CN116999427A - Application of salvianolic acid B in preparing medicament for treating alopecia - Google Patents

Application of salvianolic acid B in preparing medicament for treating alopecia Download PDF

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Publication number
CN116999427A
CN116999427A CN202311111086.0A CN202311111086A CN116999427A CN 116999427 A CN116999427 A CN 116999427A CN 202311111086 A CN202311111086 A CN 202311111086A CN 116999427 A CN116999427 A CN 116999427A
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China
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salvianolic acid
hair
alopecia
sab
application
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CN202311111086.0A
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Inventor
吴文育
刘庆梅
林尽染
周迎慧
张悦
李政
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Huashan Hospital of Fudan University
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Huashan Hospital of Fudan University
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Priority to CN202311111086.0A priority Critical patent/CN116999427A/en
Publication of CN116999427A publication Critical patent/CN116999427A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/14Drugs for dermatological disorders for baldness or alopecia

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cosmetics (AREA)

Abstract

The in-vitro and in-vivo experiments prove that the salvianolic acid B can play a role in controlling alopecia by regulating and controlling a plurality of signal paths, including the important Wnt paths in hair growth, and has great clinical value and economic benefit.

Description

Application of salvianolic acid B in preparing medicament for treating alopecia
Technical Field
The invention relates to the field of medicines, in particular to application of salvianolic acid B in preparation of a medicine for treating alopecia.
Background
Alopecia (Alopecia) is a generic term for abnormal loss of hair, a common skin condition. In recent years, the number of people suffering from alopecia is gradually increased, the trend of younger people is shown, and many people suffering from alopecia are deeply plagued by the young and middle-aged people. The most common of the alopecia diseases is androgenic alopecia, and epidemiological studies show that the prevalence of the disease in China is 21.3% for men and 6.0% for women, namely, 1 male in 5 China may have androgenic alopecia.
Hair activity and hair shaft growth are regulated by a variety of cells, wherein hair papilla is a specialized mass of fibroblasts located at the bottom of hair follicle, which is capable of inducing hair growth. The hair papilla cells can secrete various cell growth factors, and can regulate proliferation of hair papilla and perifollicular vascular endothelial cells, so that hair papilla angiogenesis is induced; meanwhile, the state of the anagen hair follicle, the duration of the anagen phase, etc. are also affected by the activity of the hair papilla cells. Hair follicles are found in androgenic alopecia and alopecia areata patients to advance to stationary phase, and this process is attended by ROS, which can be prevented or alleviated by antioxidants or ROS inhibitors of hair papilla cells.
At present, the oral medicines approved by the national drug administration for treating alopecia are only two kinds of minoxidil and finasteride. Although widely used clinically, these two drugs cannot completely block the progress of the disease, and have adverse reactions of different degrees. Minoxidil is a vasodilator and potassium channel opener, and its side effects are scalp irritation, itching, dryness, scaling, redness, contact dermatitis, hirsutism, etc. Finasteride is a type II 5 alpha-reductase inhibitor and can block T from being converted into DHT with stronger activity, so that the inhibition of androgens on hair follicles is weakened. But finasteride can cause adverse effects such as impotence, sexual dysfunction, myalgia, female-type breasts, etc. Besides drugs, treatments for alopecia include laser light and hair transplantation, and the effects of these treatments have not been progressed in breakthrough.
Therefore, there is a need in the art for a medicament for treating alopecia with remarkable therapeutic effects and little side effects.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides the following technical scheme:
the invention provides application of salvianolic acid B in preparing a medicament for treating alopecia;
further, the salvianolic acid B is shown as a formula I:
further, the hair loss treatment effect is to improve hair follicle activity and promote hair growth.
Salvianolic acid B (Salvianolic acid B, SAB, CAS No. 115939-25-8), salvianolic acid B of formula C 36 H 30 O 16 Relative molecular mass: 718.62. the salvianolic acid B is light yellow, is in powder form, has special smell, and has slightly bitter and astringent taste. The compound can be dissolved in water, ethanol and methanol, and the small molecular compound has a plurality of phenolic hydroxyl groups in the structure and has stronger oxidation resistance.
In the prior art, the sources of salvianolic acid B mainly include two types: firstly, the salvia miltiorrhiza extraction method and secondly, the chemical synthesis method. At present, a plurality of separation and extraction methods are specially used for extracting salvianolic acid B, wherein the salvianolic acid B is prepared by condensing three molecules of salvianic acid A and one molecule of caffeic acid and is obtained by extracting roots and rhizomes of Salvia Miltiorrhiza bge of Labiatae. The main technological process of the separation and preparation of the salvianolic acid B is extraction, separation, purification and other processes. The method for extracting the salvianolic acid B comprises the following steps: traditional water decoction method, ultrasonic extraction method, reflux extraction method, supercritical CO 2 Extraction, etc., and the separation method used is silica gel column chromatography, large Kong Shujiao chromatography, high performance countercurrent chromatography, etc. For the chemical synthesis method, 3-hydroxy-4-methoxybenzaldehyde (isovanillin) is used as a raw material, 4-hydroxy-5-methoxybenzopyran-2-ketone is synthesized through Claisen rearrangement, acetylation and oxidation reaction, aldol condensation reaction is carried out on the 4-hydroxy-5-methoxybenzopyran-2-ketone and methoxyisovanillin, a lactone ring is opened to generate hydroxymethyl, the hydroxymethyl is oxidized to generate aldehyde, trans-2, 3-dihydrobenzofuran is generated through cyclization under the action of hydrobromic acid, and acrylic acid is generated through condensation of aldehyde group and malonic acid, so that salvianolic acid B is obtained. Salvianolic acid B is currently marketed by various companies, such as Sigma, and the preparation method thereof is also known in the prior art.
Drawings
FIG. 1A schematic photograph of hair growth in different groups of unhairing mice
FIG. 2 in vitro culture of hair follicle shaft growth length
FIG. 3 in vitro cultured hair papilla cell ROS levels in different treatment groups
Advantageous effects
Salvianolic acid B (Salvianolic acid B, SAB) is an important water-soluble component of Saviae Miltiorrhizae radix, also called salvianolic acid B, is the only monomer component extracted from Saviae Miltiorrhizae radix on the market at present, and plays an important role in the efficacy of Saviae Miltiorrhizae radix. SAB has effects of resisting platelet aggregation, resisting thrombosis, improving microcirculation, and resisting oxidation injury. The in-vitro and in-vivo experiments prove that the salvianolic acid B can play a role in controlling alopecia by regulating and controlling a plurality of signal paths, including the important Wnt paths in hair growth, and has great clinical value and economic benefit.
Detailed Description
Examples
Test object: c57BL/6 male mice at 8 weeks of age were purchased from the experimental animal center at the university of double denier.
The test method comprises the following steps:
1) In vivo experiments
Establishment of a depilatory mouse model: the method adopts 8-week-old C57BL/6 male mice, adopts the back shaving and combines the dehairing paste mode to establish a dehairing model, and comprises the following specific modes: the razor cleans the back Mao Ti, further treating it with conventional depilatory cream for 1min, and then scrubbing the cream.
Experimental mice were grouped and treated:
(1) Grouping: first, animals were divided into two groups, control group (Control), salvianolic acid B treatment group (SAB). Each group had 6 mice.
(2) Treatment of mice: the control mice were subjected to depilation treatment, and 100ul of physiological saline was subcutaneously injected into the depilation area of the back of each day after depilation; after depilating, 100ul of SAB configured with physiological saline was injected subcutaneously into the back of each day in SAB-treated mice, and the final SAB dose was: 10 mg/kg/day.
(3) The back hair growth status of the mice was observed and photographed.
2) In vitro experiments: detection of hair follicle and papilla cell Activity
(1) In vitro hair follicle tissue culture: hair follicles were placed in 12-well cell culture plates, 1 hair follicle was placed in each well, 1ml of serum-free William's medium was added, and the culture was performed in a cell incubator.
(2) Hair follicle grouping and processing: the in vitro hair follicles were divided into two groups, control group (Control), salvianolic acid B treatment group (SAB). Each group had 6 hair follicles. SAB group SAB mother liquor prepared with PBS was added to give a final concentration of 50. Mu.g/ml. Fresh medium was changed every two days and cultivation was continued for 6 days. Meanwhile, the hairs are photographed, the lengths of the hair shafts are measured, and the difference of the growth rates of different groups of hairs and the difference of the growth periods of hair follicles are evaluated.
(3) Detection of proliferation activity of hair papilla cells: hair papilla cells were grown in DMEM medium containing 10% fetal bovine serum at 37 ℃ with 5% CO 2 Culturing in an incubator. Control cells were cultured only with DMEM and SAB-treated cells were supplemented with SAB to a final concentration of 50. Mu.g/ml. The cell proliferation detection is carried out by using a cell real-time analysis detection system xCELLigence of Roche company. And (3) staining different groups of cells by using DCFH fluorescent dye, and judging the ROS level of the cells by fluorescence intensity.
Test results:
we have found, using the depilatory mouse model, that SAB significantly promotes hair growth, more rapidly promotes hair entry into anagen phase (figure 1), demonstrating the efficacy of SAB in promoting hair growth and its activity. In vitro hair follicle cultures found that SAB promoted human hair shaft growth, with significant differences between model and SAB groups (fig. 2). In addition, the invention performs in vitro cell research on key cells in hair follicle, namely hair papilla cells, and adopts DCFH fluorescent staining, which shows that SAB can significantly promote proliferation of hair papilla cells and can reduce the level of active oxygen in hair papilla cells (figure 3).

Claims (3)

1. Application of salvianolic acid B in preparing medicine for treating alopecia is provided.
2. The use according to claim 1, wherein the salvianolic acid B is represented by formula i:
3. the use according to claim 1 or 2, wherein the alopecia treating effect is an effect of increasing hair follicle activity and promoting hair growth.
CN202311111086.0A 2023-08-30 2023-08-30 Application of salvianolic acid B in preparing medicament for treating alopecia Pending CN116999427A (en)

Priority Applications (1)

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CN202311111086.0A CN116999427A (en) 2023-08-30 2023-08-30 Application of salvianolic acid B in preparing medicament for treating alopecia

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202311111086.0A CN116999427A (en) 2023-08-30 2023-08-30 Application of salvianolic acid B in preparing medicament for treating alopecia

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CN116999427A true CN116999427A (en) 2023-11-07

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