Pharmaceutical composition with glycosaminoglycans and use thereof in the treatment of chronic ulcers

Abstract

The invention relates to a composition of glycosaminoglycans for the treatment of diabetic foot ulcer, it specifically relates to low molecular weight heparins (LMWHs) and very low molecular weight heparins (VLMWHs) in the treatment of chronic ulcers, particularly of diabetic foot ulcers, and more specifically in the manufacture of a medicinal product for the treatment of chronic ulcers, and particularly diabetic foot ulcers and pressure ulcers.

Description

FIELD OF THE INVENTION[0001]The invention relates to a composition of glycosaminoglycans for the treatment of chronic ulcers, specifically diabetic foot ulcers and pressure ulcers. It more particularly relates to compositions of low molecular weight heparins (LMWHs) and very low molecular weight heparins (VLMWHs) in the treatment of chronic ulcers, and more specifically in the manufacture of a medicinal product for the treatment of chronic ulcers.STATE OF THE ART[0002]Diabetes Mellitus (DM) is a metabolic disease which is characterized by a sustained increase of plasma glucose levels, which contributes to the onset of peripheral neuropathy and of macro- and microvascular complications. According to the data published by the World Health Organization (WHO), the incidence of DM is increasing in an alarming manner, a prevalence of 2.8% in the world population in 2000 and an increase of this figure to 4.4% in 2030 being estimated. Thus, the number of patients with DM was about 171 milli...

AI Technical Summary

Benefits of technology

[0015]In non-fractionated heparin as well as in the various LMWHs or VLMWHs obtained by known depolymerization methods (enzymatic, nitrous acid, β-elimination, etc), there is a measurement which allows determining the amount of pentasaccharide within the general structure through the quantification of the content of a specific and exclusive disaccharide unit of the pentasaccharide called D-glucuronic acid bound to N-sulfo-3-sulfo-D-glucosamine (ANS,3S). This measurement allows obtaining a good correlation between the percentage present of this disaccharide and the content of pentasaccharide in the heparin structure and therefore of anti-FXa activity of the heparin in question (Guerrini M et al. Seminars in Thrombosis and Hemostasis 2007; 33: 478-787).

[0030]This is so because the effect sought with heparin is acting in prophylaxis since, taking into account the state of the art, the amount of pentasaccharide responsible for the antithrombotic activity is more than enough to favor lower limb vascularization in patients with diabetic foot ulcer, and at doses greater than the indicated dose the general belief is that the bleeding risk increases due to the excess of said antithrombotic effect, taking into account that diabetic patients have a greater predisposition to bleeding, without realizing that what is really important is administering a larger amount of other monosaccharides which do not form part of the pentasaccharide in the formulation. Therefore, very low doses have traditionally always been used for this purpose, in which the ratio between the plasma half-life and the dose in IU of the LMWH is less than 1:500, since it is considered that the same anti-coagulating and antithrombotic effect but with a lower bleeding risk for patients who already have a complex disease such as diabetes is thus achieved.

[0033]Therefore, an important problem in the treatment of diabetic foot ulcers is achieving the effective and efficacious dose of a medicinal product, which achieves ischemic tissue regeneration and prevents the amputation of the diabetic foot and which is furthermore effective not only in prophylaxis but also as therapeutic treatment. Another additional advantage which the treatment of choice must have is that it is not very traumatic for the patient since diabetic foot ulcers are characterized by being extremely painful, therefore the route of administration must not be very traumatic in the proximity of the wound. Therefore, for the purposes of the present invention the preferred routes of administration are the parenteral route, the oral route and the topical route which is non-invasive or is directly applied on the mucosa to be treated.

Problems solved by technology

However, they are generally not used for diabetic patients who suffer from diabetic foot ulcer without peripheral arterial occlusive disease, due to the bleeding risk involved in the treatment at greater doses.

However, as has been indicated above, this approach is not carried out due to the bleeding risk involved in the treatment at greater doses.

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