BR102021006020A2 - COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PARTS OF THE TURNERA SUBULATA SM PLANT. WITH ANTIOXIDANT, ANTINOCICEPTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIC EFFECT - Google Patents

Abstract

The search for new formulas with bioactive compounds capable of presenting biological activities for the treatment and prevention of diseases is fundamental for the production of herbal medicines. The invention consists in the preparation of liquid (extracts and/or tinctures) or solid (sachet or capsule) formulations made from the flowers, leaves, stems and roots of Turnera subulata Sm., for the prevention and treatment of pain, anxiety, diabetes and inflammation. The production of the formulations takes place through mechanisms that involve the collection, washing, drying, freezing and lyophilization of the samples, for transformation into dry bran and/or extracts and/or tinctures. Consumption should be carried out by healthy or unhealthy individuals, associated or not with food preparations. The composition of flowers and leaves have antinociceptive, hypoglycemic and anti-inflammatory potential, while the stem, leaves, root have effects on acute and conic anxiety. The indicated minimum therapeutic amount is 1 mg/mL of the sachet for the plant parts.
Keywords: Bioactive Compounds. Phytotherapy. Biological Activities. Turnera subulata Sm.

Description

COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PLANT PARTS OF TURNERA SUBULATA SM. WITH ANTIOXIDANT, ANTI-COICEPTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECTS Field of Invention

[01] The present invention is located in the field of Biotechnology in Health and describes an effective therapeutic formulation of substances present in plant parts of Turnera subulata Sm. for the prevention and treatment of anxiety, pain, inflammation and diabetes.

[02] Refers to the use and administration of botanical compositions using extracts, tinctures and flours of roots, leaves, flowers and stems for the preparation of liquid or capsule formulations with beneficial effects in the prevention and treatment of anxiety, pain, inflammation and diabetes .

[03] The present invention refers to the application of extracts, tinctures and flours for the preparation of liquid formulations or capsules made from parts of plants of Turnera subulata Sm..

[04] Chemical formulations and/or capsules made from plant parts, being derived from the root, leaves, flowers and stem of Turnera subulata Sm plant parts, or a mixture of all parts, used as a herbal medicine for prevention and treating anxiety, pain, inflammation, and diabetes.

[05] This invention also extends to compositions used as flours for sachet preparation, liquid formulations and oral tinctures, linked to the prevention and treatment of anxiety, pain, inflammation and diabetes, comprising formulations from extracts and/or flour extracted from plant parts of Turnera subulata Sm. used as herbal medicine that can be ingested alone or added to food preparations, since it has pleasant organoleptic characteristics for consumption, and can easily be included in food or used separately as herbal medicine.

[06] This technology is aimed at the area of Biotechnology with an emphasis on health, and is extremely important for describing a methodology for biological activities with antioxidant action, anxiety, pain, inflammation and hyperglycemia for parts of Turnera subulata Sm plants .. This invention also extends to oral pharmaceutical compositions, linked to the prophylaxis and treatment of diseases related or not to the biological activities mentioned above, comprising formulations with fractions of the parts and their constituents extracted from the plants of Turnera subulata Sm. used as herbal medicines, alone or separately from each other, or together with another component and/or pharmacologically acceptable excipient of vegetable or synthetic origin for the treatment or prophylaxis of said ailments.

Background of the Invention

[07] Anxiety is a vague and unpleasant feeling of fear, apprehension, characterized by tension or discomfort derived from anticipation of danger, of something unknown or strange. Anxiety disorders are related to a group of responses emitted by the body in the face of stimuli or situations. These responses emitted by the body include increased blood pressure and heart rate, excessive sweating and increased motor activity with agitation and muscle stiffness, respiratory changes, for example, superficial and rapid, among other physiological changes.

[08] Nociception refers to the activation of primary sensory nerve fibers (nociceptors) by harmful stimuli, that is, potentially causing tissue damage; are high temperatures, intense mechanical disturbances and astringent chemicals. The result of nociception is pain, which can be acute or chronic. Acute pain begins with an injury or injury and substances synthesized locally and released by stimulating nerve endings (nociceptors) of thin myelinated or unmyelinated fibers; its natural evolution is remission, however, due to the prolonged activation of several neuronal pathways, the nature of the pain may change and acute pain become chronic. Chronic pain is more than a symptom, it is the disease that persists; does not disappear after healing of the lesion or is related to chronic pathological processes.

[09] Inflammation is a defense response that occurs after cellular damage caused by microbes, physical agents (radiation, trauma, burns), chemicals (toxins, caustic substances), tissue necrosis, and/or immunological reactions. The acute inflammatory reaction is characterized by a series of interrelated events, including increased blood flow and vascular permeability in the affected region, exudation of fluid (edema), localized pain, migration and accumulation of inflammatory leukocytes inward from the blood vessels. of tissue, formation of granulation tissue and tissue repair.

[10] Diabetes mellitus (DM) is understood as a heterogeneous group of metabolic disorders whose hallmark is hyperglycemia. In type 1 DM, there is an absence of insulin production by the body and its treatment necessarily requires exogenous insulin; type 2 DM, responsible for more than 90% of cases, is related to defects in insulin action, insulin secretion and regulation of hepatic glucose production, and its treatment involves taking a series of measures to obtain dietary control, which include combating obesity, promoting regular physical activity and the use of oral antidiabetic drugs, alone or in combination.

[11] Regarding generalized anxiety disorder, until a few years ago, the only alternative was benzodiazepines (BZD). However, since the introduction of buspirone, the only azapirone (azaspirone, azaperone or azaspirodecanedione) available in Brazil, the range of effective drugs for GAD has expanded. However, the side effects impair the patient's adherence and permanence in the treatment

[12] Treatment of pain and inflammation typically involves administration of a non-opioid analgesic and a non-steroidal anti-inflammatory drug (first step). For pain of moderate intensity, an analgesic associated with a weak opioid is indicated (second step). For patients with severe pain (third step), strong opioids such as morphine and oxycodone are indicated. It is still possible to associate adjuvant drugs such as antidepressants and anticonvulsants, which can be associated with any step or used alone for better pain management.

[13] In the treatment of diabetes, drug resources are usually employed at a second stage of therapy, given the inability to control glycemic levels through diet and physical exercise (if possible). Among the medicinal agents available for the therapy of diabetes are insulin and oral hypoglycemic agents (mainly biguanides and sulfonylureas). The greatest difficulty in therapy is to maintain medication constancy by the population with diabetes, as many do not adhere to the use of drugs correctly.

[14] Faced with the impact of these diseases on the world's population, and the non-adherence to medication associated with the production of side effects, as well as the expenses generated by health services, the search for different therapeutic interventions are priorities in the scientific community. Mainly, the search for plant products with antioxidant potential capable of acting as phytomedicines for the treatment and prevention of acute and chronic pain, inflammation, anxiety and diabetes mellitus.

[15] T. subulata, known as chanana, is easy to grow and adapt to different climates. Found in humid forests, fields and tropical gardens, therefore considered as a weed. In Brazil it is common in the Northeast region, occurring from sea level to 1400 m altitude, flowering and bearing fruit throughout the year. Samples of T. subulata have been wrongly identified as Turnera ulmifolia L., a species that does not occur in Brazil.

[16] The medicinal use of T. subulata in Brazil is quite common for the treatment of amenorrhea and dysmenorrhea, treatment of flu, tumors, wounds, gastrointestinal and respiratory diseases, inflammation, infection, boils and itching.

[17] Comparison measurements were performed to evaluate the antinociceptive, anti-inflammatory and hypoglycemic potential of T. subulata flowers. The anxiolytic potential of the stems and roots were also evaluated, as well as the anxiolytic and hypoglycemic action of the leaves.

[18] Initially, toxicity, antioxidant capacity, quantification of phenols and flavonoids in leaves, flowers, stems and roots were investigated.

[19] Behavioral parameters in adult Zebrafish (Danio rerio) were observed to assess locomotor activity (OFT), anxiolytic-like effect, serotonergic and GABAergic mechanism for leaf, stem and root meal.

[20] For the open field test (OFT), the animals received oral portions of the flours and extracts of leaves or stems or roots and Diazepam. Locomotor capacity was assessed for 5 minutes.

[21] For the anxiety test, the animals underwent a light and dark test. Adult zebrafish and orally treated with portions of flour and or extracts of leaves or stems or roots and Diazepam. The animals had their behavior evaluated in a glass aquarium for 5 minutes.

[22] Serotonergic involvement and GABAergic involvement were assessed using antagonists and agonists to investigate the channels acting on each system.

[23] Behavioral antinociceptive activity performed with flour and/or flower extracts. Solution concentrations of nociceptive agents and antagonists; as well as the analysis time of nociceptive behavior formalin and camphor were used. After the treatment with the flowers, the animals were evaluated and the response of the nociceptive behavior and the analgesia in the neurogenic phase and in the inflammatory phase was observed.

[24] Anti-inflammatory activity with flower and leaf flours. Abdominal edema was induced by carrageenan in an adult zebrafish model. Adult animals received flour from flowers or leaves; vehicle or diclofenac sodium, received an injection of carrageenan. The animals were weighed before treatments and after carrageenan application.

[25] Hypoglycemic activity with flour from flowers and leaves. The animals were immersed in glucose and after inducing a hyperglycemic state, the animals were treated with flour and/or extracts from flowers and leaves; positive control, metformin. Then the biochemical test was performed.

[26] Biological and in vitro assays with flours and/or extracts from parts of Turnera subulata Sm. presented results that suggest that the compositions derived from this plant have anxiolytic activity for leaves, stems and roots, flowers have antinociceptive capacity, leaves and flowers have anti-inflammatory action and hypoglycemic activity.

[27] After searches carried out on patents with the species Turnera subulata Sm. some patents were found for other species of the genus Turnera. Patent CA 2672012A1 with title: Special extract and use thereof to inhibit the degradation of cyclic guanosine monophosphate (CGMP), refers to a method for producing an extract of an unspecified plant that is part of the Turneraceae family, but nothing has to do with the patent in question.

• - EP1658854A2 Formulações úteis no tratamento da impotência masculina e feminina;
• - RU2153347C1 Medicamento homeopático Para Tratamento De Impotência;
• - WO2019206888A1 Composições Para Tratamento da Disfunção Sexual feminina;
• - US6444237B1 Composição de ervas para aumentar a resposta sexual;
• - US2014227352A1 Oral Aphrodisiac Herbal Composition And Cpsulle.
• - FR2936953 - Composition, useful e.g. to prevent or treat diseases of female libido and to improve mood of subject, comprises l-arginine, a dry extract of maca root (lepidium meyenii), and a dry extract of damiana leaves (turnera diffusa aphrodisiaca).
• - RU0002440127 - Dosage forms effective for male and female sexual frustration.
• - WO2006021930 - Aphrodisiac herbal composition for a female comprising epimedium grandiflorum, turnera diffusa var. aphrodisiaca, ilex paraguariensis and smilax spp.

[28] The other patents found refer to the use of the species Turnera diffusa for the treatment of sexual impotence. Are they:

• - EP1658854A2 Formulations useful in the treatment of male and female impotence;
• - RU2153347C1 Homeopathic Medicine For Treatment Of Impotence;
• - WO2019206888A1 Compositions for Treating Female Sexual Dysfunction;
• - US6444237B1 Herbal composition to enhance sexual response;
• - US2014227352A1 Oral Aphrodisiac Herbal Composition And Cpsulle.
• - FR2936953 - Composition, useful eg to prevent or treat diseases of female libido and to improve mood of subject, comprises l-arginine, a dry extract of maca root (lepidium meyenii), and a dry extract of damiana leaves (turnera diffusa aphrodisiaca) .
• - RU0002440127 - Dosage forms effective for male and female sexual frustration.
• - WO2006021930 - Aphrodisiac herbal composition for a female comprising epimedium grandiflorum, turnera diffusa var. aphrodisiaca, ilex paraguariensis and smilax spp.

[29] There is also a patent for the production of chewing gum for Turnera difusa -US2017135369A1 - Composition for the production of chewing gum, for nutraceutical supplement containing Turnera aphrodisiac - WO2020230011A1 - Human nutraceutical supplement, another patent for methods of extraction and purification of substances different species - WO0072861A1 - Pharmaceutical preparations of bioactive substances extracted from natural sources. Patent for the production of creams -MXMX/A/2008/011517 - Liqueur cream composition with herbal alcohol extracts, and local for skin - JP2001322941 - Skin care preparation.

[30] No registered patents were found for the species Turnera subulata Sm. with biological action for antioxidant capacity, anxiety, inflammation, pain and hyperglycemia.
Brief Description of Figures
Figure 1A. Anxiolytic activity of leaves of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 1.B. GABAergic involvement of leaves of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 1.C. Serotonergic involvement of leaves of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 2.A. Anxiolytic activity of the roots of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 2.B. GABAergic involvement of the roots of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 2.C. Serotonergic involvement of the roots of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 3.A. Anxiolytic activity of branches of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 3.B. GABAergic involvement of branches of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 3.C. Serotonergic involvement of branches of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 4.A. Antinociceptive activity of flowers of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 4.B. Mechanisms of antinociceptive action of the flowers of Turnera subulata Sm. formalin-induced in adult zebrafish (Danio rerio)
Figure 5.A. Inflammatory activity of flowers of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 5.B. Hypoglycemic action of the flowers of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 6.A. Inflammatory activity of leaves of Turnera subulata Sm. in adult zebrafish (Danio rerio)
Figure 6.B. Hypoglycemic action of the leaves of Turnera subulata Sm. in adult zebrafish (Danio rerio)

Detailed Description of the Invention

[01] The present invention presents a formulation based on the plant Turnera subulata Sm. for the treatment and prevention of diseases, with anxiolytic, antinociceptive, anti-inflammatory and hypoglycemic effect.

[02] The formulation is intended for people suffering from anxiety and/or chronic and acute pain and/or tissue inflammation and/or increased blood glucose.

[03] The formulation effectively inhibits anxiety, pain, inflammation and hyperglycemia, requiring administration in quantity or dosage or therapy, isolated or added to food preparation. By "effective amount" or "effective or therapeutic dosage" is meant "the amount of the formulation/or flour for the sachet sufficient to bring about desired therapeutic effects, thereby resulting in effective treatment or prevention of a disorder, disease or bodily condition". The formulation must be administered in dosages greater than 1 mg/mL.

[04] The formulation is derived from the parts (leaves, flowers, roots or stem) isolated from Turnera subulata Sm., for the production of a flour for preparing liquid formulations (extracts or tinctures) and or solid formulations (flours, sachets or capsules) , and can be used as tea or for food preparations.

[05] The formulation of the present invention demonstrates that there is a dose-response relationship between the amount of liquid or solid formulations of parts of the plant Turnera subulata Sm., ingested and the reduction for each effect potentiated by the isolated parts.

[06] Solid formulations comprise the preparation of a freeze-dried flour from the isolated parts of the root or stem or leaf or flowers, the mixture of flours can also be made for the preparation of teas, or other food preparations. Liquid formulations, on the other hand, comprise the isolated parts and/or mixtures for the preparation of extracts and/or tinctures for herbal purposes.

[07] The present invention can be produced by any means or method that produces the desired vegetable flour and extracts or tinctures. Exemplary methods of flour production from Turnera subulata Sm. include collecting and drying the leaves, flowers, stems and roots of the plant, followed by crushing, freezing and freeze-drying. The methods for liquid formulations such as extracts are characterized by collection, washing, drying of samples, followed by the application of volatile substances such as ethanol or methanol to obtain extracts. Such production methods are well known in the art.

[08] Solid formulations must be made from plant parts and administered orally. A preferred formulation for administration is as a dietary supplement in powder form for (sachet/capsule) alone or added to food preparations for oral administration. Nutraceutical compositions containing the aforesaid flour together with a suitable vehicle are within the scope of the invention. The means for forming such administrative forms are well known in the art. Liquid formulations should be used as herbal medicines and also administered orally.

[09] The ability of the flowers to act as an antinociceptive, the anxiolytic potential of the leaves and roots and stem, the anti-inflammatory activity and hypoglycemic capacity of the flowers and leaves, makes the present invention capable of promoting the prevention and treatment of anxiety, pain Acute and chronic inflammation and increased blood glucose in patients with diabetes mellitus (DM).

• 1. Coleta e identificação do material vegetal (folhas, flores, caule e raízes);
• 2. Lavagem e secagem das amostras;
• 3. Adição de álcool para preparo de extratos a partir das amostras;
• 4. Secagem do material por rotaevaporação;
• 5. Envase e armazenamento do extrato.

[10] Obtaining the liquid formulation (extracts) was obtained by following the steps below:

• 1. Collection and identification of plant material (leaves, flowers, stems and roots);
• 2. Washing and drying of samples;
• 3. Addition of alcohol to prepare extracts from the samples;
• 4. Drying of the material by rotary evaporation;
• 5. Filling and storage of the extract.

• 1. Coleta e identificação do material vegetal (folhas, flores, caule e raízes);
• 2. Lavagem e secagem das amostras;
• 3. Adição de álcool para preparo de tintura a partir das amostras;
• 4. Filtragem após período de incubação;
• 5. Envase e armazenamento em vidro âmbar.

[11] Obtaining the liquid formulation (tinctures) was obtained by following the steps below:

• 1. Collection and identification of plant material (leaves, flowers, stems and roots);
• 2. Washing and drying of samples;
• 3. Addition of alcohol to prepare a tincture from the samples;
• 4. Filtering after incubation period;
• 5. Filling and storage in amber glass.

• 1. Coleta e identificação do material vegetal (folhas, flores, caule e raízes);
• 2. Lavagem e secagem das amostras;
• 3. Liofilização
• 4. Pesagem das amostras
• 5. Preparo de armazenamento em sachê ou encapsulamento

[12] Obtaining the solid formulation (sachet or capsules) was obtained by following the steps below:

• 1. Collection and identification of plant material (leaves, flowers, stems and roots);
• 2. Washing and drying of samples;
• 3. Lyophilization
• 4. Sample weighing
• 5. Preparation for storage in sachet or encapsulation

Claims (7)

“COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PLANT PARTS OF Turnera subulata SM. WITH AN ANTIOXIDANT, ANTI-COCEPTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECT” is characterized by being a composition to treat or prevent anxiety, acute and chronic pain, inflammation and hyperglycemia resulting from Diabetes mellitus (DM) frames, comprising a therapeutic amount from the liquid or solid formulation for the preparation of sachet and/or capsule and/or extracts and/or tinctures of plant parts (stem, leaves, roots, and flowers) of the genus Turnera. “COMPOSITION AND FORMULATION OF SUBSTANCES FROM THE PLANT PARTS OF Turnera subulata SM., WITH AN ANTIOXIDANT, ANTINOCYCTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECT” according to claim 1, characterized by said formulations for the preparation of sachet and/or capsule and or extracts and/or tinctures of plant parts (stem, leaves, roots and flowers) of the genus Turnera derived from the leaves, flowers, roots and stem alone or mixed. “COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PLANT PARTS OF Turnera subulata SM. WITH AN ANTIOXIDANT, ANTI-COPIC, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECT” according to claim 1, characterized in that it comprises a formulation based on a plant of the genus Turnera with antioxidant, anxiolytic, antinociceptive, anti-inflammatory and hypoglycemic properties. “COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PLANT PARTS OF Turnera subulata SM. WITH AN ANTIOXIDANT, ANTINOCYCEPTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECT” according to claim 1, characterized in that it is a formulation, which can be liquid to make extracts and tinctures, or solid formulations that can be made from flour for production of sachet and or capsules. “COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PLANT PARTS OF Turnera subulata SM. WITH AN ANTIOXIDANT, ANTINOCYCEPTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECT”, characterized by being a method to treat or prevent diseases that interfere with the central nervous system (CNS) or metabolic diseases through the administration of compositions containing the aforementioned formulations. “COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PLANT PARTS OF Turnera subulata SM. WITH AN ANTIOXIDANT, ANTI-COICEPTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECT”, characterized by controlling anxiety, pain, inflammation and hyperglycemia caused by diabetes mellitus. “COMPOSITION AND FORMULATION OF SUBSTANCES OF THE PLANT PARTS OF Turnera subulata SM. WITH AN ANTIOXIDANT, ANTINOCYCEPTIVE, ANXIOLYTIC, ANTI-INFLAMMATORY AND HYPOGLYCEMIATING EFFECT”, according to claim 1, characterized in that it is a phytotherapeutic composition that can be administered orally, through extracts or tinctures or in the form of a sachet or capsule or in preparations food, used for prophylaxis and treatment of anxiety, pain, inflammation and hyperglycemia caused by diabetes mellitus.

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