PROFHILO®

Hybrid Cooperative Complexes of Hyaluronic Acid

IBSA DERMA: GENERAL OBJECTIVE

To become the
REFERENCE POINT
in the world of aesthetic medicine for

SKIN LAXITY TREATMENTS

and BIOREMODELLING

FACE BODY
It’s not Filler, It’s Bio-Remodeling
P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S

COMPOSITION
HYBRID COOPERATIVE COMPLEXES (HCC) OF:
• Low (80-100 kDa): L-HA
• High (1100-1400 kDa): H-HA

CONCENTRATION
32 mg L-HA + 32 mg H-HA in 2 ml (pre-filled syringe).
Total of 64 mg HA.
D I F F E R E N T T Y P ES O F AVA I L A B L E H A

LINEAR HA HYBRID COOPERATIVE CROSS-LINKED

COMPLEXES

• Correction and volume

• Hydration activity • Overcome the technology restoration
• Short biological activity concentration limit (3.2%) • Increased half-life (due to cross-
• Short half-life (due to • Increased half-life linked reagent)
hyaluronidase activity) • No cross-linked reagents • No or few biological activity
• Concentration limit ≤ 2.0% • Concentration limit ≤ 2.5%
HA BIOLOGICAL ACTIVITY

Different MW → different functions

Life Sci. 2009 Oct 7; 85 (15-16):573-7. Clin Dermatol. 2008 Mar-Apr;26(2):106-22.

Food Chem Toxicol. 2011 Oct;49(10): 2670-5. J Plast Reconstr Aesthet Surg. 007;60(10):1110-9. for internal use only
H Y B R I D C O O P E R AT I V E C O M P L E X E S

for internal use only

P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S
STEP 1: Obtaining HA molecules with a defined weight

▪ Through new degradation strategies

that allowed to obtain HA molecules
with a defined weight.

• Based on stabile hybrid cooperative

complexes of high and low molecular
weight Hyaluronic Acid (HA):

➢ Low (80-100 kDa): L-HA

➢ High (1100-1400 kDa): H-HA

for internal use only

P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S
STEP 2: Initial combination

▪ H-HA: longer chains tend to form weak

hydrogen bonds (H) between themselves.
(1100-1400 kDa).

▪ L-HA: shorter chains do not usually form

any kind of bond between themselves.
(80-100 kDa).

for internal use only

P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S
STEP 3: Patented thermal process

▪ THERMAL ENERGY, NO chemical agents!

▪ The mix is heated, causing the weak hydrogen

bonds (which connect H-HA molecules) to break.

for internal use only

P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S
STEP 4: The result!

▪ The temperature is lowered, causing the hydrogen

bonds to form between the H-HA and L-HA
molecules.
▪ Regardless of their weights, the 2 components (L-HA
and H-HA) have found a new comfort zone in being
together.
▪ Even when back at initial temperature the bonds
remained stable!!

for internal use only

The thermal cooling of the mixture causes the formation of a myriad of weak
bonds to hydrogen (H) between the long chains (H-HA) and short (L-HA), with
the formation of stabilized hybrid complexes. for internal use only
Product characteristics
P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S
Surprising characteristics

1. Resistance to the degradation process

2. Prolonged action

for internal use only

 P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S

Resistance to the degradation process

Prolonged action

HCC can still be degradated by hyalase

for internal use only

*Stellavato A. et al. PLoS One 2016; 11 (10): e0163510.
PROFHILO®: RHEOLOGY

▪ FLOW (tan δ): measures the flow-ability of a gel. The ability to spread along a plain.
Tan δ >1 indicates “liquid” behavior.

▪ Elasticity or Rigidity (G‘): it is the parameter that measures the ability of a gel to return to the
original form and is closely related to the ability of creating volume.

TAN DELTA
PRODUCT RIGIDITY G’
(flow)
A. CROSS-LINKED HA 0.23 95

B. CROSS-LINKED HA 0.15 162

PROFHILO® 1.36 39
for internal use only
P R O F H I L O ® : H Y B R I D C O O P E R AT I V E C O M P L E X E S
Surprising characteristics

EPIDERMIS

Flowability

DERMIS
Tissue integration

HYPODERMIS

for internal use only

Preclinical studies
MODE OF ACTION & WORDING

BIOSTIMULATION BIOREMODELING

It is the process that leads to tissue It is the process that reverses tissue
augmentation by fibroblast activation laxity facilitating extracellular matrix
and neocollagenesis (collagen type homeostasis (reestablishes elastin,
I mainly) induction through a collagen type I, III, IV and VII)
subclinical inflammatory response. restoring the viability and
Because of the time needed for metabolism of fibroblasts,
immune-mediated response to occur, keratinocytes, adipocytes and
patients’ perception of the beneficial myocytes.
effect is not immediate. Because of the time needed for
cell-mediated action, patients’
perception of the beneficial effect
PLLA is not immediate.
CaHa Keratinocytes
Fibroblasts
PCL Fibroblasts
HCC
CMC Adipocytes
Myocytes

The two categories here described significantly differ from the filling and volumetric action proper of fillers,
that express an immediate mechanical action not involving any cellular type.
for internal use only
for internal use only
HCCs MULTILAYER ACTIVITY

Remodeling of the extracellular matrix promoting and maintaining the viability of:

• KERATINOCYTES (epidermis)

• FIBROBLASTS (dermis)

• ADIPOCYTES (subcutaneous / superficial fat)

• MYOCYTES (muscles)

• OSTEOBLASTS (bones)

*Humzah, D. et al. Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand
and Where Are We Headed in Regenerative Medicine? Int. J. Mol. Sci. 2024, 25, 3216.
HCCs BIOREMODELING ACTION
Summary

Bioremodeling: it is the process that reverses tissue laxity facilitating extracellular matrix homeostasis
(reestablishes elastin, collagen type I, III, IV and VII) restoring the viability and metabolism of:

KERATINOCYTES (epidermis)

FIBROBLASTS (dermis) PROFHILO® and

PROFHILO® BODY (dermis)
ADIPOCYTES
(subcutaneous/superficial fat)

PROFHILO® STRUCTURA
MYOCYTES (muscles) (superficial fat)

OSTEOBLASTS (bones)
 for internal use only
PROFHILO®:IN VITRO STUDIES
Stellavato, Plos Online, 2016:Keratinocytes/Fibroblasts Re-Activation

Collagen and elastin gene expression in fibroblasts is twelve times higher than
the one found in cells treated with the two linear hyaluronic acids alone.
HCCs MULTILAYER ACTIVITY
Keratinocytes and Fibroblasts
Results of collagen and elastin gene expression by keratinocytes and
fibroblasts after incubation with low-concentrated HCCs or linear HA.

HCCs significantly induce collagen and elastin production

in comparison to linear HA:

Increased gene expression

Collagen Collagen type Collagen type Collagen type Elastin

type I III IV VII
Keratinocytes x x x x x

Fibroblasts x x x

→ HCCs contribute to keratinocytes and fibroblasts vitality by

promoting the production of components of extracellular matrix.

*Stellavato A. et al. PLoS One 2016; 11 (10): e0163510.

PROFHILO®:IN VITRO STUDIES
Stellavato, Cell Physiol Biochem 2017: Adipocytes Stem Cells

HCC can support adipocytes and ASC viability

for internal use only

E F F I C A C Y, O R I E N T A L M O N G O L I A N P O P U L A T I O N
Satardinova, Aesthetic Medicine 2019

1 month after all procedures:

Significant amelioration in skin hydration and wrinkle overall size

Marked improvement in skin elasticity and pigmentation reducing melanin

levels
Safety assessment of Profhilo®as derived from Wordwide
Postmarketing Data

OBJECTIVE:
make public data from post-marketing experience after 3
years of use

METHODS:
collecting post-marketing adverse event (AE) reports
received from physicians worldwide between February 9,
2015, and February 8, 2018.

for internal use only

Safety assessment of Profhilo®as derived from Wordwide
Postmarketing Data
RESULTS:

12 adverse event reports were logged in the global database, and none were considered serious;
reactions reported (e.g., swelling, edema, redness) were considered caused by hypersensitivity or by
inappropriate injection techniques.

Table 1: Sales details referring to the number of

syringes sold (in EU and non-EU countries)
Period No. of syringes sold
2015 - 2016 46.943
2016 - 2017 91.613
2017 -2018 158.201
2018 - 2019 340.828
2019 - 2020 765.966
Total 5 years 1.403.551
for internal use only
Product IFU and clinical studies:
Face
BA P I NJ EC TI O N TEC H NI Q U E: FAC E
Malar and Sub-Malar

BAP: Bio Aesthetics Points

The unique characteristics of PROFHILO®, in terms of VISCOSITY and
FLOWABILITY, allow to use the BAP technique to treat the malar and sub-
malar area.

Identify the 5 BAP Inject 0.2 ml per bolus at

injection sites on each the deep derrmis layer
side of the face

32 mg of hyaluronic acid
high molecular weight +

32 mg of hyaluronic acid
low molecular weight
for internal use only
BA P I N J EC TI O N TEC H N I Q U E: FAC E
Malar and Sub-Malar

IDENTIFYING THE BAP (Beatini et al., Aesthetic Medicine 2016)

1 Zygomatic protrusion at least 2 cm away from the lateral canthus of the eye

2 1.5 cm away from the nasal base: at the intersection between the pupil line
and the horizontal line starting from the nasal base.

3 1.5 cm anterior to the inferior margin of tragus

4 1.5 cm away from the middle of the chin

5 1.5 cm above the mandibular angle

for internal use only

E F F I C A C Y, S A F E T Y A N D T O L E R A B I L I T Y
Laurino et al, ePlasty 2015

Facial face hydration, elasticity, and trans-epidermal

water loss values significantly improved at T1 and
T2 (P <.01).

Patients were very satisfied at the end of the

treatment.

No side effects.

for internal use only

E F F I C A C Y, S A F E T Y A N D T O L E R A B I L I T Y
Rodriguez Abascal, Eur Aesth Plast Surg 2015

BEFORE AFTER TREATMENT BEFORE AFTER TREATMENT

for internal use only

E F F I C A C Y, S A F E T Y A N D T O L E R A B I L I T Y
Goltsova et al, 2019

At 1 month after treatment, there is a clear reduction in

wrinkle depth and smoothing of skin texture.

Both patient and doctor satisfaction levels were high, with

average GAIS scores of 2.6 and 2.8, respectively.

No notable side effects were recorded.

PROFHILO® CLINICAL RESULTS FOR FACE

1 MONTH AFTER 1 MONTH AFTER

BEFORE
1st TREATMENT 2nd TREATMENT

Courtesy of Dr. Giseli Petrone

PROFHILO® CLINICAL RESULTS FOR FACE

1 MONTH AFTER 1 MONTH AFTER

BEFORE
1st TREATMENT 2nd TREATMENT

Courtesy of Dr. Gabriel Siquier-Dameto

The European Aesthetic Guide Autumn 2015
Product IFU and clinical studies:
Neck
BAP TECHNIQUE (Bio Aesthetic Points): NECK
Neck

PROFHILO® and BAP Technique allow to treat

difficult areas such as the NECK.

And still only 10 points of injection and the

the same protocol (2 sessions one month
apart).
for internal use only
PROFHILO® BAP TECHNIQUE FOR NECK

1 Midline: midway between the chin edge and hyoid bone

2 Midway between the Adam’s apple and the thyroid

cartilage

3 Midway between the hyoid cartilage and the manubrium

4 Manubrium apex

5 6 Under the mandibular angle at 0.5 cm from the medial

edge of the SCM (Sternocleidomastoid Muscle)

7 8 On the horizontal axis of point 2 at 0.5 cm from the medial

edge of the SCM

9 10 On the horizontal axis of point 3 at 0.5 cm from the medial

edge of the SCM
BAP TECHNIQUE (Bio Aesthetics Points): NECK

NO TISSUE IRREGULARITIES. for internal use only

PROFHILO® NECK OUTCOMES ASSESSMENT
Visual Scales

IBSA Neck Skin Laxity Scale

IBSA Horizontal Neck Lines Scale

 for internal use only
Efficacy and safety: NECK STUDY
Caucasian population

30 days

t0 t1
First Session Second Session

Profhilo® induced skin amelioration in subjects with mild to

moderate neck skin roughness and laxity with very high
tolerability reported by both clinicians and subjects.
BAP TECHNIQUE (Bio Aesthetics Points): NECK

OPTIMAL VISIBLE RESULTS in cases of skin laxity.

for internal use only
EFFICACY: BEFORE & AFTER TREATMENT

BEFORE 1 MONTH AFTER 2° INJECTION

Courtesy of Dr R. Roxo
BAP TECHNIQUE (Bio Aesthetics Points): NECK

for internal use only

Courtesy of Dr. A. Tateo

PROFHILO NEW INJECTION TECHNIQUE
FOREHEAD AND TEMPLES TREATMENT
30 days
• 22Gx50mm cannula t0 t1
First Session Second Session
• Fanning technique

• Volume: 0,6 ml

• 22Gx50mm cannula

• Fanning technique

• Volume: 0,4 ml
PROFHILO NEW INJECTION TECHNIQUE
FOREHEAD AND TEMPLES TREATMENT
BEFORE AFTER* BEFORE AFTER*
* 3 months after beginning
of the treatment

Courtesy of D. Coimbra
Other applications
L o g o p r o d o t t o
PROFHILO®: ATROPHIC ACNE
SCARS TREATMENT
Aim and Method

✓ N° = 12 patients
Profhilo® injection with dual-plane technique:
o first pass filling the scars in the dermis (needle)
o second injection pass using a cannula immediately under the dermis
Lidocaine cream application before treatment
2 monthly injetions

✓ Clinical evaluation: Grade 1 minimal to no improvement/unsatisfied

o 4-grade rating system
Grade 2 moderate improvement/slightly satisfied
✓ Subject self-assessment. Grade 3 marked improvement/satisfied

Grade 4 near total improvement/very satisfied

Keypoints

Observed improvement in the depth of the scars after treatment

Results maintained up to 6 months after treatment (mean improvement grade 2.5 ± 0.43).

Artzi et al, J. Cosmetic Dermatology, 2019

PROFHILO®: ATROPHIC ACNE
SCARS TREATMENT
BEFORE AFTER*

Keypoints

Mean pain scores (VAS) were 2.3 ± 1.3 and 3.3 ± 0.9 after
the first and second sessions → well tolerated procedure

No serious adverse events reported.

Conclusion

Treatment with Profhilo® appears to be a

safe and efficient way to treat facial atrophic
acne scars.

* 6 months after treatment

Artzi et al, J. Cosmetic Dermatology, 2019

PROFHILO®:
REMODELING ATROPHIC SCARS
T0 T4W T8W
Aim and Method

✓ Case report: 1 patient with scar in the medial anterior region of the knee
Profhilo bolus injections in the deep dermis of the scar area
3 monthly injetions

✓ Clinical assessment:
o Visual inspection and palpation.

Keypoints
Significant improvement of scars defect after the second session. T12W T32W 3 ys after

Scars correction almost complete in 3 months after the third session.

Full correction achieved after 8 months.

Conclusion

Profhilo could be considered in the practice of dermatologist and

surgeon to optimize the outcome of the wound healing process.

Pavlova et al, Esperienze Dermatologiche, 2020

 PROFHILO®: EFFECTS ON PSORIASIS
Aim and Method

✓ N° = 5 patients
Profhilo intra- and perilesional deep-dermal bolus injection
2 monthly injetions

✓ Clinical assessment:
o Psoriasis Area and Severity Index (PASI) scale → range 0 (no disease) to 72 (maximal disease)
o Evaluation of pruritus → scale 0-10.

Keypoints
Macroscopic improvement of skin texture (redness, desquamation)

Local effect on psoriasis plaques starting from the first injection, with
reduction in the psoriasis scales.

Conclusion

Profhilo could be considered as an alternative therapeutic

approach in the management of psoriasis.

Siquier-Dameto et al, Esperienze Dermatologiche, 2020

Thank you