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BR-PI0900922-B1 - Pharmaceutical composition based on chalcones carried in dendrimers; process for carrying chalcone in dendrimers and use.

Abstract

PHARMACEUTICAL COMPOSITION BASED ON CHALCONES CARRIED IN DENDRIMERS; PROCESS FOR CARRYING CHALCONE IN DENDRIMERS AND USE The present invention describes a pharmaceutical composition containing a chalcone of general formula (I) carried in dendrimers; the process for carrying chalcones in dendrimers; the use of said pharmaceutical composition for the production of a medicament for the treatment of parasitoses and the method for treating parasitoses in human or non-human mammalian animals carrying parasitoses.

Inventors

  • Bartira Rossi Bergmann
  • Camila Alves Bandeira Falcão
  • VANESSA LÚCIA RODRIGUES FURTADO

Assignees

  • UNIVERSIDADE FEDERAL DO RIO DE JANEIRO

Dates

Publication Date
20260310
Application Date
20090331

Claims (10)

  1. 1. Pharmaceutical composition characterized by containing a pharmaceutically acceptable amount of a chalcone of general formula (I): conveyed in dendrimers, which are polyglycerol salicylate dendrimers or polyamidoamine (PAMAM) dendrimers, in addition to pharmaceutically acceptable excipients, wherein: R1 may be β-naphthyl, furanil, or benzodioxol; R2 can be H or OH; R3 can be H, OCH3, or dioxolane; R4 can be H or OCH3; and R5 can be as per the table below:
  2. 2. Pharmaceutical composition, according to claim 1, characterized in the chalcone:dendrimer molar ratio being between 2:1 and 150:1.
  3. 3. Pharmaceutical composition, according to claims 1 and 2, characterized by the chalcone:dendrimer molar ratio being between 5:1 and 50:1.
  4. 4. Pharmaceutical composition, according to any one of claims 1 to 3, characterized by the excipients employed being adopted for the production of medicines in pharmaceutical forms intended for external and/or parenteral use.
  5. 5. Process for carrying chalcones in dendrimers, characterized by occurring at room temperature, in a closed container, under agitation, in the presence of a solution of organic solvents containing a mixture of dendrimers and chalcones in different molar ratios; in which at least two of the following organic solvents are used: methanol, ethanol, isopropanol, butanol, dichloromethane, dichloroethane, chloroform, methyl chloride, carbon tetrachloride, benzene, toluene, acetone, butanone, acetonitrile, formic acid and acetic acid; in which the ratio between the solvents of said solvent solution is preferably 2:1 volume/volume (v/v); and in which it occurs over a period of time between 18 and 36 hours, in an inert nitrogen atmosphere.
  6. 6. Process according to claim 5, characterized by being employed to carry chalcones in dendrimers in any chalcone:dendrimer molar ratio between 1:1 and 500:1.
  7. 7. Process, according to claims 5 and 6, characterized by removing the solvent solution by reducing the pressure.
  8. 8. Use of pharmaceutical compositions containing chalcones and/or their pharmaceutically acceptable salts carried in dendrimers and pharmaceutically acceptable excipients, characterized by being aimed at the production of a medicine used in the treatment and/or prevention of parasitosis in human and non-human mammalian animals.
  9. 9. Use, according to claim 8, characterized by the medicament containing a molar concentration between 1μM and 50μM of chalcones of general formula (I) and/or their pharmaceutically stable salts carried in dendrimers, in addition to pharmaceutically acceptable excipients.
  10. 10. Use, according to claims 8 and 9, characterized by the parasitoses belonging to the group comprising leishmaniasis, trypanosomiasis and superficial mycoses such as dermatophytoses, dermatomycoses and candidiasis.

Description

FIELD OF THE INVENTION [01] The present invention relates to a pharmaceutical composition based on chalcones of general formula (I) or their pharmaceutically acceptable salts carried in dendrimers, in addition to pharmaceutically acceptable excipients. This invention also relates to the process of carrying the chalcones in dendrimers and the use of said pharmaceutical composition in the development of medicaments for the treatment of parasitoses. BACKGROUND OF THE INVENTION [02] Dendrimers are molecules built through radial, layered, repetitive growth from a poly-functionalized core. The resulting dendritic structure is highly branched and has a large number of functional groups on its surface. The molecule generated in the first series of reactions of dendrimer synthesis is called a 1st generation dendrimer; when another layer is added through a second series of reactions, a 2nd generation dendrimer, and so on (Tomalia and Frechet, 2001). [03] Polyamidoamine dendrimers (PAMAM) were the first class synthesized and characterized for biological use. One characteristic of dendrimers that can be pointed out as an important advantage relative to conventional polymers is their controllable synthesis and the narrow molecular weight range achieved in their preparation. They can form complexes with molecules through encapsulation or surface interactions, and can therefore serve as potential controlled drug delivery systems (Prabal et al 2004). [04] PAMAM dendrimers possess properties necessary for drug delivery and targeting due to the existence of empty spaces formed within them, which function as nanoscale reservoirs, in addition to interactive properties on the surface. The PAMAM dendrimer alone has been approved for clinical use in the topical treatment of genital herpes. [05] Parasitic diseases, including malaria, leishmaniasis, trypanosomiasis, and others, are considered one of the major public health problems in the world. However, these diseases are concentrated in countries with low-income populations, such as those in Africa, Asia, and South America. This is largely due to a lack of public policies in the areas of health and basic sanitation; these countries have the highest numbers of cases and deaths from these parasitic diseases. [06] Neglected by the private sector, the control of these endemic diseases depends almost exclusively on government initiatives, with a great lack of alternatives for chemotherapeutic treatment. The therapeutic approach for these parasitoses is complicated by serious side effects, teratogenic effects, low efficacy and the emergence of resistance to reference drugs, requiring continuous efforts aimed at developing new drugs. [07] The search for new drugs that are effective in the treatment of parasitic diseases, and that reduce the adverse effects of currently used medications, has been extensive. Chalcones have stood out for their good results as antiprotozoal substances. In addition, they have shown other properties, such as anticancer, antiviral and insecticidal activity. [08] The natural chalcone 2,6-dihydroxy-4-methoxychalcone (DMC) isolated from the plant Piper aduncum has demonstrated good activity against cutaneous leishmaniasis. Its action consists of inhibiting specific sterols of the Leishmania parasite, which are also important for fungi and trypanosomes that cause mycoses and Chagas disease, respectively. However, it has also shown a residual toxic effect against host cells. [09] Document WO 2007/106437 refers to a microbicidal agent conjugated with functionalized glycodendrimers, where a lipophilic agent enhances the microbicidal action. The mechanism of action on bacteria occurs through electrostatic interaction that interferes with bacterial metabolism. [10] Document WO 00/64486 reports a drug with biological activity via enzymatic decomposition, conjugated with 1 or more branched or unbranched water-soluble polymers. The present invention is also directed to a pharmaceutical composition. As in document EP1967212 where a dendrimic structure with 4 monomethoxypolyethylene glycol branches that can be functionalized with pharmaceutical interests. [11] Document PI0407420 describes multifunctional dendrimers and hyper-branched polymers that act as sustained-release systems for genes and pharmaceutically bioactive drugs. The dendrimers described form stable systems in the biological environment and facilitate the transport of genes and pharmaceutically bioactive drugs across the cell membrane. [12] US patent application 2007014757 describes a pharmaceutical composition containing several anti-inflammatory drugs carried in dendrimers. This pharmaceutical composition is intended for the treatment of diseases such as: arthritis, myositis, psoriasis, insect bites, atopic dermatitis, rheumatoid arthritis, multiple sclerosis and others. [13] As can be seen, the state of the art to date does not contemplate a pharmaceutical composition containing drugs with antiparasitic eff