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BR-102024017377-A2 - COMPOSITION AND USE OF MICROSPHERES BASED ON SPONDIAS PURPUREA EXTRACT AND GALACTOMANN FROM CAESALPINIA FERREA WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDA SPP. STRAINS

BR102024017377A2BR 102024017377 A2BR102024017377 A2BR 102024017377A2BR-102024017377-A2

Abstract

This invention relates to the field of Biotechnology, specifically the pharmaceutical industry, and concerns the composition and use of microspheres based on an extract of Spondias purpurea and galactomannan from Caesalpinia ferrea with antifungal activity against Candida spp. strains, characterized by comprising: dry extract of the stem bark of Spondias purpurea and galactomannan from Caesalpinia ferrea. The proposed system, the subject of this invention, has potential as an antifungal drug used in the treatment of candidiasis, and has the advantage of presenting a lower minimum inhibitory concentration for some strains used in the analysis than that of the azole used in conventional treatment (fluconazole), in addition to showing better activity against Candida spp. biofilm formation when compared to the isolated extract. What sets it apart is the use of products from the Brazilian flora: a non-cytotoxic and non-toxic bioactive ingredient, and a polymeric matrix made from a renewable and underutilized polysaccharide source, such as the seeds of Caesalpinia ferrea, strategically selected for their healing properties on injured mucous membranes.

Inventors

  • NÁGILA MARIA PONTES SILVA RICARDO
  • FRANCISCO ALESSANDRO MARINHO RODRIGUES
  • CECÍLIA ROCHA DA SILVA
  • DEYSE DE SOUSA MAIA
  • LOUHANA MOREIRA REBOUÇAS
  • TATIANA DO NASCIMENTO PAIVA COUTINHO
  • HÉLIO VITORIANO NOBRE JÚNIOR
  • DAVID ALVES DE ASSIS

Assignees

  • UNIVERSIDADE FEDERAL DO CEARÁ

Dates

Publication Date
20260310
Application Date
20240823

Claims (8)

  1. 1. MICROSPHERE COMPOSITION BASED ON SPONDIAS PURPUREA EXTRACT AND CAESALPINIA FERREA GALACTOMANN WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDA SPP STRAINS, characterized by comprising: dry extract of the stem bark of Spondias purpurea and galactomannan from Caesalpinia ferrea.
  2. 2. MICROSPHERE COMPOSITION BASED ON SPONDIAS PURPUREA EXTRACT AND GALACTOMANN FROM CAESALPINIA FERREA WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDAS PP STRAINS according to claim 1, characterized in that the dry extract of the stem bark of Spondias purpurea is obtained from hydroalcoholic extraction with 70 parts ethyl alcohol and 30 parts water.
  3. 3. MICROSPHERE COMPOSITION BASED ON SPONDIAS PURPUREA EXTRACT AND GALACTOMANN FROM CAESALPINIA FERREA WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDA SPP. STRAINS according to any of the preceding claims, characterized by the fact that the galactomannan is obtained from the endosperm of Caesalpinia ferrea.
  4. 4. MICROSPHERE COMPOSITION BASED ON SPONDIAS PURPUREA EXTRACT AND GALACTOMANN FROM CAESALPINIA FERREA WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDAS PP STRAINS according to any of the preceding claims, characterized in that the dry extract of the stem bark of Spondias purpurea comprises a concentration of gallic acid between 1.00% and 2.00% (w/w), isoquercitrin between 5.00% and 7.00% (w/w), and kaempferol-3-O-rutinoside between 3.00% and 5.00% (w/w).
  5. 5. MICROSPHERE COMPOSITION BASED ON SPONDIAS PURPUREA EXTRACT AND CAESALPINIA FERREA GALACTOMANN WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDA SPP STRAINS according to any of the preceding claims, characterized by comprising: 70.00% to 80.00% (w/w) of galactomannan from Caesalpinia ferrea and 20.00% to 30.00% (w/w) of dry extract of the stem bark of Spondias purpurea.
  6. 6. MICROSPHERE COMPOSITION BASED ON SPONDIAS PURPUREA EXTRACT AND GALACTOMANN FROM CAESALPINIA FERREA WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDA SPP. STRAINS according to any of the preceding claims, characterized in that the microsphere has a particle diameter of 2 μm to 11 μm.
  7. 7. PROCESS FOR PREPARING MICROSPHERES BASED ON SPONDIAS PURPUREA EXTRACT AND CAESALPINIA FERREA GALACTOMANN WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDA SPP STRAINS as defined in the preceding claims, characterized by comprising the following steps: a) Solubilizing the dry extract of Spondias purpurea stem bark and Caesalpinia ferrea galactomannan in water to obtain solution A under agitation at 250 RPM for 12 hours; b) Filtrating solution A through cotton filter fabric to obtain solution B; c) Drying solution B in a spray dryer with an inlet temperature of 120 °C, 100% aspiration, a flow rate of 3 mL per minute and a needle diameter of 0.7 mm to obtain the powdered microsphere.
  8. 8. USE OF MICROSPHERES BASED ON SPONDIAS PURPUREA EXTRACT AND GALACTOMANN FROM CAESALPINIA FERREA WITH ANTIFUNGAL ACTIVITY AGAINST CANDIDA SPP STRAINS as defined in the preceding claims, characterized by being for preparing a medicament to treat candidiasis.

Description

[001] The present invention relates to the field of Biotechnology, directed to the pharmaceutical industry, and concerns the composition and use of microspheres based on Spondias purpurea extract and galactomannan from Caesalpinia ferrea with antifungal activity against Candida spp strains, characterized by comprising: dry extract of the stem bark of Spondias purpurea and galactomannan from Caesalpinia ferrea. [002] The proposed system, the subject of this invention, has potential as an antifungal drug used in the treatment of candidiasis, and has the advantage of presenting a lower minimum inhibitory concentration for some strains used in the analysis, described in Table 1, than that of the azole used in conventional treatment (fluconazole), in addition to showing better activity against Candida spp. biofilm formation when compared to the isolated extract. A differentiating factor is the use of products from the Brazilian flora: a non-cytotoxic and non-toxic bioactive agent and, as a polymeric matrix, a polysaccharide from a renewable and little-used source, such as the seeds of Caesalpinia ferrea, strategically selected for its healing properties in injured mucous membranes. [003] Candida infections are of great clinical relevance, as it is a pathogen responsible for constant cases of vulvovaginal (RODRÍGUEZ-CERDEIRA et al., 2020), oropharyngeal (VILA et al., 2020), gastrointestinal (MISHRA; KOH, 2021) and serious invasive infections, such as candidemia (POISSY et al., 2020). [004] There are some risk factors for infection by this microorganism, such as prolonged hospitalization, excessive use of antibiotics, antifungals and immunosuppressants, organ transplantation, immunosuppressed individuals, among others, which can be explained by the pathogenesis of this pathogen, through its morphology, biofilm formation, its enzymes and proteins and its adaptation to variations in the environment (MBA; NWEZE, 2020). [005] Among the main pathogenic Candida species such as C. glabrata, C. parapsilosis, C. tropicalis, C. krusei and Candida albicans (C. albicans), the latter has great clinical relevance and can be found in the mucous membranes of healthy humans. However, an imbalance in the relationship between the microorganism, the microbiota or the individual's immune system can turn it into a threat, going from commensal to being considered one of the most important opportunistic pathogens responsible for cutaneous and systemic infections, in addition to determining their severity (D’ENFERT et al., 2021). [006] Another factor that has been drawing the attention of researchers and health professionals is the emergence of Candida species that are multi-resistant to available medications, causing severe infections, such as C. auris (BRAVO RUIZ; LORENZ, 2021). [007] The search for understanding the mechanisms causing the pathogenicity of C. auris, paying attention to new studies and the review of existing ones, in addition to the search for tools that can help this cause, mainly points to the use of genetics as key to this process (BRAVO RUIZ; LORENZ, 2021) [008] The antifungals normally used in the treatment of Candida infections, belonging to the azole and echinocandin classes, are no longer as effective due to the resistance mechanisms presented by the species Candida albicans, Candida dubliniensis, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida auris, raising concerns about the risk of transmission, contamination, treatment and impacts caused by patient mortality and morbidity, in addition to the costs involved, especially with C. auris, which has shown resistance to all classes of antifungals used in traditional therapy, and together with the emerging strain of C. glabrata, which has been showing multidrug resistance to conventional antifungals (ARENDRUP; PATTERSON, 2017; PRISTOV; GHANNOUM, 2019). [009] Fluconazole is one of the most widely used azoles for the treatment of superficial and systemic mycoses, and can be administered for prolonged periods, especially in hospitalized patients with compromised immunosuppression due to organ transplantation or hematological malignancy, for example, and can cause adverse effects such as hepatotoxicity, cardiac problems, neurological problems, adrenal insufficiency (BENITEZ; CARVER, 2019; E§KUT et al., 2021; WRITERS, 2020) in addition to adverse effects related to drug interactions (LEE; LEE; CHUN, 2022) [010] The implementation of efforts to discover new therapeutic targets, due to the scarcity of new drugs and the growing microbial resistance to those commonly used in conventional therapies, sparks a dedication to research into alternatives from natural sources (GUGLIELMI; PONTECORVI; ROTONDI, 2020; KOVÁCS, 2022). [011] Nature offers a wide range of an immeasurable number of molecules, among which there is a variety of benefits and which may be an accessible possibility to become a form of isolated or combined therapy (HEARD; WU; WINTER, 2021). [