WO2023061117A1 - 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途 - Google Patents

莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途 Download PDF

Info

Publication number
WO2023061117A1
WO2023061117A1 PCT/CN2022/117853 CN2022117853W WO2023061117A1 WO 2023061117 A1 WO2023061117 A1 WO 2023061117A1 CN 2022117853 W CN2022117853 W CN 2022117853W WO 2023061117 A1 WO2023061117 A1 WO 2023061117A1
Authority
WO
WIPO (PCT)
Prior art keywords
hair
pharmaceutical composition
alopecia
radishin
radishine
Prior art date
Application number
PCT/CN2022/117853
Other languages
English (en)
French (fr)
Inventor
袁其朋
刘朋涛
程立
Original Assignee
北京化工大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 北京化工大学 filed Critical 北京化工大学
Publication of WO2023061117A1 publication Critical patent/WO2023061117A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/145—Amines having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi

Definitions

  • the present invention relates to the use of radhamin in the preparation of a pharmaceutical composition for improving and treating white hair and/or alopecia, and the pharmaceutical composition contains radhamin as an active ingredient.
  • the invention also relates to a preparation method of the pharmaceutical composition.
  • White hair can be divided into two kinds of congenital and acquired, congenital white hair often has family history, acquired white hair includes senile white hair and juvenile white hair, senile white hair is relevant with old frailty, juvenile white hair White hair is related to nutritional disorders or mental factors, and some chronic disease factors may also cause white hair.
  • White hair can also be divided into physiological white hair and pathological white hair. Physiological white hair is aging white hair, and pathological white hair can be divided into nutritional and metabolic white hair, chemical white hair, hereditary white hair and so on.
  • the research in the non-patent document 1 thinks that the generation of white hair is caused by the weakening of melanin-forming function of melanocytes and the decrease of tyrosinase activity.
  • Deletion of the ⁇ -lymphocytoma-2 gene (bc1-2) induces apoptosis of melanocyte stem cells, weakens specialized enzymatic antioxidant defense systems, and exacerbates oxidative stress processes, such as reduction of catalase, which leads to peroxidation Hydrogen accumulates, causing globular melanocytes to fail and die.
  • Microphthalmia-associated transcription factor (MITF) has a transcriptional regulatory effect on the tyrosinase-related protein family and is involved in the production of melanin.
  • Alopecia is divided into normal physiological alopecia and pathological alopecia.
  • Normal hair loss can keep the hair entering the catagen phase and the hair newly entering the growth phase in a dynamic balance, so it can maintain a normal amount of hair, but pathological hair loss can cause abnormal or excessive hair loss.
  • the causes of pathological alopecia are more complicated, including for example androgenetic alopecia, neuropathic alopecia, endocrine alopecia, nutritional alopecia, and congenital alopecia.
  • Patent Document 1 records the hair loss caused by androgen metabolism disorder, which is mainly manifested in the enhanced activity of 5 ⁇ -reductase, which makes testosterone excessively converted into dihydrotestosterone. Degeneration becomes smaller, hair becomes thinner, softer, shorter, and falls off.
  • Patent Document 2 mentions that Chinese medicine believes that the following factors are related to gray hair: one is deficiency of essence and weak blood: deficiency of kidney essence cannot metabolize Yin and blood, and deficiency of Yin and blood causes the hair to lose its nourishment, so it turns gray.
  • the second is excessive blood heat: emotional agitation, resulting in water not containing wood, liver hyperactivity and blood dryness, excessive blood heat, and hair root loss of nourishment, so premature graying.
  • the third is liver stagnation and spleen dampness: stagnation of liver qi, damage to the heart and spleen, damage to the spleen, negligence of transportation and transformation, no source of qi and blood biochemistry, so gray hair.
  • Patent Document 3 discloses a capsule for treating baldness, which is composed of traditional Chinese medicine Ligustrum lucidum, lotus root, mulberry fruit, licorice, black sesame, gelatin, etc., and is processed through the technological process of capsule products.
  • Patent Document 4 discloses an UFA traditional Chinese medicine composition and its granules, which are composed of Ligustrum lucidum, Mozaolian, Polygonum multiflorum, Polygonatum and black beans, and are processed through the technological process of granule pharmaceutical products. None of these Chinese medicine therapies has found any components that have a significant effect of preventing or treating gray hair, and the side effects that multiple components bring cannot be ignored, which is also a general shortcoming of Chinese medicine therapies.
  • Patent Document 5 discloses a composition and method for controlling or slowing down hair discoloration.
  • the composition contains a catalase substance, an antioxidant and a cosmetic product carrier, and the pH value of the composition is controlled between 2 and 6. Graying (greying) of the hair can be controlled or slowed down by applying the substance containing the composition directly to the hair from the mid-shaft to the root.
  • this document has not done in-depth research on the effect of the composition on melanocytes and tyrosinase, and its effect on preventing black hair from turning white is not good, and may have potential side effects.
  • Non-Patent Document 2 discloses that radishine, as an isothiocyanate, can be extracted from natural products such as traditional Chinese medicine radish seeds and radish seeds.
  • the research on radishine is mainly focused on its anticancer function, which can efficiently induce phase II Detoxification enzymes can improve the body's ability to remove carcinogens, so it can effectively inhibit the growth and proliferation of cancer cells and kill cancer cells.
  • the research of non-patent literature 3 also shows that radishin has a good killing effect on cell lines such as lung cancer and liver cancer, and can also inhibit esophageal cancer and breast cancer cells.
  • Patent Document 1 CN108066221A
  • Patent Document 2 CN105660933A
  • Patent Document 3 CN104415101A
  • Patent Document 4 CN104606485A
  • Patent Document 5 US9265717B1
  • Non-Patent Document 1 Transcriptional regulation of tyrosinase-related proteins by MITF in normal human melanocytes, J Med Res, Mar 2013, Vol 42 No.3.58-62
  • Non-Patent Document 2 Yang, M., Ren, M., Qu, Y., Teng, W., Wang, Z., Li, H. and Yuan, Q., 2016. Sulforaphene inhibits hepatocellular carcinoma through repressing keratin 8 and activating anoikis.RSC Advances,6(74),pp.70326-70334
  • Non-Patent Document 3 Evaluation of antitumor activity and mechanism of action of a plant-derived natural compound radishin, Yue Qu, master's thesis of Beijing University of Chemical Technology, 2015, abstract
  • the present inventor discovered unexpectedly in the application research of radishin that radishin has hair growth and black hair effects.
  • the inventor has carried out in-depth research, and after preparing the composition containing radish into dosage forms such as granules, oral tablets and soft capsules and giving it to the experimenter, it is found that radish in an appropriate dose is more effective than the existing ones.
  • the technology can effectively improve and treat gray hair and/or hair loss in a shorter time.
  • the present inventors have not found the mechanism of action of radish in improving and treating gray hair and/or alopecia, and will conduct research on this aspect in the future. According to current analysis, it may be related to the antioxidant function of radish, which improves the immunity of subjects with white hair and alopecia, thereby preventing white hair or hair loss caused by excessive or abnormal reactions of the immune system.
  • radishin may also promote the expression of microphthalmia-associated transcription factor (MITF) and prevent the mutation of MITF, thereby preventing the abnormal coloring or differentiation of accelerated melanin differentiation cells caused by the mutation of MITF, thereby preventing Physiological aging of melanocytes.
  • MITF microphthalmia-associated transcription factor
  • radish may also prevent the conversion of testosterone into dihydrotestosterone (DHT) by inhibiting the activity of 5 ⁇ -reductase, thereby preventing DHT from binding to specific receptors to produce the protein that causes hair loss , to achieve the purpose of inhibiting hair loss.
  • DHT dihydrotestosterone
  • the present invention mainly relates to the following aspects:
  • radishin in the preparation of the pharmaceutical composition for improving and treating white hair and/or alopecia, it is characterized in that, described radishin is the active ingredient of described pharmaceutical composition, and based on described pharmaceutical composition
  • the total weight of the product, the content of the radishine is 0.1 to 50%.
  • the said radishin is a natural product extract, a biosynthesis product or a chemical synthesis product.
  • composition is orally administered at a dose of 5-500 mg/person/day of radishine.
  • the preparation method of the pharmaceutical composition for improving and treating white hair and/or alopecia comprising radishine it is characterized in that, described method comprises radishine as active ingredient and is contained in described pharmaceutical composition, based on The total weight of the pharmaceutical composition, the content of the radishine is 0.1-50%.
  • the pharmaceutical composition of the present invention containing radish as an active ingredient shows very significant and even amazing effects in improving and treating gray hair and/or hair loss, can significantly promote hair growth, repair and increase, and surprisingly quickly reduce hair loss amount to stop the progression of hair loss.
  • radish can promote gray hair and white hair to turn black from the root, harden the hair quality, effectively repair and improve the hair quality.
  • Rathamin has short action time, significant drug effect, and is suitable for a wide range of people.
  • the composition of the present invention is suitable for a wide range of subjects, has effects on most subjects, and is suitable for gray hair and/or hair loss caused by different reasons.
  • the prior art has not yet found a composition that can significantly improve and treat gray hair and/or alopecia in such a high proportion of the population within a short period of 1 to 3 months.
  • a and b in Figure 1 respectively show the comparison of hair photography of subjects suffering from alopecia and white hair after taking radish for 1 month and before taking it.
  • Figure 2 a and b respectively show the photographic comparison of hair of subjects with white hair after taking radish for 2 and a half months and before taking it.
  • the pharmaceutical composition of the present invention comprising radish as an active ingredient can improve and treat white hair and/or alopecia, and is suitable for congenital and acquired white hair, physiological and pathological white hair and Physiological and pathological hair loss.
  • the content of radishin contained in the pharmaceutical composition of the present invention is not limited, as long as the effect of improving and treating gray hair and/or hair loss can be achieved.
  • the pharmaceutical composition of the present invention may contain 0.1% to 50% by weight of radishin, and when the content of radishin is lower than 0.1% by weight, there is no obvious effect on improving and treating gray hair and/or alopecia due to too little radishin.
  • the radhamin content is higher than 50% by weight, the radhamin is too much and cannot be dissolved in the solvent well, so it is difficult to form a homogeneous phase.
  • the pharmaceutical composition of the present invention contains 0.5-10% by weight of radishin, within this range, radishine can significantly improve and treat gray hair and/or alopecia within a short period of time, such as 2-3 months. More preferably, the composition of the present invention comprises 1 to 5% by weight of radishin, and within this range, radishin can improve and treat gray hair and/or hair loss to a large extent in a short period of time, for example, for gray hair Or for subjects whose hair loss area accounts for more than 50% of the total head area, at least 86.8% and 89.5% of the subjects have obvious hair growth and black hair effects respectively within 3 months.
  • Ratinin of the present invention can be prepared by any method known in the art, such as natural product extraction, biosynthesis or chemical synthesis, etc., as long as the radishin extract has the effect of improving and treating gray hair and/or alopecia Can.
  • the present invention preferably uses the radish obtained by natural product extraction method, and described extract can be obtained from Brussels sprouts, cabbage, cauliflower, Chinese cabbage, kale, collard greens, broccoli sprouts, kale, broccoli, kohlrabi, mustard , turnips, radishes, arugula and watercress.
  • the preparation of radishine can adopt the following method:
  • organic solvent to extract the radhamin hydrolyzate that step (1) obtains
  • the addition of organic solvent is 0.5 ⁇ 5 times of the volume of radhamin hydrolyzate, extract 2 ⁇ 5 times, reclaim the radhamin in the hydrolyzate, collect organic
  • the solvent extraction layer was distilled under reduced pressure to obtain the crude extract of radhamone, and the organic solvent was recovered at the same time.
  • the organic solvent is an organic solvent commonly used in this field, for example, n-hexane, cyclohexane, diethyl ether, n-butanol, chloroform, dichloromethane or ethyl acetate and the like.
  • step (3) add the radhamin crude extract that step (2) obtains in the molecular distillation device and carry out primary molecular distillation, remove residual organic solvent, moisture and low-boiling point impurity components in the radhamin crude extract, collect from the primary
  • the molecular distillation device distills the heavy components flowing out of the wall to obtain the first-stage molecular distillation heavy components.
  • the primary molecular distillation conditions are: raw material holding temperature 30-60°C, vacuum degree 100-2000Pa, distillation temperature 50-100°C, feed flow rate 2-20mL/min, condensation surface temperature 0-30°C, film wiper speed 200 ⁇ 400rpm.
  • step (3) Add the primary molecular distillation heavy component obtained in step (3) into the molecular distillation device for secondary molecular distillation, remove the high-boiling impurity components in the primary molecular distillation heavy component, collect and condense from the secondary molecular distillation device
  • the light components that flow out from the surface can be used to obtain radishin products.
  • Secondary molecular distillation conditions are: raw material holding temperature 30-70°C, vacuum degree 0.1-10Pa, distillation temperature 80-200°C, feed flow rate 1-10mL/min, condensation surface temperature 0-20°C, film wiper speed 200 ⁇ 450rpm.
  • composition of the present invention can be made into an appropriate dosage form according to the shape of the product.
  • the composition of the present invention may have a composition selected from tablets, capsules, powders, powders, granules, ointments, patches, emulsions, liniments, pastes, injections, sprays, creams, lotions, Formulations in the group consisting of oils, suspensions, gels or tonics, but the present invention is not limited thereto.
  • the pharmaceutical composition of the present invention can be daily-use chemicals such as health care products, food or hair care products, as long as the effect of improving and treating gray hair and/or hair loss can be achieved, the use form of the pharmaceutical composition of the present invention is not limited to this.
  • the pharmaceutical composition of the present invention can also include other additives, such as lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc., as long as it does not affect the effect of the present invention. , any additives may be added.
  • the pharmaceutical composition of the present invention can be administered through modes such as oral administration, injection administration, skin administration or mucosal administration, as long as the effect of improving and treating gray hair and/or alopecia can be realized, the pharmaceutical composition of the present invention
  • the administration form is not limited thereto.
  • the dosage, frequency and time of administration of the pharmaceutical composition of the present invention may vary according to the gray hair or alopecia symptoms of the subject, the age of the subject, and the dosage form of the subject.
  • the radish in the pharmaceutical composition of the present invention is preferably orally administered at a dosage of 5-500 mg/person/day, more preferably at a dosage of 10-100 mg/person/day, most preferably at a dosage of 20-40 mg/day.
  • step (2) Utilize the same volume of ethyl acetate to extract the radhamin hydrolyzate obtained in step (1) for 3 times, reclaim the radhamin in the hydrolyzate, collect the ethyl acetate extraction layer, and store at 40°C and a vacuum of -0.08MPa Distill under reduced pressure to obtain 200L of crude extract of radhamone, and recover ethyl acetate simultaneously;
  • step (3) join the radhamin crude extract that step (2) obtains in the molecular distillation device and carry out first-order molecular distillation, remove residual ethyl acetate, moisture and low-boiling point impurity components in the radhamin crude extract, collect from
  • the primary molecular distillation device distills the heavy components flowing out of the wall to obtain 2000 g of the primary molecular distillation heavy components;
  • the primary molecular distillation conditions are: raw material holding temperature 60 ° C, vacuum degree 2000 Pa, distillation temperature 100 ° C, feed flow rate 2 mL/min,
  • the temperature of the condensation surface is 0°C, and the speed of the wiper is 400rpm;
  • the primary molecular distillation heavy component that step (3) obtains is joined in the molecular distillation device and carries out secondary molecular distillation, removes the high-boiling point impurity component in the primary molecular distillation heavy component, collects from secondary molecular distillation device Condensate the light components flowing out from the surface to obtain 1000g of high-purity 99.5% radhamin product; the secondary molecular distillation conditions are: raw material holding temperature 70°C, vacuum degree 0.1Pa, distillation temperature 110°C, feed flow rate 1mL/min, The temperature of the condensing surface is 0°C, and the speed of the wiper is 450 rpm.
  • the radish extract prepared by the above method is used as a raw material, mixed with other additives to prepare the pharmaceutical composition of the present invention in the form of granules, tablets and capsules.
  • Figures 1-2 are hair photographs, which show the improvement and therapeutic effect of gray hair and/or hair loss after taking radishin.
  • improvement start time means the time when gray hair turns black and/or hair loss reduction effect begins to appear, and women mainly show whether hair loss occurs when combing hair; "whether other drugs are used” means Refers to whether the subject has ever taken other drugs to improve or treat white hair and/or alopecia.
  • use time is set according to the degree of gray hair and/or hair loss of the subject, and the proportion of white hair and/or hair loss accounts for 1-10% of the whole head, and the use time is set as continuous Take radish for 1 month; subjects with white hair and/or hair loss accounting for 10-50% of the whole head, use it for 2 months; subjects with white hair and/or hair loss accounting for more than 50% of the whole head For the testers, the use time was set to 3 months.
  • "Obviously” in Table 2 means that hair growth and black hair increase significantly, and the area of hair growth or black hair is greater than 25% of the total hair area. 1% to 25% of the area, "ineffective" means no obvious effect, and the hair growth or black hair area is less than 1% of the total hair area.
  • Table 1a The improvement and therapeutic effect of men taking radish on gray hair and/or alopecia
  • Table 1b The improvement and therapeutic effect of women taking radish on gray hair and/or alopecia
  • Table 1a and Table 1b show that for subjects of different ages and sexes who suffer from different degrees of white hair and/or alopecia, after oral administration at a dose of 10-60 mg/person/day, the dosage will be reduced within 5 days to 5 days. There were different degrees of improvement during the 3-month period. As shown in No. 1 in Table 1b, the subject suffered from gray hair and alopecia at the same time, and the improvement effect appeared in a short time after taking radishone, that is, after taking radishine granules orally at a dose of 30 mg/day, After 5 days, hair loss began to decrease, and after one month, there was no hair loss and most of the white hairs turned black.
  • a and b in Figure 1 also show that the subject with serial number 2 in Table 1b who suffers from alopecia and white hair at the same time has a significant improvement in hair loss after taking radish for 1 month, and some white hair turns gray, 2 After a month, the white hair basically turns black. In this hair photograph, it was confirmed that the white hair turned black, and the blackened hair was hard and shiny, showing the black hair and hair nourishing effects of radishin.
  • Table 2 According to the severity of white hair and alopecia, the drug was administered for 1 month, 2 months, and 3 months respectively, and the improvement and treatment degree in a specific period of time were studied. It was found that the proportion of white hair or hair loss accounted for 1 After ⁇ 10% of the subjects took radish for 1 month continuously, at least 94.0% of the subjects had obvious hair growth effect, and at least 92.6% of the subjects had obvious black hair effect, which indicated that it is suitable for those with mild gray hair and alopecia Subjects, the therapeutic effect of radish is very significant.
  • compositions containing radishin of different dosage forms such as electuary, oral preparation and soft capsule can all play the effect of improving and treating gray hair and/or alopecia to experimenter, and experiment does not find that dosage form improves and treats There is a marked difference in effect.
  • the pharmaceutical composition of the present invention containing radish as an active ingredient has a very significant effect in improving and treating gray hair and/or alopecia, and has the characteristics of short drug action time, significant drug effect, and wide adaptability to people.
  • the improvement effect of gray hair and/or hair loss began to appear in 5 to 15 days, and most of the gray hair turned black after 2 to 3 months, and the effect of inhibiting hair loss was remarkable, and some even suffered from it.
  • Subject has new hair growing. Therefore, the present invention provides a new medicine and method for the improvement and treatment of gray hair and/or hair loss.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

本发明提供了莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途及该药物组合物的制备方法。所述药物组合物包含莱菔素作为有效成分，基于所述药物组合物的总重量，所述莱菔素的重量百分比含量为0.1～50％。

Description

莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途 技术领域
本发明涉及莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途，该药物组合物包含莱菔素作为有效成分。本发明还涉及该药物组合物的制备方法。
背景技术
白发症可分为先天性和后天性两种，先天性白发往往具有家族史，后天性白发包括衰老性白发和少年性白发，衰老性白发与年迈体弱有关，少年性白发与营养障碍或者精神因素有关，有些慢性疾病因素也可能导致白发。白发症还可分为生理性白发和病理性白发。生理性白发即衰老性白发，病理性白发可分为营养代谢性白发、化学性白发、遗传性白发等。
非专利文献1中的研究认为白发的产生是由黑素细胞形成黑色素的功能减弱、酪氨酸酶活降低所致。β淋巴细胞瘤-2基因(bc1-2)的缺失会引起黑素干细胞的凋亡，使专门的酶抗氧化防御系统减弱，加剧氧化应激过程，如过氧化氢酶减少，从而导致过氧化氢聚集，使球黑素细胞功能失效和死亡。小眼畸形相关转录因子(MITF)对酪氨酸酶相关蛋白家族具有转录调控作用，参与黑素的生成。
脱发分为正常的生理性脱发和病理性脱发。正常脱发能使进入退行期与新进入生长期的毛发不断处于动态平衡，故能维持正常数量的头发，但病理性脱发则导致头发异常脱落或过度脱落。造成病理性脱发的原因比较复杂，包括例如雄激素性脱发、神经性脱发、内分泌脱发、营养性脱发、先天性脱发。
专利文献1记载了雄激素代谢失常导致的脱发，主要表现在5α-还原酶活性增强，使睾酮过多地转化为双氢睾酮，后者在头皮毛囊部位大量积聚，造 成头发生长周期缩短，毛囊退化变小，毛发变细、变软、变短、脱落。
目前对白发和脱发的预防和治疗方法有中药疗法和西药疗法。专利文献2提及中医学认为下列因素与白发有关：一是精虚血弱：肾精不足，不能化生阴血，阴血亏虚，导致毛发失其濡养，故而花白。二是血热偏盛：情绪激动，致使水不涵木，肝旺血燥，血热偏盛，毛根失养，故发早白。三是肝郁脾湿：肝气郁滞、损及心脾，脾伤运化失职，气血生化无源，故而白发。
专利文献3公开了一种治疗少白头的胶囊剂，其组成是中药女贞子、早莲草、桑椹子、甘草、黑芝麻、明胶等，通过胶囊制品的工艺流程加工而成。专利文献4公开了一种乌发中药组合物及其颗粒，其组成为女贞子、墨早莲、何首乌、黄精和黑豆，通过颗粒药剂制品的工艺流程加工而成。这些中药疗法均未发现何种组分具有显著预防或治疗白发的效果，而多种组分带来的副作用不容忽视，这也是中药疗法的普遍缺点。
关于西药疗法，专利文献5公开一种控制或减缓毛发变色的组合物和方法。该组合物中含有过氧化氢酶物质、抗氧化剂和美容物载体，组合物的pH值控制到2至6之间。将含有该组合物的物质直接作用于头发的中段到根部，可以控制或减缓头发变白(变灰)。但是该文献对于组合物对黑素细胞和酪氨酸酶的影响未作深入研究，其阻止黑发变白的效果也不佳，并且可能有潜在的副作用。
非专利文献2公开了莱菔素作为异硫氰酸酯，可从中药莱菔子和萝卜种子等天然产物中提取获得，目前对莱菔素的研究主要集中于其抗癌功能，其可高效诱导Ⅱ相解毒酶，提高人体对致癌物的清除能力，因此可有效抑制癌细胞的生长增殖和杀死癌细胞。非专利文献3的研究还表明，莱菔素对肺癌和肝癌等细胞系具有良好的杀伤效果，还可抑制食管癌和乳腺癌细胞。
但是，迄今为止，莱菔素在改善和治疗白发和/或脱发方面的应用未见报道。
现有技术文献：
专利文献1：CN108066221A
专利文献2：CN105660933A
专利文献3：CN104415101A
专利文献4：CN104606485A
专利文献5：US9265717B1
非专利文献1：正常人黑素细胞MITF对酪氨酸酶相关蛋白的转录调控研究，J Med Res,Mar 2013,Vol 42 No.3.58-62
非专利文献2：Yang,M.,Ren,M.,Qu,Y.,Teng,W.,Wang,Z.,Li,H.and Yuan,Q.,2016.Sulforaphene inhibits hepatocellular carcinoma through repressing keratin 8 and activating anoikis.RSC Advances,6(74),pp.70326-70334
非专利文献3：一种植物来源天然化合物莱菔素抗肿瘤活性评价及作用机制研究，屈悦，北京化工大学硕士论文，2015，摘要
发明内容
发明要解决的问题
从背景技术可以看出，白发和脱发的产生有多种原因，无论从外观还是精神上均给人带来不良影响，而目前的中药和西药疗法存在各种缺陷和不足。中药疗法见效缓慢、多组分带来的长期副作用较大，有些方法还对人体造成较大伤害。西药疗法的作用机理不明，有效成分生发和黑发的效果不佳，治疗效果不理想。因此，寻找能有效改善和治疗白发和/或脱发的药物具有重要意义，但是目前尚未发现该方面的安全、快速、有效的药物，本申请致力于解决该问题。
用于解决问题的方案
本发明人在莱菔素的应用研究中意外发现，莱菔素具有生发和黑发效果。为证实该方面的效果，本发明人进行了深入研究，将包含莱菔素的组合物制备成冲剂、口服片和软胶囊等剂型并给予受试者后，发现适当剂量的莱菔素在比现有技术更短的时间内可实现有效改善和治疗白发和/或脱发的效果。
本发明人尚未发现莱菔素改善和治疗白发和/或脱发的作用机理，后续将进行该方面的研究。目前分析其可能与莱菔素的抗氧化功能有关，提高了白发症和脱发症受试者的免疫力，从而阻止因免疫系统的反应过度或者异常反应而导致的白发或者脱发。本发明人还认为莱菔素也可能促进了小眼畸形相关转录因子(MITF)的表达、防止MITF发生异变，从而阻止因MITF异变导致的加速黑素分化细胞的异常着色或分化，进而阻止黑素干细胞的生理老化。对于二氢睾酮(DHT)引起的脱发症，莱菔素也可能通过抑制5α-还原酶的活性，阻止睾酮转化成二氢睾酮(DHT)，进而阻止DHT与特异性受体结合产生引起脱发的蛋白质，达到抑制脱发的目的。
本发明主要涉及如下几方面：
1)、莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途，其特征在于，所述莱菔素为所述药物组合物的有效成分，且基于所述药物组合物的总重量，所述莱菔素的含量为0.1～50％。
2)、根据1)所述的用途，其特征在于，所述莱菔素的含量为0.5～10％，更优选为1～5％。
3)、根据1)或2)所述的用途，其特征在于，所述莱菔素为天然产物提取物、生物合成产物或化学合成产物。
4)、根据1)～3)任一项所述的用途，其特征在于，所述提取物从选自由抱子甘蓝、甘蓝、花椰菜、白菜、无头甘蓝、羽衣甘蓝、绿花椰菜芽、芥蓝、球花甘蓝、大头菜、芥末、芜菁、萝卜、芝麻菜和水田芥菜组成的组的天然 产物中提取获得。
5)、根据1)～4)任一项所述的用途，其特征在于，所述药物组合物以片剂、胶囊剂、散剂、粉剂、冲剂、颗粒剂、软膏剂、贴剂、乳剂、搽剂、糊剂、注射剂、喷雾剂、乳霜剂、洗剂、油剂、悬浮剂、凝胶剂或滋补剂的形式使用。
6)、根据1)～5)任一项所述的用途，其特征在于，所述药物组合物通过口服给药、注射给药、皮肤给药或粘膜给药。
7)、根据1)～6)任一项所述的用途，其特征在于，所述组合物以莱菔素的剂量为5～500mg/人/天的剂量口服给药。
8)、根据7)所述的用途，其特征在于，所述药物组合物以莱菔素的量为10～100mg/人/天的剂量口服给药，更优选为20～40mg/人/天。
9)、包含莱菔素的用于改善和治疗白发和/或脱发的药物组合物的制备方法，其特征在于，所述方法包括将莱菔素作为有效成分包含于所述药物组合物中，基于所述药物组合物的总重量，所述莱菔素的含量为0.1～50％。
发明的效果
本发明的包含莱菔素作为有效成分的药物组合物在改善和治疗白发和/或脱发中表现出非常显著甚至惊人的效果，可显著促进毛发生长、修复和增加，令人惊异地快速减少脱发量，阻止脱发的进展。同时，莱菔素可促使灰发、白发由根部开始变黑，发质变硬，有效修复和改善发质。此外，相较于现有技术，莱菔素的作用时间短、药效显著，适应人群广。
本发明的效果包括如下：
(1)受试者以剂量为10～100mg/人/天口服莱菔素后，5～15天开始出现白发和/或脱发的改善效果，20天至1个月后白发开始变黑，有明显的新发生成，2～3个月后白发大部分变黑，脱发抑制显著，甚至有部分受试者有新发 长出。与其相对，现有技术中的药物至少需要3～6个月才出现白发变黑和/或脱发受到抑制的效果。
(2)对于白发、脱发面积占全头面积1～10％给药的受试者，给药1个月后，至少94.0％的受试者有明显的生发效果，至少92.6％的受试者有明显的黑发效果；对于白发、脱发面积占全头面积大于10～50％的受试者，给药2个月后，至少92.8％的受试者有明显的生发效果，至少93.8％的受试者有明显的黑发效果；对于白发、脱发面积占全头面积大于50％的受试者，给药3个月后，至少86.8％的受试者有明显的生发效果，至少89.5％的受试者有明显的黑发效果。因此，本发明的组合物的适应人群广，对大多数受试者均有效果，并且适应于不同原因导致的白发和/或脱发。现有技术尚未发现在1～3个月的短时期内、适应如此高比例人群的显著改善和治疗白发和/或脱发的组合物。
附图说明
图1中a和b分别显示患有脱发症和白发症的受试者服用莱菔素1个月后与未服用前的毛发摄像对比图。
图2中a和b分别显示白发症的受试者服用莱菔素2个半月后与未服用前的毛发摄像对比图。
具体实施方式
本发明的包含莱菔素作为有效成分的药物组合物可改善和治疗白发和/或脱发，适用于背景技术中提及的先天性和后天性的白发、生理性和病理性的白发以及生理性和病理性的脱发。
本发明的药物组合物所包含的莱菔素的含量不受限制，只要能实现改善和治疗白发和/或脱发的效果即可。本发明的药物组合物可包含0.1％～50％重量百分比的莱菔素，莱菔素的含量低于0.1％重量百分比时，由于莱菔素过少，对改善和治疗白发和/或脱发没有明显的效果，莱菔素含量高于50％重量百分 比时，莱菔素过多，不能较好地溶于溶剂中，难以形成均相。
优选地，本发明的药物组合物包含0.5～10％重量百分比的莱菔素，在该范围内，莱菔素可在较短时间内例如2～3个月显著改善和治疗白发和/或脱发。更优选地，本发明的组合物包含1～5％重量百分比的莱菔素，在该范围内，莱菔素可实现短时间内较大程度地改善和治疗白发和/或脱发，例如对于白发或脱发面积占全头面积大于50％的受试者，至少86.8％和89.5％的受试者在3个月内分别有明显的生发和黑发效果。
本发明的莱菔素可通过本领域公知的任何方法制备，例如天然产物提取法、生物合成法或化学合成法等，只要所述莱菔素提取物具有改善和治疗白发和/或脱发的效果即可。本发明优选使用天然产物提取法得到的莱菔素，所述提取物可从抱子甘蓝、甘蓝、花椰菜、白菜、无头甘蓝、羽衣甘蓝、绿花椰菜芽、芥蓝、球花甘蓝、大头菜、芥末、芜菁、萝卜、芝麻菜和水田芥菜等植物中获得。
在本发明的一个具体实施方式中，莱菔素的制备可采用如下方法：
(1)将萝卜籽或萝卜籽芽苗粉碎或匀浆后，加入5～20倍体积的自来水、去离子水或pH值为5.0～8.0的缓冲溶液，在5～50℃条件下搅拌水解10～300分钟后，加入盐酸调节水解液pH值为1.0～3.0，静置过夜，减压过滤或离心得到莱菔素水解液。
(2)利用有机溶剂萃取步骤(1)得到的莱菔素水解液，有机溶剂加入量为莱菔素水解液体积的0.5～5倍，萃取2～5次，回收水解液中的莱菔素，收集有机溶剂萃取层，减压蒸馏得到莱菔素粗提物，同时回收有机溶剂。所述有机溶剂为本领域通常使用的有机溶剂，例如，正己烷、环己烷、乙醚、正丁醇、氯仿、二氯甲烷或乙酸乙酯等。
(3)将步骤(2)得到的莱菔素粗提物加入分子蒸馏装置中进行一级分子蒸馏，脱除莱菔素粗提物中残留的有机溶剂、水分和低沸点杂质成分，收集从一级分子蒸馏装置蒸馏壁流出的重组分，得到一级分子蒸馏重组分。一级分 子蒸馏条件为：原料保温温度30～60℃，真空度100～2000Pa，蒸馏温度50～100℃，进料流速2～20mL/min，冷凝面温度0～30℃，刮膜器转速200～400rpm。
(4)将步骤(3)得到的一级分子蒸馏重组分加入分子蒸馏装置中进行二级分子蒸馏，脱除一级分子蒸馏重组分中的高沸点杂质成分，收集从二级分子蒸馏装置冷凝面流出的轻组分，得到莱菔素产品。二级分子蒸馏条件为：原料保温温度30～70℃，真空度0.1～10Pa，蒸馏温度80～200℃，进料流速1～10mL/min，冷凝面温度0～20℃，刮膜器转速200～450rpm。
本发明的药物组合物可根据产品的形态而制成适当的剂型。例如，本发明的组合物可具有选自由片剂、胶囊剂、散剂、粉剂、颗粒剂、软膏剂、贴剂、乳剂、搽剂、糊剂、注射剂、喷雾剂、乳霜剂、洗剂、油剂、悬浮剂、凝胶剂或滋补剂组成的组中的剂型，但本发明不限于此。
本发明的药物组合物可以为保健品、食品或养发护发品等日用化学品，只要能够实现改善和治疗白发和/或脱发的效果，本发明的药物组合物的使用形式不限于此。
本发明的药物组合物可包含本领域公知的任何药学上可接受的载体和/或赋形剂，只要不影响莱菔素实现本发明效果即可。例如，可使用乳糖、葡萄糖、蔗糖、山梨糖醇、甘露醇、淀粉、糊精、阿拉伯胶、磷酸钙、藻酸盐、明胶、硅酸钙、微晶纤维素、聚乙烯吡咯烷酮、水、糖浆、甲基纤维素、羟苯甲酯、羟苯丙酯、滑石、硬脂酸镁、超级羧甲淀粉钠、植物油、动物油以及矿物油剂等，但本发明不限于此。
本发明的药物组合物除了上述成分以外，还可包含其他添加剂，如润滑剂、湿润剂、甜味剂、香味剂、乳化剂、悬浮剂、保鲜剂等，只要不影响莱菔素实现本发明效果，可添加任何添加剂。
本发明的药物组合物可通过口服给药、注射给药、皮肤给药或粘膜给药等方式给药，只要能够实现改善和治疗白发和/或脱发的效果，本发明的药物 组合物的给药形式不限于此。
本发明的药物组合物的给药剂量、给药频率和给药时间可根据受试者的白发或脱发症状、受试者年龄、药物剂型等的不同而不同。本发明的药物组合物中的莱菔素优选以剂量为5～500mg/人/天口服给药，更优选以剂量为10～100mg/人/天口服给药，最优选以剂量为20～40mg/人/天口服给药。以冲剂、口服剂和软胶囊为例，通常给药频率为1～2次/天，给药剂量为10～100mg/人/天，给药时间为5天至3个月。
下面通过实施例对本发明进行详细说明，但本发明不限于此。
实施例
<莱菔素提取物的制备>
按照如下步骤制备莱菔素提取物，以用于后述实施例的组合物中。
(1)将萝卜籽100kg粉碎或匀浆后，加入20倍体积的去离子水2000L，在室温条件下搅拌水解5h后，加入盐酸调节水解液pH值为2.0，静置过夜，离心后得到作为上清液的莱菔素水解液2000L；
(2)利用体积相同的乙酸乙酯萃取步骤(1)得到的莱菔素水解液3次，回收水解液中的莱菔素，收集乙酸乙酯萃取层，在40℃、真空度为-0.08MPa下减压蒸馏得到莱菔素粗提物200L，同时回收乙酸乙酯；
(3)将步骤(2)得到的莱菔素粗提物加入到分子蒸馏装置中进行一级分子蒸馏，脱除莱菔素粗提物中残留的乙酸乙酯、水分和低沸点杂质成分，收集从一级分子蒸馏装置蒸馏壁流出的重组分，得到一级分子蒸馏重组分2000g；一级分子蒸馏条件为：原料保温温度60℃，真空度2000Pa，蒸馏温度100℃，进料流速2mL/min，冷凝面温度0℃，刮膜器转速400rpm；
(4)将步骤(3)得到的一级分子蒸馏重组分加入到分子蒸馏装置中进行二级分子蒸馏，脱除一级分子蒸馏重组分中的高沸点杂质成分，收集从二级分子蒸馏装置冷凝面流出的轻组分，得到高纯度的99.5％的莱菔素产品1000g；二级分子蒸馏条件为：原料保温温度70℃，真空度0.1Pa，蒸馏温度110℃， 进料流速1mL/min，冷凝面温度0℃，刮膜器转速450rpm。
<以莱菔素为有效成分的本发明药物组合物的制备>
以上述方法制备的莱菔素提取物为原料，混合其他添加剂，制备冲剂、片剂和胶囊剂形式的本发明的药物组合物。
实施例1 莱菔素冲剂1的制备
取100g上述方法制备的莱菔素提取物与19.9kg糊精在100L去离子水中混合溶解，然后进行喷雾干燥。喷雾干燥的进风温度设定为180℃，出风温度调整为80℃，进液速度为5L/h，收集产品，制备莱菔素喷雾干燥粉，用于制粒机制粒，采用自动颗粒包装机以2g分装，制备0.5％莱菔素含量的莱菔素冲剂1。
实施例2 莱菔素冲剂2的制备
取100g上述方法制备的莱菔素提取物与9.9kg糊精在50L去离子水中混合溶解，以与实施例1相同的方式进行喷雾干燥，制备莱菔素喷雾干燥粉，以1g分装，制备1％含量的莱菔素冲剂2。
实施例3 莱菔素冲剂3的制备
取100g上述方法制备的莱菔素提取物与99.9kg糊精在500L去离子水中混合溶解，以与实施例1相同的方式进行喷雾干燥，制备莱菔素喷雾干燥粉，以20g分装，制备0.1％莱菔素含量的莱菔素冲剂3。
实施例4 莱菔素口服片1的制备
取100g上述方法制备的莱菔素提取物与1.9kg糊精在10L去离子水中混合溶解，以与实施例1相同的方式进行喷雾干燥，制备5％含量的莱菔素喷雾干燥粉。在干燥粉中加入硬脂酸镁50g、膨速王500g、微晶纤维素2.45kg，将粉末混合均匀后进行干法制粒，然后将制粒得到的含药颗粒进行压片，制备得到每粒500mg含有2％莱菔素的口服片1。
实施例5 莱菔素口服片2的制备
取200g上述方法制备的莱菔素提取物与1.8kg糊精在10L去离子水中混 合溶解，以与实施例1相同的方式进行喷雾干燥，制备10％含量的莱菔素喷雾干燥粉，加入硬脂酸镁50g、膨速王500g、微晶纤维素2.45kg混合后压片，制备得到每粒500mg含有4％莱菔素的口服片2。
实施例6 莱菔素口服片3的制备
取100g上述方法制备的莱菔素提取物与0.9kg糊精在5L去离子水中混合溶解，以与实施例1相同的方式进行喷雾干燥，制备10％含量的莱菔素喷雾干燥粉，加入硬脂酸镁100g、膨速王1kg、微晶纤维素7.9kg混合后压片，制备得到每粒500mg含有1％莱菔素的口服片3。
实施例7 莱菔素软胶囊1的制备
取100g上述方法制备的莱菔素提取物与4.9kg玉米油混合，以明胶为胶囊皮的主成分，按照本领域公知的方法使用模具压制制备2％含量的莱菔素软胶囊1，每粒软胶囊含内容物500mg。
实施例8 莱菔素软胶囊2的制备
取100g上述方法制备的莱菔素提取物与4.9kg大豆油混合，以与实施例7相同的方式制备2％含量的莱菔素软胶囊2，每粒软胶囊含内容物250mg。
实施例9 莱菔素软胶囊3的制备
取100g上述方法制备的莱菔素提取物与9.9kg橄榄油混合，以与实施例7相同的方式制备1％含量的莱菔素软胶囊3，每粒软胶囊含内容物500mg。
<本发明的药物组合物对白发和/或脱发的改善和治疗>
使用实施例1～9制备的莱菔素冲剂、片剂和软胶囊进行如下实验，考察莱菔素对白发和/或脱发的改善和治疗效果。
通过自愿参加的方式，选择年龄在18～65岁、白发和/或脱发症起因和症状各异、性别不限的受试者347名，服用实施例1～9制备的莱菔素冲剂、片剂或软胶囊，每日1～2次，1次1～6粒，餐后服用，以剂量为10～100mg/人/天口服给药连续1～3个月。给药剂量由以下因素决定：受试者的体重、年龄、白发和/或脱发的严重程度、受试者对药物的接受度。
实验结果如下表1～2所示，图1～2为毛发摄像图，显示了受试者服用莱菔素后白发和/或脱发的改善和治疗效果。
需要说明的是，表1a和1b中，“改善起始时间”意指开始出现白发变黑和/或脱发减少效果的时间，女性主要表现为梳头时是否脱发；“是否使用其他药物”意指受试者是否曾经服用其他药物改善或治疗白发症和/或脱发症。表2中，“使用时间”是根据受试者的白发和/或脱发程度而设定，其中白发和/或脱发比例占全头1～10％的受试者，使用时间设为连续服用1个月莱菔素；白发和和/或脱发比例占全头10～50％的受试者，使用时间设为2个月；白发和/或脱发比例占全头大于50％的受试者，使用时间设为3个月。表2中的“明显”意指生发、黑发明显增加，生发或黑发面积大于头发总面积的25％，“一般”意指生发黑发有所增加，生发或黑发面积为头发总面积的1％～25％，“无效”意指无明显效果，生发或黑发面积小于头发总面积的1％。
表1a 男性服用莱菔素对白发和/或脱发的改善和治疗效果
Figure PCTCN2022117853-appb-000001
表1b女性服用莱菔素对白发和/或脱发的改善和治疗效果
Figure PCTCN2022117853-appb-000002
表2 对白发和/或脱发有改善和治疗效果的受试者比例
Figure PCTCN2022117853-appb-000003
表1a和表1b显示，对于不同年龄和性别的、患有不同程度白发症和/或脱发症的受试者，以剂量为10～60mg/人/天口服给药后，在5天至3个月期间有不同程度的改善效果。如表1b中序号1所示，该受试者同时患有白发和脱发症，服用莱菔素后很短时间内就出现改善效果，即，在以30mg/天的剂量口服莱菔素冲剂后，5天后就开始出现脱发减少，一个月后基本不脱发且白发大部分变黑。该受试者2年前曾使用其他中药进行治疗，但持续治疗半年后白发和脱发症并未改善。对于严重的白发症受试者，如表1a中序号4的头发基本全白的受试者，1个月后白发中超过1/2变灰，2个半月后全部白发基本变黑(参见图2中a和b)。
此外，图1中a和b还显示了表1b中序号2的同时患有脱发症和白发症的受试者在服用莱菔素1个月后脱发情况明显改善，部分白发变灰，2个月后白发基本变黑。该毛发摄像图确认到白发变黑，变黑的发质硬且有光泽，显示了莱菔素的黑发和养发效果。
表2根据白发症和脱发症的严重程度而分别给药1个月、2个月、3个月，研究特定时间内的改善和治疗程度，结果发现：白发或脱发比例占全头1～10％的受试者连续服用1个月莱菔素后，至少94.0％的受试者生发效果明显， 至少92.6％的受试者黑发效果明显，说明对于白发症和脱发症较轻的受试者，莱菔素的治疗效果非常显著。对于中度白发症或脱发症的受试者，例如白发或脱发比例占全头10～50％的受试者，连续服用2个月莱菔素后，至少92.8％的受试者生发效果明显，至少93.8％的受试者黑发效果明显。甚至对于症状严重的白发或脱发比例大于全头50％的受试者，连续服用3个月莱菔素后，至少86.8％的受试者生发效果明显，至少89.5％的受试者黑发效果明显。
上述实验还显示，冲剂、口服剂和软胶囊等不同剂型的含有莱菔素的组合物对受试者均能起到改善和治疗白发和/或脱发的作用，实验未发现剂型在改善和治疗效果方面有明显差异。
产业上的可利用性
本发明的包含莱菔素作为有效成分的药物组合物在改善和治疗白发和/或脱发方面具有非常显著的效果，具有药物作用时间短、药效显著，适应人群广等特点。受试者服用本发明的药物组合物后，5～15天开始出现白发和/或脱发的改善效果，2～3个月后白发大部分变黑，脱发抑制效果显著，甚至有部分受试者有新发长出。因此，本发明为目前白发和/或脱发的改善和治疗提供了一种新的药物和方法。

Claims (9)

  1. 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途，其特征在于，所述莱菔素为所述药物组合物的有效成分，且基于所述药物组合物的总重量，所述莱菔素的含量为0.1～50％。
  2. 根据权利要求1所述的用途，其特征在于，所述莱菔素的含量为0.5～10％，更优选为1～5％。
  3. 根据权利要求1或2所述的用途，其特征在于，所述莱菔素为天然产物提取物、生物合成产物或化学合成产物。
  4. 根据权利要求1～3中任一项所述的用途，其特征在于，所述提取物从选自由抱子甘蓝、甘蓝、花椰菜、白菜、无头甘蓝、羽衣甘蓝、绿花椰菜芽、芥蓝、球花甘蓝、大头菜、芥末、芜菁、萝卜、芝麻菜和水田芥菜组成的组的天然产物中提取获得。
  5. 根据权利要求1～4中任一项所述的用途，其特征在于，所述药物组合物以片剂、胶囊剂、散剂、粉剂、冲剂、颗粒剂、软膏剂、贴剂、乳剂、搽剂、糊剂、注射剂、喷雾剂、乳霜剂、洗剂、油剂、悬浮剂、凝胶剂或滋补剂的形式使用。
  6. 根据权利要求1～5中任一项所述的用途，其特征在于，所述药物组合物通过口服给药、注射给药、皮肤给药或粘膜给药。
  7. 根据权利要求1～6中任一项所述的用途，其特征在于，所述药物组合物以莱菔素的量为5～500mg/人/天的剂量口服给药。
  8. 根据权利要求7所述的用途，其特征在于，所述药物组合物以莱菔素的量为10～100mg/人/天的剂量口服给药，更优选为20～40mg/人/天。
  9. 包含莱菔素的用于改善和治疗白发和/或脱发的药物组合物的制备方法，其特征在于，所述方法包括将莱菔素作为有效成分包含于所述药物组合物中，基于所述药物组合物的总重量，所述莱菔素的含量为0.1～50％。
PCT/CN2022/117853 2021-10-15 2022-09-08 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途 WO2023061117A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202111203285.5A CN113893237A (zh) 2021-10-15 2021-10-15 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途
CN202111203285.5 2021-10-15

Publications (1)

Publication Number Publication Date
WO2023061117A1 true WO2023061117A1 (zh) 2023-04-20

Family

ID=79192270

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/117853 WO2023061117A1 (zh) 2021-10-15 2022-09-08 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途

Country Status (2)

Country Link
CN (1) CN113893237A (zh)
WO (1) WO2023061117A1 (zh)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113893237A (zh) * 2021-10-15 2022-01-07 北京化工大学 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途
CN114588141A (zh) * 2022-03-31 2022-06-07 北京化工大学 一种用于治疗银屑病的药物

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080027129A1 (en) * 2006-06-20 2008-01-31 L'oreal Administration of 3H-1, 2-dithiole-3-thione, anethole dithiolethione, sulforaphane, phenethyl isothiocyanate, 6-(methylsulfinyl)hexyl isothiocyanate and allyl isothiocyanate for the treatment of canities
CN107375223A (zh) * 2017-06-12 2017-11-24 深圳市老年医学研究所 含莱菔素胃滞留组合物及其制备方法
CN110403909A (zh) * 2019-08-21 2019-11-05 青岛农业大学 一种莱菔素粉剂及其制备方法
CN113893237A (zh) * 2021-10-15 2022-01-07 北京化工大学 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080027129A1 (en) * 2006-06-20 2008-01-31 L'oreal Administration of 3H-1, 2-dithiole-3-thione, anethole dithiolethione, sulforaphane, phenethyl isothiocyanate, 6-(methylsulfinyl)hexyl isothiocyanate and allyl isothiocyanate for the treatment of canities
CN107375223A (zh) * 2017-06-12 2017-11-24 深圳市老年医学研究所 含莱菔素胃滞留组合物及其制备方法
CN110403909A (zh) * 2019-08-21 2019-11-05 青岛农业大学 一种莱菔素粉剂及其制备方法
CN113893237A (zh) * 2021-10-15 2022-01-07 北京化工大学 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Prescriptions of Chinese Medicine for Cosmetology", 28 February 2013, XI'AN JIAOTONG UNIVERSITY PRESS, CN, ISBN: 978-7-5605-4602-5, article HUANG, LIPING ET AL.: "Passage; Chinese Medicine Formulaology", pages: 125, XP009545856 *
PU ZHAOHE: "Raspberry is effective in treating chloasma", NONGCUN BAISHITONG, no. 11, 1 June 2009 (2009-06-01), pages 83 - 83, XP093057225, DOI: 10.19433/j.cnki.1006-9119.2009.11.063 *

Also Published As

Publication number Publication date
CN113893237A (zh) 2022-01-07

Similar Documents

Publication Publication Date Title
WO2023061117A1 (zh) 莱菔素在制备用于改善和治疗白发和/或脱发的药物组合物中的用途
JP4693963B2 (ja) エストロゲン様作用剤、コラーゲン産生促進剤、及び線維芽細胞増殖剤
JP6064156B2 (ja) 深部体温上昇剤
JP2001064192A (ja) ランゲルハンス細胞の遊走抑制剤及び抗原提示抑制剤
TWI640317B (zh) 茯苓萃取物及其活性成分於保養肌膚及／或促進傷口癒合之用途
WO2019056908A1 (zh) 铁皮石斛在制备治疗高血压药物中的应用方法
JP2000086510A (ja) ヒスタミン遊離抑制剤
EP3662891B1 (en) Composition for preventing hair loss or promoting hair growth
KR20150054439A (ko) 보리지 추출물을 포함하는 대사질환 개선, 예방 또는 치료용 조성물
JP5633028B2 (ja) 交感神経活発化剤
CN107635561B (zh) 含有茶皂醇衍生物作为活性成分的组合物
EP0952816B1 (fr) Utilisation cosmetique, dermatologique et pharmaceutique d&#39;un extrait de terminalia catappa
TW202234999A (zh) 包含發酵熟成諾麗及卡曼橘作為活性成分的組合物用於釋放壓力
EP4205558A1 (en) Health functional food, comprising siberian chrysanthemum extract, for pain relief or antioxidation
EP1536697B1 (fr) Composition comprenant en association au moins une huile de courge et au moins une huile de bourrache, son utilisation comme medicament, comme agent dermatologique ou dermato-cosmetique
JPH09208484A (ja) 活性酸素消去剤及びそれを含む組成物
KR20210058772A (ko) 탈모 치료 및 발모 촉진용 조성물
KR102179610B1 (ko) 월견자 및 의이인 정유 혼합물을 함유하는 탈모 예방 또는 발모 촉진용 조성물
KR20210018388A (ko) 식물추출물 또는 이의 분획물을 유효성분으로 함유하는 피부 상태 개선용 조성물
WO2018016455A1 (ja) 滋養強壮剤
JP6902329B2 (ja) 皮脂腺細胞の活性化の抑制剤
KR20070000675A (ko) 녹두 추출물, 백급 추출물 및 승마 추출물을 포함하는조성물 및 이의 용도
KR101273027B1 (ko) 캄페롤을 유효성분으로 함유하는 피지 분비 억제용 및항비만용 조성물
KR101420270B1 (ko) 홍삼 추출물의 감식초 반응 혼합물을 함유한 전립선 비대증의 예방 또는 치료용 조성물
JP2003026592A (ja) 甘草発酵抽出物からなる抗アンドロゲン剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 22880059

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 18288795

Country of ref document: US