The „Big 5“ active ingredients: COSSMA

Classics | Unlike in the modern and sometimes short-lived trend segment, medically oriented cosmetics rely on classics. Active ingredients, that have been used successfully for a long time and are considered to be stable. The following essay sheds light on the “Big Five” among the classics, their functional properties and the variants currently used in cosmetic products.

Hyaluronan

One of the evergreens from the functional group of “super moisturisers” is hyaluron, whose function as a moisturizer and anti-wrinkle agent has been proven in studies.

In strict scientific terms, hyaluronic acid has been called hyaluronan for several years. The term hyaluron, on the other hand, is more or less a popular name for the substance in cosmetic products. Since it has become common, it is used in this article. All terms refer to the same substance.

In the anti-ageing segment, hyaluronic acid has long been regarded as a veritable silver bullet. Just one gram can bind up to six litres of water, which means that this moisture reservoir gives the skin more elasticity and resilience. The short-chain form penetrates deeper into the skin and cushions it from the inside, while long-chain hyaluronic acid binds moisture, especially in the superficial layers of the skin, and protects against water loss and dehydration.

Various types are now used in cosmetic products (table 1). The newer generations include the acetylated form (Sodium Acetylated Hyaluronate) and the cross-linked version (Sodium Hyaluronate Crosspolymer), among other things to achieve long-lasting care effects.

Vitamin A

Another anti-ageing success formula is vitamin A, whose evidence against skin ageing, wrinkles, pigment spots, acne and large pores is proven in numerous clinical studies – it ensures:

Increase in mitotic activity

Increase in enzyme activity

Induction of collagen biosynthesis

Expression of collagen-degrading enzymes such as matrix metalloproteinase 1

Normalization of keratinisation

improvement of epithelisation

thickening of the epidermis

Regeneration of UV-damaged skin

Improving the natural functions of the skin

Positive influence on extrinsic and intrinsic skin ageing

A lack of vitamin A can cause the skin to become scaly and dry and lead to increased formation of wrinkles.

Like hyaluronic acid, there are numerous variants in cosmetic preparations (table 2). This is important to know, because in addition to the application concentration, the form used (vitamin A ester, vitamin A alcohol, etc.) has a significant influence on the cosmetic effectiveness and skin tolerance. On the formulation side, the selected vitamin A variant must also be adapted to the basis (vehicle) and chemical composition, including the pH value of the formulation.

Since retinol is very sensitive to light, air and oxidising agents, degrades quickly and irritates the skin, alternatives such as the more stable retinol esters (e.g., retinyl acetate, linoleate, palmitate) or the aldehyde form (retinal) are used. The hydroxypinacolone retinoate is of interest as a new variant. As a direct ester of retinoic acid, the active ingredient docks directly to the retinoid receptors of the skin cells and does not require conversion to retinoic acid. The advantages over retinol are the faster onset of action, better stability, and skin compatibility.

Niacinamide

Research on niacinamide in skin care unanimously shows how special this active ingredient is. New studies also show again and again that the power vitamin, also known as vitamin B3 or nicotinamide, is one of the most interesting ingredients. It ensures:

Visible refinement and reduction of enlarged pores

Smoothing fine lines and wrinkles

Strengthening the skin’s natural barrier and reducing the effects of environmental damage

Recovery from past damage and supporting skin regeneration

Improving an uneven skin tone

Since its cosmetic effectiveness is dose-dependent, it is widely used in formulations for blemished skin through to skin-rejuvenating preparations. Used at concentrations of five percent and higher, niaci-namide works through multiple signalling pathways to combat hyperpigmentation in the skin, resulting in a more even complexion.

Carnosine

A classic active ingredient is L-carnosine, a nature-identical dipeptide (β-alanyl-L-histidine), which is incorporated in products for skin rejuvenation, against wrinkles and saccharification (glycation) of skin and blood vessels or to protect against damage caused by light. It is a chemical compound composed of two amino acid residues that can be split into two amino acids by hydrolysis. Carnosine provides:

Protection of proteins from saccharification: Reacts with aldehydes, inhibits the formation of carbonylated proteins and the cross-linking of proteins

Protection of collagen and other structural proteins from premature degradation

Prevention of damage induced by visible light and infrared radiation

Inhibition of IR-A induced MMP-1 expression

Increase in collagen neosynthesis (collagen booster)

Neutralisation of free radicals and protection against oxidative stress

Vitamin C

Various vitamin C derivatives are used in cosmetics for external use (table 3). Pure vitamin C, ascorbic acid or also called L-ascorbic acid (ascorbic acid) has the most direct effect, since, in contrast to the other variants, it does not first have to be converted into the active form.

Numerous studies show that vitamin C supports collagen synthesis and fights free radicals. It is also effective against acne and age spots by inhibiting tyrosinase. However, ascorbic acid cannot be processed into a cream because the active ingredient is too susceptible to oxidation and decomposes quickly. Therefore, preparation as a lyophilisate or administration as a powder is expedient.

In the case of a serum containing ascorbic acid, the formulation should have a strictly acidic pH value to ensure the best possible penetration into the skin. The administration should be an airtight dispenser. Vitamin C derivatives that are less skin-active or more tolerable and that remain stable even in cream bases are particularly suitable for sensitive skin or the thin eye area.

Conclusion

We see that a high concentration of an active ingredient does not automatically mean a better care effect. Only the careful selection and the formulation adapted to the active ingredient ensure optimal bioavailability, good skin tolerance, high stability, and the best possible product performance.

table 1: Hyaluronic variants

Name	INCI	short description	cosmetic effect
Sodium hyaluronate	Sodium Hyaluronate	Sodium salt of hyaluronic acid, a glycosaminoglycan, and a natural component of the dermis. The active ingredient can be of high or low molecular weight.	Binds water and preserves skin moisture.
Sodium Hyaluronate Crosspolymer	Sodium hyaluronate cross polymer	Hyaluronic acid attached to a poly-mer structure, so it stays longer in the top layers of the skin for improved hydration.	Has an intensive moisturising effect and has an immediately visible anti-wrinkle effect. Forms a kind of sponge structure and thus also a depot for active ingredients and moisture for a continuous release over a longer period.
Acetylated Hyaluronic Acid	Sodium acetylated hyaluronate	Obtained by acetylation, i.e., replacing a hydrogen atom with an acetyl group. The exchange can occur either at the functional groups (-OH, -SH, -NH2) or directly at a -C-H bond. An acetyl group in turn designates the chemical structure -C(O)CH3. It is made up of the carbonyl and methyl groups and forms the acyl residue of acetic acid. Possesses both lipophilic and hydrophilic properties	The acetyl group (highly lipophilic) helps hyaluronic acid adhere firmly, reducing the evaporation effect and keeping the skin hydrated throughout the day. The increased stability against hyaluronidase (degradation enzymes) ensures a long-lasting effect. The variant retains moisture better in the epidermis, improves skin elasticity, repairs the skin barrier, and has a skin-smoothing effect.
Lipophilic hyaluronic acid	Sodium Oleoyl Hyaluronate	Transport system based on hyaluronic acid	For introducing hydrophobic active ingredients with significantly improved effectiveness of the encapsulated active ingredients. Increases sebum production, which is reduced with age.
Hydrolysed Hyaluronic Acid	Hydrolysed Hyaluronic Acid	Hydrolysate of hyaluronic acid obtained by acid, enzyme, or other hydrolysis process.	Moisturising
Hydroxypropyl-trimonium hyaluronate	Hydroxypropyl-trimonium Hyaluronate	Produced by fermentation	In addition to the basic properties of the active ingredient, this variant has a special adhesive property, so that it cannot be rinsed off so easily.
C12-13 alkylglyceryl hydrolysed hyaluronate	C12-13 Alkyl Glyceryl Hydrolysed Hyaluronates	Modified hyaluronic acid. With the added glycerine backbone, it is suitable for skin care products, serums, and lip balms.	Supports the repair of the skin barrier. Works against rough and damaged skin by increasing moisture levels in the stratum corneum and reducing transepidermal water loss.

table 2: Vitamin A variants

Name	Short description
Retinol ester	Carboxylic acid ester from the esterification reaction of retinol and palmitic acid (retinyl palmitate). Ester between acetic acid and retinol (Retinyl Acetate)Ester between linoleic acid and retinol (Retinyl Linoleate).
Vitamin A aldehyde	Aldehyde of retinol; Retinaldehyde, Axerophthal, Retinene (Retinal).
Vitamin A alcohol	A fat-soluble essential vitamin, also known as vitamin A1 or axerophthol. Belongs chemically to the diterpenoids and is a monovalent primary alcohol (retinol).
Esters of retinoic acid	Retinoid esters of synthetic origin (hydroxypinacolone retinoate). Normalises keratinisation and improves epithelization Increases cell division rate (mitotic activity). Stimulates the new formation (neosynthesis) of collagen Increases the activity of the skin’s own enzymes and stimulates the expression of collagen-degrading matrix metalloproTeinases (MMP-1). Regenerates UV-damaged skin Lightens superficial hyperpigmentation, evens out skin tone Minimises pore lumen and improves skin texture.

table 3: Vitamin C derivates

Name	Short description
Pure Vitamin C	Ascorbic Acid. Ascorbic Acid, most effective form, but unstable.
Connection between ascorbic acid and glucose	Ascorbyl Glucoside
Salty ester form	Magnesium Ascorbyl Phosphate or Sodium Ascorbyl Phosphate
Water soluble Ester form	3-O-Ethyl Ascorbic Acid or simply Ethyl Ascorbic Acid. Quite a new form, which is suitable for serums and gels as well as for a care cream. Extremely well tolerated and stable.
Fat soluble Vitamin C ester	Ascorbyl Palmitate or Ascorbyl Tetraisopalmitate Ascorbyl tetraisopalmitate is also used in encapsulated form to prevent discoloration and deterioration of the cosmetic formulation and to ensure its stability. Such a CelluCap is only released upon mechanical application (rubbing on the skin), which is intended to guarantee prolonged release and lasting effectiveness.