Application of canthaxanthin in preparation of medicine for treating and / or relieving xerophthalmia

Abstract

The invention provides application of canthaxanthin in preparation of a medicine for treating and / or relieving xerophthalmia, and relates to the technical field of medicine. According to the application, the distribution condition of an eye tissue structure drug target TMEM16A ion channel is researched, a TMEM16A conditional knockout mouse is constructed through a gene knockout means, and through research on the treatment effect of the knockout mouse, it is verified that canthaxanthin can serve as an activator of the TMEM16A ion channel, and the canthaxanthin can be used as an activator of the TMEM16A ion channel. Therefore, the purpose of application in preparation of the medicine for treating and / or relieving xerophthalmia is achieved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to the use of a canthaxanthin in the preparation of medicaments for treating and / or relieving dry eye syndrome. Background Technology

[0002] Dry eye syndrome, also known as keratoconjunctivitis sicca, is a group of diseases characterized by decreased tear film stability, accompanied by ocular surface discomfort symptoms, visual changes, tear film instability and potential ocular surface damage, as well as increased tear osmotic pressure and ocular surface inflammation, thus leading to eye discomfort symptoms.

[0003] Currently, clinical medications for treating dry eye can be broadly categorized into two types: (I) Artificial tear replacement therapy and secretagogues. There are many types of artificial tears, which can be classified as those that replenish the aqueous component, mucin component, and lipid component of the tear film. (II) Ocular surface anti-inflammatory drugs. Immune-related inflammatory cascades are key factors in the occurrence and development of dry eye. Existing anti-inflammatory drugs include glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and immunosuppressants such as cyclosporine and tacrolimus.

[0004] However, existing medications for treating dry eye have certain drawbacks, including: (1) Frequent use of artificial tears may damage the cornea, and the preservatives they contain may also cause some irritation to the eyes; (2) Frequent use of eye drops may lead to drug dependence, resulting in insufficient secretion of the body's own lubricating fluid and a decline in the body's own lubricating fluid secretion function; (3) If hygiene is not properly maintained during long-term use, pathogens may enter the eye, which may easily induce conjunctivitis and cause adverse symptoms such as swelling and pain in the eye area; (4) Anti-inflammatory drugs for the ocular surface, such as cyclosporine, may cause eye irritation. If used improperly, they may cause eye infection, which may cause redness, swelling, and pain in the patient's eyes. Patients may develop chronic inflammation of the ocular surface, and in severe cases, they may also cause symptoms such as tearing and congestion, which may also have a certain impact on the patient's vision.

[0005] In view of this, the present invention is hereby proposed. Summary of the Invention

[0006] The purpose of this invention is to provide the use of canthaxanthin (hereinafter referred to as CX) in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0007] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted: In a first aspect, the present invention provides the use of canthaxanthin in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0008] Furthermore, the use of the flavin as an activator of the TMEM16A ion channel in the preparation of drugs for the prevention and / or treatment of dry eye syndrome.

[0009] Furthermore, the TMEM16A ion channels are distributed in the cornea, fornix conjunctiva, bulbar conjunctiva, lacrimal gland, palpebral conjunctiva, and meibomian gland.

[0010] Furthermore, the use of the canthaxanthin as an agent to increase tear secretion in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0011] Furthermore, the use of the flavin as an agent for improving corneal epithelial damage in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0012] Furthermore, the use of the flavin as an agent for increasing corneal epithelial thickness in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0013] Furthermore, the use of the canthaxanthin as a reagent for reducing the expression level of inflammatory factors in corneal tissue in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0014] Furthermore, the inflammatory factors include any one or a combination of at least two of IL-1β, TNF-α, or IL-6.

[0015] Furthermore, the use of the canthaxanthin as an agent for increasing the number of conjunctival goblet cells in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0016] Furthermore, the use of the canthaxanthin as an agent for reducing the infiltration of inflammatory cells in the lacrimal gland in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0017] Secondly, the present invention provides the application of the TMEM16A ion channel as a target in the preparation of drugs for treating and / or alleviating dry eye syndrome.

[0018] Thirdly, the present invention provides a medicament for treating and / or relieving dry eye syndrome, the medicament comprising canthaxanthin; and the concentration of canthaxanthin used is 50~200 μM.

[0019] Furthermore, the drug is a topical preparation, which is administered through ocular treatment.

[0020] Furthermore, the topical preparation includes any one of eye drops, eye wash, eye drops solution, eye gel, eye ointment, or eye patch.

[0021] Furthermore, the drug also includes pharmaceutically acceptable excipients.

[0022] Compared with the prior art, the present invention has the following beneficial effects: This invention investigated the distribution of the TMEM16A ion channel, a drug target in ocular tissue structures, and found that the flavonoid can act as an activator of the TMEM16A ion channel, thus achieving its purpose of application in the preparation of drugs for treating and / or relieving dry eye syndrome. Attached Figure Description

[0023] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0024] Figure 1 This is a diagram showing the distribution of TMEM16A ion channels in the ocular tissue structure provided in Embodiment 1 of the present invention.

[0025] Figure 2A This is a corneal fluorescein sodium staining image used in the construction of the dry eye animal model provided in Embodiment 2 of the present invention.

[0026] Figure 2B The corresponding scoring chart for corneal fluorescein sodium staining (2A) during the construction of the dry eye animal model provided in Example 2 of the present invention.

[0027] Figure 2C This is a graph showing the change in tear secretion over days during the construction of the dry eye animal model provided in Embodiment 2 of the present invention.

[0028] Figure 2D This is a comparison of tear volume between mice in the model group and normal mice 10 days after injection in the construction of the dry eye animal model provided in Example 2 of the present invention.

[0029] Figure 3A The image shows the results of sodium fluorescein staining in mice treated for 7 days in Example 3 of this invention.

[0030] Figure 3B This is a comparison chart of fluorescein sodium staining scores of mice in different treatment groups after 7 days of treatment, provided in Example 3 of the present invention.

[0031] Figure 3C This is a comparison chart of tear secretion in mice in different treatment groups after 7 days of treatment, provided in Example 3 of the present invention.

[0032] Figure 3D The image shows the results of sodium fluorescein staining in mice treated for 14 days in Example 3 of this invention.

[0033] Figure 3EThis is a comparison chart of fluorescein sodium staining scores of mice in different treatment groups after 14 days of treatment, provided in Example 3 of the present invention.

[0034] Figure 3F This is a comparison chart of tear secretion in mice treated with different methods for 14 days, provided in Example 3 of the present invention.

[0035] Figure 4A The results of corneal HE staining for different treatment groups provided in Embodiment 3 of the present invention are shown in the figure.

[0036] Figure 4B This is a comparison diagram of corneal epithelial thickness in different treatment groups provided in Embodiment 3 of the present invention.

[0037] Figure 4C This is a comparison chart of the expression levels of the inflammatory factor IL-1β in different treatment groups provided in Example 3 of the present invention.

[0038] Figure 4D This is a comparison chart of the expression levels of the inflammatory factor TNF-α in different treatment groups provided in Example 3 of the present invention.

[0039] Figure 4E This is a comparison chart of the expression levels of the inflammatory factor IL-6 in different treatment groups provided in Example 3 of the present invention.

[0040] Figure 5A The image shows the results of goblet cell staining in different treatment groups provided in Example 4 of the present invention.

[0041] Figure 5B This is a comparison diagram of the number of conjunctival goblet cells in different treatment groups provided in Embodiment 4 of the present invention.

[0042] Figure 6 The images show the HE staining results of lacrimal glands in different treatment groups provided in Example 5 of this invention.

[0043] Figure 7 This is a schematic diagram of the construction of the TMEM16A conditional knockout mouse provided in Example 6 of the present invention.

[0044] Figure 8A This is an immunoblot image of the TMEM16A protein in the cornea, conjunctiva, lacrimal gland, and meibomian gland provided in Example 6 of the present invention.

[0045] Figure 8B This is a graph showing the expression levels of the TMEM16A protein in the cornea, conjunctiva, lacrimal gland, and meibomian gland, as provided in Example 6 of this invention.

[0046] Figure 9A This is a diagram showing the fluorescein staining results of the cornea of ​​a knockout mouse provided in Example 6 of the present invention.

[0047] Figure 9B This is a fluorescein sodium staining score chart of the knockout mice provided in Example 6 of the present invention.

[0048] Figure 9C This is a graph showing the tear secretion of knockout mice provided in Example 6 of the present invention.

[0049] Figure 10A The figure shows the treatment results of knockout mice in different treatment groups provided in Example 6 of the present invention.

[0050] Figure 10B This is a comparison chart of the sodium fluorescein staining scores of knockout mice in different treatment groups after 4 days of treatment, as provided in Example 6 of the present invention.

[0051] Figure 10C This is a comparison chart of tear secretion in knockout mice treated with different treatment groups for 4 days, as provided in Example 6 of the present invention.

[0052] Figure 10D This is a comparison chart of the sodium fluorescein staining scores of knockout mice in different treatment groups after 8 days of treatment, as provided in Example 6 of the present invention.

[0053] Figure 10E This is a comparison chart of tear secretion in knockout mice treated with different treatment groups for 8 days, as provided in Example 6 of the present invention. Detailed Implementation

[0054] Unless otherwise defined herein, the scientific and technical terms used in conjunction with this invention shall have the meanings commonly understood by one of ordinary skill in the art. The meaning and scope of terms shall be clear; however, in any case of potential ambiguity, the definitions provided herein shall prevail over any dictionary or foreign definitions. In this application, unless otherwise stated, the use of "or" means "and / or". Furthermore, the use of the term "comprising" and other forms is non-limiting.

[0055] Generally, the nomenclature and techniques used in cell and tissue culture, molecular biology, immunology, microbiology, genetics, and protein and nucleic acid chemistry and hybridization, together with those described herein, are those well-known and commonly used in the art. Unless otherwise stated, the methods and techniques of the present invention are generally carried out according to conventional methods well-known in the art and described in various general and more specific references, which are cited and discussed throughout this specification. Enzymatic reactions and purification techniques are carried out according to the manufacturer's instructions, as commonly practiced in the art, or as described herein. The nomenclature, laboratory procedures, and techniques used in analytical chemistry, synthetic organic chemistry, and medical and medicinal chemistry, together with those described herein, are those well-known and commonly used in the art.

[0056] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0057] In a first aspect, the present invention provides the use of canthaxanthin in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0058] As an optional implementation, the canthaxanthin is used as an activator of the TMEM16A ion channel in the preparation of medicaments for the prevention and / or treatment of dry eye syndrome.

[0059] As an optional implementation, the present invention provides the application of canthaxanthin in the preparation of an activator for TMEM16A ion channels.

[0060] In this invention, the therapeutic effect of the TMEM16A ion channel activator canthaxanthin (hereinafter referred to as CX) on dry eye syndrome was investigated. To further verify its therapeutic target TMEM16A, this invention constructed a conditional gene knockout mouse. After dry eye modeling, treatment, and related dry eye treatment efficacy evaluation methods, it was demonstrated that mice without TMEM16A knockout could be treated with CX eye drops, but mice with TMEM16A knockout did not achieve the same therapeutic effect. Based on the above experimental results, this invention concludes that TMEM16A is one of the drug targets for dry eye treatment.

[0061] As an optional implementation, the TMEM16A ion channels are distributed in the cornea, fornix conjunctiva, bulbar conjunctiva, lacrimal gland, palpebral conjunctiva, and meibomian gland.

[0062] As an optional implementation, the canthaxanthin is used as an agent to increase tear secretion in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0063] As an optional implementation, the present invention provides the use of canthaxanthin in the preparation of a reagent that increases tear secretion.

[0064] As an optional implementation, the canthaxanthin is used as an agent for improving corneal epithelial damage in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0065] In this invention, the distribution of the TMEM16A ion channel, the drug target of canthaxanthin, was discovered. Subsequently, based on the successful construction of a dry eye model, through daily eye drop treatment and experiments such as fluorescein staining and tear secretion detection after treatment, it was successfully demonstrated that CX can treat dry eye syndrome.

[0066] As an optional implementation, the present invention provides the use of canthaxanthin in the preparation of a reagent to improve corneal epithelial damage.

[0067] As an optional implementation, the canthaxanthin is used as an agent to increase corneal epithelial thickness in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0068] As an optional implementation, the present invention provides the use of canthaxanthin in the preparation of reagents that increase corneal epithelial thickness.

[0069] As an optional implementation, the canthaxanthin is used as a reagent to reduce the expression level of inflammatory factors in corneal tissue in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0070] As an optional implementation, the present invention provides the use of canthaxanthin in the preparation of a reagent that reduces the expression level of inflammatory factors in corneal tissue.

[0071] As an optional implementation, the inflammatory factors include any one or a combination of at least two of IL-1β, TNF-α, or IL-6.

[0072] As an optional implementation, the canthaxanthin is used as an agent to increase the number of conjunctival goblet cells in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0073] As an optional implementation, the present invention provides the use of canthaxanthin in the preparation of a reagent that increases the number of conjunctival goblet cells.

[0074] As an optional implementation, the canthaxanthin is used as an agent to reduce the infiltration of inflammatory cells in the lacrimal gland in the preparation of medicaments for treating and / or relieving dry eye syndrome.

[0075] As an optional implementation, the present invention provides the use of canthaxanthin in the preparation of a reagent that reduces the infiltration of inflammatory cells in the lacrimal gland.

[0076] Secondly, the present invention provides the application of the TMEM16A ion channel as a target in the preparation of drugs for treating and / or alleviating dry eye syndrome.

[0077] Thirdly, the present invention provides a drug for treating and / or relieving dry eye syndrome, the drug comprising canthaxanthin; and the concentration of canthaxanthin used is 50~200 μM, for example, 50 μM, 60 μM, 80 μM, 100 μM, 120 μM, 140 μM, 160 μM, 180 μM, 200 μM, etc.

[0078] In this invention, a drug is designed that uses TMEM16A as the drug target and canthaxanthin, a TMEM16A activator, as the main drug component, which can be used to treat dry eye syndrome, thereby achieving the effect of treating and relieving dry eye symptoms.

[0079] As an optional implementation, the drug is a topical preparation, which is administered through ocular treatment.

[0080] As an optional implementation, the topical preparation includes any one of eye drops, eye wash, eye drops, eye gel, eye ointment, or eye patch.

[0081] As an optional implementation, the drug may also include pharmaceutically acceptable excipients.

[0082] As an optional implementation, the pharmaceutically acceptable excipients include any one or a combination of at least two of the following: solvents, surfactants, suspending agents, osmotic pressure regulators, pH regulators, emulsion stabilizers, thickeners, or solubilizers.

[0083] The present invention will be further illustrated by the following examples. Unless otherwise specified, the materials in the examples are prepared according to existing methods or purchased directly from the market.

[0084] Example 1 This embodiment provides an experimental method using immunohistochemistry to study the expression of TMEM16A ion channels in different ocular tissues of mice.

[0085] The specific experimental method was as follows: Mice were euthanized by cervical dislocation, and different ocular tissues, including the cornea, conjunctiva, lacrimal gland, and meibomian gland, were removed using ophthalmic scissors. These tissues were then fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. The ocular tissue sections were dewaxed and dehydrated, then subjected to antigen retrieval and blocking. The primary antibody used was a specific antibody against TMEM16A. Subsequent secondary antibody incubation, DAB staining, hematoxylin counterstaining, dehydration, clearing, and mounting were performed. The sections were then observed and analyzed using a pathological slide scanner.

[0086] The specific experimental results are as follows: Figure 1 As shown: like Figure 1 As shown, TMEM16A is distributed in the cornea (a), fornix conjunctiva (b), bulbar conjunctiva (c), lacrimal gland (d), palpebral conjunctiva (e), and meibomian gland (f). Among them, TMEM16A ion channels are highly expressed in the cornea, palpebral conjunctiva, lacrimal gland, and meibomian gland, followed by the fornix conjunctiva and bulbar conjunctiva.

[0087] Example 2 This embodiment verifies the application of canthaxanthin (CX) as a reagent that increases tear secretion and improves corneal epithelial damage in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0088] The specific experimental method is as follows: (1) Construction of dry eye animal model: The model was induced by drug injection, with scopolamine injected subcutaneously four times a day (9:00, 12:00, 15:00, and 17:00) for 10 consecutive days. The success of the model construction was evaluated by corneal fluorescein staining and Schirmer's Test (tear secretion test).

[0089] The results are as follows Figures 2A-2D As shown, corneal fluorescein sodium staining (2A) and corresponding scores (2B) indicate that the dry eye model was successfully established; tear secretion decreased with the increase of drug injection days (2C), and tear volume decreased in mice in the model group after 10 days of drug injection (2D).

[0090] (2) Verification of treatment effect: After the model was successfully constructed, in order to study the therapeutic effect of TMEM16A ion channel activator CX on dry eye, mice in different treatment groups were set up: normal group, dry eye model group, saline group (solvent group), saline + CX group (treatment group - saline solution to dissolve or dilute canthaxanthin to 200 μM / mL), and positive control group (cyclosporine eye drops). After 7 days and 14 days of treatment, mice were stained with sodium fluorescein and photographed under cobalt blue light slit lamp and scored.

[0091] The specific test results are as follows: Figures 3A-3F As shown: like Figures 3A-3F As shown, after 7 days of CX treatment, the fluorescein staining score was significantly lower than that of the model group, and tear secretion also increased significantly. Furthermore, after 14 days of CX treatment, the fluorescein staining score was again significantly lower than that of the model group, and tear secretion also increased significantly, with a better therapeutic effect than cyclosporine, a first-line drug for dry eye. These results indicate that CX can treat dry eye by improving corneal epithelial damage and increasing tear secretion, and its therapeutic effect is better than that of cyclosporine.

[0092] Example 3 This embodiment verifies the application of canthaxanthin (CX) as a reagent that increases corneal epithelial thickness and reduces the expression level of inflammatory factors in corneal tissue in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0093] The specific experimental method is as follows: To further confirm the therapeutic effect of CX on dry eye, histopathological and biomolecular experiments were conducted to further evaluate the therapeutic effect of CX. Mice were divided into different treatment groups: normal group, dry eye model group, saline group (solvent group), saline + CX group (treatment group - saline dissolved or diluted cyclosporine to 200 μM / mL), and positive control group (cyclosporine eye drops). After 14 days of treatment, ocular surface tissues (cornea, conjunctiva, and lacrimal gland) were collected from mice in different treatment groups, and HE staining and RT-PCR were used to measure the levels of inflammatory factors in the cornea.

[0094] The specific test results are as follows: Figures 4A-4E As shown: like Figure 4A As shown, the results of corneal HE staining showed that, compared with the normal group, the epithelial cells in the dry eye model group had rough surfaces, disordered arrangement, and vacuolated cells, and the corneal stroma showed inflammatory cell infiltration. However, significant improvement was observed after CX treatment.

[0095] like Figure 4B As shown, CX treatment increases corneal epithelial thickness, and its effect is superior to cyclosporine.

[0096] like Figures 4C-4D As shown, inflammatory factors in corneal tissue were detected by RT-PCR. The results showed that CX could reduce the expression of inflammatory factors (IL-1β, TNF-α, IL-6).

[0097] Example 4 This embodiment verifies the use of canthaxanthin (CX) as a reagent to increase the number of conjunctival goblet cells in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0098] The specific experimental method is as follows: Mucin secreted by conjunctival goblet cells is a major component of the mucin layer and plays an important role in maintaining tear film and ocular surface homeostasis. Mice were divided into different treatment groups: normal group, dry eye model group, saline group (solvent group), saline + CX group (treatment group - saline dissolved or diluted canthaxanthin to 200 μM / mL), and positive control group (cyclosporine eye drops). The effect of canthaxanthin (CX) on the number of conjunctival goblet cells was verified by staining the conjunctiva of mice in different treatment groups.

[0099] The specific test results are as follows: Figures 5A-5B As shown: like Figure 5A and Figure 5B As shown, CX treatment increased the number of conjunctival goblet cells, and the effect was better than cyclosporine.

[0100] Example 5 This embodiment verifies the application of canthaxanthin (CX) as an agent that reduces the infiltration of inflammatory cells in the lacrimal gland in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0101] The specific experimental method was as follows: Mice were euthanized by cervical dislocation, and lacrimal gland tissue was removed using ophthalmic scissors. The tissue was then fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. The ocular tissue sections were dewaxed and dehydrated, stained with hematoxylin and eosin, and subsequently dehydrated, cleared, and mounted. The sections were then observed and analyzed using a pathological slide scanner.

[0102] The specific test results are as follows: Figure 6 As shown: like Figure 6 As shown, HE staining results of the lacrimal glands indicate that the lacrimal glands of the dry eye model mice exhibit disordered structure, containing numerous acinars of varying sizes, arranged in a disordered manner, and atrophied and fused, accompanied by intracellular vacuoles and extracellular infiltrating lymphocytes. CX treatment can improve the structural disorder and restore the mice to a healthy state. (Red triangle: Lymphocyte infiltration and structural disorder in lacrimal gland tissue).

[0103] Example 6 This embodiment verifies the application of canthaxanthin (CX) as an activator of the TMEM16A ion channel in the preparation of drugs for treating and / or relieving dry eye syndrome.

[0104] The specific experimental method is as follows: (1) Construction of TMEM16A conditional knockout mice: In order to confirm that the TMEM16A ion channel is a drug target for the treatment of dry eye, we constructed TMEM16A conditional knockout mice (e.g., TMEM16A ion channel knockout mice) by gene knockout. Figure 7 (As shown in the image). To confirm whether TMEM16A was knocked out, a Western blotting assay was used for further determination. The results are as follows. Figure 8A and Figure 8B As shown, the expression of TMEM16A protein was reduced in the cornea, conjunctiva, and lacrimal gland, but there was no significant change in the meibomian gland.

[0105] (2) Analysis of dry eye-related phenotypes: Subsequently, the knockout mice were analyzed for dry eye-related phenotypes, including corneal fluorescein staining and scoring; the results are as follows: Figures 9A-9C As shown in the figures, in addition to increased corneal fluorescein staining and scoring, corneal epithelial cell damage was observed in mice, and tear secretion was significantly reduced in knockout mice compared to the WT group.

[0106] (3) Verification: In order to confirm whether CX can still treat dry eye after TMEM16A knockout, that is, whether TMEM16A is a target for dry eye treatment, this embodiment sets up WT-normal group, WT-dry eye model group, WT-CX treatment group and gene knockout group (16Aflox / +; Cre / +) respectively. They are also subdivided into normal knockout, dry eye model knockout and treatment knockout group. Ten days after drug injection modeling, eye drop treatment is performed. On the 4th and 8th days of treatment, corneal fluorescein sodium staining and photography and tear secretion volume detection are performed on different groups.

[0107] The specific test results are as follows: Figures 10A-10E As shown: like Figure 10A As shown in the sodium fluorescein staining image, it can be clearly observed that CX treatment significantly improved corneal damage in the WT group, which is consistent with the results provided in the above examples. However, after knocking out TMEM16A, the effect of CX treatment on improving damage was not obvious.

[0108] like Figure 10B and Figure 10D As shown, the results of fluorescein sodium staining indicate that CX can achieve the effect of treating dry eye, but after knocking out its drug target TMEM16A, there is almost no therapeutic effect. Although CX can reduce the fluorescein sodium score in the TMEM16A knockout group on the 4th day of treatment, its significance is only one star; and on the 8th day of treatment, there is no significant difference between CX treatment and the model.

[0109] like Figure 10B C and Figure 10E As shown, the tear measurement results on the fourth day of treatment also indicate that knocking out TMEM16A can no longer promote tear secretion. The tear secretion measurement statistics on the eighth day of treatment also prove that after knocking out TMEM16A, subsequent CX treatment has no effect on promoting secretion.

[0110] In summary, TMEM16A serves as a target for canthaxanthin in the treatment of dry eye syndrome. This invention provides the application of canthaxanthin as an activator of the TMEM16A ion channel in the preparation of drugs for the prevention and / or treatment of dry eye syndrome.

[0111] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. The use of canthaxanthin in the preparation of drugs for treating and / or relieving dry eye syndrome.

2. The application according to claim 1, characterized in that, The use of the canthaxanthin as an activator of the TMEM16A ion channel in the preparation of drugs for the prevention and / or treatment of dry eye syndrome; And / or, the distribution locations of the TMEM16A ion channels include the cornea, fornix conjunctiva, bulbar conjunctiva, lacrimal gland, palpebral conjunctiva, and meibomian gland.

3. The application according to claim 1, characterized in that, The use of canthaxanthin as an agent to increase tear secretion in the preparation of drugs for treating and / or relieving dry eye syndrome.

4. The application according to claim 1, characterized in that, The use of the canthaxanthin as an agent for improving corneal epithelial damage in the preparation of drugs for treating and / or relieving dry eye syndrome.

5. The application according to claim 1, characterized in that, The use of the flavin as an agent to increase corneal epithelial thickness in the preparation of drugs for treating and / or relieving dry eye syndrome.

6. The application according to claim 1, characterized in that, The use of canthaxanthin as a reagent to reduce the expression level of inflammatory factors in corneal tissue in the preparation of drugs for treating and / or relieving dry eye syndrome; And / or, the inflammatory factors include any one or a combination of at least two of IL-1β, TNF-α, or IL-6.

7. The application according to claim 1, characterized in that, The use of the canthaxanthin as a reagent to increase the number of conjunctival goblet cells in the preparation of medicaments for treating and / or relieving dry eye syndrome.

8. The application according to claim 1, characterized in that, The use of canthaxanthin as an agent to reduce the infiltration of inflammatory cells in the lacrimal gland in the preparation of drugs for treating and / or relieving dry eye syndrome.

9. Application of TMEM16A ion channel as a target in the preparation of drugs for treating and / or alleviating dry eye syndrome.

10. A medicine for treating and / or relieving dry eye syndrome, characterized in that, The drug includes canthaxanthin; and the concentration of canthaxanthin used is 50~200 μM. Preferably, the drug is a topical preparation, which is administered through ocular treatment; Preferably, the topical preparation includes any one of eye drops, eye wash, eye drops solution, eye gel, eye ointment, or eye patch.

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