CN115227804A - A kind of hair growth liquid for preventing seborrheic alopecia and promoting hair growth and preparation method thereof - Google Patents
A kind of hair growth liquid for preventing seborrheic alopecia and promoting hair growth and preparation method thereof Download PDFInfo
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- CN115227804A CN115227804A CN202210836083.2A CN202210836083A CN115227804A CN 115227804 A CN115227804 A CN 115227804A CN 202210836083 A CN202210836083 A CN 202210836083A CN 115227804 A CN115227804 A CN 115227804A
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- hair growth
- extract
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- liquid
- seborrheic alopecia
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Abstract
Description
技术领域technical field
本发明属于日用化工和洗护技术领域,具体涉及一种防止脂溢性脱发促进生发的生发液及其制备方法。The invention belongs to the technical field of daily chemical industry and washing and care, in particular to a hair growth liquid for preventing seborrheic alopecia and promoting hair growth and a preparation method thereof.
背景技术Background technique
脂溢性脱发(SA),又名雄激素性脱发,是临床最为常见的脱发性疾病。据调查,脱发患者中80%以上为脂溢性脱发或伴随脂溢性脱发。流行病学调查显示,逐年升高,且呈年轻化趋势,不仅有碍容颜、影响美观,也给患者带来巨大的精神压力和心理负担,严重影响患者生活质量。Seborrheic alopecia (SA), also known as androgenetic alopecia, is the most common clinical hair loss disorder. According to the survey, more than 80% of hair loss patients are seborrheic alopecia or accompanying seborrheic alopecia. Epidemiological surveys show that it is increasing year by year, and it shows a younger trend, which not only hinders the appearance and affects the appearance, but also brings huge mental pressure and psychological burden to patients, which seriously affects the quality of life of patients.
男性脂溢性性脱发临床主要表现前额尤其是两颞部的发迹线逐渐上移和头顶部的头发稀疏,前额和头顶的头发逐渐脱落,可伴头部皮肤油腻、脱屑、瘙痒,女性型脂溢性脱发主要表现为弥漫性脱发,头皮中央区域毛发进行性减少及变细,而前额发际线无明显变化。该病与遗传因素及头皮雄激素异常代谢显著相关,有家族史的患者病情进展较快且在年龄上常倾向于早发。The main clinical manifestations of male seborrheic alopecia are that the hairline of the forehead, especially the two temples, gradually moves up and the hair on the top of the head is thinning, and the hair on the forehead and the top of the head gradually falls off. Seborrheic alopecia is mainly characterized by diffuse alopecia, with progressive reduction and thinning of hair in the central area of the scalp, but no obvious changes in the forehead hairline. The disease is significantly associated with genetic factors and abnormal scalp androgen metabolism. Patients with a family history of the disease progress faster and tend to have early onset with age.
脂溢性脱发主要是由雄激素及其受体异常引起,也与遗传和心理等因素有关;现代医学认为SA是一种雄激素依赖的常染色体显性多基因遗传性秃发,雄激素过多或对雄激素敏感增加是该病发生的主要因素,SA的发生与睾酮(T)及其代谢产物二氢睾酮(DHT)和雄激素受体(AR)的水平增高直接相关,而5α- 还原酶(5α-R)在其中起到重要作用,另外长期心理失衡、精神紧张、饮食失调及病菌感染为诱发或加重本病的重要因素。Seborrheic alopecia is mainly caused by abnormal androgen and its receptors, and it is also related to genetic and psychological factors; modern medicine believes that SA is an androgen-dependent autosomal dominant polygenic hereditary alopecia with excess androgen. Or increased sensitivity to androgen is the main factor in the occurrence of the disease. The occurrence of SA is directly related to the increased levels of testosterone (T) and its metabolites dihydrotestosterone (DHT) and androgen receptor (AR), while 5α-reductase (5α-R) plays an important role in it. In addition, long-term psychological imbalance, mental stress, eating disorders and bacterial infection are important factors that induce or aggravate the disease.
本发明人认为系统解决脂溢性脱发,需同时协同三个方面:一是促进毛囊细胞增殖分化,二是减少二氢睾酮(DHT)对毛囊健康的侵害,三是提供充足促角蛋白表达和合成的营养素。现已批准的药物均只针对某一方面的影响因素,而已有生发营养液产品存在成分靶点不明确、针对性不强的问题。The inventors believe that to solve seborrheic alopecia systematically, three aspects need to be coordinated at the same time: one is to promote the proliferation and differentiation of hair follicle cells; the other is to reduce the damage of dihydrotestosterone (DHT) to the health of the hair follicle; Synthetic nutrients. The currently approved drugs are only aimed at a certain aspect of the influencing factors, and some hair growth nutrient solution products have the problem of unclear composition targets and weak pertinence.
目前治疗脂溢性脱发的主要医学手段是外用米诺地尔和口服5α-还原酶(5 α-R)抑制剂雄胺类药物如非那雄胺和度他雄胺,又以非那雄胺为主。At present, the main medical methods for the treatment of seborrheic alopecia are topical minoxidil and oral 5α-reductase (5α-R) inhibitor androsteroids such as finasteride and dutasteride, and finasteride. Amines are predominant.
米诺地尔是一种非特异性的治疗脱发药物,常用浓度为20和50mg/mL,是FDA 批准的用于治疗脂溢性脱发的唯一外用药物。其防治脱发的机制有:开放钾离子通道,抑制钙离子内流,减少表皮生长因子对毛发生长的抑制,促进毛囊上皮细胞的增殖分化,上调血管内皮细胞生长因子和改善局部的血供等。但使用过程中可能引起面部和四肢多毛症,停用后治疗效果逐渐消失。部分使用者出现头皮瘙痒和头屑不良反应,也存在较多使用者长出的毛发细小,毛发无法持续增粗生长的情况。Minoxidil is a non-specific drug for the treatment of hair loss, commonly used in concentrations of 20 and 50 mg/mL, and is the only topical drug approved by the FDA for the treatment of seborrheic alopecia. Its mechanisms for preventing and treating hair loss include: opening potassium ion channels, inhibiting calcium ion inflow, reducing the inhibition of epidermal growth factor on hair growth, promoting the proliferation and differentiation of hair follicle epithelial cells, up-regulating vascular endothelial growth factor and improving local blood supply, etc. However, it may cause facial and limb hirsutism during use, and the therapeutic effect gradually disappears after discontinuation. Some users experience scalp itching and dandruff adverse reactions, and there are also many users who grow small hair, and the hair cannot continue to thicken and grow.
目前市场上充斥着许多合成的甾体和非甾体5α-R抑制剂,然而这些合成抑制剂往往都有很多不良反应,难以满足广大患者的需求。非那雄胺一种特异性针对Ⅱ型5α-还原酶(5α-R)的甾体选择性抑制剂,可以减少睾酮(T)转化为与受体结合力更强的二氢睾酮(DHT),从而减弱雄激素对脱发的影响。非那雄胺可持续改善头发的生长情况,但存在引起性功能异常、精子减少和男性乳房发育异常等不良反应。At present, there are many synthetic steroidal and non-steroidal 5α-R inhibitors on the market. However, these synthetic inhibitors often have many adverse reactions, and it is difficult to meet the needs of the majority of patients. Finasteride is a steroid-selective inhibitor specific for type II 5α-reductase (5α-R), which can reduce the conversion of testosterone (T) into dihydrotestosterone (DHT), which binds more strongly to the receptor , thereby attenuating the effect of androgens on hair loss. Finasteride can continue to improve hair growth, but it has adverse effects such as abnormal sexual function, sperm reduction and gynecomastia.
除药物治疗外,市场上也有一些复合植物成分和多肽复合成分生发液。这些生发液的植物成分功能描述为促进血液循环而非特定物质的靶向作用,存在成分作用靶点不明确,植物成分协同作用机制不明确,效果上见效慢,生产提取技术上目标成分针对性不强,定量不准确的缺陷。In addition to drug treatment, there are also some complex plant ingredients and polypeptide complex ingredients hair growth liquid on the market. The function of the plant components of these hair growth liquids is described as promoting blood circulation rather than targeting specific substances. There are unclear targets for the action of the components, the synergistic mechanism of the plant components is unclear, the effect is slow, and the target components are targeted in the production and extraction technology. Not strong, quantitatively inaccurate defects.
植物中5α-R抑制剂具有广阔的开发前景,近两年国内外已有多种植物提取物被报道具有较强的5α-R抑制活性。因此,从植物中筛选出作用明确、活性显著的5α-R抑制剂,用于新一代药效物质基础明确的脂溢性脱发健康品,将为国内外脂溢性脱发患者带来福音。5α-R inhibitors in plants have broad development prospects. In the past two years, a variety of plant extracts have been reported to have strong 5α-R inhibitory activities. Therefore, screening out 5α-R inhibitors with clear effect and significant activity from plants, which will be used in a new generation of seborrheic alopecia health products with a clear pharmacodynamic material basis, will bring good news to patients with seborrheic alopecia at home and abroad.
发明内容SUMMARY OF THE INVENTION
为了解决上述技术问题,本发明提供一种防止脂溢性脱发促进生发的生发液及其制备方法。In order to solve the above technical problems, the present invention provides a hair growth liquid for preventing seborrheic alopecia and promoting hair growth and a preparation method thereof.
本发明的目的可以通过以下技术方案实现:The object of the present invention can be realized through the following technical solutions:
一种防止脂溢性脱发促进生发的生发液,包括如下重量百分比原料: 0.005-0.03%的乙酰基四肽-3,0.01-0.1%的肉豆蔻酰五肽-17,0.005-0.025%的生物素3肽-1,1-6%的蜡菊提取液,1-6%的侧柏叶提取液,0.2-2%的雌激素类中药提取液,0.2-2%的泛醇,0.2-0.5%的苯氧乙醇,0.5-3%的矢车菊提取物, 0.01-0.02%的富勒烯衍生物,余量为醇水缓冲液。A hair growth liquid for preventing seborrheic alopecia and promoting hair growth, comprising the following raw materials by weight: 0.005-0.03% of acetyl tetrapeptide-3, 0.01-0.1% of myristoyl pentapeptide-17, 0.005-0.025% of biological 3-Peptide-1, 1-6% Helichrysum extract, 1-6% Platycladus orientalis leaf extract, 0.2-2% estrogen Chinese medicine extract, 0.2-2% Panthenol, 0.2-0.5 % phenoxyethanol, 0.5-3% cornflower extract, 0.01-0.02% fullerene derivative, and the balance is alcohol-water buffer.
乙酰基四肽-3:Acetyl Tetrapeptide-3:
毛囊的大小是由毛乳头和细胞外基质的大小决定的。健康的毛乳头会产生细胞外基质蛋白如胶原蛋白Ⅲ和固定纤维如层粘连蛋白胶原蛋白Ⅶ,使发根结实。如果细胞外基质更新出了问题,头发会变得脆弱。这样循环下去,毛囊最终会萎缩。乙酰基四肽-3通过合成纤维细胞,加速细胞外基质蛋白的合成如层粘连蛋白、胶原蛋白Ⅲ和胶原蛋白Ⅶ,直接作用于毛囊周围组织增大毛囊的体积和长度。修复表皮与真皮连接组织,促使头发固定在毛囊内。The size of the hair follicle is determined by the size of the dermal papilla and extracellular matrix. Healthy dermal papillae produce extracellular matrix proteins such as collagen III and anchoring fibers such as laminin collagen VII, which strengthen the hair roots. If there is a problem with extracellular matrix turnover, hair can become brittle. If this cycle continues, the hair follicles will eventually shrink. Acetyl tetrapeptide-3 accelerates the synthesis of extracellular matrix proteins such as laminin, collagen III and collagen VII through the synthesis of fibroblasts, and directly acts on the tissue around the hair follicle to increase the volume and length of the hair follicle. Repairs the connective tissue between the epidermis and the dermis, and promotes the fixation of the hair in the follicle.
肉豆蔻酰五肽-17:Myristoyl Pentapeptide-17:
控制毛发生长周期与毛凸和毛乳头两个组织之间复杂的相互作用有关,由于毛乳头中含有神经以及给毛发提供营养的血液供给,可促进毛发生长。肉豆蔻酰五肽-17是一种有效的促进毛发生长的五肽,直接作用于角蛋白基因,促进角蛋白生成。The control of the hair growth cycle is related to the complex interaction between the two tissues, the hair bulge and the dermal papilla, which promote hair growth due to the nerves in the dermal papilla and the blood supply that nourishes the hair. Myristoyl Pentapeptide-17 is an effective hair growth-promoting pentapeptide that acts directly on keratin genes to promote keratin production.
生物素3肽-1:Biotin 3 Peptide-1:
是一种把维生素H和Matrikine系列信号肽GHK结合的三肽。生物素3肽 -1增加细胞外基质如胶原蛋白Ⅳ和层粘连蛋白5合成,延缓毛囊衰老,改善毛囊结构,有利于头发固定在真皮毛囊内防止脱发。激活组织修复基因表达,有利于皮肤结构重建和修复。促进细胞增殖和分化,刺激头发生长。It is a tripeptide that combines vitamin H and Matrikine series signal peptide GHK. Biotin 3-peptide-1 increases the synthesis of extracellular matrix such as collagen IV and laminin 5, delays the aging of hair follicles, improves the structure of hair follicles, and helps to fix the hair in the dermal follicle to prevent hair loss. Activation of tissue repair gene expression is beneficial to the reconstruction and repair of skin structure. Promotes cell proliferation and differentiation and stimulates hair growth.
蜡菊提取物:Helichrysum Extract:
又名永久花,原产欧洲、西亚、北美,在我国新疆、山东也有种植,是一种菊科草本药用植物。其提取物中有效成分为蜡菊黄酮,总黄酮含量很高。该物质在5α-R还原酶体外试验中对5α-R还原酶的活性有很强的抑制性。进而抑制5α-R还原反应,使睾酮(T)不可被还原为二氢睾酮(DHT),降低雄激素对毛囊的抑制和毒害。Also known as permanent flower, it is native to Europe, West Asia and North America, and is also cultivated in Xinjiang and Shandong in my country. It is a medicinal herb of the Compositae family. The active ingredient in its extract is helichrysum flavonoids, and the total flavonoid content is very high. The substance has a strong inhibitory effect on the activity of 5α-R reductase in the 5α-R reductase in vitro test. In addition, the reduction reaction of 5α-R is inhibited, so that testosterone (T) cannot be reduced to dihydrotestosterone (DHT), and the inhibition and toxicity of androgens to hair follicles are reduced.
侧柏叶提取物:Arborvitae Leaf Extract:
是柏科常绿乔木,为中国特产药用植物。其提取物中有效成分为侧柏黄酮、槲皮素。该物质在5α-R还原酶体外试验中对5α-R还原酶的活性有较强的抑制性。进而抑制5α-R还原反应,使睾酮(T)不可被还原为二氢睾酮(DHT),降低雄激素对毛囊的抑制和毒害。It is an evergreen tree of Cypressaceae, which is a special medicinal plant in China. The active ingredients in its extract are thuja flavonoids and quercetin. The substance has a strong inhibitory effect on the activity of 5α-R reductase in the 5α-R reductase in vitro test. In addition, the reduction reaction of 5α-R is inhibited, so that testosterone (T) cannot be reduced to dihydrotestosterone (DHT), and the inhibition and toxicity of androgens to hair follicles are reduced.
苦参提取物:Sophora Radix Extract:
其提取物中有效成分为苦参黄酮。其作用为改善毛细血管微循环,有雌激素样作用(雄激素拮抗),亦有一定5α-R还原酶抑制性。The active ingredient in its extract is Sophora flavanone. Its role is to improve capillary microcirculation, has estrogen-like effects (androgen antagonism), and also has certain 5α-R reductase inhibitory properties.
黄芪提取物:Astragalus Extract:
其提取物中有效成分为黄芪黄酮、毛蕊异黄酮、黄芪苷。改善毛细血管微循环,有雌激素样作用(雄激素拮抗),亦有一定5α-R还原酶抑制性。The active ingredients in the extract are astragalus flavonoids, verbasco isoflavones and astragaloside. Improve capillary microcirculation, have estrogen-like effects (androgen antagonism), and also have certain 5α-R reductase inhibition.
女贞子提取物:Ligustrum lucidum extract:
其提取物中有效成分为女贞子黄酮、齐墩果酸。改善毛细血管微循环,有雌激素样作用(雄激素拮抗),亦有一定5α-R还原酶抑制性。The active ingredients in its extract are lucidum flavonoids and oleanolic acid. Improve capillary microcirculation, have estrogen-like effects (androgen antagonism), and also have certain 5α-R reductase inhibition.
泛醇:Panthenol:
也称为维生素原B5,渗透保湿剂,滋润角质层,打开皮肤通道,帮助吸收其他活性成分。刺激表皮细胞生长,抑制炎症,保护粘膜。提供毛发生长营养。Also known as provitamin B5, penetrating moisturizer, moisturizing the stratum corneum, opening skin channels and helping absorb other active ingredients. Stimulates epidermal cell growth, inhibits inflammation, and protects mucous membranes. Provides nourishment for hair growth.
进一步的,所述富勒烯衍生物包括如下步骤制成:Further, described fullerene derivative comprises the following steps to prepare:
步骤S1、将碳60加入三口烧瓶中,缓慢滴加液溴,室温下磁力搅拌72-96h,反应结束后减压抽滤,将抽出来的溴蒸汽用无水亚硫酸钠溶液吸收,将滤饼在室温下静置24h后在60℃下真空干燥10h,制得修饰富勒烯,控制碳60和液溴的用量比为400-500mg∶100mL;Step S1, adding carbon 60 to the three-necked flask, slowly adding liquid bromine, magnetic stirring at room temperature for 72-96h, vacuum filtration after the reaction, the extracted bromine vapor is absorbed with anhydrous sodium sulfite solution, and the filter cake is After standing at room temperature for 24h, vacuum drying at 60°C for 10h to obtain modified fullerene, and the dosage ratio of carbon 60 and liquid bromine is controlled to be 400-500mg:100mL;
步骤S2、将修饰富勒烯加入无水乙醇中,磁力搅拌30min,滴加质量分数 13%氢氧化钠水溶液,室温下匀速搅拌并反应6h,反应结束后滴加浓盐酸调节 pH,直至pH=5-5.6,离心,收集上清液,将上清液在45℃下旋蒸,用丙酮萃取旋蒸产物,重复三次后制得粗产品,提纯,制得富勒烯衍生物,控制修饰富勒烯、无水乙醇和氢氧化钠水溶液200-250mg∶25-30mL∶40mL。Step S2, adding the modified fullerene into anhydrous ethanol, stirring magnetically for 30 minutes, adding 13% aqueous sodium hydroxide solution dropwise, stirring at a constant speed at room temperature and reacting for 6 hours, after the reaction, add concentrated hydrochloric acid dropwise to adjust pH, until pH= 5-5.6, centrifuge, collect the supernatant, spin the supernatant at 45°C, extract the spin-evaporated product with acetone, repeat three times to obtain a crude product, purify, obtain a fullerene derivative, and control the modification to enrich Lenene, absolute ethanol and aqueous sodium hydroxide solution 200-250mg: 25-30mL: 40mL.
步骤S1中通过液溴对碳60进行修饰,制备出修饰富勒烯,其为溴代富勒烯,之后步骤S2中以溴代富勒烯、乙醇和氢氧化钠作为原料,制备富勒烯衍生物,其为带有羟基和乙氧基的两亲性富勒烯衍生物,一方面本身可以作为药物,两亲性使它能够顺利通过细胞膜的亲水和亲油区域,与生物体的相容性好;另一方面增大油溶性药物如侧柏叶提取物中的微量精油在生物体内的溶解度,有效提高药物的作用。In step S1, carbon 60 is modified by liquid bromine to prepare modified fullerene, which is bromofullerene, and then in step S2, bromofullerene, ethanol and sodium hydroxide are used as raw materials to prepare fullerene Derivatives, which are amphiphilic fullerene derivatives with hydroxyl and ethoxy groups, can be used as a drug on the one hand, and the amphiphilicity enables it to smoothly pass through the hydrophilic and lipophilic regions of the cell membrane and interact with the organism. On the other hand, it increases the solubility of trace essential oils in oil-soluble drugs such as oriental orientalis leaf extract in vivo, and effectively improves the effect of drugs.
进一步的,所述蜡菊提取液、侧柏叶提取液、雌激素类中药提取液和矢车菊提取物包括如下步骤制成:Further, the helichrysum extract, the oriental orientalis leaf extract, the estrogenic Chinese medicine extract and the cornflower extract are prepared by the following steps:
将蜡菊、侧柏叶、雌激素类中草药和矢车菊分别置于烘箱中,在40-45℃下干燥2h,之后将体积分数50%乙醇水溶液作为浸提溶剂,按照料液比1∶10的比例加入密封容器中,在60℃下浸泡2h,之后保温并在40Hz下超声2h,过滤,分别制得蜡菊提取液、侧柏叶提取液、雌激素类中药提取液和矢车菊提取物。Helichrysum, oriental orientalis leaves, estrogen-based Chinese herbal medicines and cornflower were placed in an oven, dried at 40-45 ° C for 2 hours, and then the volume fraction of 50% ethanol aqueous solution was used as the extraction solvent, according to the ratio of material to liquid 1: : The ratio of 10 was added into a sealed container, soaked at 60 ° C for 2 hours, then kept warm and ultrasonicated at 40 Hz for 2 hours, and filtered to obtain Helichrysum extract, Platycladus orientalis leaf extract, estrogenic Chinese medicine extract and cornflower respectively. Extract.
进一步地,所述雌激素类中草药为黄芪、苦参和女贞子中的任意一种或多种按任意比例混合而成。Further, the estrogenic Chinese herbal medicine is prepared by mixing any one or more of Astragalus, Sophora flavescens and Ligustrum lucidum in any proportion.
进一步的,所述醇水缓冲液为1,3-丙二醇和去离子水按照1∶50-60的重量比混合而成。Further, the alcohol-water buffer is prepared by mixing 1,3-propanediol and deionized water in a weight ratio of 1:50-60.
一种防止脂溢性脱发促进生发的生发液的制备方法,包括如下步骤:A preparation method of a hair growth liquid for preventing seborrheic alopecia and promoting hair growth, comprising the steps of:
将乙酰基四肽-3、肉豆蔻酰五肽-17、生物素3肽-1、蜡菊提取液、侧柏叶提取液、雌激素类中药提取液、泛醇、苯氧乙醇、矢车菊提取物和富勒烯衍生物混合后涡旋震荡15-30min,之后加入醇水缓冲液,制得防止脂溢性脱发促进生发的生发液。Acetyl tetrapeptide-3, myristoyl pentapeptide-17, biotin 3-peptide-1, Helichrysum extract, Platycladus orientalis leaf extract, estrogenic Chinese medicine extract, panthenol, phenoxyethanol, arrowroot The chrysanthemum extract and the fullerene derivative are mixed and shaken by vortex for 15-30 minutes, and then an alcohol-water buffer is added to prepare a hair growth solution for preventing seborrheic alopecia and promoting hair growth.
本发明的有益效果:Beneficial effects of the present invention:
本发明制备出的防止脂溢性脱发促进生发的生发液能够促进毛囊细胞增殖分化,减少二氢睾酮(DHT)对毛囊健康的侵害,提供充足促角蛋白表达和合成的营养素。添加物乙酰基四肽-3、生物素三肽-1促进毛囊细胞增殖分化;蜡菊提取物、侧柏叶提取物抑制5α-R还原反应,减少二氢睾酮(DHT)对毛囊健康的侵害,消除对毛囊生长的抑制;肉豆蔻酰五肽-17提供充足促角蛋白表达和合成的营养素,促进毛发形成和长长。The hair growth liquid for preventing seborrheic alopecia and promoting hair growth prepared by the invention can promote the proliferation and differentiation of hair follicle cells, reduce the damage of dihydrotestosterone (DHT) to the health of hair follicles, and provide sufficient nutrients for promoting keratin expression and synthesis. Additives acetyl tetrapeptide-3 and biotin tripeptide-1 promote the proliferation and differentiation of hair follicle cells; Helichrysum extract and Arborvitae leaf extract inhibit 5α-R reduction reaction and reduce the damage of dihydrotestosterone (DHT) to hair follicle health , to eliminate the inhibition of hair follicle growth; myristoyl pentapeptide-17 provides sufficient nutrients to promote keratin expression and synthesis, and promote hair formation and growth.
蜡菊提取物、侧柏叶提取物能高效抑制5α-R还原反应,减少二氢睾酮(DHT) 对毛囊健康的侵害,消除对毛囊生长的抑制。没有雄胺类药物对身体的不良作用。Helichrysum extract and Arborvitae leaf extract can effectively inhibit the 5α-R reduction reaction, reduce the damage of dihydrotestosterone (DHT) to the health of hair follicles, and eliminate the inhibition of hair follicle growth. There are no adverse effects of androgens on the body.
本发明配方中加入了多肽,具有以下功效:Polypeptides are added in the formula of the present invention, which has the following effects:
a.强的活性:活性高,低用量就能发挥功效。a. Strong activity: high activity, low dosage can be effective.
b.作用平缓确切:区别于激素类和注射产品,多肽的重要特点是作用缓和但确切。b. The effect is gentle and precise: Different from hormones and injection products, the important feature of peptides is that the effect is moderate but precise.
c.高的安全性:由于多肽与机体物质的同源性,保证了其作用于皮肤有高的相容性,避免了注射带来的安全隐患。c. High safety: Due to the homology of peptides and body substances, it is guaranteed that it has high compatibility on the skin and avoids the potential safety hazards caused by injection.
d.高的吸收性:相对于胶原蛋白,多肽分子量更小,更能渗入皮肤发挥作用。d. High absorbability: Compared with collagen, the molecular weight of polypeptide is smaller, and it can penetrate into the skin to play a role.
e.质量可控性:每一种应用的活性多肽都为单一的物质,相比植物提取物,其质量更易于控制,纯度都可达到98%以上。e. Quality controllability: Each active polypeptide used is a single substance. Compared with plant extracts, its quality is easier to control, and the purity can reach more than 98%.
而且本发明的溶剂为醇水缓冲液,其溶剂与各组分有好的相容性,不油腻,也可以与米诺地尔町擦剂搭配使用,本发明制备出的生发液在使用时涂抹于发根头皮处,每次用量2-5mL,每日1-2次,按摩吸收。Moreover, the solvent of the present invention is an alcohol-water buffer, and the solvent has good compatibility with each component, is not greasy, and can also be used in combination with minoxidil liniment. The hair growth liquid prepared by the present invention is used when Apply to the hair root and scalp, 2-5mL each time, 1-2 times a day, massage to absorb.
具体实施方式Detailed ways
下面将对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅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它实施例,都属于本发明保护的范围。The technical solutions in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.
实施例1Example 1
所述富勒烯衍生物包括如下步骤制成:Described fullerene derivative comprises the following steps to prepare:
步骤S1、将碳60加入三口烧瓶中,缓慢滴加液溴,室温下磁力搅拌72h,反应结束后减压抽滤,将抽出来的溴蒸汽用无水亚硫酸钠溶液吸收,将滤饼在室温下静置24h后在60℃下真空干燥10h,制得修饰富勒烯,控制碳60和液溴的用量比为400mg∶100mL;Step S1, add carbon 60 into the three-necked flask, slowly drop liquid bromine, stir magnetically for 72h at room temperature, filter under reduced pressure after the reaction, absorb the extracted bromine vapor with anhydrous sodium sulfite solution, and filter the cake at room temperature After standing for 24h, vacuum drying at 60°C for 10h to prepare modified fullerene, and the dosage ratio of carbon 60 and liquid bromine is controlled to be 400mg:100mL;
步骤S2、将修饰富勒烯加入无水乙醇中,磁力搅拌30min,滴加质量分数 13%氢氧化钠水溶液,室温下匀速搅拌并反应6h,反应结束后滴加浓盐酸调节 pH,直至pH=5,离心,收集上清液,将上清液在45℃下旋蒸,用丙酮萃取旋蒸产物,重复三次后制得粗产品,提纯,制得富勒烯衍生物,控制修饰富勒烯、无水乙醇和氢氧化钠水溶液200mg∶25mL∶40mL。Step S2, adding the modified fullerene into anhydrous ethanol, stirring magnetically for 30 minutes, adding 13% aqueous sodium hydroxide solution dropwise, stirring at a constant speed at room temperature and reacting for 6 hours, after the reaction, add concentrated hydrochloric acid dropwise to adjust pH, until pH= 5. Centrifuge, collect the supernatant, spin the supernatant at 45°C, extract the spin-evaporated product with acetone, repeat three times to obtain the crude product, purify, obtain the fullerene derivative, and control the modification of the fullerene , anhydrous ethanol and sodium hydroxide aqueous solution 200mg: 25mL: 40mL.
实施例2Example 2
所述富勒烯衍生物包括如下步骤制成:Described fullerene derivative comprises the following steps to prepare:
步骤S1、将碳60加入三口烧瓶中,缓慢滴加液溴,室温下磁力搅拌80h,反应结束后减压抽滤,将抽出来的溴蒸汽用无水亚硫酸钠溶液吸收,将滤饼在室温下静置24h后在60℃下真空干燥10h,制得修饰富勒烯,控制碳60和液溴的用量比为450mg∶100mL;Step S1, add carbon 60 into the three-necked flask, slowly add liquid bromine, magnetic stirring at room temperature for 80h, after the reaction is completed, filter under reduced pressure, absorb the extracted bromine vapor with anhydrous sodium sulfite solution, and filter the cake at room temperature After standing for 24h, vacuum-drying at 60°C for 10h to obtain modified fullerene, and the dosage ratio of carbon 60 and liquid bromine was controlled to be 450mg:100mL;
步骤S2、将修饰富勒烯加入无水乙醇中,磁力搅拌30min,滴加质量分数 13%氢氧化钠水溶液,室温下匀速搅拌并反应6h,反应结束后滴加浓盐酸调节 pH,直至pH=5.2,离心,收集上清液,将上清液在45℃下旋蒸,用丙酮萃取旋蒸产物,重复三次后制得粗产品,提纯,制得富勒烯衍生物,控制修饰富勒烯、无水乙醇和氢氧化钠水溶液220mg∶28mL∶40mL。Step S2, adding the modified fullerene into anhydrous ethanol, stirring magnetically for 30 minutes, adding 13% aqueous sodium hydroxide solution dropwise, stirring at a constant speed at room temperature and reacting for 6 hours, after the reaction, add concentrated hydrochloric acid dropwise to adjust pH, until pH= 5.2, centrifuge, collect the supernatant, spin the supernatant at 45°C, extract the product of the spin-evaporation with acetone, repeat three times to obtain the crude product, purify, obtain the fullerene derivative, and control the modification of the fullerene , anhydrous ethanol and sodium hydroxide aqueous solution 220mg: 28mL: 40mL.
实施例3Example 3
所述富勒烯衍生物包括如下步骤制成:Described fullerene derivative comprises the following steps to prepare:
步骤S1、将碳60加入三口烧瓶中,缓慢滴加液溴,室温下磁力搅拌96h,反应结束后减压抽滤,将抽出来的溴蒸汽用无水亚硫酸钠溶液吸收,将滤饼在室温下静置24h后在60℃下真空干燥10h,制得修饰富勒烯,控制碳60和液溴的用量比为500mg∶100mL;Step S1, add carbon 60 into the three-necked flask, slowly add liquid bromine dropwise, magnetically stir at room temperature for 96h, filter under reduced pressure after the reaction, absorb the extracted bromine vapor with anhydrous sodium sulfite solution, and filter the cake at room temperature After standing for 24h, vacuum-drying at 60°C for 10h to prepare modified fullerene, and the dosage ratio of carbon 60 and liquid bromine was controlled to be 500mg:100mL;
步骤S2、将修饰富勒烯加入无水乙醇中,磁力搅拌30min,滴加质量分数 13%氢氧化钠水溶液,室温下匀速搅拌并反应6h,反应结束后滴加浓盐酸调节 pH,直至pH=5.6,离心,收集上清液,将上清液在45℃下旋蒸,用丙酮萃取旋蒸产物,重复三次后制得粗产品,提纯,制得富勒烯衍生物,控制修饰富勒烯、无水乙醇和氢氧化钠水溶液250mg∶30mL∶40mL。Step S2, adding the modified fullerene into anhydrous ethanol, stirring magnetically for 30 minutes, adding 13% aqueous sodium hydroxide solution dropwise, stirring at a constant speed at room temperature and reacting for 6 hours, after the reaction, add concentrated hydrochloric acid dropwise to adjust pH, until pH= 5.6, centrifuge, collect the supernatant, spin the supernatant at 45°C, extract the spin-evaporated product with acetone, repeat three times to obtain the crude product, purify, obtain the fullerene derivative, and control the modification of the fullerene , anhydrous ethanol and sodium hydroxide aqueous solution 250mg:30mL:40mL.
实施例4Example 4
一种防止脂溢性脱发促进生发的生发液,包括如下重量百分比原料:0.005%的乙酰基四肽-3,0.01%的肉豆蔻酰五肽-17,0.005%的生物素3肽-1,1%的蜡菊提取液,1%的侧柏叶提取液,0.2%的黄芪提取液,0.2%的泛醇,0.2%的苯氧乙醇,0.5%的矢车菊提取物,0.01%的富勒烯衍生物,余量为醇水缓冲液。A hair growth liquid for preventing seborrheic alopecia and promoting hair growth, comprising the following raw materials by weight percentage: 0.005% of acetyl tetrapeptide-3, 0.01% of myristoyl pentapeptide-17, 0.005% of biotin 3-peptide-1, 1% Helichrysum extract, 1% Arborvitae leaf extract, 0.2% Astragalus extract, 0.2% panthenol, 0.2% phenoxyethanol, 0.5% cornflower extract, 0.01% rich lerene derivatives, and the balance is alcohol-water buffer.
该生发液包括如下步骤制成:The hair growth liquid is made by the following steps:
将乙酰基四肽-3、肉豆蔻酰五肽-17、生物素3肽-1、蜡菊提取液、侧柏叶提取液、黄芪提取液、泛醇、苯氧乙醇、矢车菊提取物和富勒烯衍生物混合后涡旋震荡15min,之后加入醇水缓冲液,制得防止脂溢性脱发促进生发的生发液。Acetyl Tetrapeptide-3, Myristoyl Pentapeptide-17, Biotin 3 Peptide-1, Helichrysum Extract, Arborvitae Leaf Extract, Astragalus Extract, Panthenol, Phenoxyethanol, Cornflower Extract After mixing with the fullerene derivative, the solution was vortexed for 15 minutes, and then an alcohol-water buffer was added to prepare a hair growth solution for preventing seborrheic alopecia and promoting hair growth.
实施例5Example 5
一种防止脂溢性脱发促进生发的生发液,包括如下重量百分比原料:0.01%的乙酰基四肽-3,0.05%的肉豆蔻酰五肽-17,0.015%的生物素3肽-1,3%的蜡菊提取液,3%的侧柏叶提取液,1%的女贞子提取液,1%的泛醇,0.3%的苯氧乙醇,1.5%的矢车菊提取物,0.01%的富勒烯衍生物,余量为醇水缓冲液。A hair growth liquid for preventing seborrheic alopecia and promoting hair growth, comprising the following raw materials by weight percentage: 0.01% of acetyl tetrapeptide-3, 0.05% of myristoyl pentapeptide-17, 0.015% of biotin 3-peptide-1, 3% Helichrysum extract, 3% Arborvitae leaf extract, 1% Ligustrum lucidum extract, 1% Panthenol, 0.3% Phenoxyethanol, 1.5% Cornflower extract, 0.01% fullerene derivatives, and the balance is alcohol-water buffer.
该生发液包括如下步骤制成:The hair growth liquid is made by the following steps:
将乙酰基四肽-3、肉豆蔻酰五肽-17、生物素3肽-1、蜡菊提取液、侧柏叶提取液、女贞子提取液、泛醇、苯氧乙醇、矢车菊提取物和富勒烯衍生物混合后涡旋震荡20min,之后加入醇水缓冲液,制得防止脂溢性脱发促进生发的生发液。Acetyl tetrapeptide-3, myristoyl pentapeptide-17, biotin 3-peptide-1, Helichrysum extract, Arborvitae leaf extract, Ligustrum lucidum extract, Panthenol, Phenoxyethanol, Cornflower The extract and the fullerene derivative were mixed and vortexed for 20 minutes, and then an alcohol-water buffer was added to prepare a hair growth solution for preventing seborrheic alopecia and promoting hair growth.
实施例6Example 6
一种防止脂溢性脱发促进生发的生发液,包括如下重量百分比原料:0.03%的乙酰基四肽-3,0.1%的肉豆蔻酰五肽-17,0.025%的生物素3肽-1,6%的蜡菊提取液,6%的侧柏叶提取液,2%的苦参提取液,2%的泛醇,0.5%的苯氧乙醇, 3%的矢车菊提取物,0.02%的富勒烯衍生物,余量为醇水缓冲液。A hair growth liquid for preventing seborrheic alopecia and promoting hair growth, comprising the following raw materials by weight percentage: 0.03% acetyl tetrapeptide-3, 0.1% myristoyl pentapeptide-17, 0.025% biotin 3 peptide-1, 6% Helichrysum extract, 6% Arborvitae leaf extract, 2% Sophora flavescens extract, 2% Panthenol, 0.5% Phenoxyethanol, 3% Cornflower extract, 0.02% Fullerene derivatives, the balance is alcohol-water buffer.
该生发液包括如下步骤制成:The hair growth liquid is made by the following steps:
将乙酰基四肽-3、肉豆蔻酰五肽-17、生物素3肽-1、蜡菊提取液、侧柏叶提取液、苦参提取液、泛醇、苯氧乙醇、矢车菊提取物和富勒烯衍生物混合后涡旋震荡30min,之后加入醇水缓冲液,制得防止脂溢性脱发促进生发的生发液。Extract Acetyl Tetrapeptide-3, Myristoyl Pentapeptide-17, Biotin 3 Peptide-1, Helichrysum Extract, Arborvitae Extract, Sophora Radix Extract, Panthenol, Phenoxyethanol, Cornflower Extract After mixing with the fullerene derivative and vortexing for 30 min, the alcohol-water buffer was added to prepare a hair growth solution for preventing seborrheic alopecia and promoting hair growth.
对比例1Comparative Example 1
本对比例与实施例4相比,未加入富勒烯衍生物。Compared with Example 4, no fullerene derivative was added in this comparative example.
对比例2Comparative Example 2
本对比例与实施例4相比,将配方调整成:1%的蜡菊提取液,1%的侧柏叶提取液,0.2%的黄芪提取液,0.2%的泛醇,0.2%的苯氧乙醇,0.5%的矢车菊提取物,0.01%的富勒烯衍生物,余量为醇水缓冲液。Compared with Example 4, the formula of this comparative example is adjusted to: 1% Helichrysum extract, 1% Platycladus orientalis leaf extract, 0.2% Astragalus extract, 0.2% Panthenol, 0.2% Phenoxy Ethanol, 0.5% cornflower extract, 0.01% fullerene derivatives, and the balance is alcohol-water buffer.
对比例3Comparative Example 3
本对比例为市售外用米诺地尔生发液。This comparative example is a commercially available topical minoxidil hair growth solution.
对比例4Comparative Example 4
本对比例为非那雄胺片,5mgx 10片/盒,实验前用体积分数75%乙醇配制成2%的溶液。This comparative example is finasteride tablets, 5mg x 10 tablets/box, which is prepared into a 2% solution with a volume fraction of 75% ethanol before the experiment.
对比例5Comparative Example 5
本对比例与实施例4相比,配方中未加入蜡菊提取液。Compared with Example 4, this comparative example does not add immortelle extract in the formula.
对比例6Comparative Example 6
本对比例与实施例4相比,配方中未加入侧柏叶提取液。Compared with Example 4, this comparative example does not add oriental orientalis leaf extract in the formula.
对比例7Comparative Example 7
本对比例与实施例4相比,配方中未加入黄芪提取液。Compared with Example 4, this comparative example does not add astragalus extract in the formula.
将实施例4-6和对比例1-3制备出的生发液通过C57BL/6小鼠的动物实验来评价生发的功效,结果如下表1所示;The hair growth solutions prepared in Examples 4-6 and Comparative Examples 1-3 were used to evaluate the efficacy of hair growth through animal experiments on C57BL/6 mice, and the results are shown in Table 1 below;
实验过程:使用C57BL/6小鼠110只,雌雄各半,6周龄,按小鼠体重编号,后采取随机排列法随机分为实施例1组、实施例2组、实施例3组、实施例4 组、实施例5组、实施例6组、对比实施例1组、对比实施例2组、对比实施例3组、对比实施例4组、米诺地尔组,每组10只。经乙醚麻醉后用松香/石蜡混合物(1∶1)热溶化后,涂于小鼠背部,待凝固变硬后揭去,以小鼠背部光滑、无伤无毛根为净。脱毛后第二天起分别于脱毛区涂抹对应的生发液,每日两次,每次2mL/只,连续涂抹30天。期间观察小鼠背部新长出毛发的和非涂抹样品的部位新长出毛发的情况,每次用图像分析仪涂抹样品部位新长出毛发的和非涂抹样品的部位新长出毛发的情况,将前后两者的比值进行对比,分别计算每只小鼠的情况并统计平均值。Experimental process: 110 C57BL/6 mice, half male and half, 6 weeks old, numbered according to the weight of the mice, and then randomly divided into Example 1 group, Example 2 group, Example 3 group, implementation Example 4 group, Example 5 group, Example 6 group, Comparative Example 1 group, Comparative Example 2 group, Comparative Example 3 group, Comparative Example 4 group, Minoxidil group, 10 in each group. After being anesthetized with ether, it was melted with a rosin/paraffin mixture (1:1) and then applied to the back of the mouse. After it was solidified and hardened, it was removed. From the second day after depilation, apply the corresponding hair growth liquid to the depilation area, twice a day, 2mL each time, for 30 days. During the period, the newly grown hairs on the back of the mice and the parts where the samples were not smeared were observed. Every time the image analyzer was used for the newly grown hairs at the smeared sample sites and the newly grown hairs at the non-smeared sample sites. The ratios of the two before and after were compared, and the situation of each mouse was calculated separately and the average value was calculated.
表1Table 1
从上表1中能够看出实施例4-6制备出的生发液疗效显著,生发液中的各种活性成分在促进头发生长方面具有协同增效的能力。It can be seen from Table 1 above that the hair growth liquid prepared in Examples 4-6 has a remarkable curative effect, and various active ingredients in the hair growth liquid have synergistic ability in promoting hair growth.
临床试验Clinical Trials
根据动物实验的结果选择有潜力的生发液进行临床试验,对实施例4-6和对比例1-3制备出的生发液进行临床试验,临床测试本发明的生发液促进头发生长的效果,临床试验对象为125名年龄为20-55岁的并有斑秃、全秃或秃顶的人,其中男性63人,女性62人。将试验人员随机分为5组,每组25人,分别使用实施例4-6和米诺地尔生发液,使用方法为取生发液约2-5mL,每日1-2 次,涂抹于脱发部位,每天早晚各一次,按摩吸收,连续使用两个月。疗效评价标准为:1)显效:停止脱发,无发区域重新长出乌黑头发;2)有效:脱发明显改善,部分无发区域重新长出乌黑头发;3)微效:脱发改善,无发区域长出毳毛;4)无效:脱发没有改善或减轻,无发区域没有长出新头发。结果见下表2 所示:According to the results of animal experiments, a potential hair growth solution was selected for clinical trials, and the hair growth solutions prepared in Examples 4-6 and Comparative Examples 1-3 were clinically tested to clinically test the effect of the hair growth solution of the present invention on promoting hair growth. The subjects were 125 people aged 20-55 with alopecia areata, alopecia totalis or baldness, including 63 males and 62 females. The test personnel were randomly divided into 5 groups, 25 people in each group, respectively using Examples 4-6 and minoxidil hair growth liquid, the use method is to take about 2-5 mL of hair growth liquid, 1-2 times a day, apply to hair loss Partially, once a day in the morning and evening, massage and absorb, and use it continuously for two months. Efficacy evaluation criteria are: 1) Marked effect: stop hair loss, black hair grows back in the hairless area; 2) Effective: hair loss is significantly improved, and black hair grows back in some hairless areas; 3) Slight effect: hair loss is improved, hairless area Veil grows; 4) Ineffective: No improvement or reduction in hair loss, no new hair grows in the hairless area. The results are shown in Table 2 below:
表2Table 2
从上表2中能够看出本发明制备出的生发液用于临床时效果显著,具有较高的实用性。It can be seen from the above table 2 that the hair growth solution prepared by the present invention has remarkable effect when used in clinic and has high practicability.
对实施例5和对比例4-7制备出的生发液对C57BL6小鼠毛发生长状况进行检测,结果如下表3所示:The hair growth liquid prepared by Example 5 and Comparative Examples 4-7 was tested for the hair growth status of C57BL6 mice, and the results were shown in Table 3 below:
实验动物laboratory animal
7周龄C57BL6BL6小鼠,雄性,SPF级,15-20g,70只。温度22-25℃,正常光照,动物喂以标准的颗粒鼠料。7-week-old C57BL6BL6 mice, male, SPF grade, 15-20g, 70 mice. The temperature was 22-25°C, normal light, and the animals were fed with standard pelleted rat feed.
(1)实验分组(1) Experimental grouping
将70只小鼠于空调房中适应性喂养1周,自由饮水进食,自然光照,随后随机将小鼠分为正常组(涂抹体积分数75%乙醇)、模型组(涂抹100μL 0.05%的睾酮溶液)实施例5组、对比例4组、对比例5组、对比例6组,对比例7 组,共6组,每组10只。70 mice were adaptively fed for 1 week in an air-conditioned room, with free access to water and natural light, and then randomly divided into a normal group (smeared with 75% ethanol by volume) and a model group (smeared with 100 μL of 0.05% testosterone solution) ) Example 5 group, comparative example 4 group, comparative example 5 group, comparative example 6 group, comparative example 7 group, a total of 6 groups, 10 in each group.
(2)动物模型的建立(2) Establishment of animal models
实验前1天将小鼠用乙醚麻醉,以松香/石蜡混合物(1:1)加热溶化后涂于 C57BL6小鼠背部约2cmX2.5 cm区域,待凝固变硬后揭去,诱导小鼠毛发由休止期进入生长期。One day before the experiment, the mice were anesthetized with ether, heated and melted with a rosin/paraffin mixture (1:1), and then applied to an area of about 2 cm×2.5 cm on the back of C57BL6 mice. The resting period enters the growing period.
(3)药物处理(3) Drug treatment
脱毛第2天,除正常组外,其余各组小鼠背部脱毛部位涂抹100μL 0.05%的睾酮溶液(0.05g睾酮溶解于100mL 75%的乙醇溶液),每天1次,连续28天. 睾酮溶液处理30min后,用同样的方法将100μL生发液溶液涂抹于脱毛区,每天1次,连续28天。On the second day of depilation, except for the normal group, 100 μL of 0.05% testosterone solution (0.05g of testosterone dissolved in 100mL of 75% ethanol solution) was applied to the back of the mice in the other groups except the normal group, once a day for 28 consecutive days. Testosterone solution treatment After 30 minutes, apply 100 μL of hair tonic solution to the hair removal area in the same way, once a day for 28 consecutive days.
7周龄小鼠脱毛后皮肤呈现粉红色,毛发进入休止期,每天观察记录小鼠皮肤颜色由粉红色变黑时间及长毛时间。After depilation, the skin of 7-week-old mice turned pink, and the hair entered the telogen phase. The time when the skin color of the mice changed from pink to black and the time of long hair were observed and recorded every day.
表3table 3
表格将模型组调整排到正常组下方The table arranges the model group adjustments below the normal group
从上表中能够看出本发明实施例相对于正常组和非那雄胺对照组(对比例 4),小鼠皮肤变色时间更短,出毛时间也大大缩短,可有效控制睾酮对毛囊的不利影响。As can be seen from the above table, the embodiment of the present invention is compared with the normal group and the finasteride control group (Comparative Example 4), the mouse skin discoloration time is shorter, and the hair growth time is also greatly shortened, which can effectively control the effect of testosterone on hair follicles. Negative Effects.
以上内容仅仅是对本发明的构思所作的举例和说明,所属本技术领域的技术人员对所描述的具体实施例做各种各样的修改或补充或采用类似的方式替代,只要不偏离发明的构思或者超越本权利要求书所定义的范围,均应属于本发明的保护范围。The above content is only an example and description of the concept of the present invention. Those skilled in the art can make various modifications or supplements to the described specific embodiments or replace them in a similar manner, as long as they do not deviate from the concept of the invention. Or beyond the scope defined by the claims, all belong to the protection scope of the present invention.
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