REACTIVATES HEALING

SWITCHES THE WOUNDFROM THE INFLAMMATORY

PROVEN LONG TERMEFFICACY AND SAFETY

and accelerates the formation of granulation tissue favoring closure

to the proliferative phase, leading to patient´s own cells to reactivate the healing process

REMARKABLE EFFICACY

in exposed bones and tendons including stagnant hard to heal wounds

Reduction in wound care expenditure and hospitalization burdens

UNIQUE MICROSPHERE TECHNOLOGY THAT REACTIVATES WOUND HEALING

2

INDICATIONS

PolyHeal® Micro, a suspension of polystyrene Negatively Charged Microspheres (NCM) in a concentration of 4.5x106 microspheres/ml, in 22% glycerol and water for injection.

TREATMENT WITH POLYHEAL® MICRO

For the treatment of ulcers of different etiologies and stagnant hard to heal wounds, including those with exposed bones and tendons without infection.

Diabetic foot ulcers, venous and arterial leg ulcers, pressure ulcers;

Post-traumatic, post-surgical wounds;

Other ulcers in co-morbid patients.

POLYHEAL® MICRO REACTIVATES THE HEALING PROCESS AND ACCELERATES THE FORMATION OF GRANULATION TISSUE FAVORING CLOSURE.1

Two outcomes can be expected after the application of PolyHeal® Micro:

Medical Device Class IIB.

FORMATION OF HEALTHY RED GRANULATION TISSUE (closure by secondary intention or skin graft)

CLOSURE BY EPITHELIALIZATION 2

1. Before application of PolyHeal® Micro 2. After application of PolyHeal® Micro

NCM provide a passive temporary surfa-ce for cell attachment and proliferation. This increases the number of cells in the wound bed, reestablishing the Extracellu-lar Matrix.

In a chronic wound situation there is an overall decrease in all components of the Extracellular Matrix. Cells lose their ability to proliferate and, as a consequence, end up in apoptosis.

3

MECHANISM OF ACTION

1. CYTOKINE MODULATION

After the application of PolyHeal® Micro, the persistent activation of the inflammatory phase is not further maintained due to local cytokine balance reestablishment.4,5

2. ADDITIONAL SURFACE AREA FOR CELL ATTACHMENT

NCM mimic the functions of native Extracellular Matrix providing an additional surface area for cell attachment, enabling cells to activate the processes aimed at wound healing, such as collagen synthesis and angiogenesis, among others.1,2

3. METALLOPROTEINASES SEQUESTRATION (MMPs)

When metalloproteinases come into contact with NCM, they can be adsorbed onto their surface favoring tissue regeneration.6,7

AFTER THE APPLICATION OF POLYHEAL® MICRO A SYNCHRONIZED SERIES OF EVENTS ARE TRIGGERED SWITCHING THE WOUND FROM THE INFLAMMATORY TO THE PROLIFERATIVE PHASE, LEADING TO PATIENT'S OWN CELLS TO REACTIVATE THE WOUND HEALING PROCESS.1,6

NCM (NEGATIVELY CHARGED MICROSPHERES)

Cell attachment to microspheres results in morphological and functional cell changes that results in its activation, proliferation and migration.2,3

The negative charge on the microsphere surface improves cell attachment and interaction.

4

RANDOMIZED CLINICAL TRIAL1

1.8 times faster (27 vs 49 days) reaching the primary endpoint of ≥ 75% coverage with LRG tissue.1x1.8

of the EB&T wounds treated with NCM compared with zero in the control group achieved ≥ 75% of coverage with LRG tissue after 4 weeks.1

57%

EXPOSED BONES AND TENDONS (EB&T)

NCM trigger the wound healing process in recalcitrant lessions, specially those with EB&T.

CLINICAL EVIDENCE

1Double-blind randomized clinical trial. Patients with hard-to-heal wounds, defined as refractory to treatment for at least 4 weeks, or those with exposed bone, tendon or ligament, were eligible for inclusion and were randomized to either NCM or control, both applied for 4 weeks. Fifty-eight patients completed the study.

The primary endpoint was defined as coverage of > 75% of the wound area by light-red granulation tissue after 4 weeks of treatment.

Treatment duration (weeks)

Per

cen

tag

e o

f p

atie

nts

(%

)50

40

30

20

10

0

0 1 2 3 4

15%

47%

NCM Control

≥ 75% coverage with light-red granulation (LRG) tissue

P=0.01

47% of patients treated with NCM reached ≥ 75% coverage with LRG tissue compared with 15% in the control group (or=5.95; P=0.01).

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REAL WORLD EVIDENCE8

50% more wounds remained closed.

Lower incidence of adverse events (14.8% vs 30% respectively).

85% reduction of hospitalizations.

Reduction of 80% in hospital length of stay (2 days vs 10 days respectively).

NCM GROUP OUTCOMES VS CONTROL

8Prospective clinical case series of patients with a hard-to-heal DFU treated with NCM. DFUs were treated daily with NCM over four weeks, although the health professional could decide to continue NCM treatment in some patients. Cases were followed up for 12 weeks. NCM treatment was completed in 17 ulcers (16 patients).

Wollina score (granulation, colour and consistency tissue), wound area (cm2), percentage reduction and wound closure (%) were measured.

3After the RCT, patients were monitored bi-weekly for an additional 8 weeks, while treated with standard wound care, at the

investigators’ discretion, and were re-evaluated 2 years after inclusion.

2-YEAR FOLLOW UP3

Long term efficacy and safety and reduction in wound care and hospitalization burdens.

Wound area reduction at 4 weeks in neuropathic and neuroischaemic DFU´s, including ulcers with EB&T.8

62%

of ulcers achieved complete healing at 12 weeks including those ulcers with EB&T.8

100%

EXPOSED BONES AND TENDONS

Wound Surface area reduction in ulcers with EB&T

Percentage of area reduction (PAR) 48% Treatment duration (weeks)

Wo

un

d S

urf

ace

Are

a (c

m2 )

2,5

2

1,5

1

0,5

00 1 2 3 4

NCM

6

CASE STUDIES

ISCHEMIC ULCER WITH EXPOSED BONE AND TENDON I 89 YEARS****

Outcome at 2 weeks: Healthy LRG tissue ≥ 75%.

NEUROISCHEMIC DIABETIC FOOT ULCER I 55 YEARS / 12 WEEKS DURATION* Outcome at 8 weeks: Complete epithelialization.

DIABETIC FOOT ULCER I 56 YEARS / 3 WEEKS DURATION** Outcome at 4 weeks: Percentage Area Reduction (PAR) > 50% and Healthy LRG tissue ≥75%.

VENOUS LEG ULCER I 57 YEARS / 8 WEEKS DURATION***

Outcome at 9 weeks: Complete epithelialization.

At baseline 22/11/2017

Size: 6 cm2

At baseline 23/05/2018

Size: 12 cm2 (upper)12 cm2 (lower)

Week 4 22/12/2017

Size: 2.16 cm2

Week 1 30/05/2018

Size: 8 cm2 (upper)7.5 cm2 (lower)

Week 8 29/01/2018

Complete epithelialization

Week 9 25/07/2018

Complete epithelialization

Week 427/04/2017

Size: 0.6 cm2

Week 2 07/06/2017

Size: 12.8 cm2

At baseline 30/03/2017

Size: 4.9 cm2

At baseline 23/05/2017

Size: 15.75 cm2

Week 1 06/04/2017

Size: 1.7 cm2

Week 1 31/05/2017

Size: 15.75 cm2

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INSTRUCTIONS FOR USEWHEN SHOULD POLYHEAL® MICRO BE APPLIED

STEPS FOR APPLICATION

PolyHeal® Micro should be used on wounds with moderate to low level of exudate.

It is recommended that PolyHeal® Micro is applied on wounds which are debrided and without infection.

EASY STEPS TO APPLY

POLYHEAL® MICRO

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For further information about the instructions for use, please visit: www.polyhealmicro.com

WOUND BED PREPARATIONdebrided and without infection.

1

APPLY POLYHEAL® MICRO DAILYin drops slowly to the wound surface.

2

wait 20 sec

COVER WOUND SURFACEwith a non-woven gauze.

3

SATURATE THE GAUZEwith PolyHeal® Micro.

4

BANDAGE THE WOUNDusing standard loose dressings.

0482

REFERENCES1. Shoham Y, et al. Wound ‘dechronification’ with negatively-charged polystyrene microspheres: a double-blind RCT. J Wound Care. 2013 Mar; 22(3):144-55. 2. Correa L, Peter R, Clerici G, Ritter V. Negatively charged microspheres provide an additional surface for cell attachment leading to proliferation, tissue regeneration and wound healing. Poster EP216. Presented in EWMA 2017. Amsterdam May 3rd-5th 2017. 3. Kaufman H, et al. Reawakening the most hard-to-heal chronic wounds: long-term outcomes of a RCT with active negatively charged microsphere(NCM) technology. Proceedings of a satellite symposium. The 27th European Wound Management Association Conference. May 4th 2017, Amsterdam 4. Brodbeck W, et al. Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro. Cytokine vol.18, issue 6, June 2002, pag. 311-319. 5. Correa L, Mediavilla E, Ritter V. NCM reestablishes local cytokine milieu to promote an anti-inflammatory type of response. Poster ID 490. Presented in GNEAUPP 2018. Valencia Nov 28th-30th 2018. 6. Govrin J, et al. New method for treating hard-to-heal wounds: clinical experience with charged polystyrene microspheres. Wounds UK. 2010; 6(4); 52-61. 7. Renò F, et al. Adsorption of matrix metalloproteinases onto biomedical polymers: a new aspect in biological acceptance. J Biomater Sci Polym Ed. 2008;19(1):19-29. 8. Lázaro - Martínez J.L, et al. Hard to heal diabetic foot ulcers treated using negatively charged polystyrene microspheres: a prospective case series. Journal of Wound Care. Vol 28. No 2. Feb 2019. 9. De Alcalá D, et al. Hard-To-Heal Wounds: Results of a treatment based on negatively charged polystyrene microspheres (NCM). EPP 292. Presented in EWMA 2018. Krakow May 9th-11th 2018.

*Illustrations provided by Mrs. Teresa Segovia Gómez, Direction Committee GNEAUPP. Spain.**Illustrations provided by Dr. José Luís Lázaro-Martínez, Diabetic Foot Unit, Universidad Complutense de Madrid. Spain.***Illustrations provided by Dra. María Teresa Cacua Sánchez. Vascular Surgeon. Centro Médico Juan Pablo II. Bogotá. Colombia.****Illustrations provided by Dr. Antonio de la Cuesta, Diabetic Foot Unit. San Lázaro Hospital, Seville. Spain.

Unique Microsphere Technology that reactivates healing, including wounds with exposed bones and tendons.6

Easy and rapid topical application in difficult access areas like interdigital or cavitated.9

Can be applied by the own patient or a trained caregiver.9

Demonstrated efficacy leading to patient´s own cells to reactivate the healing process.1,6

Rapidly produces healthy red granulation tissue, regardless of wound etiology.1,6

Offers the choice of wound closure by secondary intention or grafting.1

Proven long-term efficacy and safety. Reduction in wound care expenditure and hospitalization burdens.3

Parque Empresarial San Fernando, Edificio Dublín, 2ª planta 28830 San Fernando de Henares (Spain)Tel: +34 91 656 56 57Fax: +34 91 648 78 91international@praxisph.com

www.polyhealmicro.comPH

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This document is addressed to HCPs only.

For further information about PolyHeal® Micro, please refer to the electronic Instructions for Use at the following website: www.polyhealmicro.com/docs/instructions_for_use.pdf