Preparation of ginkgol monomer and ginkgol monomer killing acariform mite face cream and preparation method thereof

Abstract

The application discloses a preparation of ginkgol monomer and a ginkgol monomer acaricidal face cream and a preparation method, belongs to the field of medicines, and relates to the effect of ginkgol monomers on killing human acariform helminths. The face cream is composed of a ginkgol monomer part, an auxiliary phase and aminomethyl propanol, and the content of the ginkgol monomer in the face cream is 10%. The ginkgol monomer is a new use of an ideal safe and efficient natural antibacterial acaricidal medicine. The ginkgol monomer is an alkyl phenol homologous series, has a straight chain alkyl or alkenyl side chain with a length of 13-17 carbons, and has 0-2 double bonds on the side chain. The ginkgol monomer can be used as a medicine for killing human acariform helminths, and can be used in the form of independent monomers or a mixture of two or more monomers in any proportion. Compared with ginkgolic acid, the ginkgol monomer is free of a carboxyl on a benzene ring, has no irritation to the skin and no side effects, and can be used to prepare various skin external preparations.

Description

Technical Field

[0001] This invention belongs to the pharmaceutical field and relates to the application of ginkgo biloba extract in killing human mites, as well as a safe and highly effective face cream for killing mites with ginkgo biloba extract as the active ingredient and its preparation method. Background Technology

[0002] Demodex mites, also known as hair follicle mites, belong to the order Eumetracaria and the family Demodicidae. They parasitize the hair follicles and sebaceous glands of humans and mammals, with over 140 known species and subspecies. Only two species parasitize humans: *Demodex folliculorum* and *Demodex brevis*. Human Demodex mites are permanent parasites that can damage epithelial and glandular cells, causing hair follicle dilation and epithelial degeneration. Demodex mite infections can cause folliculitis, seborrheic dermatitis, acne, rosacea, blepharitis, and pruritus of the external auditory canal, severely affecting appearance and causing significant psychological distress. Infection rates are higher and the harm is greater in immunocompromised individuals. Demodex mites can be transmitted directly or indirectly through human-to-human contact, and can also cause zoonotic diseases through contact between humans and pets.

[0003] Reports from abroad indicate an infection rate of 27%-100% in the general population, while the infection rate in the domestic population is generally above 20%, reaching as high as 97.86%. The infection rate of Demodex mites is basically the same in men and women, with no significant difference. Demodex folliculorum is the most common type of infection, followed by Demodex brevis. Some patients have dual infections.

[0004] There are many topical medications for treating Demodex mites, but there is currently no definitively effective acaricide. Some commonly used medications have limited clinical efficacy, such as metronidazole cream, benzyl benzoate emulsion, permethrin cream, and sulfur ointment, all of which are effective against Demodex mites, but with limited efficacy. Oral medications, such as metronidazole and ivermectin, can cause certain adverse reactions with long-term use. Currently, there is a lack of safe and highly effective anti-Demodex mite drugs.

[0005] In the search for safe and effective drugs against Demodex mites, many traditional Chinese medicines with good insecticidal effects have been tried for the eradication of Demodex mites on the human face. Examples include: Artemisia argyi volatile oil ("A type of Artemisia argyi mite-removing cream, an extraction method for Artemisia argyi volatile oil" (application number 201610028035.5)); and a combination of the insecticidal traditional Chinese medicines Hydnocarpus anthelmintica oil, Brucea javanica oil, menthol, and bitter almond ("A cream for killing Demodex mites on the human face and its preparation method" (application number 201410632346.3)). In addition, Sichuan pepper oil, Stemona japonica oil, Artemisia argyi essential oil, eucalyptus oil, wintergreen oil, and camphor essential oil all have good effects in killing Demodex mites. Currently, the main method for killing Demodex mites on the human face is using traditional Chinese medicine essential oils. Essential oils are mixtures of volatile components from traditional Chinese medicines, and their composition is very complex, making it difficult to identify the effective insecticidal components.

[0006] Ginkgo (Ginkgo biloba L.) is a traditional Chinese medicine. Its fruit, commonly known as white fruit, has the effects of reducing phlegm, detoxifying, and killing parasites. The outer seed coat of ginkgo is a waste product of white fruit production. In addition to polysaccharides and flavonoids, the outer seed coat also contains abundant ginkgolic acid compounds, accounting for about 5% of the outer seed coat's mass. Studies have shown that ginkgolic acid and ginkgolic acid compounds have excellent antibacterial, antifungal, and antitumor effects. my country accounts for 70% of the world's ginkgo resources, and the annual production of large quantities of ginkgo fruits is accompanied by a large amount of ginkgo outer seed coat, providing ample raw materials for the preparation of ginkgolic acid compounds. Summary of the Invention

[0007] To address the aforementioned problems, this invention provides a ginkgo biloba cream capable of killing Demodex mites on the human face, along with its preparation method. The active ingredient in the cream, ginkgo biloba, is derived from the traditional Chinese medicine ginkgo and is non-irritating to human skin. It can be used to treat a range of infections caused by Demodex mites, including acne, rosacea, folliculitis, and blepharitis. The ginkgo biloba-based Demodex-killing cream provided by this invention has a well-balanced formula and can quickly penetrate the skin to achieve its mite-killing effect.

[0008] The ginkgophenol monomer involved in this invention is an alkyl or alkenyl phenol with the structure shown in general formula I, wherein R is a straight-chain alkyl or alkenyl group with a chain length of 13 to 17 carbon atoms and 0 to 2 double bonds. These alkylphenol compounds are mainly found in ginkgo leaves and ginkgo seed coats and can be extracted and separated from ginkgo seed coats.

[0009]

[0010] When preparing a face cream to kill mites, the ginkgo biloba extract used can be one of the compounds shown in structural formula 1, or a mixture of two or more of them in any proportion.

[0011] The above-mentioned objective of this invention is achieved through the following technical solution:

[0012] A ginkgo biloba-based face cream for killing Demodex mites, the face cream is composed of the active ingredient ginkgo biloba, an auxiliary agent phase and aminomethylpropanol, and the ginkgo biloba content in the face cream is 10%.

[0013] Furthermore, the composition and preparation steps of the adjuvant phase in the Ginkgo biloba-based mite-killing face cream are as follows: Take 8% glycerin, 4% butylene glycol, 0.05% hyaluronic acid, 0.05% xanthan gum, 0.6% carbomer 2020, and 0.15% methylparaben by mass fraction, mix them, add deionized water to 100% by mass fraction, stir evenly, and stir at a constant temperature of 80℃ for 10-20 minutes.

[0014] Furthermore, the composition and preparation steps of the ginkgo biloba extract in the Ginkgo biloba-killing face cream are as follows: Take 70% ginkgo biloba extract, 5% polydimethylsiloxane, 1.6% almond oil, 4% ethylhexyl palmitate, 17% caprylic / capric triglyceride (CAS: 65381-09-1), and 2.4% vitamin E, mix them evenly, and stir at a constant temperature of 80℃ for 10-20 minutes.

[0015] Further, the preparation steps of the Ginkgo biloba-based mite-killing face cream are as follows: After thoroughly mixing 0.74 parts of Ginkgo biloba powder with 3 parts of auxiliary agents, add 0.3 parts of aminomethylpropanol, stir and cool to 45°C, add 0.6 parts of 1,2-hexanediol, 0.4 parts of phenoxyethanol, and 0.1 parts of ethylhexylglycerin, and stir evenly.

[0016] The active ingredient of this invention is ginkgolide. Compared with ginkgolic acid, ginkgolide does not have a carboxyl group on its benzene ring, thus it is non-irritating to the skin and has no side effects. The resulting face cream can quickly penetrate the skin to kill mites. Detailed Implementation

[0017] Example 1: Preparation of Ginkgo biloba homologues and monomers

[0018] Take dried Ginkgo biloba outer seed coat, crush it into pieces about 3 mm in size, add petroleum ether (60-90℃) and ultrasonically extract for 6 h, remove the solvent to obtain crude petroleum ether extract; dissolve the sample in an appropriate amount of petroleum ether and load it onto a silica gel column (Φ32 x 400 mm), elute with petroleum ether: ethyl ether: formic acid (89:11:1, v / v / v), collect the ginkgolic acid fraction, repeat the purification three times to obtain a homologous mixture of ginkgolic acid.

[0019] 1.0 g of ginkgolic acid homologue and 0.02 g of Ca(OH)2 were mixed in a single-necked flask and reacted at 135–140 °C for 2 hours. After cooling to room temperature, the mixture was extracted with petroleum ether, filtered, and concentrated to obtain an oily substance. The product was dissolved in methanol, 25% ammonia was added, and the mixture was stirred for 15 min and then extracted with hexane. The organic layer was washed with 5% HCl and distilled water, and the organic phase was separated, dried over anhydrous NaSO4, and concentrated to obtain a mixture of ginkgolic acid homologues.

[0020] Preparative chromatography was used for separation. A Welch Ultimate AQ-C18 column (21.2 h Ultimate AQ-) was used; the mobile phase was methanol-water; the detection wavelength was 280 nm; and the flow rate was 24 mL / min. Ginkgo biloba extract monomers C13:0, C15:1-Δ8, C17:2-Δ9, Δ12, C15:0, C17:1-Δ10, and C17:1-Δ12 were obtained.

[0021] Example 2: A Ginkgo Biloba Homologosa Mixture Demodex Mite Killer Cream

[0022] The active ingredient in the face cream is a mixture of ginkgo biloba homologues, consisting of ginkgo biloba C13:0, C15:0, C15:1, C17:1 and C17:2, with the proportions of each homologue being 20.7%, 3.3%, 51.6%, 21.1% and 3.3%, respectively.

[0023] Face cream preparation method and steps:

[0024] (1) Take 8% glycerin, 4% butylene glycol, 0.05% hyaluronic acid, 0.05% xanthan gum, 0.6% carbomer 2020 and 0.15% methylparaben by mass fraction, add deionized water to 100% mass fraction, stir evenly, and stir at a constant temperature for 10-20 minutes for 80 minutes.

[0025] (2) Take 70% Ginkgo biloba homologue, 5% polydimethylsiloxane, 1.6% almond oil, 4% ethylhexyl palmitate, 17% caprylic / capric triglyceride (CAS: 65381-09-1), and 2.4% vitamin E by mass fraction, mix them evenly, and stir at 80°C for 10-20 minutes.

[0026] (3) After thoroughly mixing the ginkgo biloba extract (0.74 parts) from step (2) with the auxiliary agent phase (3 parts) from step (1), add 0.3 parts aminomethylpropanol, stir and cool to 45°C, add 0.6 parts 1,2-hexanediol, 0.4 parts phenoxyethanol, and 0.1 parts ethylhexylglycerol, and stir until uniform.

[0027] This resulted in a face cream containing 10% ginkgo biloba homologues that kills Demodex mites.

[0028] The mite-killing effect of Ginkgo biloba homologues-based face creams for killing Demodex mites

[0029] Demodex mites were obtained using the overnight adhesive tape method, and then flattened on glass slides for microscopic examination. A 10% Ginkgo biloba extract cream was diluted to concentrations of 50%, 25%, 12.5%, 6.25%, and 3.125% using paraffin oil as a diluent, with paraffin oil serving as a blank control. 200 μl of the solution was added to each slide, spreading it evenly to ensure sufficient contact between the oil and the mites. The slides were placed under conditions of 70–80% humidity and 26–28°C, and periodically removed for microscopic observation of mites survival.

[0030] Table 1. Killing effect of Ginkgo biloba homologue face cream on two types of Demodex mites.

[0031]

[0032] Judgment criteria: If the chelicerae and claws of the insect do not move when observed under a microscope for 1 minute, it is considered preliminarily dead; if they still do not move after 30 minutes, it is confirmed to be dead.

[0033] Example 3: A Ginkgo biloba extract C13:0 face cream for killing Demodex mites

[0034] The active ingredient in the face cream is ginkgo biloba extract C13:0 monomer.

[0035] Face cream preparation method and steps:

[0036] (1) Take 8% glycerin, 4% butylene glycol, 0.05% hyaluronic acid, 0.05% xanthan gum, 0.6% carbomer 2020 and 0.15% methylparaben by mass fraction, add deionized water to 100% mass fraction, stir evenly, and stir at a constant temperature for 10-20 minutes for 80 minutes.

[0037] (2) Take 70% Ginkgo biloba extract C13:0, 5% polydimethylsiloxane, 1.6% almond oil, 4% ethylhexyl palmitate, 17% caprylic / capric triglyceride (CAS: 65381-09-1), and 2.4% vitamin E by mass fraction, mix them evenly, and stir at 80°C for 10-20 minutes.

[0038] (3) After thoroughly mixing the ginkgo biloba extract (0.74 parts) from step (2) with the auxiliary agent phase (3 parts) from step (1), add 0.3 parts aminomethylpropanol, stir and cool to 45°C, add 0.6 parts 1,2-hexanediol, 0.4 parts phenoxyethanol, and 0.1 parts ethylhexylglycerol, and stir until uniform.

[0039] This resulted in a face cream containing 10% Ginkgo biloba extract (C13:0) that kills Demodex mites.

[0040] The mite-killing effect of Ginkgo biloba extract C13:0 face cream for killing Demodex mites

[0041] Demodex mites were obtained using the overnight adhesive tape method, and then flattened on glass slides for microscopic examination. Using paraffin oil as a diluent, 10% Ginkgo biloba extract C13:0 demodex mite-killing cream was diluted to concentrations of 50%, 25%, 12.5%, 6.25%, and 3.125%, respectively, with paraffin oil serving as a blank control. 200 μl of the solution was added to each slide, spreading it evenly to ensure full contact between the oil and the mites. The slides were placed under conditions of 70–80% humidity and 26–28°C, and periodically removed for microscopic observation of mites survival.

[0042] Table 2. Killing effect of Ginkgo biloba extract C13:0 face cream on two types of Demodex mites.

[0043]

[0044] Judgment criteria: If the chelicerae and claws of the insect do not move when observed under a microscope for 1 minute, it is considered preliminarily dead; if they still do not move after 30 minutes, it is confirmed to be dead.

[0045] Example 4: Ginkgo biloba extract C17:1 isomer mixture face cream for killing Demodex mites

[0046] The active ingredient in the face cream is a 1:1 mixture of two isomers of ginkgo biloba extract, C17:1-Δ10 and C17:1-Δ12.

[0047] Face cream preparation method and steps:

[0048] (1) Take 8% glycerin, 4% butylene glycol, 0.05% hyaluronic acid, 0.05% xanthan gum, 0.6% carbomer 2020 and 0.15% methylparaben by mass fraction, add deionized water to 100% mass fraction, stir evenly, and stir at a constant temperature for 10-20 minutes for 80 minutes.

[0049] (2) Take 70% Ginkgo biloba extract C17:1 isomer mixture, 5% polydimethylsiloxane, 1.6% almond oil, 4% ethylhexyl palmitate, 17% caprylic / capric triglyceride (CAS: 65381-09-1), and 2.4% vitamin E by mass fraction, mix them evenly, and stir at 80°C for 10-20 minutes.

[0050] (3) After thoroughly mixing the ginkgo biloba extract (0.74 parts) from step (2) with the auxiliary agent phase (3 parts) from step (1), add 0.3 parts aminomethylpropanol, stir and cool to 45°C, add 0.6 parts 1,2-hexanediol, 0.4 parts phenoxyethanol, and 0.1 parts ethylhexylglycerol, and stir until uniform.

[0051] This resulted in a face cream containing a mixture of 10% Ginkgo biloba C17:1 isomers, which is used to kill Demodex mites.

[0052] The mite-killing effect of a face cream containing a mixture of Ginkgo biloba C17:1 isomers and Demodex mites.

[0053] Demodex mites were obtained using the overnight adhesive tape method, and then flattened on glass slides for microscopic examination. Ginkgo biloba extract cream (a mixture of Ginkgo biloba C17:1 isomers) was diluted to concentrations of 50%, 25%, 12.5%, 6.25%, and 3.125% using liquid paraffin oil as a solvent, with paraffin oil serving as a blank control. 200 μl of the solution was added to each slide, spreading it evenly to ensure sufficient contact between the oil and the mites. The slides were placed under conditions of 70–80% humidity and 26–28°C, and periodically removed for microscopic observation of mites survival.

[0054] Table 3. The killing effect of the Ginkgo biloba extract C17:1 isomer mixture face cream on two types of Demodex mites.

[0055] Judgment criteria: If the chelicerae and claws of the insect do not move when observed under a microscope for 1 minute, it is considered preliminarily dead; if they still do not move after 30 minutes, it is confirmed to be dead.

[0056] Table 3. The killing effect of the Ginkgo biloba extract C17:1 isomer mixture face cream on two types of Demodex mites.

[0057]

[0058] Judgment criteria: If the chelicerae and claws of the insect do not move when observed under a microscope for 1 minute, it is considered preliminarily dead; if they still do not move after 30 minutes, it is confirmed to be dead.

Claims

1. A Ginkgo biloba-based face cream for killing Demodex mites, characterized in that... The face cream is composed of the active ingredient ginkgo biloba extract, auxiliary agents, and aminomethylpropanol. The ginkgo biloba extract content in the face cream is 10%. The composition and preparation steps of the adjuvant phase in the Ginkgo biloba-based mite-killing face cream are as follows: Take 8% glycerin, 4% butylene glycol, 0.05% hyaluronic acid, 0.05% xanthan gum, 0.6% carbomer 2020 and 0.15% methylparaben by mass fraction, mix them, add deionized water to 100% by mass fraction, stir evenly, and stir at 80℃ for 10-20 minutes. The composition and preparation steps of the ginkgo biloba extract in the Ginkgo biloba-killing face cream are as follows: Take 70% ginkgo biloba monomer, 5% polydimethylsiloxane, 1.6% almond oil, 4% ethylhexyl palmitate, 17% caprylic / capric triglyceride, and 2.4% vitamin E, mix them evenly, and stir at 80℃ for 10-20 minutes. The ginkgophenol monomer is an alkyl or alkenyl phenol with the structure shown in general formula I, where R is a straight-chain alkyl or alkenyl group with a chain length of 13–17 carbon atoms and 0–2 double bonds.

2. The method for preparing a ginkgo biloba-based face cream for killing Demodex mites as described in claim 1, characterized in that... Follow these steps: Mix 0.74 parts of ginkgo biloba extract with 3 parts of the auxiliary agent, add 0.3 parts of aminomethylpropanol, stir and cool to 45°C, add 0.6 parts of 1,2-hexanediol, 0.4 parts of phenoxyethanol, and 0.1 parts of ethylhexylglycerin, and stir until homogeneous.

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