阅读说明：本技术 化合物与微生素e的组合在制备抗衰老药物或者化妆品中的用途 (Application of combination of compound and vitamin E in preparation of anti-aging drugs or cosmetics ) 是由 张海涛 王青 于 2020-09-12 设计创作，主要内容包括：本发明涉及涉及抗衰老抗氧化的化合物与微生素E的组合在制备药物或者抗衰老化妆品中的用途。本发明通过实验发现式(I)化合物和微生素E的组合具有较好的抗氧化效果,具有防止细胞衰老的功能。通过将所述的化合物和微生素E的组合制备成为相应的防衰老药物或者防衰老化妆品具有较好的商业价值。(The invention relates to application of a combination of an anti-aging and anti-oxidation compound and vitamin E in preparation of a medicament or an anti-aging cosmetic. Experiments show that the combination of the compound shown in the formula (I) and the vitamin E has a good antioxidant effect and has a function of preventing cell aging. The combination of the compound and the vitamin E has good commercial value when being prepared into the corresponding anti-aging medicament or anti-aging cosmetic.)

1. Use of a compound of formula (I) in combination with vitamin E in the manufacture of a medicament for the treatment of cellular oxidation and cellular senescence; the compound has a structural formula as follows:

2. use according to claim 1, characterized in that: the medicament further comprises a pharmaceutically acceptable carrier.

3. Use according to claim 1 or 2, characterized in that the medicament is in unit dosage form, such as tablets, pills, capsules, powders, granules, suspensions, metered aerosol or liquid sprays, drops, ampoules, transdermal patches.

4. Use according to claim 3, characterized in that said cells are human epidermal keratinocytes.

5. Use of a compound of formula I in combination with vitamin E for the preparation of a cosmetic product for preventing skin aging; the compound has a structural formula as follows:

6. use according to claim 5, characterized in that the cosmetic product also contains a whitening component.

7. Use according to claim 6, characterized in that the cosmetic product is in the form of an emulsion.

Technical Field

The invention belongs to the field of medicines, and particularly relates to application of a combination of an anti-aging and anti-oxidation compound and vitamin E in preparation of medicines or anti-aging cosmetics.

Background

The anti-aging mechanism is one of the hot topics studied at present, and with the continuous development of biochemistry and molecular biology technologies, researches related to cell aging such as oxygen radicals, antioxidants, stem cell technologies, telomeres, genes and the like are more and more emphasized, and become hot spots of anti-aging researches. The study demonstrated that age was related toThe generation of free radicals in the cells is increased, the free radicals have destructive effect on the cells, and the next generation of damaged cells is damaged, so that the damage and death of the cells are increased, thereby causing aging. In the experimental research of anti-aging, peroxisome exists in the organism, and the main function of peroxisome is to generate and eliminate H ₂0₂Has the important function of preventing active oxygen damage in vivo. How to reduce the generation of free radicals is also a hot issue in the present research.

Research shows that in the aging process, harmful factors such as external physical damage, biochemical poison, DNA replication error in vivo, spontaneous hydrolysis reaction, Reactive Oxygen Species (ROS) and the like continuously damage DNA, so that gene mutation, translocation, telomere shortening, chromosome number abnormality and the like are caused, and the integrity and stability of a genome are damaged. Accumulation of somatic mutations can be observed in cells of an aging body. In order to maintain the stability of genome, the body develops a complex DNA repair mechanism, if the repair mechanism is destroyed, the aging of the body and the occurrence of related diseases are accelerated, and a plurality of diseases which are shown as premature senility, such as xeroderma pigmentosum, Werner syndrome, Bloom syndrome, Cockayne syndrome and the like are all involved in the defect of the DNA damage repair mechanism. Along with the progress of aging, the expression level of the mitotic checkpoint gene BubR1 in tissues is reduced, and studies show that over-expression of BubR1 can ensure accurate separation of chromosomes in vivo and prolong the life of mice. In addition to nuclear genes, mitochondrial genes (mtDNA) play an important role in the aging process of the body. The DNA polymerase gamma is responsible for the replication of mtDNA, and the mutation or deletion of the mtDNA of the mouse knocked out by the DNA polymerase gamma gene is shown as premature senility and shortened life span. Unlike nuclear DNA, mtDNA lacks an integral repair mechanism, and early mutated mtDNA can clonally amplify, causing mitochondrial respiratory chain damage, thereby promoting the onset of senescence. The nuclear fiber layer provides a scaffold for nuclear membrane and chromatin, and also plays an important role in maintaining genome stability.

Cellular senescence refers to the arrest of the cell cycle, permanently disabling division. Aging is a process of decreased cell adaptation, cessation of proliferation and death, and the properties of tumor cells are opposite, but both are caused by progressive accumulation of lesions and are merely different in performance. Unlike quiescent and terminally differentiated cells, senescent cells are mainly characterized by the following characteristics: high expression of p16INK4a and p19ARF, cell cycle arrest at G1 phase; chromatin remodeling to form senescence-associated heterochromatin aggregates (SAHF); expressing senescence-associated β -galactosyl glycinase (SABG); DNA Damage Response (DDR) persists with increased expression of P53. However, increasing the expression of P16. sup. INK4a, P19. sup. ARF, and P53 in mice can not only inhibit tumor but also prolong life span, and decrease the expression of P53 can accelerate aging, because cellular aging is also a compensatory mechanism of the body. The immune system can recognize and eliminate senescent cells, progenitor cells in tissues are differentiated to form young cells to replace the senescent cells, decay or diffusion of potential harmful cells such as tumor cells is prevented, but as the body ages, cell aging is accelerated, the elimination of the senescent cells by the immune system is slowed, and the number of the senescent cells in the body is increased. The phenomenon that senescent cells act on surrounding cells by secreting pro-inflammatory factors and matrix metalloproteinases is called the senescence-associated secretory phenotype (SASP). SASP and NF-kB are over activated, the immune system is disordered, autophagy function is reduced and other factors act on the body together to cause inflammatory aging. Many inflammatory factors such as IL-1, Tumor Necrosis Factor (TNF), interferon, etc. are present in increasing amounts in the aging body. Inflammatory aging is associated with the development of many ARD's, such as atherosclerosis, type 2 diabetes, alzheimer's disease, tumors, and the like. The aged mice tend to be younger by inhibiting NF- κ B through drug or gene manipulation. The expression of NF-. kappa.B in the hypothalamus results in a decrease in the secretion of gonadotropin-releasing hormone (GnRH), thereby promoting aging of the body. The long-term aspirin administration can prolong the life of mice and promote the healthy aging of human bodies.

Many anti-aging drugs are researched at present, and many drugs play an anti-aging role by acting on signal paths related to aging, and representative drugs comprise rapamycin, metformin, resveratrol and the like. Rapamycin is a novel immunosuppressant, and acts on mTOR to inhibit the mTOR signaling pathway, so that the downstream production of mTORC1 and S6K is reduced, and the anti-aging effect is achieved. The medicine can prolong the life of mouse by 60%, and the rapamycin analog RAD001 can improve the immunosenescence of the elderly. Rapamycin causes side effects including cataract, hematopoietic dysfunction, metabolic disorders (e.g., hyperglycemia, hyperinsulinemia, insulin resistance), etc., some of which are due to the fact that rapamycin inhibits mTORC1 as well as mTORC 2. However, whether rapamycin or its analogs, there is currently a lack of sufficient clinical evidence to demonstrate its anti-aging effects in humans. Metformin is a common drug for treating type 2 diabetes in clinic, and the incidence of cardiovascular diseases and cancers can be reduced by taking the drug for a long time. Metformin can prolong the life of nematodes and mice, and the anti-aging effect is considered to be related to activation of AMPK pathway, so that the anti-aging effect of metformin in human body is to be proved by further clinical tests. Resveratrol is a polyphenol compound, can improve the activity of SIRT1, and maintains the normal function of mitochondrial respiratory chain. Resveratrol can prolong the life of mice on high-fat diet but can not prolong the life of mice on normal diet, and the metabolic disorder can be improved by administering resveratrol to obese people, while the metabolic function of the body can not be enhanced by adding resveratrol to non-obese women with normal sugar tolerance. Spermidine is a polyamine, can prolong the life of yeast, Drosophila and mouse, has autophagy inducing effect, and can improve memory of aged Drosophila and improve cardiovascular health of mouse.

CN103936608B discloses a novel chalcone compound with anti-aging effect, which can obviously inhibit H₂O₂A decrease in induced telomerase activity; can be used as raw material medicine for preparing various dosage forms of medicines related to delaying senility or regulating immunity and promoting brain function; can be used as raw material medicine for preparing various dosage forms of medicines related to delaying senility or regulating immunity and promoting brain function.

Although some anti-aging drugs exist at present, the types and types of drugs are not abundant enough, and the selection opportunities are not many, so that continuous research and development are needed to meet the social needs.

Disclosure of Invention

The invention overcomes the defects of the prior art and provides a new application of a new compound capable of delaying senility.

When the applicant researches skin anti-aging, the existing compound library is utilized to carry out specific screening on skin cells, and the compound capable of delaying skin cell aging is obtained.

The compound is of formula (I):

the compounds of formula I are typically used in the form of pharmaceutical compositions comprising one or more compounds of formula I and a pharmaceutically acceptable carrier. Preferably, these compositions are in unit dosage forms, such as tablets, pills, capsules, powders, granules, suspensions, metered aerosol or liquid sprays, drops, ampoules, transdermal patches; for painting or coating or otherwise administering the drug.

The principal active ingredients are typically mixed in a pharmaceutically acceptable carrier such as conventional tableting ingredients, for example corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate and dicalcium phosphate, or gums, dispersants, suspending agents or surfactants such as sorbitan monooleate and polyethylene glycol, and other pharmaceutically acceptable diluents such as water, to form a homogeneous preformulation composition containing the compound of the invention or a pharmaceutically acceptable salt thereof.

When referring to these preformulation compositions as homogeneous, it is meant that the active ingredient is dispersed evenly throughout the composition so that the composition may be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules.

In a further aspect, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier, a compound of formula I. Preferably, the pharmaceutical composition is in a unit dosage form suitable for topical administration, such as an ointment or spray.

Further, the application of the compound shown in the formula I in preparing a pharmaceutical composition for treating human epidermal keratinocyte senescence is also provided.

Further, the human epidermal keratinocytes are human epidermal keratinocytes commercialized in the art.

The invention also provides a cosmetic for preventing skin aging, which contains the compound shown in the formula I.

Further, the application of the compound in the formula I in preparing cosmetics for preventing skin aging is also provided.

Further, the most important contribution of the present invention is the discovery that the combination of a compound and microorganism E significantly enhances the antioxidant and anti-aging effects of the cells.

Advantageous effects

According to the invention, researches show that the combination of the compound shown in the formula (I) and the vitamin E has a good antioxidant effect and a function of preventing cell aging. The combination of the compound and the vitamin E has good commercial value when being prepared into the corresponding anti-aging medicament or anti-aging cosmetic.

Drawings

FIG. 1 results of the Effect of Compounds on ROS expression in human epidermal keratinocytes

FIG. 2H at different concentrations₂O₂Graph of results for human epidermal keratinocytes under injury

FIG. 3 Compound at H₂O₂Functional outcome map in injury

FIG. 4 Compound at H₂O₂Functional verification result diagram in injury

Detailed Description

The present invention is described in detail below by way of examples, it should be noted that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention, and those skilled in the art can make some insubstantial modifications and adaptations of the present invention based on the above-described disclosure.