Fresh gastrodia elata extract as well as preparation method and application thereof

Abstract

The invention provides a fresh Gastrodia elata Blume extract, a preparation method of the fresh Gastrodia elata Blume extract, and application of the fresh Gastrodia elata Blume extract in the fields of cosmetics and medicines. Belongs to the technical field of cosmetics and medicines. According to the present invention, the fresh gastrodia elata extract product ZTM-11, the fresh gastrodia elata extract product ZTM-14, the fresh gastrodia elata extract product ZTM-14-1, the fresh gastrodia elata extract product ZTM-14-2, the fresh gastrodia elata extract product ZTM-14-3, the fresh gastrodia elata extract product ZTM-14-5 and the fresh gastrodia elata extract product ZTM-14-6 are subjected to a low concentration (1 [mu] M) so as to significantly promote the secretion of # imgabs0 # collagen in human dermis fibroblasts (HDFa); and under the concentration, no cytotoxicity exists. The extracts can be used for preparing anti-aging drugs or skin care products.

Description

Technical Field

[0001] The present invention belongs to the field of cosmetics and pharmaceutical technology, and specifically relates to the field of botanical medicine technology, and more specifically, to fresh gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6, their pharmaceutical compositions, their preparation methods, and their applications in the preparation of drugs and cosmetics. Background Art

[0002] Collagen is a major structural protein in the extracellular matrix of mammals. It is widely present in skin, bones, muscles and other tissues. It is mainly involved in physiological and biochemical behaviors such as cell proliferation, differentiation, migration and signal transduction, and plays a supporting, repairing and protecting role for tissue cells [Ye Tao, Xiang Qi, Yang Yan, Huang Yadong. Research progress on the development and application of collagen. Journal of Biotechnology, 2023, 39(3): 942–960]. Among them, type I collagen (collagen I) is the most abundant protein in human skin, accounting for about 70% of the dry weight of the skin. Type I collagen can increase skin elasticity and delay skin aging [Zhang Yuhan, Zhou Jingxuan, Zhang Nanhai, Zhao Liang, Zhang Liebing, Zhou Feng. Research progress on collagen peptides and elastin peptides to improve skin photoaging. Food Research and Development, 2023, 44(11): 208–215]. In addition, on the wound surface, type I collagen promotes wound healing by providing structural support for cell attachment and migration. However, animal-derived type I collagen may be immunogenic, and problems related to the processing technology, degradation rate and sterilization process of type I collagen limit its application [Cheng Y., Li Y., Huang S., Yu F., Bei Y., Zhang Y., Tang J., Huang Y., Xiang Q. Hybrid freeze-dried dressings composed of epidermal growth factor and recombinant human-like collagen enhance cutaneous wound healing in rats. Front. Bioeng. Biotechnol., 2020, 8: 742]. Therefore, screening plant extracts and natural products with the activity of promoting collagen secretion is a current research hotspot.

[0003] The traditional Chinese medicine Gastrodia elata is the dried tuber of the orchid plant Gastrodia elata Blume [Chinese Pharmacopoeia Committee. Pharmacopoeia of the People's Republic of my country (Part I). Beijing: China Medical Science and Technology Press. 2020, 59-60], and is a precious Chinese medicinal material. Fresh Gastrodia elata is a very good food [Zhao Xiaohui, Xu Danxian, Luan Jie, Duan Zhimin, Lin Ji, Xu Yan. Analysis and evaluation of nutritional components of fresh Gastrodia elata from Xiaocaoba, Yiliang, Zhaotong. Journal of Food Safety and Quality, 2017, 8(10), 3727-3731]. However, there are relatively few studies on the biological activity of fresh Gastrodia elata, especially no reports on its ability to promote collagen secretion.

[0004] So far, there is no report in the prior art about fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6, nor is there any report about their ability to promote collagen secretion. Summary of the invention

[0005] The object of the present invention is to provide fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6, their pharmaceutical compositions, their preparation methods, and their uses in the preparation of medicines and cosmetics in view of the above-mentioned deficiencies in the prior art.

[0006] In order to achieve the above-mentioned object of the present invention, the present invention provides the following technical solutions:

[0007] Fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 are prepared by the following method:

[0008] Take the peeled fresh Gastrodia elata, cut it into small pieces, freeze-dry it with liquid nitrogen, and grind it into powder;

[0009] Take the powder, add 70% ethanol, perform ultrasonic-assisted extraction for 1 hour at room temperature, filter, evaporate the filtrate to dryness, and obtain extract ZTM-11; take the powder, add distilled water, perform ultrasonic-assisted extraction for 1 hour at 60°C, filter, evaporate the filtrate to dryness, and obtain extract ZTM-14;

[0010] Take the powder, add pure water, and extract with ultrasonic assistance at 60°C for 1h, and filter to obtain the filtrate. The remaining filter residue is extracted 3 times in the same way, and the filtrate is combined and evaporated to obtain the extract; take the extract, add distilled water to prepare a suspension, use D101 macroporous adsorption resin for column chromatography, and elute with distilled water, 10% ethanol, 50% ethanol and 90% ethanol respectively. After recovering the solvent, the distilled water elution part ZTM-14-1, the 10% ethanol elution part ZTM-14-2, and the 50% ethanol elution part ZTM-14-3 are obtained respectively; take the extract, add distilled water, and after the extract is completely dissolved, add anhydrous ethanol dropwise, and stand for 5h until a precipitate is precipitated, filter, and evaporate the filtrate to obtain ZTM-14-5; after the precipitate is dried, ZTM-14-6 is obtained.

[0011] The preparation method of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 comprises the following steps:

[0012] Take the peeled fresh Gastrodia elata, cut it into small pieces, freeze-dry it with liquid nitrogen, and grind it into powder;

[0013] Take the powder, add 70% ethanol, perform ultrasonic-assisted extraction for 1 hour at room temperature, filter, evaporate the filtrate to dryness, and obtain extract ZTM-11; take the powder, add distilled water, perform ultrasonic-assisted extraction for 1 hour at 60°C, filter, evaporate the filtrate to dryness, and obtain extract ZTM-14;

[0014] Take the powder, add pure water, and extract with ultrasonic assistance at 60°C for 1h, and filter to obtain the filtrate. The remaining filter residue is extracted 3 times in the same way, and the filtrate is combined and evaporated to obtain the extract; take the extract, add distilled water to prepare a suspension, use D101 macroporous adsorption resin for column chromatography, and elute with distilled water, 10% ethanol, 50% ethanol and 90% ethanol respectively. After recovering the solvent, the distilled water elution part ZTM-14-1, the 10% ethanol elution part ZTM-14-2, and the 50% ethanol elution part ZTM-14-3 are obtained respectively; take the extract, add distilled water, and after the extract is completely dissolved, add anhydrous ethanol dropwise, and stand for 5h until a precipitate is precipitated, filter, and evaporate the filtrate to obtain ZTM-14-5; after the precipitate is dried, ZTM-14-6 is obtained.

[0015] The application of the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 in the preparation of anti-aging drugs.

[0016] The fresh gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 are used in the preparation of an active agent for promoting collagen secretion.

[0017] The pharmaceutical composition is composed of any one of the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 or any combination thereof and a pharmaceutically acceptable carrier.

[0018] The pharmaceutical composition is used in the preparation of anti-aging drugs and in the preparation of an active agent for promoting collagen secretion.

[0019] The preparation method of the pharmaceutical composition comprises the following steps: preparing fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 by the above-mentioned preparation method, taking at least one of them, and adding a pharmaceutically acceptable carrier.

[0020] The application of the fresh gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 in the preparation of cosmetics.

[0021] A cosmetic comprising at least one of the fresh gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 as an active ingredient.

[0022] The method for preparing cosmetics comprises the following steps: adopting the above-mentioned preparation method to prepare fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6, taking at least one of them, and adding common cosmetic auxiliary materials.

[0023] In the present invention, when the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 or their compositions are used to prepare drugs, the content of the compounds or their compositions in the drugs is preferably 0.1-99%; in the pharmaceutical composition, the content of any one of the active ingredients or any combination thereof in the pharmaceutical composition is preferably 0.5-90%. The pharmaceutical composition of the present invention is preferably used in the form of a dosage per unit body weight. In the present invention, the prepared drugs are preferably administered in two forms: injection (intravenous injection, intramuscular injection) and oral administration. The pharmaceutical preparations include tablets, capsules, nasal sprays, pills, dripping pills, etc., including but not limited to the above-mentioned preparations.

[0024] In the present invention, when fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 are used to prepare cosmetics, the preparation of the cosmetics is not limited and can be prepared by conventional cosmetic preparation methods.

[0025] Compared with the prior art, the present invention has the following advantages:

[0026] 1. The present invention provides fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6, which have the effect of promoting collagen secretion at a relatively low concentration (1 μg / mL).

[0027] 2. Fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 were not toxic to adult dermal fibroblasts at the concentrations at which they exerted their efficacy.

[0028] 3. Use fresh Gastrodia elata for extraction, the raw materials are easily available, the process is simple and the cost is low.

[0029] 4. Extracted from fresh Gastrodia elata, its natural ingredients are better preserved. DETAILED DESCRIPTION

[0030] The following embodiments of the present invention are used to further illustrate the essential content of the present invention, but the present invention is not limited thereto.

[0031] Example 1

[0032] Preparation of fresh Gastrodia elata extracts ZTM-11, ZTM-12, ZTM-13 and ZTM-14:

[0033] Take the peeled fresh Gastrodia elata, cut it into small pieces, freeze-dry it with liquid nitrogen, and grind it into powder.

[0034] Take 20 g of powder, add 400 mL of 70% ethanol, perform ultrasonic-assisted extraction for 1 h at room temperature, filter, and evaporate the filtrate to dryness to obtain an extract (ZTM-11; 0.9 g).

[0035] Take 20 g of powder, add 400 mL of distilled water, and perform ultrasonic-assisted extraction for 1 h at room temperature. Filter and evaporate the filtrate to dryness to obtain an extract (ZTM-12; 3.4 g).

[0036] Take 20 g of powder, add 400 mL of 70% ethanol, extract with ultrasound assistance at 60° C. for 1 h, filter, and evaporate the filtrate to dryness to obtain an extract (ZTM-13; 0.8 g).

[0037] Take 20 g of powder, add 400 mL of distilled water, and extract with ultrasound assistance at 60°C for 1 h. Filter and evaporate the filtrate to dryness to obtain an extract (ZTM-14; 2.7 g).

[0038] Example 2

[0039] Preparation of fresh Gastrodia elata extracts ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-4, ZTM-14-5 and ZTM-14-6:

[0040] Take the peeled fresh Gastrodia elata, cut it into small pieces, add liquid nitrogen to freeze-dry, and grind it into powder. Take 20g of powder, add 400mL of pure water, and extract it with ultrasonic assisted extraction at 60℃ for 1h, and filter to obtain the filtrate. The remaining filter residue is extracted 3 times in the same way. Combine the filtrate and evaporate to dryness to obtain the extract (7.1g).

[0041] Take 5.9g of extract, add distilled water to prepare a suspension, and use D101 macroporous adsorption resin for column chromatography. Elution is carried out with distilled water, 10% ethanol, 50% ethanol and 90% ethanol, respectively. After recovering the solvent, the distilled water elution portion (ZTM-14-1; 4.5g), 10% ethanol elution portion (ZTM-14-2; 0.44g), 50% ethanol elution portion (ZTM-14-3; 0.03g) and 90% ethanol elution portion (ZTM-14-4; 0.02g) are obtained respectively.

[0042] Take 1g of extract, add 20mL of distilled water, and after the extract is completely dissolved, add 40mL of anhydrous ethanol dropwise, and let it stand for 5 hours until a precipitate is precipitated, and filter it. After the filtrate is partially evaporated to dryness, ZTM-14-5 (0.2g) is obtained; after the precipitate is dried, ZTM-14-6 (0.7g) is obtained.

[0043] Example 4

[0044] Experiment on promoting type I collagen secretion by fresh Gastrodia elata extracts ZTM-11, ZTM-12, ZTM-13, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-4, ZTM-14-5 and ZTM-14-6.

[0045] 1. Cells

[0046] Human dermal fibroblasts-adult (HDFa) were purchased from Beina Biotechnology.

[0047] 2. Reagents

[0048] DMEM (high glucose) medium, PBS, Hank's balanced salt solution (HBSS), penicillin-streptomycin and fetal bovine serum (FBS) were purchased from Hyclone; 0.25% trypsin (containing EDTA) was purchased from ThermoFisher; transforming growth factor beta (TGF-β) was purchased from Peprotech; collagen ELISA kit was purchased from TaKaRa; MTS reagent was purchased from Promega.

[0049] 3. Experimental Methods

[0050] On a 96-well cell culture plate, HDFa cells were mixed with the sample to be tested, and a blank control without extract and a TGF-β positive control were set; cultured at 37°C, 5% CO2 for 3 days, the cell culture supernatant was collected and stored at -80°C; MTS was added, and the OD value at 490nm was detected by MTS colorimetry; the secretion of type I collagen was detected according to the method provided in the collagen ELISA kit, and the OD value was measured by a microplate reader, and the detection wavelength was 450nm. The increase rate of type I collagen secretion was calculated.

[0051] Type I collagen secretion increase rate (%) = (OD 450 nm / Cell viability / blank well OD 450 nm -1)×100%

[0052] 4. Experimental Results

[0053] The present invention evaluates the activity of fresh Gastrodia elata extract in promoting the secretion of type I collagen in HDFa cells, and the test results are shown in Table 1. At a concentration of 1 μg / mL, extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 have a significant promoting effect on the secretion of type I collagen, and the increase rates of type I collagen secretion are 17.0%, 26.4%, 26.8%, 33.2%, 36.7%, 17.4% and 17.6%, respectively, and these extracts have no toxicity to HDFa cells.

[0054] Table 1. Effect of fresh Gastrodia elata extract on the secretion of type I collagen in HDFa cells

[0055]

[0056] Embodiment 5:

[0057] Ampoule: 2 mg of at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, and ZTM-14-6, and 10 mg of sodium chloride;

[0058] Preparation method: dissolve at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, ZTM-14-6 and sodium chloride in an appropriate amount of water for injection, filter the resulting solution, and fill it into an ampoule bottle under sterile conditions.

[0059] Embodiment 6:

[0060] Capsules: 10 mg of at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, and ZTM-14-6, 187 mg of lactose, and 3 mg of magnesium stearate;

[0061] Preparation method: Mix at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, and ZTM-14-6 with an auxiliary agent, sieve, and mix evenly. Put the resulting mixture into hard gelatin capsules, each capsule weighing 200 mg and containing 10 mg of active ingredient.

[0062] Embodiment 7:

[0063] Cream formula (W %) containing at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, and ZTM-14-6:

[0064]

[0065] The cosmetics of the present invention are prepared by conventional methods for preparing cosmetics.

[0066] Embodiment 8:

[0067] Emulsion formula (W %) containing at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, and ZTM-14-6:

[0068]

[0069]

[0070] The cosmetics of the present invention are prepared by conventional methods for preparing cosmetics.

[0071] Embodiment 9:

[0072] Tablets: 10 mg of at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, and ZTM-14-6, 180 mg of lactose, 55 mg of starch, and 5 mg of magnesium stearate;

[0073] Preparation method: Mix at least one of fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5, ZTM-14-6, lactose and starch, evenly moisten with water, sieve and dry the moistened mixture, sieve again, add magnesium stearate, and then compress the mixture into tablets, each tablet weighing 250 mg and containing 10 mg of extract.

Claims

1. Fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6, characterized in that: It is prepared by the following method: Take the peeled fresh Gastrodia elata, cut it into small pieces, freeze-dry it with liquid nitrogen, and grind it into powder; Take the powder, add 70% ethanol, perform ultrasonic-assisted extraction for 1 hour at room temperature, filter, evaporate the filtrate to dryness, and obtain extract ZTM-11; take the powder, add distilled water, perform ultrasonic-assisted extraction for 1 hour at 60°C, filter, evaporate the filtrate to dryness, and obtain extract ZTM-14; Take the powder, add pure water, and extract with ultrasonic assistance at 60°C for 1h, and filter to obtain the filtrate. The remaining filter residue is extracted 3 times in the same way, and the filtrate is combined and evaporated to obtain the extract; take the extract, add distilled water to prepare a suspension, use D101 macroporous adsorption resin for column chromatography, and elute with distilled water, 10% ethanol, 50% ethanol and 90% ethanol respectively. After recovering the solvent, the distilled water elution part ZTM-14-1, the 10% ethanol elution part ZTM-14-2, and the 50% ethanol elution part ZTM-14-3 are obtained respectively; take the extract, add distilled water, and after the extract is completely dissolved, add anhydrous ethanol dropwise, and stand for 5h until a precipitate is precipitated, filter, and evaporate the filtrate to obtain ZTM-14-5; after the precipitate is dried, ZTM-14-6 is obtained.

2. A method for preparing fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6, characterized in that: The method comprises the following steps: Take the peeled fresh Gastrodia elata, cut it into small pieces, freeze-dry it with liquid nitrogen, and grind it into powder; Take the powder, add 70% ethanol, perform ultrasonic-assisted extraction for 1 hour at room temperature, filter, evaporate the filtrate to dryness, and obtain extract ZTM-11; take the powder, add distilled water, perform ultrasonic-assisted extraction for 1 hour at 60°C, filter, evaporate the filtrate to dryness, and obtain extract ZTM-14; Take the powder, add pure water, and extract with ultrasonic assistance at 60°C for 1h, and filter to obtain the filtrate. The remaining filter residue is extracted 3 times in the same way, and the filtrate is combined and evaporated to obtain the extract; take the extract, add distilled water to prepare a suspension, use D101 macroporous adsorption resin for column chromatography, and elute with distilled water, 10% ethanol, 50% ethanol and 90% ethanol respectively. After recovering the solvent, the distilled water elution part ZTM-14-1, the 10% ethanol elution part ZTM-14-2, and the 50% ethanol elution part ZTM-14-3 are obtained respectively; take the extract, add distilled water, and after the extract is completely dissolved, add anhydrous ethanol dropwise, and stand for 5h until a precipitate is precipitated, filter, and evaporate the filtrate to obtain ZTM-14-5; after the precipitate is dried, ZTM-14-6 is obtained.

3. Use of the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 according to claim 1 in the preparation of anti-aging drugs.

4. Use of the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 described in claim 1 in the preparation of an active agent for promoting collagen secretion.

5. A pharmaceutical composition, consisting of any one of the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 according to claim 1 or any combination thereof and a pharmaceutically acceptable carrier.

6. Use of the pharmaceutical composition according to claim 4 in the preparation of anti-aging drugs and in the preparation of an active agent for promoting collagen secretion.

7. The method for preparing the pharmaceutical composition according to claim 4, characterized in that: The method comprises the following steps: firstly preparing fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 by the preparation method described in claim 2, and then taking at least one of them and adding a pharmaceutically acceptable carrier.

8. Use of the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 according to claim 1 in the preparation of cosmetics.

9. A cosmetic comprising at least one of the fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 according to claim 1 as an active ingredient.

10. The method for preparing cosmetics according to claim 9, characterized in that: The method comprises the following steps: firstly preparing fresh Gastrodia elata extracts ZTM-11, ZTM-14, ZTM-14-1, ZTM-14-2, ZTM-14-3, ZTM-14-5 and ZTM-14-6 by the preparation method described in claim 2, and then taking at least one of them and adding common cosmetic auxiliary materials.

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