TWI673071B - Ophthalmic composition - Google Patents

Abstract

The invention discloses an ophthalmic composition comprising 0.5-10% (w / v) of γ-PGA and 0.1-2.0 ppm of ClO ₂ . The ophthalmic composition can be used as a contact lens maintenance solution.

Description

Ophthalmic composition

The invention relates to an ophthalmic composition, particularly a preservative-free composition, which can be used for cleaning, moisturizing and / or disinfecting contact lenses.

Modern technology is constantly progressing, and many products that pay attention to lightness, comfort, and time-saving gradually replace the untimely items, creating a variety of items. Contact lenses have gradually evolved from early hard lenses to soft lenses, and even today's popular multi-color lenses, which solves the obstacles and weight of eyeglass frames, the risk of possible breakage of eyeglass lenses, and brings benefits to athletes and players, dancers, and performers. For greater convenience, it is a medical device that has aesthetics and provides human vision correction. However, contact lenses are in direct contact with the cornea for a long time. In order to avoid infection and discomfort, cleaning and maintenance related products of contact lenses are particularly important. Contact lenses are directly attached to the surface of the eyeball. When the cleaning or maintenance solution contains irritating ingredients or pollution occurs, it may cause eye infections and inflammation. According to statistics, the most common eye conditions in contact lens groups include red eyes, dry eyes, and allergies, which are mostly caused by contact lens maintenance solutions or related preservation products.

Contact lens preservation supplies refer to the products necessary for daily cleaning, sterilization, rinsing and storage of contact lenses, including contact lens storage boxes, cleaning solutions, rinsing solutions, multifunctional maintenance solutions, physiological saline, hydrogen peroxide system, deproteinized tablets, etc. . Generally speaking, contact lens maintenance fluids have cleaning, sterilizing, and moisturizing effects. They can be divided into cleaning fluids, soaking fluids / preservatives, rinsing fluids, disinfecting fluids, and lubricants. (With cleaning and storage functions), three-in-one (with cleaning, storage and disinfection functions) or multi-functional products, according to different use needs. (1) Cleaning solution: Cleaning is mainly to remove dirt or foreign particles attached to the surface of contact lenses, and to remove eye secretions such as proteins adsorbed on contact lenses. Common ingredients include surfactants and enzymes. The interface active cleaning solution uses mechanical friction to dissolve impurities for cleaning, and the enzyme (papaya enzyme or pancreatic enzyme) cleaning solution uses chemical bonding to achieve cleaning effects. (2) Disinfectant: Disinfection is mainly to remove pathogenic and toxin factors, such as bacteria, viruses, amoeba, and Pseudomonas aeruginosa. Common chemicals include chlorbutamine or alcohol and disinfectants containing hydrogen peroxide. Chemical disinfection solution is simple and universal. The contact lens can be immersed in the medicine for several hours to achieve the disinfection effect, but it is easy to cause eyeball irritation and allergic reactions. The hydrogen peroxide itself has a bactericidal effect, and then the platinum ring tablets and physiological saline can be used for neutralization to achieve disinfection, but if the neutralization is not complete, it may cause damage to the eyes. (3) Wetting liquid: The main function of wetting is to form a moisturizing layer on contact lenses, increase the moisturizing degree of lenses, and reduce the dryness and discomfort of the eyeballs after wearing contact lenses. Common ingredients include methyl cellulose and hyaluronic acid. (4) Rinse solution: Rinsing is mainly to remove impurities such as impurities and bacteria on the lens, and it is usually physiological saline. (5) Soaking solution: The soaking solution can also be said to be a preservation solution. Its main function is antiseptic. After soaking, it can achieve the effect of sterilization and preservation. Often contains certain preservative ingredients. (6) Deproteinizing solution: The main function is to remove the protein secretions accumulated on the lens. Because the eyes secrete proteins to resist the invasion of bacteria or viruses, the accumulation of secretions in the pores of contact lenses reduces oxygen permeability. Therefore, regular use of protease-free enzyme tablets or enzyme solutions can prolong the life of contact lenses and reduce Eyeball friction irritation.

According to the survey, as many as 6 to 70% of people wearing contact lenses are prone to some eye conditions, including dryness, redness, and allergies, which are mostly caused by contact lens maintenance fluid. In order to facilitate storage in hot and humid environments and extend the useful life of the product after it is opened, contact lens maintenance solutions often contain preservatives in addition to cleaning, sterilizing, moisturizing, and deproteinizing ingredients. However, preservatives mainly cause The culprit of red eyes and allergies. Early maintenance liquids contain mercury, which can easily cause allergic reactions. Although most current commercial products use no mercury and choose to add qualified preservatives, they can reduce the chance of allergies, but still cause damage to the cornea. Or cause adverse reactions such as inflammation, which may even cause allergic conjunctivitis in the long term.

Considering that preservatives are prone to cause allergic problems, maintenance liquid products without preservatives have been derived, but because of this, most of them do not have the function of antibacterial preservation. As a result, maintenance liquids can easily breed bacteria or cause pollution over time, which can cause eyes Irritation and inflammation, and even cause eye diseases such as corneal ulcers. Although contact lenses can be immersed in 3% hydrogen peroxide to disinfect and then neutralize the hydrogen peroxide with platinum tablets and physiological saline, the advantages are less allergic reactions, time saving, and good bleaching effect, but there may be problems of incomplete neutralization. Toxicity and damage to eyeballs and corneal cells. In addition, hydrogen peroxide will turn into water after neutralization, and it does not have sterilization function. If the lens is soaked for a week, it will be worn without disinfection, which means no sterilization, but it will cause bacteria to grow and affect eye health.

In addition, because contact lens lenses can absorb tears and make the eyes lack of oxygen, resulting in dehydration and dryness of the eyes, relative dry eye symptoms occur, leading to imbalance in the quality or quantity of tear fluid, and serious cases may cause corneal injury. Therefore, it is generally recommended to use a maintenance solution containing a wetting component of a macromolecular polymer to keep the eyes moist. At present, ingredients such as hyaluronic acid or methyl cellulose are mostly used to provide eye wetness. However, although this type of wetting fluid can bring short-term soothing effects and comfort to contact lens wearers, it still cannot be achieved. Long-term locks moisture and effectively reduces the incidence of dry eye. In addition, a preservative is often added as a bacteriostatic agent to the composition of the moisturizing fluid, but it will easily cause toxic damage to the cornea.

In view of the above, there is still a need for a contact lens maintenance solution that does not contain a preservative, but can have both antibacterial and wetting effects.

It was unexpectedly discovered in the present invention that an ophthalmic composition containing a specific amount of γ-PGA and a specific amount of ClO ₂ has an excellent antibacterial effect, and in particular, can provide synergy against fungi (for example, Candida albicans) ( synergistic) antibacterial effect.

The present invention provides an ophthalmic composition comprising γ-PGA and ClO ₂ . Preferably, the content of γ-PGA is 0.5 to 10% (w / v), and the content of ClO ₂ is 0.1 to 2.0 ppm.

According to some specific embodiments of the present invention, the content of γ-PGA is 1 to 8% (w / v), preferably 1 to 5% (w / v), and more preferably 1 to 2% (w / v). . In a specific embodiment of the present invention, the ophthalmic composition comprises about 1.5% (w / v) of γ-PGA.

According to some specific embodiments of the present invention, the content of ClO ₂ is 0.3 to 1.8 ppm, preferably 0.5 to 1.5 ppm, and more preferably 1.0 to 1.5 ppm (w / v). In a specific embodiment of the invention, the ophthalmic composition comprises about 1.25 ppm of ClO ₂ .

According to a specific embodiment of the present invention, the ophthalmic composition includes about 1.5% (w / v) of γ-PGA and about 1.25 ppm of ClO ₂ .

The ophthalmic composition of the present invention is preferably in a liquid state, and it can be used as a contact lens maintenance solution.

It should be understood that the foregoing general description and the following detailed description are provided for the purpose of example and explanation only, and are not intended to limit the present invention.

The present invention provides an ophthalmic composition comprising γ-PGA and ClO ₂ . Preferably, the content of γ-PGA is 0.5 to 10% (w / v), and the content of ClO ₂ is 0.1 to 2.0 ppm.

According to some specific embodiments of the present invention, the content of γ-PGA is 1 to 8% (w / v), preferably 1 to 5% (w / v), and more preferably 1 to 2% (w / v). . In a specific embodiment of the present invention, the ophthalmic composition comprises about 1.5% (w / v) of γ-PGA.

γ-poly glutamic acid (γ-PGA) was first found in the cell wall of Bacillus anthracis in 1973. It is a natural product that can be synthesized by the fermentation of microorganisms (such as Bacillus subtilis natto). Polymer materials have many excellent properties, including non-toxicity, high biocompatibility and biodegradability ... etc.

According to some specific embodiments of the present invention, the content of ClO ₂ is 0.3 to 1.8 ppm, preferably 0.5 to 1.5 ppm, and more preferably 1.0 to 1.5 ppm (w / v). In a specific embodiment of the invention, the ophthalmic composition comprises about 1.25 ppm of ClO ₂ .

According to a specific embodiment of the present invention, the ophthalmic composition includes about 1.5% (w / v) of γ-PGA and about 1.25 ppm of ClO ₂ .

The ophthalmic composition of the present invention is preferably in a liquid state, and it can be used as a contact lens maintenance solution.

The ophthalmic composition of the present invention has an excellent antibacterial effect, and in particular, can provide a synergistic antibacterial effect against fungi (for example, Candida albicans).

According to some embodiments of the present invention, the ophthalmic composition further comprises hyaluronic acid to increase the moisturizing effect.

According to some specific embodiments of the present invention, the ophthalmic composition further comprises conventional buffer components, such as CaCl ₂ , KCl, NaCl, Na ₂ HPO ₄ , and the like.

According to some specific embodiments of the present invention, the ophthalmic composition further comprises a conventional nonionic surfactant, including but not limited to Poloxamer, for example, Poloxamer-407.

According to some specific embodiments of the present invention, the ophthalmic composition further includes tea polyphenols, including, but not limited to, catechin, epicatechin (EC), and epigallocatechin , EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG). In a specific embodiment of the present invention, the ophthalmic composition further comprises EGCG.

The invention is further elucidated by the following examples, which are provided for illustrative purposes and not for restrictive purposes.

Example 1. Cytotoxicity and antibacterial properties of ophthalmic composition

Materials and methods

Ophthalmic composition formula

The formulation of the ophthalmic composition used in this example is shown in Table 1 below.

Table 1. Formulations of ophthalmic compositions

It also contains buffer components: CaCl ₂ 0.015g, KCl 0.15g, NaCl 0.45g, Na ₂ HPO ₄ 0.45-1.8g, pH = 6.5-7.5, and surfactant poloxamer-407, 0.05-0.5g.

2. Cytotoxicity test

Take 100 μL of L929 (mouse lung fibroblast cell line, Food Industry Development Institute, deposit number BCRC 60091) at a concentration of 1 × 10 ⁵ cells / mL into a 96-well dish. Incubate for 24 ± 2 hours at 1% carbon dioxide and 37 ± 1 ℃. Aspirate the culture solution, add 100 μL of the prepared ophthalmic composition dilution solution (add the complete cell culture solution as a dilution solution at a ratio of 0.2g ± 10% / mL), and add 5 ± 1% carbon dioxide at a temperature of 37 ± Incubate at 1 ° C for 24 hours. The positive (10% DMSO), negative (whole cell culture) control group and the ophthalmic composition dilution were all tested in triplicate. Replace the cell culture solution with 50 μl of dimethyl mercaptan diphenyltetrazole olfactory solution (MTT, Sigma, Cat No. 298931) (1 mg / mL MTT in serum-free cell culture solution). Incubate for 2 hours ± 10 minutes under the environment of ± 1% carbon dioxide and temperature 37 ± 1 ℃. The dimethyl mercaptan diphenyltetrazole olfactory solution was removed, and 100 μl of DMSO was added, and then allowed to stand at room temperature for 10 minutes to dissolve formazan blue-violet crystals. A disc enzyme immunoassay was used to detect the absorption at a wavelength of 570 nm (reference wavelength 650 nm).

3. Antibacterial effect test

The antibacterial effects of the ophthalmic compositions of Formulae 1 and 2 on 3 strains were tested. The three strains were thawed and cultured for 2 days. Take one colony from the plate to the bacterial solution tube and culture for 2 days. Strain growth standard curve was used to measure OD value (E. coli, OD = 1, number of bacteria: 1x10 ⁹ ; Staphylococcus aureus, OD = 1, number of bacteria: 2.5x10 ⁸ ; Candida albicans, OD = 1, number of bacteria : 1.6x10 ⁶ ), diluted 10: 1 with water to adjust the concentration of bacteria solution to 10 ⁶ cfu / ml. Add 0.1ml of the bacteria solution to the ophthalmic composition of Formulas 1 and 2, and mix thoroughly to completely disperse the bacteria. The bacterial group (E. coli, Staphylococcus aureus) was cultured at 25 ° C, and the fungal group (Candida albicans) was cultured at 35 ° C. On the 3rd to 7th days, take 1 ml of sample solution, and serially dilute 10 ³ , 10 ² , and 10 ¹ times the bacterial count to evaluate the antibacterial effect.

result

Cytotoxicity

Compared to the control group (untreated), cells treated with the ophthalmic composition of Formula 1 had an average survival rate of 89% (results not shown), and cells treated with the ophthalmic composition of Formula 2 had an average survival rate of 77. % (Results not shown).

Antibacterial effect

The antibacterial effects of the ophthalmic compositions of Formulas 1 and 2 on the three strains are shown in Table 2 below.

Table 2. The bacterial counts of the three strains (n = 2 in each group of the experimental group)

The results show that γ-PGA and ClO ₂ alone have no obvious antibacterial effect on Candida albicans (formulations 1 and 3-6), but combined use can achieve unexpected synergistic effects, and it is difficult to kill white fungi. Candida has excellent antibacterial effect (Recipe 2), and can also kill E. coli or Staphylococcus aureus.

Those skilled in the art will understand that the above-mentioned specific embodiments can be modified without departing from the main inventive concept. Therefore, it can be understood that the present invention is not limited to the specific embodiments disclosed, but is intended to cover any modification within the spirit and scope of the present invention as defined by the scope of the patent application.

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Claims (1)

A use of a combination of γ-PGA and ClO ₂ for preparing a contact lens maintenance liquid, wherein the γ-PGA and the ClO ₂ are present in the contact lens maintenance liquid at the following concentration: 1-5 g / 100 ml of γ-PGA And ClO _{2 at} 0.1-2.0 ppm; wherein the combination of γ-PGA and ClO ₂ can inhibit (1) Candida albicans to a bacterial count below 2.0x10 ⁴ cfu / ml; (2) E. coli to a bacterial count of 5.0x10 ⁶ cfu / ml; and (3) Staphylococcus aureus to 1.0x10 ⁵ cfu / ml or less.