CN111956619A

CN111956619A - Freeze-dried powder preparation for preventing myopia and improving eyesight and preparation method thereof

Info

Publication number: CN111956619A
Application number: CN202010939413.1A
Authority: CN
Inventors: 唐亚雷
Original assignee: Shanghai Kuangshi Medical Co ltd
Current assignee: Shanghai Kuangshi Medical Co ltd
Priority date: 2020-09-09
Filing date: 2020-09-09
Publication date: 2020-11-20

Abstract

The invention relates to the technical field of eye care products, in particular to a freeze-dried powder preparation for myopia prevention and vision improvement, which consists of freeze-dried powder and solvent liquid; the raw materials of the freeze-dried powder comprise (a) active ingredients, (b) excipients and (c) emulsifiers. The active ingredients include sodium hyaluronate, lutein, ascorbic acid, oligopeptide-1, oligopeptide-5 and pyrimidine carboxylic acid. Excipients include mannitol and sodium chondroitin sulfate. The emulsifier comprises hydrogenated lecithin. The solvent comprises micromolecular alcohol, taurine, rubusine, retinol, sodium chloride, lysozyme and deionized water. The freeze-dried powder preparation is obtained by dissolving freeze-dried powder in solvent liquid. The invention also provides a preparation method of the freeze-dried powder preparation for preventing myopia and improving eyesight. Test results show that the health care product can effectively moisturize, relieve, reduce pressure, resist inflammation, activate, supplement nutrition and enhance immunity, and has good nursing effects on myopia prevention and vision improvement. And the medicament can be dissolved and used at one time, has no stimulation, no toxic or side effect and is safe to use.

Description

Freeze-dried powder preparation for preventing myopia and improving eyesight and preparation method thereof

Technical Field

The invention relates to the technical field of eye care products, in particular to a freeze-dried powder preparation for preventing myopia and improving eyesight and a preparation method thereof.

Background

Survey data shows that the number of myopia people in China is as high as 4 hundred million, wherein the number of myopia people in China is about 2.7 hundred million. The incidence rate of myopia of primary and secondary school students is more than 50%, the detection rate of related poor eyesight such as astigmatism, blur, presbyopia and the like is increased, and the eye health is seriously influenced. More than 80% of myopia is related to acquired factors, including increasingly heavy work and study burden, long-time internet surfing and bad life style of using a mobile phone instead of movement, environmental pollution and damage and the like. Scientifically, the decline of vision such as myopia, astigmatism and the like is also caused by aging of the body. Aging refers to a general degeneration of the body, which is caused by the body's cell population being impacted and damaged by the above factors for a long time in the life cycle of a human body, resulting in gradual deterioration of the functions of the body's tissues and organs and a decrease in the immune functions of the body.

Therefore, relaxing and repairing damaged cells of the body in time, recovering cell activity, and exciting cellular immunity and self-healing functions, namely 'cell anti-aging' is an effective method for preventing myopia and improving vision, and the method can be called 'eyeball cell anti-aging'. The method specifically comprises timely and regular decontamination and cleaning, water replenishing and moisture preserving, relieving and pressure reducing, bacteriostasis and toxin expelling, nutrition replenishing, immunity enhancing and the like.

Nowadays, once the eyesight of teenagers is degraded, such as myopia, astigmatism, presbyopia and the like, the people mostly wear glasses for correction or surgical treatment, and the prevention also advocates a correct eye use method and good living habits and healthy exercises, but the prevention and the protection are not much by adopting non-treatment and non-medicine daily care products of 'eyeball cell anti-aging'.

Disclosure of Invention

The invention aims to provide a daily care product which is based on the principle of eyeball cell anti-aging, adopts a modern high-performance biological active substance formula, has the functions of decontamination, cleaning, water replenishing, moisture retention, pressure relief, inflammation resistance, activation, nutrition replenishment and immunity enhancement, and particularly relates to a freeze-dried powder preparation for myopia prevention and vision improvement and a preparation method thereof.

As a specific technical solution, the invention provides a freeze-dried powder preparation for myopia prevention and vision improvement, which comprises freeze-dried powder and solvent liquid; the raw materials of the freeze-dried powder comprise (a) active ingredients, (b) excipients and (c) emulsifiers. The active ingredients are characterized by comprising sodium hyaluronate, lutein, ascorbic acid, oligopeptide-1, oligopeptide-5 and pyrimidine carboxylic acid. The concentration of the active ingredients in the raw materials of the freeze-dried powder is 0.7-3.0 wt%; the excipient is characterized by comprising mannitol and sodium chondroitin sulfate. The concentration of excipient in the raw material of freeze-dried powder is 3.0-5.0 wt%; the emulsifier is characterized by comprising hydrogenated lecithin. The concentration of the emulsifier in the raw material of the freeze-dried powder is 0.1-0.5 wt%; the balance of the raw materials of the freeze-dried powder is deionized water.

The second aspect of the invention provides a solvent solution for fusing the freeze-dried powder. The solvent is characterized by comprising micromolecular alcohol, taurine, rubine, retinol, sodium chloride, lysozyme and deionized water. The solvent comprises, by total mass percent, 1-3% of micromolecular alcohol, 0.5-1.5% of rubusoside, 0.2-0.5% of taurine, 0.02-0.05% of retinol, 0.01-0.05% of sodium chloride, 0.01-0.05% of lysozyme and the balance of deionized water.

The third aspect of the present invention provides a method for preparing a composite preparation, that is, a method for preparing a lyophilized powder preparation of the present invention, which comprises the steps of:

freeze-drying powder preparation:

weighing the components in respective containers according to the formula amount at room temperature, marking and placing on a feeding vehicle according to the feeding sequence.

Adding deionized water into a vacuum homogenizing emulsifying pot at room temperature, heating to 85-90 ℃, preserving heat for 30 minutes for sterilization, then cooling to 80 ℃, adding mannitol, and stirring for dissolving uniformly.

And cooling to 50 ℃ while stirring, sequentially adding sodium hyaluronate and sodium chondroitin sulfate, stirring for 10 minutes, and fully mixing and dissolving uniformly. Adding hydrogenated lecithin, stirring for 10min, mixing thoroughly, dissolving, and homogenizing for 4 min.

Cooling to 40 deg.C, adding lutein, stirring for 10min, and homogenizing for 4min to mix thoroughly and dissolve. Sequentially adding ascorbic acid and pyrimidine carboxylic acid, stirring for 10min, and fully mixing and dissolving uniformly.

Cooling to below 20 deg.C, sequentially adding oligopeptide-1 and oligopeptide-5, stirring, mixing, and dissolving.

Sampling and detecting appearance, smell, color and pH value, meeting the quality control standard requirements, and filtering and discharging to obtain the freeze-dried liquid.

And (3) taking the freeze-drying solution for physicochemical and microbial index inspection, quantitatively filling 1.5ml or 2ml of the freeze-drying solution into a cleaned and sterilized 5ml or 10ml penicillin bottle, and filling into a tray and half plugging.

And (3) putting the tray into a freeze dryer, starting the freeze dryer, freezing the freeze-dried liquid in the bottle to-50 ℃ from room temperature, and maintaining for 3-4 hours to fully freeze the freeze-dried liquid.

Gradually heating the frozen and compacted freeze-dried liquid from-50 ℃ to-25 ℃, wherein the heating rate is about 0.17-1 ℃/min, the temperature is maintained for 12-16 hours, and the vacuum degree is 0.05 mbar.

And then heating from-25 ℃ to 0 ℃, wherein the heating rate is about 0.5-1 ℃/min, the temperature is maintained for 8-12 hours, and the vacuum degree is 0.1 mbar.

And finally, heating from 0 ℃ to 25 ℃, wherein the heating rate is about 0.5-1 ℃/min, the temperature is maintained for 6-10 hours, and the vacuum degree is 0.15 mbar.

And after freeze-drying is finished, keeping the vacuum degree in the freeze dryer bin, pressing a plug, removing vacuum and opening the bin. And then, pricking an aluminum cover, performing lamp inspection (appearance inspection), physicochemical inspection and microbial inspection, and performing subsequent packaging (labeling, boxing and the like) to obtain a finished freeze-dried powder product with the net content of 0.15 g/bottle (5ml bottle) or 0.2 g/bottle (10ml bottle) if the finished freeze-dried powder product is qualified.

Solvent preparation:

Adding deionized water into a vacuum homogenizing emulsifying pot at room temperature, heating to 85-90 ℃, preserving heat for 30 minutes for sterilization, then cooling to 40 ℃, sequentially adding glycerol, theophylline and taurine, and stirring for dissolving uniformly.

Adding retinol and sodium chloride in turn, and stirring to dissolve uniformly.

Cooling to below 20 deg.C, adding lysozyme, stirring, mixing and dissolving.

Sampling to observe appearance, color, smell, viscosity and pH value, meeting the requirements of quality control standard, filtering and discharging to obtain a semi-finished solvent solution, sampling to perform semi-finished product inspection, filling 5ml or 10ml of qualified solution into a cleaned and sterilized 5ml or 10ml penicillin bottle, sampling to perform lamp inspection (appearance inspection) and physicochemical and microbial inspection, and packaging (labeling, boxing and the like) to obtain a finished solvent solution with a net content of 5 ml/bottle or 10 ml/bottle.

Preparing a freeze-dried powder preparation:

and opening the bottle caps of the prepared freeze-dried powder finished product and the solvent finished product respectively, pouring all the solvent finished product into the freeze-dried powder finished product bottle, covering the bottle cap, and gently shaking to completely dissolve the freeze-dried powder to form a uniform transparent solution, namely the freeze-dried powder preparation.

The fourth aspect of the present invention provides a method for using the above lyophilized powder preparation, which is characterized by comprising two methods: first (see fig. 1): pouring the prepared lyophilized powder into a special silica gel eye liquid cup, fitting the cup on eye orbit, tilting head backward to make the solution contact eyeball fully, blinking and rotating for several times, keeping for 1-2 min, and pouring out the solution. Second (see fig. 2): pouring the prepared freeze-dried powder preparation into a cup of an atomization spray gun of a professional eye beautifying instrument, and then carrying out flexible atomization spray cleaning on eyes.

Has the advantages that: the invention provides a freeze-dried powder preparation for myopia prevention and vision improvement nursing, which adopts modern biotechnology high-function active peptide, vitamin, pyrimidine carboxylic acid and the like as unique functional components and innovative formula, and adopts vacuum freeze drying technology to prepare the freeze-dried powder preparation, on one hand, the activity of the active peptide and the vitamin is effectively protected, on the other hand, no preservative is added, the freeze-dried powder preparation can be used after being dissolved once, has no irritation, no toxic or side effect and is safer to use. Can effectively decontaminate and clean, moisturize and moisten, relieve and reduce pressure, resist inflammation and activate, supplement nutrition, enhance immunity and have good nursing effect on myopia prevention and vision improvement.

Drawings

FIG. 1: a first usage diagram that may be exemplified by the product of the present invention;

FIG. 2: a second usage diagram that may be exemplified by the product of the invention;

FIG. 3: example 3 product moisture retention test results (for 12 consecutive days);

FIG. 4: example 3 product moisture retention test results (after 7 days of rest);

FIG. 5: example 3 product Water locking Capacity test results;

FIG. 6: example 3 product percutaneous water loss (TEWL) test results;

FIG. 7: example 3 product damage resistance (uv UVA exposure) test results.

Detailed Description

Unless otherwise indicated, implied from the context, or customary in the art, all parts and percentages herein are by weight and the testing and characterization methods used are synchronized with the filing date of the present application. To the extent that a definition of a particular term disclosed in the prior art is inconsistent with any definitions provided herein, the definition of the term provided herein controls.

The technical features of the technical solutions provided by the present invention are further clearly and completely described below with reference to the specific embodiments, and the scope of protection is not limited thereto.

The words "preferred", "preferably", "more preferred", and the like, in the present invention, refer to embodiments of the invention that may provide certain benefits, under certain circumstances. However, other embodiments may be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, nor is it intended to exclude other embodiments from the scope of the invention. The sources of components not mentioned in the present invention are all commercially available.

As a specific embodiment, the first aspect of the present invention provides a lyophilized powder formulation for myopia prevention and vision improvement, the lyophilized powder raw materials comprising (a) an active ingredient, (b) an excipient, and (c) an emulsifier.

In a preferred embodiment, the (a) active ingredients in the raw material of the lyophilized powder include sodium hyaluronate, lutein, ascorbic acid, oligopeptide-1, oligopeptide-5 and pyrimidine carboxylic acid, and the concentration of the active ingredients in the raw material of the lyophilized powder is 0.7-3.0 wt%, preferably 1.2-3.0 wt%, more preferably 1.5-2.5 wt%.

In a preferred embodiment, the excipient (b) in the raw material of the lyophilized powder comprises mannitol and sodium chondroitin sulfate, and the concentration of the excipient in the raw material of the lyophilized powder is 3.0-5.0 wt%, preferably 3.5-5.0 wt%, and more preferably 4.0-4.5 wt%.

In a preferred embodiment, the emulsifier (c) in the raw material of lyophilized powder comprises hydrogenated lecithin, and the concentration of the emulsifier in the raw material of lyophilized powder is 0.1-0.5 wt%, preferably 0.2-0.5 wt%, more preferably 0.3-0.4 wt%.

(a) Active ingredient

The sodium hyaluronate is also called sodium hyaluronate or sodium uronate, and is abbreviated as HA. The eye care product is prepared by fermenting lactococcus lactis, has a molecular weight of 60-130 ten thousand daltons, is a humectant and a repairing agent widely used in cosmetics, and also has a good function in eye care. Water retention: HA HAs strong moistening and lubricating effects on eyes, obviously prolongs the tear film break-up time (BUT), stabilizes the tear film, and can effectively relieve eye diseases such as dry eye surface, congestion and the like; repairing property: HA is combined through a receptor, protein kinase is activated, actin filaments on cytoskeleton are pulled to react and the like, and cell movement and proliferation are promoted, so that cornea and conjunctiva injury healing is promoted, the cornea and the conjunctiva are repaired, and eyes are protected; the synergy is as follows: HA can enable active matters to stay in the conjunctival sac for a long time through physical adhesion and membrane affinity, so that the bioavailability of the active matters is improved, a quasi-slow release effect is exerted, and the effect is improved; comfort: the unique macromolecular reticular structure and the characteristic of the non-Newtonian fluid of the HA can cover the periphery of a pain receptor, reduce discomfort or pain caused by illumination stimulation, pollutant stimulation and mechanical stimulation and increase the comfort of eyes.

The xanthophyll is a carotenoid extracted from corn, marigold, etc. and having vitamin A activity, and is called lutein. Has antioxidant effect, and can help retina of eye resist ultraviolet injury, promote blood circulation, and relieve and balance intraocular pressure.

The ascorbic acid, i.e., vitamin C, is one of the most needed vitamins for metabolism in the human organs. Has strong antioxidant and antidotal effects. Can reduce the fragility of the capillary vessels of the eye membrane and prevent the incomplete function of the capillary vessels, etc.

The oligopeptide-1 is a condensation product of glycine, histidine and lysine. Has the effects of promoting epidermal cell regeneration, accelerating the renewal of aged cells, synergistically resisting aging and the like, and has the effect of repairing ocular and corneal injuries.

The oligopeptide-5 is a protein consisting of 73 amino acids. The cornea repair liquid can promote the proliferation and the renewal of keratinocytes and stimulate the regeneration, the differentiation and the migration of epithelial cells around wounds, so that the cornea of the eye can be effectively repaired and the health of the retina can be maintained.

The pyrimidine carboxylic acid is a compound represented by the general formula (I):

wherein R1 and R2 are each independently selected from-H, -OH, -CH₃、-CH₂CH₃、-CH₂CH (OH) Ra, wherein Ra is selected from-H, C1-C4 alkane. In a more preferred embodiment, R1 and R2 are each independently selected from-H, -OH, -CH₃、-CH₂CH₃. In a most preferred embodiment, the pyrimidine carboxylic acid is a tetrahydro-methyl pyrimidine carboxylic acid and/or a hydroxy-tetrahydro-methyl pyrimidine carboxylic acid.

The tetrahydro-methyl pyrimidine carboxylic acid, namely Ectoin, is a micromolecular amino acid derivative prepared by a biological fermentation technology. Can effectively improve the immune protection capability of skin cells, increase the cell repair capability and ensure that the skin can effectively resist the invasion of microorganisms and allergens. Therefore, the composite material is used for whole cell protection of pollution resistance, allergen resistance, ultraviolet light resistance, blue light resistance and other exogenous damage factors.

In a preferred embodiment, the active ingredients, namely lutein, ascorbic acid, oligopeptide-1, oligopeptide-5 and tetrahydro-methyl pyrimidine carboxylic acid, are contained in the raw material of the lyophilized powder in a mass ratio of (0.01-0.05): (0.05-0.2): (0.0005-0.001): (0.0005-0.001): (0.5-2.0), more preferably (0.03-0.05): (0.1-0.2): (0.0008-0.001): (0.0008-0.001): (1.0-2.0).

(b) Excipient

The excipient may be selected from saccharides and sugar alcohols. So long as it contains at least one or more of the saccharides that form an amorphous state upon lyophilization as described below.

The saccharide which forms an amorphous state upon lyophilization is not limited to the following, and examples thereof include monosaccharides such as glucose and fructose, and disaccharides such as maltose, lactose, sucrose and trehalose.

Specific examples of the sugar alcohol that forms an amorphous state upon lyophilization are not limited to the following, and examples thereof include inositol and sorbitol.

Water-soluble sugars are preferably used, and a sugar selected from mannitol and sodium chondroitin sulfate is particularly preferably used.

In a preferred embodiment, the excipient mannitol and the sodium chondroitin sulfate in the raw material of the lyophilized powder have a mass ratio of (3.0-5.0): (0.03-0.1.), more preferably (3.0-4.0): (0.03-0.05).

The mannitol, also known as mannitol, is prepared from starch sugar or sucrose as a raw material, and is a commonly used humectant for medicines and cosmetics. The freeze-dried powder also serves as a main excipient in the invention.

The sodium chondroitin sulfate is a proteoglycan widely existing in cartilage of sharks, cattle, pigs and chickens, is distributed on extracellular matrix and cell surface of animal tissues, has effects of oxygenation, nourishing and lubrication, can remarkably improve moisture retention, repair dryness, and enhance eyeball cutin moisture retention and oxygen supply barrier functions. The freeze-dried powder excipient also serves as a freeze-dried powder auxiliary excipient in the invention.

The chondroitin sulfate sodium is mainly sulfated chain mucopolysaccharide sodium salt, is viscous after being dissolved in water, and is found by experiments of an inventor that the content of the chondroitin sulfate sodium is not suitable for being large, otherwise, the chondroitin sulfate sodium is easy to cause that a system cannot be uniformly dispersed. The appearance of the freeze-dried powder is required to be compact and smooth without collapse, and in order to ensure that the appearance state is better, the inventor can just solve the problem when adding hydrogenated lecithin into the freeze-dried powder, and can also ensure the quick dissolution and use effect of the product.

(c) Emulsifier

To improve the solubility and apparent clarity of the compositions of the present invention, a suitable amount of emulsifier is added.

Examples of emulsifiers suitable for the present invention include sorbitan sesquioleate, polysorbate, hydrogenated lecithin and the like.

In a preferred embodiment, the emulsifier is preferably hydrogenated lecithin, and the concentration in the raw material of the lyophilized powder is 0.1-0.5 wt%, preferably 0.2-0.5 wt%, more preferably 0.3-0.4 wt%.

The hydrogenated lecithin is a natural emulsifier prepared by the hydrogenation reaction of lecithin extracted from soybeans. Can emulsify some water-insoluble oily components to form a submicron to nanometer liposome wrapping structure, and has good solubilization and penetration effects.

Experiments show that the solubility of the lutein insoluble in water is remarkably increased after the lutein is emulsified and wrapped by hydrogenated lecithin, and the dissolution becomes completely transparent and clear by properly adjusting the proportion of the rubusoside and the tetrahydro-methylpyrimidine carboxylic acid. The reason is probably that the lutein is wrapped in the inner layer by the hydrogenated lecithin to form liposome arrangement with hydrophilic outer layer and lipophilic inner layer, and the repulsion force between the hydrogenated lecithin is reduced after the lutein is protonated in a rubusoside and tetrahydro-methyl-pyrimidine-carboxylic acid system, so that the lutein wrapped in the hydrogenated lecithin has better hydrophilicity, better permeability and slow release, and the treated freeze-dried powder has good effect.

In a second aspect of the present invention, there is provided a vehicle for mixing the above-mentioned lyophilized powders. The solvent comprises micromolecular alcohol, taurine, rubusoside, retinol, sodium chloride, lysozyme and deionized water. .

In a preferred embodiment, the freeze-dried powder and the solvent liquid are mixed according to the proportion of 1g/100mL, namely when the packaging mass of the freeze-dried powder is 0.05g, the solvent liquid is mixed with the solvent liquid with the volume of 5 mL.

In a preferred embodiment, the solvent liquid comprises 1-3% of small molecular alcohol, 0.5-1.5% of rubusoside, 0.2-0.5% of taurine, 0.02-0.05% of retinol, 0.01-0.05% of sodium chloride, 0.01-0.05% of lysozyme and the balance of deionized water by mass percentage.

Examples of the small molecule alcohol include glycerin and propylene glycol; glycerol is preferred.

The betaine is extracted from beet root, mainly contains trimethylglycine, has long-acting moisturizing and anti-allergy repairing effects, provides sufficient water and nutrients for cuticle, activates cells, and enhances moisturizing and barrier functions.

The taurine is a free amino acid existing in animal tissue cells, has the functions of improving nerve conduction and vision, is beneficial to improving eyesight and maintaining normal functions of eye cell membranes.

The lysozyme is a natural antibacterial agent, has the characteristics of antivirus and bacteriostasis effects, safety, no toxicity, good stability and the like, and is also used as a preservative in the invention.

In a preferred embodiment, the vehicle further comprises an inorganic salt, and the inorganic salt suitable for the vehicle of the present invention is sodium chloride, which serves to balance the osmotic pressure of the solution.

The deionized water is ultrapure water which is prepared by carrying out two-stage Reverse Osmosis (RO) and Electric Desalting (EDI) on tap water and then distilling. Sterilizing at 90 deg.C for 30min before use.

As a specific embodiment, the third aspect of the present invention provides a method for preparing the lyophilized powder and the solution, comprising the following specific steps:

1. freeze-drying powder preparation:

(1) weighing the components in respective containers according to the formula amount at room temperature, marking and placing on a feeding vehicle according to the feeding sequence.

(2) Adding deionized water into a vacuum homogenizing emulsifying pot at room temperature, heating to 85-90 deg.C, maintaining the temperature for 30min for sterilization, cooling to 80 deg.C, adding mannitol, and stirring for dissolving uniformly.

(3) And cooling to 50 ℃ while stirring, sequentially adding sodium hyaluronate and sodium chondroitin sulfate, stirring for 10 minutes, and fully mixing and dissolving uniformly. Adding hydrogenated lecithin, stirring for 10min, mixing thoroughly, dissolving, and homogenizing for 4 min.

(4) Cooling to 40 deg.C, adding lutein, stirring for 10min, and homogenizing for 4min to mix thoroughly and dissolve. Sequentially adding ascorbic acid and tetrahydro-methyl pyrimidine carboxylic acid, stirring for 15-20 min, and mixing and dissolving.

(5) Cooling to below 20 deg.C, sequentially adding oligopeptide-1 and oligopeptide-5, stirring for 10min, and mixing and dissolving.

(6) Sampling and detecting appearance, smell, color and pH value, meeting the quality control standard requirements, and filtering and discharging to obtain the freeze-dried liquid.

(7) And (3) taking the freeze-drying solution for physicochemical and microbial index inspection, quantitatively filling 1.5ml or 2ml of the freeze-drying solution into a cleaned and sterilized 5ml or 10ml penicillin bottle, and filling into a tray and half plugging.

(8) Putting the tray into a freeze dryer, starting the freeze dryer, freezing the freeze-dried liquid in the bottle from room temperature to-50 ℃, and maintaining for 3-4 hours to fully freeze the freeze-dried liquid.

(9) Gradually heating the frozen lyophilized solution from-50 deg.C to-25 deg.C, at a heating rate of 0.17-1 deg.C/min for 12-16 hr, and under a vacuum degree of 0.05 mbar.

(10) Then heating from-25 deg.C to 0 deg.C, heating rate is about 0.5-1 deg.C/min, maintaining for 8-12 hr and vacuum degree is 0.1 mbar.

(11) Finally, raising the temperature from 0 deg.C to 25 deg.C, raising the temperature rate at about 0.5-1 deg.C/min, maintaining for 6-10 hr and vacuum degree at 0.15 mbar.

(12) And after freeze-drying is finished, keeping the vacuum degree in the freeze dryer bin, pressing a plug, removing vacuum and opening the bin. And then, pricking an aluminum cover, performing lamp inspection (appearance inspection), physicochemical inspection and microbial inspection, and performing subsequent packaging (labeling, boxing and the like) to obtain a finished freeze-dried powder product with the net content of 0.15 g/bottle (5ml bottle) or 0.2 g/bottle (10ml bottle) if the finished freeze-dried powder product is qualified.

2. Preparation of a solvent solution:

(2) Adding deionized water into a vacuum homogenizing emulsifying pot at room temperature, heating to 85-90 deg.C, maintaining the temperature for 30min for sterilization, cooling to 40 deg.C, sequentially adding glycerol, theophylline and taurine, stirring for 15-20 min, and dissolving uniformly.

(3) Adding retinol and sodium chloride in turn, stirring for 10 minutes and dissolving uniformly.

(4) Cooling to below 20 deg.C, adding lysozyme, stirring for 10min, and mixing.

(5) Sampling to observe appearance, color, smell, viscosity and pH value, meeting the requirements of quality control standard, filtering and discharging to obtain a semi-finished solvent solution, sampling to perform semi-finished product inspection, filling 5ml or 10ml of qualified solution into a cleaned and sterilized 5ml or 10ml penicillin bottle, sampling to perform lamp inspection (appearance inspection) and physicochemical and microbial inspection, and packaging (labeling, boxing and the like) to obtain a finished solvent solution with a net content of 5 ml/bottle or 10 ml/bottle.

As a specific embodiment, the freeze-dried powder preparation is prepared by dissolving freeze-dried powder in solvent liquid. The method comprises the following steps of opening bottle caps of prepared freeze-dried powder finished products and solvent liquid finished products respectively, pouring all the solvent liquid finished products into a freeze-dried powder finished product bottle, covering the bottle cap, and gently shaking to enable the freeze-dried powder to be completely dissolved to form a uniform and transparent solution.

As a specific embodiment, a fourth aspect of the present invention provides a method of using a lyophilized powder formulation. Two methods can be used as described in the figures.

As shown in fig. 1, when the first method is used, more specifically, the operation steps are that the prepared freeze-dried powder finished product and solvent liquid finished product are respectively opened, the solvent liquid is completely poured into the freeze-dried powder bottle, the bottle stopper is covered and the bottle stopper is gently shaken to completely dissolve the freeze-dried powder to form a uniform transparent solution, then the solution is poured into a special silica gel eye liquid making cup, the cup is tightly attached to the eye orbit, the head is tilted backwards, the solution is fully contacted with the eyeball and is blinked and rotated for a plurality of times, and after the solution is kept for about 3-5min, the solution is poured out.

As shown in the attached figure 2, when the second method is adopted, more specifically, the operation steps are that the prepared freeze-dried powder finished product and the solvent liquid finished product are respectively opened, the solvent liquid is completely poured into the freeze-dried powder bottle, the bottle stopper is covered and the bottle stopper is gently shaken to ensure that the freeze-dried powder is completely dissolved to form a uniform transparent solution, then the uniform transparent solution is poured into a specialized atomization spray gun cup of the eye beautifying instrument, and then the eyes are cleaned and moistened by flexible spray.

The present invention is described in detail below with reference to examples, which are provided for the purpose of further illustration only and are not to be construed as limiting the scope of the present invention, and the insubstantial modifications and adaptations thereof by those skilled in the art based on the teachings of the present invention will still fall within the scope of the present invention.

Example 1

Embodiment 1 provides a lyophilized powder preparation for myopia prevention and vision improvement, which comprises two parts of lyophilized powder and solvent, wherein the components in percentage by mass are as follows:

freeze-drying powder: the freeze-dried powder comprises, by total weight of the freeze-dried powder, 3.0% of mannitol, 0.1% of hydrogenated lecithin, 0.05% of sodium hyaluronate, 0.02% of sodium chondroitin sulfate, 0.01% of lutein, 0.05% of ascorbic acid, 0.5% of tetrahydro-methylpyrimidine carboxylic acid, oligopeptide-10.0005%, oligopeptide-50.0005% and the balance of deionized water.

Solution of a medium: based on the total weight of the solvent, the solvent comprises 1% of glycerol, 0.5% of rubusoside, 0.2% of taurine, 0.001% of lysozyme, 0.02% of retinol, 0.01% of sodium chloride and the balance of deionized water.

The preparation method comprises the following steps:

freeze-drying powder preparation:

(1) weighing the components in respective containers according to the formula ratio at room temperature, marking and placing on a feeding vehicle according to the feeding sequence;

(2) adding deionized water into a vacuum homogenizing emulsifying pot at room temperature, heating to 90 deg.C, maintaining the temperature for 30min for sterilization, cooling to 80 deg.C, adding mannitol, stirring and dissolving;

(3) cooling to 50 deg.C under stirring, sequentially adding sodium hyaluronate and sodium chondroitin sulfate, stirring for 10min, mixing and dissolving completely, adding hydrogenated lecithin, stirring for 10min, mixing and dissolving completely, and homogenizing for 4 min; cooling to 40 deg.C, adding lutein, stirring for 10min, homogenizing for 4min to make it fully mixed and dissolved, sequentially adding ascorbic acid and tetrahydro-methylpyrimidine carboxylic acid, stirring for 10min, and fully mixing and dissolving;

(4) cooling to below 20 deg.C, maintaining vacuum in the pot, sequentially adding oligopeptide-1 and oligopeptide-5, stirring for 10min, mixing and dissolving;

(5) sampling to detect appearance, smell, color and pH value, and filtering and discharging to obtain lyophilized liquid; 2ml of the solution is quantitatively filled into a cleaned and sterilized 10ml penicillin bottle, and is filled into a tray and is half plugged;

(6) putting the tray into a freeze dryer, starting the freeze dryer, freezing the freeze-dried liquid in the bottle from room temperature to-50 ℃, and maintaining for 4 hours to fully freeze the freeze-dried liquid;

(7) gradually heating the frozen and compacted freeze-dried liquid from-50 ℃ to-25 ℃, wherein the heating rate is about 0.17-1 ℃/min, maintaining for 15h, and the vacuum degree is 0.05 mbar;

(8) heating from-25 ℃ to 0 ℃, wherein the heating rate is about 0.5-1 ℃/min, maintaining for 10h, and the vacuum degree is 0.1 mbar;

(9) finally, heating from 0 ℃ to 25 ℃, wherein the heating rate is about 0.5-1 ℃/min, the temperature is maintained for 8 hours, and the vacuum degree is 0.15 mbar;

(10) and after freeze-drying is finished, keeping the vacuum degree in the freeze dryer bin, pressing a plug, removing vacuum and opening the bin. And then, pricking an aluminum cover, performing lamp inspection (appearance inspection), physicochemical inspection and microbial inspection, and performing subsequent packaging (labeling, boxing and the like) to obtain a finished freeze-dried powder product with the net content of 0.2 g/bottle after the product is qualified.

Preparation of a solvent solution:

(2) adding deionized water into a vacuum homogenizing emulsifying pot at room temperature, heating to 90 deg.C, maintaining the temperature for 30min for sterilization, cooling to 40 deg.C, sequentially adding glycerol, theophylline and taurine, stirring for 15min, and dissolving uniformly.

(3) Sequentially adding retinol and sodium chloride, stirring for 10min, and dissolving.

(4) Cooling to below 20 deg.C, adding lysozyme, stirring for 10min, mixing and dissolving

(5) Sampling to observe appearance, color, smell, viscosity and pH value, meeting the requirements of quality control standard, filtering and discharging to obtain a semi-finished product of the solvent liquid, then sampling to perform semi-finished product inspection, namely quantitatively filling 10ml of qualified product into a cleaned and sterilized 10ml penicillin bottle, sampling to perform lamp inspection (appearance inspection) and physicochemical and microbial inspection, and packaging (labeling, boxing and the like) to obtain a finished product of the solvent liquid with the net content of 10 ml/bottle.

Preparation of lyophilized powder preparation:

and opening the bottle caps of the freeze-dried powder finished product and the solvent liquid finished product at room temperature, adding 10mL of the solvent liquid finished product into 0.10g of the freeze-dried powder finished product, and slightly shaking to dissolve uniformly to obtain a compound preparation, namely the freeze-dried powder preparation.

Example 2

Embodiment 2 provides a lyophilized powder preparation for myopia prevention and vision improvement, which comprises two parts of lyophilized powder and solvent, wherein the components in percentage by mass are as follows:

freeze-drying powder: the total weight of the freeze-dried powder is taken as a reference, and the freeze-dried powder comprises 4.0% of mannitol, 0.3% of hydrogenated lecithin, 0.07% of sodium hyaluronate, 0.03% of sodium chondroitin sulfate, 0.03% of lutein, 0.1% of ascorbic acid, 1.0% of tetrahydro-methyl pyrimidine carboxylic acid, oligopeptide-10.0007%, oligopeptide-50.0007% and the balance of deionized water.

Solution of a medium: based on the total weight of the solvent, the solvent comprises 2% of glycerol, 1% of rubine, 0.3% of taurine, 0.002% of lysozyme, 0.03% of retinol, 0.02% of sodium chloride and the balance of deionized water.

The preparation method of the lyophilized powder preparation is the same as that of example 1.

Example 3

Embodiment 3 provides a lyophilized powder preparation for myopia prevention and vision improvement, which comprises two parts of lyophilized powder and solvent, wherein the components in percentage by mass are as follows:

freeze-drying powder: the freeze-dried powder comprises, by total weight of the freeze-dried powder, 5.0% of mannitol, 0.5% of hydrogenated lecithin, 0.1% of sodium hyaluronate, 0.05% of sodium chondroitin sulfate, 0.05% of lutein, 0.2% of ascorbic acid, 2.0% of tetrahydro-methylpyrimidine carboxylic acid, oligopeptide-10.001%, oligopeptide-50.001% and the balance of deionized water.

Solution of a medium: based on the total weight of the solvent, the solvent comprises 3% of glycerol, 1.5% of theophylline, 0.5% of taurine, 0.003% of lysozyme, 0.05% of retinol, 0.05% of sodium chloride and the balance of deionized water.

Example 4

Embodiment 4 provides a lyophilized powder preparation for myopia prevention and vision improvement, which comprises two parts of lyophilized powder and solvent, wherein the components in percentage by mass are as follows:

freeze-drying powder: the freeze-dried powder comprises, by total weight of the freeze-dried powder, 2.0% of mannitol, 0.1% of hydrogenated lecithin, 0.05% of sodium hyaluronate, 0.05% of lutein, 0.05% of ascorbic acid, 0.5% of tetrahydro-methylpyrimidine carboxylic acid, oligopeptide-10.0005%, oligopeptide-50.0005% and the balance of deionized water.

Example 5

Embodiment 5 provides a lyophilized powder preparation for myopia prevention and vision improvement, which comprises two parts of lyophilized powder and solvent, wherein the components by mass percent are as follows:

freeze-drying powder: the total weight of the freeze-dried powder is taken as a reference, and the freeze-dried powder comprises 2.0% of mannitol, 0.1% of hydrogenated lecithin, 0.05% of sodium hyaluronate, 0.02% of sodium chondroitin sulfate, 0.05% of lutein, 0.05% of ascorbic acid, oligopeptide-10.0005%, oligopeptide-50.0005% and the balance of deionized water.

Example 6

Embodiment 6 provides a lyophilized powder preparation for myopia prevention and vision improvement, which comprises two parts of lyophilized powder and solvent, wherein the components in percentage by mass are as follows:

freeze-drying powder: based on the total weight of the freeze-dried powder, the freeze-dried powder comprises 2.0% of mannitol, 0.1% of hydrogenated lecithin, 0.05% of sodium hyaluronate, 0.02% of sodium chondroitin sulfate, 0.3% of lutein, 0.05% of ascorbic acid, 0.1% of tetrahydro-methyl pyrimidine carboxylic acid, oligopeptide-10.0005%, oligopeptide-50.0005% and the balance of deionized water.

Example 7

Embodiment 7 provides a lyophilized powder preparation for myopia prevention and vision improvement, which comprises two parts of lyophilized powder and solvent, wherein the components in percentage by mass are as follows:

freeze-drying powder: based on the total weight of the freeze-dried powder, the freeze-dried powder comprises 2.0% of mannitol, 0.05% of sodium hyaluronate, 0.02% of sodium chondroitin sulfate, 0.05% of lutein, 0.05% of ascorbic acid, 0.1% of tetrahydro-methylpyrimidine carboxylic acid, oligopeptide-10.0005%, oligopeptide-50.0005% and the balance of deionized water.

Evaluation of Performance：

The lyophilized powder preparations of each example were used as a test substance to evaluate the following properties.

1. Sensory and physicochemical indexes: the test results are shown in Table 1.

TABLE 1 sensory, physicochemical indices

2. The hygiene indexes are as follows: the test results are shown in Table 2.

TABLE 2 hygiene index

Remarking: A. in each embodiment, the freeze-dried powder, the solution medium and the preparation are detected, and the detection items and index requirements are the same; B. the detection method comprises the following steps: cosmetic safety specifications (2015 edition).

3. Irritation (eye irritation test): the test was carried out using the test specimen of example 3, and the test results are shown in Table 3.

TABLE 3 eye irritation test

The test method comprises the following steps: the test substance is dripped into the conjunctival sac of eyes at one side of the rabbit, the eyes are closed for one second, and the eyes at the other side are not treated to be used as self control. Observation and rating were required after dropping the test substance according to the cosmetic safety specifications (2015 edition).

4. And (3) testing the efficacy:

A. moisture retention test: the test results are shown in FIG. 3 (moisture retention test pattern/used for 12 days) and FIG. 4 (moisture retention test pattern/used for 7 days).

The test method comprises the following steps: selecting 6 female healthy volunteers, and using the test sample and the placebo on the left half face and the right half face respectively, wherein the use is performed once a day for 12 days; the test sample was the product of example 3. The skin moisture content (SKICON-200 EX-USB) was tested double-blindly, randomly, for

days

8,9,10,11,12 and 19 (after 7 days of inactivity).

The results show that the test samples were effective in increasing skin moisture compared to placebo, which increased skin moisture by nearly one-fold after 8 days of use compared to the placebo group. Even after 7 days of rest, skin moisture levels remained at a higher level and significantly higher than those of the placebo group.

B. Moisturizing barrier function enhancement test: 1) the water locking capability test result is shown in figure 5; 2) the results of the percutaneous water loss (TEWL) test are shown in figure 6.

The test method comprises the following steps: dry weight method of weighing filter paper. The test sample was the product of example 3. That is, soaking the filter paper in the test object to make it wet to saturation, and weighing; the filter paper was dried under controlled conditions and the weight of the filter paper was measured every 30 min.

The results show that: the test sample showed stronger water-locking ability than hyaluronic acid HA (130 ppm molecular weight, 0.1% concentration), indicating that the skin moisturizing barrier water-locking function was enhanced.

The test method comprises the following steps: selecting 13 dry skin volunteers, applying to the marked skin area on one side of the face once a day for 5 days, wiping off with gloved fingers after each application and allowing the skin to dry for 1 hour, and measuring TEWL value with a percutaneous moisture loss tester (VAPO SCAN AS-VT100 RS); the test sample was the product of example 3.

The results show that: the test sample can obviously reduce the loss of water through epidermis, and the skin moisturizing barrier function is enhanced.

C. And (3) damage resistance test: the test results are shown in FIG. 7.

The test method comprises the following steps: ultraviolet UVA irradiation damage repair test method. That is, keratinocytes (HaCaT) were irradiated with ultraviolet UVA (5J/cm2) to measure the migration value (. mu.m) of the DNA of the keratinocytes.

The results show that: the DNA migration value of keratinocytes after 12 hours pretreatment with the test sample was less than 38(μm) after UVA irradiation compared to the control sample without pretreatment, indicating that the test sample (product of example 3) significantly reduced UVA damage to cellular DNA.

D. Inhibition of bacterial Lipopolysaccharide (LPS) -induced inflammatory responses test: the test results are shown in Table 5.

TABLE 5 inhibition of inflammatory response test results

The test method comprises the following steps: keratinocytes (HaCaT) were pretreated with a test sample and LPS (10. mu.g/ml, Pseudomonas aeruginosa-derived), and the expression of IL-1. alpha. (interleukin IL-1. alpha.), IL-6 (interleukin-6), IL-8 (interleukin-8), TNF-. alpha (tumor necrosis factor-alpha), and IkB-alpha (arrestin-alpha) which are each inflammatory factor involved in degradation was examined in comparison with the untreated sample.

The results show that: the test sample (product of example 3) can effectively inhibit the degradation of I kappa B-alpha and the expression of related inflammatory factors, thereby inhibiting inflammatory response induced by LPS.

5. Human body effect verification test: the test results are shown in Table 6.

The test method comprises the following steps: the product of example 3 was subjected to a test for efficacy, and the results of the tests for efficacy and irritation before and after use were shown in Table 6.

TABLE 6 volunteer effects

Remarking: 1) the using method comprises the following steps: following the first application method, the effect is reported after one bottle (5ml) for each morning and one month (not less than 22 days). Using effect evaluation criteria: obvious effect, namely the original daily feeling of dryness, eye swelling, easy fatigue, blur and other uncomfortable symptoms after use is selected as the option of 'obvious improvement' or 'good effect'; effective-after-use, the user often feels dry and astringent, eye swelling, easy fatigue, blurring and other uncomfortable symptoms every day and has an option of improving or having an effect; ineffectiveness-no improvement or no effect of the original discomfort symptoms after use. 2) The effective rate is as follows: (the number of effective people + the number of effective people)/the total number of used people is multiplied by 100 percent.

Note 1: the self-diagnosis approximation degree is 200 DEG and 300 DEG; note 2: the self-diagnosis approximation degree is 300 DEG and 400 DEG; note 3: the self-describing no myopia is confirmed, but the eyes usually feel acid and swollen, hyperemia and unclear conditions after people see things for a short time; note 4: the diagnosis can be confirmed without myopia, but the eyes are easy to feel fatigue, dry and itchy, and the eyes can not be clear when looking far or near, and the eyes are like to have discomfort such as ghosting.

6. Typical use cases are:

a typical use case one:

miss Yang, women, age 32. The self-diagnosis of moderate myopia in both eyes is carried out by performing refractive correction operation, and the vision is 0.6 on the left and 0.5 on the right. Eyes feel sore and bloated, and the eyes look blurred for about 3 months. The hospitalization diagnosis is eye fatigue and mild infection. After a certain amount of eye drop is opened, the eye drop can be used for 1 month, and the improvement is not obvious. After the product of the embodiment 3 is used for 25 times in a month, no acid swelling feeling is fed back, congestion disappears, eyes are clear, moist and comfortable, blur is obviously improved, the left 0.7 and the right 0.6 of visual examination are restored to the normal state before. Has no irritation feeling when used.

Example two is typically used:

dun classmate, male, 17 years old. The mild myopia of both eyes can be confirmed by self-describing. After the eyes are normally read and learned for 1 month, the eyes are easy to fatigue, people can be blurred for a short time when seeing far and near dry things, and the eyes are dry and uncomfortable after getting up in the morning with eye droppings. The eye drops and other methods for treatment are prescribed in doctors, and the complete improvement is not seen. Parents try to use the product of the embodiment 3 for 28 times in a month, the eyes are fed back to relieve much, the fatigue is caused in the past, the eyes are not clearly seen, the phenomena of dryness and eye droppings are avoided, and the eyes feel comfortable. The effect on the tested sample is satisfactory. Has no irritation feeling when used.

Example three is typically used:

beam lady, 59 years old. The eyes can be diagnosed with myopia and presbyopia for twenty years, and the glasses are worn at ordinary times. However, in recent years, eyes are often swollen, foreign bodies exist in eyes, and the eyes are blurred. The diagnosis after hospitalization is not related to cataract, glaucoma and senile eye diseases, and the doctor advices to pay attention to rest and nutrition supplement. The eye lotion for moisturizing and relieving is prepared. But the improvement after use is not great. The product of this embodiment 3 on probation totally 30 times, feedback eyes acid swelling, foreign body sensation disappear, and the state and stability of recovering to see the thing, no longer good time bad. The effect on the tested sample is very satisfactory. Has no irritation feeling when used. Example four is typically used:

mr. Weekly, IT male, age 27. No myopia. However, due to the working relationship, the time of each day is very long when facing computers and mobile phones. Often feel swollen, dry and itchy eyes, and the head is raised and the eyes look far away, and the eyes are blurred and the eyes can recover normal vision for a long time. After 22 times of using the product of the embodiment 3, the blurred vision of the far and near east and west can be quickly recovered to be normal after feedback work, the eyes are not swollen and tired, and the eyes are fresh and comfortable. Has no irritation feeling when used.

The total using effect verification test shows that: the formulations of the present invention all had significant efficacy to the user, consistent with efficacy testing results. And the human body does not have irritation and any other adverse reactions when used, and the result is consistent with the animal irritation test result.

Claims

1. A lyophilized powder preparation for preventing myopia and improving vision is characterized by comprising lyophilized powder and solvent; the raw materials of the freeze-dried powder comprise (a) active ingredients, (b) excipients and (c) emulsifiers.

2. The lyophilized powder formulation of claim 1, wherein the active ingredients comprise sodium hyaluronate, lutein, ascorbic acid, oligopeptide-1, oligopeptide-5 and pyrimidine carboxylic acid, and the concentration of the active ingredients in the raw material of the lyophilized powder is 0.7-3.0 wt%.

3. The lyophilized powder formulation of claim 1, wherein the excipient comprises mannitol and sodium chondroitin sulfate, and the concentration of the excipient in the lyophilized powder material is 3.0-5.0 wt%.

4. The lyophilized powder formulation of claim 1, wherein the emulsifier comprises hydrogenated lecithin, and the concentration of emulsifier in the lyophilized powder material is 0.1-0.5 wt%.

5. The lyophilized powder formulation of claim 1, further comprising deionized water as a solvent, with the balance being the concentration in the lyophilized powder material.

6. The lyophilized powder formulation of claim 2, wherein the pyrimidine carboxylic acid is a compound represented by general formula (i):

wherein R1 and R2 are each independently selected from-H, -OH, -CH₃、-CH₂CH₃、-CH₂CH (OH) Ra, wherein Ra is selected from the group consisting of-H, C1-C4 alkanes.

7. The lyophilized powder preparation of claim 6, wherein the lyophilized powder is prepared by uniformly mixing the raw materials for preparing the lyophilized powder, freezing the mixture into a solid state, and performing vacuum-pumping dehydration.

8. Lyophilized powder formulation according to any of claims 1-7, wherein the vehicle is used to fuse the lyophilized powder; and the solvent comprises micromolecular alcohol, taurine, rubusoside, retinol, sodium chloride, lysozyme and deionized water.

9. A method for preparing the lyophilized powder preparation according to any one of claims 1 to 8, comprising a method for preparing the lyophilized powder and a solution, comprising the steps of:

s1, preparation of freeze-dried powder:

(1) uniformly stirring and dissolving preparation raw materials of the freeze-dried powder;

(2) filtering and discharging after sampling and detecting are qualified to obtain freeze-dried liquid;

(3) taking the freeze-drying liquid for physicochemical and microbial index inspection, quantifying and filling after the freeze-drying liquid is qualified, and dishing and half plugging;

(4) fully freezing the freeze-drying liquid;

(5) freeze-drying the frozen freeze-drying liquid;

(6) after freeze-drying, carrying out appearance inspection, physicochemical inspection and microbial inspection, and packaging to obtain a freeze-dried powder finished product;

s2, preparation of a solvent:

(1) uniformly stirring and dissolving the preparation raw materials of the solvent liquid;

(2) sampling, observing, filtering and discharging to obtain a semi-finished solution of the solvent after meeting the quality control standard requirement; sampling, checking semi-finished product, checking appearance, physicochemical inspection, and microorganism inspection, and packaging to obtain solvent solution.

10. A use method of the freeze-dried powder preparation according to any one of claims 1 to 8, characterized in that the freeze-dried powder and the solvent are fused with each other to form a uniform transparent solution, the solution is poured into an eye fluid cup to be used for being attached to eyes, or the solution is added into a sprayer to carry out flexible atomization spray cleaning on eyes for use.