Lexicon - skin care instant reports

Volume XX - Nr.1 - June 2005

History and up-date on the active principle which changed the formulation method of cellulite lesion treatment products

Iodotrat ® (Vevy Codex 18.0364) was developed in 1978 because of the need for a truly effective and harmless active principle to prevent and treat local hydrolipo-dystrophy. Research was almost immediately geared towards iodinized molecules.

The first obstacle we encountered was that the use of elementary iodine was not allowed in cosmetic products on the grounds that iodine in complex compounds (PVP, cetyl,.) releases elementary iodine, and due to evidence that inorganic iodine and its salts (K e Na) strongly irritate cells.

Therefore, researchers decided to produce an organic iodinized compound, namely an amine, that would ensure the greatest stability under all conditions. It is worth describing the approach that led to the development of this active principle.

Local hydrolipodystrophy, commonly called “cellulitis”, is the consequence of poor lipid metabolism, which involves genetic predisposition and life style errors. It is a dysmorphism that is supported and amplified by female hormones, which favor water retention, especially in declivous zones where muscles are often less used and fat can therefore build-up more easily.

Such dysmorphism is characterized by hardening of the adipic lobules, which are mainly located in the buttocks and behind the thighs. These areas are more subject to compression due to the frequent sitting position.

Female adipose lobules are rectangular and are larger than male adipose lobules, furthermore, their septa are at right angles to the surface. Therefore, when the connective tissue is weakened by the circulating estrogen, the lobules press up against the dermis and the skin takes on an uneven appearance.

• Some factors, called “life style errors”, that quicken the acquired trend include:
• significant hormonal variations (during pregnancy or when taking contraceptives,the oestrogen and progesterone levels influence the amount of fat that is absorbed/released by the body); continuous intake of nicotine (which is known to be an arterioloconstrictor);
• poor/bad nutrition (many substances, such as fried foods, alcohol, caffeine, and sugar strongly irritate the liver, and affect the venous system);
• insufficient intake of liquids (namely water which would help local detoxification);
• insufficient physical aerobic activity (insufficient lymph and blood circulation impairs tissue exchange and causes poor tissue oxygenation );
• excessive exposure to the sun (this causes vein wall dilatation and reduces vein elasticity, thus increasing permeability and causing transudation and hence, local imbalance).

Mastocytes are relatively large cells that characterize the connective tissue of many mammals. They contain the usual organelles that are typically found in metabolically active cells, including the organelles that are assigned to protein biosynthesis.

They also include subspherical cytoplasmic granules that have a high intergranular heparin content, sulphurated proteoglycan and other vasoactive substances, such as histamine and serotonin. In man, mast cells share some of the functional characteristics of basophilic granulocytes, and can also synthesize other anaphylaxis-correlated substances.

These substances are released when an immune reaction occurs, and involve particular globulins related to specific membrane receptors. The vessels located in the adipose tissue are always surrounded by a variable number of mast cells.

In healthy tissue, the tight network of blood vessels and of the lymphatic system provide the fat with the nourishment and oxygen it needs, thus ensuring adequate elimination of the toxins.

In normal conditions, the granules in the mast cells, which are made up of vasoactive substances, move towards the edges of the cell so that their membranes merge with the plasmalemma, and then the contents are expelled.

In unhealthy tissue, blood and lymphatic microcirculation are strongly slowed down, and may even be interrupted because the capillary system of the dermis stagnates, leading to important modifications in the subcutaneous fat tissue and in the surrounding collagen fibre matrix.

In cellulitic lesion, the vessels appear asphyxiated due to their sclerotic reaction. Furthermore, the number of mastocytes decreases and they contain fewer granules, thus showing a reduction in their main activity. All this leads to abnormal fat accumulation in the subcutaneous layer. Since eliminating toxins is now impossible, the lipocytes begin to swell. They are soon covered in a stiff, compact layer of collagen and become nodule-like.

They are now no longer fit to enter the degradation cycle which should transform them and thus produce energy. These conditions are further worsened by the fact that the connective tissue containing the adipose lobules thickens and contracts, thereby creating actual anchorage points, which further highlight the hollows of the skin.

By acting on the lipometabolism in a timely way, its functions can be restored as closely as possible to normal levels. Stimulating the mastocyte function promotes degranulation, i.e., the release of vasoactive substances which are indispensable mediators for activating the circulatory system.

Iodotrat promotes mast cell stimulation, which is mediated by the beta-receptors of the membrane. In particular, the cells are activated by the interference with the membrane polarity, which facilitates the opening of calcium channels. This activates 3-Hydroxyacyl CoA Dehydrogenase at the adipocyte level.

This is an enyzmatic action which is part of the fatty acid degradation process that provides energy at the end of this cycle. These effects have never been observed with other organic iodated molecules.

It was also seen that the number of mast cells and the quantity of granules increased in the presence of Iodotrat. Furthermore, inflammatory lymphocyte infiltration decreased significantly and the interstitial oedema progressively regressed.

Moreover, an objective cutaneous improvement in both the appearance of the treated area and at palpation was observed during clinical tests. The amount of iodine that is absorbed with each daily application of an O/W emulsion containing recommended levels of Iodotrat(0.6% - 0.8%) suffices to produce the desired effect, without altering physiologic blood levels.

These experiments were carried out by testing various doses, and they showed that even much higher doses did not improve the results. We also observed that the useful concentration rate remains unaltered per time and surface unit, most likely due to both better drainage of the circulation system and to saturation of the enzymatic systems.

The safe and proper use of Iodotrat requires some comments on its specific characteristics.

First of all, it is a water soluble, low molecular weight (293.5 Dalton) molecule that is purified by double crystallization, and therefore completely without free-iodine. This guarantees that when it is properly spread, it will penetrate through the horny layer. This product is extremely easy to use because it is very stable, even when exposed to high temperatures (80-100°C), to the sun, and to artificial UV rays.

When used at the recommended dose, the solution has a eudermal (5.5) pH value. It must be stressed that there is no hemolytic action, as occurs with escin, and no muscle relaxing action, as is the case with xanthine derivatives, theophylline, theobromine, caffeine and aminophylline. Furthermore, there are no potential allergic reactions, as has been observed with proteases.

Lastly, Iodotrat has been subjected to a very strict toxicological protocol, which guarantees maximum safety:

• acute oral and intraperitoneal toxicity
• sub acute toxicity [15 wks]
• chronic toxicity [6 months]
• irritation of the eyes
• acute and sub acute irritation of the skin
• embriotoxic and teratogen activity
• carcinogen activity
• cutis sensitization activity [Magnusson e Kligman]
• cutis sensitization activity in man [Quisno]

Many formulations may be suggested, see formulas.

Both Zedomine® (Vevy Codex 13.1250) and Zedomine-2® (Vevy Codex 13.3152) are Iodotrat synergists. They are compounds of essential oils that can activate microcirculation and facilitate both drainage of the lymphaticsystem and tissue exchange.

Formula # 3, which is the most elaborate of the three proposals, has been thoroughly studied in order to provide the best guarantee regarding the use of Iodotrat and to check the stability of the active principle once it has been added to the end product.

Some samples were tested in the dark for sixty days, others under direct sunlight, some at -5°C, at +40°C and at +55°C (which is an extremely severe test), and no organoleptic or chemo-physical variations were observed.

After eighteen months of checking, we found no significant variations in pH measurements. Analytical centrifuge testing, which lasted the same length of time, also revealed no signs of syneresis.

Thermal-viscosity trend was measured four times during this eighteen month period, at the temperature values that the end product would normally be used at, and the data were almost overlapping.

The product was finally acknowledged as a “safe active” after a search had been carried out for the possible, but undesirable presence of free elementary iodine in both the pure active principle and in the end product.

All the test substances were placed in a boiling water bath for ten minutes and then analyzed according to the starch method, which is known to be highly sensitive.

The absolute absence of free iodine was definitively proved on the samples of all the batches that were tested, including those produced twenty years earlier.

Formulas