Active TECHNICAL FILE ingredients - Lucas Meyer Cosmetics

Activeingredients

IBR-SNOWFLAKE®

Summer snowflake bulb extract -Safe and natural alternative to Botox injections-Helps to reduce sweating, the appearance of wrinkles and keeps a fresh look while exercising

TECHNICAL FILE

Freezing power for fresh and flawless skin

Technical File IBR-Snowflake®

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TECHNICAL FILE IBR-SNOWFLAKE®

ContentsSUMMARY ...................................................................................................................................................... 2 INTRODUCTION .............................................................................................................................................. 3 BOTOX: FROM BACTERIA TO BEAUTIFUL & FRESH.... ....................................................................................... 3

BOTOX AND SWEATING ........................................................................................................................................ 4

WHAT IF NATURE HOLDS THE SOLUTION? ....................................................................................................... 4 THE POWER OF SUMMER SNOWFLAKE FLOWER ........................................................................................................... 4

ON THE SUSTAINABILITY SIDE… ................................................................................................................................ 5

IBR-SNOWFLAKE®’S MECHANISM OF ACTION AND CONCEPT ........................................................................................ 6

CLINICALLY PROVEN ............................................................................................................................................... 7

EFFICACY STUDIES ........................................................................................................................................... 8 CLINICAL STUDIES ......................................................................................................................................... 11

CLINICAL EVALUATION ON WRINKLE REDUCTION .......................................................................................... 11

CLINICAL EVALUATION ON WRINKLE REDUCTION .......................................................................................... 14

Assessment of anti-wrinkle efficacy by clinical grading ................................................................................ 15

CLINICAL EVALUATION ON SWEAT REDUCTION UNDER EFFORT .................................................................... 19

COSMETIC APPLICATIONS ............................................................................................................................. 23 RECOMMENDATIONS FOR USE ...................................................................................................................... 23

TECHNICAL FILE


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SUMMARY

INCI NAME

CAS

EINECS

IBR-Snowflake® all natural

Glycerin (1°) (and) Water (2°) (and) Leucojum Aestivum Bulb Extract

IBR- Snowflake®

Water (2°) (and) Leucojum Aestivum Bulb Extract

(1°) 56-81-5, (2°) 7732-18-5

(1°) 200-289-5, (2°) 231-791-2

ORIGIN Extract derived from summer snowflake bulbs (Leucojum Aestivum)

COSMETIC PROPERTIES

• Muscle relaxant • Smoothens facial wrinkles and expression lines • Effective after 7 days of use (Botox-like efficacy) • Reduce sweating after exercise

SKIN BENEFITS / POTENTIAL CLAIMS

• Natural & fast-acting ingredient • Smoothens facial wrinkles and expression lines in 7 days • Gain a youthful natural look • Reduces excessive sweating after exercise

APPLICATIONS

• Anti-age • Day care • Active Beauty care • Body care • Men care • Deodorant • Makeup • Dermocosmetic

RECOMMENDED DOSAGE 0.5-1%

USAGE pH RANGE 3.0 – 8.0

INCORPORATION Should be incorporated at the end of the formulation at a temperature < 40°C

INCOMPATIBILITIES No known incompatibility


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INTRODUCTION

BOTOX: FROM BACTERIA TO BEAUTIFUL & FRESH.... Botulinum toxin (Botox) is a neurotoxin produced by the anaerobic bacterium Clostridium botulinum. In 1895, it was recognized as the cause of botulism, a frequently fatal form of food poisoning. In 1965, Drachman demonstrated paralysis of chick’s muscles after botulinum toxin injection, a finding that encouraged Allan Scott, an ophthalmologist, to investigate it further for treatment of crossed eyes. In 1989, the FDA approved Botox for treatment of crossed eyes, uncontrollable blinking and hemifacial spasm. Over the next years, research exploded in this area; different toxins were developed, and botulinum toxin was approved for several other applications including dermocosmetic applications like the treatment of hyperfunctional facial lines (2002) and hyperhidrosis (2004) [1].

The face is the focus of human interactions. Significant changes of facial morphology and appearance influence age perception and consequently self-esteem [2]. We all experience a range of emotions every day, each coming with a different facial expression. After hundreds of different facial expressions per day, 365 days per year, for several decades, expression lines begin to take shape. As we age, the muscle tone of our facial muscles increases. This along with decreased collagen metabolism results in expression wrinkles [3]. Botox injection is an effective and safe treatment to reduce the appearance of expression wrinkles. Botox works by blocking nerve signals in the muscles where it is injected, temporarily freezing the affected muscle. Without movement of these selected muscles, certain wrinkles may be softened, reduced, or even removed. Botox effects start to show three days after injection with maximal effects evident after 2 weeks [4,5]. According to the American Society of Plastic Surgeons (ASPS), 7.2 million Botox injections were performed in 2017, increasing by 2% from 2016. Non-surgical procedures such as Botox are becoming an increasingly important part of younger US women's repertoire to prevent the onset of lines and wrinkles. The popularity of Botox is paralleled by a marked decrease in the more invasive, costly and 'permanent' face lift procedures. This is a growing universal movement, with 11% of Chinese women aged 25-29 having used Botox or a spot removal treatment in the last six months.


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However, settling into a dermatologist's chair for injections isn't as easy as it sounds, especially if one is uneasy with the sight of sharp objects. Shots can be painful and can cause bruising and are costly as well. Too much Botox looks unnatural, generating an expressionless face. These led skincare brands to offer a 'botox-like look' without the time, cost and possible complications of receiving a Botox injection. BOTOX AND SWEATING Sweating is natural body response to increased body temperature. Hyperhidrosis is defined as sweating in excess of what is required to regulate body temperature. As many as 1.3 million Americans are diagnosed with severe hyperhidrosis. Affected patients are vulnerable in occupational and social situations, leading to diminished physical and emotional well-being, difficulty in personal relationships, and social stigmatization. Botox has emerged as an important treatment option for patients overwhelmed with focal hyperhidrosis. The toxin temporarily inhibits the release of acetylcholine, preventing the hyperstimulation of eccrine sweat glands that leads to excessive sweating [6]. More recently, many celebrities are adding a little pit-stop to their wellness routines. Chrissy Teigen, the famous model, revealed recently one of the industry’s best secrets in her Instagram stories (Aug 2019), detailing that Botox keeps her perspiration-free. “Botoxed my armpits. Truly best move I have ever made… I can wear silk again without soaking” [7]. Fitness and exercise have become the new social currency and an occasion for social interaction. This is driving the millennial desire to look both fashionable and to be “ready for anything”. The ambition to lead more active and healthier lifestyles is driving the athleisure trend in the personal care industry. This has been prompting several retailers to launch their own collections for both active men and women. Athleisure personal care innovation includes skin cooling makeup that is sweat-resistant, sun-care products that work better when exposed to water, and shampoo that counters hair loss due to sporting activities [8]. Attentive to the market needs, IFF/Lucas Meyer has developed IBR-Snowflake®, a new innovative botanical solution with Botox-like efficacy, not to make your makeup sweat proof but to reduce sweating in the first place…

WHAT IF NATURE HOLDS THE SOLUTION? THE POWER OF SUMMER SNOWFLAKE FLOWER

Leucojum aestivum is a relatively small bulbous crop, usually grown for landscaping and rock gardens. This species originates from the Mediterranean area, where summers are hot and dry, but winter conditions are favorable for plant growth and development. Its common name is summer snowflake or summer snowbell.

In Israel, sprouting begins in the fall, leaves and floral stalks elongate through the winter and spring, and summer dormancy is common. L. aestivum is a Central-South-European/Western-Asiatic species whose distribution in the North reaches Ireland, Czech Republic and Slovakia, and in the East Turkey, the Crimea and Iran. In its native distribution area it occupies muddy wetland habitats near rivers, lakes or on the banks of canals [9].


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L. aestivum naturally produces some neurotoxic substances as a means of defense against herbivores and pathogens [9]. This inspired us to develop a Botox-like active ingredient, IBR-Snowflake®.

The snowflake flower symbolizes purity and hope. In a known painting from the 15th century, “The Paradise Garden”, snowflake flowers are part of the garden idyll showing a symbolic cure to the hardships endured by the people of the time.

ON THE SUSTAINABILITY SIDE… Israel has a nature protection plan that contributes to maintaining endemic species while preserving ecological balance, both locally and countrywide. IFF/Lucas Meyer Cosmetics only uses bulbs originating from cultivated fields, with well-balanced reserves of plant materials for regrowth. We also make sure our source material is collected under long-term cooperation agreements with local growers. We use natural and environmentally friendly extraction, with no chemical solvents or processing aids, and no chemical waste is being generated during the production.

MEDICINAL PROPERTIES OF LEUCOJUM AESTIVUM

According to the International Plant Genetic Resources Institute, L. aestivum is considered a Medicinal Plant, containing several pharmaceutically important alkaloids in its bulbs and leaves. These alkaloids are approved drugs for the treatment of patients suffering from senile dementia of the Alzheimer type, poliomyelitis, alcohol and nicotine dependence and other neurological diseases [9].


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IBR-SNOWFLAKE®’S MECHANISM OF ACTION AND CONCEPT With IBR-Snowflake®, IFF/Lucas Meyer cosmetics has developed a technology that captures and transfers the plant’s defense mechanism as power to freeze away facial expression lines & sweat. IBR-Snowflake® is a natural, aqueous extract derived from summer snowflake bulbs. In vitro, the extract potently blocks muscle contraction in a contractile neuron-muscle co culture.

Blocking nerve signals and temporarily freezing muscle action is an efficient Botox-like strategy. With its muscle relaxant activity, IBR-Snowflake®:

1. Softens and reduces expression lines (crow’s feet and forehead).

2. Reduces sweat excretion after exercise.


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CLINICALLY PROVEN

In a clinical study on women, IBR-Snowflake® significantly smoothened facial wrinkles and expression lines in the crow’s feet & forehead areas. In the same study, the IBR-Snowflake® significantly reduced sweating after exercise, generating a fresh and flawless look.


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EFFICACY STUDIES


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IN-VITRO: MUSCLE CONTRACTION ASSAY

BACKGROUND In vitro, a Botox-like effect can be observed on a contractile nerve-muscle co-culture. The principle of this study is based on the counting of the muscular contractions during a given time, before and after treatment with the product. OBJECTIVE The aim of the study was to evaluate the Botox-like effect of IBR-Snowflake® via the observation of muscle contractions in a muscle-nerve co-culture. PROTOCOL Materials The study was performed on a co-culture of human muscle cells and embryonic spinal cord nerve cells. IBR-Snowflake® was tested at 1.5% dilution in culture medium. The negative control was the culture medium alone. The positive control was carisoprodol, a drug which blocks muscular contractions in a reversible way. Methods The trial was carried out on the 21st day of culture. The cells were observed well per well, under a microscope equipped with a motorized stage piloted by LUCIA software, as well as with a camera connected to a computer allowing the recording of video sequences. A contractile fiber was selected, the XY coordinates of the fiber were registered by the LUCIA software. The frequency of the contractions of the fiber were manually counted over 30 seconds, and a video sequence was recorded (T0). The same operations were carried out on 3 wells for each sample /condition tested. The products and the references were applied on the nerve-muscle culture, and the trial system was incubated at 37°C, 5% of CO2. After 2 h, 6 h and 24 h of incubation, the contraction frequencies were again counted over 30 seconds, and a video sequence was recorded for each count. The number of contractions obtained in presence of the product was expressed as a percentage compared to the initial number of contractions. A product is considered to have a Botox-like effect if a significant reduction or a blocking of the muscular contractions frequency was observed in at least 2 out of 3 culture wells.


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RESULTS

After as little as 2 hours, muscle contractions are completely stopped with treatment with 1.5% IBR-Snowflake®. These results are comparable to those observed with the positive control, while untreated cells continue to contract normally.

CONCLUSION

IBR-Snowflake® effectively blocks muscle contraction


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CLINICAL STUDIES

CLINICAL EVALUATION ON WRINKLE REDUCTION OBJECTIVE The aim of the study was to evaluate the capacity of IBR-Snowflake® to reduce the appearance of wrinkles (Botox-like effects). PROTOCOL Subjects Two groups of 21 healthy female volunteers, 40-65 years of age, showing moderate wrinkling in the crows’ feet area, were included in this clinical trial with informed consent. Tested product A simple cream containing 2% IBR-Snowflake® was used for this study, alongside a placebo product in which the active ingredient was replaced with water and glycerin (to account for the glycerin content in IBR- Snowflake®).

Ingredient (INCI) ACTIVE formula %

PLACEBO %

Water QS 100.00 QS 100.00 Potassium Palmitoyl Hydrolyzed Wheat Protein (and) Glyceryl Stearate (and) Cetearyl Alcohol 8.00 8.00

Isohexadecane 8.00 8.00 Caprylic/capric Triglyceride 8.00 8.00 Propylene glycol 5.00 5.00 PPG-15 Stearyl Ether 2.00 2.00 Magnesium aluminum silicate 2.00 2.00 Leucojum aestivum bulb extract (IBR-Snowflake®) 2.00 0.00 Benzyl Alcohol (and) Dehydroacetic Acid (and) Benzoic Acid (and) Sorbic Acid 1.00 1.00

Cetearyl Alcohol 0.50 0.50 Xanthan gum 0.20 0.20

Test conditions Measurements were performed on D0 before product application, and again on D28, following 4 weeks of twice-daily application.


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METHODS Microrelief replica image analysis The study was run based on a double-blind, split-face design (active vs. placebo), allowing for each subject to become their own control. Silicone imprints of the subjects’ skin were taken at the crows’ feet area at each study time point. These imprints were analysed with a Skin Image Analyser® (S.I.A), using oblique lighting (35°) to cast shadows, which were then recorded with a digital camera linked to a computer. A 1 cm2 area was studied. The resulting digitized images enabled the analysis of the skin surface relief using the QUANTIRIDES® - MONADERM software, focusing on microrelief furrow counts. Microrelief furrows are defined as having a depth inferior to 55 µm. furrows with a minimum surface of 0.03 mm2 were detected. STATISTICAL METHODS Results were analyzed using a Student’s paired t-test, with p=0 RESULTS

2% IBR-Snowflake® in formulation delivers a clear and significant reduction in the number of microrelief furrows, vs. D0 and placebo.


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Illustrative images are presented below (subject #8):

CONCLUSION

IBR-Snowflake® delivers a significant anti-wrinkle effect for smooth skin


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CLINICAL EVALUATION ON WRINKLE REDUCTION

OBJECTIVE The aim of the study was to evaluate the capacity of IBR-Snowflake® to reduce the appearance of wrinkles as well as effort-induced sweating (Botox-like effects). PROTOCOL Subjects Two groups of 27 healthy Portuguese female volunteers, 35-50 years of age, with skin phototype II to IV (Fitzpatrick), of all skin types, with self-assessed excessive sweat and the capability of performing physical exercise, were included in this clinical trial with informed consent. Tested product A simple gel-cream containing 1% IBR-Snowflake® was used for this study, alongside a placebo product in which the active ingredient was replaced with water and glycerin (to account for the glycerin content in IBR- Snowflake®).

INCI/chemical name ACTIVE formula %

PLACEBO %

Water 84.35 84.85 Butylene glycol 4.00 4.00 Dipropylene glycol 1.00 1.00 Hexylene glycol 1.00 1.00 Polysorbate 20 1.00 1.00 Hydrogenated polydecene 1.50 1.50 Cyclomethicone 4.00 4.00 Leucojum aestivum bulb extract (IBR-Snowflake®) 1.00* 0.00 Glycerol 0.0 0.50 Carbomer 0.80 0.80 Triethanolamine 0.70 0.70 Phenoxyethanol 0.40 0.40 Methyl paraben 0.15 0.15 EDTA 0.10 0.10

Test conditions The tested product was applied twice a day at home by the panelists, following initial training by CRO clinicians. One group of panelists was assigned the product, and the second group was assigned the placebo (using double-blind product encoding). The product was left on skin after application. Measurements were taken before application on D0 and after 3, 7, and 14 days of application. On D0, D7, and D14, measurements related to perspiration rate were taken before and after exercise. Product consumption was checked at the end of the study.


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METHODS General conditions All evaluations were performed in a fully controlled room and after an initial acclimatization period of at least 20 min in a climate-controlled room (T = 21 ± 2°C; RH = 55 ± 10%). To avoid circadian changes, two evaluation periods were defined (9h00m-13h00m and 13h00m-19h00m). Each subject chose, on the first day, the best hour to be evaluated. All evaluations were performed during the chosen period of the day for each panelist. Perspiration was triggered by 20 min of exercise on a treadmill. Anti-wrinkle effect by image analysis (AEVA 3D) 3D images of the skin topography were obtained using a stereo camera combined with a fringe projection system (AEVA-HE, Eotech, France). A fringe standard is projected on the skin and detected by the dual cameras of the optical system. The 3D effect is calculated by the deflection in the fringes which represent qualitatively and quantitatively the skin profile, and by the stereo-combination of the image projected by both cameras. The areas evaluated were the crow´s feet and the upper part of the forehead.

Assessment of anti-wrinkle efficacy by clinical grading

Anti-wrinkle efficacy was assessed using a photographic scale based on the reference standard for the Japanese Cosmetic Industry Association. The system consists of a photograding scale of 8 degrees, which allow to easily quantify the wrinkling aspect. The grading scale is described in the following figure:

Wrinkle Grading scale according with Japanese Cosmetic Industry Association and Ooe,M. et al..

The use of intermediate half-point grades was allowed so as to introduce additional resolution to the process of clinical evaluation of wrinkles.


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Illustrative imaging by Visia®-CA Standardized photographic images were obtained with normal and cross-polarized lighting for both hemifaces and full face (frontal angle) before, during and after the treatment (D0, D7 and D14) using the VISIA®-CA (Canfield, USA) system in order to provide general macrophotography records. STATISTICAL METHODS Resulting data and percentage variations were submitted to the Paired Student’s t-Test or the Wilcoxon test (*p<0.05). RESULTS Anti-wrinkle effect (AEVA 3D image analysis) In the crow’s feet area: Instrumental analysis 1% IBR-Snowflake® in formulation delivers a rapid anti-wrinkle effect in the crow’s feet area, showing a reduction in wrinkle counts and volume already after three days of use, with statistical significance vs. D0 and vs. placebo at D7 and D14.

Illustrative photographs:


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Clinical grading Clinical grades of wrinkling at the crow’s feet show a significant anti-wrinkle effect at D14 (with statistical break vs. D0 and placebo) with 1% IBR-Snowflake® in formulation.

In the forehead area: In the forehead area, 1% IBR-Snowflake® in formulation shows a strong advantage vs. placebo in wrinkle counts and depth (with statistical significance at D14).


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Illustrative photographs:

CONCLUSION

IBR-Snowflake® delivers a rapid and strong anti-wrinkle effect for flawless skin


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CLINICAL EVALUATION ON SWEAT REDUCTION UNDER EFFORT

OBJECTIVE The aim of the study was to evaluate the capacity of IBR-Snowflake® to reduce the appearance of wrinkles as well as effort-induced sweating (Botox-like effects). PROTOCOL Subjects Two groups of 27 healthy Portuguese female volunteers, 35-50 years of age, with skin phototype II to IV (Fitzpatrick), of all skin types, with self-assessed excessive sweat and the capability of performing physical exercise, were included in this clinical trial with informed consent. Tested product A simple gel-cream containing 1% IBR-Snowflake® was used for this study, alongside a placebo product in which the active ingredient was replaced with water and glycerin (to account for the glycerin content in IBR- Snowflake®).

INCI/chemical name ACTIVE formula %

PLACEBO %

Water 84.35 84.85 Butylene glycol 4.00 4.00 Dipropylene glycol 1.00 1.00 Hexylene glycol 1.00 1.00 Polysorbate 20 1.00 1.00 Hydrogenated polydecene 1.50 1.50 Cyclomethicone 4.00 4.00 Leucojum aestivum bulb extract (IBR-Snowflake®) 1.00* 0.00 Glycerol 0.0 0.50 Carbomer 0.80 0.80 Triethanolamine 0.70 0.70 Phenoxyethanol 0.40 0.40 Methyl paraben 0.15 0.15 EDTA 0.10 0.10

Test conditions The tested product was applied twice a day at home by the panelists, following initial training by CRO clinicians. One group of panelists was assigned the product, and the second group was assigned the placebo (using double-blind product encoding). The product was left on skin after application. Measurements were taken before application on D0 and after 3, 7, and 14 days of application. On D0, D7, and D14, measurements related to perspiration rate were taken before and after exercise. Product consumption was checked at the end of the study.


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METHODS General conditions All evaluations were performed in a fully controlled room and after an initial acclimatization period of at least 20 min in a climate-controlled room (T = 21 ± 2°C; RH = 55 ± 10%). To avoid circadian changes, two evaluation periods were defined (9h00m-13h00m and 13h00m-19h00m). Each subject chose, on the first day, the best hour to be evaluated. All evaluations were performed during the chosen period of the day for each panelist. Perspiration was triggered by 20 min of exercise on a treadmill. Sweat excretion and skin barrier function assessment by TEWL Trans Epidermal Water Loss (TEWL) assessment was assessed using a Tewameter™ (Courage & Khazaka, Germany), based on Fick´s law: dm/dt=-D.A.dp/dx – Where A: area (m2); m: amount of water (g); t: time (h); D: diffusion coefficient (0.0877 g/m.h.mmHg); p: environment vapor pressure (mmHg); x: distance between the skin and the measurement point (m). The diffusion flux, dm/dt, shows the amount of water transported by m2 for a determined period of time, which is directly proportional to the surface area (A) and the concentration gradient (dp/dx). The measurement was carried out on the forehead. This method was used to evaluate sweat excretion by comparing values before and after exercise, normalized per exercise unit time. Illustrative imaging by Visia®-CA Standardized photographic images were obtained with normal and cross-polarized lighting for both hemifaces and full face (frontal angle) before, during and after the treatment (D0, D7 and D14) using the VISIA®-CA (Canfield, USA) system in order to provide general macrophotography records. STATISTICAL METHODS Resulting data and percentage variations were submitted to the Paired Student’s t-Test or the Wilcoxon test (*p<0.05). RESULTS Sweat excretion rate reduction

a. By image analysis of Silflo silicone imprints 1% IBR-Snowflake® in formulation delivered a rapid and very strong reduction in the number of active sweat glands (perspiration droplets) observed upon standardized exercise. This reduction is significant vs. D0 at D7 and D14, and vs. placebo at D14.


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Illustrative images are presented below (volunteer #8); all imprints shown below were taken after standardized exercise.

By TEWL 1% IBR-Snowflake® in formulation delivered a rapid and strong reduction in excretion rates (calculated as the difference in skin barrier function, as measured by TEWL, after vs. before exercise, normalized for the exercise time). Statistical analysis shows the effect is significant vs. D0 from D7, and continues to build in magnitude and acquires significance vs. placebo at D14.


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CONCLUSION

IBR-Snowflake® reduces sweat production for a fresh look at the gym


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CONCLUSION Significant changes of facial morphology and appearance as well as excessive sweating influence social perception and, consequently, self-esteem. Botox injection is an efficient approach to smoothen expression lines and reduce excessive sweating. However, it requires expensive visits to the dermatologist and may have undesired side effects. Consumers are looking for a safe, non-invasive cosmetic alternative to Botox injections. IFF/Lucas Meyer Cosmetics have developed the perfect botanical active to reduce the appearance of wrinkles and reduce excessive sweating after exercise. IBR-Snowflake® reduces facial muscle contraction. Without movement of these muscles, wrinkles may appear softened and reduced. In the same way, affecting muscle contraction around sweat glands reduces sweat excretion. This is the perfect solution for beauty conscious active women.

COSMETIC APPLICATIONS • Anti-age • Day care • Active Beauty care • Body care • Men care • Deodorant • Makeup • Dermocosmetic

RECOMMENDATIONS FOR USE IBR-Snowflake® can be added to aqueous gels, gel-creams and emulsions. FORMULATION It is recommended to introduce IBR- Snowflake® at a temperature below 40°C. RECOMMENDED DOSAGE Preventive action: 0.5% Optimal action: 1%


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REFERENCES

1. Jabbari B. History of Botulinum Toxin Treatment in Movement Disorders. Tremor Other Hyperkinet Mov (N Y) 2016; 6: 394.

2. Finn CJ, et al. Social implications of hyperfunctional facial lines. Dermatol Surg. 2003;29:450-455. 3. Coleman SR and Grover R. The anatomy of the aging face: Volume loss and changes in 3-dimensional

topography. Aesthet Surg J. 2006;26(1 Suppl):S4-S9. 4. Carruthers A, et al. Efficacy and safety of onabotulinumtoxin A for the treatment of crow’s feet lines:

A multicenter, randomized, controlled trial. Dermatol Surg. 2014;40:1181-1190. 5. Fagien S, et al. Forehead line treatment with onabotulinumtoxin A in subjects with forehead and

glabellar facial rhytids: A phase 3 study. Dermatol Surg. 2017;43:S274-S284. 6. Doft MA, et al. Treatment of Hyperhidrosis With Botulinum Toxin. Aesthetic Surgery Journal, Volume 32,

Issue 2, February 2012, Pages 238–244, 7. https://www.harpersbazaararabia.com/beauty/expertise/say-goodbye-to-sweat-patches-forever 8. https://www.cosmetics-technology.com/research-reports/athleisure-trend-opportunities-skincare/ 9. Parolo G, et al. Biological flora of Central Europe: Leucojum aestivum L. Perspectives in Plant Ecology,

Evolution and Systematics 13 (2011) 319–330

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