present invention, the coating layer is formed of acetylated or acrylated chitosan.

According to another embodiment of the present invention, in the ophthalmic formulation for treating glaucoma according to the present invention, the nanoparticles are formed by disulfide bonding between albumin molecules.

According to another embodiment of the present invention, in the medicament for treating glaucoma according to the present invention, the drug is characterized in that latanoprost is used.

According to another embodiment of the present invention, there is provided a method for preparing an ophthalmic formulation for treating glaucoma, comprising the steps of: thiolating albumin to form thiols; and administering thiolated albumin and a drug for treating glaucoma to disulfide bonding and desolvation And a coating layer forming step of forming a coating layer surrounding the drug-bearing albumin nanoparticles, wherein the coating layer is formed on the tear film And is biodegraded by an existing enzyme.

According to another embodiment of the present invention, in the method for preparing an ophthalmic formulation for treating glaucoma according to the present invention, the thiolation step is characterized in that albumin is dissolved in a solvent and 2-Iminothiolane hydrochloride is added and reacted.

According to another embodiment of the present invention, in the method for preparing an ophthalmic formulation for treating glaucoma, the particle forming step comprises adding a drug for treating glaucoma to an albumin solution into which a thiol group is introduced, And the thiol group is allowed to have a cystine bond.

According to another embodiment of the present invention, in the method for manufacturing an ophthalmic solution for treating glaucoma, the particle forming step comprises slowly adding a solution in which a drug for treating glaucoma is dissolved in an albumin solution into which a thiol group has been introduced, Separating into two layers of hydrophilic property, and applying energy to a place where layer separation has occurred.

According to another embodiment of the present invention, in the method for manufacturing an ophthalmic formulation for treating glaucoma, the coating layer forming step may be carried out by injecting albumin nanoparticles carrying a glaucoma drug onto the surface of an acetylated chitosan solution, The nanoparticles are reacted with a chitosan to cover the albumin nanoparticles by an attractive force, and then treated with an ultrasonicator for a predetermined time in order to homogenize the coated nanoparticles.

The above-described incidence is implemented by an embodiment having the following configuration in order to achieve the above-mentioned object.

It is an object of the present invention to provide an anti-glaucoma medicament for treating glaucoma in which the retention time at the surface of the cornea is increased to continuously release the drug to increase the effective time and reduce the amount of drug circulating throughout the body.

It is also an object of the present invention to provide an eye drop formulation for treating glaucoma which does not release a drug during storage.

It is another object of the present invention to provide an anti-glare agent for treating glaucoma in which a coating layer on the surface of nanoparticles is slowly decomposed by enzymes present in tears and drugs can be released in a sustained release form from nanoparticles.

FIG. 1 is a chart showing the results of measurement using dynamic light scattering of D-HSA-NPs. FIG.
2 is a chart showing the results of measurement using dynamic light scattering of D-tHSA-NPs.
FIG. 3 is a chart showing measurement results using dynamic light scattering of CD-tHSA-NPs. FIG.
4 is a chart showing measurement results using dynamic light scattering of HSA NPs.
5 is a chart showing the results of measurement using dynamic light scattering of Acrylated chi HSA NPs.
6 is a chart showing the results of measurement using dynamic light scattering of Acrylated chi HSA NPs (2: 1).
7 is a chart showing the results of measurement using dynamic light scattering of Acrylated chi HSA NPs (1: 2).
FIG. 8 is a graph showing the results of measurement using dynamic light scattering of albumin nanoparticles loaded with chitosan-coated glaucoma therapeutic drug prepared in (5) of Example 1. FIG.
9 is a chart showing the measurement results of surface charge values of D-tHSA-NPs and CD-tHSA-NPs.
10 is a chart showing the measurement results of surface charge values of HSA NPs and Acrylated chi HSA NPs.
11 is a chart showing the measurement results of surface charge values of HSA NPs and Acrylated chi HSA NPs (2: 1).
12 is a chart showing the measurement results of surface charge values of HSA NPs and Acrylated chi HSA NPs (1: 2).
Figure 13 is an SEM image of D-tHSA-NPs and CD-tHSA-NPs.
FIG. 14 is a SEM image of HSA NPs, Acrylated chi HSA NPs, Acrylated chi HSA NPs (2: 1) and Acrylated chi HSA NPs (1: 2).
15 is a fluorescence microscope image of Acrylated chi HSA NPs.
16 is a graph showing the results of measurement of surface charge values before and after the reaction of CD-tHSA-NPs and Lysozyme.
17 is a chart showing SEM images before and after CD-tHSA-NPs and Lysozyme reactions.
Figure 18 shows the drug release results of HSA NPs, Acrylated chi HSA NPs, and Acrylated chi HSA NPs supplemented with Lysozyme.

Hereinafter, an eye drop formulation for treating glaucoma according to the present invention will be described in detail with reference to the accompanying drawings. Unless defined otherwise, all terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs and, if conflict with the meaning of the terms used herein, It follows the definition used in the specification. Further, the detailed description of known functions and configurations that may unnecessarily obscure the subject matter of the present invention will be omitted. Throughout the specification, when an element is referred to as "including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise.

An ophthalmic solution for treating glaucoma according to an embodiment of the present invention comprises a drug for treating glaucoma, albumin nanoparticles carrying the drug, and a coating layer surrounding the nanoparticles, wherein the coating layer is biodegradable . The eye drop formulation has a certain shape and diameter but preferably a spherical shape and a diameter of 100 to 300 nm.

The drug for treating glaucoma is carried on albumin nanoparticles. Various drugs that can treat glaucoma can be used. For example, latanoprost may be used. The albumin nanoparticle may be formed by a method of forming a coating layer on the outer side of a drug for the treatment of glaucoma and may be formed by various methods capable of forming spherical and nano-sized particles. For example, Disulfide bonds. The coating layer is formed outside the albumin nanoparticles and is biodegraded by an enzyme present in the tears (for example, lysozyme, etc.). For example, the amine group, which is a polymer capable of biodegrading by an enzyme (lysozyme) Percent acetylation and / or acrylated chitosan can be used (if the degree of acetylation or acrylation of chitosan is varied, the rate of degradation can be different). In the ophthalmic drug preparation, the drug is present in the form that it is not present as a single molecule but is carried on the albumin nanoparticle, that is, the retention time is increased at the surface of the cornea of the ophthalmic drug preparation and the drug is continuously released, It is possible to reduce the amount of drug circulating throughout the body. In addition, the above-mentioned dosage form can form a coating layer biodegraded by enzymes present in the tears on the outer side of the albumin nanoparticles carrying the drug, so that the drug can not be released during storage, thereby increasing the period of use. In addition, since the coating layer on the surface of the nanoparticles is gradually decomposed by the enzyme present in the tear agent, the ophthalmic drug composition may be prepared by varying the thickness of the coating layer along the outer surface of the albumin nanoparticle or varying the degree of acetylation or acrylation of the chitosan. The coating layer formed on the outer side of the albumin nanoparticles carrying the nanoparticles can be decomposed along the outer surface of the nanoparticles so that the drug can be released from the nanoparticles in a sustained release form.

The method for preparing an ophthalmic formulation for treating glaucoma having the above-described structure comprises the steps of: forming a particulate albumin nanoparticle by reacting albumin with a drug for treating glaucoma; And a coating layer forming a coating layer surrounding the drug-bearing albumin nanoparticles. The albumin nanoparticles carrying the drug can be prepared by utilizing the effect of aggregation due to the difference in polarity of the protein. Since latanoprost, which has a hydrophobic property, has a strong affinity to the four hydrophobic sites present in the albumin molecule, It can be carried on nanoparticles.

In the step of forming particles, the drug-containing albumin nanoparticles are formed. The drug for treating albumin and glaucoma is dissolved in a solvent, the ethanol is titrated and aggregated, and glutaraldehyde is added to crosslink the amine groups of albumin bound to the drug .

In the coating layer formation step, albumin nanoparticles carrying a glaucoma drug are injected onto the surface of an acetylated or acrylated chitosan solution, and the chitosan is reacted to enclose the albumin nanoparticles by an electrostatic attraction, For a predetermined period of time by using an ultrasonicator. The coating layer forming step may further include a step of irradiating ultraviolet rays with a photoinitiator after the ultrasonic treatment. That is, the albumin nanoparticles carrying the drug have a negative electrostatic property. Since the chitosan is a polymer having a positive charge property, the surface of the albumin nanoparticle can be coated with electrostatic attraction.

A method of preparing an ophthalmic formulation for treating glaucoma according to another embodiment of the present invention includes a thiolization step of thiolizing albumin and a step of administering the medicament through disulfide bonding and desolvation using thiolated albumin and a drug for treating glaucoma A particle forming step of forming albumin nanoparticles, and a coating layer forming step of forming a coating layer surrounding the drug-bearing albumin nanoparticles. Since the coating layer forming step is performed in the same manner as the coating layer forming step described above, a description thereof will be omitted.

The thiolation step is a step of introducing a thiol group to the albumin, which comprises dissolving albumin in a solvent and adding 2-Iminothiolane hydrochloride to the reaction.

In the particle formation step, a drug for treating glaucoma is added to an albumin solution into which a thiol group is introduced, and ethanol is titrated to induce cystine bonding of the thiol group. In the particle forming step according to another embodiment, the solution in which the drug for treating glaucoma is dissolved is added to the albumin solution into which the thiol group is introduced, and the solution is separated into hydrophobic and hydrophilic two layers. In the layer separation, .

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these are only for the purpose of illustrating the present invention in more detail, and the scope of the present invention is not limited thereto.

Example 1 Preparation of albumin nanoparticles coated and coated with glaucoma treatment drug

(1) 20 mg of human serum albumin and 1 mg of latanoprost (120 μL) were dissolved in 2 mL of tertiary distilled water and stirred for 1 hour. The pH was adjusted to about 8 by adding NaOH to the albumin and latanoprost mixture , 3 mL of ethanol is added at a rate of 1 mL / minute, 5 μL of 8% glutaraldehyde is added to induce stabilization by cross-linking amine groups of latanoprost-linked albumin, and the mixture is stirred for 48 hours. Thereafter, acetonitrile and ethanol used to dissolve latanoprost were vaporized, and centrifugation was performed at 13000 rpm for 10 minutes to remove non-granulated latanoprost and albumin to form albumin nanoparticles (D-HSA -NPs).

(2) Dissolve 20 mg of albumin in the third distilled water, add 4 mg of 2-Iminothiolane hydrochloride, react at room temperature for one hour to introduce a thiol group into the albumin molecule, remove the 2-Iminothiolane hydrochloride that was not introduced, 1 mg of latanoprost (acetonitrile solution 120 μL) was added to the albumin solution, and the mixture was stirred for 1 hour. The ethanol was titrated at a rate of 1 mL / minute, and the resulting thiol group was stirred for 48 hours so as to cross-link the cystine bond. Thereafter, acetonitrile and ethanol used to dissolve latanoprost were vaporized, and centrifugation was carried out at 13000 rpm for 10 minutes to remove non-granulated latanoprost and albumin to form albumin nanoparticles (D-tHSA -NPs).

(3) Chitosan (molecular weight: 50 kDa), a polymer in which 30% of the amine groups in the polymer chain were substituted with acetyl groups, was coated with albumin nanoparticles containing a drug for treating glaucoma. Specifically, 50 μL of a 30% acetylated chitosan solution (0.5 mg / mL) was placed in a 200 μL tube and then 50 μL of D-tHSA-NPs solution (20 mg / mL) was slowly injected onto the surface of the chitosan solution, Are reacted for 30 minutes to enclose them by electrostatic attraction, and then treated with an ultrasonicator for 10 seconds in order to homogenize the coated nanoparticles. Thereafter, centrifugation was carried out at 13000 rpm for 10 minutes to remove non-granulated chitosan to obtain albumin nanoparticles (C-D-tHSA-NPs) carrying the glaucoma therapeutic drug coated with chitosan.

(4) 40 mg of human serum albumin was dissolved in 1 ml of distilled water, adjusted to pH 8 by addition of 0.2 M NaOH to form albumin solution, and 2 mg of 2-iminothiolane hydrochloride was dissolved in 1 ml of tertiary distilled water After 2-IH solution was formed, the albumin solution and 2-IH solution were mixed at a ratio of 1: 1 by volume and reacted for 1 hour at room temperature. Then, 2-Iminothiolane hydrochloride not introduced into the centrifuge at 4000 rpm using a 30 kDa centricone was removed To form a thiolated albumin solution. 5 mg of latanoprost drug is dissolved in 1 ml of ACN to form drug solution. After dissolving the drug solution and the thiolated albumin solution, ethanol was added dropwise to titrate the resulting thiol group. The resulting thiol group was cystine-bound to be cross-linked for 24 hours, and used for dissolving latanoprost for 24 hours After acetonitrile and ethanol were evaporated, the mixture was centrifuged at 13200 rpm for 10 minutes to remove the non-granulated latanoprost and albumin, leaving only the pellet, centrifuging at 3000 rpm for 5 minutes to obtain supernatant, To obtain nanoparticles (HSA NPs). 500 μl of the drug-bearing nanoparticles obtained above was added slowly to the surface of 500 μl of a 5 mg / ml 30% acrylated chitosan aqueous solution. The mixture was kept at room temperature for 2 hours to react, and after 2 hours After thoroughly pipetting and performing bath sonication 10 s and vortexing 10 s in order, centrifuge at 13200 rpm for 10 min, remove supernatant, leave only pellet, add 1 ml of third distilled water, and pipet and sonicate sufficiently to release pellet Acrylated chitosan coated nanoparticle was prepared.) 1ul photoinitiator was added and crosslinked by UV irradiation for 1 minute at 254nm wavelength. Acrylated chi HSA NPs with chitosan coated glaucoma treatment drug was obtained.

(5) 40 mg of human serum albumin was dissolved in 1 ml of distilled water, adjusted to pH 8 by addition of 0.2 M NaOH to form albumin solution, and 2 mg of 2-iminothiolane hydrochloride was dissolved in 1 ml of tertiary distilled water After 2-IH solution was formed, the albumin solution and 2-IH solution were mixed at a ratio of 1: 1 by volume and reacted for 1 hour at room temperature. Then, 2-Iminothiolane hydrochloride not introduced into the centrifuge at 4000 rpm using a 30 kDa centricone was removed To form a thiolated albumin solution. 2 mg of latanoprost drug is dissolved in 200 ul of chloroform to form drug solution. When the drug solution is slowly added to the thiolated albumin solution, it is separated into hydrophobic and hydrophilic two layers. Energy is applied by using tip sonic at the place where the layer separation occurs (at this time, Energy is applied), and nitrogen gas is used to rapidly blow out chloroform. After centrifugation at 13200 rpm for 10 min, the supernatant was removed. The pellet was removed, and 1 ml of distilled water was added. The pellet was removed by pipetting and bath sonication. The micropellets were then centrifuged at 3000 rpm for 5 min. And the supernatant is obtained to obtain drug-supported nanoparticles (HSA NPs). On the surface of 500 μl of a 5 mg / ml 30% acrylated chitosan aqueous solution, 500 μl of the drug-bearing nanoparticles obtained above was slowly added to the surface without dropping, and the mixture was kept at room temperature for about 2 hours for reaction. After pipetting, pipetting and bath sonication were performed, followed by bath sonication 10 s and vortexing 10 s, followed by centrifugation at 13200 rpm for 10 min. The supernatant was removed and the pellet was left alone. (Acrylated chitosan coated emulsion type nanoparticle was completed.) And photoinitiator 1ul was added and crosslinked by UV irradiation for 1 minute at 254nm wavelength band to obtain albumin nanoparticles containing chitosan-coated glaucoma treatment drug.

<Example 2> Characterization of albumin nanoparticles

(1) albumin nanoparticles were measured using a dynamic light scattering method, and the results are shown in FIGS. 1 to 8. Figure 1 shows the results of measurement of D-HSA-NPs, Figure 2 shows the results of measurement of D-tHSA-NPs, Figure 3 shows the results of measurement of CD-tHSA-NPs, FIG. 5 shows measurement results of Acrylated chi HSA NPs, and FIG. 6 shows measurement results of Acrylated chi HSA NPs (2: 1) (compared with Acrylated chi HSA NPs prepared in Example 1 (4) FIG. 7 shows the measurement results of Acrylated chi HSA NPs (1: 2) (Acrylated chi HSA NPs prepared in (4) of Example 1) FIG. 8 shows the results of measurement of albumin nanoparticles loaded with the chitosan-coated glaucoma-treated drug prepared in Example 1 (5) .

(2) The loading efficiency of the drug was calculated by the amount of latanoprost initially administered and the difference in the amount of unattached latanoprost in the supernatant obtained by centrifugation of the particles, and the results are shown in Table 1 below.

(3) In Figures 1 to 8, D-HSA-NPs, D-tHSA-NPs, D-tHSA-NPs, HSA NPs, Acrylated chi HSA NPs, Acrylated chi HSA NPs (1: 2), the chitosan-coated glaucoma-treated drug-bearing albumin nanoparticles prepared in (5) of Example 1 have a uniform particle distribution and a particle diameter of 200 to 300 nm, Table 1 shows that D-HSA-NPs has a loading efficiency of 29.31%, D-tHSA-NPs has a loading efficiency of 35.82%, and HSA-NPs has a loading efficiency of 76.21%. That is, it can be seen that uniform nano-sized particles can be produced by the above-described production method. It is also known that albumin nanoparticles carrying a drug formed by disulfide bond can bind albumin nanoparticles carrying a drug cross- The binding force is stronger than that of the drug.

D-HSA-NPs D-tHSA-NPs HSA NPs Loading efficiency (%) 29.31 35.82 76.21

Example 3 Identification of Coating Layer of Albumin Nanoparticles

(1) CD-tHSA-NPs (centrifuged CD-tHSA-NPs) were dispersed in phosphate buffered saline (PBS) NPs, Acrylated chi HSA NPs, Acrylated chi HSA NPs (2: 1), Acrylated chi HSA (2: 1) NPs (1: 2) were placed in salt-free tertiary distilled water to measure the surface charge value, and the results are shown in FIGS. 10 to 12.

(2) D-tHSA-NPs and C-D-tHSA-NPs were measured by SEM and the results are shown in Fig. 13 (a) is an image of D-tHSA-NPs, and Fig. 13 (b) is an image of C-D-tHSA-NPs. HSA NPs, Acrylated chi HSA NPs, Acrylated chi HSA NPs (2: 1) and Acrylated chi HSA NPs (1: 2) were measured by SEM and the results are shown in Fig. Acrylated chi HSA NPs were measured by fluorescence microscopy and the results are shown in Fig. Acrylated chi HSA In the preparation of NPs, Alexa 555 (red fluorescence) dyed Acrylated chitosan and Alexa 488 (green fluorescence red) stained HSA were used. FIGS. 15 (a) Fig. 15 (c) is a synthesized image of (a) and (b). Fig.

(3) Albumin has a negative charge surface and chitosan has a positive charge property. In FIG. 9, D-tHSA-NPs has a negative charge value and CD-tHSA-NPs has a positive charge value. HSA NPs have positive charge values with Acrylated chi HSA NPs, Acrylated chi HSA NPs (2: 1) and Acrylated chi HSA NPs (1: 2) with negative charge values. Figures 13 and 14 show particle images by chitosan coating And the red fluorescence image and the green fluorescence image can be confirmed through FIG. It can be seen that the coating layer is formed on the albumin nanoparticles carrying the glaucoma treatment drug.

Example 4 Confirmation of Coat Layer Degradation of Albumin Nanoparticles by Lysozyme

(1) Since the concentration of Lysozyme present in actual human leakage is 1.7 mg / mL, when the CD-tHSA-NPs is used as an anti-ocular drug, (1.7 mg / ml Lysozyme solution). Specifically, the Lysozyme solution (3.4 mg / mL) dissolved in the same conditions as the CD-tHSA-NPs solution (10 mg / mL) dispersed in pH 7.4 PBS was mixed and reacted at 37 ° C. for 24 hours and 48 hours After 72 hours, centrifuge at 13000 rpm for 10 minutes to remove lysozyme and degraded chitosan from the solution and re-disperse in distilled water. Thereafter, surface charge values of albumin nanoparticles degraded by lysozyme in each time period were measured, and the results are shown in FIG. The solution before and after the reaction of the Lysozyme solution was taken by SEM and the results are shown in Fig. 17 (a) is a pre-reaction image, and Fig. 17 (b) is an image after 24 hours of reaction.

(2) A solution of the same concentration of HSA NPs (sample 1) and a solution of Acrylated chi HSA NPs (sample 2) were prepared and a simulated tear solution (1.7 mg / ml Lysozyme solution) After each of the samples 1 to 3 was inserted into a dialysis membrane, 10 ml of PBS was added to a 50 ml tube, and a dialysis membrane containing the sample was inserted. Then, each solution (sample, 1, 2 And 3) were measured. The results are shown in Fig.

(3) Referring to FIG. 16, the negative charge value is measured 24 hours after the Lysozyme solution reaction, and the albumin nanoparticles are connected with the chitosan coating. FIG. 17 shows that the nanoparticles connected after 24 hours of the Lysozyme solution reaction are significantly reduced, Of the chitosan is decomposed. 18 shows that the nanoparticles coated with chitosan (sample 2) had a slower drug release rate than the chitosan-coated nanoparticles (sample 1), and the nanoparticles coated with chitosan mixed with the leakage solution 3) was faster than the nanoparticles coated with chitosan (sample 2) in which the leakage solution was not mixed. Thus, it can be seen that the leakage enzyme has a function of decomposing chitosan. Thus, when coated with chitosan, the release of the chitosan is eliminated and the rapidly loaded glaucoma drug is released when the capsule is reacted with the leakage enzyme in the tears, .

While the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, Should be interpreted as falling within the scope of.

Claims (12)

In eye drop preparations,
Wherein the eye drop preparation comprises a drug for treating glaucoma, albumin nanoparticles carrying the drug, and a coating layer surrounding the nanoparticles,
Wherein the coating layer is biodegraded upon administration of the eye drop formulation. The method of claim 1, wherein the coating layer
Wherein the agent is degraded by an enzyme contained in tears. The eye drop formulation according to claim 1,
Wherein the composition has spherical shape. The eye drop formulation according to claim 1,
Wherein the medicament has a diameter of 100 to 300 nm. The method of claim 1, wherein the coating layer
Acetylated or acrylated chitosan. &Lt; RTI ID = 0.0 &gt; 11. &lt; / RTI &gt; The method of claim 1, wherein the nanoparticles
Wherein the medicament is formed by disulfide bonds between albumin molecules. 2. The method of claim 1,
Wherein the latanoprost is used as a medicament for treating glaucoma. In a method for producing an eye drop formulation,
The preparation method of eye drop preparations comprises a thiolation step of thiolizing albumin, a particle formation step of forming drug-supported albumin nanoparticles through disulfide bonding and desolvation process using thiolated albumin and a drug for treating glaucoma And a coating layer forming a coating layer surrounding the drug-bearing albumin nanoparticles,
Wherein the coating layer is biodegraded by an enzyme present in tears when the ophthalmic solution is administered. 9. The method of claim 8, wherein the thiolation step comprises
And dissolving albumin in a solvent and adding 2-Iminothiolane hydrochloride to the mixture to react. 9. The method according to claim 8,
A method for preparing glaucoma medicament for treating glaucoma by adding a drug for treating glaucoma to albumin solution into which a thiol group is introduced and titrating ethanol to induce cystine bonding of the thiol group. 9. The method according to claim 8,
Wherein the solution containing the drug for treating glaucoma is slowly added to the albumin solution into which the thiol group has been introduced to separate into hydrophobic and hydrophilic two layers and energy is applied to the layer separation. The method according to claim 10, wherein the coating layer forming step
The albumin nanoparticles loaded with the glaucoma drug were injected into the surface of the acetylated chitosan solution, and the chitosan was reacted with the albumin nanoparticles by electrostatic attraction so as to cover the albumin nanoparticles. To uniformize the coated nanoparticles, Wherein the glaucoma treatment is performed for a predetermined period of time using an ultrasound machine.

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