Gel eye pad for treating xerophthalmia as well as preparation method and application of gel eye pad

Abstract

The invention relates to the technical field of eye care products, in particular to a gel eye patch for treating xerophthalmia and a preparation method and application thereof.The preparation method comprises the steps that a gelatin solution, a carboxymethyl chitosan solution and a borneol solution are mixed, shaped and soaked, soaked gel is obtained, a gel matrix is placed on the soaked gel, the gel eye patch is obtained after soaking, and the gel eye patch is used for treating xerophthalmia. And soaking in a sodium sulfate solution for 30 minutes, and the mass percentage of the sodium sulfate solution is 15%. When the gel eye pad acts on the periphery of the eye, the borneol is combined with the transient receptor potential cation channel subfamily M member 8 on the ocular surface, so that the lacrimation is stimulated by activating the cold-sensitive primary afferent neuron. A layer of gel is added on the eye pad to prepare the double-layer gel eye pad. And the upper gel can be physically isolated, so that the irritation of the volatility of borneol to eyes is avoided. The traditional Chinese medicine composition can safely, quickly and effectively promote tear secretion of a patient suffering from the xerophthalmia, and irritation is effectively avoided while the xerophthalmia is treated.

Description

Technical Field

[0001] The invention relates to the technical field of eye care products, in particular to a gel eye patch for treating dry eyes and a preparation method and application thereof. Background Art

[0002] With the development of social economy, the frequency of using electronic devices has increased, and the number of people working at desks for long periods of time and working at close range has increased year by year. The incidence of dry eye syndrome has also increased year by year. The incidence of dry eye syndrome in my country has reached 21-30%. Dry eye syndrome can cause a lot of eye discomfort, such as dry eyes and itching. Some patients may even suffer from severe corneal epithelial damage, a large amount of eye secretions, conjunctival congestion, and serious eye lesions, which will seriously affect vision in the long run.

[0003] Dry eye is a series of syndromes caused by the lack of liquid components of the tear film due to abnormal mucus secretion and meibomian gland dysfunction. It is mainly divided into rapid tear evaporation and insufficient secretion. Therefore, the main symptom of dry eye patients is a significant decrease in tear secretion, which causes eye discomfort.

[0004] The breakthrough discovery of the menthol receptor TRPM8 channel has enriched people's understanding of cold-triggered neural perception and its mechanism of adaptation to environmental temperature. This achievement was awarded the Nobel Prize in Physiology or Medicine in 2021. Under physiological conditions, TRPM8 acts as a temperature channel for sensing cold stimuli, transmitting non-harmful temperature stimuli to initiate cold perception, thereby playing a role in regulating body temperature. The TRPM8 channel is activated at 8°C to 28°C, and the activity of TRPM8 increases when the temperature drops. In addition, TRPM8 can also be activated by cold stimuli such as menthol and borneol. This cold receptor sensory neuron exists on the surface of the human eye, can regulate tear secretion, and has many connections with the clinical manifestations of dry eyes.

[0005] Borneol is a processed product of the resin of the plant borneol of the Dipterocarpaceae family. It can also be synthesized by chemical methods such as camphor and turpentine. The "Tang Materia Medica" records the properties of borneol: "It tastes bitter and slightly cold." Borneol has the effects of opening all the orifices, dispersing stagnant fire, removing cataracts and improving eyesight, reducing swelling and relieving pain. It is mainly used to treat aphrodisiacs caused by stroke, coma caused by fever, epilepsy, phlegm, qi stagnation, deafness, laryngeal paralysis, mouth sores, otitis media, carbuncle, hemorrhoids, eye cataracts, and pinworm disease. The "Compendium of Materia Medica" by Li Shizhen, a doctor in the Ming Dynasty, records that borneol has the function of "opening all the orifices and dispersing stagnant fire." The "Compendium of Materia Medica" also records that "borneol is spicy, fragrant, good at dispersing and unblocking, and has a very quick effect. All diseases of sudden qi stagnation, phlegm and coma cannot be cured without it."

[0006] Invention patent CN117298073A relates to a transdermal pharmaceutical composition for treating dry eye, which contains low-concentration menthol as the only active ingredient and pharmaceutically acceptable excipients for dissolving menthol, and the mass concentration of menthol is 3%-10%. The pharmaceutical composition contains only low-concentration menthol, which can be used around the eyes (including the skin of the upper eyelid and lower eyelid), or the skin on both sides of the nose and the nasolabial groove, and can safely, quickly and effectively promote the tear secretion of dry eye patients themselves. This patent uses menthol as an active ingredient, while borneol as an active ingredient can have a stronger analgesic effect than menthol, and effectively treats the symptoms of red and swollen eyes caused by dry eye. In addition, the preparation of this patent is only to add menthol to liquid excipients such as vegetable oil to form a liquid preparation. The present invention is to load borneol into a gel, which is more convenient to use than applying a liquid preparation. Summary of the invention

[0007] In order to solve the above problems, the present invention provides a gel eye patch for treating dry eye, and a preparation method and application thereof. The present invention takes TRPM8 channel as a starting point, uses TRPM8 channel agonist borneol as an effective ingredient, and plays a role in promoting tear secretion and treating dry eye.

[0008] In order to achieve the above object, the present invention provides the following technical solutions:

[0009] The present invention provides a method for preparing a gel eye patch for treating dry eyes, comprising the following steps:

[0010] 1) mixing, shaping and soaking a gelatin solution, a carboxymethyl chitosan solution and a borneol solution to obtain an immersion gel;

[0011] The mass percentage of the gelatin solution is 20%;

[0012] The mass percentage of the carboxymethyl chitosan solution is 2%;

[0013] The mass percentage of the borneol solution is 5-15%;

[0014] The volume ratio of the gelatin solution, carboxymethyl chitosan solution and borneol solution is 10:1:0.25;

[0015] 2) placing the gel matrix on the soaking gel in step 1) to obtain a gel eye patch after soaking;

[0016] The steps 1) and 2) are both soaked in sodium sulfate solution for 30 minutes, and the mass percentage of the sodium sulfate solution is 15%.

[0017] Preferably, the mass percentage of the borneol solution in step 1) is 7-12%.

[0018] Preferably, the mass percentage of the borneol solution is 10%.

[0019] Preferably, the mixing conditions in step 1) include: temperature of 55° C., time of 10 min, and rotation speed of 300 rpm.

[0020] Preferably, the solvent of the gelatin solution in step 1) is water;

[0021] The solvent of the carboxymethyl chitosan solution is water;

[0022] The solvent of the borneol solution is N-methylpyrrolidone.

[0023] Preferably, in step 2), the volume ratio of the gel matrix to the soaking gel is 1:1.5.

[0024] Preferably, the components of the gel matrix include gelatin solution and carboxymethyl chitosan solution;

[0025] The mass percentage of the gelatin solution is 20%;

[0026] The mass percentage of the carboxymethyl chitosan solution is 2%;

[0027] The volume ratio of the gelatin solution to the carboxymethyl chitosan solution is 10:1.

[0028] The present invention also provides a gel eye patch prepared by the preparation method described in the above technical solution.

[0029] The present invention also provides the use of the gel eye patch described in the above technical solution in the preparation of a drug for treating dry eye.

[0030] The present invention also provides the use of the gel eye patch described in the above technical solution in the preparation of a medicine for prolonging the time of eye moistening.

[0031] The present invention applies the gel eye patch containing borneol to the skin around the eye (skin at the lower eyelid), can activate the TRPM8 receptor on the ocular surface, promote tear secretion, effectively treat dry eye, and is easy to use. The preparation process of the gel eye patch is simple, and the irritation and sensitization of the product to the skin are reduced.

[0032] The present invention uses gelatin and carboxymethyl chitosan as gel matrix, and does not need to add any crosslinking agent, and can form gel through physical crosslinking of the two. The Hofmeister effect, a phenomenon related to the type and concentration of salt ions, is used to enhance the hydrophobic interaction and mechanical properties of the gel.

[0033] Borneol acts on the thermoreceptor TRPM8 ion channel to allow Ca 2+It enters the cells and "tricks" the human nerves into feeling a cool sensation similar to cooling down, and promotes the secretion of tears to relieve dry eyes. There is a temperature difference between the gel and the skin, and heat exchange occurs, causing the skin temperature to drop and the gel temperature to rise, which accelerates the evaporation of water inside the gel, taking away a lot of heat and further reducing the temperature. This is based on the above-mentioned concept of nerve induction and the high specific heat capacity of water.

[0034] Beneficial effects of the present invention:

[0035] The preparation method of the gel eye patch proposed by the present invention does not involve any chemical reaction in the entire preparation process, but is achieved by physically cross-linking gelatin and carboxymethyl chitosan. Compared with the chemical cross-linking method, this method has the advantage of not containing chemical cross-linking agents that may cause toxicity, has high biosafety, and is conducive to biomedical or pharmacological applications; the gel with a three-dimensional network structure finally prepared is also a network structure formed by physical cross-linking, without any toxic side effects; and, through a suitable formula design, borneol is loaded into the hydrogel system, which can activate the TRPM8 receptor on the ocular surface, promote tear secretion, and relieve dry eye syndrome; in addition, a layer of blank matrix is ​​covered on the basis of the eye patch to physically isolate the volatility of the borneol and avoid irritation during use. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required to be used in the embodiments are briefly introduced below.

[0037] Figure 1 A schematic diagram of a gel eye patch;

[0038] Figure 2 This is the preliminary product image of the gel eye patch;

[0039] Figure 3 This is a cropped product image of the gel eye patch. DETAILED DESCRIPTION

[0040] The present invention provides a method for preparing a gel eye patch for treating dry eyes, comprising the following steps:

[0041] 1) mixing, shaping and soaking a gelatin solution, a carboxymethyl chitosan solution and a borneol solution to obtain an immersion gel;

[0042] The mass percentage of the gelatin solution is 20%;

[0043] The mass percentage of the carboxymethyl chitosan solution is 2%;

[0044] The mass percentage of the borneol solution is 5-15%;

[0045] The volume ratio of the gelatin solution, carboxymethyl chitosan solution and borneol solution is 10:1:0.25;

[0046] 2) placing the gel matrix on the soaking gel in step 1) to obtain a gel eye patch after soaking;

[0047] The steps 1) and 2) are both soaked in sodium sulfate solution for 30 minutes, and the mass percentage of the sodium sulfate solution is 15%.

[0048] The present invention mixes, shapes and soaks gelatin solution, carboxymethyl chitosan solution and borneol solution to obtain soaking gel; the mass percentage of the gelatin solution is 20%; the mass percentage of the carboxymethyl chitosan solution is 2%; the mass percentage of the borneol solution is 5-15%; the volume ratio of the gelatin solution, carboxymethyl chitosan solution and borneol solution is 10:1:0.25. In the present invention, the mass percentage of the borneol solution is preferably 7-12%. In the present invention, the mass percentage of the borneol solution is preferably 10%. The present invention has no special restrictions on the source of the borneol, and both natural borneol and artificial borneol are acceptable. In the present invention, the solvent of the gelatin solution is preferably water. The present invention preferably places gelatin in deionized water, swells at room temperature for half an hour, and then heats and dissolves at 60°C to obtain a gelatin solution. In the present invention, the solvent of the carboxymethyl chitosan solution is preferably water. In the present invention, the solvent of the borneol solution is preferably N-methylpyrrolidone. N-methylpyrrolidone has good solubility for borneol and good biocompatibility, and has been used as a solvent for periodontitis treatment drugs. In the present invention, the mixing conditions preferably include: temperature of 55°C, time of 10 minutes, and rotation speed of 300 rpm.

[0049] The present invention places the gel matrix on the soaking gel to obtain the gel eye patch after soaking. The present invention uses sodium sulfate solution for soaking, the soaking time is 30 minutes, and the mass percentage of the sodium sulfate solution is 15%.

[0050] In the present invention, the volume ratio of the gel matrix to the soaking gel is 1:1.5. The selected mold specifications are circular molds with a diameter of 35 mm and a diameter of 40 mm. The prepared soaking gel has a diameter of 35 mm and a thickness of about 2.3 mm. After adding the gel matrix, the diameter of the gel eye patch is 40 mm and the thickness is about 3 mm. In the present invention, the components of the gel matrix preferably include gelatin solution and carboxymethyl chitosan solution; the mass percentage of the gelatin solution is preferably 20%; the mass percentage of the carboxymethyl chitosan solution is preferably 2%; the volume ratio of the gelatin solution to the carboxymethyl chitosan solution is preferably 10:1.

[0051] The present invention also provides a gel eye patch prepared by the preparation method described in the above technical solution.

[0052] The present invention also provides the use of the gel eye patch described in the above technical solution in the preparation of a drug for treating dry eye.

[0053] The present invention also provides the use of the gel eye patch described in the above technical solution in the preparation of a medicine for prolonging the time of eye moistening.

[0054] In the present invention, the method of using the gel eye patch preferably includes: placing it on the skin around the eyes (skin at the lower eyelid) and leaving it on for 3-5 minutes.

[0055] In order to further illustrate the present invention, the present invention is described in detail below in conjunction with embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0056] Example 1

[0057] Single layer gel eye patch B1:

[0058] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0059] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 5%.

[0060] Step 3: Mix the gelatin solution, carboxymethyl chitosan solution and borneol solution in a volume ratio of 10:1:0.25 to obtain 2250 μL of a mixture; stir the mixture at 55° C. and 300 rpm for 10 min, inject the mixture into a mold with a diameter of 35 mm, and cool it.

[0061] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch B1 with a mass of 2 g.

[0062] Example 2

[0063] Single layer gel eye patch B2:

[0064] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0065] Step 2: dissolving borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 7%.

[0066] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0067] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch B2 with a mass of 2 g.

[0068] Example 3

[0069] Single layer gel eye patch B3:

[0070] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0071] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0072] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0073] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch B3 with a mass of 2 g.

[0074] Example 4

[0075] Single layer gel eye patch B4:

[0076] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0077] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 12%.

[0078] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0079] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch B4 with a mass of 2 g.

[0080] Example 5

[0081] Single layer gel eye patch B5:

[0082] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0083] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 15%.

[0084] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0085] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch B5 with a mass of 2 g.

[0086] Example 6

[0087] Double-layer gel eye patch B6:

[0088] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0089] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0090] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed in a volume ratio of 10:1:0.25 to obtain a mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0091] Step 4: De-molding the gel, soaking it in a 15% by mass sodium sulfate solution for 30 minutes to obtain a soaked gel eye patch with a mass of 2 g.

[0092] Step 5: Place the soaked gel eye patch in a mold with a diameter of 40 mm, add the blank matrix after mixing, heating and stirring the gelatin solution and carboxymethyl chitosan solution in a volume ratio of 10:1, and the volume ratio of the blank matrix to the soaked gel is 1:1.5, that is, the volume of the mixture in the mold is 3750 μL, cool, and demold. Soak in a 15% sodium sulfate solution for 30 minutes to obtain a double-layer gel eye patch B6 with a mass of 3.3 g. The mass percentage of the gelatin solution in step 5 is 20%, and the mass percentage of the carboxymethyl chitosan solution is 2%.

[0093] Comparative Example 1

[0094] Single layer gel eye patch C1:

[0095] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0096] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0097] Step 3: The gelatin solution and the borneol solution were mixed at a volume ratio of 11:0.25 to obtain a mixture of 2250 μL. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0098] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch C1.

[0099] Comparative Example 2

[0100] Single-layer gel eye patch C2:

[0101] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0102] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0103] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed in a volume ratio of 8:3:0.25 to obtain a mixture of 2250 μL. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0104] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch C2.

[0105] Comparative Example 3

[0106] Single-layer gel eye patch C3:

[0107] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0108] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0109] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 6:5:0.25 to obtain 2250 μL of a mixture, which was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold and cooled.

[0110] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch C3.

[0111] Comparative Example 4

[0112] Single-layer gel eye patch C4:

[0113] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, and borneol.

[0114] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0115] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0116] Step 4: De-molding the gel to obtain a single-layer gel eye patch C4.

[0117] Comparative Example 5

[0118] Single-layer gel eye patch C5:

[0119] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0120] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0121] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0122] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 3 hours to obtain a single-layer gel eye patch C5.

[0123] Comparative Example 6

[0124] Single-layer gel eye patch C6:

[0125] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 10% sodium sulfate solution by weight, and borneol.

[0126] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0127] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0128] Step 4: The gel was demoulded and immersed in a 10% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch C6.

[0129] Comparative Example 7

[0130] Single-layer gel eye patch C7:

[0131] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 20% sodium sulfate solution by weight, and borneol.

[0132] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0133] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0134] Step 4: The gel was demoulded and immersed in a 20% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch C7.

[0135] Comparative Example 8

[0136] Single-layer gel eye patch C8:

[0137] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium chloride solution by weight, and borneol.

[0138] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 10%.

[0139] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.25 to obtain 2250 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0140] Step 4: The gel was demoulded and immersed in a 15% by mass sodium chloride solution for 30 minutes to obtain a single-layer gel eye patch C8.

[0141] Comparative Example 9

[0142] Single-layer gel eye patch C9:

[0143] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0144] Step 2: dissolving borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 7%.

[0145] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.35 to obtain 2270 μL of a mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0146] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch C9.

[0147] Comparative Example 10

[0148] Single-layer gel eye patch C10:

[0149] Step 1: prepare raw materials, including 20% ​​gelatin solution by weight, 2% carboxymethyl chitosan solution by weight, 15% sodium sulfate solution by weight, and borneol.

[0150] Step 2: dissolve borneol in N-methylpyrrolidone to prepare a borneol solution with a mass percentage of 5%.

[0151] Step 3: The gelatin solution, carboxymethyl chitosan solution and borneol solution were mixed at a volume ratio of 10:1:0.5 to obtain 2300 μL of the mixture. The mixture was stirred at 55° C. and 300 rpm for 10 min, then injected into a mold with a diameter of 35 mm and cooled.

[0152] Step 4: The gel was demoulded and immersed in a 15% by mass sodium sulfate solution for 30 minutes to obtain a single-layer gel eye patch C10.

[0153] Test Example 1

[0154] The properties, forming properties, adhesion properties, tensile properties and stability of the borneol gel eye patches prepared in Examples 1 to 6 and Comparative Examples 1 to 10 were evaluated. The results are shown in Tables 1 and 2.

[0155] Evaluation method: Forming performance evaluation method, observe the difficulty of demoulding the gel eye patch, and whether the shape of the gel eye patch is complete after demoulding, whether there is any deformation or damage, and whether there are any bubbles.

[0156] Adhesion performance evaluation method: the gel eye patch is placed on the eye surface to observe its adhesion to the skin and whether it will fall off.

[0157] The tensile performance evaluation method is to stretch the eye patch to observe whether it can return to its original shape and whether the gel eye patch is damaged.

[0158] The stability evaluation method is to observe whether it can maintain its original shape at body temperature and whether it melts.

[0159] Evaluation criteria: Forming performance is divided into good (gel eye patch can be completely demolded without bubbles); fair (gel eye patch can be demolded, but the gel eye patch after demolding has defects, a few bubbles, or the gel swells or shrinks); poor (gel eye patch cannot be completely demolded from the mold).

[0160] Adhesion performance is divided into good (adheres to the skin without falling off, strong adhesion); fair (can adhere to the skin, but may fall off); poor (cannot adhere to the skin).

[0161] The tensile properties are divided into good (after stretching, it can return to its original shape without damage); fair (after stretching, it can return to its original shape with some damage); and poor (after stretching, it is completely damaged).

[0162] Stability is divided into good (maintains original shape at body temperature, does not melt, and exists stably); average (maintains original shape at body temperature, slightly melts, becomes sticky); poor (cannot maintain original shape at body temperature, melts)

[0163] Table 1 Evaluation results of the gel eye patches prepared in Examples 1 to 6

[0164]

[0165]

[0166] Table 2 Evaluation results of gel eye patches prepared in Comparative Examples 1 to 10

[0167] Forming performance Adhesion performance Tensile properties stability Single layer gel eye patch C1 generally good generally Poor Single layer gel eye patch C2 generally good good generally Single layer gel eye patch C3 generally good good generally Single layer gel eye patch C4 generally good Poor Poor Single layer gel eye patch C5 General (contraction) Poor good Poor Single layer gel eye patch C6 General (swelling) good Poor good Single layer gel eye patch C7 General (contraction) Poor good good Single layer gel eye patch C8 General (swelling) good Poor good Single layer gel eye patch C9 generally good generally generally Single layer gel eye patch C10 generally good Poor Poor

[0168] Conclusion: Although gelatin alone can be used as the eye patch matrix, it has poor stability at body temperature and will melt. When gelatin and carboxymethyl chitosan are selected as the matrix, hydrogen bonds can be generated between the two substances to form physical cross-links, which improves the stability of the eye patch. At body temperature, the eye patch can maintain its original shape. And considering the cost, when the volume ratio of gelatin to carboxymethyl chitosan is 10:1, the formability, adhesion, stretchability and stability can achieve a good effect.

[0169] Sodium sulfate solution can enhance the gel's formability and tensile properties after soaking, and the type, concentration, and soaking time of the salt solution will affect the properties of the eye patch. Specifically, when the concentration of sodium sulfate solution is lower than 15%, the gel eye patch will swell and the tensile properties will decrease after soaking for 30 minutes. When the concentration is higher than 15%, the gel eye patch will shrink and the adhesion properties will decrease after soaking for 30 minutes. When the concentration of sodium sulfate solution is fixed at 15%, the tensile properties increase significantly with the increase of soaking time, but it will also cause its adhesion properties to decrease. In addition, when the 15% sodium sulfate solution is changed to a 15% sodium chloride solution, the gel eye patch will also swell after soaking for 30 minutes. Therefore, 15% sodium sulfate solution and soaking for 30 minutes are selected as the final prescription for the preparation of gel eye patches.

[0170] In addition, increasing the volume of borneol solution added will be detrimental to its molding, but increasing the concentration of borneol without expanding its volume can ensure that the gel eye patch has a better molding effect. By investigating the volume of borneol solution added, it was found that when the volume ratio was gelatin: carboxymethyl chitosan: borneol solution = 10:1:0.25, the gel had a better molding result. After soaking in sodium sulfate solution for 30 minutes, the gel can have better tensile properties while maintaining adhesion properties.

[0171] Since comparative examples 1-10 have deficiencies in forming performance, adhesion performance, tensile performance, and stability, they are no longer examined in the subsequent test examples of the irritation and therapeutic effects of the eye patch.

[0172] Test Example 2

[0173] The skin irritation of the borneol gel eye patches prepared in Examples 1 to 6 was evaluated. The results are shown in Table 3.

[0174] Invite 5 volunteers to score the gel eye patch, and take the average of the scores.

[0175] The scoring criteria are as follows: 0 points (non-irritating); 1 point (almost non-irritating); 2 points (slightly irritating but acceptable); 3 points (irritating); the lower the score, the better the compliance, and the higher the score, the worse the compliance (n=5).

[0176] Table 3 Skin irritation of gel eye patches prepared in Examples 1 to 6

[0177]

[0178]

[0179] Test Example 3

[0180] The volatile irritation of the borneol gel eye patches of Examples 1 to 6 was evaluated. The results are shown in Table 4.

[0181] Invite 5 volunteers to score the gel eye patch, and take the average of the scores.

[0182] The scoring criteria are as follows: 0 points (non-irritating); 1 point (almost non-irritating); 2 points (slightly irritating but acceptable); 3 points (irritating); the lower the score, the better the compliance, and the higher the score, the worse the compliance (n=5).

[0183] Table 4 Volatile irritation of the gel eye patches prepared in Examples 1 to 6

[0184] Eye irritation Stimulus response scoring evaluate Blank Group No obvious abnormality 0 No odor Single layer gel eye patch B1 No obvious abnormality 0.2 Slight odor Single layer gel eye patch B2 No obvious abnormality 0.4 Slight odor Single layer gel eye patch B3 No obvious abnormality 0.6 Smell Single layer gel eye patch B4 No obvious abnormality 0.6 Smell Single layer gel eye patch B5 No obvious abnormality 0.8 Smell Double layer gel eye patch B6 No obvious abnormality 0.4 Slight odor

[0185] Conclusion: With the increase of borneol concentration, the borneol smell increases and the overall irritation score shows an upward trend, but the gel eye patch has no obvious irritation overall. Covering the gel eye patch with a layer of blank matrix can reduce the volatile smell of borneol and reduce its volatile irritation.

[0186] Test Example 4

[0187] The borneol gel eye patches prepared in Examples 1 to 6 were evaluated for relieving dry eye syndrome with eyes open. The results are shown in Table 5.

[0188] Invite 5 volunteers to rate the gel eye patch, and take the average of the scores. Also take the average of the time it takes for each volunteer to feel moist.

[0189] The scoring criteria are as follows: the therapeutic performance of the eye patch is scored on a 1-10 point scale, 1-3 points (weak cooling sensation, weak ability to relieve eye soreness and fatigue, weak moistening sensation, and weak overall comfort), 4-6 points (average cooling sensation, average ability to relieve eye soreness and fatigue, average moistening sensation, and average overall comfort), 7-10 points (obvious cooling sensation, obvious ability to relieve eye soreness and fatigue, obvious moistening sensation, and obvious overall comfort), the higher the score, the better the performance (n=5).

[0190] Table 5 Evaluation results of borneol gel eye patches prepared in Examples 1 to 6 for relieving dry eye syndrome with eyes open

[0191] Cooling sensation Improvement of eye fatigue Moist eyes Moisture sensation time Overall comfort rating Blank Group 2 1.2 0.8 / 4.4 Single layer gel eye patch B1 5.2 4.8 6.4 15min 5.6 Single layer gel eye patch B2 7 5 7.2 6min 30s 6.6 Single layer gel eye patch B3 8.2 7.4 8.4 3min 35s 8.6 Single layer gel eye patch B4 8.8 7.2 8.4 3min 20s 7.4 Single layer gel eye patch B5 8.8 7.4 8.6 2min 45s 7.6 Double layer gel eye patch B6 8.2 7.6 8.4 3min 33s 8.8

[0192] Conclusion: As the concentration of borneol increases, the cooling effect of the gel eye patch and the moist feeling of the eyes are enhanced, and the time for the eyes to produce moist feeling is shortened. However, as the concentration of borneol increases, its skin irritation and volatile irritation will also increase, and the overall comfort score will also decrease. Therefore, the single-layer gel eye patch B3, that is, when the borneol concentration is 10%, can produce better cooling effect and eye moist feeling, and the overall comfort is also higher. In addition, in the existing product compound betamethasone camphor milk, its specification is 5mg in 1g, while the single-layer gel eye patch B3 has a mass of 2g and contains 5mg of borneol. Therefore, the borneol content of the gel eye patch is within the safe range and has a certain degree of biosafety.

[0193] Test Example 5

[0194] The borneol gel eye patches prepared in Examples 1 to 6 were evaluated for relieving dry eye syndrome in a closed-eye state. The results are shown in Table 6.

[0195] Invite 5 volunteers to rate the gel eye patch, and take the average of the scores. Also take the average of the time it takes for each volunteer to feel moist.

[0196] The scoring criteria are as follows: the therapeutic performance of the eye patch is scored on a 1-10 point scale, 1-3 points (weak cooling sensation, weak ability to relieve eye soreness and fatigue, weak moistening sensation, and weak overall comfort), 4-6 points (average cooling sensation, average ability to relieve eye soreness and fatigue, average moistening sensation, and average overall comfort), 7-10 points (obvious cooling sensation, obvious ability to relieve eye soreness and fatigue, obvious moistening sensation, and obvious overall comfort), the higher the score, the better the performance (n=5).

[0197] Table 6 Evaluation results of borneol gel eye patches prepared in Examples 1 to 6 for relieving dry eye syndrome in the closed eye state

[0198] Cooling sensation Improvement of eye fatigue Moist eyes Moisture sensation time Overall comfort rating Blank Group 2 1.2 0.8 / 2 Single layer gel eye patch B1 5.2 4.8 6.4 15min 32s 5.4 Single layer gel eye patch B2 7 5.2 7.2 6min 7 Single layer gel eye patch B3 8.2 7.6 8.4 3min 35s 8.2 Single layer gel eye patch B4 8.6 7.4 8.4 3min 20s 8.8 Single layer gel eye patch B5 8.8 7.4 8.6 3min 8.8 Double layer gel eye patch B6 8.2 7.6 8.4 3min 33s 8.2

[0199] Conclusion: When the eyes are closed, the gel eye patch still has good therapeutic properties, which shows that the gel eye patch does not stimulate the eyes through the volatilization of borneol to promote tear secretion, but the borneol acts on the temperature receptor TRPM8 ion channel. This is because when the gel eye patch is placed on the lower eyelid, there will be a corresponding cool feeling, and this cool feeling is produced by the activation of the TRPM8 receptor, that is, by stimulating the human nerves, sensing a cool experience similar to cooling, thereby further stimulating the secretion of tears.

[0200] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing a gel eye patch for treating dry eyes, characterized in that: The following steps are involved: 1) mixing, shaping and soaking a gelatin solution, a carboxymethyl chitosan solution and a borneol solution to obtain an immersion gel; The mass percentage of the gelatin solution is 20%; The mass percentage of the carboxymethyl chitosan solution is 2%; The mass percentage of the borneol solution is 5-15%; The volume ratio of the gelatin solution, carboxymethyl chitosan solution and borneol solution is 10:1:0.25; 2) placing the gel matrix on the soaking gel in step 1) to obtain a gel eye patch after soaking; The steps 1) and 2) are both soaked in sodium sulfate solution for 30 minutes, and the mass percentage of the sodium sulfate solution is 15%.

2. The preparation method according to claim 1, characterized in that: The mass percentage of the borneol solution in step 1) is 7-12%.

3. The preparation method according to claim 1 or 2, characterized in that: The mass percentage of the borneol solution is 10%.

4. The preparation method according to claim 1, characterized in that: The mixing conditions in step 1) include: temperature of 55° C., time of 10 min, and rotation speed of 300 rpm.

5. The preparation method according to claim 1, characterized in that: The solvent of the gelatin solution in step 1) is water; The solvent of the carboxymethyl chitosan solution is water; The solvent of the borneol solution is N-methylpyrrolidone.

6. The preparation method according to claim 1, characterized in that: In the step 2), the volume ratio of the gel matrix to the soaking gel is 1:1.

5.

7. The preparation method according to claim 1 or 6, characterized in that: The components of the gel matrix include gelatin solution and carboxymethyl chitosan solution; The mass percentage of the gelatin solution is 20%; The mass percentage of the carboxymethyl chitosan solution is 2%; The volume ratio of the gelatin solution to the carboxymethyl chitosan solution is 10:

1.

8. A gel eye patch prepared by the preparation method according to any one of claims 1 to 7.

9. Use of the gel eye patch according to claim 8 in the preparation of a drug for treating dry eye.

10. Use of the gel eye patch according to claim 8 in the preparation of a drug for prolonging the time of eye moistening.

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