TW201406382A - Compound composition having retina protection function and application thereof - Google Patents

Abstract

This invention discloses a compound composition having retina protection function, comprising the constituents of: 1.00-3.00wt% of water-soluble lutein, 0.80-1.20wt% of L-aspartic acid potassium, 0.1-0.2wt% of hyaluronic acid, 0.08-0.12wt% of vitamin B5, 0.08-0.12wt% of vitamin B6, 0.04-0.07wt% of vitamin B12, 0.04-0.07wt% of vitamin C, 0.04-0.07wt% of vitamin E, 0.03-0.06wt% of chamomile extract, 0.03-0.06wt% of black currant extract, 0.003-0.006wt% of bilberry (blueberry) extract, 0.003-0.006wt% of eyebright powder, 0.003-0.006wt% of zinc, 0.003-0.006wt% of calendula extract, 0.003-0.006wt% of ginkgo extract, 0.03-0.06wt% of medlar, 0.03-0.06wt% of anthocyanin, and 0.05-0.07wt% of grape seed. The compound composition of this invention can be applied to being made into various dosage form products, particularly made into eye relaxation care solution or eye drops being best. This invention can be used by the user without foreign body sensation while being absorbed quickly, capable of achieving eye moisturizing effect and efficacy of effectively fighting against fatigue.

Description

Compound composition and application with retinal protection function

The present invention relates to an ophthalmic compound composition and application, and more particularly to a compound composition and application having a retinal protection function.

With the great changes in the nature of work, the working environment and the type of entertainment activities, it has become inevitable that long-term use of the eyes will become the norm. Because of this, modern eye care and eye disease prevention and aging prevention are also One of the issues that are getting more and more attention. In particular, eye changes often due to progressive age, including normal vision loss and morbidity changes, often severely affect the function of the eye, including: development of cataract, hardening, opacification, and flexibility (pliability) ) reduction, and lens yellowing; corneal yellowing and opacification; presbyopia; trabecular occlusion, resulting in intraocular pressure accumulation and glaucoma; increased floating matter in the posterior aqueous humor; iris enlargement and reduction in large areas; age-related Age-related macular degeneration (AMD); formation of atherosclerotic deposits in retinal arteries; dry eye syndrome; and reduction in sensitivity and light level adaptation of retinal rods and cones. Age-related visual deterioration includes impairment of visual sensitivity, visual contrast, color and depth susceptibility, lens conditioning, light sensitivity, and dark adaptation. Age-related changes also include changes in the appearance of the iris color and the formation of the elderly ring. These changes may occur in various components of the eye, including the cornea, sclera, trabeculae, iris, lens, posterior chamber water, and retina, which may be affected by aging and excessive eyesight.

Lutein is the most important nutrient component of the human retina. Lutein in the human body can also filter more than 90% of the blue light wavelength to avoid the damage of this strong light. Blue light may promote the oxidation. Lutein provides nutritional support for the eye and skin, in the macula of the eye's retina (center of vision), and the crystal contains high amounts of lutein. Lutein is an important component of the macula of the retina. It has been used in the European and American medical circles to prevent senile macular degeneration in recent years. It is also effective for other retinopathy such as myopia.

The macula is located in the center of the retina of the fundus. There is a large amount of lutein in the retinal tissue layer of the macula. Early anatomists called the area "macular" or "yellow" because of the high concentration of lutein. Rendered in yellow. The macula is where the photoreceptor cells gather, responsible for providing color and detail in the center of the field of view. In recent years, research on macular pigment (MP) has become a hot topic. How to develop an eyedrop that can quickly absorb and effectively protect the retinal function for the research of this technical field, so that modern people can relieve eye fatigue and avoid eye damage caused by excessive eyesight, which has become a development The subject matter.

Accordingly, it is an object of the present invention to provide a compound composition which can quickly absorb and effectively protect retinal function.

The technical means adopted by the present invention to solve the problems of the prior art is a compound composition having a protective function of the retina, the components of which include: 1.00 - 3.00 wt% of water-soluble lutein, 0.80-1.20 wt% of L - Aspartate potassium, 0.1%-0.2% by weight hyaluronic acid, 0.04-0.12 wt% vitamin B, 0.04-0.07 wt% vitamin C, 0.04-0.07 wt% vitamin E, 0.03-0.06 wt% chamomile Extracts, 0.03-0.06 wt% black currant extract, 0.003-0.006 wt% mulberry blueberry extract, 0.003-0.006 wt% of millet grass powder, 0.003-0.006 wt% zinc, 0.003-0.006 wt% calendula extract , 0.003-0.006 wt% of Ginkgo biloba extract, 0.03-0.06 wt% of medlar, 0.03-0.06 wt% anthocyanin, 0.05-0.07 wt% of grape seed.

The vitamin B component of the above composition having retinal protective function may include vitamin B5, vitamin B6 and vitamin B12; preferably 0.08-0.12 wt% of vitamin B5, 0.08-0.12 wt% of vitamin B6, 0.04-0.07 Wt% of vitamin B12.

The pH of the compound composition having the retinal protective function can be preferably adjusted to between 3.5 and 5.8 by a pH adjusting agent, wherein the pH adjusting agent comprises a phosphate, a borate, an acetate buffer and a citric acid. salt.

The viscosity of the compound composition having the retinal protective function can be preferably adjusted to between 10 and 25000 mpas by a viscosity improving agent, wherein the viscosity improving agent comprises hydroxypropylmethylcellulose or carboxymethylcellulose. Sodium salt, methyl cellulose, polyvinyl tetrahydropyrrolidone, polyvinyl alcohol, dextran and polyacrylic acid.

The compound composition with retinal protection function can adjust the tension value by a force regulator, wherein the tonicity modifier comprises: sodium chloride, potassium chloride, glycerin, mannitol, sorbitol, sodium borate And sodium acetate.

When the compound composition having the retinal protective function is in the eye drop form, it is supplemented to 100 wt% with a solvent, preferably a water or an organic solvent, and may further comprise a pharmaceutically acceptable adjuvant. In addition, 0.01 wt% of benzylamine hydrochloride can be added.

Through the technical means adopted by the present invention, by its unique soothing fatigue Fang, with small molecularly effective ingredients can directly penetrate into the cornea and be absorbed by the body, breaking through the body's absorption barrier and improving bioavailability. Break through the multi-effect ingredients directly into the eye absorption rate problem, and the unique small molecule effect component can directly penetrate into the cornea and be absorbed by the body to achieve the highest absorption rate. In addition, with a unique soothing fatigue formula, it can effectively relieve eye fatigue and achieve preventive health effects. The components of the present invention are completely soluble in solubility, and have no foreign body sensation when used, and the water-soluble leaf yellow contained therein. It can also effectively prevent macular degeneration of the retina, and the hyaluronic acid contained in it can achieve moisturizing effect, fully moisturize the eyes, relieve fatigue, and effectively relieve dryness and discomfort of the eyes.

The compound composition with retinal protection function of the present invention is divided into a solution type (for example, eye drops), and can be processed by a conventional process in the technical field of the present invention, and is made into a double-layer ingot by an ingot-forming technique. A dosage form of an ingot or a sustained-release ingot, or directly filled into a capsule shell to form a capsule dosage form, can also be formulated into a health-care nutritional supplement beverage type, and the compound composition can be applied to various market requirements, and is designed into various dosage forms. The above various dosage forms can be widely used in the fields of health foods and pharmaceuticals, and the added value of related products is enhanced.

The invention discloses a compound composition with retinal protection function, the components mainly comprising: water-soluble lutein, potassium L-aspartate, hyaluronic acid, vitamin B5, vitamin B6, vitamin B12, vitamin C, vitamin E, Chamomile extract, blackcurrant extract, mulberry blueberry extract, millet grass powder, zinc, calendula extract, ginkgo extract, hazelnut, anthocyanin, grape seed; and add chlorine as needed The benzylamine is described in the range of composition ratios as follows.

Example 1: Anti-fatigue eye drops

The compound composition having the retinal protective function of the present invention is organized as shown in Table 1 in terms of the components and composition ratios of the eye drop type.

The formula weight provided in Table 1 is only a preferred embodiment, and the actual blending can still be appropriately adjusted according to the scale range shown in the table, and the eye drops prepared in the above ratio can be additionally added with other suitable pharmacy as needed. An acceptable adjuvant. The extracts in Table 1 were purchased from Taiwan Tongyuan Enterprise, Mao Shi Xingye, and Luodun Trading Company. The solvent used in the above eye drops is usually a water-soluble solvent (e.g., water), and other pharmaceutically acceptable organic solvents may be used, as is known in the art.

In the preparation, it is usually necessary to simultaneously adjust the pH value, tension and viscosity of the eye drops. In order to adjust the appropriate pH, a conventional pH adjuster such as an acid or a base, or a suitable buffer such as a phosphate buffer, a borate buffer, an acetate buffer, or a citrate buffer may be used. . In order to adjust the tonicity of the product, a tonicity adjusting agent commonly used for this purpose, for example, sodium chloride, potassium chloride, glycerin, mannitol, sorbitol, sodium borate, sodium acetate or the like can be used. The viscosity is adjusted by using an appropriate viscosity enhancer in the amount to obtain a desired viscosity level in a prescription. Typical examples include cellulose derivatives such as hydroxypropyl methylcellulose (HPMC), Carboxymethylcellulose sodium salt, methylcellulose, polyvinyltetrahydropyrrolidone, polyvinyl alcohol, dextrans, polyacrylic acid, and the like. The amount of such polymers added will depend, in addition to the desired level of viscosity, on the polymer used, which can be readily determined by those skilled in the art. In addition to increasing viscosity, the use of these polymers also has other Benefits such as the lubricating effect on the eyes and the stabilization effect on the tear film are beneficial for patients suffering from, for example, dry eyes.

If an antimicrobial agent is required, for example, when the preparation is packaged in a multi-dose container, in the case where it is not packaged in a single-dose container, an agent known to be useful for the purpose may be used, for example, four stages. An ammonium compound such as benzalkonium chlride, benzyl alcohol, mercury salt, thimersal, chiorohexidine, chlorobutanol or the like, alone or in combination.

The anti-fatigue eye drops of the invention are all prepared by a aseptic process, and the filling process of the liquid medicine is carried out in a dust-free and sterile environment, and the steps include: blowing, blowing, filling, sealing and un-boiling, etc. In particular, the blowing, filling, and sealing steps therein are completed in one operation. In addition, the syrup bottle and liquid medicine will not be in direct contact with the operator before sealing, and the filling machine has the functions of automatic cleaning (CIP) and automatic sterilization (SIP), so it can maintain excellent production quality.

The anti-fatigue eye drops of the present invention are typically used in an amount of 15 ml, the pH is preferably adjusted to between 3.5 and 5.8, and the viscosity is preferably adjusted to between 10 and 25,000 mpas.

In the above anti-fatigue eye drops, the small molecularly effective components can be effectively absorbed by the human body through the following three absorption routes, breaking through the barrier of eye absorption.

Absorption pathway I:

After the eye drops drip into the eye, the small molecularly active components are directly absorbed by the blood vessels around the eye.

Absorption pathway II:

The small molecule effect component penetrates into the cornea of the eye, passes through the anterior chamber water, is discharged into the crystal lens from the drainage point through the aqueous humor circulation, enters the vitreous body, and is absorbed through the surrounding retinal blood vessels.

Absorption pathway III:

By the unique high intestinal absorption rate and bioavailability of the eye drops, the nasolacrimal duct enters the nasal cavity and is absorbed into the gastrointestinal wall through the esophagus.

Example 2: Positive effects of anti-fatigue eye drops on ocular macular pigments and other functions and effects of ophthalmic drops and oral supplements

In order to confirm the positive effect and efficacy of the anti-fever eye drops of the above-mentioned Example 1 on ocular function, the clinical effects of ophthalmic drops and oral supplements were compared in this example. The experimental method is as follows:

The right eye of 43 subjects was measured by Macular Pigment Optimal Density (HOD) using a Heterochromatic flicker photometry (HFP) to measure glare tolerance, time contrast sensitivity, spatial contrast sensitivity, At the same time monitor vision, intraocular pressure.

The test components were two groups: (1) Oral supplement group: 22 subjects were administered lutein oral supplement, and 30 mg of lutein was administered daily. (2) Ophthalmic drop group: 21 subjects were treated with eye drops containing 15 mg/10 ml of water-soluble lutein twice a day for eye function to confirm the ophthalmic drop containing water-soluble lutein. The efficacy of the agent is compared with oral lutein. The following tests were performed on the subjects: Macular Pigment Optimal Density (MPOD) test, Spatial contrast sensitivity (SCS), and Time contrast sensitivity (TCS).

1. Objects and methods

1.1 Subject inclusion criteria

A total of 43 subjects aged 50-65 years (each subject examined the right eye for a total of 43 eyes).

I. Age is 50 to 65 years old, regardless of gender.

II. Exclusion of internal and external eye diseases and family disease history.

III. Normal color vision. No history of epilepsy. No smoking history.

This experiment was approved by the Human Body Testing Committee of Taipei Veterans General Hospital.

1.2 Experimental methods

1.2.1 Measurement of macular pigment density

Macular pigment density was measured using Heterochromatic flicker photometry (HFP).

The instrument and method for detecting the macular pigment density in this experiment only changed the scintillation light frequency and the position of the paracentral fixation point in HFP based on the experiment of Tang et al. (Ophthalmology and Physiological Optics, 2004, No. 06). In this experiment, The detection light blue flicker frequency is 14 Hz, the reference light green light flicker frequency is 10 Hz, and the side center 7° is selected as the detection reference point.

1.2.2 Measurement of spatial contrast sensitivity

The spatial contrast sensitivity function was measured using the VSG series software (Cambridge Research System, HK). The inspection distance is 2.5 m, and the excitation target is a disc with a diameter of 1.4°, on which is a sinusoidal modulation separation grid. The contrast sensitivity at 6.0, 12.0, 24.0 c/d spatial frequency was measured. The grating acuity is detected using a square wave bar grid to record the sensitivity at maximum contrast. Bar grid brightness is measured by a spectrophotometer (Topcon SR-3). Use the test lens to correct the refractive error of the test object before the test. The inspection was carried out in a dark room with a check distance of 2.5 m. The detection of each spatial frequency occurred in a random sequence, and the entire inspection process took about 7 minutes.

1.2.3 Measurement of time contrast sensitivity

The time contrast sensitivity function is also measured using the VSG series software. The inspection distance is 2.5 m, and the green spot with the visual target of 1° is stimulated. The brightness of the spot changes sinusoidally, and the center has a cross-gaze target. The contrast sensitivity at 6.0, 12.0, 24.0, 32.0 Hz was measured. The Critical Flicker Frequency (CFF) is measured at the highest point of contrast. The inspection was carried out in a dark room with a check distance of 2.5 m. The detection of each time frequency appeared in a random sequence and the entire inspection took about 10 minutes.

1.2.4 Statistical methods

The comparison of spatial and temporal contrast sensitivity functions was analyzed by one-way ANOVA in SPSS 13.0 statistical suite software. The t-test was used to compare the grid vision and flash fusion frequencies.

2 results

2.1 Macular pigment optical density (MPOD)

The experimental results are shown in Table 2 and Figure 1. The subjects were randomly divided into two groups, the ophthalmic drop group and the oral group. The average macular pigment density of the eye drops group and the oral group at the beginning of the experiment (Day 0) were 0.34±0.0456, 0.35, respectively. ±0.0362.

After 84 days of administration of lutein, the mean values of macular pigment density in the ophthalmic drop group and the oral group were increased to 0.46 ± 0.04 and 0.39 ± 0.03, respectively.

Table 2: Comparison of macular pigment density values (MPOD) between ophthalmic drops and oral groups

2.2 Spatial contrast sensitivity (SCS)

The experimental results are shown in Table 3 and Figure 2. The subjects were randomly divided into two groups, the ophthalmic drop group and the oral group. The mean spatial contrast sensitivity of the eye drops group and the oral group at the beginning of the experiment (Day 0) were 33.41±0.0446, respectively. c/d, 33.42 ± 0.0395 c/d.

Table 3: Comparison of spatial contrast sensitivity (SCS) between ophthalmic drops and oral groups

After 84 days of administration of lutein, the mean spatial sensitivity of the eye drops group and the oral group increased to 38.21 ± 0.03 c / d, 34.65 ± 0.04 c / d.

2.3 Time contrast sensitivity (TCS)

The experimental results are shown in Table 4 and Figure 3. The subjects were randomly divided into two groups, the ophthalmic drop group and the oral group. The mean contrast sensitivity of the eye drops group and the oral group at the beginning of the experiment (Day 0) were 37.96±0.03, respectively. c/d, 37.41 ± 0.04 c/d. After 84 days of administration of lutein, the mean time-sensitive contrast sensitivity of the ophthalmic drop group and the oral group was increased to 42.43±0.04 c/d and 38.28±0.04 c/d.

Table 4: Comparison of time contrast sensitivity (TCS) between ophthalmic drop group and oral group

From the above experimental results, the spatial density (MPOD), spatial contrast sensitivity (SCS), time contrast sensitivity between the two groups after 84 days of supplementation with ophthalmic drops and oral supplementation were given. (TCS) are all significantly different. The results of the above studies showed that the visual function indexes of the ophthalmic drops containing the water-soluble lutein were higher than the general lutein oral group, and the clinical study confirmed the ophthalmic drops containing water-soluble lutein. The exact effect.

In addition, the compound composition with retinal protection function of the present invention can directly penetrate into the cornea and be absorbed by the human body by using the unique small molecular effect component of the eye drop type. In order to achieve the highest absorption rate, and with a unique soothing fatigue and moisturizing formula, it can effectively relieve eye fatigue, and indeed achieve preventive health effects, and fully moisturize the eyes, soothe fatigue, effectively relieve dryness and discomfort of the eyes, and add water to dissolve Lutein has the efficacy of preventing macular degeneration of the retina.

It can be seen from the above embodiments that the compound composition with retinal protection function provided by the present invention has industrial utilization value, but the above description is only for the preferred embodiment of the present invention, and those skilled in the art should be Other modifications may be made in light of the above teachings, but such changes are still within the spirit of the invention and the scope of the invention as defined below.

Figure 1 shows the comparison of the macular pigment density value (MPOD) of the eye drop group (Eyedrop Group) and the oral group (Oral Group); the second figure shows the eye drop group (Eyedrop Group) and the oral group (Oral) Group) spatial contrast sensitivity (SCS) comparison trend chart; Figure 3 shows the time contrast sensitivity (TCS) comparison trend chart of the eye drop group (Eyedrop Group) and the oral group (Oral Group).

Claims (12)

A compound composition having retinal protection function, comprising: 1.00 - 3.00 wt% of water-soluble lutein, 0.80-1.20 wt% of L-aspartate, 0.1% - 0.2 wt% of hyaluronic acid, 0.04-0.12 wt% of vitamin B, 0.04-0.07 wt% of vitamin C, 0.04-0.07 wt% of vitamin E, 0.03-0.06 wt% of chamomile extract, 0.03-0.06 wt% of black currant extract, 0.003 -0.006 wt% of mulberry blueberry extract, 0.003-0.006 wt% of millet grass powder, 0.003-0.006 wt% zinc, 0.003-0.006 wt% calendula extract, 0.003-0.006 wt% of ginkgo extract, 0.03 - 0.06 wt% of medlar, 0.03-0.06 wt% anthocyanin, 0.05-0.07 wt% of grape seed. The compound composition having retinal protective function according to claim 1, wherein the vitamin B is selected from the group consisting of 0.08-0.12 wt% of vitamin B5, 0.08-0.12 wt% of vitamin B6, and 0.04-0.07 wt%. A group consisting of vitamin B12, and any combination thereof. The compound composition having retinal protective function according to claim 1, wherein the compound composition further comprises 0.01 wt% of benzylamine hydrochloride. The compound composition having retinal protection function according to claim 1, wherein the pH of the compound composition is adjusted to between 3.5 and 5.8 by a pH adjusting agent. A compound composition having retinal protective function as described in claim 4, wherein the pH adjusting agent comprises a phosphate, a borate, an acetate buffer, and a citrate. A compound composition having retinal protection function as described in claim 1, wherein the viscosity of the compound composition is adjusted to 10 by a viscosity enhancer Between 25,000 mpas. A compound composition having retinal protective function as described in claim 6 wherein the viscosity enhancer comprises hydroxypropylmethylcellulose, sodium carboxymethylcellulose, methylcellulose, polyvinyltetra Hydropyrrolidone, polyvinyl alcohol, dextran, and polyacrylic acid. The compound composition having retinal protection function according to claim 1, wherein the compound composition is adjusted by a force adjusting agent comprising: sodium chloride, potassium chloride , glycerin, mannitol, sorbitol, sodium borate and sodium acetate. The compound composition having retinal protective function according to claim 1 of the patent application may further comprise a solvent supplemented to 100 wt%, and the solvent is water or an organic solvent. The compound composition having retinal protective function according to claim 1, wherein the compound composition further comprises a pharmaceutically acceptable adjuvant. A compound composition having retinal protective function as described in claim 1, wherein the composition of the compound composition is a solution, a tablet or a capsule. The compound composition having retinal protection function according to claim 1, wherein the retinal protection function is to prevent degeneration of the macula or to reduce excessive fatigue of the eye.