CN110882173A - Formula of external daily chemical for preventing and treating alopecia by targeting hair follicle stem cells - Google Patents

Formula of external daily chemical for preventing and treating alopecia by targeting hair follicle stem cells Download PDF

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CN110882173A
CN110882173A CN201911235567.6A CN201911235567A CN110882173A CN 110882173 A CN110882173 A CN 110882173A CN 201911235567 A CN201911235567 A CN 201911235567A CN 110882173 A CN110882173 A CN 110882173A
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formula
stem cells
hair follicle
follicle stem
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CN110882173B (en
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贺鑫
王文娟
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Northwest A&F University
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    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
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Abstract

The invention discloses an external daily chemical product for preventing and treating alopecia by targeting hair follicle stem cells, which belongs to the technical field of daily chemicals, and the final concentration of the components of a formula is 1-40mmol/L of L-cysteine, 5-400 mu mol/L of resveratrol, α -tocopherol, 2-600 mu mol/L of ascorbic acid, 4-20mmol/L of astaxanthin, 2-50 mu mol/L of astaxanthin, 1-20mmol/L of L-lactic acid and 0.5-30 mu mol/L of D-biotin.

Description

Formula of external daily chemical for preventing and treating alopecia by targeting hair follicle stem cells
Technical Field
The invention belongs to the technical field of daily chemicals, and relates to an external daily chemical formula for preventing and treating alopecia by targeting hair follicle stem cells.
Background
Hair has a key-modifying effect on the appearance of humans, and thus hair loss seriously affects the quality of life. Pathological alopecia refers to abnormal or excessive hair loss, and is the root cause of the abnormal or excessive hair loss, namely, the physical, chemical or biological factors induce the damage of hair follicle stem cells or accelerate the aging process of the hair follicle stem cells. The differentiation of hair follicle stem cells produces the hair itself, so that it is the basis for the growth of hair, and its damage and aging cause a serious problem of alopecia.
About 10% of oxygen consumed by hair follicle stem cells is converted into reactive oxygen species and related free radicals, and the high reactivity thereof generates extensive protein and DNA damage, thus greatly accelerating the aging progress of the stem cells. Because of the problems of increased life expectancy, increased environmental pollution, overnutrition of the population and the like, the factors of aging, toxin damage, endocrine imbalance, lipid metabolism disorder and the like which induce reactive oxygen species damage become more serious day by day, and further, the serious problems of continuous rising of the incidence rate of alopecia, gradual reduction of the incidence age and the like are caused. The data of the world health organization show that the incidence rate of alopecia of young and middle-aged men in China is increased by more than 10 times compared with that before 20 years, and more than 12 percent of people have alopecia symptoms, wherein the alopecia ratio before 30 years is up to 84 percent.
However, the existing alopecia prevention and treatment schemes pay less attention to the hair follicle stem cells, and few technologies aiming at the hair follicle stem cells cannot solve the problems from the core reason of hair follicle stem cell damage and cell structure updating, so the prevention and treatment effect is poor. For example, patent application No. 201910070671.8, by isolating the patient's own hair follicle stem cells, expanding in vitro culture, and then autologous transplantation; the technology has high cost and poor reliability, the cell transplantation has carcinogenic risk, and the key problem of autologous stem cell damage and aging is not solved. There is also a patent of using a hair tonic containing a stem cell growth factor and a plant extract and a method of using the same (application No. 201811513545.7), which claims that hair loss can be treated by making a spray solution using a stem cell growth factor and a plant extract; however, the stem cell factor is difficult to prepare and store, and the quality control of the product is difficult, so that the method has the problems of high price, unstable effect and the like.
Disclosure of Invention
The invention aims to provide an external daily chemical formula for preventing and treating alopecia by relieving active oxygen cluster damage and improving stem cell proliferation activity, which comprises 1-40mmol/L of L-cysteine, 5-400 mu mol/L of resveratrol, α -tocopherol, 4-20mmol/L of ascorbic acid, 2-50 mu mol/L of astaxanthin, 1-20mmol/L of L-lactic acid and 0.5-30 mu mol/L of D-biotin.
All components of the formula are required to be extracted from plants or microorganisms, so that the pure natural sources of the raw materials are ensured, and the safety coefficient of the formula is improved; but the relevant extraction process is not in the scope of patent protection. The preparation method adopts the prior art and can be obtained by mixing all the components of the formula.
The components in the formula have definite molecular structures and stable physicochemical properties, and the theoretical speculation and the experiment prove that the problem of mutual interference does not exist, so that the preparation method has no special requirements on the adding sequence of the components and the like.
The L-cysteine is a basis for synthesizing small molecular sulfhydryl compounds such as glutathione and the like in vivo, regulates key processes such as cell iron death and the like, and is also one of chemical bases of the hair follicle stem cells for resisting aging and toxin damage. The L-cysteine used in the formula can obviously improve the proliferation and differentiation activity of the hair follicle stem cells, so as to play a role in preventing and treating alopecia, and in addition, the cysteine is also a nutrient substance which is greatly consumed in hair growth. The L-cysteine used in the formula is required to be extracted from animal hair by enzymolysis.
The existing research shows that the resveratrol compound has the effects of oxidation resistance, inflammation resistance, cancer resistance, cardiovascular protection and the like, and can also protect mitochondria from being damaged by reactive oxygen species, and the invention also proves that the resveratrol compound can improve the proliferation activity of hair follicle stem cells; the resveratrol used in the formula is obtained by extracting traditional Chinese medicine plants such as giant knotweed rhizome and the like.
α -tocopherol is the most active vitamin E subtype, is also a nonpolar antioxidant with extremely high safety, and can be used for preventing and treating infertility, burn, cold injury, climacteric syndrome, etc. the invention proves that it can effectively resist lipid peroxidation and promote the proliferation activity of hair follicle stem cells, and the formula requires α -tocopherol to be extracted from olive oil, etc.
Ascorbic acid, also known as vitamin C, is a safe and low-toxicity polar phase antioxidant, and can be used as a hydrogen donor to effectively scavenge free radicals in an aqueous phase system. The early work of the invention finds that the cysteine can be reduced into the cysteine, and the important protein is protected from being damaged by free radicals, so that the proliferation activity of the hair follicle stem cells can be effectively improved. The formula is obtained by extracting plants such as Chinese date with ascorbic acid.
Astaxanthin is a mauve crystal carotenoid, the capacity of quenching singlet oxygen and capturing free radicals of the astaxanthin is more than 10 times higher than that of β -carotene, and the astaxanthin is internationally applied to the fields of health-care food, high-grade cosmetics, medicines and the like.
The previous work of the invention proves that the concentration of lactic acid in the culture solution is improved, the proliferation activity of hair follicle stem cells can be stimulated, and the formula of the L-lactic acid is required to be extracted by a microbial enzyme fermentation method.
D-biotin, also known as vitamin H, vitamin B7 or coenzyme R, has physiological functions of preventing skin diseases, promoting lipid metabolism and the like, is widely applied at present, and is recognized to be capable of effectively preventing and treating hair loss and juvenile poliosis. The formulation with D-biotin requires extraction from microbial fermentive fermentation. Compared with the prior art, the invention has the following advantages:
on the aspect of safety, all components of the formula are from recognized low-toxicity compounds, and the toxicity of hair follicle stem cells of the formula is specially checked in a preliminary experiment, so that the use dose is ensured not to exceed 5% of a toxicity threshold value; the effect is increased by means of a small dose of the composite formulation. In addition, all components of the formula are extracted from plants or microorganisms, so that the pure natural sources of the raw materials are ensured, and the safety factor of the formula is further improved.
On the action mechanism and effect, by targeting hair follicle stem cells, on one hand, the active oxygen radical scavenger with polarity and non-polarity phases is comprehensively applied, the microenvironment and intracellular free radical level of the hair follicle stem cells are reduced, and the hair follicle stem cells are prevented from being damaged; on the other hand, by improving the proliferation activity of the hair follicle stem cells (the highest is improved by 135%, compared with the formula A, the formula B and the formula C on the market, the proliferation activity is improved by more than 70%), the updating frequency of important organelles and related structures is greatly increased, the related cell structures need to be duplicated before the cells divide each time, so that the aged and damaged cell structures can be diluted, the cell structures are one of basic mechanisms of the stem cells for resisting aging, and finally the alopecia problem can be radically cured.
In the subsequent development, the high-flux hair follicle stem cell proliferation activity detection method is utilized, statistical analysis is carried out on the basis of obtaining a large amount of data, and the action range and the toxicity threshold value of each component of the formula are accurately ascertained, so that the final concentration of each component has certain latitude, and the product development and marketing are facilitated.
Drawings
FIG. 1 is final concentration gradient data for L-cysteine;
figure 2 is final concentration gradient data for resveratrol;
FIG. 3 is α -tocopherol final concentration gradient data;
FIG. 4 is final concentration gradient data for ascorbic acid;
FIG. 5 is data of final concentration gradient of astaxanthin;
FIG. 6 is final concentration gradient data for L-lactic acid;
FIG. 7 is final concentration gradient data for D-biotin;
FIG. 8 is comparative study data of the inventive formulation with a commercially popular formulation.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to the accompanying drawings and the detailed description.
Example 1 basis and safety assessment experiments for concentration ranges in formulations of the invention
Based on literature search and previous experimental research of the inventor, the concentration gradient of a certain component in a formula is selected to carry out a CCK8 cell viability experiment, data of 6 independent experiments are used for carrying out T test, P & lt 0.05 is taken as a difference significance standard, the onset and actual effect range of the component in the formula are analyzed, in order to improve the safety of the formula, the lowest dose of P & lt 0.01 is taken as a toxicity dose threshold of the component, and the following data are obtained:
FIG. 1 is a graph showing final concentration data of L-cysteine (effective range of 1-40mmol/L, toxicity threshold of 800mmol/L, which is 20 times or more of the maximum effective dose, and is excellent in safety), FIG. 2 is a graph showing final concentration data of resveratrol (effective range of 5-400. mu. mol/L, toxicity threshold of 6000. mu. mol/L, which is 15 times or more of the maximum effective dose, and is excellent in safety), FIG. 3 α is a graph showing final concentration data of tocopherol (effective range of 20-600. mu. mol/L, toxicity threshold of 8000. mu. mol/L, which is 13 times or more of the maximum effective dose, and is excellent in safety), FIG. 4 is a graph showing final concentration data of ascorbic acid (effective range of 4-20mmol/L, toxicity threshold of 400mmol/L, which is 20 times or more of the maximum effective dose, and is excellent in safety), FIG. 5 is a graph showing final concentration data of astaxanthin (effective range of 2-50mmol/L, toxicity threshold of 1000mmol/L, which is 20 times or more of the maximum effective dose, which is excellent in safety), FIG. 6 is a graph showing final concentration data of astaxanthin (effective range of 1-30L, which is 30.1-30 mmol/L, which is 0.7 times or more of the maximum effective dose, and is 0.9 times or more of the maximum effective dose, and is excellent in safety).
Example 2 Effect data of the inventive formulations at optimal concentrations
According to the method for measuring cell viability in example 1, the optimal concentration of each component is taken on the basis of the data, and the formula is compared with a commercially popular formula (6 independent experiments show that the formula can finally increase the cell viability of the hair follicle stem cells by 217.5 percent and increase the cell viability by 78.3 percent compared with the best commercially available formula).
The above description is only a preferred embodiment of the present invention, and the scope of the present invention is not limited thereto, and any simple modifications or equivalent substitutions of the technical solutions within the scope of the present invention disclosed by the present invention, which can be obviously obtained by those skilled in the art, should also be considered as the scope of the present invention.

Claims (1)

1. An external daily chemical for preventing and treating alopecia by targeting hair follicle stem cells is characterized in that the final concentration range of each component of the formula of the daily chemical is 1-40mmol/L of L-cysteine, 5-400 mu mol/L of resveratrol, 20-600 mu mol/L of α -tocopherol, 4-20mmol/L of ascorbic acid, 2-50 mu mol/L, L-1-20 mmol/L, D-biotin.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112294791A (en) * 2020-11-06 2021-02-02 中国海洋大学 Application of astaxanthin ester in hair growth promoting product
CN114917181A (en) * 2022-05-16 2022-08-19 中国海洋大学 Separable microneedle patch and preparation method and application thereof

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