CN108310442A - Ophthalmic composition - Google Patents

Abstract

The present invention discloses an ophthalmic composition, which comprises 0.5-10% (w/v) of γ-PGA and 0.1× ^10-4-2.0 × ^10-4 % (v/v) of ClO ₂ . The ophthalmic composition can be used as a contact lens care solution.

Description

Ophthalmic Composition

【Technical field】

The present invention relates to an ophthalmic composition, in particular to an ophthalmic composition without preservatives, which can be used for cleaning, moisturizing and/or disinfecting contact lenses.

【Background technique】

With the continuous advancement of modern technology, many products that emphasize lightness, comfort, and time-saving gradually replace outdated items, creating a variety of items. Contact lenses have gradually developed from early hard lenses to soft lenses, and even today's popular colored multi-style lenses, which solve the obstacles and weight of the spectacle frame, and the risk of possible cracking of the spectacle lens, and provide sports for athletes, players, dancers, and performers. Bringing greater convenience, it is a medical device that is aesthetically pleasing and provides human vision correction. However, contact lenses are in direct contact with the cornea of the eye for a long time. In order to avoid infection and discomfort, cleaning and maintenance related products for 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 is polluted, it may cause eye infection, inflammation and other problems. According to statistics, the eye conditions most likely to occur in contact lens groups include red eyes, dry eyes and allergies, and these are mostly symptoms caused by contact lens maintenance solutions or related preservation products.

Contact lens preservation supplies refer to the necessary products for daily cleaning, sterilization, flushing and storage of contact lenses, including contact lens preservation boxes, cleaning solutions, rinsing solutions, multi-functional maintenance solutions, physiological saline, hydrogen oxygen systems, protein-free tablets, etc. . Generally speaking, contact lens maintenance solutions mainly have the functions of cleaning, sterilizing, and moistening, and can be divided into cleaning solutions, soaking solutions/preservation solutions, rinse solutions, disinfectants, lubricants, etc., and there are single and two-in-one solutions on the market. (with cleaning and storage functions), 3-in-1 (with cleaning, storage and disinfection functions) or multi-functional products to meet different usage needs. (1) Cleaning solution: Cleaning is mainly to remove dirt or impurity particles attached to the contact lens surface, and to remove eye secretions such as proteins adsorbed on the contact lens. Common ingredients include surfactants, enzymes. The surface active cleaning solution uses mechanical friction to dissolve impurities for cleaning, while the enzyme (papaya enzyme or pancreatic enzyme) cleaning solution uses chemical bonding to achieve cleaning effect. (2) Disinfectant: Disinfection is mainly to remove pathogenic and toxin factors, such as bacteria, viruses, amoebas, Pseudomonas aeruginosa, etc. Common ones include chemicals containing cloxidine chloride or alcohols, and disinfectants containing hydrogen peroxide. Chemical disinfectants are simple and common. Soaking contact lenses in liquid medicine for several hours can achieve the disinfection effect, but it is easy to cause eye irritation and allergic reactions. Hydrogen peroxide itself has a bactericidal effect, and then use platinum ring tablets and saline to neutralize to achieve disinfection, but if the neutralization is not complete, it may cause damage to the eyes. (3) Moisturizing solution: The main function of wetting is to form a moisturizing layer on the contact lens, increase the moisture retention of the lens, and reduce the dryness and discomfort of the eyeball after wearing the contact lens. Common ingredients include methylcellulose, hyaluronic acid, etc. (4) Flushing solution: Flushing is mainly to wash away impurities and bacterial cells on the lens, and it is generally physiological saline. (5) Soaking solution: The soaking solution can also be called a preservation solution. Its main function is antisepsis, and it can achieve the effect of sterilization and preservation after soaking. Often contain some preservative ingredients. (6) Deproteinizing solution: the main function is to remove the protein secretion accumulated on the lens. Since the eyes secrete protein to resist the invasion of bacteria or viruses, the accumulation of secretions in the pores of the contact lens will reduce the oxygen permeability. Eye rubbing irritation.

According to the survey, as many as 60-70% of the groups who wear contact lenses are prone to some eye conditions, including eye dryness, redness, allergies and other discomforts, and these are mostly symptoms caused by contact lens maintenance solutions. In order to facilitate preservation in a hot and humid environment and prolong the service life of the product after opening, in addition to cleaning, sterilizing, moisturizing, and protein-removing ingredients, most contact lens care solutions also add preservatives. However, preservatives are the main cause. The culprit of red eyes and allergies. The early care solutions contained mercury, which could easily cause allergic reactions. Although most of the current commercially available products are mercury-free and add qualified preservatives, which can reduce the chance of inducing allergies, they will still cause damage to the cornea of the eyeball. Or cause adverse reactions such as inflammation, and may even cause allergic conjunctivitis in the long run.

Considering the problem that preservatives are likely to cause allergies, skin care products that do not contain preservatives have been derived, but most of them do not have the function of antibacterial preservation, which leads to the growth of bacteria or pollution in the skin care products over time, which can cause eye damage. Adverse reactions such as irritation and inflammation, and even eye diseases such as corneal ulcers. Although contact lenses can be soaked in 3% hydrogen peroxide for disinfection, and then neutralized with platinum tablets and normal saline to neutralize the hydrogen peroxide, the advantages are less allergic reactions, time saving, and good bleaching effect, but there may be problems of incomplete neutralization. Toxicity and damage to eyeball and corneal cells. In addition, hydrogen peroxide will turn into water after neutralization, and has no bactericidal function. If the lens is soaked for a week and put on without disinfection, it means that there is no sterilization, but it will allow bacteria to proliferate and affect eye health.

In addition, contact lens lenses will absorb tears and make the eyes hypoxic, resulting in dehydration and dryness of the eyes, resulting in relative dry eye syndrome, resulting in an imbalance in the quality or quantity of tears, and may cause corneal damage in severe cases. Therefore, it is generally recommended to use a maintenance solution containing a moisturizing ingredient of a macromolecular polymer to keep the eyes moist. Currently on the market, ingredients such as hyaluronic acid or methylcellulose are often added to provide eye moisture. However, although such wetting solutions can bring temporary relief and comfort to contact lens wearers, they still cannot achieve Long-lasting moisture lock and effectively reduce the incidence of dry eye syndrome. In addition, preservatives are often added to the composition of the wetting solution as a bacteriostatic agent, which will easily cause toxic damage to the cornea.

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

【Content of invention】

In the present invention, it is unexpectedly found that the ophthalmic composition containing a specific amount of γ-PGA and a specific amount of _ClO has an excellent antibacterial effect, especially can provide synergistic ( synergistic) antibacterial effect.

The present invention provides an ophthalmic composition, which comprises 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 0.1x 10 ^-4 -2.0x 10 ^-4 % (v/v).

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), more preferably 1 to 2% (w/v) . In a specific embodiment of the invention, the ophthalmic composition comprises about 1.5% (w/v) γ-PGA.

According to some specific embodiments of the present invention, the content of ClO ₂ is 0.1x 10 ^-4 -1.8x 10 ^-4 % (v/v), preferably 0.5x 10 ^-4 -1.5x 10 ^-4 % (v/ v), more preferably 1.0x 10 ^-4 -1.5x 10 ^-4 % (v/v). In a specific embodiment of the present invention, the ophthalmic composition comprises about 1.25 x 10 ^-4 % (v/v) ClO ₂ .

According to a specific embodiment of the present invention, the ophthalmic composition comprises about 1.5% (w/v) γ-PGA and about 1.25×10 ⁻⁴ % (v/v) ClO ₂ .

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

It should be understood that both the foregoing general description and the following detailed description are by way of example and explanation only, rather than limiting the invention.

【Detailed ways】

The present invention provides an ophthalmic composition, which comprises 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 0.1x 10 ^-4 -2.0x 10 ^-4 % (v/v).

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), more preferably 1 to 2% (w/v) . In a specific embodiment of the present invention, the ophthalmic composition comprises 1.5% (w/v) γ-PGA.

γ-polyglutamic acid (γ-PGA) was first discovered in 1973 to exist in the cell wall of Bacillus anthracis (Bacillus anthracis). A natural polymer material with many excellent properties, including non-toxic, high biocompatibility and biodegradability...etc.

According to some specific embodiments of the present invention, the content of ClO ₂ is 0.3x 10 ^-4 -1.8x 10 ^-4 % (v/v), preferably 0.5x 10 ^-4 -1.5x 10 ^-4 % (v/v v), more preferably 1.0x 10 ^-4 -1.5x 10 ^-4 % (v/v). In a specific embodiment of the present invention, the ophthalmic composition comprises 1.25 x 10 ^-4 % (v/v) ClO ₂ .

According to a specific embodiment of the present invention, the ophthalmic composition comprises about 1.5% (w/v) γ-PGA and 1.25×10 ⁻⁴ % (v/v) ClO ₂ .

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

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

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

According to some embodiments of the present invention, the ophthalmic composition further comprises conventional buffer components, for example, CaCl ₂ , KCl, NaCl, Na ₂ HPO ₄ . . . and so on.

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

According to some embodiments of the present invention, the ophthalmic composition further includes EDTA-2Na.

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

Detailed ways

The invention is further illustrated by the following examples, which are offered for purposes of illustration, not limitation.

Example 1. Cytotoxicity and Antibacterial Properties of Ophthalmic Compositions

Materials and methods

1. Ophthalmic composition formula

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

Table 1. Formulation (100ml) of the ophthalmic composition

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, Institute of Food Industry Development, Registration No. BCRC 60091) cell suspension at a concentration of 1×10 ⁵ cells/mL and add it to a 96-well plate. % carbon dioxide, temperature 37 ± 1 ° C environment for 24 ± 2 hours. Aspirate the culture solution, add 100 μL of the prepared ophthalmic composition dilution (add the complete cell culture solution at a ratio of 0.2g±10%/mL as the dilution), and add 5±1% carbon dioxide at a temperature of 37±1 Incubate at ℃ for 24 hours. Positive (10% DMSO), negative (whole cell culture fluid) control groups and ophthalmic composition dilutions were tested in triplicate. Replace the cell culture medium with 50 μl of dimethylthiol diphenyltetrazolium sniffing solution (MTT, Sigma, Cat No. 298931) (1 mg/mL MTT is dissolved in serum-free cell culture medium) at 5 ± 1 % carbon dioxide, temperature 37 ± 1 ° C environment for 2 hours ± 10 minutes. The dimethyl mercaptan diphenyl tetrazolium sniffing solution was removed, 100 μl of DMSO was added and left to stand at room temperature for 10 minutes to dissolve formazan blue-purple crystals. Detect the absorbance at 570nm wavelength (reference wavelength 650nm) with a plate-type enzyme immunoassay analyzer.

3. Antibacterial effect test

The antibacterial effects of the ophthalmic compositions of formulations 1 and 2 against three bacterial strains were tested. The three strains were thawed separately and cultured for 2 days. Take one colony from each plate and transfer it to the bacterial solution tube, and cultivate it for 2 days. Use the growth standard curve of the strain to measure the OD value (Escherichia coli, OD=1, bacterial count: 1×10 ⁹ ; Staphylococcus aureus, OD=1, bacterial count: 2.5×10 ⁸ ; Candida albicans, OD=1, bacterial count: : 1.6x10 ⁶ ), serially diluted 10:1 with water to adjust the bacterial concentration to 10 ⁶ cfu/ml. Take 0.1ml of the bacteria solution and add it to the ophthalmic compositions of formulas 1 and 2, and mix well to completely disperse the bacteria. The bacterial group (Escherichia coli, Staphylococcus aureus) was cultured at 25°C, and the fungal group (Candida albicans) was cultured at 35°C. On the 3rd to 7th day, take 1ml of the sample solution, serially dilute 10 ³ , 10 ² , and 10 ¹ times to count the number of bacteria to evaluate the antibacterial effect.

result:

1. Cytotoxicity

Compared with the control group (untreated), the average survival rate of the cells treated with the ophthalmic composition of formula 1 was 89% (results not shown), and the average survival rate of the cells treated with the ophthalmic composition of formula 2 was 77%. % (results not shown).

2. Antibacterial effect

The antibacterial effects of the ophthalmic compositions of formulations 1 and 2 against the three bacterial strains are shown in Table 2 below.

Table 2. Bacterial quantity of 3 kinds of bacterial strains (experimental group each group n=2)

Concentration (cfu/ml) control group Recipe 1 Recipe 2 Recipe 3 Recipe 4 Recipe 5 Recipe 6 Escherichia coli 10 ⁵ -10 ⁶ 0 0 0 0 0 5.06x10 ⁶ Staphylococcus aureus 10 ⁵ -10 ⁶ 0 0 1.2x10 ⁵ 1x10 ⁵ 4.8x10 ⁵ 6.6x10 ⁵ Candida albicans 10 ⁵ -10 ⁶ 2.54x10 ⁴ 0 6x10 ⁶ 6x10 ⁶ 6x10 ⁶ 8.4x10 ⁵

The results show that γ-PGA and ClO ₂ alone have no obvious antibacterial effect on Candida albicans (Formula 1 and Formula 3-6), but when used in combination, they can achieve unexpected synergistic effects, and have no obvious antibacterial effect on Candida albicans, which is more difficult to kill. Candida has excellent antibacterial effect (recipe 2), and can also kill Escherichia coli or Staphylococcus aureus at the same time.

Those skilled in the art of the present invention will understand that various modifications and substitutions can be made to the above-mentioned specific embodiments without departing from the main inventive concepts of the present invention. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the invention as defined by the claims.

Claims (10)

1. An ophthalmic composition, characterized by comprising 0.5-10% (w/v) γ-PGA and 0.1x10 ^-4 -2.0x10 ^-4 % (v/v) ClO ₂ . 2. The ophthalmic composition according to claim 1, comprising 1-5% (w/v) of [gamma]-PGA. 3. The ophthalmic composition according to claim 2, comprising 1-2% (w/v) of [gamma]-PGA. 4. The ophthalmic composition according to claim 3, comprising 1.5% (w/v) of γ-PGA. 5. The ophthalmic composition of claim ¹ , comprising ^{0.5x10-4-1.5x10-4} % (v/v) _ClO2 . 6. The ophthalmic composition according to claim 5, comprising ^1.0x10-4 - ^1.5x10-4 % (v/v) _ClO2 . 7. The ophthalmic composition according to claim 6, comprising ^1.25x10-4 % (v/v) _ClO2 . 8 . The ophthalmic composition according to claim 1 , comprising 1.5% (w/v) γ-PGA and 1.25×10 ⁻⁴ % (v/v) ClO ₂ . 9. The ophthalmic composition of claim 1, which is in a liquid state. 10. The ophthalmic composition according to claim 9, which is a contact lens care solution.