TAGRAVIT TM R1 Encapsulated pure retinol. March 2015

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1 TAGRAVIT TM R1 Encapsulated pure retinol March 2015

2 Retinol- Background Retinol is a form of Vitamin A having a small molecular structure with MW of g/mol. Retinol can penetrate the outer layers of skin. Retinol accelerates mitosis, increases enzyme activity and normalizes keratinisation, which improves the cell renewal process. It exerts its anti-ageing benefits via: 1. Enhanced epidermal proliferation. 2. Increased collagen production. 3. Increase in elastin production and assembly. As a result the epidermis and dermis grow thicker and the skin becomes more elastic. This reduces wrinkles and lines in number, area, length and width. Int J Cosmet Sci 2011 Feb; 33:62-9.

3 Retinol- Challenges in formulating While retinol is among skincare s most popular ingredients, it nevertheless poses certain problems to product developers and bring many challenges to skincare formulations: 1. Retinol is hydrophobic compound that is liposoluble. 2. Retinol is highly unstable in the presence of heavy metals, oxygen and other oxidants. 3. Retinol is very sensitive to acidic conditions. 4. Retinol is highly sensitive to light. All results in loss of activity and discoloration of the formulation. Formulating with retinol is also time consuming and results in increased production cost. Thus, the vehicle used for retinol delivery would play a crucial role in eliciting its efficacy, as retinol is extremely unstable and easily gets degraded to biologically inactive forms on exposure to light and air.

4 Tagra Solution Microencapsulation technology platform which combines high loading, optimal protection/isolation and release of active ingredients. Polymeric shell Retinol US Patent Application No. 7,838,037 CHINA Patent Application No. ZL Method for Production of Single- and Multi-Layer Microcapsules

5 Tagra Solution con t Continuous (aqueous) phase Extraction agent Active Polymer dissolved in organic solvent Homogenize Add second continuous phase while stirring Droplet formation Solvent removal Washing & drying

6 Tagra Solution con t As a raw material Tagra s microcapsules appears in a powder form (Fig.1.) and do not break during its incorporation into the formulation. Figure.1. Figure.2. Figure.3. Once incorporated into the formulation, the microcapsules become elastic and soft maintaining their original spherical shape (Fig.2.). The polymeric shell protects the active ingredients by preventing cross reactions with other ingredients composing the formulation. Upon application, while rubbing the formulation into skin, the polymeric shell collapse (Fig.3.) and the microcapsules begin to fracture, releasing the encapsulated active. Microcapsules breaks down to invisible particles, but still retain a portion of the payload to continue and deliver over time.

7 Tagravit TM R1- Encapsulated Retinol Description: Tagravit TM R1 is a polymeric microcapsule delivery system. It is an inert carrier that protects and stabilizes the Retinol in formulation until its release on the skin by a mechanical pressure such as a rubbing action. Product Specification: Appearance Color- Loading- 7% Average particle size- Storage Conditions- Shelf life- Free flowing powder Light Yellow ~30 micron Closed containers, <10 C 12 months

8 TagravitTM R1- Size and Shape

9 Tagravit TM R1- Stability Study Tagravit TM R1 stability was measured using HPLC method compared to free retinol (non encapsulated) in a gel formulation. The gel was incorporated with 0.1% of retinol (1.45% of Tagravit TM R1) at 40 C for 100 days.

10 Tagravit TM R1- Stability Study con t Tagravit TM R1 stability was physically observed and compared to free retinol (non encapsulated) in a gel formulation. The gel was incorporated with 0.1% of retinol (1.45% of Tagravit TM R1) at 40 C for 360 days. By formulating with the Tagravit TM R1 the discoloration of the gel formulation was prevented. Tagravit R1 Free Retinol Tagravit R1 Free Retinol Tagravit R1 Free Retinol Day 1 Day 100 Day 360 Tagravit TM R1 Microcapsules successfully protect Retinol from oxidation and degradation as active raw material in cosmetic formulations.

11 Tagravit TM R1- Efficacy test

12 Tagravit TM R1- Efficacy test con t

13 Tagravit TM R1- Efficacy test con t Mean changes of parameters Rz (averaged depth of roughness) and Ra (arithmetic mean roughness) at areas 1 to 5 after 4 week treatment with base night cream and base night cream incorporated with 1.5% Tagravit R1 microcapsules as compared to untreated volunteers. Area 1 in proximity, area 5 in distance to the eye.

14 Tagravit TM R1- Efficacy test con t Mean changes of parameters Rz and Ra in the periorbital zone (average of the 5 subareas) after 4 week treatment with base night cream and base night cream incorporated with 1.5% Tagravit R1 microcapsules as compared to untreated volunteers. Area 1 in proximity, area 5 in distance to the eye.

15 Tagravit TM R1- Efficacy test con t

16 Tagravit TM R1- Benefits Significantly improves the stability of retinol, resulting in formulations that are more effective with maximum efficacy. Formulating with Tagravit TM R1 results in prolonged product shelf life by enhancing formulation stability. It is easy to use and handle- free flowing powder form. Tagravit TM R1 prevents discoloration of the formulation. Targeted release of retinol Non-nano product- average particle size ~30 micron Tagravit TM R1 can be used in any kind of vehicle- gels, lotions, creams, emulsions.

17 Tagravit TM R1- Typical applications Anti-ageing and skin rejuvenation products Make-ups and Foundations with skin care benefits Daily use moisturizers and lotions Facial and body masks Hand and body lotions Anti-acne products Skin lightening

18 Tagravit TM R1 For samples request and technical support please contact Dr. Danny Goldstein at: Mobile:

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