Barbara Brockway explains how some ingredients can be used to make actives more effective and therefore more affordable
Formulators are forever being asked to do the impossible and usually the impossible has to be done cheaply and by yesterday. In order to keep formulators on track, the large number of competing ingredient manufacturers carry out research; they source ingredients, extract, distil, ferment, grind, synthesize, fractionate, filter and/or blend materials, as well as run expensive in vitro and in vivo experiments to demonstrate the efficacy and the safety of their ingredients. New sophisticated screening techniques, (such as cDNA micro array analysis), can quickly tell ingredient producers which materials affect cells at the gene level (Fletcher, 2001).
Results from these rapid screening techniques are fuelling the growth of the cosmeceutical market and, despite knowing the danger of making claims for cosmetics that border on drug claims, the attraction of having these more effective actives is just too tantalizing to resist. As a consequence, formulators are under pressure to use these potent actives but they also need to keep within strict budgets. The tremendous upstream effort put in by manufacturers results in very desirable but understandably very expensive actives. In fact they are often so expensive that most formulators use them at levels below the recommended levels where they are far too weak to be truly effective. One way to make expensive actives more affordable is to look for synergy with other materials in the formula so that their activity is boosted.
COMBINING FOR EFFICACY
A few formulators are already asking suppliers about ingredients that can be combined with the really expensive actives so that together they will deliver the required efficacy and remain affordable. Fortunately, unlike product formulators, the chemists who develop ingredients have both the time and equipment needed to balance blends of ingredients and optimise them for both price and potency. One example of a successfully optimised blend that can be used as a substitute for hyaluronic acid is Active Concepts’ AC Moisture-Plex Advanced. It comprises substances that are nearly all very familiar to formulators, ie glycerin, water, sodium PCA, urea, trehalose, polyquaternium-51 and sodium hyaluronate. The benchmark for this blend was sodium hyaluronate, which is a wonderful but expensive active with benefits ranging from feel to moisturisation. Care was taken to make the blend feel right, give equal or better moisturisation and be more cost effective. Sodium hyaluronate was kept in the blend for any specific biological activity it might have and also so it could be included on the product label.
The formulator can always choose to use the individual substances (guessing the optimum ratios) but when it comes to manufacture, they would need to purchase each substance separately. Formulas seldom use the complete order quantities so partly used containers for each substance will be left in the inventory. The purchase of a single blend however normally means only one container need remain so there will be less waste.
PHYSICAL HEAT
The study of chemical kinetics has resulted in the well known a rule of thumb: when the temperature of a reaction mixture is increased by 10°C then the time it takes for the reaction to take place halves (Connors, 1990). This is why stability can be crudely predicted from trials carried out at elevated temperatures. So why not recommend heat or include an active that will deliver physical heat when formulating with ingredients such as DHA that need to react.
Obviously raising the temperature of skin by 10°C is not to be taken seriously but even an increase of a few degrees will help secure a reaction and would be useful when an active has to be included in the product at a low level. Asking users of skin and body care products to sauna after application might only work in Nordic countries but it is worth considering when developing spa products. Cosmetic grade dry zeolite and certain anhydrous propylene glycols give out heat when hydrated. Distinctive Cosmetic Ingredients has developed Natural Hot, a range of self-heating ingredients based on anhydrous calcium chloride and magnesium sulphate which release a burst of heat as soon as they are hydrated. Estée Lauder’s Idealist Micro-D Deep Thermal Refinisher (now relaunched as Idealist Dual-Action Refinishing Treatment) is probably the best example of its use. These thermal generating ingredients are excellent for cleansing products and acne treatments where deep pore cleansing may be desired. They also offer the formulator a source of heat for increasing the reaction rate of accompanying actives.
Heating hair is not as contentious as heating skin. Many consumers routinely use heated curling/straightening tongs or hairdryers. Formulators developing hair care products already take heat into consideration but they probably spend most of their time looking for materials that will protect hair from heat damage rather than using heat to accelerate reactions and thus helping ingredients go further. Salvona’s SalSphere, HydroSal, MicroSal and MultiSal microsphere systems can all be made so that they are triggered by heat to release their contents. These vehicles will deliver actives for shine, repair, hair regrowth, moisturisation, colour retention and fragrance (Shefer and Shefer, 2003).
INCREASED CIRCULATION
Massage increases the blood flow in the microcapillaries and ensures that ample blood is supplied to every living skin cell, which in turn ensures that the cells can efficiently respire; taking in glucose and nutrients and exchanging oxygen for carbon dioxide. The capillary blood takes away expelled waste products preventing any build up, which could restrict further metabolism. It is well known that massaging with anti-cellulite creams containing actives such as caffeine helps destroy cellulite much faster than using the caffeine creams without massage. It therefore follows that products, which increase circulation can be thought of as alternatives to physical massage and are suitable for boosting the activity of not only anti-cellulites but any product whose efficacy depends on cell metabolism. One unusual active that increases microcirculation is Active Concepts’ fermented Red Pepper Capsicum annum. Surprisingly, the fermented pepper extract is no longer ‘hot’ but it is very effective at increasing circulation (figure 1).
INCREASING METABOLISM
Just as humans release adrenaline for fight or flight when they are in danger, bacteria and yeast cells have also evolved molecules to help them escape from aggressive surroundings. These systems are complex but are becoming better understood. It is known that they involve molecules such as heat shock proteins, which have become highly conserved throughout evolution. It is therefore not surprising to discover that even human cells will respond to these chemical signals. Extracts made from bacteria and yeast cells that have been cultured in hostile environments can increase human cell metabolism so can be used to energise cells and potentiate the action of ingredients whose activity depends on cell metabolism.
The first of these actives has now had a very long history of safe use. Live yeast cell derivative (LYCD) was first described by George Sperti in the 1930s and went on to be used in American Home Products’ anti-hemorrhoid cream, Preparation H. Legend has it that some adventurous fashion models brought about the crossover of the ingredients in hemorrhoid creams and those used in cosmetics when they began to dab creams containing LYCD on their faces to reduce the bags under their tired eyes. As would be expected, the swelling subsided and the practice spread by word of mouth and so a core cosmetic raw material was born (Herman, 2001). LYCD was used to stimulate oxygen consumption and combat irritation but like all actives that increase ATP turnover, it can be used to potentiate the activity of some actives by squeezing small effects into a shorter period and making them more apparent. Of course combining increased circulation with increased metabolism could amplify small effects even further.
DELIVERY SYSTEMS
Encapsulation systems such as liposomes, Salvona’s many microspheres, microsponges and Soliance’s Spherulites etc offer special advantages. These tiny discrete capsules can be packed with actives yet can be used in the product at low concentrations, making the final concentration of the active in the bulk very low. When they deliver their cargo they unload locally the full concentration of active (ie the bang) and the product performs as if the active had been present in the bulk at the much higher, more expensive quantities. They are the simplest way to achieve more bang for your buck and although there is an added cost required to encapsulate actives, this approach can make very expensive actives more affordable.
Other types of useful delivery systems include films that hold actives on the skin. These too enable a formulator to use lower amounts of an active as they ensure that the active remains on the skin or hair for longer. Grant Industries uses InvisaSkin (dimethylacrylamide/acrylic acid polystyrene ethyl methacrylate copolymer) to hold its series of bioactive peptides on skin for extended periods to help with their potency. This polymer has an advantage over other film formers because its ultra thin layer stays tightly adhered to skin for hours, even resisting being washed-off by soap and water. As the name suggests, it is almost invisible to the eye. It ebbs and flows with movement so it does not pull when it dries. InvisaSkin has been used to deliver drugs into eyes so is especially gentle and safe.
When the formula calls for a film that does pull – ie one which will control wrinkles and smooth fine lines – gums such as acacia gum blended with hydrolysed biopolymer, as in Soliance’s Easyliance, has been shown to be very effective. This natural polymer could also be used to hold actives on skin.
Unipex has an interesting polysaccharide derived from microorganisms that live in the deepest abyssal zone, 3,000 metres down in the sea. These microbes live beside smoking undersea chimneys that pump corrosive mineral fluids from deep within the earth’s crust. This polysaccharide helps protect the snow-white carpets of bacteria that live in this hostile environment and has been shown to protect skin.
Other marine polymers that could be used as delivery films include FMC BioPolymer’s Carrageenan and Active Concepts’ Phytogel Hydrolyzed Fucus Vesiculosus Protein derived from Fucus vesiculosus.
Film formers from terrestrial sources include Active Concepts’ Phytocoll, extracted from yeast, and Alban Muller International’s Vegetensor, a plant complex that combines the remarkable film forming properties of pea proteins with the gelling and smoothing power of sclerotium gum derived from Sclerotium rolfsii. In aqueous solution, Vegetensor has a lifting effect that instantly reduces the appearance of fine lines. By modifying the rheology of a product, these natural, water soluble polymers have been shown to enhance SPF, making the effects of sunscreens go further.
Hydrophobic film forming polymers are often used to increase water resistance and therefore enhance the SPF of sun care formulations. The water resistance of the two sunscreens was shown to be improved when Wacker-Belsil Silicones RG 100 (cyclopentasiloxane, dimethicone/
vinyltrimethylsiloxysilicate crosspolymer) was added (Schlosser and Fry, 2002). Occlusive films are effective but they too can be made even more effective if the formula contains elements that soften the skin and make it more accommodating to actives.
SOLVENTS & SOFTENERS
Interest has been growing in molecules such as isosorbide dimethyl ether (DMI, Dottisol), which is used in research to improve drug solubility (Zia et al, 2005). DMI is proving to be useful when investigating actives that need to travel through the stratum cornea. It will improve the finish of DHA products by aiding penetration and helping the colour spread more evenly. Another molecule that aids penetration is urea. This will soften skin and hair and make it easier for actives to penetrate (Lodén and Maibach).
PRESERVATION
Because of potential irritation, sensitivity and expense, it is important to keep levels of preservatives as low as possible. The formula should only contain sufficient preservative to subdue any dangerous microbes that are either present in the final filled product or added later during normal use (Brewster, 2007). Synergistic blends of phenoxyethanol and chlorphenesin have recently found favour. Challenge testing has shown that including small amounts of chlorphenesin in products preserved with phenoxyethanol allows the level of phenoxyethanol to be dramatically reduced and the products still pass the test. Unfortunately, even phenoxyethanol is beginning to fall out of favour so many companies are searching for alternatives.
It has been known for generations that preservatives can also be assisted by other ingredients in the product. Because these actives have a variety of main functions, from moisturising to fragrance, they can be combined to produce self-preserving formulas, eliminating the need for parabens, phenoxyethanol and the other preservatives which are currently unpopular in cosmetics. Active Micro systems offers a whole range of sustainable natural extracts that are being combined to make all natural, fully sustainable products. Many of these materials originated as foods so are also becoming popular because of the emerging trend for food ingredients in cosmetics. Also with the current concerns about swine flu, Active Micro Systems’ Leuconstoc kimchi ferment is especially interesting as the lack of cases of SARS and reduced incidence of bird flu on the Korean peninsula, as compared to the rest of Asia, has been attributed to their consumption of Kimchi. Botanical extracts and essential oils, which have a history of being hostile to microbes, are now being studied in earnest, driven by the market’s desire to be greener.
The moment of satisfaction comes when the formula is finished. It has passed stability and fulfilled all the requirements in the brief. The formulator has achieved the impossible thanks to their skill at combining ingredients that at first glance seem to have unrelated effects but together actually achieved more bang for their buck.
