IconicA

For decades vitamin A has been, and still is, the go to ingredient for anti-aging cosmetic products. Although the term “anti-aging” may be as dated as is the word “groovy” it remains the premier ingredient for this category. Recently, this go to ingredient has been improved. 

Until now retinol has been the vitamin A of choice for cosmetics. With the invention of IconicA®, retinaldehyde, a superior form of vitamin A, has been stabilized and is able to be harnessed for cosmetic use. 

Retinaldehyde is a better choice for vitamin A use in cosmetics than is retinol. Retinol must first be converted into retinaldehyde by our skin and subsequently converted into retinoic acid before it is used to combat skin wrinkles and uneven skin tones. When we use retinaldehyde in cosmetic products we avoid this conversion and the skin irritation that accompanies the chemical reaction.

Retinaldehyde has remained almost unused in the industry due to its inherent instability. IconciA® is stabilized retinaldehyde that comes in powder form and is easily added to almost any cream or lotion. In a 1999 French study retinaldehyde treatment tended to increase dermal thickness and reduce cutaneous stiffness.A 

Dr Surbhi (MD Skin) states that retinaldehyde is the best retinoid available without the prescription and studies show that retinaldehyde at the concentration of 0.05% for 3-4 months increases the thickness, collagen production and elasticity of your skin.B 

The best vitamin A skin care products contain stabilized retinaldehyde using IconicA®.

A) Diridollou S et al., Efficacy of topical 0.05% retinaldehyde in skin aging by ultrasound and rheological techniques., Dermatology. 1999;199 Suppl 1:37-41.
B) https://www.dermatocare.com/blog/is-retinol-or-retinoid-the-best-anti-ageing-ingredient-dermatocare-research

Introduction

Retinaldehyde γ-Cyclodextrin Hemiacetal (RCH) is a unique delivery system for Vitamin A, more specifically retinaldehyde (RAL). Even though RAL is the most bioavailable form of vitamin A it has been rarely used due to its severe instability. A new delivery system utilizing a “transient” hemiacetal bond stabilizes RAL for use in cosmetic preparations. This hemiacetal bond holds RAL in a stabilized form due to the unusual emulsification that forces a finished product, with an oil-in-water type emulsion, into an equilibrious state due to pH manipulation of the environment combined with hydrogen-bonding. 1, 2, 3, 4 

Vitamin A has been, and still is, the predominant anti-aging material in topical skin care products.5 The reduction in fine lines, wrinkles and other signs of aging are greatly improved with the application of creams and lotions containing vitamin A derivatives. Since the 1990’s RAL has been the preferred nonprescription, i.e., not retinoic acid, form of vitamin A for these applications. Unfortunately, RAL has not been widely used due to its instability. This is no longer true, RCH stabilizes RAL for use in these cosmetic products. In fact, clinical tests indicate that RCH improves the anti-aging performance of this preferred form of vitamin A.

Discussion

“Transient” is a misnomer for this particular molecule. This hemiacetal bond protects the RAL from degradation utilizing the protective nature of these hemiacetal bonded materials. 1, 2, 3, 4

The hemiacetal is formed under alkaline conditions. Further reaction to the acetyl is prevented from forming due to the alkaline environment in the continuous water phase on the external part of the cyclodextrin ring as well as a hydrophobic environment on the inside of the ring.

This inner oil environment also aids in preventing further reaction of the hemiacetal formed. Under acidic conditions the reaction would proceed to completion. This diagram depicts the oil droplet protecting the hemiacetal bond with hydrogen bonding in the continuous water phase maintaining the somewhat spherical hydrophobic environment on the inner side of the cyclodextrin ring.

Analytical Corroboration

This “transient” hemiacetal bond, RCH, has been analytically identified.6 Analytically, the existence of this hemiacetal was confirmed using LC-MS and HPLC/UV analysis. RCH Powder contains approximately 3.75% RAL. This is a combination of the RAL peak and the peak from the fragment from RCH. 6

This molecule has an approximate molecular weight of 370, this is a fragment of the RCH molecule generated during analytical testing.

Genetic Studies

In vitro studies were conducted identifying key factors in upregulation and downregulation of human genes of interest.13

It was found that RCH …

•  is anti-inflammatory     •  enhances barrier function

•  is an antioxidant     •  increases cell turnover

•  protects collagen

Methods / Results

Several third party double blind clinicals were conducted testing RCH. It was found that RAL when delivered via this vehicle to the skin had an effect on many anti-aging parameters. In fact it was determined that RCH delivered RAL and “ … produced a statistically significant decrease (improvement) in clinical grading scores for all graded efficacy parameters evaluated. …” 7, 8, 9 The parameters evaluated were Crow’s Feet, Fine Lines, Overall Evenness of Skin Tone, Overall Photo Damage, Tactile Smoothness and Visual Smoothness.

The VISIA-CR, a facial imaging system for clinical research developed by Canfield, was used in several studies to assess the effect of RCH and RAL in vivo on human skin.10 One of the most useful measurements the VISIA-CR performs is a wrinkle count for facial images. Competing anti-aging materials are used on the face with initial wrinkle counts and then counts sometime after using these materials for a predetermined length of time.10 These images show quantifiable wrinkle reduction when using a lotion containing RCH.

 

Wrinkle Reduction - Over 4 Weeks when using a cream containing RCH

In a separate third party double blind clinical it was determined (using the VISIA-CR) that the number of wrinkles vastly improved using RCH. Four products were tested, all in the same lotion base:9

Lotion Base (Placebo)  average increase +2.06

Retinol improvement - average decrease -3.31

Retinaldehyde improvement - average decrease -2.65

Retinaldehyde γ-Cyclodextrin Hemiacetal improvement - average decrease -4.20 

The increase in wrinkle count for the lotion base can be attributed to less volume of wrinkles with some wrinkles becoming two where there used to be one. This can happen when the middle of a wrinkle is no longer visible. In this way a positive number may in fact be an indication of wrinkle reduction. It is shown in this study that RCH is 25% better than retinol over an eight week period in this lotion base. The data also suggests that RAL alone deteriorates quickly when used in cosmetics without RCH stabilization.

In addition to wrinkle count reduction the VISIA-CR can show volume reduction in wrinkles, pore size changes, evaluate the redness and overall skin tone evenness/improvement, etc.10 The great aspect in using this technology software is that unbiased clinical studies can be performed. In one study lasting 4 weeks a cream containing RCH had a better than 70% reduction in the redness feature of one subject.

 

Redness Reduction - over 4 weeks when using a cream containing RCH

Another study shows the dramatic effect RCH has on melasma reduction. The following images show what 12 weeks of RCH application (in a lotion) does for evenness of skin tone and lightening of melasma.11

The underlying brown pigmentation in this individual’s face is greatly reduced over a 12 week period.

 

Melasma Reduction – Over 12 weeks when using a cream containing RCH

 

Conclusions

Although numerous human clinicals conducted 15-25 years ago concluded that retinaldehdye has a good tolerance profile (non-irritating) compared to retinoic acid, retinaldehdye has been used sparingly.13 It has also been verified that retinaldehyde significantly repairs elastic fibers and collagen alteration induced by ultraviolet, long wave (UVA) exposure.14 By utilizing the unique delivery system outlined here, Retinaldehyde γ-Cyclodextrin Hemiacetal, the elusive anti-aging Vitamin A material retinaldehyde may finally be extensively employed by cosmetic creams and lotions. 

This is exciting news when we see the impressive skin improvements with regard to anti-aging and overall skin tone and skin health when Retinaldehyde γ-Cyclodextrin Hemiacetal is applied. Retinaldehyde γ-Cyclodextrin Hemiacetal Powder is easily added to finished formulations near the end of processing, allowing small entrepreneurs as well as the multi-national mass market anti-aging companies to have product lines utilizing this technology.

References

1) Peter, et al., U.S. Pat. 8,410,079
2) Peter, et al., U.S. Pat. 8,569,269
3) Peter, et al., U.S. Pat. 8,586,730
4) Peter, et al., U.S. Pat. 8,871,748
5) Sam Dhatt, Vitamin A: New Applications and Outcomes, Skin, Inc., 2013 September
6) Impact Analytical, Report Number R140504, September 2014
7) Stephens and Associates, Stephens and Associates, A Single-Center, Pilot Trial to Evaluate the Efficacy and Tolerability of Topical Products Designed to Enhance the Appearance of the Face in Women with Mild
to Moderate Photodamaged Skin, Stephens Study Number: C12-D121
8) Stephens and Associates, A Single-Center, Pilot Trial to Evaluate the Efficacy and Tolerability of Topical Products Designed to Enhance the Appearance of the Face in Women with Mild to Moderate Photodamaged Skin,
Stephens Study Number: C13-C066
9) Stephens and Associates, A Single-Center, Pilot Trial to Evaluate the Efficacy and Tolerability of Topical Products Designed to Enhance the Appearance of the Face in Females with Mild to Moderate Photodamaged Skin,
Stephens Study Number: C15-C156
10) Canfield Scientific, Inc., 4 Wood Hollow Road, Parsippany, NJ 07054 (http://www.canfieldsci.com/imaging-systems/visia-cr)
11) CoValence, Inc., various in-house studies
12) Genemarkers LLC, Project Report 024-022, June 6, 2013
13) Boisnic, et al., Repair of UVA-induced elastic fiber and collagen damage by 0.05% retinaldehyde cream in an ex vivo human skin model, Dermatology. 1999;199 Suppl 1:43-8
14) Fluhr, et al., Tolerance profile of retinol, retinaldehyde and retinoic acid under maximized and long-term clinical conditions, Dermatology. 1999;199 Suppl 1:57-60