Patent Application
20100267663
This invention concerns a new composition, both for pharmaceutical use and in a medical device form, as well as for cosmetics, able to obstruct the sclerotic fibre process, to prevent the formation of hypertrophic and scars and already formed cheloids, as well as aiding the cicatrisation process, improving the biomechanical properties of the cutis (such as elasticity and stretchability), restraining cicatrisation retraction phenomena.
The physiological response of the organism to a continual loss of cutaneous solution is characterized by a complex mechanism of articulated events between them, which only in recent years has been almost fully cleared up.
Independently from the type of wound, whether acute or chronic, and the entity of the loss of tissue, the healing of each wound proceeds in phases that overlap over time and which cannot be separated one from the other.
Repair of the tissue is a dynamic and interactive process that takes place normally in our organism and that involves soluble mediators, extracellular matrix and blood and parenchyma cells.
The physiologic tissue repair process is traditionally subdivided into 3 phases:
1. Inflammation phase (from 0 to 3 days)
2. Proliferative phase (from 3 to 24 days)
3. Maturation or Epithelialisation phase (from 6-10 days to 12-24 months)
The first phase can be subdivided into the coagulative and inflammatory phases.
The hypertrophic cicatrices and cheloids represent an exaggerated response of the biosynthesis of the fibroblasts characterised by abnormal deposits of collagen fibres (collagen hypertrophy) e by a reduced quantity of hyaluronic acid. Hyaluronic acid is a polymer of a saccharide nature that belongs to the chemical family of the glycosaminoglycans (GAGs) made up of repetitive glucuronic and acetylglucosamine acid units. Such macromolecule is abundant in different tissues where it performs specific functions to adjust the remodelling of the cutaneous matrix, to regulate the nutritive exchanges between cells and tissues and to determine cellular migration, proliferation and differentiation.
Attention was given to hyaluronic acid both on an epidermis and dermis level. This macromolecule polysaccharide can be synthesized both by keratinocytes and fibroblasts.
Hyaluronic acid is quickly depolymerised by an enzymatic (hyaluronidase enzyme) and its half-life in the cutis is a few days.
Hyaluronic acid can also be depolymerised by radical. The free radicals, whatever way they are generated by the cutis, can attack the molecule dividing it into smaller sized fragments. As a result of the depolymerisation, whether enzymatic or oxidative, there is a reduction in the dimensions of the molecules and as a direct consequence, a reduction in the capacity of the polya to ligate water. This process lead to a macroscopic drop in the viscoelasticity parameters of the cutis and a reduction of the organisation of the extra cellular matrix characterized by a loss in quality of the collagen fibre that tends to aggregate in increasing dimensioned structures with less elasticity.
Hyaluronic acid is able to prevent the formation of fibrosclerotic tissue and modulates the biosynthesis of collagen on the part of the fibroblasts.
On the basis of an exaggerated response in the formation of hypertrophic cicatrices and/or cheloids a chronic inflammation condition is revealed.
This invention was conceived starting from the considerations above and its objective is to provide a pharmaceutical or cosmetic composition or medical device that has the possibility of intervening directly and simultaneously against the physiology of cicatrisation, by formulating the formation of soluble collagen, blocking cutaneous hypertrophy, facilitating biosynthesis of hyaluronic acid and blocking the inflammatory process.
More precisely, this invention proposes a composition formulated for a single and/or combined use of fucose (and/or FROPs) with dimethyl sulfone mainly but not fully used for the indications above described in combination with acetylglucosamine.
In fact, fucose (and/or FROPs) may be used on its own to prevent the formation of hypertrophic scars and/or cheloids and to contrast the dimensions when already formed.
Fucose (and/or the FROPs) can be used in a single combination with acetylglucosamine.
Fucose (and/or the FROPs) can be used in a single combination with Dimethyl sulfone.
Dimethyl sulfone and fucose can be used in combination with acetylglucosamine.
The composition of this invention may be applied on the skin, whether intact or injured, and used for internal purposes in the pharmaceutical form of tablets, capsules, drops, intramuscular, intravenous, intra-joints, intracutaneous injections etc.
It was surprisingly found that fucose (and/or FROPs) used both individually or in combination with both dimethyl sulfone and acetylglucosamine can exert remarkable activity in the modulating the cicatrisation process. Among other things the combination in the use of fucose (and/or FROPs), of dimethyl sulfone and acetylglucosamine can simultaneously act as a stimulator of the biosynthesis of hyaluronic acid and is able to inhibit both oxidative depolarization and enzymic.
Fucose (and/or FROPs) specifically stimulates the production of glycosaminoglycans (including hyaluronic acid) and in addition heparin sulphate which is able to inhibit the hyaluronidase enzyme (the enzyme appointed for the depolymerisation of hyaluronic acid), helps in the remodelling of the extra cellular matrix, and stimulates the production of tropocollagen.
Dimethyl sulfone acting as a strong anti-inflammatory, inhibits the allergic response caused by xenobiotics, is able to protect both the keratinocytes and fibroblasts from the detrimental action carried out by ultraviolet radiation, and inhibits the action of cytokines, among which interleukin 1-alpha.
Dimethyl sulfone and fucose (and/or FROPs) carry out a marked antioxidant and anti-free liberal activity.
Acetylglucosamine also carries out a marked anti-inflammatory and anti-free radical activity and furthermore, forming one of the two molecules of some glycosaminoglycans (among which hyaluronic acid) it behaves as a stimulator of the biosynthesis of the polysaccharides acting as a biochemical precursor of the same biosynthesis. Acetylglucosamine is also able to act as an efficient antioxidant and to inhibit the depolymerisation of hyaluronic acid mediated by free radicals.
In this invention fucose (and/or FROPs) may be used both in the levorotatory and dextrorotatory forms, and in racemica mixtures, both in the cis and trans forms. Furthermore fucose (and/or FROPs) and Dimethyl sulfone and acetylglucosamine, differently combined between them, can be used in different ponderal ratios.
Fucose (and/or FROPs) may be used individually in a percentage in weight that goes from 0.01% to 90%. Preferably, depending on the form of administration and the pharmaceutical and/or cosmetic form or in a general sense the chemical-physical form used, fucose can be used in a percentage in weight of between 0.2% and 30%. Better still fucose (and/or FROPs) may be used between 0.5% and 10% in weight.
Fucose (and/or FROPs) may be used in a percentage in weight from 0.01% al 90% when associated with dimethyl sulfone with the latter in a percentage in weight from 0.1% to 90%. Preferably depending on the form of administration and the pharmaceutical and/or cosmetic form or in a general sense the chemical-physical form used fucose (and/or FROPs) will be used in a percentage in weight from 0.2% to 30% when dimethyl sulfone is used in a percentage in weight from 0.5% to 50%.
Even more precisely fucose (and/or FROPs) will be used in a percentage in weight from 0.5% to 10% when dimethyl sulfone is used in a percentage in weight from 1% to 20%.
Fucose (and/or FROPs) may be used with a percentage in weight that goes from 0.01% to 90% when associated with acetylglucosamine with the latter in a percentage in weight from 0.01% to 90%. Preferably, depending on the form of administration and the pharmaceutical and/or cosmetic form or in a general sense the chemical-physical form used fucose (and/or FROPs) is used in a percentage in weight from 0.2% to 30% when acetylglucosamine is in a percentage in weight from 0.5% to 30%.
More precisely still fucose (and/or FROPs) will be used in a percentage in weight from 0.5% to 10% when acetylglucosamine is in a percentage in weight from 2% to 10%.
Dimethyl sulfone may be used in a percentage in weight from 0.1% to 90% when associated with acetylglucosamine with the latter in a percentage in weight from 0.01 to 90%. Preferably depending on the form of administration and the pharmaceutical and/or cosmetic form used dimethyl sulfone will be used in a percentage in weight from 0.5% to 50% when acetylglucosamine is in a percentage in weight from 0.5% to 30%.
Still more precisely dimethyl sulfone will be used in a percentage in weight from 1% to 20% when acetylglucosamine is in a percentage in weight from 2% to 10%.
Fucose (and/or FROPs) may be used in a percentage in weight from 0.01% to 90% when associated with dimethyl sulfone with the latter in a percentage in weight from 0.1% to 90% and acetylglucosamine in a percentage in weight from 0.01% to 90%.
Preferably, depending on the form of administration and the pharmaceutical and/or cosmetic form used fucose (and/or FROPs) will be used in a percentage in weight from 0.2% to 30% when dimethyl sulfone is in a percentage in weight from 0.5% to 50% and acetylglucosamine is in a percentage in weight from 0.5% al 30%.
Still more precisely fucose (and/or FROPs) will be used in a percentage in weight from 0.5% al 10% when dimethyl sulfone is in a percentage in weight from 1% to 20% and acetylglucosamine is in a percentage in weight from 2% to 10%.
Phial to be injected via intramuscular, intracutaneous and/or subcutaneous.
Method of preparation: dissolve the dimethyl sulfone by shaking in water at a temperature of 35° C.; when the solution is limpid add the fucose, continue shaking maintaining the temperature constant. Sterilize when solution is limpid.
Phial to be injected via intramuscular, intracutaneous and/or subcutaneously.
Method of preparation: dissolve the dimethyl sulfone by shaking in water at a temperature of 35° C.; when the solution is limpid add the fucose, continue shaking and add the acetylglucosamine keeping the temperature constant. Sterilize when solution is limpid.
Phial to be injected via intramuscular, intracutaneous and/or subcutaneously.
Method of preparation: dissolve the acetylglucosamine by shaking in water at a temperature of 35° C.; when the solution is limpid add the fucose, continue shaking maintaining the temperature constant. Sterilize when solution is limpid.
Method of preparation: dissolve the dimethyl sulfone by shaking in water at a temperature of 35° C.; when the solution is limpid add acetylglucosamine and fucose; continue shaking maintaining the temperature constant. When solution is limpid mix in the propylene glycol and glycerol, continue to shake.
Method of preparation: dissolve the acetylglucosamine by shaking in water at a temperature of 35° C.; when solution is limpid add the fucose, continue to shake maintaining the temperature constant.
When solution is limpid mix in the propylene glycol and the glycerol, continue to shake.
Method of preparation: dissolve the dimethyl sulfone by shaking in water at a temperature of 35° C. when solution is limpid dissolve the acetylglucosamine; continue to shake maintaining the temperature constant.
When solution is limpid mix in the propylene glycol and the glycerol, continue to shake.
Method of preparation: dissolve the dimethyl sulfone by shaking in water at a temperature of 35° C.; when the solution is limpid dissolve the acetylglucosamine and the fucose, continue to shake and keep the temperature constant. When the solution is limpid mix in the propylene glycol and the glycerol, continue to shake.
Mix in the dimetil isosorbide to the previous solution; when solution is limpid disperse the Xanthine gum. Leave it to shake until a medium viscosity limpid gel is formed.
Method of preparation: dissolve the dimethyl sulfone by shaking in water at a temperature of 35° C.; when solution is limpid dissolve the acetylglucosamine, continue to shake and maintain the temperature constant. When solution is limpid mix in the propylene glycol and the glycerol, continue to shake.
Mix in the dimetil isosorbide to the previous solution; when solution is limpid disperse the xanthine gum. Leave it to shake until a medium viscosity limpid gel is formed.
Method of preparation: dissolve the acetylglucosamine by shaking in water at a temperature of 35° C.; when the solution is limpid dissolve the fucose, continue to shake and keep the temperature constant. When the solution is limpid add the propylene glycol and the glycerol, continue to shake.
Mix in the dimetil isosorbide to the previous solution; when solution is limpid disperse the xanthine gum. Leave it to shake until a medium viscosity limpid gel is formed.
Method of preparation: dissolve the dimethyl sulfone by shaking in water at a temperature of 35° C., when solution is limpid dissolve the fucose, always shaking and maintain the temperature constant. When solution is limpid mix in the propylene glycol and the glycerol, always by shaking.
Mix in the dimetil isosorbide to the previous solution; when solution is limpid disperse the xanthine gum. Leave it to shake until a medium viscosity limpid gel is formed.
Method of preparation: put the polyoxyethylene-2-Stearyl Ether, Polyoxyethylene-21-Stearyl Ether, Octanoic/Decanoic acid triglyceride, 2-Hydroxyethyl Palmitate in a container and shake, heating the content to +80° C. Dissolve the fucose in water, shake and heat to 35° C.; Weigh the water in a separate container and, by shaking dissolve the ethylenediaminetetraacetic disodium salt acid in it. When the solution is limpid, shake to mix the glycerol vegetal, propylene glycol and the preservatives.
Dispel the xanthine gum the previous limpid solution.
Allow to shake until a homogenous dispersion has been reached, at a temperature of +80° C.
Using a turbine mix the phases, and bring temperature to +80° C. Cool to +40° C. and add, by shaking and using a turbine the phase containing fucose. Continue the cooling operations of the emulsion until the temperature reaches +25° C.
Method of preparation: put the Polyoxyethylene-2-Stearyl Ether, Polyoxyethylene-21-Stearyl Ether, Octanoic/Decanoic acid triglyceride, 2-Hydroxyethyl Palmitate in a container and shake, heating the content to +80° C. Dissolve the dimethyl sulfone in water, shake and heat to 35° C.; when the solution is limpid dissolve fucose, always by shaking and maintaining the temperature constant. Weigh the water in a separate container and, by shaking dissolve the ethylenediaminetetraacetic disodium salt acid in it. When the solution is limpid, shake to mix the glycerol vegetal, propylene glycol and the preservatives.
Dispel the xanthine gum the previous limpid solution.
Allow to shake until a homogenous dispersion has been reached, at a temperature of +80° C.
Using a turbine mix the phases, bring temperature to +80° C. Cool to +40° C. and add, by shaking and using a turbine the phase containing fucose and dimethyl sulfone. Continue the cooling operations of the emulsion until the temperature reaches +25° C.
Method of preparation: put the Polyoxyethylene-2-Stearyl Ether, Polyoxyethylene-21-Stearyl Ether, Octanoic/Decanoic acid triglyceride, 2-Hydroxyethyl Palmitate in a container and shake, heating the content to +80° C. Dissolve the fucose in water, shake and heat to 35° C.; when the solution is limpid dissolve the acetylglucosamine, always by shaking and maintaining the temperature constant. Weigh the water in another recipient and, by shaking, dissolve the ethylenediaminetetraacetic disodium salt acid in it. When the solution is limpid, shake to mix the glycerol vegetal, propylene glycol and the preservatives.
Dispel the xanthine gum the previous limpid solution.
Allow to shake until a homogenous dispersion has been reached, at a temperature of +80° C.
Using a turbine mix the phases, bring temperature to +80° C. Cool to +40° C. and add, by shaking and using a turbine the phase containing fucose and Acetyl glucosamine. Continue the cooling operations of the emulsion until the temperature reaches +25° C.
Method of preparation: put the Polyoxyethylene-2-Stearyl Ether, Polyoxyethylene-21-Stearyl Ether, Octanoic/Decanoic acid triglyceride, 2-Hydroxyethyl Palmitate in a container and shake, heating the content to +80° C. Dissolve the dimethyl sulfone in water, shake and heat to 35° C.; when the solution is limpid dissolve fucose, always by shaking and maintaining the temperature constant, when the solution is limpid dissolve the Acetylglucosamine, always by shaking and maintaining the temperature constant. Weigh the water in another container and by shaking, dissolve the Ethylenediaminetraacetic acid disodium salt. When the solution is limpid, shake to mix the glycerol vegetal, propylene glycol and the preservatives.
Dispel the xanthine gum the previous limpid solution.
Allow to shake until a homogenous dispersion has been reached, at a temperature of +80° C.
Using a turbine mix the phases, bring temperature to +80° C. Cool to +40° C. and add, by shaking and using a turbine the phase containing fucose and dimethyl sulfone and acetylglucosamine. Continue the cooling operations of the emulsion until the temperature reaches +25° C.
Method of preparation: the ingredients are loaded into the mixer in a specific order and for a set period. After mixing, the composition is pre-compressed. The composition pre-compressed in this way is fed into the compressor, from which the shaped tablets exit, ready to be covered using an appropriate machine.
Method of preparation: the ingredients are loaded into the mixer in a specific order and for a set period. After mixing, the composition is pre-compressed. The composition pre-compressed in this way is fed into the compressor, from which the shaped tablets exit, ready to be covered using an appropriate machine.
Method of preparation: the ingredients are loaded into the mixer in a specific order and for a set period. After mixing, the composition is pre-compressed. The composition pre-compressed in this way is fed into the compressor, from which the shaped tablets exit, ready to be covered using an appropriate machine.
| Number | Date | Country | Kind |
|---|---|---|---|
| BS2007A000178 | Nov 2007 | IT | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/IT2008/000675 | 10/30/2008 | WO | 00 | 5/17/2010 |
