Very low molecular weight Hyaluronic Acid
- A breakthrough in anti-ageing properties -
• 50 KDa Hyaluronic Acid
• Increased permeation through the skin compared to
high molecular weight hyaluronic acid
• Rejuvenates the skin by improving its viscoelastic
• Significantly decreases deep wrinkles
INCI Name (CTFA name) In parallel, intensive developments have been made
to check if molecular weight reduction would provide
Under evaluation by the CTFA
even more skin care benefits. This lead to the
introduction of HyaCare® 50, a new and unique very
low molecular weight hyaluronic acid (50Kda)
Chemical and physical properties produced by fermentation of Bacillus subtilisis using
(not part of specifications) an environmentally friendly aqueous recovery
Solubility in water 10g/100g
In-vitro penetration study
Hyaluronic acid (HA) is a non-sulfated
glycosaminoglycan (GAG), naturally distributed in The penetration of different molecular weight
human body. Hyaluronic acid is the major fractions has been evaluated using side by side
component of the extra cellular matrix. It is found in diffusion cells and tritiated hyaluronic acid on
high quantity in the skin where it is produced mainly dermatomed skin from the porcine ear. The receptor
by both fibroplasts and keratinocytes. was filled with PBS buffer and the donor with
radiolabeled HA solution. After incubation for 5 h
One of its main functions is to hold the water in the and 22 h at room temperature, the receptor phase
intercellular matrix of the connective tissue. This was removed and radioactivity was determined by
water-binding capacity contributes significantly to liquid scintillation counting.
the elasticity of the skin. Hyaluronic acid plays the
role of water pump maintaining the elasticity by
acting as a water reservoir. Hyaluronic acid is also 150
involved in tissue repair. While it is abundant in
extracellular matrices, it also contributes to tissue
hydrodynamics, movement and proliferation of cells, 100 First bar: flux at 5 hr
and participates in a number of cell surface receptor
Second bar: flux at 22 hr
interactions, notably those including its primary
receptor, CD44. 50
When skin is excessively exposed to UV-B rays, it
becomes inflamed and the cells in the dermis stop 0
producing hyaluronic acid and increase the rate of its 50K 300K 800K 1500K
degradation. With aging, the quantity of hyaluronic HA molecular weight (Da)
acid and its degree of polymerisation decrease
leading to a decrease in the water content hold by Figure 1: Influence of HA MW on percutaneous transport
the connective tissue and a loss of elasticity that As seen in figure 1, HyaCare® 50 shows a much
manifests itself in wrinkles. stronger permeation through the skin in comparison
to higher molecular weight products.
In normal human skin, hyaluronic acid exists as a
polymer of medium molecular weight (600-1,000
Kda). The physiological degradation of hyaluronic In- DNA-
In-vitro DNA-Chip analysis
acid in the skin is done via internalisation by the The study was performed at the University of
keratinocytes and fragmentation by hyaluronidases. Regensburg (D).
The effect of HyaCare® 50 on gene expression was
High molecular weight hyaluronic acid has been used analyzed using DNA-chip technology and SkinEthics
for many years as natural moisturizer in the cosmetic models. It was demonstrated that HyaCare® 50
industry. In 2003 the FDA has approved hyaluronic changed the regulation of more than 40 genes,
acid injections for filling soft tissue defects such as namely upregulation of detoxification and cell-cell
facial wrinkles. Hyaluronic acid injections temporarily adhesion genes. From this result it can be
smooth wrinkles by adding volume under the skin, anticipated that HyaCare® 50 has positive effects on
with effects typically lasting for six months. detoxification mechanisms and tautness of the skin.
This FDA approval and the significant trend for botox
like cosmetics reinforced the demand for hyaluronic
acid. Hyaluronic acid is now not only considered a
moisturizer but as a relevant anti-aging ingredient.
Our in vivo data on our medium molecular weight
HyaCare® confirmed this statement.
In-vivo efficacy study
Long-term evaluation of skin elasticity and
% decrease in viscoelastic ratio
roughness 40 **
The study was performed at ISPE srl., Milan (I). 35
Skin elasticity and skin roughness of an O/W cream
relative to t0
containing 0.1 % HyaCare® 50 in comparison to a 25
placebo formulation were evaluated. The 20 * Placebo
measurements were carried out in a climatic room
(24°C; 50 % rh) in order to keep the temperature and
the humidity during the measurements constant. 0
Each of the 12 volunteers was required not to wash 4 8
their face for at least 3 hours before performing the Time (weeks) * significant
measurements. The assessment was performed on ** highly significant
the face, where half of the face was treated with the 3:
Figure 3: Decrease in the skin viscoelastic ratio after 4
cream containing HyaCare® 50 and the other half formulations
and 8 weeks application of test formulations
with the placebo cream. The side of application on
the face (left or right) of the two products was Skin image analysis showed a significant decrease of
randomised. maximum skin roughness of 10% of the area treated
with HyaCare® 50 formulation (figure 4).
At the beginning of the study instrumental
evaluation of skin elasticity and roughness were
carried out onto the left and right peri-ocular areas,
roughness value relative to t0
marked out in a reproducible way. The subjects
% decrease in maximum
applied the products on the face at home once a day 11 * *
for 8 weeks. After 4 weeks and at the end of the 9
treatment the subject returned to the laboratory for 7 HA50
the instrumental measurement.
The area treated with the formulation containing -1
HyaCare® 50 showed a significant increase of the 4 8
overall elasticity value, equal to 14% after 4 and 8 Time (weeks)
weeks of application (figure 2).
Figure 4: Maximum Roughness ratio after 4 and 8 weeks
application of test formulations
These data confirmed the anti-wrinkle activity of
% increase in overall elasticity
20 HyaCare® 50 mainly in terms of decrease of deep
15 * * wrinkles as illustrated in figures 5 and 6.
relative to t0
Figure 2: Overall skin elasticity after 4 and 8 weeks
application of test formulations
The area treated with HyaCare® 50 showed as well a
Figure 5: Skin image analysis before and after 4 weeks of
highly significant decrease in the viscoelastic ratio
treatment with HyaCare® 50
(R6) equal to 36% after 8 weeks. This reflects the
rejuvenation of the skin through the increase of its
elastic component (figure 3).
Figure 6: Skin image analysis before, after 4 and 8 weeks
of treatment with HyaCare® 50
Preparation Guide Line Formulations
HyaCare® 50 is completely soluble in water and can
be processed cold. For the preparation of both O/W Anti-
O/W Anti-Wrinkle Cream - Filler effect
or W/O emulsions it should be added to the water 534/3/3
phase. In O/W emulsions HyaCare® 50 might reduce Phase A
the viscosity of the emulsion. The desired viscosity
TEGOSOFT® CI (Cetearyl Isononanoate) 5.0%
of O/W emulsions can be adjusted by increasing the
amount of polyacrylates (e.g. TEGO® Carbomer) or by TEGOSOFT® Liquid 5.0%
increasing the concentration of consistency Cetearyl Ethylhexanoate)
enhancers, e.g. TEGO® Alkanol 18 (Stearyl alcohol), TEGOSOFT® DC (Decyl Cocoate) 4.0%
TEGO® Alkanol 1618 (Cetearyl alcohol), TEGIN® M or TEGO® Alkanol 1618 (Cetearyl Alcohol) 3.0%
TEGIN® 4100 (Glyceryl Stearate). HyaCare® 50 shows
TEGIN® 4100 Pellets (Glyceryl Stearate) 1.0%
good compatibility with other ingredients.
Stearic Acid 1.0%
Tocopheryl Acetate 2.0%
Recommended usage concentration Phase B
0.01 – 0.2% of HyaCare® 50 TEGO® Care CG 90 (Cetearyl Glucoside) 1.0%
(Ceramide 3; Ceramide 6II; Ceramide 1;
Phytosphingosine; Cholesterol; Sodium
Lauroyl Lactylate; Carbomer;
HyaCare® 50 is suitable for O/W and W/O Xanthan Gum)
formulations of: HyaCare® 50 0.2%
• Moisturizing products (facial and body care) Glycerin 3.0%
• Anti-aging creams and lotions Allantoin 0.1%
• Sun care applications Water 69.2%
Storage TEGO® Carbomer 134 (Carbomer) 0.1%
For short term (few weeks), the product can be Mineral Oil (30 mPa s) 0.4%
stored at room temperature. For long term (over Phase D
several months), the product should be stored in a
Sodium Hydroxide (10% in water) q.s.
cool place (4 °C). Avoid freezing. The unopened
product is expected to be stable up to 36 months. Phase Z
Preservative, perfume q.s.
1kg package 1. Heat phase A and B separately to approx. 80°C.
2. Add phase A to phase B with stirring 1).
4. Cool with gentle stirring to approx. 60°C and
Hazardous goods classification add phase C.
Information concerning 5. Homogenize for a short time.
6. Cool with gentle stirring and add phase D
• classification and labelling according to below 40°C.
regulations for transport and for dangerous 1) Important : If phase A has to be charged into the
substances vessel first, phase B must be added without stirring.
• protective measures for storage and handling
• measures in accidents and fires
• toxicity and ecological effects
is given in our material safety data sheets.
W/O Night Cream – Intensive Repair
ABIL® EM 90 2.0%
(Cetyl PEG/PPG-10/1 Dimethicone)
ISOLAN® GI 34 (Polyglyceryl-4 Isostearate) 1.0%
TEGOSOFT® OS (Ethylhexyl Stearate) 5.0%
Paraffinum Perliquidum 12.0%
Paracera W 80 1.2%
(Microcrystalline Wax, Paramelt, B.V)
Hydrogenated Castor Oil 0.8%
HyaCare® 50 0.2%
TEGO® Cosmo C 100 (Creatine) 0.5%
Sodium Chloride 0.5%
Preservative, perfume q.s.
1. Heat phase A to approx. 80°C.
2. Add phase B (80°C or room temperature) slowly
3. Homogenise for a short time.
4. Cool with gentle stirring below 30°C and