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CN-121987800-A - External eye protection liquid for relieving eye fatigue and preparation method thereof

CN121987800ACN 121987800 ACN121987800 ACN 121987800ACN-121987800-A

Abstract

The invention discloses an external eye protection liquid for relieving eyestrain and a preparation method thereof, the eye protection liquid comprises a plant source calcium channel blocker, a divalent metal ion source, a temperature-sensitive gel matrix and a eutectic solvent system, has unique reversible phase transformation characteristic, is a flowable sol when stored at low temperature, and rapidly undergoes in-situ phase transformation to form semi-solid gel after contacting the ocular surface. In the preparation process, the choline chloride-propylene glycol eutectic solvent is adopted to carry out low-temperature in-situ extraction on plant raw materials, the extracting solution is directly used as a functional component to be reserved in the preparation, and the cold-dissolution compounding process of poloxamer matrix is matched, so that the damage of high temperature to active ingredients is avoided in the whole process. The invention solves the problems of short retention time, low bioavailability and drug effect damage of the traditional aqueous solution on the ocular surface by a high-temperature process, and effectively relieves the deep eye fatigue by a physical and physiological dual mechanism.

Inventors

  • SHAO JIN

Assignees

  • 上海明融医药科技有限公司

Dates

Publication Date
20260508
Application Date
20260306

Claims (8)

  1. 1. The external eye protection liquid for relieving eyestrain is characterized by being a temperature-sensitive in-situ gel preparation, and the preparation raw materials of the eye protection liquid comprise a plant source calcium channel blocker, a divalent metal ion source, a temperature-sensitive gel matrix, a solvent system and pharmaceutically acceptable auxiliary materials; The eye protection liquid has reversible sol-gel phase transition characteristic that the eye protection liquid is in a flowing sol state in an environment of 25 ℃ and below, and in-situ phase transition is carried out to form a semisolid gel state in an eye surface temperature environment of 33-35 ℃; The bioadhesion retention time of the eye protection liquid on the eye surface after the phase change is more than or equal to 15 minutes.
  2. 2. The external eye drop for relieving eyestrain as recited in claim 1, wherein the temperature sensitive gel matrix is compounded from poloxamer 407 and poloxamer 188; the eye protection liquid comprises, by weight, 18% -22% of poloxamer 407, 2% -5% of poloxamer 188, and 4:1-6:1 of poloxamer 407 and poloxamer 188.
  3. 3. The external eye protection solution for relieving eye fatigue according to claim 1, wherein the plant-derived calcium channel blocker is one or more selected from puerarin, total glucosides of paeony, ligustrazine, tetrandrine; The divalent metal ion source is selected from at least one of L-aspartic acid magnesium, magnesium gluconate, magnesium sulfate and taurine magnesium to provide magnesium ions; the molar ratio of the plant source calcium channel blocker to the divalent metal ion source is 1 (0.5-0.8).
  4. 4. The external eye drop for relieving eyestrain as claimed in claim 1, characterized in that the solvent system includes a eutectic solvent (DES) prepared by mixing hydrogen bond acceptor choline chloride with hydrogen bond donor propylene glycol in a molar ratio of 1:2 to 1:3; And the eutectic solvent is used as an extraction medium to extract the plant source calcium channel blocker, and then is directly remained in the eye protection liquid without separation to be used as a moisturizing and permeation promoting component.
  5. 5. The external eye drop for relieving eye strain according to any one of claims 1 to 4, wherein the eye drop forms a gel layer (2) having a refractive index (nD) of 1.350-1.365 and a refractive index difference of 0.011-0.026 with the human cornea (1) in an environment of 33-35 ℃, so that the eye drop can form a light scattering resting layer having a fog vision lasting for 3-5 minutes on the surface of the eye after application.
  6. 6. The eye protection solution for external use for relieving eye fatigue according to claim 1, wherein the pH value of the eye protection solution is 6.0-7.5, and the osmotic pressure is 260-320 mOsm/kg.
  7. 7. A method for preparing the external eye protection liquid for relieving eye fatigue according to any one of claims 1 to 6, comprising the steps of: (1) In-situ DES extraction, namely mixing and heating a hydrogen bond acceptor and a hydrogen bond donor to prepare a eutectic solvent (DES), adding plant raw material powder containing a plant source calcium channel blocker for extraction, filtering to remove solid residues to obtain a DES extract containing active ingredients, wherein the step does not comprise the operation of removing the DES solvent; (2) Preparing a matrix by a cold dissolution method, namely dispersing the temperature-sensitive gel matrix in a buffer solution in a low-temperature environment of 4-10 ℃, standing and swelling for 12-24 hours until a clear and transparent micelle solution is formed; (3) Adding the DES extracting solution obtained in the step (1) and a divalent metal ion source into the micelle solution obtained in the step (2) under the condition that the temperature of the system is maintained to be lower than 15 ℃, and uniformly stirring and mixing; (4) Post-treatment, namely adjusting pH value and osmotic pressure, cold-filtering and sterilizing by a microporous filter membrane with the thickness of 0.22 mu m, and sub-packaging.
  8. 8. The method according to claim 7, wherein the extraction temperature in the step (1) is 40-65 ℃, and the whole process operation temperature of the steps (2) to (4) is controlled between 4-15 ℃ without involving high temperature distillation or reflux extraction step above 100 ℃.

Description

External eye protection liquid for relieving eye fatigue and preparation method thereof Technical Field The invention relates to the technical field of medicinal preparations, in particular to an external eye protection liquid for relieving eye fatigue and a preparation method thereof. Background Visual fatigue has become a common phenomenon in modern society, and its core pathological mechanism is persistent spasm caused by prolonged contraction of ciliary muscle and excessive accumulation of intracellular calcium ions. The conventional products for relieving eye fatigue in the market are mostly traditional aqueous solution preparations (eye drops or eye washing solutions), and the preparations mainly have two major technical bottlenecks, namely, the preparation has extremely short retention time of ocular surfaces, is usually flushed by tears or excreted through nasolacrimal ducts within 1-2 minutes after dripping, so that the effective components of the medicine are difficult to penetrate cornea epithelium to reach deep ciliary muscle tissues, and the action mechanism is limited to promoting microcirculation of eyes or simple cooling sense and lacks specific intervention for ciliary muscle spasms. In addition, in terms of preparation process, the existing plant eye-protection preparation usually adopts traditional methods such as high-temperature distillation or water boiling and alcohol precipitation to extract active ingredients. However, many plant active molecules (e.g., anthocyanins, flavonoid glycosides) with excellent soothing efficacy are thermally unstable and are highly susceptible to structural degradation or loss of activity in high temperature environments above 100 ℃ for long periods of time, resulting in a significant decrease in the efficacy of the final product. Meanwhile, the traditional extraction process often requires the use of organic solvents and involves complex solvent removal steps, which not only increases energy consumption, but also may introduce a risk of solvent residue. Therefore, developing a novel eye protection preparation which can be extracted at normal temperature, stay for a long time and can deeply block the spasmodic mechanism is a technical problem to be solved at present Disclosure of Invention Aiming at the technical defects that the ophthalmic preparation (eye drops and eye washing liquid) in the prior art has short retention time on the ocular surface, the medicine active ingredients are difficult to permeate into the ciliary muscle deep layer, the traditional high-temperature preparation process is easy to damage plant thermosensitive active ingredients and the like, the invention provides the eye fatigue relieving eye protection liquid based on the temperature-sensitive gel and ion blocking technology and the preparation method thereof. The invention aims to prolong the retention time of the medicine through physical phase change, relieve muscle spasm through a specific ion channel blocking mechanism and retain the activity of the medicine through a normal-temperature in-situ extraction process. In order to achieve the above purpose, the present invention adopts the following technical scheme: an external eye protection liquid for relieving eyestrain, which is a temperature-sensitive in-situ gel preparation, and comprises the following preparation raw materials: Plant source calcium channel blocker, divalent metal ion source, temperature sensitive gel matrix, solvent system and pharmaceutically acceptable auxiliary materials. The eye protection liquid has reversible sol-gel phase transition characteristic, is in a flowable sol state in an environment of 25 ℃ and below, generates in-situ phase transition to form a semisolid gel state in an eye surface temperature environment of 33-35 ℃, and has bioadhesion retention time of the eye surface of more than or equal to 15 minutes after the phase transition. Further, the temperature-sensitive gel matrix is preferably formed by compounding poloxamer 407 and poloxamer 188, wherein the content of the poloxamer 407 is 18% -22%, and the content of the poloxamer 188 is 2% -5%. Further, the plant source calcium channel blocker is selected from one or more of puerarin, total glucosides of paeony, ligustrazine and tetrandrine, the divalent metal ion source is selected from at least one of L-magnesium aspartate, magnesium gluconate and magnesium sulfate, and preferably, the molar ratio of the plant source calcium channel blocker to the divalent metal ion source is1 (0.5-0.8). Further, the solvent system comprises a eutectic solvent (DES) which is prepared by mixing choline chloride of a hydrogen bond acceptor and propylene glycol of a hydrogen bond donor according to a molar ratio of 1:2 to 1:3, and the eutectic solvent is used as an extraction medium to extract the plant source calcium channel blocker, and then the plant source calcium channel blocker is directly remained in the eyeshield liquid without separation to serv