Cosmeceuticals are rapidly being developed with newer products entering the market on a regular basis
Introduction Cosmetic pharmaceuticals, or cosmeceuticals, are cosmetic products that contain biologically active ingredients  and claim to have medicinal or drug-like benefits . Raymond Reed, founding member of the US Society of Cosmetic Chemists, coined the term in 1961 . However, the use of cosmeceuticals as therapies can be traced back to early man [4, 5]. Around 10,000 BC, ancient Egyptians first started applying scented oils and ointments to clean and soften skin and mask body odor . Development of cosmetics with health claims is rapidly advancing, especially after the identification of alpha hydroxyl acids (AHAs) as anti-wrinkle agents . Yet, some of these products are not labeled as ‘cosmeceuticals’ due to regulatory difficulties e.g., FDA regulations in the USA . Examples include daily skincare products such as sunscreen agents, anti-wrinkle lotions and anti-perspiration products; and topical remedies focusing on the treatment of acne, hair loss and cellulite.
These products cross female and male markets, and male grooming is one of the fastest growing markets . In 2004, the U.S. market for cosmeceutical products was valued at $12.4 billion and is expected to grow to over $16 billion by 2010 .
Major indications for cosmeceuticals
Pigmentation and skin-disorders Human skin is an extremely complicated tissue defined as a three tiered structure, epidermis, the outermost layer, the dermis, and the deepest, the hypodermis.
Ultraviolet radiation (UV, 100-400 nm ) is believed to contribute to skin aging and skin cancer. All of its subdivided bands, Near-UV (UVA), Mid-UV (UVB), and Far-UV (UVC), can tan or burn skin to differing degrees.
UVC (100-290 nm) is mostly blocked by the Earth’s ozone layer. The small percentage that gets through can penetrate the epidermis and slightly deeper.
The outmost layer of skin reflects 70% of UVB rays (290-320 nm) with the remainder penetrating the epidermis where rays are partially absorbed by the keratinocytes and melanin. Only 10 % reach the upper dermis. Due to their short wavelength, UVB rays have high energy levels and are therefore biologically very active, causing sunburn.
Possessing the longest wavelengths (320-400 nm), 80% of UVA reaches as far as the dermis and the remaining 20% penetrate considerably deeper. UVA can be more dangerous than UVB because it cannot be blocked by glass and its effects are not immediately visible.
To protect the skin from solar radiation, melanocytes, which reside in the basal layer of epidermis, absorb UV rays resulting in tanning of the skin [9, 10].
UV light may also cause a reduction in immune defenses and lead to cancer. UVA and UVB rays decrease the number of Langerhans cells that protect against foreign substances. This lowering of immune surveillance in turn has a harmful effect, as pre-cancerous cells can no longer be eliminated. UVA and UVB also trigger the formation of free oxygen radicals in the cellular cytoplasm. These radicals are toxic to the proteins as a consequence of membrane lipid peroxidation (the free radicals influences disulfide bond formation between proteins), and responsible for DNA damage [10, 31]. The occurrence of melanoma (skin cancer) is higher among fair-skinned people with blond or red hair who are more prone to sunburn; however, it can also occur among people who have frequently suffered sunburn before the age of 15 .
Products that screen UV light are given a sun protection factor (SPF). The SPF value indicates how long a topical sunscreen remains effective on the skin. A user can determine the duration of effectiveness simply by multiplying the SPF by the length of time it takes for him or her to suffer a burn without sunscreen. For example, SPF 15 means that a user can nominally remain in the sun 15 times longer than would otherwise cause them to have sunburn .
Common active ingredients in suncare products :
Photo-protection—iron chelators Iron chelators have been studied in animal models and in humans. 2-furilioxime demonstrated a sun protection factor of 3 measured by erythema, sunburn cell formation and induction of ornithine decarboxylase.
Self-tanning—DHA agents These agents are characterized by dihydroxyacetone (DHA), which reacts with amino acids in the outer stratum corneum to produce a temporary brown color resembling a tan.
Aftersun—others Antioxidants, e.g., vitamins, trace metal, and others chemical entities are capable of inactivating the free radicals such as ROS that are highly reactive and potentially damaging. A number of antioxidants have been studied for prevention of photoaging.
Vitamin C, ascorbic acid, is involved in both collagen synthesis and as an important antioxidant in human metabolism. It has UV light-protective capabilities and is known as one of the best anti-aging ingredients, improving skin clarity and smoothing wrinkles. There is a variety of forms: L-ascorbic acid, sodium ascorbate, ascorbyl palmitate and vitamin C ester. Previously, vitamin C was stabilized in heavy oil-based formulas as it deteriorates rapidly on contact with air. Today, the molecule is stabilized with additional ingredients for use in many types of skincare products .
Vitamin E has eight molecular forms of tocopherols and tocotrienols, of which tocopherol is predominantly utilized as an antioxidant in humans. Vitamin E is a powerful antioxidant that helps prevent signs of premature aging and reduces flaky, dry skin. It is easy to formulate because it is lipid-soluble.
Selenium, a trace metal, is essential in human metabolism as a cofactor for the enzyme glutathione peroxidase, a quencher of free radicals. Topical treatment using L-selenomethionine in photoaging demonstrated protection against erythema and blistering in mice and decreased tanning in nine human subjects.
The US sun care market, valued at $863 million in 2001, will reach $1.1 billion by 2006 .
Vichy and La Roche-Posay are the two of the only three brands labeled as cosmeceuticals by L’Oréal . Among them, La Roche-Posay is the first skincare center in Europe widely recommended by dermatologists .
Vichy—sun protection and prevention Vichy Thermal Water: Rich in calcium and magnesium, it contains 17 mineral salts and 13 trace elements and claims to provide the skin with a health concentrate to quickly sooth the skin leaving it well mineralized and more resistant.
CAPITAL SOLEIL creams and lotions (SPF 15-60): A sunblock product, ingredients include Mexoryl® SX and XL (These protect against cellular DNA changes generated by UV rays, and are the first short anti-UVA filters that are photostable, and offer advanced sun protection that provides wide-spectrum filters against UVA and UVB rays) and multivitamin E (an anti-oxidant complex, which neutralizes free radicals generated in the skin by UVA rays; it is one of the most widely used antioxidants in cosmetic markets and has been clinically proven).
CAPITAL SOLEIL AFTER-SUN: An after sun product, ingredients include PCA clay (an anti-oxidant complex) and polytocopherol, which aid the skin's natural self-defense system and promote cellular repair.
La Roche-Posay Laboratoire Pharmaceutique—anti-aging and skin problem treatment La Roche-Posay Thermal Spring Water: Different from Vichy Thermal Water, the unique La Roche-Posay water is the only thermal spring water that contains selenium, a substance known for its anti-radical properties. The spring water also contains a range of other trace elements and mineral salts like calcium, silica, magnesium, strontium, zinc and copper. Its potent action on the skin as well as its efficacy in a variety of dermatological situations has been demonstrated in many different research publications. It reportedly soothes and softens, inhibits inflammation and quenches free radicals; it is effective in combating aging of skin, it inhibits carcinogenesis and it helps calm certain inflammatory conditions that affect skin.
Wrinkles and skin aging Photoaging, or solar elastosis, is premature aging of the skin due directly to UV and especially UVA rays . In addition to intrinsic aging, this sun-induced aging of skin is characterized as wrinkles, roughness, a lack of elasticity, de-or hyper-pigmentation marks, a variety of benign or malignant tumors and a coarse thickened horny layer due to collagen and elastin fiber aggregating after UVA irradiation.
Of the three skin compartments (epidermis, dermis and hyperdermis), the dermis is the most deeply altered during the process of aging. The appearance of wrinkles results from the production of ‘advanced glycation end’ (AGE) products’ in the dermis by the contact between glucose and proteins with a long half-life, collagen and elastin.
Common active ingredients in anti-aging products : These include three generations of retinoids, hydroxy acids and vitamins.
Retinoids are the prototypic cosmeceutical ingredients currently used to combat wrinkles.
When retinol was applied to 53 patients of at least 80 years of age, it demonstrated increased fibroblast growth and collagen synthesis and reduced levels of matrix-degrading metalloproteinase after 7 days . Renova, a vitamin A derivative has recently acquired FDA approval as a prescription anti-aging drug.
In the 1980s, thensecon-generation retinoid, tretinoin (all-trans retinoic acid; vitamin A), was clinically proved to have definite effects on fine wrinkles, roughness, and mottled hyperpigmentation, and continues to be of central interest . It appears to be a biologically active molecule in most systems by which its precursor or related molecules of retinol (vitamin A alcohol), retinal palmitate (the usual dietary source of vitamin A), and isotretinoin (13-cis retinoic acid) function. However, tretinoin penetrates skin less readily than retinol.
Tazatotene is a third generation retinoid with rapid and comprehensive efficacy in clinical treatment of photodamaged skin . During a period of 24 weeks, in a trial of 563 patients, fine and course wrinkles, mottled hyperpigmentation, lentigines, elastosis, pore size, irregular hypopigmentation, and tactile roughness were significantly improved.
Alpha-hydroxy acids (AHAs) are members of the largest group of naturally occurring molecules, and include lactic acids, glycolic acids and citric acids. These could vie with retinoids as key cosmeceuticals. A high concentration of 50% glycolic acids, used as a peel for example, exhibits improvement in rough texture, fine wrinkling and hyperpigmentation. Even in lower concentration, a definite effect was shown by a combination of 8% glycolic acid and 8% L-lactic acid on similar symptoms.
Beta-hydroxy acid (BHA; salicylic acid) reduces cornecyte adhesion through exfoliation of skin surface. An application of 1.5% or 2% salicylic acid twice daily for 12 weeks caused a global improvement in appearance. BHA is more effective and milder than AHAs.
Vitamins are generally thought of as cofactors in a host of enzymatic processes many of which involve the skin.
The anti-aging skincare cosmeceutical market, with retail sales of about $1 billion in 2000, is growing at an annual rate of 15%, reported by Front Line Strategic
Management Consulting of California . Demand for anti-aging products is estimated to reach $30 billion by 2009 according to Freedonia Group Inc .
Estée Lauder is the leading company in prestige anti-aging markets. It offers a variety of cosmeceutical products ranging from Advanced Night Repair Protective Recovery Complex to refine the ‘first-sign’ to Perfectionist [CP+] with Poly-Collagen Peptides to correct deep wrinkles.
Estée Lauder—first-sign refining and correcting of deep wrinkles Advanced Night Repair Protective Recovery Complex—first-sign refining
Targeted liposome delivery system neutralizes 90% of skin-damaging free radicals generated by UV light, pollutants and oxidants, and repairs the damage by enhancing the skin’s own natural repair rate. It delivers advanced levels of hydration with proven hyaluronic acid to boost the effectiveness of nourishers. Clinical tests prove these levels of moisturization increase cumulatively with continued use, reducing existing lines and wrinkles and reportedly prevent the future signs of aging.
New Perfectionist [CP+] with Poly-Collagen Peptides Correcting Serum for Lines/Wrinkles/Age Spots—deep wrinkle correction
Poly-Collagen Peptides are designed to prevent degradation by the skin’s natural surface enzymes. This patent-pending triple enzyme technology makes it effective on even the most prominent wrinkles. Clinically, the length, depth and number of lines and wrinkles appear reduced up to 36% on the first day of application; after one week, deeper wrinkles look leveled and natural collagen production is amplified, age spots appear to fade away; after a month, there is 55% reduction in the look of lines and wrinkles, 54% increase in skin's clarity, and 53% improvement in skin tone.
Hair loss—hair damage Changes in hair growth are not only of cosmeceutical significance but can also be associated with underlying disease .
The entire hair consists of the hair follicle, sebaceous gland, hair muscles (arrector pili) and in some instances the apocrine gland. The average human scalp is covered by 100,000 hair follicles. Hair has a keratinized structure that is pushed upward from the hair follicle . The normal hair growing process obeys a cyclical pattern, with a growing phase (anagen) for around 1,000 days on the scalp followed by a few days of an atrophy phase (catagen) and then a resting phase (telogen) of 100 days before entering into the next cycle .
Over time, the number of follicles capable of growing hair declines naturally. The decline is especially visible on the top of the head. Some follicles increasingly produce only fine, short non-pigmented hairs that look more like vellus hairs than terminal hairs. In older women, this leads to a general thinning of hair . The situation is more obvious and severe in men leading to male pattern baldness [20, 22].
Other external factors leading to hair loss include stress and lifestyle, hormonal imbalances, and genetic factors.
Common active ingredients in hair loss products 
Melatonin is most widely used to stimulate human hair growth. In animal tests, increased DNA synthesis was found in Cashmere goat follicles kept in hair organ culture over a time of period of 120 hours. In a clinical placebo-controlled pilot-study, 40 women with alopecia diffusa were supplied with 0.1% melatonin daily. After 6 months, frontal hair counts showed a significant increase of anagen hair.
Many pharmaceutical companies have developed products for use in hair loss.
Propecia® (1 mg. finasteride) , developed by Merck, is the first oral therapy (FDA-approved) indicated for the treatment of male pattern hair loss in men only. Safety and efficacy were demonstrated in men, aged 18 to 41, with mild to moderate hair loss of the vertex and anterior mid-scalp area .
Regaine® In 1988, Pharmacia & Upjohn Company introduced the first FDA-approved product, Regaine® (minoxidil 5%) proven to regrow hair and to stop hair loss . The company holds a patent for using minoxodil with a DHT inhibitor, or anti-androgen .
Minoxidil works by opening potassium channels in the cells of the follicle, stimulating dormant hair follicles and reversing the miniaturization of follicles. This makes minoxidil the drug of choice for treating all types of hair loss since it has a very specific action without unwanted side effects. Clinical studies showed that patients receiving minoxidil grew 25% more hair than those receiving placebo. Additionally, minoxidil also increased the hair weight or thickness of existing hairs.
Minoxidil, however, does not reduce or remove DHT, which is the cause of androgenic alopecia. However, this can be remedied by using a DHT inhibitor in combination with minoxidil. Some dermatologists have recommended using minoxidil in conjunction with finasteride and studies have shown that these two drugs work synergistically together giving far better results than either drug on its own .
In March 2005, Shiseido Co., Japan's leading cosmetics maker, launched a medicated adenosine hair-restorer for male pattern baldness under the name Adenogen . Shiseido has set a sales target of 1 million bottles in fiscal 2005, which it predicts it will achieve comfortably .
Deal news In May 2005, Elizabeth Arden entered into an exclusive co-marketing agreement with Allergan, to re-launch a newly-formulated Prevage anti-aging formula on a global basis. Scott Beattie, Elizabeth Arden CEO, described this technology as a “breakthrough” in skincare .
Also in May 2005, L’Oreal, the word’s largest beauty company, acquired SkinCeuticals, a professional skincare company. SkinCeuticals’ sales in 2004 amounted to $35 million and the brand is one of the fastest growing in the US professional premium skincare market. The acquisition of SkinCeuticals allows L’Oreal to strengthen its position in high-performance professional skincare .
Acknowledgement I would like to express my sincere gratitude to my supervisor, Dr. Joanna Entwistle at Bridgehead Consulting for her patient guidance and support throughout the composition of this article. I also thank Dr Matthew Hughes, my lecturer at University of Nottingham, for his revisions.