The advent of the SARS-CoV-2 virus and the corresponding COVID-19 pandemic placed tremendous pressure on frontline health care workers and created concerns among non-medical people who have contact with infected individuals. As a result, there is acute need for sanitizing products. In the rush to meet needs, alcohol-based hand sanitizing products are frequently difficult to find. One common problem with alcohol-based hand sanitizers is that the alcohol is used as the antimicrobial and antiviral active. While very effective active for killing opportunistic microorganisms, alcohol can be quite aggressive to the skin’s barrier functions when used repeatedly. It is not uncommon for frequent users of alcohol-based sanitizing products to report very dry hands and even cracking of the skin which can be a potential source of microbe introduction. FDA recognized this problem when it allowed the inclusion of glycerin into the approved formulations. However, while glycerin is a well-established skin moisturizer, it is only one component of the complex mixture of moisture binding molecules that make up the natural moisturizing factor (NMF) of the skin. Alcohol-based hand sanitizers are very effective at stripping skin oils and lipids as well as remove key elements of the NMF from the skin’s epidermis.

This article examines alcohol-based sanitizing spray formulations that have been developed to include components from the skin’s natural moisturizing factor. Studies examined the moisturizing benefits of these products compared against placebo sanitizing sprays. In addition, a small, real-world use study, conducted with nurses at a long-term care facility, included the NMF-fortified sanitizing sprays with their normal regimen of sanitizing products.

In December 2019, a novel virus (SARS-CoV-2) emerged as a threat to humans first appearing in recognizable form in Wuhan, China and resulted in a pandemic of infections related to COVID-19 virus.^1,2 Since that discovery, the virus has spread rapidly and was declared a global pandemic by WHO in March of 2020.³ The sudden emergence of the virus, made it difficult for formulators to produce hand sanitizers fast enough to fill the need from the numerous frontline healthcare providers battling the virus and caring for critically ill and potentially vulnerable patients.⁴ Due to these merging problems, the FDA issued temporary guidelines for companies who may not be familiar with how to effectively make ethyl alcohol-based hand sanitizers to properly manufacture and label these products.⁵

The speed with which manufacturers are producing these products means little attention is paid to the critical aspects of how these aggressive ethyl alcohol and isopropyl alcohol-based formulas strip the skin of key elements that keep it moisturized.⁶ At the mantle pH of the skin, many important molecules including lactic acid and pyrrolidone carboxylic acid, which comprise part of the skin’s natural moisturizing factor, become somewhat soluble in alcohol. In addition, alcohol, particularly isopropyl alcohol, strips important lipids from the stratum corneum. To compensate for these effects, most alcohol-based hand sanitizers include glycerin (glycerol) to help moisturize the skin.⁴ While these formulations are very effective at killing viruses and other microorganisms they are designed to attack, with repeated applications, they can damage skin. It is not uncommon for health workers to follow repeated use of hand sanitizers with applications of hand moisturizers. But this can be somewhat problematic as it places a new product on top of the sanitizer that may influence the efficacy of the sanitizer or possibly introduce new contaminants.

Most alcohol-based hand sanitizers are offered as gels. The best ingredients that can be used to thicken alcohol-based hand sanitizing formulations are acrylate-based polymers. These polymers are readily soluble in both the water and alcohol used to make hand sanitizing gels. However, acrylates have one important functional flaw—they are notoriously ineffective at maintaining rheology when formulations contain higher concentrations of salts.⁷ Under circumstances of higher salt concentrations, the polymers lose their ability to maintain viscosity. Therefore, the addition of molecules like lactic acid, pyrrolidone carboxylic acid and urea, will result in liquefaction of the gels, effectively eliminating their gel-like structure.

Sprays are another practical way to deliver hand sanitizers. However, sprays are not as popular in small handheld products because they tend to be runny. But, elimination of the problem associated with the acrylate polymers does offer an opportunity to create hand sanitizing products that could potentially include Natural Moisturizing Factors components of the skin. This work details our efforts to produce and test hand sanitizing sprays containing components of the NMF delivered by adding a unique blend of such ingredients available commercially as BP-BotaniDew NMF (INCI: Water (and) Citrullus lanatus (Watermelon) Fruit Extract (and) Chenopodium quinoa Extract (and) Urea (and) Sucrose (and) Glycerin (and) Sodium Lactate (and) Sodium PCA) from BotanicalsPlus, Fairfield, NJ.⁸


Materials and Methods

Aspects of the methods and results of this study are being currently being reviewed.⁹ Hand sanitizers utilized in this study were made following the ingredients shown in Table 1.

BP-BotaniDew NMF was used as is. Skin hydration studies were conducted using the DermaLab Combo Corneometer instrument [Cortex Instruments, Hadsund, Denmark].¹⁰ Each site was analyzed eight times for each measurement and the resulting values were averaged. Statistical analysis was done using Microsoft Excel and were baseline normalized and paired.

For the analysis of skin moisturization, four volunteers were employed for the glycerin-based assays and five volunteers were employed for the glycereth-26 studies. All were advised as to how the studies would progress, signed informed consent and were free to leave at any time during the study. All the volunteers completed the studies. The individuals involved in the studies were all males between the ages of 17 and 60 with Fitzpatrick Type skin III-IV. Individual’s hands were marked into four quadrants as shown below in Figure 1.

This allowed for application of the two active formulations containing 3% and 5% BP-BotaniDew NMF and a site for the placebo on the same hand. The final site was maintained as an untreated control site measured at every time point. Prior to commencing the studies, each site was analyzed for its moisture content to obtain a baseline measurement. When calculating the statistical analysis of each treatment, the test values were normalized by subtracting the baseline measurement from the individual test values. This helped account for variations in moisture content seen across the surface of the hand from each site.

While the products were designed as sprays, for the purposes of these studies, the products were applied by saturation of a Q-Tip and application of the formulations directly to the back of the hand at the appropriate site. This helped keep the amount of product applied to each site very uniform. After application, the volunteers allowed the products to dry and sat for 15 minutes whereupon hydration measurements were made again and the products reapplied. This was done for a series of six time points over a 90-minute time frame. The room where the testing took place was maintained at 22oC and 30 RH.

Volunteer Nurse Hand Application Study
For this study, four sets of spray samples containing glycerin with 5% BP-BotaniDew NMF and glycereth-26 with 5% BP-BotaniDew NMF were prepared and provided to the head nurse at the Lopatcong Care Center in Phillipsburg, NJ. The head nurse coordinated the study with four participating nurses who employed the test products. Because the nurses deal with patients, they had to maintain their standard sanitizing procedures and products. The study simply included the hand sanitizer sprays on their carts that they carry with them when visiting patients. For the purposes of the study, we asked the nurses not to apply the products prior to attending to patients but to use them only when they were doing routine hand sanitizing operations outside of the patient visits. At the end of the study, the volunteer nurses were provided with a simple questionnaire that contained the following questions:

1. On a scale of 1 to 10, with 1 being “Strongly Dislike” and 10 being “Strongly Like,” how would you rate Hand Sanitizer 4 versus your current commercial hand sanitizer?
2. On a scale of 1 to 10, with 1 being “Strongly Dislike” and 10 being “Strongly Like,” how would you rate Hand Sanitizer 5 versus your current commercial hand sanitizer?
3. On a scale of 1 to 10, with 1 being “Strongly Prefer Hand Sanitizer #4” and 10 being “Strongly Prefer Hand Sanitizer 5,” which product did you prefer using?
4. On a scale of 1 to 10, with 1 being “Strongly Prefer a Spray” and 10 being “Strongly Prefer a Gel,” how would you rate these hand sanitizing sprays?
5. On a scale of 1 to 10, with 1 being “Product Was Easy to Use” and 10 being “Product Was Difficult to Use,” how would you rate Hand Sanitizer 4?
6. On a scale of 1 to 10, with 1 being “Product was Easy to Use” and 10 being “Product Was Difficult to Use,” how would you rate Hand Sanitizer 5
7. One a scale of 1 to 10, with 1 being “Very Drying” and 10 being “Very Moisturizing,” how would you rate Hand Sanitizer 4?
8. One a scale of 1 to 10, with 1 being “Very Drying” and 10 being “Very Moisturizing,” how would you rate Hand Sanitizer 4?

Hand Moisturization Study Results
The results of the hand moisturizing studies employing the glycerin-based hand sanitizing sprays on four volunteer’s hands can be seen in Figure 2. The results of the hand sanitizing studies employing the glycereth-26-based hand sanitizing sprays of five volunteer’s hands can be seen in Figure 3.

Volunteer Nurse Hand Applications Study Results
The numerical averages taken from the data from the study involving four nurses working at a long-term care facility handling is shown in Figure 4.

Discussion
The spread of the SARS-CoV-2 virus and resultant COVID-19 infections has brought into stark reality that constant and repeated use of alcohol-based hand sanitizers can be extremely damaging to the skin’s stratum corneum. The damage to healthcare workers’ hands can be partly mitigated by the use of gloves, but it is normal behavior for healthcare workers to remove their gloves and immediately either wash their hands or, when rushed, simply apply an alcohol-based hand sanitizer. In some cases, for particular healthcare workers, the damage from the hand sanitizers can be enough to cause epidermal cracks which expose deeper skin layers which may lead to infection.

The general public and healthcare workers cannot stop using hand sanitizers and are, in fact, being encouraged by government officials to use them frequently during the SARS-CoV-2 outbreak.⁵ Formulating alcohol-based hand sanitizers with glycerin offers some modest improvements in improving skin moisturization, but glycerin is only one part of a complex mixture of molecules that comprise the NMF of skin.7 Other formulations may employ the popular moisturizing polysaccharides found in aloe vera, however, aloe vera is not a component of the skin’s NMF. It is used because it can be formulated into high alcohol systems, but it does not have any impact on replenishing the NMF of the skin. The use of alcohol-based sanitizers strips more than just glycerin from the skin. Important components of the NMF include pyrrolidone carboxylic acid (PCA), lactic acid, urea and glycerin among others. Alcohol is effective at removing all of these important skin moisturizing molecules. Even low molecular weight hyaluronic acid may be removed from the skin by alcohol applications.

BP-BotaniDew NMF is a unique, naturally sourced mixture of important NMF molecules as well as some important botanical components that can offer skin moisturizing benefits.*⁹ However, the bulk of the product is comprised of salts which means that attempting to formulate this blend into acrylate polymer-thickened gels cannot be accomplished. Sprays offer a means of potentially putting practical amounts of these important ingredients into a sanitizing product. However, the high alcohol levels requires the use of co-solvents to help dissolve the ingredients into stable, clear formulations.

In this study, two well-known hydrophilic solvents, glycerin and glycereth-26, were examined for their ability to bring 3% and 5% of BP-BotaniDew NMF into clear, stable 2-propanol-based hand sanitizing formulations. These formulations were examined in clinical hand moisturizing studies comparing the formulations against placebo formulations which contained only additional water in place of the BP-BotaniDew NMF. It was found that in both formulations employing the BP-BotaniDew NMF, there was a statistically significant increase in skin moisturization within the first 45 minutes of application compared to the placebo and this improvement continued to the end of each 90-minute study.

To further investigate the efficacy of these formulations in a real world, high impact situation, four nurses working at a long-term care facility volunteered to include alcohol sanitizing sprays containing BP-BotaniDew NMF at 5% in either glycerin or glycereth-26 for one week for each spray. The nurses continued to use their standard hand sanitizing treatments and were told not to use the experimental treatment during patient visits. The experimental products were only used during routine activities not involving patients. After two weeks in which the nurses applied each experimental formulation for one week, they were asked to fill out a simple questionnaire with eight numerically based questions. From these questions, the data was plotted in Figure 4 and the following observations were found:

1. Overall, the nurses preferred the experimental spray products over existing products that included sprays and gels;
2. The nurses slightly preferred the formulation containing the glycerin over the formulation containing the glycereth-26, but both offered superior moisturizing benefits compared to standard hand sanitizing products; and
3. The volunteers found the spray products were easy to use and superior to their existing commercial products.

This study examined the benefit of adding components of the Natural Moisturizing Factor into standard 2-propanol-based hand sanitizing spray formulations by incorporating one of two emollient co-solvents, glycerin or glycereth-26, to help solubilize the BP-BotaniDew NMF ingredients. Clinical examination of the formulations demonstrated that the addition of at least 3% BP-BotaniDew NMF to the hand sanitizers significantly improved the moisturizing benefits of the formulations compared to placebo formulations without the BP-BotaniDew NMF. In a cursory study of real-world application, nurses working in a long-term care facility used the two formulations containing 5% BP-BotaniDew NMF ingredients and noted that the formulations seemed to be superior to their existing sanitizing ingredients and that both formulations showed superior moisturizing benefits versus their existing sanitizing products. This study suggests that incorporation of ingredients that can mimic the molecules normally stripped from the skin by alcohol hand sanitizers can be restored if formulated into alcohol-based products in an effective and stable way. Such formulations could potentially improve the aesthetic performance of such aggressive sanitizing products and improve user compliance which is critical for the effective use of such life-saving products. 

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