Use of ginseng and its monomeric compounds for killing mites

Abstract

The present invention provides a use of Jingwia ginseng, a Jingwia extract, a Jingwia monomeric compound, or a salt, ester, isomer, solvate, or derivative thereof in the manufacture of a miticide product, wherein the monomeric compound is one or more selected from gentiopicroside, loganic acid, swelloside, lobric acid, scopoletin, rubimaylin, and swerthiamarin.

Description

[Technical field]

[0001] The present invention relates to the field of medicine and daily care, specifically to the use of Zingiber officinale and its monomeric compounds, especially gentiopicroside, in 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 (Arachnid, Acarina) are micro-in vitro parasites that usually infect the cutaneous pilosebaceous unit. Among the wide variety of reported species, at least Demodex follicularis and Demodex sebacea have already been found on the human body surface, mainly infecting 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, abnormal eyelash alignment, conjunctivitis and blepharoconjunctivitis, pterygium, keratitis, eyelid basal cell carcinoma, etc. Demodex also feeds on lipids and may 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, and may also lead to the formation of chalazion. 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 Dermatology 170, 1219-1225).

[0004] Mite-related diseases (e.g. eye and skin diseases) are currently not given enough importance in clinical practice, and are often misdiagnosed as bacterial diseases, with typical antibiotic treatments often having no clear therapeutic effect. Summary of the Invention [Means for solving the problem]

[0005] A first aspect of the present invention provides the use of Zingiber officinale in the manufacture of an acaricidal product.

[0006] Specifically, the above-mentioned Zingiber officinale may be the only active ingredient for killing mites, or may be combined with other identical or different active ingredients for killing mites.

[0007] A second aspect of the present invention provides the use of an extract of Zingiber officinale in the manufacture of an acaricidal product.

[0008] Specifically, the above-mentioned Zhimingui extract can be obtained by one or more combinations of suitable herbal medicine extraction methods known in the art, such as decoction, soaking, percolation, reflux, steam distillation, ultrasonic extraction, etc. In one embodiment of the present invention, the above-mentioned Zhimingui extract can be obtained by decoction.

[0009] Specifically, the above-mentioned Zingiber officinale extract comprises: (1) mixing and soaking Zingiber officinale with an extraction solvent; It is prepared by a process comprising heating the mixture of step (1) to boiling, followed by step (2) of decoction and filtration.

[0010] In one embodiment of the invention, the extraction solvent is water.

[0011] Specifically, the immersion time is 1 to 24 hours (specifically, for example, 1, 2, 3, 4, 5, 6, 12, 18, or 24 hours).

[0012] Specifically, the brewing time is 10 to 60 minutes (specifically, for example, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 minutes).

[0013] Specifically, the method comprises: The method may further include a step (3) of heating the filtrate obtained in step (2) to boiling together with an extraction solvent, followed by decoction and filtration, and combining the filtrates obtained in steps (2) and (3).

[0014] Suitably, the method further comprises subjecting the obtained filtrate to one or more of the following processing steps: homogenous mixing, concentration, quantification, sterilization, etc.

[0015] Specifically, the above-mentioned Zingiber officinale extract contains one or more of gentiopicroside, loganic acid, swelloside, lobric acid, scopoletin, rubimaylin, and swerthiamarin.

[0016] More specifically, the above-mentioned Zingiber officinale extract contains gentiopicroside.

[0017] A third aspect of the present invention provides the use of a monomeric Zingiber officinale compound or a salt, ester, isomer, solvate or derivative thereof in the manufacture of an acaricidal product.

[0018] Specifically, the salts, esters, isomers, solvates and derivatives of the above-mentioned gingyo monomeric compounds are the corresponding pharma-ceutically acceptable salts, esters, isomers, solvates and derivatives.

[0019] Specifically, the monomer compound is one or more selected from gentiopicroside, loganic acid, swelloside, lobric acid, scopoletin, rubimaylin, and sweltiamarin.

[0020] Specifically, the monomeric compound is gentiopicroside.

[0021] A fourth aspect of the present invention provides the use of gentiopicroside or a salt, ester, isomer, solvate or derivative thereof in the manufacture of an acaricidal product.

[0022] Specifically, the salts, esters, isomers, solvates and derivatives of the above-mentioned gingyo monomeric compounds are the corresponding pharma-ceutically acceptable salts, esters, isomers, solvates and derivatives.

[0023] In particular, the acaricidal products of the invention are useful for both therapeutic and / or preventive purposes and for non-therapeutic and / or preventive purposes.

[0024] 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.

[0025] In one embodiment of the invention, the acaricidal product of the invention is a pharmaceutical composition.

[0026] In particular, the pharmaceutical composition further comprises a pharma- ceutically acceptable auxiliary material.

[0027] Specifically, the pharmaceutical composition of the present invention is useful for the prevention and / or treatment of diseases caused by mites.

[0028] Specifically, the disease may be an eye disease, a skin disease, an allergic disease, or the like.

[0029] 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.

[0030] 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.

[0031] Specifically, the allergic disease may be one or more of allergic asthma, allergic rhinitis, allergic dermatitis, and the like.

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] Specifically, the various dosage forms of the above pharmaceutical composition of the present invention can be prepared by common preparation methods in the pharmaceutical field. For example, the ophthalmic preparation techniques can be adopted from "Ophthalmic Drugs and Formulations" (China Light Industry Press, 2010), "Development and Production of Eye Drops" (China Light Industry Press, 2009), etc.

[0037] 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.

[0038] 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.).

[0039] In another embodiment of the present invention, the acaricidal product of the present invention is a cosmetic product.

[0040] In particular, the cosmetic product further comprises auxiliary materials acceptable in the field of cosmetics.

[0041] 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.

[0042] Specifically, the cosmetic product of the present invention may be a cosmetic product for use on parts of the body other than the face, such as neck cream, shampoo, body wash, soap, hair styling product, body lotion, lip balm, and the like.

[0043] 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.

[0044] Specifically, the various forms of the above-mentioned cosmetic product of the present invention may be produced by a general production method in the cosmetics field.

[0045] 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.

[0046] In another embodiment of the present invention, the above-mentioned miticide product of the present invention may be an miticide capable of killing and suppressing mites that may infest articles used in daily life (e.g., pillowcases, pillow stuffing, sheets, bedding, mattresses, clothing, carpets, cushions, sofas, summer mats, stuffed toys, air conditioners, etc.).

[0047] Specifically, the miticide may contain any suitable auxiliary material that can achieve the desired performance.

[0048] Specifically, the miticide may be in the form of a spray, a lotion, a patch, a small package, or the like.

[0049] 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.

[0050] 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.

[0051] 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 Zingiber officinale, a Zingiber officinale extract, a Zingiber officinale monomeric compound (particularly gentiopicroside) or a salt, ester, isomer, solvate, derivative thereof or the above-mentioned pharmaceutical composition of the present invention.

[0052] Specifically, the disease may be an eye disease, a skin disease, an allergic disease, or the like.

[0053] 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.

[0054] 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.

[0055] Specifically, the allergic disease may be one or more of allergic asthma, allergic rhinitis, allergic dermatitis, and the like.

[0056] The present invention also provides 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 Zingiber officinale, a Zingiber officinale extract, a Zingiber officinale monomeric compound, or a salt, isomer, solvate, or derivative thereof.

[0057] The present invention also provides the use of Zingiber officinale, Zingiber officinale extract, Zingiber officinale monomeric compound or a salt, isomer, solvate or derivative thereof in the manufacture of a medicament for treating and / or preventing mite-induced eye disease.

[0058] In particular, reports proving the relationship between mites and eye disease include the following:

[0059] 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 can cause eye disease when they infect the skin of the face.

[0060] 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.

[0061] As revealed by 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 disrupts the balance of the extraocular ecosystem.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] As revealed by the study 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 is a carrier of the bacillus and may play a role in the pathogenesis of blepharitis as a co-pathogen.

[0066] 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.

[0067] 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.

[0068] As revealed by the study "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, and ocular demodex brevis is one of the important etiologies of meibomian gland cysts.

[0069] 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.

[0070] Specifically, the dosage of the above-mentioned Ginger, Ginger extract, Ginger monomer compound (particularly gentiopicroside) or its salt, ester, isomer, solvate, derivative or the above-mentioned 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 the like.

[0071] After comparing the killing effects of several kinds of herbal medicines against mites, it was found that Jingyuan can effectively shorten the survival time of mites, and several kinds of Jingyuan monomer compounds were screened and used in mite killing experiments. As a result, compared with the control group, all of these monomer compounds shortened the survival time of mites, and gentiopicroside in particular was able to significantly shorten the survival time of mites, which is useful for mite killing and inhibition products (such as medicines, cosmetics, daily necessities, etc.). The use provided by the present invention can effectively utilize natural resources and increase the utility and commercial value of Jingyuan. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0072] 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.

[0073] Unless otherwise specified, in the present invention, Jingyue refers to the Chinese herbal medicine Jingyue, which is the dried root of Gentiana macrophylla Pall., Gentiana straminea Maxim., Gentiana crassicaulis Duthie ex Burk. or Gentiana dahurica Fisch. of the Gentianaceae family, which is roasted, washed to remove foreign matter, impregnated, sliced ​​thickly and dried. It has a hot and bitter taste and warming properties, and acts on the stomach, liver and gallbladder, plays the role of eliminating cold and dampness, expelling damp heat, eliminating paralysis and pain, and releasing deficiency heat.

[0074] The herbal monomer refers to a compound obtained from a single herbal medicine (e.g., obtained by extraction), particularly a compound having therapeutic or health-friendly effects, for example, the Jingyu monomer compound according to the present invention refers to a monomer compound obtained from Jingyu, such as, but not limited to, gentiopicroside (CAS: 20831-76-9), loganic acid (CAS: 22255-40-9), swelloside (CAS: 14215-86-2), lobricic acid (CAS: 6812-81-3), scopoletin (CAS: 92-61-5), rubimaylin (CAS: 55481-88-4), and swerthiamarin (CAS: 17388-39-5). The herbal monomer compound according to the present invention may be a commercially available product, or may be obtained from the corresponding herbal medicine when used (e.g., obtained by extraction), or may be synthesized by a method known in the art, or may be obtained by other suitable means.

[0075] 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).

[0076] 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

[0077] Example 1 1. Experimental method: 1. Experimental subjects This study strictly adhered to the ethical principles of the Declaration of Helsinki (Procedure for the Ethical Review of Biomedical Research Involving Humans). Demodex mites were collected from patients with confirmed ocular Demodex infection. Those who met the inclusion criteria were interviewed and signed an informed consent form before participating in the study. 2. Demodex folliculorum testing Demodex examination was performed by standard eyelash microscopy (12,20), i.e., 12 eyelashes were plucked (3 eyelashes per eyelid), and the freshly plucked eyelashes were placed on a glass slide (3 per slide) and observed under a standard light microscope. All stages of Demodex were counted and morphologically classified (specific standard:head-to-body ratio of 1:1 was defined as sebaceous Demodex and head-to-body ratio of 1:3-1:4 was defined as follicular Demodex). Only fully exposed adult mites were included in the study (larvae and eggs were not studied as they are more vulnerable in the early stages of life). 3. In Vitro Cultivation of Demodex mites Based on the Demodex test, 35 μl of each solution was added to each slide, and the worms were observed once every 2 hours to see if they were alive or not. The worms (body, limbs, etc.) were observed under a microscope to see if they were moving or not to see if they were dead or not. In the experiment, two experimenters who were experienced with 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°C and a humidity of 96%, and the slides were transported in a wet box during observation to ensure high humidity conditions. 4. Drugs 4.1 Seven types of herbal medicine The herbal medicines used in this study (Aster, Aster, Scutellaria, Radix Ginseng, Radix Ginseng, Radix Ginseng, Radix Ginseng, and Radix Chrysanthemum) were all purchased from the Chinese medicine pharmacy of Guangdong Provincial Hospital of Traditional Chinese Medicine. Among these, Aster, Radix Ginseng, Scutellaria, Radix Ginseng, Radix Ginseng, and Radix Chrysanthemum were purchased from Kang Mei Pharmaceutical Co., Ltd., and Aster and Radix Ginseng were purchased from Lingnan Chinese Herbal Medicine Pieces Co., Ltd. 4.2 Manufacturing method of herbal decoction Weigh out 60g of dried herbs using an electronic balance and place them in a clay pot. Add 10 times the amount of water (600ml) and soak overnight. Heat over high heat until the liquid boils, then decoct over medium heat for 15 to 30 minutes (15 minutes for flowers and 30 minutes for rhizomes). Filter through gauze, add 500ml of water to the filtrate, decoct and filter in the same manner as above, and combine the two filtrates in the same beaker, mix evenly, heat to evaporate, and concentrate the liquid to 100ml. Allow to cool to room temperature and transfer to a 100ml test tube to determine the constant volume. The experimental groups were the herbal decoctions prepared by the above methods, and the negative control group was sterilized water. 4.3 The positive controls were tea tree essential oil and terpinen-4-ol, the main component of tea tree essential oil. Tea tree oil (TTO) and terpinen-4-ol (T4O) were purchased from Milwaukee, WI, USA, and all were diluted with sterilized water to a final concentration of 10%. 5. 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 consistent 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. 6. Experimental Results: 1. Significant reduction in the in vitro survival time of Demodex folliculorum by Zingyou Demodex mites were cultured in vitro under a humidity of 96% and a temperature of 20℃, and the survival status of Demodex mites was dynamically observed and the survival time was recorded. The experimental results are shown in Table 1. Compared with the negative control group, the survival time of Demodex mites in the Zingiber officinale group was significantly shorter than that of the control group (21.44 ± 9.76 vs. 50.81 ± 19.90, P < 0.001), and the in vitro survival time of Demodex mites was shorter than that of the TTO and T4O groups (21.61 ± 11.95 vs. 41.39 ± 19.33, 21.61 ± 11.95 vs. 40.50 ± 13.12, P < 0.01), and the remaining six herbal medicines showed no significant difference in the in vitro survival time of Demodex mites compared with the control group, TTO and T4O groups (P > 0.05). Interestingly, TTO and its main active ingredient, T4O, which are thought to be capable of killing mites in vitro, showed no significant difference in Demodex survival time compared to the negative control aqueous solution in this in vitro culture experiment (P>0.05). [Table 1]

[0078] Example 2: Primary in vitro screening of the effect of herbal medicine monomers on Demodex survival time method: 1. Herbal Medicine Monomers According to the experimental results of Example 1, Ginseng can significantly shorten the in vitro survival time of Demodex folliculorum, so this herbal medicine monomer was used, and the English name and molecular formula of the monomer are shown in the table below. [Table 2] 2. Preparation of herbal monomer solution The powders of the reference herbal medicine monomers shown in Table 2 were dissolved in dimethyl sulfoxide (DMSO) and then diluted with sterile distilled water to a final concentration of 10% DMSO, and a control test was performed, which showed that this concentration could 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 culture of Demodex mites As in Example 1, 35 μl of each solution was added per slide, and the worms were observed once every 2 hours under an optical microscope to see if they were alive. The worms (body, limbs, etc.) were observed under a microscope to see if they were moving to determine if they were dead or not. In the experiment, two experimenters who were experienced with Demodex mites observed and judged them separately, and if the results of the judgments differed, another experienced experimenter judged them separately. The in vitro culture was carried out in an artificial climate room at a temperature of 20°C and a humidity of 96%, and the slides were transported in a wet box during the observation to ensure a high humidity state. 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 consistent 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 herbal medicine monomer on survival time of Demodex folliculorum Demodex mites were cultured in vitro in an environment with 96% humidity and 20°C temperature, and the survival status of Demodex mites was dynamically observed and the survival time was recorded. The results are shown in Table 3. Compared with the negative control 10% DMSO, all of the Zingiber monomer compounds shown in Table 2 could shorten the in vitro survival time of Demodex mites, and in particular, the survival time of Demodex mites in the gentiopicroside group was significantly shorter than that of the control group (37.31±36.06 vs. 80.79±25.34, P<0.001). [Table 3]

[0079] Example 3: Clinical study of treatment of mite-induced dry eye (1) Inclusion and Exclusion Criteria 1.Case Selection Criteria (1) Patients who meet the diagnostic criteria for dry eye based on their medical history (2) Age: 18 to 70 years old (3) Regardless of gender (4) People who can cooperate with treatment 2.Case Exclusion Criteria (1) Patients with iridocarcinoma diagnosed by slit-lamp examination; (2) Patients with high or low intraocular pressure (3) Patients with eyelid skin ruptures and corneal epithelial infiltration lesions on the corneal surface (4) Patients with systemic diseases, such as Sjögren's syndrome due to liver and kidney dysfunction (5) Anyone under 18 years of age or 70 years of age or older; (6) Those whose mental state makes them unable to cooperate with the evaluator (7) Pregnant or breastfeeding women 3. Suspension and Removal Criteria (1) Those who are unable or unwilling to continue treatment due to other illnesses during treatment (2) Those who are unable to cooperate during treatment or whose symptoms have worsened and who do not wish to continue treatment. (3) Those who, contrary to the study program, have used drugs other than those used in the study. (4) Those who ultimately lack sufficient information to be able to judge a therapist. (2) End point indicator Patients underwent an ocular surface discomfort score, general eye examination (visual acuity, intraocular pressure, slit-lamp examination), three dry eye parameters (conjunctival hyperemia score, BUT test, Schirmer I test), ocular surface disease index score (OSDI), dry eye meter, and ocular Demodex test before and weekly after treatment. (3) Statistics 1. Sample content estimation Considering that dry eye is a common ocular surface disease in clinical practice, the positive rate of ocular Demodex folliculorum reached 23.8%-90.0%. According to the calculation formula for the quantity of samples for efficacy testing of quantitative data, there were 30 patients in each of the experimental and control groups. 2. Statistics and analysis of research data Statistical processing was performed using SPSS20.0 software and Excel. Paired sample t-tests were used for normally distributed data of quantitative data, chi-square tests for measured data, and non-parametric tests for non-normally distributed data. Results were expressed as mean ± standard difference x+s, with statistical significance determined by P<0.05.

[0080] 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.

[0081] The foregoing embodiments and methods described herein are subject to the capabilities, experience and preferences of those skilled in the art.

[0082] 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. Use of Gingyo in the manufacture of Demodex acaricidal products.

2. Use of a hot water extract of Gingyo in the manufacture of an anti-Demodex mites product.

3. 2. Use of a Demodex isolated compound or a salt, ester or solvate thereof in the manufacture of a Demodex miticide product, comprising: The use, wherein the isolated compound is one or more selected from gentiopicroside, loganic acid, swelloside, lobric acid, scopoletin, rubimaylin, and swerthiamarin.

4. The use according to claim 3, wherein the isolated compound is selected from gentiopicroside.

5. The use according to any one of claims 1 to 4, wherein the Demodex mites are one or more of the following species: Demodex, Demodex folliculorum.

6. The use according to any one of claims 1 to 5, wherein the Demodex mite-killing product is a pharmaceutical composition, a cosmetic or a miticide.

7. The pharmaceutical composition is for preventing and / or treating a disease caused by Demodex mites infection, The use according to claim 6, wherein the disease is selected from eye diseases, skin diseases and allergic diseases.

8. 8. The use according to claim 7, 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, basal cell carcinoma of the eyelid, dry eye, and chalazion.

9. 8. The use according to claim 7, wherein the skin disease is selected from seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, sarcoptic mange, and basal cell carcinoma.

10. The use according to claim 7, wherein the allergic disease is selected from allergic asthma, allergic rhinitis and allergic dermatitis.

11. The use according to claim 7, wherein the pharmaceutical composition is a topical formulation.

12. The use according to claim 7, wherein the pharmaceutical composition is an ophthalmic formulation or a topical skin formulation.

13. 13. The use according to claim 12, wherein the ophthalmic formulation is selected from eye drops, eye ointments, ophthalmic gels, eye emulsions, ophthalmic suspensions, ophthalmic films, eye washes, and intraocular injections.

14. The use according to claim 12, wherein the topical dermatological preparation is selected from the group consisting of aerosols, powders, lotions, tinctures, liniments, coatings, ointments, gels, pastes and emulsions.

15. The use according to claim 7, wherein the pharmaceutical composition is a human pharmaceutical composition or a veterinary pharmaceutical composition.

16. The use according to claim 6, wherein the form of the cosmetic product is selected from the group consisting of 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, and eyebrow powder.

17. The use according to claim 6, wherein the form of the acaricide is selected from the group consisting of a spray, a lotion, a patch, and a small package.

18. 1. Use of Zingiber officinale, a hot water extract of Zingiber officinale, an isolated compound of Zingiber officinale or a salt or solvate thereof in the manufacture of a medicament for treating and / or preventing a disease caused by Demodex mites, comprising: The use, wherein the isolated compound is one or more selected from gentiopicroside, loganic acid, swelloside, lobric acid, scopoletin, rubimaylin, and swerthiamarin.

19. 19. The use according to claim 18, wherein the disease is selected from eye diseases, skin diseases and allergic diseases.

20. 20. The use according to claim 19, 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, basal cell carcinoma of the eyelid, dry eye, chalazion.

21. 20. The use according to claim 19, wherein the skin disease is selected from seborrheic dermatitis, acne, rosacea, pityriasis follicularis, perioral dermatitis, demodex, sarcoptic mange, and basal cell carcinoma.

22. 20. The use according to claim 19, wherein the allergic disease is selected from allergic asthma, allergic rhinitis, and allergic dermatitis.

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