Hydrolyzed Hyaluronic Acid: properties, uses, pros, cons, safety

Hydrolyzed Hyaluronic Acid is a chemical compound, a form of hyaluronic acid used in various cosmetic and personal care products. It is derived from hyaluronic acid through hydrolysis using acid, enzymes, or other methods. This process enhances its moisturizing and penetration properties, providing deep hydration and improving skin texture.

Chemical Composition and Structure

Hydrolyzed Hyaluronic Acid is a hydrolysate of hyaluronic acid, obtained by breaking down hyaluronic acid molecules into smaller fragments through hydrolysis. This process can be performed using acids, enzymes, or other hydrolytic methods. The resulting chemical structure consists of shorter chains of hyaluronic acid, which allow for better skin penetration and enhanced moisturizing effectiveness.

Physical Properties

Hydrolyzed Hyaluronic Acid typically appears as a white or off-white powder that is highly soluble in water. When hydrated, it forms a clear and viscous solution that provides a smooth, non-greasy texture, making it suitable for various cosmetic formulations. Its reduced molecular size allows for deeper penetration into the skin layers, enhancing hydration and skin firmness.

Chemical Industrial Synthesis Process

• Preparation of reagents. The main raw materials include hyaluronic acid (HA), distilled water, and a hydrolytic agent such as an acid (e.g., hydrochloric acid), an enzyme (e.g., hyaluronidase), or another method of hydrolysis.
• Solubilization. Hyaluronic acid is solubilized in distilled water to obtain a hyaluronic acid solution.
• Acid hydrolysis.

If using an acid: The acid, such as hydrochloric acid (HCl), is added to the hyaluronic acid solution under continuous stirring. The mixture is heated to a controlled temperature (approximately 40-60°C) for a specified time to allow the hydrolysis reaction.

• Enzymatic hydrolysis.

If using an enzyme: The enzyme, such as hyaluronidase, is added to the hyaluronic acid solution under continuous stirring. The mixture is maintained at an optimal temperature for enzymatic activity (approximately 30-37°C) for a specified time.

• Hydrolysis by other methods.

If using another hydrolysis method: Follow the specific reaction conditions for the hydrolytic agent used.

• Neutralization. After hydrolysis, if an acid was used, the mixture is neutralized with a base, such as sodium hydroxide (NaOH), to reach a neutral pH.
• Filtration. The hydrolyzed solution is filtered to remove any solid impurities or inactivated enzymes.
• Concentration. The filtered solution is concentrated by vacuum evaporation to obtain a more concentrated hydrolyzed hyaluronic acid solution.
• Drying. The concentrated solution is dried by lyophilization to obtain a dry product.
• Grinding. The dried product is ground to obtain a fine and uniform powder.
• Classification. The dried powder is classified to ensure a uniform particle size. This step may involve sieving or the use of air classifiers.
• Stabilization. The hydrolyzed hyaluronic acid is stabilized to ensure its stability during transportation and storage, preventing aggregation and degradation.
• Quality control. The hydrolyzed hyaluronic acid undergoes rigorous quality testing to ensure it meets standards for purity, safety, and functionality. These tests include chemical analysis, spectroscopy, and physical tests to determine particle size and rheological properties.

What it is used for and where

Cosmetics - INCI Functions

Hair conditioning agent. A significant number of ingredients with specific and targeted purposes may co-exist in hair shampoo formulations: cleansers, conditioners, thickeners, matting agents, sequestering agents, fragrances, preservatives, special additives. However, the indispensable ingredients are the cleansers and conditioners as they are necessary and sufficient for hair cleansing and manageability. The others act as commercial and non-essential auxiliaries such as: appearance, fragrance, colouring, etc. Hair conditioning agents have the task of increasing shine, manageability and volume, and reducing static electricity, especially after treatments such as colouring, ironing, waving, drying and brushing. They are, in practice, dispersants that may contain cationic surfactants, thickeners, emollients, polymers. The typology of hair conditioning agents includes: intensive conditioners, instant conditioners, thickening conditioners, drying conditioners. They can perform their task generally accompanied by other different ingredients.

Humectant. Hygroscopic compound used to minimise water loss in the skin and to prevent it from drying out by facilitating faster and greater absorption of water into the stratum corneum of the epidermis.  The epidermis is the most superficial of the three layers that make up human skin (epidermis, dermis and hypodermis) and is the layer that maintains hydration in all three layers. In turn, the epidermis is composed of five layers: horny, the most superficial, granular, spinous, shiny, and basal. Humectants have the ability to retain the water they attract from the air in the stratum corneum and have the function of moisturising the skin. They are best used before emollients, which are oil-based.

Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Applications

Moisturizers and Creams: Hydrolyzed Hyaluronic Acid is widely used in moisturizers and creams for its ability to provide deep and long-lasting hydration. It helps maintain skin moisture and improve skin elasticity.

Anti-Aging Products: Due to its ability to penetrate deeply into the skin, this ingredient is commonly found in anti-aging products. It helps reduce the appearance of wrinkles and fine lines, improving skin texture and radiance.

Serums and Essences: In serums and essences, Hydrolyzed Hyaluronic Acid acts as a powerful hydrating agent, enhancing the penetration and effectiveness of active ingredients. It provides immediate and long-term hydration, making the skin smoother and more radiant.

Hair Care Products: It is also used in hair care products such as shampoos and conditioners to improve hair hydration and shine, making hair softer and more manageable.

Eye Care: The ingredient is ideal for use in eye creams and gels due to its gentle yet effective moisturizing properties, helping to reduce puffiness and dark circles.

Safety 

Hydrolyzed Hyaluronic Acid is generally considered safe for use in cosmetic and personal care products. It is non-irritating and suitable for all skin types, including sensitive skin. The ingredient is biodegradable and poses minimal risk to the environment when disposed of properly. As with all cosmetic ingredients, it is important to use it within the recommended guidelines to ensure safety and efficacy.

Hyaluronic acid (HA) is a polysaccharide belonging to the class of glycosaminoglycans, involved in tissue repair processes and in their regeneration. It is a fundamental component of the extracellular matrix, which contributes to an optimal performance of the repair processes by providing the appropriate degree of hydration, which facilitates cell migration (1).

 Hyaluronic acid is a natural component present in abundance in load-bearing joints of the human body (2), has the property of retaining skin moisture (3), has anti-inflammatory, antioxidant, and antibacterial effects for the treatment of periodontal diseases ( 4). However, the lubricating effect of hyaluronic acid is generally of short duration and the duration of its biological effects is not predictable (5).

References__________________________________________________________________________

(1) Laliscia C, Delishaj D, Fabrini MG, Gonnelli A, Morganti R, Perrone F, Tana R, Paiar F, Gadducci A. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit? J Contemp Brachytherapy. 2016 Dec;8(6):512-517. doi: 10.5114/jcb.2016.64511.

Abstract. Purpose: The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT).....Conclusions: These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.

(2) Correia CR, Moreira-Teixeira LS, Moroni L, Reis RL, van Blitterswijk CA, Karperien M, Mano JF. Chitosan scaffolds containing hyaluronic acid for cartilage tissue engineering. Tissue Eng Part C Methods. 2011 Jul;17(7):717-30. doi: 10.1089/ten.tec.2010.0467.

Abstract. Scaffolds derived from natural polysaccharides are very promising in tissue engineering applications and regenerative medicine, as they resemble glycosaminoglycans in the extracellular matrix (ECM). In this study, we have prepared freeze-dried composite scaffolds of chitosan (CHT) and hyaluronic acid (HA) in different weight ratios containing either no HA (control) or 1%, 5%, or 10% of HA. We hypothesized that HA could enhance structural and biological properties of CHT scaffolds. To test this hypothesis, physicochemical and biological properties of CHT/HA scaffolds were evaluated. Scanning electron microscopy micrographs, mechanical properties, swelling tests, enzymatic degradation, and Fourier transform infrared (FTIR) chemical maps were performed. To test the ability of the CHT/HA scaffolds to support chondrocyte adhesion and proliferation, live-dead and MTT assays were performed. Results showed that CHT/HA composite scaffolds are noncytotoxic and promote cell adhesion. ECM formation was further evaluated with safranin-O and alcian blue staining methods, and glycosaminoglycan and DNA quantifications were performed. The incorporation of HA enhanced cartilage ECM production. CHT/5HA had a better pore network configuration and exhibited enhanced ECM cartilage formation. On the basis of our results, we believe that CHT/HA composite matrixes have potential use in cartilage repair.

(3) Kablik J, Monheit GD, Yu L, Chang G, Gershkovich J. Comparative physical properties of hyaluronic acid dermal fillers. Dermatol Surg. 2009 Feb;35 Suppl 1:302-12. doi: 10.1111/j.1524-4725.2008.01046.x.

Abstract. Background: Hyaluronic acid (HA) fillers are becoming the material of choice for use in cosmetic soft tissue and dermal correction. HA fillers appear to be similar, but their physical characteristics can be quite different. These differences have the potential to affect the ability of the physician to provide the patient with a natural and enduring result.....Conclusion: Combining the objective factors that influence filler performance with clinical experience will provide the patient with the optimal product for achieving the best cosmetic result. A careful review of these gel characteristics is essential in determining filler selection, performance, and patient expectations.

(4)  Jentsch H, Pomowski R, Kundt G, Göcke R. Treatment of gingivitis with hyaluronan. J Clin Periodontol. 2003 Feb;30(2):159-64. doi: 10.1034/j.1600-051x.2003.300203.x. 

Abstract. Objectives: Hyaluronic acid (hyaluronan) is a glycosaminoglycan with anti-inflammatory and antiedematous properties. It was evaluated in a gel formulation for its effect in the treatment of plaque-induced gingivitis.....Conclusions: These data suggest that a hyaluronan containing gel has a beneficial effect in the treatment of plaque-induced gingivitis.

(5) Huang YC, Huang KY, Yang BY, Ko CH, Huang HM. Fabrication of Novel Hydrogel with Berberine-Enriched Carboxymethylcellulose and Hyaluronic Acid as an Anti-Inflammatory Barrier Membrane. Biomed Res Int. 2016;2016:3640182. doi: 10.1155/2016/3640182. 

 Abstract. An antiadhesion barrier membrane is an important biomaterial for protecting tissue from postsurgical complications. However, there is room to improve these membranes. Recently, carboxymethylcellulose (CMC) incorporated with hyaluronic acid (HA) as an antiadhesion barrier membrane and drug delivery system has been reported to provide excellent tissue regeneration and biocompatibility. The aim of this study was to fabricate a novel hydrogel membrane composed of berberine-enriched CMC prepared from bark of the P. amurense tree and HA (PE-CMC/HA). In vitro anti-inflammatory properties were evaluated to determine possible clinical applications. The PE-CMC/HA membranes were fabricated by mixing PE-CMC and HA as a base with the addition of polyvinyl alcohol to form a film. Tensile strength and ultramorphology of the membrane were evaluated using a universal testing machine and scanning electron microscope, respectively. Berberine content of the membrane was confirmed using a UV-Vis spectrophotometer at a wavelength of 260 nm. Anti-inflammatory property of the membrane was measured using a Griess reaction assay. Our results showed that fabricated PE-CMC/HA releases berberine at a concentration of 660 μg/ml while optimal plasticity was obtained at a 30 : 70 PE-CMC/HA ratio. The berberine-enriched PE-CMC/HA had an inhibited 60% of inflammation stimulated by LPS. These results suggest that the PE-CMC/HA membrane fabricated in this study is a useful anti-inflammatory berberine release system.