WO2021213483A1 - 化合物在抑制或杀灭螨虫中的应用 - Google Patents

化合物在抑制或杀灭螨虫中的应用 Download PDF

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WO2021213483A1
WO2021213483A1 PCT/CN2021/089105 CN2021089105W WO2021213483A1 WO 2021213483 A1 WO2021213483 A1 WO 2021213483A1 CN 2021089105 W CN2021089105 W CN 2021089105W WO 2021213483 A1 WO2021213483 A1 WO 2021213483A1
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Prior art keywords
alkyl
cycloalkyl
nhc
carbon atom
nhso
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PCT/CN2021/089105
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English (en)
French (fr)
Inventor
张岩
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Smilebiotek Zhuhai Ltd
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Zhuhai Qiwei Bio Technology Ltd
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Priority to JP2022564789A priority Critical patent/JP7607867B2/ja
Priority to CA3176168A priority patent/CA3176168A1/en
Priority to EP21792591.6A priority patent/EP4122468A4/en
Priority to KR1020227036906A priority patent/KR20230004529A/ko
Priority to NZ793402A priority patent/NZ793402A/en
Priority to US17/920,731 priority patent/US20230172945A1/en
Priority to MX2022013312A priority patent/MX2022013312A/es
Priority to AU2021261807A priority patent/AU2021261807B2/en
Application filed by Zhuhai Qiwei Bio Technology Ltd filed Critical Zhuhai Qiwei Bio Technology Ltd
Priority to IL297567A priority patent/IL297567A/en
Priority to BR112022021549A priority patent/BR112022021549A2/pt
Publication of WO2021213483A1 publication Critical patent/WO2021213483A1/zh
Priority to ZA2022/11389A priority patent/ZA202211389B/en
Anticipated expiration legal-status Critical
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/02—Acaricides
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    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
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    • A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
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    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
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    • A01N45/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds having three or more carbocyclic rings condensed among themselves, at least one ring not being a six-membered ring
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    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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Definitions

  • the present invention relates to the field of medicine, in particular to the application of compounds having the structure of formula I, II or III in inhibiting or killing mites.
  • Mites belong to a class of tiny animals in the Arthropod phylum Arachnida.
  • the body size is generally about 0.5 mm, some as small as 0.1 mm, and most species are less than 1 mm. It has been found that the mites have a very close relationship with the health of humans and animals (such as dogs, cats and other pets), such as gamma mites, chiggers, scabies, demodex mites, acaroid mites, dust mites and tarsal mites can suck blood and damage the skin. Cause "rosacea" or demodex, allergies, urinary tract mites, lung mites, intestinal mites and scabies, etc., seriously endangering the health of humans and animals.
  • Demodex mites are microscopic ectoparasites that usually infect the sebaceous gland units of skin hair follicles.
  • Demodex folliculorum and Demodex sebaceous have been found on the human body, and they mainly reside in hair follicles, sebaceous glands, and meibomian glands.
  • Demodex can swallow epithelial cells of hair follicles, cause hair follicle expansion and hair loss, manifested as clinical blepharitis, meibomian gland dysfunction, eyelash loss, abnormal eyelash arrangement, conjunctivitis and blepharoconjunctivitis, pterygium, keratitis , Eyelid basal cell carcinoma, etc.
  • Demodex can also swallow lipids and cause dry eyes.
  • demodex mites can also cause obstruction of the meibomian gland discharge duct through mechanical obstruction, causing difficulty in lipid discharge and excessive secretion retention, leading to the formation of chalazion.
  • the clinical manifestations of demodex infection of eye disease mainly include: recurrent red and itchy eye edges; dry eyes, eye burning sensation, eye foreign body sensation, photophobia, increased secretion; may be accompanied by repeated eyelash loss; severe cases involving cornea There may be blurred vision and decreased vision.
  • Demodex infection is related to a variety of common skin diseases, including seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, and basal cells. Cancer, etc. (see, for example, Luo, X., Li, J., Chen, C., Tseng, S. & Liang, L.
  • Demodex mites are often located in the sebaceous glands and meibomian glands. Occupy the human eyelash hair follicles, they can cause eye diseases when they infect the skin of the face.
  • Ocular Demodicosis as a Potential Cause of Ocular Surface Inflammation (Cornea 36 Suppl 1(Suppl 1): s9-s14) proves that Demodex short and Demodex folliculorum are two kinds of Demodex that cause ocular mitosis in humans. There is a positive correlation between human age and the risk of disease, and there is a strong positive correlation between eye mite disease and ocular surface inflammation.
  • Demodex species in human ocular disease new clinical pathological aspects (International ophthalmology 37(1): 303-312) Studies have shown that Demodex short mites and Demodex folliculorum are related to the pathogenesis of external eye diseases, and ocular acariasis can cause extraocular diseases. The ecological environment is out of balance.
  • 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 the potential for demodex infections as several ocular surface diseases.
  • the etiology, demodex parasites on the front structures of the eyes such as eyelids, eyelashes and ocular surface will cause human eye mites disease and the incidence is positively correlated with age.
  • demodex The relationship between demodex and ocular discomfort (Investigative ophthalmology & visual science 51(6): 2906-2911) proposed that the number of demodex mites is positively correlated with the severity of eye disease and the age of the patient.
  • Demodex mites (Clinics in dermatology 32(6):739-743) proposed that Demodex infection can cause chronic blepharitis, and the prevalence of chronic blepharitis is positively correlated with the number of mites and the age of the patient.
  • Demodex is a carrier of Bacillus, which can play a role in the pathogenesis of blepharitis as a co-pathogen.
  • Bacillus oleronius and Demodex mite infection in patients with chronic blepharitis (Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 1020-1025) Occurrence, and it is a carrier of Bacillus, which can act as a co-pathogen in the development of blepharitis.
  • the present invention provides a series of compounds that can be used to inhibit or kill mites.
  • R 2 , R 3 , R 6 , R 7 , R 8 , and R 9 are independently selected from 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, NH 2 .
  • R 4 is selected from H, C 1-8 alkyl, O (C 1-8 alkyl), NH (C 1-8 alkyl), N (C 1-8 alkyl) 2 , C 3-11 cycloalkane Group, O (C 1-8 cycloalkyl), OH, NH 2, or, when there is a double bond between carbon atom No. 1 and carbon atom No. 4 , R 4 does not exist.
  • R 5 is selected from H, C 1-8 alkyl, O (C 1-8 alkyl), NH (C 1-8 alkyl), N (C 1-8 alkyl) 2 , C 3-11 cycloalkane Group, O (C 1-8 cycloalkyl), OH, NH 2, or, when there is a double bond between carbon atom 2 and carbon atom 3, R 5 does not exist.
  • the compound of formula I described in the present invention is a compound of formula I-1:
  • n is an integer of 1-4, for example, 1, 2, 3, and 4.
  • R 2 , R 3 , R 6 , R 7 , R 8 , and R 9 are independently selected from H, C 1-3 alkyl, O (C 1-3 alkyl), C 3-6 cycloalkyl , OH, NH 2 .
  • R 2 , R 3 , R 6 , R 7 , R 8 , and R 9 are independently selected from H or methyl.
  • R 4 is selected from H, C 1-3 alkyl, O (C 1-3 alkyl), C 3-6 cycloalkyl, O (C 1-3 cycloalkyl), OH.
  • R 4 is selected from H or methyl.
  • R 5 is selected from H, C 1-3 alkyl, O (C 1-3 alkyl), C 3-6 cycloalkyl, O (C 1-3 cycloalkyl), OH.
  • R 5 is selected from H or methyl.
  • R 10 and R 13 are independently selected from H, C 1-3 alkyl, O (C 1-3 alkyl), C 3-6 cycloalkyl, OH, NH 2 .
  • R 10 and R 13 are independently selected from H or methyl.
  • R 14 when there is a single bond between R 14 and carbon atom No. 8, R 14 is selected from H, C 1-3 alkyl, O (C 1-3 alkyl), C 3-6 cycloalkyl, OH , NH 2 , and the hydrogen atom on carbon atom 8 is also substituted by R 14 ; when R 14 and carbon atom 8 are double bonds, R 14 is selected from CH2, CH (C 1-3 alkyl), C(C 1-3 alkyl) 2 . Specifically, when R 14 is a single bond with carbon atom No. 8, R 14 is selected from H or a methyl group, and the hydrogen atom on carbon atom No. 8 is also substituted by H or a methyl group; when R 14 and When there is a double bond between carbon atoms on the 8th, R 14 is selected from CH 2 (methylene).
  • the compound of formula I is dandelion sterol, taraxacilrol, taraxazone aceton, querconic acid, taraxacum sterol acetate, acetyl taraxacum terpene alcohol, lupinone or its salt, isomer Body, solvate.
  • the compound of formula II is:
  • R 17 , R 19 , R 21 , and R 22 are independently selected from H, C 1-8 alkyl, O (C 1-8 alkyl), C 3-11 cycloalkyl, aryl, heteroaryl, C 3-11 heterocycloalkyl, O(C 1-8 cycloalkyl) or groups of formula II-1, II-2, II-3:
  • R 17 , R 19 , R 21 , and R 22 are independently selected from H, C 1-3 alkyl, O (C 1-3 alkyl), or groups of formula II-1 and II-2. More specifically, R 17 , R 19 , R 21 , and R 22 are independently selected from H or methyl.
  • the compound of formula II is geraniol or a salt, isomer, or solvate thereof.
  • the compound of formula III is:
  • R 25 is selected from
  • the compound of formula III of the present invention is a compound of formula III-1 or III-2:
  • the carbon atom No. 1 and the carbon atom No. 2 in the formula III-1 are selected from a double bond or a single bond.
  • R 32 does not exist; when the carbon atom No. 1 and the carbon atom No.
  • R 25 is selected from
  • R 30 , R 31 , R 33 , R 34 , and R 35 are selected from H, methyl, and OH.
  • R 32 does not exist.
  • the compound described in formula III is sorrel, plasterin, gentiopicrin, loganylic acid or a salt, isomer, or solvate thereof.
  • the compounds of the present invention or their salts, isomers, and solvates can be used as the sole active component for inhibiting or killing mites, or can be combined with other components with the same or different activities for inhibiting or killing mites. Kill mites.
  • the compound of the present invention can be obtained by extracting from natural plants, such as natural plants such as dandelion, gentian, gentian, and chrysanthemum, and the extraction method can be a conventional method in the art.
  • the compounds of the present invention can also be prepared by chemical synthesis or biosynthesis.
  • acaricidal products of the present invention can be used for therapeutic/or preventive purposes, and can also be used for non-therapeutic/or preventive purposes.
  • the aforementioned mites of the present invention may be one or more of Demodex mites, dust mites, and scabies mites.
  • the above-mentioned mites of the present invention are Demodex mites, such as Demodex folliculorum and Demodex sebaceous.
  • the above-mentioned acaricidal product of the present invention is a pharmaceutical composition.
  • the above-mentioned pharmaceutical composition further comprises pharmaceutically acceptable excipients.
  • the above-mentioned pharmaceutical composition of the present invention is used to prevent and/or treat diseases caused by mite infection.
  • the aforementioned diseases may be eye diseases, skin diseases, allergic diseases, and the like.
  • the above-mentioned eye diseases may be blepharitis, meibomian gland dysfunction, meibomitis, eyelash loss, abnormal eyelash alignment, glaucoma, cataracts, ocular folliculitis, conjunctivitis, blepharoconjunctivitis, pterygium, One or more of keratitis, eyelid sagging and ectropion, basal cell carcinoma of the eyelid, dry eye, chalazion, etc.; it may have one or more symptoms selected from the following: red and itchy eyes, dry eyes , Eye burning, foreign body sensation, photophobia, increased ocular secretions, eyelash loss, blurred vision, decreased vision, etc.
  • the aforementioned skin disease may be one or more of seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodicosis, scabies, basal cell carcinoma, and the like.
  • the above-mentioned allergic disease may be one or more of allergic asthma, allergic rhinitis, allergic dermatitis, and the like.
  • the above-mentioned pharmaceutical composition may be in any dosage form suitable for administration, such as an external preparation, especially an ophthalmic preparation, an external preparation for the skin, and the like.
  • the above-mentioned ophthalmic preparations may be eye drops, eye ointments, ophthalmic gels, ophthalmic emulsions, ophthalmic suspensions, ophthalmic membranes, eye washes, intraocular injections, and the like.
  • the ophthalmic preparations may include pharmaceutically acceptable excipients, such as pH regulators, solubilizers, osmotic pressure regulators, viscosity regulators, antioxidants, bacteriostatic preservatives, buffers, suspending agents, Local anesthetics, surfactants, solubilizers, wetting agents, emulsifiers, stabilizers, fillers, protective agents, solvents, etc.
  • pharmaceutically acceptable excipients such as pH regulators, solubilizers, osmotic pressure regulators, viscosity regulators, antioxidants, bacteriostatic preservatives, buffers, suspending agents, Local anesthetics, surfactants, solubilizers, wetting agents, emulsifiers, stabilizers, fillers, protective agents, solvents, etc.
  • the above-mentioned external preparations for skin may be aerosols, powders, lotions, tinctures, liniments, coatings, ointments, gels, pastes, emulsions, and the like.
  • the various dosage forms of the above-mentioned pharmaceutical composition of the present invention can be prepared according to conventional production methods in the pharmaceutical field.
  • the above-mentioned pharmaceutical composition of the present invention may contain 0.01-99.5% by weight (specifically, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7 %, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%) active ingredients.
  • the above-mentioned pharmaceutical composition can be used for humans, and can also be used as a veterinary medicine for non-human animals, such as non-human mammals, such as pet animals (such as dogs, cats, rabbits, rats, etc.), livestock animals (such as, Horses, cows, sheep, pigs, dogs, rabbits, etc.) and other animals.
  • non-human mammals such as pet animals (such as dogs, cats, rabbits, rats, etc.), livestock animals (such as, Horses, cows, sheep, pigs, dogs, rabbits, etc.) and other animals.
  • the above-mentioned acaricide products of the present invention are cosmetics.
  • the aforementioned cosmetics also include auxiliary materials acceptable in the cosmetics field.
  • the above-mentioned cosmetics of the present invention may be cosmetics for the face, such as facial cleanser, soap, softening lotion, toner, skin care lotion, gel, facial cream, sunscreen, essence, facial mask, gel, liquid foundation, scrub paste.
  • cosmetics for the face such as facial cleanser, soap, softening lotion, toner, skin care lotion, gel, facial cream, sunscreen, essence, facial mask, gel, liquid foundation, scrub paste.
  • the aforementioned cosmetics of the present invention may be cosmetics for other parts of the face, such as neck cream, shampoo, shower gel, soap, conditioner, body lotion, scrub and the like.
  • the aforementioned cosmetics of the present invention may also be cosmetics for the eyes and around the eyes, such as eye cream, mascara, eyeliner powder, eyeliner, eyeliner, eye shadow powder, eye shadow cream, eyebrow pencil, eyebrow powder and the like.
  • the various forms of the aforementioned cosmetics of the present invention can be prepared according to conventional production methods in the cosmetics field.
  • the aforementioned cosmetics of the present invention may contain 0.01-99.5% by weight (specifically, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%) active ingredients.
  • the above-mentioned acaricide products of the present invention are acaricides, which can be used to kill and inhibit items in the living environment (eg, pillowcases, pillow cores, bed sheets, bedding, mattresses, clothing, carpets). , Cushions, sofas, summer mats, plush toys, air conditioners, etc.) may live in mites.
  • acaricides which can be used to kill and inhibit items in the living environment (eg, pillowcases, pillow cores, bed sheets, bedding, mattresses, clothing, carpets).
  • Cushions, sofas, summer mats, plush toys, air conditioners, etc.) may live in mites.
  • the above-mentioned acaricide may contain any suitable auxiliary materials that can achieve the desired performance.
  • the above-mentioned acaricide may be in the form of sprays, lotions, patches, small packages, and the like.
  • the various forms of the above-mentioned acaricides of the present invention can be prepared according to conventional production methods in the field of daily care products.
  • the above-mentioned acaricide of the present invention may contain 0.01-99.5% by weight (specifically, 0.01%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7 %, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%) active ingredients.
  • the present invention also provides a method for preventing and/or treating diseases caused by mite infection, which comprises administering the above-mentioned compound of the present invention or its salt, isomer, solvate (especially dandelion sterol, dandelion) to a subject in need thereof Tetraol, taraxacum acetophenone, quercetin, taraxacum sterol acetate, acetyl dandelion alcohol, lupinone or its salt, isomer, solvate, or geraniol or its salt, isomer, solvate , Or, the steps of swerbin, swerbin, gentiopicrin, loganic acid or its salt, isomer, solvate) or the above-mentioned pharmaceutical composition of the present invention.
  • the aforementioned diseases may be eye diseases, skin diseases, allergic diseases, and the like.
  • the above-mentioned eye diseases may be blepharitis, meibomian gland dysfunction, meibomitis, eyelash loss, abnormal eyelash alignment, glaucoma, cataracts, ocular folliculitis, conjunctivitis, blepharoconjunctivitis, pterygium, One or more of keratitis, eyelid sagging and ectropion, basal cell carcinoma of the eyelid, dry eye, chalazion, etc.; it may have one or more symptoms selected from the following: red and itchy eyes, dry eyes , Eye burning sensation, foreign body sensation, photophobia, increased ocular secretions, loss of eyelashes, blurred vision, decreased vision, etc.
  • the aforementioned skin disease may be one or more of seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodicosis, scabies, basal cell carcinoma, and the like.
  • the above-mentioned allergic disease may be one or more of allergic asthma, allergic rhinitis, allergic dermatitis, and the like.
  • the aforementioned subject may be any animal receiving the prevention and/or treatment, particularly mammals, such as humans, cats, dogs, rabbits, mice, horses, cattle, sheep, pigs, and the like.
  • the above-mentioned subject is a human; in another embodiment of the present invention, the above-mentioned subject is a non-human animal.
  • the above-mentioned method is a method for treating and/or preventing ocular diseases caused by mites, which comprises administering the above-mentioned compound of the present invention or a salt, isomer, or isomer thereof to the eyes of a subject in need thereof.
  • Solvates (especially taraxacum sterol, taraxacilrol, taraxacum aceton, quercetin, taraxacum sterol acetate, acetyl taraxacum terpene alcohol, lupinone or its salts, isomers, solvates, or, geraniol or Its salts, isomers, solvates, or, sagelanin, sagelanin, gentiopicrin, loganylic acid or its salts, isomers, solvates) or the above-mentioned pharmaceutical composition of the present invention A step of.
  • the above-mentioned ocular administration can be administered in the form of eye drops, eye ointments, ophthalmic gels, ophthalmic emulsions, ophthalmic suspensions, ophthalmic films, eye washes, and intraocular injections.
  • the administration amount of the compound of the present invention or the above-mentioned pharmaceutical composition of the present invention may vary according to the route of administration, the age, weight of the subject, the type and severity of the disease to be treated, etc., and may be administered one or more times.
  • the compounds of the present invention can reduce the survival time of mites, especially taraxazone, geraniol, gentiopicroside and taraxerol acetate significantly shorten the survival time of mites.
  • mites killing and suppression products such as medicines, cosmetics, daily necessities, etc.
  • the term "animal” generally refers to vertebrates, especially mammals, including humans.
  • the term “non-human animal” refers to any vertebrate other than humans, especially mammals.
  • the non-human animal in the present invention is a domestic animal, that is, an animal that is raised and domesticated by humans and whose reproduction can be artificially controlled for functions such as food, labor, fur, pets, experiments, etc. , Such as economic animals, pet animals, laboratory animals, etc.
  • Pet animals such as dogs, cats, rabbits, rats (such as guinea pigs, hamsters, gerbils, chinchillas, squirrels, etc.).
  • Experimental animals such as monkeys, dogs, rabbits, cats, mice (such as rats, mice), etc.
  • Example 1 The effect of in vitro preliminary screening of compounds on the survival time of Demodex mites
  • the monomer was purchased from Chengdu Refines Biotechnology Co., Ltd. as a standard product.
  • Table 1 Chinese and English names and molecular formulas of Chinese medicine monomers
  • the powder of the reference compound shown in Table 1 was dissolved in dimethyl sulfoxide (DMSO) first, and then diluted with sterilized double-distilled water to make the final concentration of DMSO 10%. After a control test, this concentration could not shorten the creep shape. The survival time of the mites.
  • the negative control is DMSO mixed with sterile water, and the final concentration is 10%.
  • the survival time of Demodex in the glycoside group was significantly shorter than that in the control group (37.31 ⁇ 36.06vs.80.79 ⁇ 25.34, P ⁇ 0.001).
  • the survival time of Demodex in the other monomer compound group was not significantly different from that in the control group. (P>0.05).

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Abstract

一系列化合物在抑制或杀灭螨虫中的应用，通过对比发现，与对照组相比，该化合物可减少螨虫的存活时间，特别是蒲公英赛醇、香叶木素和蒲公英甾醇醋酸酯可显著缩短螨虫存活时间，可用于螨虫杀灭和抑制产品(如药品、化妆品、日用品等)。

Description

化合物在抑制或杀灭螨虫中的应用 技术领域
本发明涉及医药领域，具体涉及具有式I、II或III结构的化合物在抑制或杀灭螨虫中的应用。
背景技术
螨虫属于节肢动物门蛛形纲广腹亚纲的一类体型微小的动物，身体大小一般都在0.5毫米左右，有些小到0.1毫米，大多数种类小于1毫米。现发现螨虫与人类和动物(如狗、猫等宠物)的健康关系非常密切，诸如革螨、恙螨、疥螨、蠕形螨、粉螨、尘螨和蒲螨等可吸血、侵害皮肤，引起“酒糟鼻”或蠕螨症、过敏症、尿路螨症、肺螨症、肠螨症和疥疮等，严重危害人类和动物的身体健康。
蠕形螨属螨虫是通常感染皮肤毛囊皮脂腺单位的微观体外寄生虫。在所报导物种中，至少毛囊蠕形螨和皮脂蠕形螨已在人类体表上发现，其主要寄居在毛囊和皮脂腺、睑板腺。蠕形螨可吞噬毛囊上皮细胞，引起毛囊扩张和脱毛，表现为临床上的睑缘炎、睑板腺功能障碍、睫毛脱落、睫毛排列异常、结膜炎和睑结膜炎、翼状胬肉、角膜炎、眼睑基底细胞癌等。蠕形螨还可吞噬脂质，引起干眼。此外，蠕形螨还可以通过机械性的阻塞造成睑板腺排出管道阻塞，引起脂质排出困难和过量的分泌物潴留，导致霰粒肿的形成。蠕形螨感染眼病的临床表现主要包括：反复发作的眼边红痒；眼干、眼烧灼感、眼部异物感、畏光、分泌物增多；可伴有反复睫毛脱落；重者累及角膜时可有视物模糊、视力下降。除了以上眼病，近年有不少研究指出蠕形螨感染和多种常见的皮肤疾病相关，包括脂溢性皮炎、痤疮、酒糟鼻、毛囊性糠疹、口周皮炎、蠕形螨病、基底细胞癌等(参见，例如，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 dermatology 170,1219-1225)。
特别地，螨虫与眼部疾病的关系被得到证实的报道包括：
Human Permanent Ectoparasites；Recent Advances on Biology and Clinical Significance of Demodex Mites:Narrative Review Article(Iranian journal of parasitology 12(1):12-21)表明了短蠕形螨位于皮脂腺和睑板腺，毛囊蠕形螨常占据人类睫毛毛囊部位，它们感染脸部皮肤后会引起眼病。
Ocular Demodicosis as a Potential Cause of Ocular Surface Inflammation(Cornea 36 Suppl 1(Suppl 1):s9-s14)证明了短蠕形螨和毛囊蠕形螨是两种致使人类患眼螨病的蠕形螨，同时人类年龄与患病风险呈正相关性，眼螨病与眼表炎症状况有很强的正相关性。
Demodex species in human ocular disease:new clinicopathological aspects(International ophthalmology 37(1):303-312)研究表明短蠕形螨和毛囊蠕形螨与外眼疾病的发病机制有关，而眼螨病会导致眼外生态环境失衡。
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)中描述了蠕形螨感染是几种眼表疾病的潜在病因，蠕形螨寄生在眼睛的前部结构如眼睑、睫毛和眼表会致使人类患眼螨病且发病率与年龄呈正相关。
The relationship between demodex and ocular discomfort(Investigative ophthalmology&visual science 51(6):2906-2911)提出了蠕形螨的数量与眼病的严重程度及患者的年龄呈正相关性。
Demodex mites(Clinics in dermatology 32(6):739-743)提出了蠕形螨感染会引发慢性睑缘炎，慢性睑缘炎患病率与螨虫的数量和患者年龄成正相关。
Quantitative Analysis of the Bacteria in Blepharitis With Demodex Infestation(Frontiers in microbiology 9:1719)研究表明短蠕形螨和毛囊蠕形螨感染会导致眼部疾病的发生，且患病率与螨虫数量和患者年龄呈正相关。蠕形螨是芽孢杆菌的携带者，其可作为共病原体在睑缘炎的发病机制中发挥作用。
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)认为蠕形螨可导致睑缘炎疾病的发生，且其是一种芽孢杆菌的携带者，其可在睑缘炎的发展过程中起到了共病原体的作用。
Correlation between ocular Demodex infestation and serum immunoreactivity to Bacillus proteins in patients with Facial rosacea(Ophthalmology 117(5):870-877.e871)提出了干眼症患者眼部蠕形螨感染的发生率低于非干眼症患者，螨虫感染和细菌感染可以并存于眼表炎症中。
High prevalence of demodex brevis infestation in chalazia(American journal of ophthalmology 157(2):342-348.e341)研究表明了成人和患有睑板腺囊肿的儿科患者中短蠕形螨病的发病率很高，眼部蠕形螨病是睑板腺囊肿的一大病因。
螨虫引起的疾病(如眼部疾病、皮肤疾病)目前在临床还没有引起足够重视，经常被误诊为细菌性疾病等，常规抗菌药治疗常常无明显疗效。
因此，本发明提供了一系列化合物，可用于抑制或杀灭螨虫。
发明内容
式I所述的化合物或其盐、异构体、溶剂化物在制备抑制或杀灭螨虫产品中的应用，所述的式I化合物为：
Figure PCTCN2021089105-appb-000001
其中，R 1选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH 2、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH 2、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，或者，R 1与5号碳原子之间为双键时，R 1选自O或S。
R 2、R 3、R 6、R 7、R 8、R 9独立地选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8 烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2。
R 4选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，或者，当1号碳原子与4号碳原子之间为双键时，R 4不存在。
R 5选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，或者，当2号碳原子与3号碳原子之间为双键时，R 5不存在。
6号碳原子与7号碳原子之间为双键或单键。
R 10和R 13独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 1-8炔基、CH＝CH(C 1-8烷基)、CH＝CH 2、C(C 1-8烷基)＝CH 2、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
R 11和R 12独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 1-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，或者，R 11和R 12为碳原子并且与其之间的碳原子形成5-8元环，所述环上的任意碳原子上的H可被C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2、C 2-8烯基、C 2-8炔基、CH＝CH 2、C(C 1-8烷基)＝CH 2、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2所取代。
具体地，本发明所述的式I化合物为式I-1的化合物：
Figure PCTCN2021089105-appb-000002
其中，当R 14与8号碳原子之间为单键时，R 14选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，并且，8号碳原子上的氢原子任选的被R 14取代；当R 14与8号碳原子之间为双键时R 14选自O、S、CH 2、CH(C 1-8烷基)、C(C 1-8烷基) 2。
R 15选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
n为1-4的整数，例如为1、2、3、4。
具体地，R 1选自H、C 1-3烷基、OH、OC(＝O)(C 1-3烷基)、(C 1-3烷基)CO 2H、CF 3、CHF 2、CH 2F，或者，R 1与5号碳原子之间为双键时，R 1为O。更具体地，R 1选自OH、OC(＝O)(C 1-3烷基)。特别具体地，R 1选自OH、OC(＝O)CH 3。
具体地，R 2、R 3、R 6、R 7、R 8、R 9独立地选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2。特别具体地，R 2、R 3、R 6、R 7、R 8、R 9独立地选自H或甲基。
具体地，1号碳原子与4号碳原子之间为单键，R 4选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、O(C 1-3环烷基)、OH。特别具体地，1号碳原子与4号碳原子之间为单键，R 4选自H或甲基。
具体地，2号碳原子与3号碳原子之间为单键，R 5选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、O(C 1-3环烷基)、OH。特别具体地，2号碳原子与3号碳原子之间为单键，R 5选自H或甲基。
具体地，6号碳原子与7号碳原子之间为单键。
具体地，R 10和R 13独立地选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2。特别具体地，R 10和R 13独立地选自H或甲基。
具体地，当R 14与8号碳原子之间为单键时，R 14选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2，并且，8号碳原子上的氢原子同样被R 14取代；当R 14与8号碳原子之间为双键时R 14选自CH2、CH(C 1-3烷基)、C(C 1-3烷基) 2。特别具体地，当R 14与8号碳原子之间为单键时，R 14选自H或甲基，并且，8号碳原子上的氢原子同样被H或甲基取代；当R 14与8号碳原子之间为双键时R 14选自CH 2(亚甲基)。
具体地，R 15选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH 2、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2。特别具体地，R 15选自H、C 1-3烷基、C(CH 3)＝CH 2。
在本发明的具体实施方式中，所述的式I化合物为蒲公英甾醇、蒲公英赛醇、蒲公英赛酮、栎樱酸、蒲公英甾醇醋酸酯、乙酰蒲公英萜醇、羽扇烯酮或其盐、异构体、溶剂化物。
式II所述的化合物或其盐、异构体、溶剂化物在制备抑制或杀灭螨虫产品中的应用，所述的式II化合物为：
Figure PCTCN2021089105-appb-000003
其中，R 16、R 18、R 20、R 23、R 24独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8 烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
R 17、R 19、R 21、R 22独立地选自H、C 1-8烷基、O(C 1-8烷基)、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)或式II-1、II-2、II-3的基团：
Figure PCTCN2021089105-appb-000004
具体地，R 16、R 18、R 20、R 23、R 24独立地选自H、卤素、C 1-3烷基、O(C 1-3烷基)、NH(C 1-3烷基)、N(C 1-3烷基) 2、C 3-11环烷基、OH、NH 2、OC(＝O)(C 1-3烷基)、C(＝O)(C 1-3烷基)、(C 1-3烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C 2-3烯基、C 2-3炔基、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2。更具体地，R 16、R 18、R 20、R 23、R 24独立地选自H或甲基。
具体地，R 17、R 19、R 21、R 22独立地选自H、C 1-3烷基、O(C 1-3烷基)或式II-1、II-2的基团。更具体地，R 17、R 19、R 21、R 22独立地选自H或甲基。
在本发明的具体实施方式中，所述的式II化合物为香叶木素或其盐、异构体、溶剂化物。
式III所述的化合物或其盐、异构体、溶剂化物在制备抑制或杀灭螨虫产品中的应用，所述的式III化合物为：
Figure PCTCN2021089105-appb-000005
其中，R 25选自
Figure PCTCN2021089105-appb-000006
R 26为碳原子，其与R 27和R 28中至少一个形成5-8元环，并且R 27和R 28中不与R 26成环的 基团选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
R 29选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
具体地，本发明所述的式III化合物为式III-1或III-2的化合物：
Figure PCTCN2021089105-appb-000007
其中，R 30、R 31、R 33、R 34、R 35选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
式III-1中1号碳原子与2号碳原子之间选自双键或单键。当III-1中1号碳原子与2号碳原子 之间选自双键时，R 32不存在；当III-1中1号碳原子与2号碳原子之间选自单键时，R 32选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
具体地，R 25选自
Figure PCTCN2021089105-appb-000008
具体地，R 27和R 28中不与R 26成环的基团选自H、C 1-3烷基、O(C 1-3烷基)、O(C 1-3环烷基)、C 2-3烯基、C 2-3炔基、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2、OC(＝O)(C 1-3烷基)、C(＝O)(C 1-3烷基)、(C 1-3烷基)CO 2H、CO 2H。更具体地，R 27和R 28中不与R 26成环的基团选自H、CH＝CH 2、CO 2H。
具体地，R 30、R 31、R 33、R 34、R 35选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH 2、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2。特别具体地，R 30、R 31、R 33、R 34、R 35选自选自H、甲基、OH。
具体地，III-1中1号碳原子与2号碳原子之间选自双键时，R 32不存在。
在本发明的具体实施方式中，式III所述的化合物为獐牙菜苦苷、獐牙菜苷、龙胆苦苷、马钱苷酸或其盐、异构体、溶剂化物。
具体地，本发明所述的化合物或其盐、异构体、溶剂化物可以作为唯一的抑制或杀灭螨虫活性组分，也可以与其他相同或不同的活性的组分组合用于抑制或杀灭螨虫。
本发明所述的化合物可以通过天然植物提取得到，例如蒲公英、秦艽、龙胆、菊花等天然植物，所述的提取方法可以为本领域常规的方法。
本发明所述的化合物也可以通过化学合成或生物合成制备得到。
具体地，本发明上述杀螨产品可用于治疗/或预防目的，也可用于非治疗/或预防目的。
具体地，本发明上述螨虫可以为蠕形螨、尘螨、疥螨等中的一种或多种。在本发明的一个实施例中，本发明上述螨虫为蠕形螨，如毛囊蠕形螨和皮脂蠕形螨。
在本发明的一个实施方式中，本发明上述杀螨产品为药物组合物。
具体地，上述药物组合物还包含药学上可接受的辅料。
具体地，本发明上述药物组合物用于预防和/或治疗螨虫感染引起的疾病。
具体地，上述疾病可以为眼部疾病、皮肤疾病、过敏性疾病等。
具体地，上述眼部疾病可以为睑缘炎、睑板腺功能障碍、睑板炎、睫毛脱落、睫毛排列异常、青光眼、白内障、眼部毛囊炎、结膜炎、睑结膜炎、翼状胬肉、角膜炎、眼睑松弛和外翻、眼睑基底细胞癌、干眼症、霰粒肿等中的一种或多种；其可具有选自以下的一种或多种症状：眼部红痒、眼干、眼烧灼感、异物感、畏光、眼部分泌物增多、睫毛脱落、视物模糊、视力下降等。
具体地，上述皮肤疾病可以为脂溢性皮炎、痤疮、酒糟鼻、毛囊性糠疹、口周皮炎、蠕形螨病、疥螨病、基底细胞癌等中的一种或多种。
具体地，上述过敏性疾病可以为过敏性哮喘、过敏性鼻炎、过敏性皮炎等中的一种或多种。
具体地，上述药物组合物可以为任何适宜施用的剂型，如外用制剂，特别是眼用制剂、皮肤外用制剂等。
具体地，上述眼用制剂可以为滴眼剂、眼膏剂、眼用凝胶剂、眼用乳剂、眼用混悬剂、眼用膜剂、洗眼剂、眼内注射剂等。
具体地，所述的眼用制剂可以包括药学上可接受的辅料，例如pH调节剂、助溶剂、渗透压调节剂、粘度调节剂、抗氧化剂、抑菌防腐剂、缓冲剂、助悬剂、局部麻醉剂、表面活性剂、增溶剂、润湿剂、乳化剂、稳定剂、填充剂、保护剂、溶剂等。
具体地，上述皮肤外用制剂可以为气雾剂、粉剂、洗剂、酊剂、搽剂、涂膜剂、软膏剂、凝胶剂、糊剂、乳剂等。
具体地，本发明上述药物组合物的各种剂型可以按照药学领域的常规生产方法制备。
具体地，本发明上述药物组合物可以含有重量比为0.01-99.5％(具体如，0.01％，0.1％、0.5％、1％、2％、3％、4％、5％、6％、7％、8％、9％、10％、20％、30％、40％、50％、60％、70％、80％、90％、95％、99％、99.5％)的活性成分。
具体地，上述药物组合物可用于人类，也可作为兽用药用于非人类动物，例如非人类哺乳动物，例如宠物动物(如，狗、猫、兔、鼠等)、家畜动物(如，马、牛、羊、猪、狗、兔等)等动物。
在本发明的另一个实施方式中，本发明上述杀螨产品为化妆品。
具体地，上述化妆品还包含化妆品领域可接受的辅料。
具体地，本发明上述化妆品可以为用于面部的化妆品，如洗面奶、香皂、柔肤水、爽肤水、护肤乳、凝露、面霜、防晒霜、精华液、面膜、凝胶、粉底液、磨砂膏。
具体地，本发明上述化妆品可以为用于面部以外其他部位的化妆品，如颈霜、洗发水、沐浴露、香皂、护发素、身体乳、磨砂膏等。
具体地，本发明上述化妆品还可以为用于眼睛和眼周的化妆品，如眼霜、睫毛膏、眼线粉、眼线膏、眼线笔、眼影粉、眼影膏、眉笔、眉粉等。
具体地，本发明上述化妆品的各种形式可以按照化妆品领域的常规生产方法制备。
具体地，本发明上述化妆品可以含有重量比为0.01-99.5％(具体如，0.01％，0.1％、0.5％、1％、2％、3％、4％、5％、6％、7％、8％、9％、10％、20％、30％、40％、50％、60％、70％、80％、90％、95％、99％、99.5％)的活性成分。
在本发明的另一个实施方式中，本发明上述杀螨产品为杀螨剂，其可用于杀灭和抑制生活环境中物品(如，枕套、枕芯、床单、被褥、床垫、衣物、地毯、坐垫、沙发、凉席、毛绒玩具、空调等等)上可能寄居的螨虫。
具体地、上述杀螨剂可包含可实现所需性能的任何适宜的辅料。
具体地、上述杀螨剂可以为喷雾剂、洗剂、贴片、小包装等形式。
具体地，本发明上述杀螨剂的各种形式可以按照日护产品领域的常规生产方法制备。
具体地，本发明上述杀螨剂可以含有重量比为0.01-99.5％(具体如，0.01％，0.1％、0.5％、1％、2％、3％、4％、5％、6％、7％、8％、9％、10％、20％、30％、40％、50％、60％、70％、80％、90％、95％、99％、99.5％)的活性成分。
本发明还提供一种预防和/或治疗螨虫感染引起的疾病的方法，其包括向需要其的受试者施用本发明上述化合物或其盐、异构体、溶剂化物(特别是蒲公英甾醇、蒲公英赛醇、蒲公英赛酮、栎樱酸、蒲公英甾醇醋酸酯、乙酰蒲公英萜醇、羽扇烯酮或其盐、异构体、溶剂化物，或，香叶木素或其盐、异构体、溶剂化物，或，獐牙菜苦苷、獐牙菜苷、龙胆苦苷、马钱苷酸或其盐、异构体、溶剂化物)或本发明上述药物组合物的步骤。
具体地，上述疾病可以为眼部疾病、皮肤疾病、过敏性疾病等。
具体地，上述眼部疾病可以为睑缘炎、睑板腺功能障碍、睑板炎、睫毛脱落、睫毛排列异常、青光眼、白内障、眼部毛囊炎、结膜炎、睑结膜炎、翼状胬肉、角膜炎、眼睑松弛和外翻、眼睑基底细胞癌、干眼症、霰粒肿等中的一种或多种；其可具有选自以下的一种或多种症状：眼部红痒、眼干、眼烧灼感、异物感、畏光、眼部分泌物增多、睫毛脱落、 视物模糊、视力下降等。
具体地，上述皮肤疾病可以为脂溢性皮炎、痤疮、酒糟鼻、毛囊性糠疹、口周皮炎、蠕形螨病、疥螨病、基底细胞癌等中的一种或多种。
具体地，上述过敏性疾病可以为过敏性哮喘、过敏性鼻炎、过敏性皮炎等中的一种或多种。
具体地，上述受试者可以为接受该预防和/或治疗的任何动物，特别是哺乳动物，如人类、猫、狗、兔、鼠、马、牛、羊、猪等。在本发明的一个实施例中，上述受试者为人类；在本发明的另一个实施例中，上述受试者为非人类动物。
在本发明的一个实施方式中，上述方法为治疗和/或预防螨虫引起的眼部疾病的方法，其包括向需要其的受试者眼部施用本发明上述化合物或其盐、异构体、溶剂化物(特别是蒲公英甾醇、蒲公英赛醇、蒲公英赛酮、栎樱酸、蒲公英甾醇醋酸酯、乙酰蒲公英萜醇、羽扇烯酮或其盐、异构体、溶剂化物，或，香叶木素或其盐、异构体、溶剂化物，或，獐牙菜苦苷、獐牙菜苷、龙胆苦苷、马钱苷酸或其盐、异构体、溶剂化物)或本发明上述药物组合物的步骤。
具体地，上述眼部施用可以为以滴眼剂、眼膏剂、眼用凝胶剂、眼用乳剂、眼用混悬剂、眼用膜剂、洗眼剂、眼内注射剂形式施用。
具体地，本发明的化合物或本发明上述药物组合物的施用量可根据用药途径、受试者的年龄、体重、所治疗的疾病的类型和严重程度等变化，可以一次或多次施用。
通过对比发现，与对照组相比，本发明所述的化合物均可减少螨虫的存活时间，特别是蒲公英赛醇、香叶木素、龙胆苦苷和蒲公英甾醇醋酸酯显著缩短螨虫存活时间，可用于螨虫杀灭和抑制产品(如药品、化妆品、日用品等)。
具体实施方式
除非另有定义，本发明中所使用的所有科学和技术术语具有与本发明涉及技术领域的技术人员通常理解的相同的含义。
在本发明中，术语“动物”一般是指脊椎动物，特别是哺乳动物，包括人类。术语“非人类动物”是指除了人类之外的任何脊椎动物，特别是哺乳动物。在本发明的一些实施方案中，本发明中所述非人类动物为家养动物，即由人类饲养驯化，且可以人为控制其繁殖的动物，用于例如食用、劳役、毛皮、宠物、实验等功能，例如经济动物、宠物动物、实验动物等。经济动物，如家畜，例如猪、牛、羊、马、驴、狐、貉、貂、骆驼等。宠物动物，如狗、猫、兔、鼠(如豚鼠、仓鼠、沙鼠、龙猫、松鼠等)等。实验动物，如猴、狗、 兔、猫、鼠(如大鼠、小鼠)等。
下面将结合本发明实施例，对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1：体外初筛化合物对蠕形螨生存时间的影响
方法：
1.单体化合物
选取此单体化合物，单体中英文名称及分子式见下表1：
单体购于成都瑞芬思生物科技有限公司，为标准品。
表1：中药单体中英文名称及分子式
编号 中文名称 英文名称 分子式
1 蒲公英甾醇 Taraxasterol C30H50O
2 蒲公英赛醇 Taraxerol C30H50O
3 龙胆苦苷 Gentiopicroside C16H20O9
4 蒲公英赛酮 Taraxerone C30H48O
5 香叶木素 Diosmetin C16H12O6
6 獐芽菜苷 Sweroside C16H22O9
7 栎樱酸 Roburic acid C30H48O2
8 蒲公英甾醇醋酸酯 Taraxasterol acetate C32H52O2
9 乙酰蒲公英萜醇 Taraxeryl acetate C32H52O2
10 羽扇烯酮 Lupenone C30H48O
11 獐牙菜苦苷 Swertiamarine C16H22O10
12 马钱苷酸 Loganic acid C16H24O10
2.化合物溶液的制备
将表1中所示化合物参考品粉末先于二甲基亚砜(DMSO)溶解，再用灭菌双蒸水稀释，使DMSO的终浓度为10％，经对照试验，此浓度不能缩短蠕形螨存活时间。阴性对照为与灭菌水混合的DMSO，终浓度为10％。
3.蠕形螨体外培养
每张玻片上加入35μl不同溶液，每2个小时在光学显微镜下观察一次虫体是否存活。通过显微镜下观察虫体是否活动(身体，四肢等)来判断其是否死亡，实验过程中由两位熟练的蠕形螨相关实验者分别观察并判定，若判定结果不相同，则请第三位熟练的实验者进行独立判定。体外培养在气候箱中进行，温度20℃，湿度96％，玻片在观察中湿盒运输已保证高湿状态。
4.统计方法
本实验采用SPSS22.0统计软件进行统计，因共用Shapiro-Wilk检验进行正态性检验，Bartlett检验进行方差齐性检验，对符合正态分布且方差齐的数据进行单因素方差分析(One-way ANOVA)，有统计学意义时应用Bonferroni法进行组间两两比较；数据不符合正态分布时使用Kruskal-Wallis检验进行统计分析，检验标准α＝0.05。
5.实验结果：
化合物对毛囊蠕形螨存活时间的影响
在湿度96％，温度20℃的环境下体外培养蠕形螨，动态观察蠕形螨存活情况并记录存活时间。结果如表2所示。与阴性对照10％DMSO相比，蒲公英赛醇组的蠕形螨体外存活时间显著缩短(37.91±20.96vs.80.79±25.34,P＝0.006)，香叶木素组的蠕形螨体外存活时间显著缩短(35.92±14.82vs.80.79±25.34,P＝0.001)，蒲公英甾醇醋酸酯组的蠕形螨体外存活时间较对照组显著缩短(37.91±20.96vs.80.79±25.34,P＜0.001)，龙胆苦苷组的蠕形螨存活时间较对照组显著缩短(37.31±36.06vs.80.79±25.34,P＜0.001)，其余单体化合物组的蠕形螨存活时间与对对照组相比并未见显著差异(P＞0.05)。
表2化合物外对毛囊蠕形螨存活时间的影响
编号 单体名称 存活时间(小时) 蠕形螨数量(N)
对照 10％DMSO 80.79±25.34 36
1 蒲公英甾醇 68.28±31.30 6
2 蒲公英赛醇 37.91±20.96 ** 11
3 龙胆苦苷 37.31±36.06 *** 15
4 蒲公英赛酮 62.06±28.97 8
5 香叶木素 35.92±14.82 ** 10
6 马钱苷酸 61.56±22.84 8
7 獐芽菜苷 60.79±25.98 7
8 栎樱酸 63.41±12.20 9
9 蒲公英甾醇醋酸酯 34.14±22.96 *** 13
10 乙酰蒲公英萜醇 70.57±27.45 12
11 羽扇烯酮 66.25±31.22 5
12 獐牙菜苦苷 59.68±10.97 7
用Duncan法进行多重比较，与对照组相比，P *：P＜0.05，P **：P＜0.01，P ***＜0.001。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换等，均应包含在本发明的保护范围之内。
本发明中描述的前述实施例和方法可以基于本领域技术人员的能力、经验和偏好而有所不同。
在本发明中仅按一定顺序列出方法的步骤并不构成对方法步骤顺序的任何限制。

Claims (19)

  1. 式I所述的化合物或其盐、异构体、溶剂化物在制备抑制或杀灭螨虫产品中的应用，所述的式I化合物为：
    Figure PCTCN2021089105-appb-100001
    其中，R 1选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH 2、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH 2、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，或者，R 1与5号碳原子之间为双键时，R 1选自O或S，
    R 2、R 3、R 6、R 7、R 8、R 9独立地选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，
    R 4选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，或者，当1号碳原子与4号碳原子之间为双键时，R 4不存在，
    R 5选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，或者，当2号碳原子与3号碳原子之间为双键时，R 5不存在，
    6号碳原子与7号碳原子之间为双键或单键，
    R 10和R 13独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 1-8炔基、CH＝CH(C 1-8烷基)、CH＝CH 2、C(C 1-8烷基)＝CH 2、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8 烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，
    R 11和R 12独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 1-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，或者，R 11和R 12为碳原子并且与之间的碳原子形成5-8元环，所述环上的任意碳原子上的H可被C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2、C 2-8烯基、C 2-8炔基、CH＝CH 2、C(C 1-8烷基)＝CH 2、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2所取代。
  2. 权利要求1所述的应用，所述的式I化合物为式I-1的化合物：
    Figure PCTCN2021089105-appb-100002
    其中，当R 14与8号碳原子之间为单键时，R 14选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8 烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，并且，8号碳原子上的氢原子任选的被R 14取代；当R 14与8号碳原子之间为双键时R 14选自O、S、CH 2、CH(C 1-8烷基)、C(C 1-8烷基) 2，
    R 15选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，
    n为1-4的整数，例如为1、2、3、4。
  3. 权利要求1或2所述的应用，R 1选自H、C 1-3烷基、OH、OC(＝O)(C 1-3烷基)、(C 1-3烷基)CO 2H、CF 3、CHF 2、CH 2F，或者，R 1与5号碳原子之间为双键时，R 1为O，
    R 2、R 3、R 6、R 7、R 8、R 9独立地选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2，
    1号碳原子与4号碳原子之间为单键，R 4选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、O(C 1-3环烷基)、OH，
    2号碳原子与3号碳原子之间为单键，R 5选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、O(C 1-3环烷基)、OH，
    6号碳原子与7号碳原子之间为单键，
    R 10和R 13独立地选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2，
    当R 14与8号碳原子之间为单键时，R 14选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2，并且，8号碳原子上的氢原子同样被R 14取代；当R 14与8号碳原子之间为双键时R 14选自CH 2、CH(C 1-3烷基)、C(C 1-3烷基) 2，
    R 15选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH 2、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2；特别优选的，R 15选自 H、C 1-3烷基、C(CH 3)＝CH 2。
  4. 权利要求1-3任一项所述的应用，所述的式I化合物为蒲公英甾醇、蒲公英赛醇、蒲公英赛酮、栎樱酸、蒲公英甾醇醋酸酯、乙酰蒲公英萜醇、羽扇烯酮或其盐、异构体、溶剂化物。
  5. 式II所述的化合物或其盐、异构体、溶剂化物在制备抑制或杀灭螨虫产品中的应用，所述的式II化合物为：
    Figure PCTCN2021089105-appb-100003
    其中，R 16、R 18、R 20、R 23、R 24独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，
    R 17、R 19、R 21、R 22独立地选自H、C 1-8烷基、O(C 1-8烷基)、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)或式II-1、II-2、II-3的基团：
    Figure PCTCN2021089105-appb-100004
  6. 权利要求5所述的应用，R 16、R 18、R 20、R 23、R 24独立地选自H、卤素、C 1-3烷基、O(C 1-3烷基)、NH(C 1-3烷基)、N(C 1-3烷基) 2、C 3-11环烷基、OH、NH 2、OC(＝O)(C 1-3烷基)、C(＝O)(C 1-3烷基)、(C 1-3烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C 2-3烯基、C 2-3 炔基、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2，
    R 17、R 19、R 21、R 22独立地选自H、C 1-3烷基、O(C 1-3烷基)或式II-1、II-2的基团。
  7. 权利要求5或6所述的应用，所述的式II化合物为香叶木素或其盐、异构体、溶剂化物。
  8. 式III所述的化合物或其盐、异构体、溶剂化物在制备抑制或杀灭螨虫产品中的应用，所述的式III化合物为：
    Figure PCTCN2021089105-appb-100005
    其中，R 25选自
    Figure PCTCN2021089105-appb-100006
    R 26为碳原子，其与R 27和R 28中至少一个形成5-8元环，并且R 27和R 28中不与R 26成环的基团选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，
    R 29选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8 烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
  9. 权利要求8所述的应用，所述的式III化合物为式III-1或III-2的化合物：
    Figure PCTCN2021089105-appb-100007
    其中，R 30、R 31、R 33、R 34、R 35选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，
    式III-1中1号碳原子与2号碳原子之间选自双键或单键，
    当III-1中1号碳原子与2号碳原子之间选自双键时，R 32不存在；当III-1中1号碳原子与2号碳原子之间选自单键时，R 32选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2。
  10. 权利要求9所述的应用，其中，R 25选自
    Figure PCTCN2021089105-appb-100008
    R 27和R 28中不与R 26成环的基团选自H、C 1-3烷基、O(C 1-3烷基)、O(C 1-3环烷基)、C 2-3烯基、C 2-3炔基、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2、OC(＝O)(C 1-3烷基)、C(＝O)(C 1-3烷基)、(C 1-3烷基)CO 2H、CO 2H，
    R 30、R 31、R 33、R 34、R 35选自H、C 1-3烷基、O(C 1-3烷基)、C 3-6环烷基、OH、NH 2、CH＝CH(C 1-3烷基)、C(C 1-3烷基)＝CH 2、C(C 1-3烷基)＝CH(C 1-3烷基)、C(C 1-3烷基)＝C(C 1-3烷基) 2；特别优选的，R 30、R 31、R 33、R 34、R 35选自选自H、甲基、OH，
    III-1中1号碳原子与2号碳原子之间选自双键，R 32不存在。
  11. 权利要求8-10任一项所述的应用，所述的式III化合物为獐牙菜苦苷、獐牙菜苷、龙胆苦苷、马钱苷酸或其盐、异构体、溶剂化物。
  12. 如权利要求1-11任一项所述的应用，其特征在于，所述螨虫为蠕形螨、尘螨、疥螨中的一种或多种。
  13. 如权利要求1-11任一项所述的应用，其特征在于，所述抑制或杀灭螨虫产品为药物组合物、化妆品或杀螨剂。
  14. 如权利要求13所述的应用，其特征在于，所述药物组合物为用于预防和/或治疗螨虫感染引起的疾病的药物组合物；
    所述疾病选自：眼部疾病、皮肤疾病、过敏性疾病；
    优选地，所述眼部疾病选自：睑缘炎、睑板腺功能障碍、睑板炎、睫毛脱落、睫毛排列异常、青光眼、白内障、眼部毛囊炎、结膜炎、睑结膜炎、翼状胬肉、角膜炎、眼睑松弛和外翻、眼睑基底细胞癌、干眼症、霰粒肿；
    优选地，所述皮肤疾病选自：脂溢性皮炎、痤疮、酒糟鼻、毛囊性糠疹、口周皮炎、蠕形螨病、疥螨病、基底细胞癌；
    优选地，所述过敏性疾病选自：过敏性哮喘、过敏性鼻炎、过敏性皮炎。
  15. 如权利要求13所述的应用，其特征在于，所述药物组合物为外用制剂，优选为眼用制剂或皮肤外用制剂；
    优选地，所述眼用制剂选自：滴眼剂、眼膏剂、眼用凝胶剂、眼用乳剂、眼用混悬剂、眼用膜剂、洗眼剂、眼内注射剂；
    优选地，所述皮肤外用制剂选自：气雾剂、粉剂、洗剂、酊剂、搽剂、涂膜剂、软膏剂、凝胶剂、糊剂、乳剂。
  16. 如权利要求13所述的应用，其特征在于，所述药物组合物为人用药物组合物或兽用药物组合物。
  17. 如权利要求13所述的应用，其特征在于，所述化妆品的形式选自：洗面奶、香皂、柔肤水、爽肤水、护肤乳、凝露、面霜、防晒霜、精华液、面膜、凝胶、粉底液、磨砂膏、颈霜、洗发水、沐浴露、护发素、身体乳、眼霜、睫毛膏、眼线粉、眼线膏、眼线笔、眼影粉、眼影膏、眉笔、眉粉。
  18. 如权利要求13所述的应用，其特征在于，所述杀螨剂的形式选自：喷雾剂、洗剂、贴片、小包装。
  19. 一种治疗和/或预防螨虫引起的眼部疾病的方法，所述的方法包括向需要其的受试者眼部施用式I化合物，所述的式I化合物为：
    Figure PCTCN2021089105-appb-100009
    其中，R 1选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 2-8炔基、CH＝CH 2、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH 2、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，或者，R 1与5号碳原子之间为双键时，R 1选自O或S，
    R 2、R 3、R 6、R 7、R 8、R 9独立地选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，
    R 4选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，或者，当1号碳原子与4号碳原子之间为双键时，R 4不存在，
    R 5选自H、C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2，或者，当2号碳原子与3号碳原子之间为双键时，R 5不存在，
    6号碳原子与7号碳原子之间为双键或单键，
    R 10和R 13独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 1-8炔基、CH＝CH(C 1-8烷基)、CH＝CH 2、C(C 1-8烷基)＝CH 2、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，
    R 11和R 12独立地选自H、卤素、C 1-8烷基、O(C 1-8烷基)、S(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、芳基、杂芳基、C 3-11杂环烷基、O(C 1-8环烷基)、S(C 1-8环烷基)、NH(C 1-8环烷基)、N(C 1-8环烷基)(C 1-8烷基)、OH、NH 2、SH、SO 2(C 1-8烷基)、C 2-8烯基、C 1-8炔基、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2、OC(＝O)(C 1-8烷基)、C(＝O)(C 1-8烷基)、(C 1-8烷基)CO 2H、CO 2H、CN、CF 3、CHF 2、CH 2F、NO 2、C(＝O)NH(C 1-8烷基)、C(＝O)N(C 1-8烷基) 2、N(C 1-8烷基)C(＝O)NH(C 1-8烷基)、N(C 1-8烷基)C(＝O)N(C 1-8烷基) 2、NHC(＝O)NH(C 1-8烷基)、NHC(＝O)N(C 1-8烷基) 2、NHC(＝O)NH 2、N(C 1-8烷基)SO 2NH(C 1-8烷基)、N(C 1-8烷基)SO 2N(C 1-8烷基) 2、NHSO 2NH(C 1-8烷基)、NHSO 2N(C 1-8烷基) 2，或者，R 11和R 12为碳原子并且与之间的碳原子形成5-8元环，所述环上的任意碳原子上的H可被C 1-8烷基、O(C 1-8烷基)、NH(C 1-8烷基)、N(C 1-8烷基) 2、C 3-11环烷基、O(C 1-8环烷基)、OH、NH 2、C 2-8烯基、C 2-8炔基、CH＝CH 2、C(C 1-8烷基)＝CH 2、CH＝CH(C 1-8烷基)、C(C 1-8烷基)＝CH(C 1-8烷基)、C(C 1-8烷基)＝C(C 1-8烷基) 2所取代。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4545067A1 (de) 2023-10-25 2025-04-30 Infectopharm Arzneimittel und Consilium GmbH Hochdosierte dermal applizierbare permethrin-zubereitung mit erhöhtem drugload im zielkompartiment zur verbesserten behandlung von ektoparasiten befall

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115607586B (zh) * 2020-04-24 2024-12-10 广州医科大学 蒲公英及其单体化合物在杀螨中的应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101692822A (zh) * 2009-10-27 2010-04-14 北京农学院 羽扇豆醇的新用途
CN101731215A (zh) * 2010-01-14 2010-06-16 北京农学院 乙酰蒲公英萜醇杀螨剂及其制备方法
CN108651465A (zh) * 2018-07-24 2018-10-16 江西省科学院应用化学研究所 一种环烯醚萜苷在制备农药的应用
CN110804499A (zh) * 2019-11-11 2020-02-18 高艳艳 一种除螨洗衣液及其制备方法
CN110946815A (zh) * 2018-09-25 2020-04-03 元穗生物科技(上海)有限公司 天然草本止痒防螨喷剂

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6009791B2 (ja) * 2012-03-28 2016-10-19 ホーユー株式会社 Ｈｄｃ活性化阻害剤、ｈｄｃ活性化阻害剤組成物、鎮痒剤及び鎮痒剤組成物
CN103432312B (zh) * 2013-07-25 2015-09-16 天津必佳药业集团有限公司 一种治疗猪疥螨病的中药组合物
CN104042804A (zh) * 2014-06-12 2014-09-17 沈莉芬 一种用于治疗面部螨虫感染的中药软膏
CN115607586B (zh) * 2020-04-24 2024-12-10 广州医科大学 蒲公英及其单体化合物在杀螨中的应用
CN115607589B (zh) * 2020-04-24 2024-06-04 广州岐微生物医药科技有限公司 秦艽及其单体化合物在杀螨中的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101692822A (zh) * 2009-10-27 2010-04-14 北京农学院 羽扇豆醇的新用途
CN101731215A (zh) * 2010-01-14 2010-06-16 北京农学院 乙酰蒲公英萜醇杀螨剂及其制备方法
CN108651465A (zh) * 2018-07-24 2018-10-16 江西省科学院应用化学研究所 一种环烯醚萜苷在制备农药的应用
CN110946815A (zh) * 2018-09-25 2020-04-03 元穗生物科技(上海)有限公司 天然草本止痒防螨喷剂
CN110804499A (zh) * 2019-11-11 2020-02-18 高艳艳 一种除螨洗衣液及其制备方法

Non-Patent Citations (14)

* Cited by examiner, † Cited by third party
Title
AMERICAN JOURNAL OF OPHTHALMOLOGY, vol. 157, no. 2, pages 342 - 348
CHEN, W.PLEWIG, G: "Human demodicosis: revisit and a proposed classification", THE BRITISH JOURNAL OF DERMATOLOGY, vol. 170, pages 1219 - 1225, XP071167748, DOI: 10.1111/bjd.12850
CLINICAL MICROBIOLOGY AND INFECTION: THE OFFICIAL PUBLICATION OF THE EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES, vol. 18, no. 10, pages 1020 - 1025
CLINICS IN DERMATOLOGY, vol. 32, no. 6, pages 739 - 743
FENG BO, ZHU HEYUN GUAN JIAO HAO CHENGYI DUAN JINGCAN GU JINGKAI: "Comparative Study on Pharmacokinetics of Gentiopicroside and Gentianae Radix Extract in Rats", ZHONGYAOCAI - JOURNAL OF CHINESE MEDICINAL MATERIALS, GUOJIA YIYAO GUANLIJU, CN, vol. 36, no. 5, 31 May 2013 (2013-05-31), CN , pages 783 - 786, XP055860103, ISSN: 1001-4454, DOI: 10.13863/j.issn1001-4454.2013.05.028 *
INTERNATIONAL OPHTHALMOLOGY, vol. 37, no. 1, pages 303 - 312
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 51, no. 6, pages 2906 - 2911
IRANIAN JOURNAL OF PARASITOLOGY, vol. 12, no. 1, pages 12 - 21
KARINCAOGLU, YTEPE, B.KALAYCI, B.ATAMBAY, M.SEYHAN, M: "Is Demodex folliculorum an aetiological factor in seborrhoeic dermatitis?", CLINICAL AND EXPERIMENTAL DERMATOLOGY, vol. 34, pages e516 - 520, XP071607261, DOI: 10.1111/j.1365-2230.2009.03343.x
LUO, X.LI, J.CHEN, C.TSENG, S.LIANG, L, OCULAR DEMODICOSIS AS A POTENTIAL CAUSE OF OCULAR SURFACE INFLAMMATION, vol. 36, no. 1, pages s9 - s14
OPHTHALMIC & PHYSIOLOGICAL OPTICS: THE JOURNAL OF THE BRITISH COLLEGE OF OPHTHALMIC OPTICIANS (OPTOMETRISTS, vol. 40, no. 4, pages 389 - 432
OPHTHALMOLOGY, vol. 117, no. 5, pages 870 - 877
SHANG XIAOFEI; GUO XIAO; YANG FENG; LI BING; PAN HU; MIAO XIAOLOU; ZHANG JIYU: "The toxicity and the acaricidal mechanism againstPsoroptes cuniculiof the methanol extract ofAdonis coeruleaMaxim", VETERINARY PARASITOLOGY, ELSEVIER SCIENCE, AMSTERDAM., NL, vol. 240, 20 April 2017 (2017-04-20), NL , pages 17 - 23, XP085048143, ISSN: 0304-4017, DOI: 10.1016/j.vetpar.2017.04.019 *
TIAN YE, LI CHAOPIN, DENG YUN: "Anti-mite Activity and Skin Safety of Herba Taraxaci Extract for Demodex Folliculorum", CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, ZHONGGUO YUFANG YIXUE KEXUEYUAN JISHENGCHONGBING YANJIUSUO, CN, vol. 25, no. 2, 30 April 2007 (2007-04-30), CN , pages 133 - 136, XP055860104, ISSN: 1000-7423 *

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* Cited by examiner, † Cited by third party
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EP4545067A1 (de) 2023-10-25 2025-04-30 Infectopharm Arzneimittel und Consilium GmbH Hochdosierte dermal applizierbare permethrin-zubereitung mit erhöhtem drugload im zielkompartiment zur verbesserten behandlung von ektoparasiten befall
WO2025088039A1 (de) 2023-10-25 2025-05-01 Infectopharm Arzneimittel Und Consilium Gmbh Hochkonzentrierte dermal applizierbare permethrin-zubereitung mit erhöhtem drugload im zielkompartiment zur verbesserten behandlung von ektoparasiten-befall

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