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BR-102024018101-A2 - PROCESS FOR OBTAINING CURCUMIN MICROCAPSULES AND PHOTOLARVICIDAL FORMULATIONS

BR102024018101A2BR 102024018101 A2BR102024018101 A2BR 102024018101A2BR-102024018101-A2

Abstract

The present invention applies to the field of vector management in public health, and relates to a photoactivatable larvicide and its production process in microcapsules comprising the active pharmaceutical ingredient (API), the photosensitizer (PS) "curcumin," and the inactive excipients "D-mannitol and starch," obtaining formulations based on curcumin microcapsules and proportions of active ingredients D-mannitol, starch, and pectin in the form of pressed pellets. The resulting formulation is used to inactivate larvae of the Aedes aegypti vector in conjunction with a light source, which can be artificial or solar, in the control of this vector, reducing the insect population and thus the transmission rates of the viruses.

Inventors

  • Vanderlei Salvador Bagnato
  • ALESSANDRA RAMOS LIMA
  • MATHEUS GARBUIO
  • Natalia Mayumi Inada
  • Kleber Thiago De Oliveira
  • LUCAS DANILO DIA
  • Ana Paula Da Silva

Assignees

  • VANDERLEI SALVADOR BAGNATO
  • EMIPHARMA INDUSTRIA E COMERCIO DE PRODUTOS FARMACOS LTDA

Dates

Publication Date
20260317
Application Date
20240903

Claims (4)

  1. 1) A photosensitive larvicide composition characterized by comprising the photosensitizing active ingredient curcumin and the inert excipients D-mannitol and starch, in the proportion of 10-20% curcumin, and the excipients D-mannitol and starch in the range of 30-50%, respectively, formulated with the following steps: I) The photosensitizer curcumin (10-20% mass/mass) is initially mixed in 0.01-0.150 L of ethanol, maintained under magnetic stirring (10 to 2000 rpm) until solubilization; II) The excipients, starch (40-50% mass/mass) and D-mannitol (20-30% mass/mass), are mixed in 0.01-2 L of water, maintained under stirring (10 to 2000 rpm) until dissolution; III) Solutions I and II are mixed under magnetic stirring (10 to 2000rpm) until homogenization and dissolution, IV) The mixture is transferred to an atomizer for drying the formulation using the spray dryer technique, under the following conditions: temperature (intlet: 130-140°C; Outlet: 70-80°C), drying flow rate (1.20-1.50m3/min), compressed air flow rate (0.3L/h), compressed air pressure (6 bar) and atomizer nozzle diameter (1.22 mm), obtaining a microencapsulated powder.
  2. 2) A photosensitive larvicide composition, according to claim 1, characterized by comprising the production steps of a formulation F1: I) active ingredient curcumin microencapsulated 5-10% (w/w), excipient D-mannitol 20-30% and starch 50-60% (w/w), II) Mixing in a mortar of the active ingredient microencapsulated and excipients, III) Compressing 200 mg of the formulation in a press with a force of 4 kN, obtaining a pellet of formulation F1.
  3. 3) A photosensitive larvicide composition, according to claim 1, characterized by comprising the production steps of formulation F2: active ingredient microencapsulated curcumin 5-10% (w/w), excipient D-mannitol 20-30% / starch 20-25% and pectin 30-35% (w/w), II) Mixing the microencapsulated active ingredient and excipients in a mortar, III) Compressing 200 mg of the formulation in a press with a force of 4 kN, obtaining a pellet of formulation F2.
  4. 4) A photosensitive larvicide composition, according to claim 1, characterized by comprising the production steps of formulation F3: active ingredient microencapsulated curcumin 5-10% (w/w), excipient D-mannitol 20-30%/ starch 20-30% and pectin 40-42.5% (w/w), II) Mixing the microencapsulated active ingredient and excipients in a mortar, III) Compressing 200 mg of the formulation in a press with a force of 4kN, obtaining a pellet of formulation F3.

Description

[1] The present invention applies to the field of vector management in the area of public health, and relates to a photoactivatable larvicide and its production process in microcapsules comprising the active pharmaceutical ingredient (API) the photosensitizer (PS) “curcumin” and the inactive excipients “D-mannitol and starch”, obtaining formulations based on curcumin microcapsules and proportions of active ingredients D-mannitol, starch and pectin in the form of pressed pellets and the resulting formulation being used to inactivate larvae of the Aedes aegypti vector associated with a light source, which may be artificial or solar, in the control of this vector, reducing the insect population, and thus the virus transmission rates. [2] The arboviruses Dengue, Zika, Yellow Fever and Zika are transmitted by the bite of the vector mosquito Ae. aegypti. These are responsible for Dengue, Chikungunya, Yellow Fever and Zika infections that share some clinical characteristics that lead to incorrect diagnoses and reports in the absence of laboratory tests (WHO, 2024). [3] Furthermore, arboviruses, transmitted by the vector Ae. aegypti, constitute a global public health problem that affects the population, reducing the quality of life and overburdening the public health system. 2/29 Reducing the rate of virus transmission and consequently infection can be achieved through methods of controlling the Ae. aegypti vector in the larval and adult stages. [4] Control methods can be traditional mechanical, biological and chemical methods or emerging methods such as Wolbachia suppression and genetically modified mosquitoes. Traditional methods can be carried out in an integrated manner. Emerging methods are not well disseminated in vector control. Therefore, the prevailing and most widely used method is chemical control, both in the larval and adult stages of the insect (Kumar et al. BMJ Public Health, 2, 2024, e000342). However, the use of this control method has been limited by reduced effectiveness and increasing resistance to the chemical method, in addition to harming the environment. [5] Currently, despite scientific advances, there is still no vaccine or drug that guarantees immunity or treatment for all infections caused by arboviruses transmitted by the Ae. aegypti vector. There is only an approved vaccine for the Dengue virus (KALLÁS, E.G et al. N English J Med 390, 2024, 397-408). Therefore, the development of methods and molecules with effective formulations for integrated and sustainable management that are less aggressive to the environment are fundamental for the control of the Ae. aegypti vector. [6] Thus, it proposes the use of curcumin, a photosensitive molecule, already used in photodynamic processes as a therapy for cancer and inactivation of microorganisms. This molecule has shown great potential as a photosensitive larvicide in the area of vector management, here called photolarvicides. Despite its promising properties, curcumin faces significant challenges, such as its low solubility and the need to develop methods that improve this aspect and ensure the controlled release of the active ingredient. In addition, it is crucial to minimize the reactivity of the molecule in adverse environments, such as exposure to light, oxygen and pH variations, to increase the residual action of the photosensitive larvicide in potential breeding sites. [7] Photolarvicides are activated when they interact with a light source at wavelengths ranging from ultraviolet to visible (artificial light: fluorescent lamp, light-emitting diode and solar irradiation), forming reactive oxygen species that are highly reactive and cause oxidation to the target organisms, leading to death. These processes are known as photodynamic inactivation. [8] In this context, the present invention aimed at the development and production of a microcapsule with the photosensitizer curcumin, 4/29 which is formulated and acts as a photolarvicide against the larvae of the mosquito Ae. aegypti. [9] The curcumin microcapsule production process was carried out via spray dryer encapsulation. Inactive excipients, among biopolymers, can act as encapsulating agents, with a promising variety that performs the function of improving solubility, stability and controlled release of the active ingredient, such as D-mannitol and starch. [10] Thus, the present invention proposes a spray dryer encapsulation process with the excipients D-mannitol and starch with the active ingredient “curcumin”, obtaining curcumin-based microcapsules. The curcumin microcapsules can be formulated with other excipients such as pectin and pressed into pellet form. [11] In this way, the tablet system favors the controlled release of the active ingredient, which, in the biopolymer microcapsule, in this case the present invention, curcumin is dispersed in the potential breeding ground of Ae. aegypti larvae, guaranteeing the stability and prolonged residual effect of the formulation. [12] Theref