SPHINGOKINE NP

The Multilayer Skin Activator

Reduces skin sagging Plumps and densifies the skin Reshapes dermal scaffold Flattens wrinkle depth Tightens the skin structure and tones skin tissues Usage concentration: 0.02- 0.5% Personal Care

INCI name (PCPC name) (PCPC Caprooyl Phytosphingosine (proposed)

communication between keratinocytes and fibroblasts and dermal matrix stimulation by keratinocyte-derived signals. In the dermal parts of the human skin, SPHINGOKINE NP supports the dermal scaffold function by inducing fibroblast-derived signals for improved ECM (extracellular matrix) organization. In addition, dermal matrix formation is stimulated by keratinocyte- and adipocyte-derived signals. The activity of SPHINGOKINE NP proceeds even into the deep layer of the skin, the adipose tissue. Stimulation of adipocytes by SPHINGOKINE NP leads to induced cross-talk between adipocytes and fibroblasts, which ultimately results in additional support of dermal ECM. Besides that, adipose matrix formation and modulation of lipogenesis is stimulated by SPHINGOKINE NP, which results in denser subcutaneous fat tissue. This results in visibly plumped and reshaped skin.

Chemical and physical properties (not part of specifications) Form Active matter powder 90%

Introduction The skin as the largest human organ functions as a mechanical and chemical protection barrier between the body and the environment. It is made up of different layers, the outermost epidermis with the main barrier function and the subjacent dermis. Below the dermis the hypodermis or subcutaneous tissue is located. Communication between the cells within a certain skin layer, but also across different skin layers and between different skin cell types is very important for the proper function of the skin. This communication takes place via cell signaling molecules like adiponectin and leptin which are capable of controlling the action of the surrounding tissue. The unique short-chain ceramide SPHINGOKINE NP was found to stimulate the cross-talk between cells throughout the skin. It provides multilayer activity improving the state of the various skin layers (Figure 1). It functions as signaling sphingolipid. Due to deep penetration of SPHINGOKINE NP, the molecule can reach all different skin layers from the epidermis to the dermis and even the subcutaneous tissue.

In vivo facial study

Caucasian women (aged 50-70 years) participated in this study. Both formulations, one containing 0.2% SPHINGOKINE NP and the vehicle formulation were each tested by 30 volunteers in a half-side test. The formulations were applied twice daily on the face. The skin measurements were carried out at the beginning and after 4, 8, and 12 weeks in temperature and humidity-controlled rooms (24 2C, 50 10% relative humidity). The following parameters have been evaluated: skin roughness (wrinkle depth), skin density/echogenicity, the sagging degree of the skin. Finally digital images have been taken. Figure 2 shows the degree of skin sagging during the application period. Treatment with SPHINGOKINE NP decreased skin sagging already after 8 weeks and maintains by extended application.
Skin sagging - difference of expert grading score to start -0,12 T4-T0 -0,14 -0,16 -0,18 T8-T0 T12-T0

+
-0,20 -0,22

+ 10% reduced sagging *

Figure 1: Working mechanism of SPHINGOKINE NP

-0,24 Vehicle 0.2% SPHINGOKINE NP

In the epidermis SPHINGOKINE NP functions as signaling molecule for keratinocyte differentiation. This leads to strengthening, densifying and smoothing effects of the stratum corneum, the protection barrier of the human skin. In addition, factors that stimulate dermal cells (fibroblasts) are induced by SPHINGOKINE NP, leading to improved

sagging Figure 2: Degree of sagging skin relative to the beginning after 4, 8, and 12 weeks of application of experts. SPHINGOKINE NP graded by experts. (Statistics: tstart). Students t-test + p<0.05 vs. start).

The reduction of sagging skin degree after application of SPHINGOKINE NP can also be seen in the images in figure 3.

dermal scaffold is reshaped and the subcutis is densified and plumped.

Figure 3: Digital images of two representative volunteers. weeks (a) before, (b) 12 weeks after application of 0.2% SPHINGOKINE NP.

The sagging skin regions in the chin area have been improved and the contour of the face is visibly lifted. In addition, it can be seen that the depth of oral commissures and smile lines in the area at the mouth can be reduced by SPHINGOKINE NP. These findings can further be confirmed by measuring skin echogenicity/skin density. SPHINGOKINE NP markedly improved skin echogenicity/skin density already after 8 weeks of application compared to the vehicle (Figure 4). A significant increase in echogenicity of more than 200% compared to the vehicle formulation could be observed after 12 weeks.
Skin echogenicity - difference to start [%] 4 3 2 1

Figure 5: Ultrasound scanner picture of one panelist

Finally, the skin roughness was evaluated. Figure 6 shows that application of SPHINGOKINE NP led to a decrease of skin roughness. This effect was statistically significant compared to the vehicle control already after 8 weeks of application. After 12 weeks about 5-fold improvement of wrinkle depth compared to the vehicle formulation could be observed.
Skin roughness - delta Sa [ m]

220% improved density * ++

0 T4-T0 -2 T8-T0 T12-T0

**
-4

++ (*)

++

+
0 T4-T0 -1 -2 T8-T0 T12-T0

-6

**

-8

5-fold reduced wrinkle depth *

Vehicle 0.2% SPHINGOKINE NP

+
Vehicle 0.2% SPHINGOKINE NP

Figure 4: Skin echogenicity/skin density relative to the echogenicity/skin beginning after 4, 8, and 12 weeks of application of NP. tSPHINGOKINE NP. (Statistics: Students t-test ++ vehicle). p<0.01, + p<0.05 vs. start; ** p<0.01 vs. vehicle).

(Sa)/wrinkle Figure 6: Skin surface roughness (Sa)/wrinkle depth relative to the beginning after 4, 8, and 12 weeks of NP. tapplication of SPHINGOKINE NP. (Statistics: Students ttest ++ p<0.01 vs. start; ** p<0.01, (*) p<0.1 vs. vehicle). vehicle).

An example picture taken from the ultrasound scanner illustrates quite well these results. The images show ultrasound pictures of the skin at the defined time points. The lighter the structures appear, the denser is the skin tissue. Application of SPHINGOKINE NP leads to structure improvement of all skin layers. The epidermis is strengthened, the

These effects can also be seen in the PRIMOS Pico images in figure 7. The depth of the wrinkles near the eye is visibly reduced 12 weeks after application of 0.2% SPHINGOKINE NP.

To the best of our knowledge, there are no 3rd party rights covering the usage of SPHINGOKINE NP in cosmetic formulations. Formulation hints SPHINGOKINE NP is best soluble in polar oils like TEGOSOFT G 20 and TEGOSOFT APM or in solubilizers like pentylene glycol. Therefore, it is recommended to substitute a part of the oil phase by these polar oils. For cold processed emulsions it is recommended to solubilize SPHINGOKINE NP in pentylene glycol. Preparation of an O/W emulsion (cream or lotion): SPHINGOKINE NP is added to the oil phase of the emulsion which has to be heated to 75-80 C until SPHINGOKINE NP is completely solubilized. Then the emulsion is prepared as usual. The emulsion viscosity can be adjusted by using hydrocolloids like carbomer (TEGO Carbomer types) or xanthan gum. Preparation of a W/O emulsion (cream or lotion): SPHINGOKINE NP is added to the oil phase of the emulsion and heated up to 75-80C until it is completely solubilized. Then the emulsion is prepared as usual.

Figure 7: PRIMOS Pico images of two representative volunteers volunteers. (a) before, (b) 12 weeks after application of 0.2% SPHINGOKINE NP.

The results of this study demonstrate that SPHINGOKINE NP reduces signs of gravitational aging. SPHINGOKINE NP has a multilayer activity which could be shown in various in vitro studies on different skin cells. It improves keratinocytefibroblast and adipocyte-fibroblast cross-talk. Thereby, SPHINGOKINE NP provides a reshaped dermal scaffold and supports the structure of adipose tissue leading to plumped and densified skin. These effects lead to reduced skin sagging, significantly tighter skin and toned skin tissues. In addition, wrinkles can be flattened by application of SPHINGOKINE NP. Taken together, SPHINGOKINE NP is an innovative active ingredient for different kinds of anti-aging applications like anti-sagging products, shaping creams for face and body and products for improving facial contours. A detailed test summary report (technical dossier) is available on request.

Recommended usage concentration 0.02 0.5%, clinically tested at 0.2%

applications Possible applications Anti-aging face care Anti-sagging products Facial contour products Shaping creams and lotions

Packaging 0.25 kg

Claim summary Reduces skin sagging Plumps and densifies the skin Reshapes dermal scaffold Flattens wrinkle depth Tightens the skin structure and tones skin tissues Hazardous goods classification Information concerning classification and labelling according to regulations for transport and for dangerous substances protective measures for storage and handling measures in accidents and fires toxicity and ecological effects

Patent position A patent application describing the use of SPHINGOKINE NP in cosmetic formulations for reduction of skin sagging was filed by Evonik Industries AG.

is given in our material safety data sheets.

Guide Line Formulations Face Lifting Serum (MAC 753/2/7) Phase A TEGO Care LTP (Sorbitan Laurate; Polyglyceryl-4 Laurate; Dilauryl Citrate) TEGOSOFT G 20 (Octyldodecanol) TEGOSOFT OS (Ethylhexyl Stearate) TEGOSOFT CT (Caprylic/Capric Triglyceride) TEGO Carbomer 140 (Carbomer) TEGO Carbomer 141 (Carbomer) Xanthan Gum Phase B Glycerin HyaCare 50 (Hydrolized Hyaluronic Acid) SKINMIMICS (Ceteareth-25; Glycerin; Cetyl Alcohol; Behenic Acid; Cholesterol; Ceramide NP; Ceramide NS; Ceramide EOS ; Ceramide EOP; Ceramide AP; Caprooyl Phytosphingosine; Caprooyl Sphingosine) Water Phase C Sodium Hydroxide (10 %) Phase D Sphingokine NP Pentylene Glycol Phase Z Preservative, Perfume Preparation:
1. 2. 3. 4.

Shaping Body Lotion (MAC 753/2/5) Phase A 2.00% 4.00% 7.00% 2.00% 0.15% 0.15% 0.10% 3.00% 0.10% 1.00% TEGO Care LTP (Sorbitan Laurate; Polyglyceryl-4 Laurate; Dilauryl Citrate) TEGOSOFT G 20 (Octyldodecanol) TEGOSOFT OS (Ethylhexyl Stearate) TEGOSOFT CT (Caprylic/Capric Triglyceride) TEGO Carbomer 140 (Carbomer) TEGO Carbomer 141 (Carbomer) Xanthan Gum Phase B Glycerin Water Phase C Sodium Hydroxide (10%) Phase D 79.00% q.s. 0.10 % 1.40 % SPHINGOKINE SPHINGOKINE NP Pentylene Glycol Phase Z Preservative, Perfume Preparation: 1. 2. 3. 4. Mix ingredients of phase A. Combine phase A and B without stirring. Homogenize. Add phases C, D and Z and stir well. 0.05% 1.95% q.s. 2.00%

4.00% 7.00% 2.00% 0.15% 0.15% 0.10% 3.00% 80.60% q.s.

q.s.

Mix ingredients of phase A. Combine phase A and B without stirring. Homogenize. Add phases C, D and Z and stir well.

Especially concerning Active Ingredients This product information is not intended to provide legal or regulatory advice about product uses or claims in any jurisdiction and should not be relied upon for such guidance (especially in the United States, Canada, and Mexico). Since global regulatory requirements differ, parties accessing this information are solely responsible for determining whether the products and/or claims comply with applicable local laws and regulations, including but not limited to import and export regulations. Please contact your local Evonik representative for more product information. Evonik assumes no liability for any use of our products that is not in compliance with the requirements of the country of the user

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