Hyaluronic Acid Is Good for Skin Care Products

Hyaluronic acid (HA) is a polysaccharide composed of repeating units of N-acetyl-D-glucosamine and β-D-glucuronic acid linked by β-1,3-glycosidic bonds. The length and molecular weight of the hyaluronic acid molecule chain varies, The number of disaccharides is generally 300-11000 pairs, and the molecular weight ranges from 0.2 × 106 to 7.0 × 106. Hyaluronic acid is white, amorphous, odourless, and easily soluble in water, ether and other organic solvents. Its aqueous solution is acidic and negatively charged, and it moves towards the positive electrode during electrophoresis.

When the concentration is very high, hydrogen bonds form between the molecules, causing them to cross-link and exist in a network-like form. It has high viscoelasticity and osmotic pressure. In the 1930s, Mayer, a professor of ophthalmology at Columbia University in the United States, and others were the first to use an extraction method using animal tissue as a raw material to isolate hyaluronic acid from the vitreous body of a cow's eye. As one of the most widely distributed acidic mucopolysaccharides in the human body, hyaluronic acid is mainly found in the connective tissue matrix. and is one of the components of the skin. It has a good moisturising effect and is therefore widely used in cosmetics. It is known as the natural moisturising factor (NMF).

Hyaluronic acid binds to the CD44 receptor on cells and causes cell differentiation. When epidermal cells mutate into squamous cell carcinoma, the differentiation of epidermal cells also stops. Hyaluronic acid is a signalling substance that reflects cell physiology. It binds to receptors on the surface of epidermal cells to produce an irritating effect, which slows down differentiation towards apoptosis. Hyaluronic acid can remove reactive oxygen species generated by ultraviolet radiation in epidermal cells, thereby preventing skin damage. It is called an efficient scavenger of free radicals[1]. Free radicals cause lipid oxidation, and hyaluronic acid reacts with free radicals to decompose and then precipitate. Currently, the production of hyaluronic acid has been switched from extracting it from animal tissue to producing it using microbial fermentation, which has increased production and reduced costs[2].

1 Application of hyaluronic acid in cosmetics

1.1 Moisturising effect

The main function of hyaluronic acid in cosmetics is to hydrate and moisturise, and its advantages are that its moisturising properties are less affected by the surrounding environment and it can retain moisture for a long time. Hyaluronic acid has the highest moisture absorption capacity at low humidity compared to glycerin, etc. [3], while its moisture absorption capacity at high humidity is the lowest. This property can be used to suitably moisturise the skin in different seasons and environments with different humidity levels. Hyaluronic acid is rarely used alone as a moisturising agent, but is often used in combination with other moisturising agents.

1.2 Emulsifier

Hyaluronic acid and phospholipids can form a stable emulsion when mixed in the oil and water phases without the addition of other emulsifiers. The emulsifier composed of hyaluronic acid and phospholipids is characterised by its emulsifying and moisturising properties, which are unmatched by other emulsifiers. A safe and effective emulsifier like hyaluronic acid can be used in the preparation of various cosmetics [4].

1.3 Thickening agent

Hyaluronic acid (molecular weight 3000kD) solution has a high viscosity[5]. Similarly, polyoxyethylene (molecular weight 100 ~ 5000kD) is one of the common thickening agents in cosmetics. The viscosity of the mixture of the two is greater than the sum of their respective viscosities. Therefore, hyaluronic acid-polyoxyethylene solution is a good thickening agent with excellent moisturizing properties. It can be used in creams, lotions, and other cosmetics, and is especially suitable for making various translucent viscoelastic gels, such as shaving gels, eye gels, sunscreens, etc.[6].

1.4 Fragrance fixative

Hyaluronic acid has the characteristic of surrounding substances with molecular sacs, so it can be used in fragrance products. Hyaluronic acid can be used as a fixative to bind the fragrance, reducing the rate of fragrance volatilisation and making the fragrance last longer. It is suitable for use in perfumes and other cosmetics. Hyaluronic acid has two other advantages: ① it reduces the adverse stimulation of fragrances on sensitive skin; ② it prevents certain fragrances from reacting with skin secretions to prevent the formation of unpleasant odours in creams, lotions, gels, etc.[7]

1.5 The nutritional effects of hyaluronic acid

Hyaluronic acid forms a film on the skin surface, which is beneficial for the adsorption of active substances by the stratum corneum. Hyaluronic acid can directly penetrate the dermis, promote skin tissue metabolism, and transport nutrients, thereby improving the physiological properties of the skin, thus achieving an effective supply of nutrients and producing a nourishing skin function [25]. For example, in facial masks and facial cleansers.

1.6 The antibacterial and anti-inflammatory effects of hyaluronic acid

Animals containing a small amount of hyaluronic acid can inhibit bacteria and play an anti-inflammatory role. Hyaluronic acid has the characteristic of forming a film, which can easily form a hydrated film to separate bacteria and play an anti-inflammatory effect. In addition, proteins and hyaluronic acid combine to form protein complexes in the skin matrix. This substance is abundant in the intercellular spaces and can form a gel that binds cells, ensuring the normal metabolism and water retention function of cell tissue, preventing harmful substances from invading cells, preventing the occurrence of various infections, and providing a certain degree of protection for the skin[8]. It has a wide range of applications in cosmetology and clinical medicine.

1.7 The restorative effect of hyaluronic acid

Hyaluronic acid can repair cell damage [9]. Hyaluronic acid levels increase at the wound site. During the different stages of wound healing, hyaluronic acid and fibrin play structural and regulatory roles together. Hyaluronic acid and the fibrin matrix promote or induce cell migration and regulate the functions of many cells involved in the inflammatory process. At the same time, Hyaluronic acid has excellent moisturising properties, maintains the relative stability of skin moisture, maintains an appropriate intracellular and intercellular water content, ensures a relative balance and free movement of various nutrients (including inorganic salts), and provides wound healing [10-11]. Studies have shown that when the skin has ulcers and minor burns, applying products containing hyaluronic acid can relieve pain, accelerate wound healing, and reduce the occurrence of scars.

1.8 Sun protection with hyaluronic acid

Exposure to UV light can lead to lipid peroxidation, damage cell membranes and cause pigmentation [12]. It can also limit the access of enzymes that catalyse lipid peroxidation to cell membranes, thereby reducing the entry and exit of free radicals outside the cell. Skin care products containing hyaluronic acid can induce cell differentiation. Combining sun protection with hyaluronic acid has a synergistic effect, as in the case of the Yilian Multi-Whitening Sunscreen [13].

1.9 The lubricating effect of hyaluronic acid

Hyaluronic acid is a polysaccharide with good film-forming properties [14-16]. When used on the skin, hyaluronic acid skincare products can be observed to have a good lubricating effect. When hyaluronic acid is used, a hydrated film forms on the skin surface, giving the skin a lubricated feeling. This effect cannot be compared with that of other skincare products.

1.10 The cosmetic effect of hyaluronic acid

Hyaluronic acid is a glycosaminoglycan that is not species-specific, is a component of the human body and does not cause an immune response. Lipid injections containing it have good compatibility and high safety, and generally do not cause allergic reactions, making hyaluronic acid an ideal filler material. Hyaluronic acid is injected into the desired area to fill it from the inside, restoring the skin's original radiance [17-19].

2. Application of hyaluronic acid derivatives in cosmetics

Hyaluronic acid has a short residence time in vivo and in vitro, which affects its efficacy. Because it has multiple functional groups on the surface, including carboxyl groups, it can be chemically modified to give it better rheological properties and resistance to enzymatic hydrolysis, increasing its prospects for development in the cosmetics field. Since hyaluronic acid has multiple sites that can be modified, such as carboxyl groups and hydroxyl groups, it is easy to transform it into amphoteric derivatives [20-23].

2.1 Sodium hyaluronate

Sodium hyaluronate (SH) is the sodium salt of hyaluronic acid. It is white and fibrous, has good moisturising properties, is easily soluble in water but insoluble in organic solvents such as ether [24-25]. SH aqueous solution is fluid and has good rheological properties. According to research, the human body contains more than 70% water, and it is very important to maintain a large amount of water in the body [26]. As people age, the amount of SH in the skin decreases, which leads to a decrease in skin moisture, rough skin, loss of elasticity, and the appearance of wrinkles [27]. Exogenous SH can effectively supplement the skin's endogenous SH, thereby preventing skin aging and having a beautifying effect. At present, SH is widely used in moisturizing products such as skin creams and lotions [28-29]. In addition, SH has also begun to be used in the medical cosmetology industry, and various beauty and health products have already appeared abroad[30], such as Hylaform, which can effectively eliminate frown lines, smile lines, and wrinkles around the eyes and nose as an injection, and can also increase the width of the nose and make the lips plump and bright[31], making people look younger and more beautiful. Injections containing SH are hypoallergenic[32] and easy to promote.

2.2 Acetylated hyaluronic acid

The hydroxyl groups of hyaluronic acid can undergo acylation reactions with anhydrides or acid chlorides to form ester compounds. Takashi[33] reported a method for synthesising acetylated hyaluronic acid (Ac-Hyal) using acetic anhydride as the acylation reagent. The physicochemical properties of this substance vary depending on the degree of substitution of the acetyl group. The higher the degree of substitution, the stronger the hydrophobicity of Ac-Hyal. Compared to hyaluronic acid, Ac-hyaluronic acid compounds exhibit superior moisturising and skin-softening properties when the degree of substitution is 3.0. As Ac-hyaluronic acid is soluble in organic solvents such as a 90% ethanol solution, it can be used as a superior moisturiser in both water-based and oil-based cosmetics [33-35].

2.3 Hyaluronate esters

Kana et al. [36-38] used acid hyaluronan or hyaluronan-TBA to react with trimethylsilyldiazomethane in the presence of dimethyl sulfoxide (DMSO) and methanol to form methyl hyaluronate. After methylation, hyaluronan's resistance to hyaluronidase degradation is enhanced. Methyl hyaluronate has different degrees of esterification, and its application fields are also different. It can be used in cosmetics, biomedicine, wound healing, various forms of tissue engineering scaffolds such as dressings, films, fibers and other broader fields. Lipoic acid (LA) is a biocompatible active molecule that can be rapidly degraded in the body. Picotti et al. [39] 40 - combined with LA to prepared a lipoic acid hyaluronic acid gel (Lipohyal). Lipohyal can be used in the cosmetics field for moisturising and anti-ageing, and also as an adjuvant to treat skin damage, such as burns, ulcers, wounds, dermatitis, radiation-induced skin hyperthermia, etc.

2.4 Hyaluronic acid hydrazide derivatives

After the adipic acid dihydrazide (ADH) compound is linked to hyaluronic acid, the remaining -NH2 can be linked to other carboxyl groups in the hyaluronic acid molecule, cross-linking the hyaluronic acid molecules within or between molecules. After the solvent evaporates, the soft, fluid gel can be modified into a hyaluronic acid hydrogel film with greater mechanical hardness, soluble and biodegradable hyaluronic acid hydrogel film with good biocompatibility. In addition, He Yanli et al. [41-43] also studied the biocompatibility of hyaluronic acid-ADH films and concluded that they have good resistance to enzymatic hydrolysis and biocompatibility.

Under the catalysis of acid, disulfide is refluxed into diester in ethanol, and diester is hydrolyzed into corresponding dihydrazine [44]. Shu et al. used hyaluronic acid and disulfide to cross-link and prepare a gel film, which showed great potential value in clinical applications such as wound healing and tissue repair after performance testing.

Zhang Wenqiang et al. [45-48] added hyaluronic acid to sodium tripolyphosphate (STMP) at a certain mass ratio, stirred well in a three-necked flask, allowed it to rapidly stir at pH 10 and 50 °C for 12 h, then subjected the resulting solution to two-stage dialysis with distilled water, purified it, and formed a film at room temperature. The water absorption capacity of the resulting film decreases, its water retention performance improves, and the film has better resistance to degradation. Both water retention performance and degradation resistance improve with increasing degree of cross-linking.

3 Prospects

At present, with the continuous development of the cosmetics industry, the pursuit of natural and safe cosmetic ingredients has become a future development trend. The continuous expansion of the application fields of hyaluronic acid and the development and application of its derivatives will inevitably become a research hotspot. In particular, China's cosmetics industry started late, and most raw materials need to be imported. The development of hyaluronic acid derivatives with new functions, high efficiency and non-toxicity has become one of the urgent problems to be solved in the development of China's cosmetics industry.

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