Mesotherapy is a mildly invasive procedure involving several subcutaneous drug injections, which are performed simultaneously. The concept is to inject a very small amount of active compounds (hyaluronic acid, vitamins, antioxidants, enzymes, humectants, …) and the aim is to stimulate the biosynthetic capacity of fibroblasts, increase collagen and elastin production and to give active essential molecules for a fibroblasts environment. Numerous studies suggest that the mesotherapy procedure improves skin hydration and mechanical properties; however, some results have not been statistically significant. In this study, we investigated an antiaging treatment as a complementary approach to a non-surgical rejuvenating procedure after 5 sessions of mesotherapy. Our main objective was to assess the improvement of face, neck and neckline skin quality, after intradermal microinjections of NCTF 135HA <sup>®</sup>. This mixture, manufactured by FILORGA Laboratories, includes a non-cross- linked hyaluronic acid, vitamins, antioxidants, mineral salts and enzymes. A statistically significant decrease in the depth of crow’s-feet wrinkles (43.3%) and in pore size (58.5%) was observed. Also, dermatological scores showed a significant decrease, and data suggest that skin tone was improved with a brighter tone. The injected mixture could then have an action on the skin pigmentation process with a photoprotective effect. Evolution of Dermis density was also investigated and an increase of dermal density and thickness were highlighted, showing an improvement of skin firmness with significant increases of dermis thickness (20%) and dermis density (24%), indicating a neocollagen activity.
Skin aging is a very complex biological and physiological process, divided in two parts: The chronological or intrinsic aging process, associated with the genetic background, and the extrinsic aging, including adverse environmental events such as exposure to solar UV, pollutants, heavy metal, nanoparticles, smoking, stress and lifestyle, which can alter gene expression and skin defects [
Topical products such as anti-aging cosmetic creams require a prolonged period for few results while plastic surgery involves invasive procedures. Monotherapy, on the other hand, is a mildly invasive procedure involving several subcutaneous drug injections that are performed simultaneously. The concept is to inject a very small amount of active compounds (hyaluronic acid, vitamins, antioxidants, enzymes, humectants, ...) [
The main objective of this study is to assess the improvement of face, neck and neckline skin quality, after intradermal microinjections of NCTF 135HA®. This mixture, manufactured by FILORGA Laboratories, includes a non-cross-linked hyaluronic acid, vitamins, antioxidants, mineral salts and enzymes. The study protocol involves 5 sessions of mesotherapy. Biometrological tests were performed by the GREDECO center: dermatological scores, profilometry, standardized photographic assessment, skin color analysis by chromameter, and high frequency ultrasound imaging. The secondary aim is to assess the patient’s tolerability.
Twenty healthy females between 32 and 67 years old (mean age: 49.25 years) were enrolled in the study between January and June 2014. They exhibited a healthy Caucasian skin type on the anatomic area studied. Nine had already received esthetic treatment: wrinkle filling, lifting, abdominoplasty, blepharoplasty and breast enlargement operations.
Two participants stopped after the first cure: the first could not come anymore and the 2nd exhibited urticarial rash at the injection site.
・ Inclusion criteria
Age between 35 and 65 years old, skin phototypes I-III patients who consult for wrinkle management, skin hydration and skin tone improvement.
Furthermore, all participants have no adverse effects to mesotherapy, hypersensitivity or allergy to any constituent of the investigated product: NCTF 135HA®.
All participants were dedicated to the present study and signed an informed consent form, including not modifying their way of life and no sunbathing.
・ Exclusion criteria
Participants with phototype V and over, as well as those enrolled in any clinical evaluation of drugs or medical devices, were excluded.
Also, participants could not be involved in another clinical study and could not use products, techniques or surgery with an anti-wrinkling action.
Furthermore, patients with non-resorbable material fillers, acute inflammation, scars with pigmentation defects, keloid scars, facial herpes, congenital or acquired disorders of the coagulation system, viral or bacterial infection and with a history of auto-immune disease, were excluded. Taking certain medications was another possible cause of the exclusion criteria of the clinical trial, such as oral and injectable corticoid therapy (<3 months), chemotherapy and immunosuppressive therapy (<2 years). Finally, pregnant and lactating women were not included in the clinical trial.
The pilot study was set to evaluate the efficacy of NCTF® 135HA and consisted of 5 injection sessions at: Day 0, D15, D30, D60 and D90. The injections were given on the face, neck and neckline skin.
Twenty women were involved: Dr S. Boisnic (GREDEDCO) for evaluation and to Dr A. Grand-Vincent as investigator and trained physician for injection.
The NCTF 135HA has the following composition (
Prior inclusion, one visit was performed to check that participants would fit with the inclusion criteria.
During each session, the following volumes were injected:
・ 3.36 ml for Session 1;
・ 3.72 ml for Session 2;
・ 4.47 ml for Session 3;
・ 4.92 ml for Session 4;
・ 5.58 ml for Session 5.
Data represent the average injected volume.
The first session was conducted without applying a local topical anaesthetic cream. For the following sessions, 60% of participants applied EMLA® cream 1 hour before injection.
Evaluations were conducted by Dr Boisnic from GREDECO (Research Group of Evaluation in Dermatology and Cosmetology) and with Dr. Anne Grand-Vincent.
The clinical assessment was implemented by a scoring dermatological system,
Class | Components |
---|---|
Vitamins | Vitamin A (Retinol) Vitamin C (Ascorbic acid) Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 (Nicotinamide) Vitamin B5 (Pantothenic acid) Vitamin B6 (Pyridoxin) Vitamin B8 (Biotin) Vitamin B9 (Folic acid) Vitamin B10 (p-aminobenzoic acid) Vitamin B12 (Cyanocobalamin) |
Mineral salts | Calcium chloride, Potassium chloride, Magnesium sulfate, Sodium acetate, sodium chloride, sodium dihydrogen phosphate |
Amino acids | Alanine, Asparagine, Arginine, Aspartic acid, Cystine, Glutamine, Glutamic acid, Glycin, Histidine, Hydroxyproline, Isoleucine, Leucine, Lysine, Methionine, Ornithine, Phenylalanine, Proline, Serine, Taurine, Threonine, Tryptophan, Tyrosine, Valine. |
Antioxidants and other compounds | Deoxyadenosine, Deoxycytidine, Deoxyguanosine, Deoxythymidine, Methylcytosine, TPP, CoA, FAD, NAD, NADP, UTP, Glutathione, Non-reticulated sodium hyaluronate |
with regard to the depth of wrinkles, on a scale of 0 - 4 (4 for deeper wrinkles) and skin radiance (4 for dull skin). The biometrological assessment was carried out using various techniques:
・ Standardized photos of face and ¾ (Canon EOS 50D, Macro-14EX ring) with lamps recreating the daylight without flash (Lastolite® Ray D8 C5600);
・ Profilometric (SkinStation®) measurements of fine lines and crow’s feet wrinkles: 3D visualization with color scale to assess wrinkle volume: red for deeper wrinkles, yellow for the skin surface and blue-green for raised skin relief;
・ Macrophotography (Proscope® × 30) to assess average pore size in micrometer unit;
・ Chromametric (Chromameter Konica Minolta CR/DP-400) analysis to assess skin tone homogeneity L parameter;
・ Determination of the dermis thickness and density on the cheek, using High Frequency Ultrasound method (Monaderm® 20 MHz).
All results were expressed in the form of average +/− standard deviation, the statistical test was a test of Student.
The method of High Frequency Ultrasound is a non-invasive technique used to evaluate dermal changes with aging [
・ Primary Objective
Evaluation of skin quality for the face, neck and neckline skin.
All in-vitro evaluations were conducted at GREDECO:
- Dermatologic scores;
- Prolilometry;
- Photos;
- Macroscopy;
- Chromametry;
- Cutaneaous Echography (high frequency).
・ Secondary Objectives
Ø Tolerance;
Ø Satisfaction rating of physician;
Ø Satisfaction rating of participant.
In our study, a statistically significant decrease of 43.3% (score of 1.23 versus 2.17; p = 0.0214 × 10−9) in the depth of crow’s-feet wrinkles was observed after 5 sessions of mesotherapy. These results were achieved by dermatological scoring (Lemperle scale). This decline had already started after 15 days and increased after 90 days of treatment (
One can see that mesotherapy visibly reduces the volume of crow’s-feet wrinkles. The results of profilometric measurements have shown a significant
decrease of wrinkle volume by 32.9% (mean depth of 18.10 versus 26.98 V/mm2, p = 0.0265 × 10−6) (
To complete the assessment of mesotherapy on mechanical skin properties, we tried to show treatment efficacy on the reduction of pore size. Our study highlighted a clear decrease in pore size from the 15th day, as shown in
One can explain the efficiency on skin mechanical properties (increase of the skin firmness pulling a reduction of the size of the pores) by analyzing the mixture composition and the technique (
The NCTF 135 HA® product consists of a mixture of vitamins, inorganic salts, antioxidants, amino acids and hyaluronic acid [
Moreover, hyaluronic acid plays a key role in the hydration of the extracellular space. HA promotes an enabling environment for cell development and allows inflammatory modulation [
Ascorbic acid is involved in the function of different enzymes and in collagen
synthesis. Vitamin C is a co-factor for hydroxylation of prolyl and lysyl residues of procollagen [
Loss of proteoglycan hydrophilic properties and glycation products in the papillary dermis, were highlighted by a High Frequency Ultrasound method: The formation of subepidermal low echogenicity band. Physiologically, the Grenz zone is a hypoechoic area with elastotic material. After treatment with topical vitamin C, the ultrasound analysis showed a hyperechoic area [
One can see a decrease of more than 50% at the end of treatment, assuming a significant increase in skin pigmentation homogeneity.
Radiance dermatological scores and the Chromametric biometrological method indicated an improvement of the skin’s appearance: Radiance scores showed a significant decrease of score values of 49%, 32% (mean score 1.48 versus 2.94; p = 0.0165 × 10−7). These values suggest that skin tone was improved, with a brighter tone. Chromametric measurements showed a statistically significant decrease of the gap of pigmentation between the interior and exterior of the cheek (L* parameter). This decrease suggests better skin homogeneity. Our study shows a significant increase of 52.13% (1.01 versus 2.11; p = 0.0012) of the skin homogeneity after treatment.
Results obtained with chromameter measurements showed an illuminating and brightening activity. The injected mixture was able to have an action on the skin pigmentation process with a photoprotective effect [
Buz et al., in a study concerning the use of GSH in burns, explored the efficiency of mesotherapy in the treatment of dermal burns. The best result of the wound healing process is achieved with glutathione, compared with taurine and L-carnitine treatment. These compounds act as anti-glycan molecules, decreasing the glycation effect of ROS on glycogen fibers. Then, the oxidized thiol form of glutathione is an effective inhibitor of metalloproteinase activity [
A study of wound healing in aged rats, showed that a topical application of a mix of aminoacids, modulated an inflammatory response, thus increasing endothelial nitric oxide synthase and the Transforming growth factor (TGF-b1) [
High Frequency Ultrasound (HFU) is one of the reference techniques used to evaluate age related skin changes. One can see in
HFU was used to evaluate treatment efficacy by carrying measurement before and after treatment on 2 participants:
Before the multiple micro-injections of NCTF 135 HA product, one can observe low-echogenic band-like structure (SLEB], which is considered as an indicator of aged skin and more particularly of photo-aged skin [
The assessment by High Frequency Ultrasound shows an improvement of skin firmness with an increase of dermis thickness of 20.15% (1.6 versus 1.34 mm; p = 0.000023) and a significant increase of the dermis density of 24.19% (61.41 versus 49.45%; p = 0.000011), indicating a neo-collagenesis activity (
In our study, we highlighted significant changes in SLEB density related to an
increase of dermal density and thickness after 120 days of treatment. Skin improvement may be explained by different actions: stimulation of injections and induced low inflammatory process and localized vasodilatation [
Tedeschi et al. showed that mesotherapic treatment based on Hyaluronic acid product increased the dermal collagen density with fibroblast activation and confirm that mesotherapy may be useful in the treatment of skin aging and photoaging. [
Ultrasonic data suggest that collagen synthesis increased significantly, related to the decrease of low echogenic pixels. After treatment, different studies underline the major role of ascorbic acid in the remodeling and the integrity of Extra Cellular Matrix. [
Global satisfaction assessment was done at the end of 5th and last treatment. The physician was satisfied of very satisfied in 100% of the case, very satisfied in 74% (14/18 patients). The patients were satisfied or very satisfied in 95% of the case (17/18 patients), very satisfied in 45% (8/12 patients).
Tolerance after injection was rated as excellent, the local side effects were limited with some cases of erythema, bruises and superficial transient bleeding. One out of twenty participants was discontinued following an allergic reaction at puncture sites. Another subject was excluded for medical problems, not related to the treatment.
This study demonstrated the efficiency and the tolerance of a multicomponent mesotherapy formulation, improving skin elastic parameters and skin radiance. Mesotherapy technique with a multicomponent solution, can decelerate the signs of ageing and visibly rejuvenate the skin. This improvement is associated with this specific technique and the use of mixed active ingredients, which protect the cells from the damaging action of free-radicals, increasing the collagen synthesis by activation of fibroblasts. Moreover, active ingredients have a very interesting effect on the inflammatory process. The dermic high frequency ultrasound confirmed biometrological tests and dermatological scores, by showing a marked improvement in skin conditions.
Brief information and informed consent were drawn up for this observational study.
The study was commissioned by FILORGA Laboratories.
Dr. Catherine Salomon is the medical director of Filorga Laboratories.
Grand-Vincent, A., Boisnic, S., Salomon, C., Prinderre, P. and Piccerelle, P. (2017) Clinical Assessment of a Mesotherapy Formulation for Skin Rejuvenation in Healthy Volunteers. Journal of Cosmetics, Dermatological Sciences and Applications, 7, 291-305. https://doi.org/10.4236/jcdsa.2017.74026