Search

CN-119367286-B - Eye drops for xerophthalmia

CN119367286BCN 119367286 BCN119367286 BCN 119367286BCN-119367286-B

Abstract

The invention relates to an eye drop for dry eye, which comprises, by mass, 0.1% -0.5% of chondroitin sulfate, 0.06% -0.3% of sericin nanoparticles containing astaxanthin, 0.1% -0.3% of sodium hyaluronate, 0.05% -0.1% of vitamin E, 0.9-1.0% of sodium chloride, 0.05% -0.1% of poloxamer, 0.01% -0.1% of EDTA, a phosphate buffer solution and the balance of water, wherein the particle size of the sericin nanoparticles containing astaxanthin is 50-300nm, and the pH of the eye drop is regulated to 6.8-7.9 by the phosphate buffer solution. The eye drop can effectively relieve dry eye symptoms, provide long-time wetting and protection, simultaneously reduce ocular inflammation and oxidative stress, remarkably improve the dry eye symptoms, and has high use safety.

Inventors

  • TIAN LEI
  • JIE YING
  • YU LINRONG
  • LIU ZIYU
  • LI YAQIONG
  • CHEN XIAONIAO

Assignees

  • 北京市眼科研究所
  • 首都医科大学附属北京同仁医院

Dates

Publication Date
20260512
Application Date
20241108

Claims (9)

  1. 1. The eye drop for dry eye is characterized by comprising, by mass, 0.1% -0.5% of chondroitin sulfate, 0.06% -0.3% of sericin nanoparticles containing astaxanthin, 0.1% -0.3% of sodium hyaluronate, 0.05% -0.1% of vitamin E, 0.9-1.0% of sodium chloride, 0.05% -0.1% of poloxamer, 0.01% -0.1% of EDTA, phosphate buffer solution and the balance of water, wherein the particle size of the sericin nanoparticles containing astaxanthin is 50-300nm, and the pH of the eye drop is regulated to 6.8-7.9 by the phosphate buffer solution.
  2. 2. The eye drop according to claim 1, wherein the composition of the eye drop comprises chondroitin sulfate 0.1%, sericin nanoparticles containing astaxanthin 0.1%, sodium hyaluronate 0.2%, vitamin E0.05%, sodium chloride 0.9%, poloxamer 0.075%, EDTA 0.05%, phosphate buffer and the balance water, and the eye drop has a pH of 7.4.
  3. 3. The dry eye drop of claim 1, wherein the drop is free of chemical preservatives.
  4. 4. A method of preparing the eye drop for dry eye according to any one of claims 1 to 3, comprising the steps of: s1, preparing sericin nano-particles containing astaxanthin Dissolving sericin in water or phosphate buffer solution to form a first solution, dissolving astaxanthin in absolute ethyl alcohol or 95% ethanol to obtain a second solution, adding the second solution into the first solution, stirring at high speed or performing ultrasonic treatment to form stable emulsion, cooling to 2-8 ℃, centrifuging, separating out centrifugal precipitate, and freeze-drying to obtain sericin nanoparticles containing astaxanthin; s2, adding sodium chloride, sodium hyaluronate, chondroitin sulfate, sericin nano-particles containing astaxanthin, vitamin E, poloxamer and EDTA into sterile water, uniformly stirring, adding phosphate buffer solution, uniformly stirring, regulating pH to 6.8-7.9, filtering with a 0.22 mu m filter membrane, and sub-packaging the filtered solution into sterile eye drops.
  5. 5. The process of claim 4, wherein in S1, the concentration of sericin in the first solution is 1-5%, the first solution is prepared by adding sericin powder into water or phosphate buffer solution, stirring while adding until completely dissolving, controlling the temperature at 25-45 ℃ during dissolving, and passing through a 0.45 μm filter membrane after dissolving to obtain the first solution.
  6. 6. The process of claim 5, wherein in S1, the concentration of astaxanthin in the second solution is 0.1-1%, and the second solution is prepared by adding astaxanthin powder into absolute ethanol or 95% ethanol at room temperature, stirring until completely dissolved, and passing through 0.45 μm filter membrane.
  7. 7. The method according to claim 5 or 6, wherein in S1, the first solution and the second solution are prepared according to a volume ratio of 5:1-1:1, the second solution is slowly added into the first solution, and simultaneously, the second solution is stirred at a high speed of 1000-3000 rpm, and is continuously stirred for 10-30min until stable emulsion is formed, wherein the temperature in the emulsification process is not more than 25 ℃, then, the emulsion is rapidly transferred into an ice bath or a refrigerator, and is rapidly cooled to 4-8 ℃ for 0.5-1h, centrifuged for 10-20min at 10000-15000g, and the precipitate is separated and frozen and dried after centrifugation, thus obtaining the sericin nanoparticle containing astaxanthin.
  8. 8. The method according to claim 7, wherein in S1, the supernatant separated after centrifugation is recovered after centrifugation at 10000 to 15000g for 10 to 20 minutes, and sterilized for preparing the first solution.
  9. 9. The method according to claim 4, wherein in S2, the mixture is packaged in sterile eye drops bottles and sterilized by irradiation with 10-20 kGy gamma rays at 4-10 ℃ and then put in storage.

Description

Eye drops for xerophthalmia Technical Field The invention relates to the technical field of ophthalmic medicines, in particular to a xerophthalmia eye drop. Background Dry eye is a disease that causes dry eye symptoms such as discomfort and visual function abnormalities of the eye, which are associated with abnormalities in tear fluid volume or quality, and dry eye can cause disorders on the surface of the eye such as the cornea. This abnormality in tear fluid volume mainly refers to a state of low tear secretion, which is an index of dry eye based on tear fluid volume. For abnormalities in tear quality, abnormalities in tear components (such as small amounts of lipid or protein components contained in tears) can degrade the stability of the tear film, which can lead to dryness of the eye surface, even with tear secretion. Astaxanthin (Astaxanthin) is known to be a potent natural antioxidant with a variety of biological activities including antioxidant, anti-inflammatory, immunomodulating and photoprotection. Astaxanthin is used for preparing eye drops, and can provide potential treatment or prevention effects for various eye problems. There are several patent applications in which astaxanthin is added as an active ingredient to eye drops. For example, CN107106627a discloses an eyedrop dispenser and an antioxidant eyedrop composition, which mainly comprises antioxidant components such as green tea extract, resveratrol, astaxanthin, etc. CN117752597a discloses an eye drop for alleviating dry eye, which comprises sorbitol, resveratrol, modified chitosan, a prune extract, a dandelion extract, ethylenediamine tetraacetic acid, astaxanthin, vitamin a, dextran and hyaluronic acid. Although astaxanthin has antioxidant, antiinflammatory, immunomodulating and photoprotection effects Efficacy, however, still presents challenges in making eye drops, ① solubility-astaxanthin is poor in water and the use of an appropriate solvent or carrier is required to improve its solubility and bioavailability. ② Stability-astaxanthin is easily degraded under the conditions of illumination, high temperature and oxidation, and how to ensure the stability of astaxanthin in eye drops, especially in the processes of production sterilization, storage and transportation, is a problem to be solved. In addition, the safety of eye drops is also a problem to be improved. Disclosure of Invention First, the technical problem to be solved In view of the above-mentioned shortcomings and disadvantages of the prior art, the invention provides an eye drop for dry eye, which is coated by sericin and astaxanthin, and utilizes the high hydrophilicity and film forming property of sericin to improve the stability and bioavailability of astaxanthin, and simultaneously, the sericin also has the characteristics of moisture retention, antioxidation, antibiosis and the like, thereby being beneficial to improving dry eye, and solving the technical problems of poor solubility and stability existing in the eye drop by directly adding astaxanthin. (II) technical scheme The invention provides an eye drop for dry eye, which comprises, by mass, 0.1% -0.5% of chondroitin sulfate, 0.06% -0.3% of sericin nanoparticles containing astaxanthin, 0.1% -0.3% of sodium hyaluronate, 0.05% -0.1% of vitamin E, 0.9-1.0% of sodium chloride, 0.05% -0.1% of poloxamer, 0.01% -0.1% of EDTA, phosphate buffer solution and the balance of water, wherein the particle size of the sericin nanoparticles containing astaxanthin is 50-300nm, and the pH of the eye drop is regulated to 6.8-7.9 by the phosphate buffer solution. According to the preferred embodiment of the invention, the composition of the eye drops for dry eye comprises 0.1% of chondroitin sulfate, 0.1% of sericin nano-particles containing astaxanthin, 0.2% of sodium hyaluronate, 0.05% of vitamin E, 0.9% of sodium chloride, 0.075% of poloxamer, 0.05% of EDTA, phosphate buffer solution and the balance of water, wherein the pH of the eye drops is 7.4. According to a preferred embodiment of the present invention, the dry eye drops are free of preservative. In a second aspect, the present invention provides a method for preparing an eye drop for dry eye, comprising: s1, preparing sericin nano-particles containing astaxanthin Dissolving sericin in water or phosphate buffer solution to form a first solution, dissolving astaxanthin in absolute ethyl alcohol or 95% ethanol to obtain a second solution, adding the second solution into the first solution, stirring at high speed or performing ultrasonic treatment to form stable emulsion, cooling to 2-8 ℃, centrifuging, separating out centrifugal precipitate, and freeze-drying to obtain sericin nanoparticles containing astaxanthin; S2, adding sodium chloride, sodium hyaluronate, chondroitin sulfate, sericin nano-particles containing astaxanthin, vitamin E and poloxamer into sterile water, uniformly stirring, adding phosphate buffer solution, uniformly stirring, regulating the pH value to 6.8-7.