Low-irritation preservative-free eye lotion and preparation method thereof
By combining low-irritant soothing and antioxidant active ingredients with moisturizing and lubricating polymers, along with osmotic pressure regulators and pH stabilizers, a preservative-free eye drop has been prepared. This solves the problems of packaging waste and eye health associated with eye drops, achieving both immediate soothing and long-lasting moisturizing effects.
Patent Information
- Application Number
- CN202510879571.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-27
- Publication Date
- 2025-10-31
AI Technical Summary
Existing eye drops have packaging waste issues, single-dose types are costly, and multi-dose types contain preservatives that are harmful to eye health, and long-term use can cause eye inflammation.
This eye drop is formulated using a combination of low-irritant, soothing, and antioxidant active ingredients and moisturizing and lubricating polymers, along with osmotic pressure regulators and pH stabilizers. It avoids the use of preservatives and is prepared through a specific process to ensure antibacterial effects and gentleness.
It achieves a fast and long-lasting moisturizing effect during use, relieving eye fatigue and dryness, providing long-lasting hydration, inhibiting microbial growth, and is preservative-free and non-irritating to the eyes. It also meets the body's osmotic pressure to ensure eye health.
Smart Images
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of eye drops technology, specifically relating to a low-irritant and preservative-free eye drop and its preparation method. Background Technology
[0002] With the widespread use of electronic products, prolonged use of electronic devices is more likely to cause irreversible damage to the eyes, exacerbating problems such as vision loss, dry and tired eyes, and increasing the risk of developing retinal diseases.
[0003] To alleviate eye discomfort, more and more people are using eye drops or lubricating eye products. These products are typically packaged in both single-dose and multi-dose types. Single-dose products use disposable packaging to control microorganisms and usually do not require preservatives, but this method is costly, wasteful of packaging materials, and requires a high-quality production environment. Multi-dose products usually require preservatives to prevent microbial growth during their use (common preservatives include quaternary ammonium salts such as benzalkonium chloride and benzalkonium bromide; alcohols such as benzyl alcohol and chlorobutanol; and acids such as sorbic acid). However, clinical studies have shown that long-term use of preservative-containing eye drops can cause varying degrees of pathological changes in patients' eyes, such as tear film instability, ocular surface inflammation, and a reduction in the number of subbasal nerves.
[0004] Eye drops need to be safe and have low irritation, so it's necessary to find an ingredient that can replace existing preservatives to improve the formula's preservative effect, while also being gentle enough not to irritate the eyes. The active ingredients in eye drops should effectively improve eye fatigue and provide long-lasting relief from eye discomfort. Summary of the Invention
[0005] To address the shortcomings of existing technologies, this invention provides a low-irritant, preservative-free eye drop and its preparation method. This invention addresses the problems of single-dose eye drops leading to packaging waste and multi-dose eye drops containing preservatives, which can be detrimental to eye health with long-term use. The low-irritant, preservative-free eye drop provided by this invention has shown good performance in consumer trial ratings and antibacterial performance tests. It is non-irritating to the eyes and contains ingredients that effectively inhibit microbial growth, ensuring that the eye drop will not breed microorganisms during its shelf life without compromising its gentleness.
[0006] The technical solution provided by this invention is as follows:
[0007] A low-irritant, preservative-free eye drop, comprising at least:
[0008] Soothing and antioxidant active ingredients and / or moisturizing and lubricating polymers;
[0009] And deionized water;
[0010] The weight percentage of the soothing and antioxidant active ingredient is 0.001-5 wt%.
[0011] The weight percentage of the moisturizing and lubricating polymer is 0.01-1 wt%.
[0012] Both soothing and antioxidant active ingredients and moisturizing and lubricating polymers help relieve eye fatigue and dryness. However, when only soothing and antioxidant active ingredients are added, the soothing effect is only noticeable for a short time after application. In contrast, the moisturizing and lubricating polymers do not have a noticeable soothing effect immediately after application, but their effect is longer-lasting, providing long-lasting moisturization and lubrication. The combination of the two can provide a quick and long-lasting moisturizing effect during use.
[0013] Specifically, the soothing and antioxidant active ingredients are selected from one or more of the following: blueberry extract, cassia seed extract, scutellaria baicalensis extract, centella asiatica extract, houttuynia cordata extract, chamomile extract, buddleja officinalis extract, tea polyphenol extract, wolfberry extract, wild chrysanthemum extract, or lutein.
[0014] In the above technical solutions, each soothing and antioxidant active ingredient helps to immediately relieve eye fatigue.
[0015] Specifically, the moisturizing and lubricating polymer is selected from one or more of sodium hyaluronate, hydroxyethyl cellulose, polyethylene glycol, chitosan, carboxymethyl cellulose, hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, or polyacrylic acid.
[0016] In the above technical solutions, each moisturizing and lubricating polymer can provide long-lasting lubrication and moisturizing effects to the eyes, effectively relieving dry eyes.
[0017] Preferred:
[0018] Low-irritant and preservative-free eye drops contain soothing antioxidant actives, moisturizing and lubricating polymers, and deionized water;
[0019] The soothing and antioxidant active ingredients are one or more combinations of Centella asiatica extract, Buddleja officinalis extract, and lutein.
[0020] The moisturizing and lubricating polymer is one or more of sodium hyaluronate, carboxymethyl cellulose, and polyvinyl alcohol.
[0021] Based on the above technical solution: low-irritant and preservative-free eye drops not only provide rapid and long-lasting moisturizing effects during use, but also have outstanding soothing effects and can effectively remove redness.
[0022] Furthermore, the low-irritant and preservative-free eye drops also include p-hydroxybenzophenone, wherein the weight percentage of p-hydroxybenzophenone is 0.1-0.3 wt%, and the p-hydroxybenzophenone is one or both of p-hydroxyacetophenone or p-hydroxybutanone.
[0023] The inventors discovered that adding one or both of p-hydroxyacetophenone or p-hydroxybutanone can effectively inhibit the growth of microorganisms, ensuring the sterility of the eye drops during their shelf life. Furthermore, at this concentration, p-hydroxyacetophenone does not affect the mildness of the eye drops system, and it is essentially non-irritating when applied to the eyes.
[0024] Furthermore, the low-irritant and preservative-free eye drops also include an osmotic pressure regulator, wherein the osmotic pressure regulator has a weight percentage of 0.8-0.9 wt%, and the osmotic pressure regulator is sodium chloride or potassium chloride. The osmotic pressure regulator adjusts the osmotic pressure of the eye drops to 280-320 mOsm / L, consistent with the osmotic pressure of human blood plasma, ensuring that the eye drops will not affect the activity of eye cells.
[0025] Furthermore, the low-irritant and preservative-free eye drops also include a pH stabilizer, the amount of which is used to adjust the pH to 6-8, close to the pH of human tears, and the pH stabilizer is a phosphate buffer solution.
[0026] Furthermore, the low-irritant and preservative-free eye drops also include a solubilizer selected from one or a combination of two of hydrogenated castor oil and glycerin. The total mass of the solubilizer is 3-5 times that of the oil-soluble active ingredient, enabling the oil-soluble active ingredient to dissolve in water into a homogeneous and transparent solution.
[0027] Furthermore, low-irritant and preservative-free eye drops do not contain preservatives.
[0028] The present invention also provides a method for preparing a low-irritant and preservative-free eye drop. In the method, p-hydroxybenzophenone is pre-dissolved in a water bath at 50°C, and then the components are mixed at room temperature, filtered, and the clear liquid is collected to obtain a clear and transparent eye drop.
[0029] The beneficial effects of this invention are as follows:
[0030] 1. The eye drops of the present invention contain soothing and antioxidant active ingredients and moisturizing and lubricating polymers, which can relieve eye discomfort immediately and moisturize for a long time, have a certain moisturizing effect on the eyes, and effectively relieve eye fatigue.
[0031] 2. It contains no preservatives and will not harm eye health with long-term use. Detailed Implementation
[0032] The principles and features of the present invention are described below. The embodiments given are only for explaining the present invention and are not intended to limit the scope of the present invention.
[0033] Unless otherwise specified, the test methods used in the embodiments are conventional methods; unless otherwise specified, the materials and reagents used are commercially available.
[0034] Blueberry extract, cassia seed extract, scutellaria baicalensis extract, centella asiatica extract, houttuynia cordata extract, chamomile extract, buddleja officinalis extract, tea polyphenol extract, wolfberry extract, and wild chrysanthemum extract are all available for purchase.
[0035] Example 1
[0036] A low-irritant, preservative-free eye drop is composed of the following ingredients: Centella asiatica extract 1wt%, sodium hyaluronate 0.05wt%, glycerin 0.15wt%, sodium chloride 0.85wt%, p-hydroxyacetophenone 0.2wt%, a suitable amount of phosphate buffer solution to stabilize the pH between 7.1 and 7.3, and the balance being deionized water. Centella asiatica has a soothing and moisturizing effect, while sodium hyaluronate has a lubricating and moisturizing effect, providing long-lasting hydration. The addition of p-hydroxyacetophenone inhibits the growth of microorganisms in the eye drop. Microbial detection results of the sample in Example 1: initial contamination bacteria <1 cfu / ml, molds and yeasts <1 cfu / ml, pathogenic bacteria not detected. Sterility testing was performed according to the sterility test method in the Chinese Pharmacopoeia, and the result was sterile on day 14.
[0037] Example 2
[0038] A low-irritant, preservative-free eye drop is composed of the following ingredients: Centella asiatica extract 1 wt%, glycerin 0.15 wt%, sodium chloride 0.85 wt%, p-hydroxyacetophenone 0.2 wt%, a suitable amount of phosphate buffer solution to stabilize the pH between 7.1 and 7.3, and the balance being deionized water. Centella asiatica has a soothing and moisturizing effect; the addition of p-hydroxyacetophenone inhibits the growth of microorganisms in the eye drop. Microbial detection results of the sample in Example 2: initial contamination bacteria <1 CFU / ml, molds and yeasts <1 CFU / ml, pathogenic bacteria not detected. Sterility testing was performed according to the sterility test method in the Chinese Pharmacopoeia, and the result was sterile on day 14.
[0039] Example 3
[0040] A low-irritant, preservative-free eye drop is composed of the following ingredients: 0.05 wt% sodium hyaluronate, 0.15 wt% glycerin, 0.85 wt% sodium chloride, 0.2 wt% p-hydroxyacetophenone, a suitable amount of phosphate buffer solution to stabilize the pH between 7.1 and 7.3, and the balance being deionized water. Sodium hyaluronate has a lubricating and moisturizing effect, providing long-lasting hydration; the addition of p-hydroxyacetophenone inhibits the growth of microorganisms in the eye drop. Microbial detection results of the sample in Example 3: initial contamination bacteria <1 CFU / ml, molds and yeasts <1 CFU / ml, pathogenic bacteria not detected. Sterility testing was performed according to the sterility test method in the Chinese Pharmacopoeia, and the result was sterile on day 14.
[0041] Example 4
[0042] This low-irritant, preservative-free eye drop is composed of the following ingredients: 0.01 wt% lutein, 0.5 wt% Buddleja officinalis extract, 0.5 wt% carboxymethyl cellulose, 0.05 wt% hydrogenated castor oil, 0.85 wt% sodium chloride, 0.1 wt% p-hydroxyacetophenone, 0.1 wt% p-hydroxybutanone, a suitable amount of phosphate buffer solution to stabilize the pH between 7 and 7.2, and the balance being deionized water. Buddleja officinalis extract has heat-clearing and detoxifying effects, helping to eliminate eye inflammation and reduce symptoms such as redness, swelling, and pain. Lutein, a type of vitamin also known as plant lutein, is the main pigment in the macular region of the human retina and helps nourish normal vision. Carboxymethyl cellulose increases the viscosity of tears, prolonging their residence time on the ocular surface, helping to keep the eyes moist and providing long-lasting lubrication to reduce dryness. Example 4: Microbial test results of the sample: initial contaminating bacteria <1 cfu / ml, molds and yeasts <1 cfu / ml, pathogenic bacteria not detected. Sterility testing was performed according to the sterility test method in the Chinese Pharmacopoeia, and the result was sterility on day 14.
[0043] Example 5
[0044] A low-irritant, preservative-free eye drop is composed of the following ingredients: 0.01 wt% lutein, 0.5 wt% Buddleja officinalis extract, 0.05 wt% hydrogenated castor oil, 0.85 wt% sodium chloride, 0.1 wt% p-hydroxyacetophenone, 0.1 wt% p-hydroxybutanone, a suitable amount of phosphate buffer solution to stabilize the pH between 7 and 7.2, and the balance being deionized water. Buddleja officinalis extract has a heat-clearing and detoxifying effect, which can help eliminate eye inflammation and reduce symptoms such as redness, swelling, and pain in the eyes. Lutein is a type of vitamin, also known as plant lutein, and is the main pigment in the macular region of the human retina, helping to nourish the eyes and maintain normal vision. Example 5: Sample microbial test results: initial contaminating bacteria <1 cfu / ml, mold and yeast <1 cfu / ml, pathogenic bacteria not detected. Sterility testing was performed according to the sterility test method in the Chinese Pharmacopoeia, and the result was sterile on day 14.
[0045] Example 6
[0046] A low-irritant, preservative-free eye drop is composed of the following ingredients: 0.5 wt% carboxymethyl cellulose, 0.05 wt% hydrogenated castor oil, 0.85 wt% sodium chloride, 0.1 wt% p-hydroxyacetophenone, 0.1 wt% p-hydroxybutanone, a suitable amount of phosphate buffer solution to stabilize the pH between 7 and 7.2, and the balance being deionized water. Carboxymethyl cellulose increases the viscosity of tears, prolonging their residence time on the ocular surface, helping to maintain eye moisture, providing long-lasting lubrication, and reducing eye dryness. Example 6: Microbiological test results: initial contaminating bacteria <1 CFU / ml, molds and yeasts <1 CFU / ml, pathogenic bacteria not detected. Sterility testing was performed according to the sterility test method in the Chinese Pharmacopoeia, and the result was sterile on day 14.
[0047] The above embodiments were subjected to relevant tests.
[0048] 1. Cytotoxicity test
[0049] ① L-929 cells were cultured in MEM medium containing 10% fetal bovine serum and penicillin (100 U / mL, streptomycin 100 μg / mL) and incubated at 37°C in a 5% CO2 incubator. Cells were digested with 0.25% trypsin (containing EDTA) to prepare a single-cell suspension, and the cell concentration was adjusted to 1×10⁻⁶ cells / mL. 5 per mL, prepare 1×10 5 Cell suspension of 100 μL / mL was seeded into 96-well culture plates. A negative control (complete culture medium), a positive control (complete culture medium containing 10% DMSO), and diluted samples of eye drops from Examples 1-6 (the eye drops samples from Examples 1-6 were diluted with the complete culture medium at a volume ratio of 1:10) were set up. Each group had 6 parallel wells, and 100 μL of cell suspension was seeded into each well.
[0050] ② After incubating in a CO2 incubator (containing 5% carbon dioxide gas by volume, the same below) at 37°C for 24 hours, discard the original culture medium. Add 100 μL of the eye drops used in Examples 1-6 to dilute the sample, negative control (complete culture medium), and positive control (containing 10% DMSO complete culture medium), respectively, and continue to incubate in a 37°C, 5% CO2 incubator for 24 hours. Observe the cell morphology under a microscope.
[0051] ③ After 24 hours of incubation, discard the supernatant, add 50 μL of 1 mg / mL MTT solution to each well, and continue incubation at 37°C in a 5% CO2 incubator for 2 hours. Then, remove the supernatant, add 100 μL of isopropanol, and shake on a shaker until the crystals are completely dissolved. Measure the absorbance using a microplate reader with 570 nm as the main absorption wavelength and 650 nm as the reference wavelength.
[0052] ④ Calculate cell viability using the following formula:
[0053]
[0054] OD a The absorbance values (OD) represent the positive control group and the eye drop sample group. b The absorbance value represents the negative control group. If the cell viability is <70%, it indicates that the sample has potential cytotoxicity.
[0055] ⑤ The cell viability of the samples in the final examples 1-6 was all above 93%, indicating no cytotoxicity.
[0056] 2. Skin irritation patch test
[0057] Using sodium lauryl sulfate (SLS) as an irritant, an inflammatory lesion model was established using a 3% high concentration and a skin occlusion patch method to evaluate the soothing efficacy of the samples.
[0058] Qualified spot testing devices with an area not exceeding 50 mm and a depth of approximately 1 mm were selected. A blank control group was set up using physiological saline, a positive control group using 3% SLS solution, and a sample group consisting of a mixture of the eye drops from Examples 1-6 and 3% SLS. The blank control group, positive control group, and sample group were placed in their respective spot testing device chambers, with each group using approximately 0.020 mL-0.025 mL. All spot testing devices were applied to the flexor side of the subject's forearm using hypoallergenic adhesive tape, and the palm was gently pressed to ensure even application to the skin for 24 hours. Skin reactions were observed and recorded according to the standards in Table 1 30 minutes after removing the test substance spot testing devices (until the indentation disappeared).
[0059] 1. Test subjects: 26 healthy adult subjects, regardless of gender, all subjects had no skin diseases and the skin in the test area was intact.
[0060] 2. Test area: forearm.
[0061] 3. Time: Comprehensive evaluation after 24 hours of use.
[0062] 4. Groups: Sample group (3% SLS and sample mixture), blank control group (physiological saline), positive control group (3% SLS solution).
[0063] 5. Evaluation method: Questionnaires will be filled out with rating levels, and the final scores will be the average of the scores.
[0064] 6. The grading criteria for skin reaction in the skin occlusion patch test are shown in Table 1 below:
[0065] Table 1. Grading of skin reactions in patch tests
[0066]
[0067]
[0068] The soothing effects of Examples 1-6 are evaluated in Table 2 below.
[0069] Group total mean Example 1 0 0 Example 2 10 0.4 Example 3 13 0.5 Example 4 13 0.5 Example 5 10 0.4 Example 6 18 0.7 Blank control group 0 0 Positive control group 70 2.7
[0070] The results of the skin irritation patch test showed that the samples in Examples 1-6 all had a certain soothing effect, with Example 1 showing the most obvious effect, which was no different from the blank control group.
[0071] 3. Consumer testing:
[0072] Ten subjects with symptoms of eye fatigue, dryness, and low tear secretion were selected through a tear secretion experiment. Both commercially available eye drops (product a) and samples b from Examples 1-6 were used. The trial method was as follows: After using a computer and experiencing eye fatigue and dryness, one drop of product a was instilled into the left eye, and one drop of product b was simultaneously instilled into the right eye. The effectiveness of the eye drops in relieving eye fatigue and dryness, as well as their irritation levels, were assessed immediately after application (1 minute) and 60 minutes later. Subjects provided their subjective descriptions and ratings. When the subjects experienced eye fatigue and dryness again, one drop of product b was instilled into the left eye, and one drop of product a was simultaneously instilled into the right eye. The effectiveness of the eye drops in relieving eye fatigue and dryness, as well as their irritation levels, were assessed immediately after application (1 minute) and 60 minutes later. The average score from the two evaluations was calculated (out of 10 points; a higher score indicates higher satisfaction).
[0073] Sample Name 1-minute rating 60min rating Irritating Effect on reducing redness Commercially available product a 6.3 6.7 8.3 8.0 Example 1 Sample 9.0 8.9 9.1 9.5 Example 2 Sample 8.5 7.4 8.9 8.5 Example 3 Sample 7.7 8.8 9.0 8.4 Example 4 Sample 8.8 8.3 9.0 8.8 Example 5 Sample 8.7 7.2 9.0 8.2 Example 6 Sample 7.1 8.3 8.8 8.2
[0074] Trial results show that the low-irritant, preservative-free eye drops provided by this invention have lower irritation levels than commercially available products (whose main ingredients include sodium hyaluronate, trehalose, and vitamin A). Both the soothing and antioxidant active ingredients and the moisturizing and lubricating polymer help relieve eye fatigue and dryness. However, the soothing and antioxidant active ingredients alone only provide a noticeable soothing effect for a short period after application, while the moisturizing and lubricating polymer does not provide a noticeable soothing effect immediately after application, but its effect is longer-lasting, providing long-lasting moisturizing and lubrication.
[0075] Meanwhile, we also found that Centella asiatica extract, in synergy with sodium hyaluronate, has a significant advantage in reducing redness as shown in the table above, indicating that Centella asiatica and sodium hyaluronate have a good soothing effect, which is consistent with the conclusion of the patch experiment.
[0076] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A low-irritant and preservative-free eye drop, characterized in that, At least including: Soothing and antioxidant active ingredients and / or moisturizing and lubricating polymers; And deionized water; The weight percentage of the soothing and antioxidant active ingredient is 0.001-5 wt%. The weight percentage of the moisturizing and lubricating polymer is 0.01-1 wt%.
2. The low-irritation and preservative-free eye drops according to claim 1, characterized in that: The soothing and antioxidant active ingredients are selected from one or more of the following: blueberry extract, cassia seed extract, scutellaria baicalensis extract, centella asiatica extract, houttuynia cordata extract, chamomile extract, buddleja officinalis extract, tea polyphenol extract, wolfberry extract, wild chrysanthemum extract, or lutein.
3. The low-irritation and preservative-free eye drops according to claim 1, characterized in that: The moisturizing and lubricating polymer is selected from one or more of sodium hyaluronate, hydroxyethyl cellulose, polyethylene glycol, chitosan, carboxymethyl cellulose, hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, or polyacrylic acid.
4. The low-irritation and preservative-free eye drops according to claim 1, characterized in that: The low-irritant and preservative-free eye drops comprise at least a soothing and antioxidant active ingredient, a moisturizing and lubricating polymer, and deionized water. The soothing and antioxidant active ingredients are one or more combinations of Centella asiatica extract, Buddleja officinalis extract, and lutein. The moisturizing and lubricating polymer is one or more of sodium hyaluronate, carboxymethyl cellulose, and polyvinyl alcohol.
5. The low-irritant and preservative-free eye drops according to any one of claims 1 to 4, characterized in that: It also includes p-hydroxybenzophenone, wherein the p-hydroxybenzophenone has a weight percentage of 0.1-0.3 wt%; The p-hydroxyacetone is one or both of p-hydroxyacetophenone or p-hydroxybutanone.
6. The low-irritant and preservative-free eye drops according to any one of claims 1 to 4, characterized in that: It also includes an osmotic pressure regulator, wherein the osmotic pressure regulator has a weight percentage of 0.8-0.9 wt%; The osmotic pressure regulator is sodium chloride or potassium chloride.
7. The low-irritant and preservative-free eye drops according to any one of claims 1 to 4, characterized in that: It also includes a pH stabilizer, which is a phosphate buffer solution, and the pH value of the low-irritant and preservative-free eye drops is 6-8.
8. The low-irritant and preservative-free eye drops according to any one of claims 1 to 4, characterized in that: It also includes a solubilizer, the amount of which is 3-5 times the total weight of the oil-soluble soothing and antioxidant active ingredients and the oil-soluble moisturizing and lubricating polymer.
9. The low-irritation and preservative-free eye drops according to claim 8, characterized in that: The solubilizer is selected from one or a combination of two of hydrogenated castor oil or glycerin.
10. A method for preparing a low-irritant and preservative-free eye drop according to any one of claims 1 to 9, characterized in that: Mix the components at room temperature.