CN113679666A - OK lens lubricating liquid and OK lens product for preventing and treating myopia - Google Patents
OK lens lubricating liquid and OK lens product for preventing and treating myopia Download PDFInfo
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- CN113679666A CN113679666A CN202110876207.5A CN202110876207A CN113679666A CN 113679666 A CN113679666 A CN 113679666A CN 202110876207 A CN202110876207 A CN 202110876207A CN 113679666 A CN113679666 A CN 113679666A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A61P27/00—Drugs for disorders of the senses
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- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
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- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
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Abstract
The invention provides a lubricating liquid for an OK mirror and an OK mirror product for preventing and treating myopia. The lubricating liquid for an OK mirror comprises: 0.001-0.05% (w/v) atropine medicine, 0.5-1.5% (w/v) sodium hyaluronate, an acid-base regulator and an osmotic pressure buffering agent, and the viscosity of the lubricating liquid for the OK mirror is 6-30 mps. The sodium hyaluronate in the lubricating liquid and the ocular fibronectin promote the adhesion and the extension of corneal epithelial cells, accelerate the adhesion and the extension of the epithelial cells, can relieve epithelial injury, epithelial edema, corneal epithelial damage and the like of the OK mirror to the cornea of the eye, improve the shaping effect of the OK mirror to the ocular surface morphology, and ensure that the OK mirror is not easy to deviate; the atropine medicine has low concentration and is attached to the OK lens in the form of lubricating liquid, so that the in vivo bioavailability of the atropine medicine is greatly improved, and the aim of improving the curative effect of the OK lens on controlling the myopia of teenagers and children is fulfilled.
Description
Technical Field
The invention relates to the technical field of eye health products, in particular to a lubricating liquid for an OK mirror and an OK mirror product for preventing and treating myopia.
Background
With the entrance of various electronic devices such as computers, mobile phones, electronic game machines and the like into the society and families, the electronic devices bring great convenience to work and study of people and influence the eyesight of people. Due to the prolonged use of these electronic devices, over-use of the eyes and vision after prolonged overload, a persistent debilitating condition occurs with the main symptoms: blurred vision, dry eyes, congestion and photophobia are usually accompanied by general symptoms, such as difficulty in concentration, listlessness, hypomnesis, insomnia, dysphoria, etc., which greatly affect the life and physical health of people.
Environmental factors and genetic factors are two important factors causing juvenile myopia, particularly the environmental factors, and short-distance eye use for long-time work and study is a main cause of juvenile myopia. At present, the treatment means for myopia comprises surgery and non-surgery, because teenagers are in the growth and development stage, the dioptric system of eyes is not stable, and the surgical treatment is not preferred. Non-surgical treatment of myopia, including medical device treatments such as Orthokeratology (OK) glasses; and the myopia of the teenagers and children is controlled by adopting a drug treatment means such as low-concentration atropine drug eye drops and the like.
The Orthokeratology (OK) mirror is a lens with a certain radian made of light-transmitting materials, which originates from the United states in the 60 th 20 th century, is placed in front of the cornea in an eyelid when in use, changes the central cornea form to be flat through a central flat base arc and a peripheral steeper reverse arc, reduces the refractive power of the cornea optical area, and improves the naked eye vision of a patient. However, at present, several common side effects and problems of long-time wearing of the orthokeratology lens are not negligible, such as 1: the cornea is anoxic, and the corneal endothelial cells are easy to malfunction after the hypoxia, so that corneal edema, corneal bleb and the like are caused; 2: the lens has single design radian, and in order to enhance and control myopia, a series of gradually-changed and flat common hard contact lenses need to be replaced, so that the naked eye vision can be improved to a certain extent; 3: the cornea shaping mirror has poor centering performance and is easy to shift, and the vision can not be corrected after the shift, but the situation of astigmatism aggravation can be caused; 4: because the formation reason of myopia is that the front and back diameters of the eyeball are lengthened besides the curvature of the cornea is enlarged, and the front and back diameters of the eyeball cannot be controlled to be lengthened by the corneal plastic lens, the degrees of some myopes can still be increased even if the corneal plastic lens is worn by the myopes caused by the lengthening of the front and back diameters of the eyeball; 5: after the orthokeratology mirror is placed in the eye, the orthokeratology mirror can act on the specific biological tissue environment of the human body, and can also have certain influence on the biocompatibility of the human body tissue, so that certain negative influence can be generated on the eye and the body part of the human body; 6: the orthokeratology lens has large pressure on the central cornea, and can cause corneal reaction, such as edema, corneal epithelial punctate exfoliation and the like, so that the patient has uncomfortable symptoms of foreign body sensation, photophobia, stabbing pain, lacrimation and the like, and even the tolerance of the patient to wearing the orthokeratology lens is influenced; 7: the correction effect of the orthokeratology mirror has certain reversibility, and for partial myopia patients, once the orthokeratology mirror is worn by a user, the shape of the cornea can be gradually restored, so that myopia needs to be controlled for partial myopia groups, and the myopia can be effectively controlled by wearing the mirror for a long time. At present, the research reports of documents show that the myopia control effect by adopting a corneal plastic mirror (OK mirror) can be slowed down by about 60 to 80 percent every year. On the other hand, before the orthokeratology lens is worn, a drop of lubricating liquid is dripped on the concave surface of the lens surface, and the main function is to cover the lens surface to prevent the surface from drying and the adhesion of deposits, not only for lubrication, but also for preventing bubbles under the lens from influencing the effect. Similarly, when the lens is taken, the lubricating liquid is dripped mainly for lubricating the contact part of the eye and the cornea shaping lens, so that the lens can be taken down more easily, and the foreign body sensation and the additional side effect damage to the eye are avoided. At present, components of lubricating liquid for Orthokeratology (OK) lens are generally artificial tears, water, sodium chloride, disodium ethylene diamine tetraacetate, polyhexamethylene biguanide, poloxamer, taurine, hydroxypropyl methylcellulose, pearl layer powder, natural borneol, borax, boric acid and the like, but the active components only have lubricating effect and do not have the effect of preventing and treating myopia of teenagers and children.
Directly dropping atropine eye drops is one of the most common methods for diagnosing and treating patients in ophthalmology at present, and has the advantages of simplicity, convenience, practicability, medicament conservation, quick action, easy absorption and the like. However, due to the special physiological structure of human eyes, the absorption of the liquid medicine in the eyes and the feeling of the patient are affected by dropping the eye drops. Research on ophthalmologists, Cao wenzhu and the like, in the department of ophthalmology, otorhinolaryngology, affiliated to the university of Compound denier shows that the eye conjunctival sac can contain 30 mu L of liquid at most under the normal condition of human eyes, wherein the volume of tears is 7-9 mu L, so that the eye conjunctival sac can contain about 20 mu L of liquid medicine at most after the volume of tears is removed. Generally, one drop of eye drop has a volume of about 40 to 50 μ L, and the difference between the bioavailability and the absorption rate of the eye drop dropped into the conjunctival sac of the eye is large due to the difference between the head position, manipulation, eye dropping mode, blinking, shaking head and the like of the eye drop of a patient, and the absorption rate of the active ingredients of the eye drop is generally only about 20% by the effective dropping amount of one drop of eye drop dropped into the eye.
Therefore, according to the existing research report, after one drop of eye drop (calculated according to 50 μ L) is added, the absorption of the active ingredient of the eye drop is only 20% by 20 μ L/50 μ L by 8% according to the maximum value (the volume of the eye drop is 50 μ L, the volume of the eye conjunctival sac is 20 μ L, and the absorption of the active ingredient of the eye drop is 20%) due to the volume of the eye conjunctival sac and the mode of the eye drop and the influence of the absorption of the active ingredient of the eye drop; thus, the eye drop is wasted, the efficacy of the active ingredients of the eye drop is reduced, and most importantly, the therapeutic effect of the eye drop is poor due to the low absorption of the active ingredients, and the therapeutic effect of one drop of the eye drop is not achieved at all, so that the effective bioavailability of the active ingredients of the eye drop in the body needs to be improved. The higher the concentration of the atropine medicines, the better the effect of controlling myopia, but the high-concentration atropine medicine eye drops have the phenomena of strong mydriasis, photophobia, blurred vision and the like due to obvious side effects, and are easy to cause discomfort of patients, and the high-concentration atropine medicine eye drops may cause adverse events, such as the problems of allergic conjunctivitis, allergic blepharitis and the like, and the high-concentration atropine medicine eye drops may cause retinal light damage, complicated cataract, early presbyopia and the like after long-term use. The atropic eye drops with low concentration rarely occur, even though the conditions of cycloplegia, photophobia, near object blurring and the like occasionally occur, which are generated by using the atropic eye drops, the atropic eye drops can be quickly recovered after stopping the drug application, but the atropic eye drops with high concentration are difficult to recover, even can generate great damage to eyes, and damage the physical health of teenagers and children. Accordingly, the therapeutic effect of the atropine eye drops at low concentration is also greatly reduced.
Furthermore, the most common side effects of wearing the orthokeratology lens are corneal hypoxia, which easily causes corneal endothelial cell dysfunction after hypoxia, corneal edema, corneal bleb, lens shift, low patient audience rate, corneal infection and ulcer caused by improper daily care, and for some myopia children, the myopia treatment effect is slow or not obvious, and the orthokeratology lens needs to be used for a long time.
Disclosure of Invention
The invention mainly aims to provide a lubricating liquid for an OK mirror and an OK mirror product for preventing and treating myopia, so as to solve the problem that the eyesight improvement effect is limited due to damage to a cornea caused by the OK mirror in the prior art.
In order to achieve the above object, according to one aspect of the present invention, there is provided a lubricating liquid for an OK mirror, comprising: 0.001-0.05% (w/v) atropine medicine, 0.5-1.5% (w/v) sodium hyaluronate, an acid-base regulator and an osmotic pressure buffering agent, wherein the viscosity of the lubricating liquid for the OK lens is controlled at 6-30 mps.
Further, the atropine medicament is used in an amount of 0.005-0.02% (w/v), preferably sodium hyaluronate in an amount of 0.8-1.3% (w/v), preferably the atropine medicament is selected from any one or more of atropine sulfate, scopolamine, DL-hyoscyamine sulfate, atropine and atropine derivatives.
Further, the pH value of the lubricating liquid for the OK mirror is adjusted to be 5.5-7.5 by the acid-base adjusting agent, the osmotic pressure of the lubricating liquid for the OK mirror is adjusted to be 260-320 mOsm/L by the osmotic pressure buffering agent, and the viscosity of the lubricating liquid for the OK mirror is adjusted to be 10-20 mps.
Further, the acid-base modifier is one or more selected from the group consisting of sodium dihydrogen phosphate, disodium hydrogen phosphate, tartaric acid, sodium tartrate, acetic acid, sodium acetate, boric acid and salts thereof, borax, citric acid, sodium citrate, glycine and hydrochloric acid buffer, oxalic acid and sodium oxalate buffer, and sodium carbonate and sodium bicarbonate buffer, and optionally, the sodium salt may be replaced by a potassium salt.
Further, the acid-base regulator is a phosphate buffer salt system, a borate buffer salt system, a citrate buffer salt system, a phosphate and borate mixed buffer salt system, a phosphate and citrate mixed buffer salt system, a borate and citrate mixed buffer salt system, a phosphate and borate and citrate mixed buffer salt system; more preferably, the phosphate buffer salt system is a phosphate buffer salt system consisting of sodium dihydrogen phosphate and disodium hydrogen phosphate, the borate buffer salt system is a borate buffer salt system consisting of boric acid and borax buffer solution, and the citrate buffer salt system is a citrate buffer salt system consisting of citric acid and sodium citrate.
Further, the osmotic pressure buffer is one or more selected from the group consisting of sodium chloride, mannitol, albumin, polyethylene glycol, glucose and boric acid.
Further, the lubricating liquid for the OK mirror further comprises a thickening agent, wherein the thickening agent is one or more selected from methylcellulose, polyvinyl alcohol, polyethylene glycol, carboxymethyl cellulose, polyvinylpyrrolidone, chitosan and chondroitin sulfate.
Further, the lubricating liquid for the OK mirror further comprises 0-0.05% (w/v) of a bacteriostatic agent, wherein the bacteriostatic agent is selected from one or more of boric acid, ethylparaben, methylparaben, propylparaben, phenylmercuric acetate, sorbic acid, chlorobutanol, benzalkonium chloride and benzalkonium bromide.
Further, the lubricating liquid for the OK lens further comprises one or more of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, pyruvate, carotene, taurine, vitamin E, vitamin B6 and other vitamins with auxiliary effects, mint, natural borneol and dipotassium glycyrrhizinate.
According to another aspect of the present invention, there is provided an OK mirror product for preventing and treating myopia, comprising an OK mirror and a lubricating liquid used in cooperation therewith, wherein the lubricating liquid is any one of the lubricating liquids for OK mirrors.
By applying the technical scheme of the invention, the sodium hyaluronate in the lubricating liquid and the ocular fibronectin promote the adhesion and extension of corneal epithelial cells, accelerate the adhesion and extension of epithelial cells, relieve epithelial injury, epithelial edema, corneal epithelial damage and the like of an OK mirror to an ocular cornea, improve the shaping effect of the OK mirror to the ocular surface morphology, ensure that the OK mirror is not easy to deviate, thereby effectively achieving the purpose of improving the curative effect of the OK mirror on controlling juvenile myopia and increasing the ocular bioavailability of atropine medicines. The OK mirror is immersed in the lubricating liquid, so that the lubricating effect can be effectively achieved, the defect of a lacrimal fluid layer can be made up, the corneal plastic mirror can better play a role, and the vision of a patient after taking the mirror the next day is more ideal; and because the concentration of the atropine medicament in the lubricating liquid is lower, and the atropine medicament is attached to the OK lens in the form of the lubricating liquid, the absorption of the atropine medicament is facilitated, the in-vivo bioavailability of the atropine medicament is greatly improved, the administration is safer, and the treatment effect is better.
Detailed Description
It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail with reference to examples.
As analyzed by the background technology of the application, the OK mirror can cause damage to the cornea when being worn, and in order to solve the problem, the application provides a lubricating liquid for the OK mirror and an OK mirror product for preventing and treating myopia.
In one exemplary embodiment of the present application, there is provided a lubricating liquid for an OK mirror, including: 0.001-0.05% (w/v) atropine medicine, 0.5-1.5% (w/v) sodium hyaluronate, an acid-base regulator and an osmotic pressure buffering agent, and the viscosity of the lubricating liquid for the OK mirror is 6-30 mps.
The sodium hyaluronate in the lubricating liquid and the ocular fibronectin promote the adhesion and extension of corneal epithelial cells, accelerate the adhesion and extension of epithelial cells, relieve epithelial injury, epithelial edema, corneal epithelial damage and the like of an OK mirror to an ocular cornea, improve the shaping effect of the OK mirror to the ocular surface morphology, and ensure that the OK mirror is not easy to deviate, thereby effectively achieving the aim of improving the curative effect of the OK mirror on controlling juvenile myopia and increasing the ocular bioavailability of the atropine medicament. Before wearing the OK mirror, the OK mirror is immersed into the lubricating liquid, so that the lubricating effect can be effectively achieved, the lachrymal fluid layer can be made up, the corneal plastic mirror can better play a role, and the vision of a patient after taking the mirror the next day is more ideal; and because the concentration of the atropine medicament in the lubricating liquid is lower, and the atropine medicament is attached to the OK lens in the form of the lubricating liquid, the absorption of the atropine medicament is facilitated, the in-vivo bioavailability of the atropine medicament is greatly improved, the administration is safer, and the treatment effect is better.
The atropine with low concentration plays a role in controlling myopia by acting on retina and sclera, and can thicken scleral nerve layer mediated by M1 and M4 receptors; the cornea shaping mirror (OK mirror) directly acts on the cornea and then forms a myopic defocus effect on the retina, the action directions of the cornea shaping mirror and the OK mirror are different and do not influence each other, so that the cornea shaping mirror and the OK mirror can play a role of mutual compensation, the low-concentration atropine medicine in the lubricating liquid is matched with the OK mirror, the myopia is prevented and treated from two angles, the effects of the atropine medicine and the OK mirror complement each other, and the myopia prevention and treatment effect of teenagers and children is improved.
When the content of the atropine medicament in the lubricating liquid is low, side effects caused by high-concentration atropine medicament rarely occur, and even though the conditions of cycloplegia, photophobia, near object blurring and the like caused by using the atropine medicament eye drops occasionally occur, the atropine medicament eye drops can be quickly recovered after stopping taking the medicament.
In order to further exert the efficacy of the atropine medicament, the dosage of the atropine medicament is preferably 0.005-0.02% (w/v). In addition, in order to improve the adhesion of the lubricating fluid on the OK mirror, the amount of sodium hyaluronate used is preferably 0.8% to 1.3% (w/v). Preferably, the atropine drug is selected from one or more of atropine sulfate, hyoscyamine, DL-hyoscyamine sulfate, atropine, and atropine derivative, such as preferably atropine sulfate or atropine.
In some embodiments of the present application, the pH of the lubricating liquid for the OK mirror is adjusted to 5.5 to 7.5 by the acid-base adjusting agent (the pH value is based on the accuracy detectable by the pH detector, and may also be converted into other equivalent pH value units, or may be based on the added amount). The osmotic pressure buffer adjusts the osmotic pressure of the lubricating fluid for the OK lens to 260-320 mOsm/L (the osmotic pressure value is based on the accuracy which can be detected by an osmotic pressure detector, and can also be converted into other equivalent osmotic pressure numerical units, or is based on the addition amount). The viscosity of the lubricating liquid for the OK mirror can be further adjusted to 10-20 mps, so that the stimulation of the lubricating liquid to eyes can be further reduced.
The ph adjusting agent used in the present application may be a ph adjusting agent commonly used in eye drops, and in order to avoid excessive influence of the ph adjusting agent on the lubricity of the lubricating fluid, the ph adjusting agent is preferably one or more selected from the group consisting of sodium dihydrogen phosphate, disodium hydrogen phosphate, tartaric acid, sodium tartrate, acetic acid, sodium acetate, boric acid and salts thereof, borax, citric acid, sodium citrate, glycine and hydrochloric acid buffer, oxalic acid and sodium oxalate buffer, and sodium carbonate and sodium bicarbonate buffer, and optionally, the sodium salt may be replaced with a potassium salt.
In some embodiments, a buffer system is selected as an acid-base regulator to further adapt to changes of the ocular environment, and preferably, the acid-base regulator is a phosphate buffer salt system, a borate buffer salt system, a citrate buffer salt system, a phosphate and borate mixed buffer salt system, a phosphate and citrate mixed buffer salt system, a borate and citrate mixed buffer salt system, or a phosphate and borate and citrate mixed buffer salt system; the phosphate buffer salt system is a phosphate buffer salt system consisting of sodium dihydrogen phosphate and disodium hydrogen phosphate, the borate buffer salt system is a borate buffer salt system consisting of boric acid and borax buffer solution, and the citrate buffer salt system is a citrate buffer salt system consisting of citric acid and sodium citrate; more preferably a phosphate buffer salt system, a mixed system of the phosphate buffer salt system and a borate buffer salt system or a mixed system of the phosphate buffer salt system and a citrate buffer salt system, wherein the ratio of the two components in the mixed system is 1: 3-3: 1, and the preferable ratio is 1: 1; more preferably, the phosphate buffer salt system, the borate buffer salt system and the citrate buffer salt system are mixed, and the ratio of the three buffer salt systems in the mixed system is 1: 1: 1.
in addition, the osmotic buffering agents used in the present application may also employ those commonly used in the art, for example, the osmotic buffering agents used in the present application include, but are not limited to, one or more of the group consisting of sodium chloride, mannitol, albumin, polyethylene glycol, glucose, and boric acid. Preferably, the boric acid (borax) or sodium chloride or polyethylene glycol or mannitol, or the boric acid (borax) and sodium chloride are mixed in a mixing ratio of 0: 1-1: 0 (w: w), preferably 0.5: 1-2: 1 (w: w), more preferably 1: 1 (w: w).
In the present application, on the basis of providing the lubricating liquid for the OK mirror with sodium hyaluronate, in order to further flexibly adjust the viscosity of the lubricating liquid for the OK mirror, it is preferable that the lubricating liquid for the OK mirror further includes a thickener, and the thickener is one or more selected from methylcellulose, polyvinyl alcohol, polyethylene glycol, carboxypropyl methylcellulose, polyvinylpyrrolidone, hypromellose, chitosan, and chondroitin sulfate.
The lubricating liquid is sterilized before filling, and the sterilization method is a filter membrane filtration or hot pressing method, and can also be a dry heating method, a radiation method, an ultraviolet sterilization method, a low-temperature intermittent sterilization method and the like; the aseptic subpackaging method is single-dose aseptic subpackaging, and can also be multi-dose aseptic subpackaging or other aseptic subpackaging modes. In some embodiments of the present application, in order to prolong the shelf life and use cleanness of the lubricating liquid for OK mirror, it is preferable that the lubricating liquid for OK mirror further comprises 0% to 0.05% (w/v) of a bacteriostatic agent selected from one or more of boric acid, ethylparaben, methylparaben, propylparaben, phenylmercuric acetate, sorbic acid, chlorobutanol, benzalkonium chloride and benzalkonium bromide.
The lubricating liquid for the OK mirror can be added with auxiliary components to improve the comprehensive effect of visual health besides the functional components, for example, the lubricating liquid for the OK mirror also comprises one or more of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, pyruvate, carotene, taurine, vitamin E, vitamin B6 and other vitamins, mint, natural borneol and dipotassium glycyrrhizinate with auxiliary effects.
In another exemplary embodiment of the present application, there is provided an OK mirror product for preventing and treating myopia, comprising an OK mirror and a lubricating fluid used in combination with the OK mirror, wherein the lubricating fluid is any one of the lubricating fluids for the OK mirror.
The sodium hyaluronate in the lubricating liquid and the ocular fibronectin promote the adhesion and the extension of corneal epithelial cells, accelerate the adhesion and the extension of the epithelial cells, can relieve epithelial injury, epithelial edema, corneal epithelial damage and the like of an OK mirror to an eye cornea, improve the shaping effect of the OK mirror to the ocular surface form, and ensure that the OK mirror is not easy to deviate, thereby effectively achieving the aim of improving the curative effect of the OK mirror on controlling the myopia of teenagers, and increasing the ocular bioavailability of the atropine medicine eye drops. Before wearing the OK mirror, the OK mirror is immersed into the lubricating liquid, so that the lubricating effect can be effectively achieved, the lachrymal fluid layer can be made up, the corneal plastic mirror can better play a role, and the vision of a patient after taking the mirror the next day is more ideal; and because the concentration of the atropine medicament in the lubricating liquid is lower, and the atropine medicament is attached to the OK lens in the form of the lubricating liquid, the absorption of the atropine medicament is facilitated, the in-vivo bioavailability of the atropine medicament is greatly improved, the administration is safer, and the treatment effect is better. The low-concentration atropine medicine in the lubricating liquid is matched with the OK glasses to prevent and treat myopia from two angles, and the effects of the atropine medicine and the OK glasses complement each other, so that the myopia prevention and treatment effect of teenagers and children is improved.
When the lubricating liquid for the OK mirror and the OK mirror are used in a matched mode, the OK mirror is soaked in the lubricating liquid for storage or is soaked for 1-24 hours before use; or directly dripping the lubricating liquid into the eyes during the period of using the OK glasses, or dripping the lubricating liquid into the eyes after picking up the OK glasses, or continuously wearing the OK glasses after picking up the OK glasses and soaking the OK glasses in the lubricating liquid for 1-4 h. The time for wearing the OK glasses for one time can be 1-18 h; the OK lens can also be selected from other corneal contact lenses with myopia correction function, including soft corneal contact lenses and rigid gas-permeable corneal contact lenses.
For a better understanding of the present invention, the present invention will be described in detail with reference to the following examples, but it should be understood that these examples are for illustrative purpose only and are not intended to limit the present invention, and that the present invention may be modified in a simple manner without departing from the spirit of the present invention.
In the present invention, all operations are carried out at room temperature, normal pressure and under the exclusion of light unless otherwise specified.
Stock solution
The compound medicine lubricating liquid and the single medicine lubricating liquid are prepared by the following preparation process to research the difference of the comparison safety and the curative effect, namely:
1. weighing sodium hyaluronate, adding 80% of injection water (temperature 70 ℃), fully stirring and uniformly mixing, then fixing the volume and replenishing water to 100%, and stirring and uniformly mixing to prepare an aqueous solution containing 0.8% (w/v) of sodium hyaluronate;
2. cooling the feed liquid obtained in the step 1 to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v);
3. sequentially adding an osmotic pressure buffering agent sodium chloride (the osmotic pressure is adjusted to be 300mOsm/L) and an acid-base regulator phosphate buffer salt system (the pH is adjusted to be 6.0) into the solution obtained in the step 2;
mixing, stirring, filtering with 0.22 μm microporous membrane according to requirements of eye drop in Chinese pharmacopoeia 2020 edition (four), sterilizing, packaging single dose sterile, and testing to obtain lubricating liquid A: sodium hyaluronate + atropine sulphate, in addition, the following lubricating fluids were used for comparison:
lubricating fluid B: atropine sulfate, 0.01% (w/v) aqueous solution;
lubricating fluid C: sodium hyaluronate, an aqueous solution containing 0.8% (w/v) of sodium hyaluronate;
lubricating fluid D: shurun liquid (market brand)
Eye irritation investigation
A plurality of bottles are respectively extracted from different lubricating liquids prepared under the conditions of the stock solution, namely the lubricating liquid A/B/C/D by adopting a random sampling method. Taking 6 healthy young rabbits with the age of 90-150 days and half female and male, bringing into the standard: firstly, no external eye diseases exist; the light reflection of the pupils of the two eyes is normal; and no crooked neck. The color and blood vessel distribution of the conjunctiva were observed under normal conditions. The eyelids are then pulled into a ring shape and the nasolacrimal duct is pressed with fingers (to prevent the liquid medicine from flowing into the nasolacrimal duct and being absorbed). One eye is used as a control, and normal saline is dripped into the eye; the eye on the other side is respectively dripped with the different lubricating liquids, the volume of the lubricating liquid used each time is 0.1mL, and the liquid medicine is left to flow out naturally after 1 min. Tear secretion was examined 1 time every 5min within 30min after administration. Within 3h after administration, the eyelid is slightly opened every 1h, and the local reactions of cornea, iris and conjunctiva of rabbit eyes are observed and checked by professional equipment such as a slit lamp microscope, a low power microscope and the like, so that the rabbit eyes are qualified by patients without obvious irritation symptoms such as congestion, lacrimation, photophobia, edema and the like. The results show that all the groups of lubricating fluids have no irritation according to the judgment of the severity degree of irritation experiments.
Toxicology experimental study
Acute toxicity test: taking 12 healthy young rabbits with the age of 90-150 days and half female and half male, and bringing the rabbits into the standard that the rabbits have no external eye diseases; the light reflection of the pupils of the two eyes is normal; and no crooked neck. The groups were randomly divided into a blank control group and a dosing group, and 6 animals were administered to each group. Distilled water is dripped into the blank control group, the lubricating liquid prepared under the conditions of the 'stock solution' -lubricating liquid A/B/C is dripped into the administration group, the dosage of the lubricating liquid is 50 times of the dosage of the adult planned daily drops, and the animal is observed for 7 days to see whether abnormal change occurs.
(II) long-term toxicity test: taking 24 healthy young rabbits with the age of 90-150 days and half female and half male, and bringing the rabbits into the standard that the rabbits have no external eye diseases; the light reflection of the pupils of the two eyes is normal; and no crooked neck. The random classification was four groups: blank control group and administration group, and the administration group was divided into high dose group, medium dose group and low dose group, each group containing 6 animals. Distilled water is dripped into the blank control group, different lubricating liquids prepared under the conditions of the 'stock solution' -lubricating liquid A/B/C are respectively dripped into the administration group, wherein the dosages of the high dosage group, the medium dosage group and the low dosage group are respectively 10 times, 20 times and 30 times of the daily dosage of adult droplets. The medicine is stopped after eight continuous weeks once a day, reversible reaction in a recovery period of two weeks is observed, and the appearance, the weight, the food intake, hematology, biochemistry, main organ coefficients and pathological tissue morphology of animals are found abnormally during the observation period, and the comprehensive evaluation results according to each data show that: the lubricating liquid of each group has good safety and no adverse reaction.
Clinical efficacy comparison study
A random sampling method is adopted, a plurality of bottles are respectively extracted from different lubricating liquids prepared under the conditions of 'stock solution' -lubricating liquid A/B/C/D by adopting an optimized formula obtained after the optimization test and capable of ensuring the safety, and a medical institution is entrusted to carry out clinical tests by adopting a random double-blind method on the basis of ensuring the medication safety of children according to the existing clinical experimental data.
The test object is a myopic child aged 6-12 years old, and the myopic progress is as follows: the diopter range of at least one eye with myopia is (1.0D to 5.0D), after cleaning the lens before sleeping every day at night, immersing the cornea shaping mirror (OK mirror) into different lubricating liquid A/B/C/D for one hour, immediately taking out and wearing the cornea shaping mirror (OK mirror), and dripping 1-2 drops of the lubricating liquid A/B/C/D before getting off the mirror in the next morning. After 6 months of continuous use, the eyesight of the myopia patients of the teenagers and the influence on the ocular Surface morphology of the myopia patients are controlled by using different lubricating liquid combined with corneal plastic lenses (OK lenses), wherein the influences comprise the degree of corneal epithelial injury (corneal epithelial fluorescein staining), SRI (Surface Regular index, corneal topography examination-corneal Surface rule index) and Tear film rupture time (TBUT) which are respectively shown in the following tables 1, 2, 3 and 4, and the confidence interval is 95%.
The test results of comparison of various parameters of the lubricating liquid A, B, C, D show that compared with the atropine sulfate lubricating liquid with sodium hyaluronate, which is used alone for Orthokeratology (OK) mirror and the atropine sulfate lubricating liquid without sodium hyaluronate, the lubricating liquid with sodium hyaluronate and the common lubricating liquid sold in the market, the atropine sulfate lubricating liquid with sodium hyaluronate has better effect of controlling myopia of teenagers and children and higher safety in the process of combining the Orthokeratology (OK) mirror, and achieves unexpected synergistic effect.
Table 1: influence of different myopia correction modes on eyesight of myopia patient
Table 2: comparison of degree of damage (%)
Table 3: effect of different myopia correction modalities on SRI (corneal surface regularity index) values for myopes
Table 4: effect of different myopia correction modalities on tear film break-up time (TBUT) in myopes
Example 1
Weighing sodium hyaluronate, adding 60% of injection water (at 60 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.001% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 260mOsm/L, adding a phosphate buffer system, adjusting pH to 5.5, mixing uniformly, stirring fully, filtering with 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 7 mps.
Example 2
Weighing sodium hyaluronate, adding 90% of injection water (temperature 90 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume, preparing an aqueous solution containing 1.5% (w/v) of sodium hyaluronate, and stirring and uniformly mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.02% (w/v); adding boric acid into the solution, adjusting osmotic pressure to 320mOsm/L, adding a citrate buffer system, adjusting pH to 6.0, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 28 mps.
Example 3
Weighing sodium hyaluronate, adding 70% of injection water (at the temperature of 90 ℃) according to the composition ratio of the added solid mass and the water volume, fully stirring and uniformly mixing, then carrying out constant volume water supplement to 100% to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and stirring and uniformly mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding polyethylene glycol into the solution, adjusting osmotic pressure to 320mOsm/L, adding a citrate buffer system, adjusting pH to 4.5, mixing well, stirring thoroughly, filtering with 0.22 μm microporous membrane according to the requirements of Chinese pharmacopoeia 2020 (four), sterilizing, single-dose sterile packaging, and testing with lamp to obtain lubricating fluid with viscosity of 8 mps.
Example 4
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.0% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.02% (w/v); adding boric acid into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 (four), sterilizing, performing single dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 17 mps.
Example 5
Weighing sodium hyaluronate, adding 75% of injection water (temperature 80 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.001% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 305mOsm/L, adding a citrate buffer system, adjusting pH to 4.4, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 25 mps.
Example 6
Weighing sodium hyaluronate, adding 60% of injection water (temperature is 90 ℃), fully stirring and uniformly mixing, then fixing the volume and replenishing water to 100%, preparing an aqueous solution containing 1.0% (w/v) of the weighed sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.005% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 305mOsm/L, adding a citrate buffer system, adjusting pH to 4.4, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 15 mps.
Example 7
Weighing sodium hyaluronate, adding 90% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.3% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.04% (w/v); adding mannitol into the solution, adjusting osmotic pressure to 310mOsm/L, adding a borate buffer system, adjusting pH to 5.8, mixing well, stirring thoroughly, filtering with 0.22 μm microporous membrane according to the requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, single-dose sterile packaging, and testing with lamp to obtain lubricating fluid with viscosity of 19 mps.
Example 8
Weighing sodium hyaluronate, adding 90% of injection water (temperature 60 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1% (w/v) of sodium hyaluronate, and stirring and uniformly mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.02% (w/v); adding polyethylene glycol into the solution, adjusting osmotic pressure to 305mOsm/L, adding a citrate buffer system, adjusting pH to 7.5, mixing well, stirring thoroughly, filtering with 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, single-dose sterile packaging, and testing with lamp to obtain lubricating fluid with viscosity of 17 mps.
Example 9
Weighing sodium hyaluronate, adding 60% of injection water (temperature is 90 ℃), fully stirring and uniformly mixing, then fixing the volume and replenishing water to 100%, preparing an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and stirring and uniformly mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.02% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 305mOsm/L, adding a phosphate buffer system, adjusting pH to 6.7, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 9 mps.
Example 10
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 312mOsm/L, adding a phosphate buffer system, adjusting pH to 7.5, mixing uniformly, stirring fully, filtering with 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 8 mps.
Example 11
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.02% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to be 315mOsm/L, adding a phosphate buffer system, adjusting pH to be 6.5, mixing uniformly, stirring fully, filtering with a 0.22-micron microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 28 mps.
Example 12
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.0% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.005% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 15 mps.
Example 13
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.3% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 18 mps.
Example 14
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 27 mps.
Example 15
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 8 mps.
Example 16
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.0% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 16 mps.
Example 17
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.05% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 9 mps.
Example 18
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.02% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 8 mps.
Example 19
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.005% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 7 mps.
Example 20
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.001% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 6 mps.
Example 21
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.05% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 30 mps.
Example 22
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.7% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 10 mps.
Example 23
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 1.4% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 20 mps.
Comparative example 1
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.3% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 6 mps.
Comparative example 2
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 2.0% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 45 mps.
Comparative example 3
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.1% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 8 mps.
Comparative example 4
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.5% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22-micrometer microporous filter membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 6 mps.
Comparative example 5
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 0.2% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with the viscosity of 3 mps.
Comparative example 6
Weighing sodium hyaluronate, adding 80% of injection water (at 85 ℃), fully stirring and uniformly mixing, then adding water to 100% by volume to prepare an aqueous solution containing 2.3% (w/v) of sodium hyaluronate, and uniformly stirring and mixing; cooling the feed liquid to room temperature, and adding atropine sulfate to prepare an aqueous solution with the concentration of 0.01% (w/v); adding sodium chloride into the solution, adjusting osmotic pressure to 310mOsm/L, adding a phosphate buffer system, adjusting pH to 6.5, mixing uniformly, stirring fully, filtering with a 0.22 μm microporous membrane according to the related requirements of Chinese pharmacopoeia 2020 edition (four), sterilizing, performing single-dose sterile subpackaging, and performing light inspection to obtain the lubricating liquid with viscosity of 50 mps.
The technical effects of the cornea shaping mirror (OK mirror) combined with the lubricating liquid of the different pharmaceutical compositions described in examples 1 to 23 and comparative examples 1 to 6 were tested by the same test methods as the above-mentioned eye irritation, toxicological safety and clinical efficacy, and the results are all non-irritating to eyes and safe to use, and the results of the related technical effects are shown in the following Table 5(P < 0.05)
Table 5: summary of technical effects of different lubricants on myopia control
From the above description, it can be seen that the above-described embodiments of the present invention achieve the following technical effects:
1. the compound medicine composition lubricating liquid improves the curative effect mechanism of the orthokeratology lens by adding the sodium hyaluronate into the atropine sulfate lubricating liquid in the process of wearing and using the orthokeratology lens (OK lens), overcomes some problems and defects in the using process of the current orthokeratology lens, accelerates the corneal repair, ensures that the orthokeratology lens is not easy to shift, and improves the aim of controlling the myopia curative effect of teenagers and children by utilizing the method of supplementing the effects of the orthokeratology lens, the atropine sulfate lubricating liquid and the atropine sulfate lubricating liquid;
2. according to the compound medicine composition lubricating liquid, the action mechanisms and the target points of the compound medicine composition and the corneal plastic lens in the process of controlling the myopia of teenagers and children are different, the problem that the effect of part of patients is not obvious or slight when the atropine eye drops or the corneal plastic lens is used alone at present is greatly improved, the effect and the function of the compound medicine and the corneal plastic lens are greatly improved, and the audience rate and the practicability of myopia patients are improved.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A lubricating liquid for an OK mirror, comprising: 0.001-0.05% (w/v) atropine medicine, 0.5-1.5% (w/v) sodium hyaluronate, an acid-base regulator and an osmotic pressure buffering agent, wherein the viscosity of the lubricating liquid for the OK mirror is controlled at 6-30 mps.
2. The lubricating fluid for an OK mirror as claimed in claim 1, wherein the amount of said atropine drug is 0.005-0.02% (w/v), preferably the amount of said sodium hyaluronate is 0.8-1.3% (w/v), preferably said atropine drug is selected from any one or more of atropine sulfate, scopolamine DL-sulfate, atropine, and atropine derivatives.
3. The lubricating fluid for an OK mirror as claimed in claim 1, wherein the pH adjusting agent adjusts the pH of the lubricating fluid for an OK mirror to 5.5-7.5, the osmotic pressure buffering agent adjusts the osmotic pressure of the lubricating fluid for an OK mirror to 260-320 mOsm/L, and the viscosity of the lubricating fluid for an OK mirror is 10-20 mps.
4. The lubricating fluid for an OK mirror according to any one of claims 1 to 3, wherein the acid-base modifier is one or more selected from the group consisting of sodium dihydrogen phosphate, disodium hydrogen phosphate, tartaric acid, sodium tartrate, acetic acid, sodium acetate, boric acid and salts thereof, borax, citric acid, sodium citrate, glycine and hydrochloric acid buffer, oxalic acid and sodium oxalate buffer, and sodium carbonate and sodium bicarbonate buffer, and optionally, the sodium salt may be replaced with a potassium salt.
5. The lubricating fluid for the OK mirror as claimed in any one of claims 1 to 3, wherein the pH regulator is a phosphate buffer salt system, a borate buffer salt system, a citrate buffer salt system, a phosphate and borate mixed buffer salt system, a phosphate and citrate mixed buffer salt system, a borate and citrate mixed buffer salt system, a phosphate and borate and citrate mixed buffer salt system; more preferably, the phosphate buffer salt system is a phosphate buffer salt system consisting of sodium dihydrogen phosphate and disodium hydrogen phosphate, the borate buffer salt system is a borate buffer salt system consisting of boric acid and borax buffer solution, and the citrate buffer salt system is a citrate buffer salt system consisting of citric acid and sodium citrate.
6. The lubricating fluid for an OK mirror according to any one of claims 1 to 3, wherein the osmotic pressure buffer is one or more selected from the group consisting of sodium chloride, mannitol, albumin, polyethylene glycol, glucose, and boric acid.
7. The lubricating fluid for the OK mirror as claimed in any one of claims 1 to 3, wherein the lubricating fluid for the OK mirror further comprises a thickener, wherein the thickener is one or more selected from methylcellulose, polyvinyl alcohol, polyethylene glycol, carboxymethyl cellulose, polyvinylpyrrolidone, chitosan and chondroitin sulfate.
8. The lubricating fluid for an OK mirror according to any one of claims 1 to 3, further comprising 0% to 0.05% (w/v) of a bacteriostatic agent selected from one or more of the group consisting of boric acid, ethylparaben, methylparaben, propylparaben, phenylmercuric acetate, sorbic acid, chlorobutanol, benzalkonium chloride and benzalkonium bromide.
9. The lubricating fluid for the OK mirror as claimed in any one of claims 1 to 3, wherein the lubricating fluid for the OK mirror further comprises one or more of ethylenediamine tetraacetic acid, disodium ethylenediamine tetraacetic acid, pyruvate, carotene, taurine, vitamin E, vitamin B6 and other auxiliary vitamins, mint, natural borneol and dipotassium glycyrrhizinate.
10. An OK mirror product for preventing and treating myopia, comprising an OK mirror and a lubricating liquid used in cooperation with the OK mirror, wherein the lubricating liquid is the lubricating liquid for the OK mirror in any one of claims 1 to 9.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202110876207.5A CN113679666A (en) | 2021-07-30 | 2021-07-30 | OK lens lubricating liquid and OK lens product for preventing and treating myopia |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202110876207.5A CN113679666A (en) | 2021-07-30 | 2021-07-30 | OK lens lubricating liquid and OK lens product for preventing and treating myopia |
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| CN111803441A (en) * | 2020-06-10 | 2020-10-23 | 西安交通大学医学院第二附属医院 | Sodium hyaluronate eye drops containing 0.01% atropine and preparation method thereof |
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