Use of compounds in controlling or controlling mites

Abstract

The present invention provides a series of compounds for use in the control or eradication of mites. Comparison results show that the compounds can shorten the survival time of mites compared to the control group. In particular, taraxerol, diosmetin and taraxasterol acetate can shorten the survival time of mites, and can be used in mite control and eradication products (e.g., medicines, cosmetics, daily necessities, etc.).

Description

[Technical field]

[0001] The present invention relates to the pharmaceutical field, specifically to the use of compounds of the formula I, II or III structure in controlling or combating mites. [Background technology]

[0002] Mites are small animals of the subclass Platypus of the class Arachnida in the phylum Arthropoda, with a body size of usually around 0.5 mm, some as small as 0.1 mm, and many species less than 1 mm. Currently, mites are closely related to the health of humans and animals (e.g., pets such as dogs and cats), and it has been discovered that mites such as leather mites, chiggers, scabies mites, demodex mites, dust mites, and lice mites suck blood, invade the skin, and cause rosacea, demodex, allergies, urinary tract mites, pulmonary mites, intestinal mites, and scabies, causing serious damage to the health of humans and animals.

[0003] Demodex mites are microscopic ectoparasites that usually infect the cutaneous pilosebaceous units. At least two reported species, Demodex follicularis and Demodex sebacea, have been found on the human body surface and mainly infest hair follicles, sebaceous glands, and meibomian glands. Demodex feeds on hair follicle epithelial cells, causing hair follicle dilation and hair loss, which is clinically manifested as blepharitis, meibomian gland dysfunction, eyelash loss, eyelash irregularity, conjunctivitis and blepharoconjunctivitis, pterygium, keratitis, eyelid basal cell carcinoma, etc. Demodex also feeds on lipids and can cause dry eye. Demodex can also cause mechanical obstruction of the meibomian gland excretory duct, leading to difficulty in lipid excretion and excessive secretion retention, which can lead to the formation of chalazions. The clinical symptoms of Demodex eye disease are mainly recurrent redness and itching of the eye margins, dry eyes, burning eyes, foreign body sensation in the eye, fear of light, increased secretions, recurrent loss of eyelashes, and in severe cases, the cornea may be affected, causing blurred vision and reduced visual acuity.In addition to the above eye diseases, many studies in recent years have shown that Demodex folliculorum infection can lead to a variety of common skin diseases, including seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, and basal cell carcinoma (e.g., Luo, X., Li, J., Chen, C., Tseng, S. & Liang, L. Ocular Demodicosis as a Potential Cause of Ocular Surface Inflammation. Cornea 36 Suppl 1, S9-s14;Karincaoglu, Y., Tepe, B., Kalayci, B., Atambay, M. & Seyhan, M. Is Demodex folliculorum an aetiological factor in seborrhoeic dermatitis? Clinical and experimental dermatology 34, e516-520;Chen, W. & Plewig, G. Human demodicosis: revisit and a proposed classification. The British journal of (See Dermatology 170, 1219-1225).

[0004] In particular, reports proving the relationship between mites and eye disease include the following:

[0005] Human Permanent Ectoparasites; Recent Advances on Biology and Clinical Significance of Demodex Mites: Narrative Review Article (Iranian journal of parasitology 12(1):12-21) demonstrates that Demodex mites are present in sebaceous glands, meibomian glands, and pilonidal glands, often parasitizing the hair follicles of human eyelashes, and that infection of facial skin can cause eye disease.

[0006] Ocular Demodicosis as a Potential Cause of Ocular Surface Inflammation (Cornea 36 Suppl 1(Suppl 1):s9-s14) demonstrates that Demodex mites and Demodex folliculorum are the two species of demodex that cause ocular mite infection in humans, that human age is proportional to the risk of disease, and that ocular mite infection is strongly positively correlated with the condition of the ocular surface.

[0007] As revealed in the study "Demodex species in human ocular disease: new clinicopathological aspects" (International ophthalmology 37(1):303-312), Demodex mites and Demodex folliculorum are linked to the pathogenesis of external eye diseases, while ocular mitosis leads to an imbalance in the extraocular ecosystem.

[0008] Ocular Demodex: a systematic review of the clinical literature (Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists) 40(4):389-432) describes that Demodex infection is a potential etiological agent for multiple ocular surface diseases, and that when Demodex infests anterior structures of the eye, such as the eyelids, eyelashes, and ocular surface, it causes ocular mite disease in humans, and that the incidence is positively correlated with age.

[0009] The relationship between demodex and ocular discomfort (Investigative ophthalmology & visual science 51(6):2906-2911) noted that the number of Demodex mites was positively correlated with the severity of eye disease and the age of the patient.

[0010] Demodex mites (Clinics in dermatology 32(6):739-743) indicates that Demodex mites infection causes chronic blepharitis, and that the incidence of chronic blepharitis is positively correlated with the number of mites and the age of the patient.

[0011] As revealed by the study in Quantitative Analysis of the Bacteria in Blepharitis With Demodex Infestation (Frontiers in microbiology 9:1719), Demodex and Demodex folliculorum infections cause eye disease and the prevalence is positively correlated with the number of mites and the age of the patient. Demodex mites are carriers of the Bacillus and may play a role in the pathogenesis of blepharitis as a co-pathogen.

[0012] According to Bacillus oleronius and Demodex mite infestation in patients with chronic blepharitis (Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 18(10):1020-1025), Demodex mites can cause the development of blepharitis disease and are also carriers of Bacillus, functioning as co-pathogens during the progression of blepharitis.

[0013] Correlation between ocular Demodex infestation and serum immunoreactivity to Bacillus proteins in patients with Facial rosacea (Ophthalmology 117(5):870-877.e871) suggests that the incidence of Demodex infection in the eyes of dry eye patients is lower than that of non-dry eye patients, and that mite and bacterial infections can coexist in ocular surface inflammation.

[0014] As evidenced by a study published in High prevalence of demodex brevis infestation in chalazia (American journal of ophthalmology 157(2):342-348.e341), the incidence of demodex brevis is extremely high among adults and pediatric patients with meibomian gland cysts, making ocular demodex brevis one of the important etiologies of meibomian gland cysts.

[0015] Currently, mite-related diseases (e.g. eye and skin diseases) are not given sufficient importance in clinical practice, and are often misdiagnosed as bacterial diseases, with typical antibiotic treatments often having no clear therapeutic effect.

[0016] Thus, the present invention provides a series of compounds useful for controlling or combating mites. Summary of the Invention [Means for solving the problem]

[0017] 1. Use of a compound represented by the following formula I or a salt, isomer or solvate thereof in the manufacture of a product for controlling or eliminating mites. [ka] (In the formula, R1 is H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH2, CH=CH(C 1-8 alkyl), C(C 1-8 alkyl)=CH2, C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 or, if there is a double bond between R1 and the fifth carbon atom, R1 is selected from O or S. R2, R3, R6, R7, R8, and R9 are independently H, C 1-8 Alkyl, O(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, O(C 1-8 cycloalkyl), OH, and NH2. R4 is H, C 1-8 Alkyl, O(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, O(C 1-8 cycloalkyl), OH, NH2 、 Or, when there is a double bond between the first and fourth carbon atoms, R4 is absent. R5 is H, C 1-8 Alkyl, O(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, O(C 1-8 cycloalkyl), OH, NH2 、 Or, when there is a double bond between the second and third carbon atoms, R5 is absent. There is a double bond or a single bond between the sixth and seventh carbon atoms. R 10 and R 13 are independently H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 1-8 Alkynyl, CH=CH(C 1-8 alkyl), CH=CH2, C(C 1-8 alkyl)=CH2, C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2. R 11 and R 12 are independently H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 1-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2, or R 11 and R 12 are carbon atoms, and form a 5- to 8-membered ring with the carbon atoms between them, and H on any carbon atom on the ring is C 1-8 Alkyl, O(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, O(C 1-8 Cycloalkyl), OH, NH2, C 2-8 Alkenyl, C2-8 Alkynyl, CH=CH2, C(C 1-8 alkyl)=CH2, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 may be substituted with alkyl)2.

[0018] Specifically, the formula I compound of the present invention is a compound of formula I-1. [ka] (In the formula, R 14 If there is a single bond between and the carbon atom numbered 8, R 14 H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2, and the hydrogen atom on the carbon atom numbered 8 is optionally selected from R 14 is replaced by R 14 If there is a double bond between and the carbon atom numbered 8, R 14 are O, S, CH2, CH(C 1-8 alkyl), C(C 1-8 alkyl)2. R 15 H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2. n is an integer of 1 to 4, for example, 1, 2, 3, or 4. Specifically, R1 is H, C 1-3 Alkyl, OH, OC(=O)(C 1-3 Alkyl), (C 1-3 or, if there is a double bond between R1 and the fifth carbon atom, R1 is O. More specifically, R1 is selected from OH, OC(=O)(C 1-3 alkyl). More specifically, R1 is selected from OH, OC(=O)CH3. Specifically, R2, R3, R6, R7, R8, and R9 are independently H, C 1-3 Alkyl, O(C 1-3 Alkyl), C 3-6 cycloalkyl, OH, NH2. Particularly preferably, R2, R3, R6, R7, R8, R9 are independently selected from H or methyl. Specifically, the bond between the first and fourth carbon atoms is a single bond, and R4 is H, C 1-3 Alkyl, O(C 1-3 Alkyl), C 3-6 Cycloalkyl, O(C 1-3 cycloalkyl), OH. Particularly specifically, there is a single bond between the first and fourth carbon atoms, and R4 is selected from H or methyl. Specifically, the bond between the second and third carbon atoms is a single bond, and R5 is H, C 1-3 Alkyl, O(C 1-3 Alkyl), C 3-6 Cycloalkyl, O(C 1-3 cycloalkyl), OH. Particularly specifically, there is a single bond between the second and third carbon atoms, and R5 is selected from H or methyl. Specifically, there is a single bond between the sixth and seventh carbon atoms. Specifically, R 10 and R 13 are independently H, C 1-3 Alkyl, O(C 1-3 Alkyl), C 3-6 cycloalkyl, OH, NH2. Particularly preferred are R 10 and R 13 is independently selected from H or methyl. Specifically, R 14 If there is a single bond between and the carbon atom numbered 8, R 14 is H, C 1-3 Alkyl, O(C 1-3 Alkyl), C 3-6 cycloalkyl, OH, and NH2, and the hydrogen atom on the carbon atom numbered 8 is similarly selected from R 14 is replaced by R 14 If there is a double bond between and the carbon atom numbered 8, R 14 is CH2, CH(C 1-3 alkyl), C(C 1-3 alkyl)2. Particularly preferred are 14 If there is a single bond between and the carbon atom numbered 8, R 14is selected from H or methyl, and the hydrogen atom on the carbon atom numbered 8 is similarly replaced with H or methyl; R 14 If there is a double bond between and the carbon atom numbered 8, R 14 is selected from CH2 (methylene). Specifically, R 15 is H, C 1-3 Alkyl, O(C 1-3 Alkyl), C 3-6 Cycloalkyl, OH, NH2, CH=CH(C 1-3 alkyl), C(C 1-3 alkyl)=CH2, C(C 1-3 Alkyl)=CH(C 1-3 alkyl), C(C 1-3 Alkyl)=C(C 1-3 alkyl)2. Particularly preferred are 15 is H, C 1-3 alkyl, C(CH3)=CH2.

[0019] In specific embodiments of the invention, the compound of formula I is taraxasterol, taraxerol, taraxerone, lobric acid, taraxasterol acetate, taraxerol acetate, lupenone, or a salt, isomer or solvate thereof.

[0020] The present invention relates to the use of a compound represented by the following formula II or a salt, isomer or solvate thereof in the manufacture of a product for controlling or controlling mites. [ka] (In the formula, R 16 , R 18 , R 20 , R 23 , R 24 are independently H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2. R 17 , R 19 , R 21 , R 22 are independently H, C 1-8 Alkyl, O(C 1-8 Alkyl), C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C1-8 cycloalkyl) or groups of formula II-1, II-2, II-3. [ka] Specifically, R 16 , R 18 , R 20 , R 23 , R 24 are independently H, halogen, C 1-3 Alkyl, O(C 1-3 alkyl), NH(C 1-3 alkyl), N(C 1-3 Alkyl)2, C 3-11 Cycloalkyl, OH, NH2, OC(=O)(C 1-3 alkyl), C(=O)(C 1-3 Alkyl), (C 1-3 Alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C 2-3 Alkenyl, C 2-3 Alkynyl, CH=CH(C 1-3 alkyl), C(C 1-3 Alkyl)=CH(C 1-3 alkyl), C(C 1-3 Alkyl)=C(C 1-3 More specifically, R 16 , R 18 , R 20 , R 23 , R 24 is independently selected from H or methyl. Specifically, R 17 , R 19 , R 21 , R 22 are independently H, C 1-3 Alkyl, O(C 1-3 alkyl) or groups of formula II-1, II-2. More specifically, R 17 , R 19 , R 21 , R 22 is independently selected from H or methyl.

[0021] In a specific embodiment of the invention, the compound of formula II is diosmetin or a salt, isomer or solvate thereof.

[0022] The present invention relates to the use of a compound represented by the following formula III or a salt, isomer or solvate thereof in the manufacture of a product for controlling or controlling mites. [ka] (In the formula, R 25 teeth [ka] is selected from. R 26 is a carbon atom, and R 27 and R 28 and R 27 and R 28 Of which R 26 The groups that do not form a ring are H, halogen, and C. 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2. R 29 H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2.

[0023] Specifically, the compound of formula III of the present invention is a compound of formula III-1 or III-2. [ka] (In the formula, R 30 , R 31 , R 33 , R 34 , R 35 H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11 Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2. In formula III-1, the bond between the first carbon atom and the second carbon atom is selected from a double bond or a single bond. In formula III-1, when the bond between the first carbon atom and the second carbon atom is selected from a double bond, R 32 is not present, and in III-1, when a single bond is selected between the first carbon atom and the second carbon atom, R 32 H, halogen, C 1-8 Alkyl, O(C 1-8 alkyl), S(C 1-8 alkyl), NH(C 1-8 alkyl), N(C 1-8 Alkyl)2, C 3-11 Cycloalkyl, aryl, heteroaryl, C 3-11Heterocycloalkyl, O(C 1-8 Cycloalkyl), S(C 1-8 Cycloalkyl), NH(C 1-8 Cycloalkyl), N(C 1-8 Cycloalkyl)(C 1-8 alkyl), OH, NH2, SH, SO2(C 1-8 Alkyl), C 2-8 Alkenyl, C 2-8 Alkynyl, CH=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=CH(C 1-8 alkyl), C(C 1-8 Alkyl)=C(C 1-8 alkyl)2, OC(=O)(C 1-8 alkyl), C(=O)(C 1-8 Alkyl), (C 1-8 alkyl)CO2H, CO2H, CN, CF3, CHF2, CH2F, NO2, C(=O)NH(C 1-8 alkyl), C(=O)N(C 1-8 Alkyl)2, N(C 1-8 Alkyl)C(=O)NH(C 1-8 alkyl), N(C 1-8 Alkyl)C(=O)N(C 1-8 alkyl)2, NHC(=O)NH(C 1-8 alkyl), NHC(=O)N(C 1-8 alkyl)2, NHC(=O)NH2, N(C 1-8 Alkyl)SO2NH(C 1-8 alkyl), N(C 1-8 Alkyl)SO2N(C 1-8 alkyl)2, NHSO2NH(C 1-8 alkyl), NHSO2N(C 1-8 alkyl)2. Specifically, R 25 teeth [ka] is selected from. Specifically, R 27 and R 28 Of these, R 26 The groups that do not form a ring are H and C.1-3 Alkyl, O(C 1-3 alkyl), O(C 1-3 Cycloalkyl), C 2-3 Alkenyl, C 2-3 Alkynyl, CH=CH(C 1-3 alkyl), C(C 1-3 Alkyl)=CH(C 1-3 alkyl), C(C 1-3 Alkyl)=C(C 1-3 alkyl)2, OC(=O)(C 1-3 alkyl), C(=O)(C 1-3 Alkyl), (C 1-3 alkyl)COH, COH. More specifically, R 27 and R 28 Of these, R 26 The groups that do not form a ring are selected from H, CH=CH2, and CO2H. Specifically, R 30 , R 31 , R 33 , R 34 , R 35 is H, C 1-3 Alkyl, O(C 1-3 Alkyl), C 3-6 Cycloalkyl, OH, NH2, CH=CH(C 1-3 alkyl), C(C 1-3 alkyl)=CH2, C(C 1-3 Alkyl)=CH(C 1-3 alkyl), C(C 1-3 Alkyl)=C(C 1-3 alkyl)2. Particularly preferred are 30 , R 31 , R 33 , R 34 , R 35 is selected from H, methyl, and OH. Specifically, in III-1, when a double bond is selected between the first and second carbon atoms, R 32 does not exist.)

[0024] In specific embodiments of the invention, the compound of formula III is swertiamarin, swelloside, gentiopicroside, loganic acid or a salt, isomer or solvate thereof.

[0025] Specifically, the compounds of the present invention or their salts, isomers, and solvates may be the sole active ingredient for controlling or eliminating mites, or may be used in combination with other, same or different, active ingredients for controlling or eliminating mites.

[0026] The compounds of the present invention may be extracted from natural plants such as dandelion, ginger, gentian, and chrysanthemum, and the extraction method may be a method commonly used in this field.

[0027] The compounds of the present invention may be prepared by chemical synthesis or biosynthesis.

[0028] In particular, the above-mentioned acaricide products of the present invention are useful for both therapeutic and / or prophylactic purposes and for non-therapeutic and / or prophylactic purposes.

[0029] Specifically, the mite of the present invention may be one or more of Demodex, dust mites, Sarcoptes scabiei, etc. In one embodiment of the present invention, the mite of the present invention is Demodex, such as Demodex folliculorum and Demodex sebaceus.

[0030] In one embodiment of the invention, the acaricide product of the invention is a pharmaceutical composition.

[0031] In particular, the pharmaceutical composition further comprises a pharma- ceutically acceptable auxiliary material.

[0032] Specifically, the pharmaceutical composition of the present invention is useful for the prevention and / or treatment of diseases caused by mites.

[0033] Specifically, the disease may be an eye disease, a skin disease, an allergic disease, or the like.

[0034] Specifically, the eye disease may be one or more of blepharitis, meibomian gland dysfunction, blepharitis, eyelash loss, eyelash irregularity, glaucoma, cataract, ocular folliculitis, conjunctivitis, blepharoconjunctivitis, pterygium, keratitis, ptosis and ectropion of eyelid, eyelid basal cell carcinoma, dry eye, chalazion, etc., and may be accompanied by one or more symptoms selected from bloodshot or itchy eyes, dry eyes, burning eyes, foreign body sensation in eyes, fear of light, increased eye discharge, eyelash loss, blurred vision, decreased eyesight, etc.

[0035] Specifically, the skin disease may be one or more of seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, sarcoptic mange, basal cell carcinoma, and the like.

[0036] Specifically, the allergic disease may be one or more of allergic asthma, allergic rhinitis, allergic dermatitis, and the like.

[0037] Specifically, the pharmaceutical composition may be in any dosage form suitable for administration, such as an external preparation, particularly an ophthalmic preparation, an external dermatological preparation, and the like.

[0038] Specifically, the ophthalmic preparation may be eye drops, eye ointments, ophthalmic gels, eye emulsions, ophthalmic suspensions, ophthalmic films, eye washes, intraocular injections, and the like.

[0039] Specifically, the ophthalmic formulations may include pharma- ceutically acceptable auxiliary materials, such as pH adjusters, cosolvents, osmolality adjusters, viscosity adjusters, antioxidants, bacteriostatic preservatives, buffers, suspending agents, local anesthetics, surfactants, solubilizers, lubricants, emulsifiers, stabilizers, fillers, protective agents, solvents, and the like.

[0040] Specifically, the skin topical preparation may be an aerosol, a powder, a lotion, a tincture, a liniment, a coating, an ointment, a gel, a paste, an emulsion, or the like.

[0041] Specifically, the various dosage forms of the above-mentioned pharmaceutical composition of the present invention can be produced by general manufacturing methods in the pharmaceutical field.

[0042] Specifically, the pharmaceutical composition of the present invention may contain 0.01 to 99.5% by weight (specifically, for example, 0.01% by weight, 0.1% by weight, 0.5% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 95% by weight, 99% by weight, 99.5% by weight%) of the active ingredient.

[0043] Specifically, the pharmaceutical composition may be used in humans, or may be used as a veterinary drug in non-human animals, such as non-human mammals, including pet animals (e.g., dogs, cats, rabbits, mice, etc.) and livestock animals (e.g., horses, cows, goats, pigs, dogs, rabbits, etc.).

[0044] In another embodiment of the present invention, the acaricidal product of the present invention is a cosmetic product.

[0045] In particular, the cosmetic product further comprises auxiliary materials acceptable in the field of cosmetics.

[0046] Specifically, the cosmetic product of the present invention may be a facial cosmetic product, such as a facial cleanser, a soap, an emollient lotion, a cleansing lotion, a skin care lotion, a gel, a face cream, a sunscreen cream, an essence, a facial mask, a gel, a liquid foundation, or a lip balm.

[0047] Specifically, the cosmetic product of the present invention may be a cosmetic product for use on areas other than the face, such as neck cream, shampoo, body wash, soap, hair styling product, body lotion, lip balm, and the like.

[0048] Specifically, the cosmetic product of the present invention may also be a cosmetic product for the eyes and around the eyes, such as eye cream, mascara, eyeliner powder, eyeliner cream, eyeliner, eyeshadow powder, eyeshadow cream, eyebrow paint, eyebrow powder, etc.

[0049] Specifically, the various forms of the cosmetic product of the present invention may be produced by a general production method in the cosmetics field.

[0050] Specifically, the above-mentioned cosmetic product of the present invention may contain 0.01 to 99.5% by weight (specifically, for example, 0.01% by weight, 0.1% by weight, 0.5% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 95% by weight, 99% by weight, 99.5% by weight%) of the active ingredient.

[0051] In another embodiment of the present invention, the above-mentioned mite control product of the present invention is an acaricide capable of eliminating and suppressing mites that can infest items used in daily life (e.g., pillowcases, pillow stuffing, sheets, bedding, mattresses, clothing, carpets, cushions, sofas, summer mats, stuffed toys, air conditioners, etc.).

[0052] Specifically, the miticide may contain any suitable auxiliary material that can achieve the desired performance.

[0053] Specifically, the miticide may be in the form of a spray, a lotion, a patch, a small package, or the like.

[0054] Specifically, the various forms of the acaricide of the present invention may be prepared by the manufacturing methods commonly used in the field of daily care products.

[0055] Specifically, the above-mentioned miticide of the present invention may contain 0.01 to 99.5% by weight (specifically, for example, 0.01% by weight, 0.1% by weight, 0.5% by weight, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 95% by weight, 99% by weight, 99.5% by weight) of the active ingredient.

[0056] The present invention also provides a method for the prevention and / or treatment of a mite-infected disease, comprising the step of administering to a subject in need thereof the above-mentioned compounds of the present invention or their salts, isomers or solvates (in particular taraxasterol, taraxerol, taraxerone, lobric acid, taraxasterol acetate, taraxerol acetate, lupenone or its salts, isomers or solvates; diosmetin or its salts, isomers or solvates; swertiamarin, swelloside, gentiopicroside, loganic acid or its salts, isomers or solvates) or the above-mentioned pharmaceutical composition of the present invention.

[0057] Specifically, the disease may be an eye disease, a skin disease, an allergic disease, or the like.

[0058] Specifically, the eye disease may be one or more of blepharitis, meibomian gland dysfunction, blepharitis, eyelash loss, eyelash irregularity, glaucoma, cataract, ocular folliculitis, conjunctivitis, blepharoconjunctivitis, pterygium, keratitis, ptosis and ectropion of eyelid, eyelid basal cell carcinoma, dry eye, chalazion, etc., and may be accompanied by one or more symptoms selected from bloodshot or itchy eyes, dry eyes, burning eyes, foreign body sensation in eyes, fear of light, increased eye discharge, eyelash loss, blurred vision, decreased eyesight, etc.

[0059] Specifically, the skin disease may be one or more of seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, sarcoptic mange, basal cell carcinoma, and the like.

[0060] Specifically, the allergic disease may be one or more of allergic asthma, allergic rhinitis, allergic dermatitis, and the like.

[0061] In particular, said subject may be any animal, in particular a mammal, that is to undergo this prevention and / or treatment, such as a human, cat, dog, rabbit, rat, horse, cow, goat, pig, etc. In one embodiment of the invention, said subject is a human, in another embodiment of the invention, said subject is a non-human animal.

[0062] In one embodiment of the invention, the method is a method for treating and / or preventing mite-induced eye disease, comprising the step of administering to the eye of a subject in need thereof a compound of the invention or a salt, isomer or solvate thereof (in particular taraxasterol, taraxerol, taraxerone, lobric acid, taraxasterol acetate, taraxerol acetate, lupenone or a salt, isomer or solvate thereof; diosmetin or a salt, isomer or solvate thereof; sweltiamarin, swelloside, gentiopicroside, loganic acid or a salt, isomer or solvate thereof) or a pharmaceutical composition of the invention.

[0063] Specifically, the ocular administration may be in the form of eye drops, eye ointments, ophthalmic gels, eye emulsions, ophthalmic suspensions, ophthalmic films, eye washes, or intraocular injections.

[0064] Specifically, the dosage of the compound of the present invention or the above pharmaceutical composition of the present invention may be administered once or multiple times depending on the route of administration, the age and weight of the subject, the type and severity of the disease to be treated, and other variables.

[0065] As a result of the comparison, compared with the control group, all of the compounds presented in the present invention can shorten the survival time of mites, and in particular, taraxerol, diosmetin, gentiopicroside, and taraxasterol acetate can significantly shorten the survival time of mites, and can be used in mite extermination and inhibition products (e.g., medicines, cosmetics, daily necessities, etc.). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0066] Unless otherwise defined, all scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains.

[0067] In the present invention, the term "animal" generally refers to vertebrates, particularly mammals including humans. The term "non-human animal" refers to any vertebrate other than humans, particularly mammals. In some embodiments of the present invention, the non-human animal in the present invention is a livestock animal that is bred and domesticated by humans and whose reproduction can be artificially controlled, and is used for purposes such as food, labor, fur, pets, and experiments, and includes economic animals, pet animals, and laboratory animals. Examples of economic animals include livestock animals such as pigs, cows, goats, horses, donkeys, foxes, raccoon dogs, minks, and camels. Examples of pet animals include dogs, cats, rabbits, and mice (e.g., guinea pigs, hamsters, gerbils, Totoro, squirrels, etc.). Examples of laboratory animals include monkeys, dogs, rabbits, cats, and mice (e.g., rats and mice).

[0068] The technical solutions of the present invention will be described clearly and completely below with reference to the embodiments of the present invention, but obviously, the described embodiments are only a part of the embodiments of the present invention, and do not represent all of the embodiments. All other embodiments that a person skilled in the art can implement based on the embodiments of the present invention without creative efforts belong to the patent scope of the present invention. EXAMPLES

[0069] Example 1: Primary in vitro screening of compounds for their effect on Demodex survival time method 1. Single Compound The English names and molecular formulas of the selected single compounds are shown in Table 1 below. These compounds were standard products purchased from Chengdu Ruifensi Biotechnology Co., Ltd. [Table 1] 2. Preparation of Compound Solutions The powder of the compound reference product shown in Table 1 was dissolved in dimethyl sulfoxide (DMSO) and then diluted with sterile distilled water to a final DMSO concentration of 10%. A control test was performed, and this concentration did not shorten the survival time of Demodex mites. The negative control was DMSO mixed with sterile water to a final concentration of 10%. 3. In Vitro Cultivation of Demodex mites 35μl of each solution was added per slide, and the mites were observed once every 2 hours under an optical microscope to see if they were alive or not. The mites (body, limbs, etc.) were observed under a microscope to see if they were moving or not to determine whether they were dead or not. In the experiment, two experimenters experienced in Demodex mites observed and judged them separately, and if the judgment results differed, the other experienced experimenter judged them separately. In vitro culture was performed in an artificial climate room with a temperature of 20℃ and a humidity of 96%, and the slides were transported in a wet box during observation to ensure high humidity conditions. 4.Statistical methods In this experiment, statistics were performed using SPSS22.0 statistical software, normality tests were performed using the Shapiro-Wilk test, homogeneity tests were performed using the Bartlett test, and one-way ANOVA was performed for data that conformed to normal distribution and had uniform variances. If there was statistical significance, two groups were compared using the Bonferroni method. If the data did not conform to normal distribution, statistical analysis was performed using the Kruskal-Wallis test, with the test standard set at α = 0.05. 5. Experimental Results Effect of compounds on survival time of Demodex mites Demodex mites were cultured in vitro under an environment of 96% humidity and 20°C temperature, and the survival of the mites was dynamically observed and the survival time was recorded. The results are shown in Table 2. Compared with the negative control 10% DMSO, the in vitro survival time of Demodex mites was significantly shortened in the taraxerol group (37.91±20.96 vs. 80.79±25.34, P=0.006), the diosmetin group (35.92±14.82 vs. 80.79±25.34, P=0.001), the taraxasterol acetate group (37.91±20.96 vs. 80.79±25.34, P<0.001), and the gentiopicroside group (37.31±36.06 vs. 80.79±25.34, P<0.001). P<0.001), and the remaining single compound groups showed no significant difference in Demodex survival time compared to the control group (P>0.05). [Table 2]

[0070] The above is merely a preferred embodiment of the present invention, and is not intended to limit the present invention. All modifications, equivalent substitutions, etc. made without departing from the spirit and principles of the present invention are intended to be included in the patent scope of the present invention.

[0071] The foregoing embodiments and methods described herein are subject to the capabilities, experience and preferences of those skilled in the art.

[0072] In the present invention, the order of the method steps described is not intended to limit the order of the method steps in any way.

Claims

1. A product for controlling or controlling Demodex mites comprising taraxasterol, taraxerone, taraxerol acetate, lupenone or a salt or solvate thereof.

2. 2. The product of claim 1, wherein the Demodex mites are one or more of the following: Demodex folliculorum, Demodex mites.

3. The product according to any one of claims 1 to 2, wherein the product for controlling or controlling Demodex mites is a pharmaceutical composition, a cosmetic product or an acaricide.

4. The pharmaceutical composition is a pharmaceutical composition for preventing and / or treating a disease caused by Demodex mites infection, The disease is selected from eye diseases, skin diseases, and allergic diseases.

4. The article of manufacture according to claim 3.

5. 5. The product of claim 4, wherein the eye disease is selected from blepharitis, meibomian gland dysfunction, blepharitis, eyelash loss, eyelash irregularities, glaucoma, cataracts, ocular folliculitis, conjunctivitis, blepharoconjunctivitis, pterygium, keratitis, ptosis and ectropion of the eyelid, basal cell carcinoma of the eyelid, dry eye, and chalazion.

6. 5. The product of claim 4, wherein the skin disease is selected from seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, sarcoptic mange, and basal cell carcinoma.

7. The product of claim 4, wherein the allergic disease is selected from allergic asthma, allergic rhinitis, and allergic dermatitis.

8. The product of claim 3 , wherein the pharmaceutical composition is a topical formulation.

9. The product of claim 3 , wherein the pharmaceutical composition is an ophthalmic formulation or a topical dermatological formulation.

10. 10. The article of manufacture of claim 9, wherein the ophthalmic formulation is selected from eye drops, eye ointments, ophthalmic gels, eye emulsions, ophthalmic suspensions, ophthalmic films, eye washes, and intraocular injections.

11. 10. The product of claim 9, wherein the topical skin formulation is selected from an aerosol, a powder, a lotion, a tincture, a liniment, a coating, an ointment, a gel, a paste, and an emulsion.

12. The method of claim 3, wherein the pharmaceutical composition is a human pharmaceutical composition or a veterinary pharmaceutical composition.

13. 4. The product of claim 3, wherein the form of the cosmetic product is selected from facial cleanser, soap, emollient lotion, cleansing lotion, skin care lotion, gel, face cream, sunscreen cream, essence, facial mask, gel, liquid foundation, lip balm, neck cream, shampoo, body soap, hair styling product, body lotion, eye cream, mascara, eyeliner powder, eyeliner cream, eyeliner, eyeshadow powder, eyeshadow cream, eyebrow paint, eyebrow powder.

14. 4. The product of claim 3, wherein the form of the miticide is selected from a spray, a lotion, a patch, and a small package.

15. A pharmaceutical composition for treating and / or preventing diseases caused by Demodex mites, comprising one or more of taraxasterol, taraxerone, taraxerol acetate, lupenone or salts or solvates thereof.

16. The pharmaceutical composition according to claim 15, wherein the disease is selected from eye diseases, skin diseases, and allergic diseases.

17. 17. The pharmaceutical composition of claim 16, wherein the eye disease is selected from blepharitis, meibomian gland dysfunction, blepharitis, eyelash loss, eyelash irregularity, glaucoma, cataract, ophthalmic folliculitis, conjunctivitis, blepharoconjunctivitis, pterygium, keratitis, ptosis and ectropion of the eyelid, eyelid basal cell carcinoma, dry eye, and chalazion.

18. 17. The pharmaceutical composition of claim 16, wherein the skin disease is selected from seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, sarcoptic mange, and basal cell carcinoma.

19. The pharmaceutical composition according to claim 16, wherein the allergic disease is selected from allergic asthma, allergic rhinitis, and allergic dermatitis.

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