WO2016193780A1 - Procédé permettant d'obtenir une composition pharmaceutique hypoglycémique à base de nanomatériaux de tio2 et de stevia rebaudiana bertoni - Google Patents

Procédé permettant d'obtenir une composition pharmaceutique hypoglycémique à base de nanomatériaux de tio2 et de stevia rebaudiana bertoni Download PDF

Info

Publication number
WO2016193780A1
WO2016193780A1 PCT/IB2015/054094 IB2015054094W WO2016193780A1 WO 2016193780 A1 WO2016193780 A1 WO 2016193780A1 IB 2015054094 W IB2015054094 W IB 2015054094W WO 2016193780 A1 WO2016193780 A1 WO 2016193780A1
Authority
WO
WIPO (PCT)
Prior art keywords
srb
nanomatrices
extract
tio2
stevia rebaudiana
Prior art date
Application number
PCT/IB2015/054094
Other languages
English (en)
Inventor
José Albino MORENO-RODRÍGUEZ
Original Assignee
Benemérita Universidad Autónoma De Puebla
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Benemérita Universidad Autónoma De Puebla filed Critical Benemérita Universidad Autónoma De Puebla
Priority to PCT/IB2015/054094 priority Critical patent/WO2016193780A1/fr
Publication of WO2016193780A1 publication Critical patent/WO2016193780A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • the present invention relates to a process for the preparation of a hypoglycemic pharmaceutical composition based on T1O2 nanomaterials and Stevia Rebaudiana Bertoni (SrB), and to the delivery of SrB/Ti02 nanomatrices on hyperglycemia and hyperlipidemia in alloxan-induced diabetes mellitus (DM) and diabetes mellitus type 1 (DM1 ) models.
  • SrB Stevia Rebaudiana Bertoni
  • Stevia Rebaudiana Bertoni is a small bush native to the northern part of Paraguay and of adjacent zones of Brazil. The plant's leaves have been utilized to sweeten food.
  • Genus Stevia includes more than 200 species and only two of them contain steviol glycosides, SrB being the variety that contains the sweetest compounds. Glycosides perform numerous important roles in live organisms, they are hydrolyzed in the presence of water and an enzyme, thereby generating important sugars in the metabolism of the plant. The four main glycosides present in SrB are dulcoside A (0.3%), rebaudioside C (0.6%), rebaudioside A (3.8%) and stevioside (91 %). Other minor glycosides include rebaudioside B, D E and F, steviolbioside and rubososide.
  • Rebaudioside A is from 250 to 450 times sweeter when compared with sucrose, thus having the highest sweetening power of all glycosides of these leaves.
  • Glycosides of Stevia have a sweetness without calories and only a small quantity is necessary for sweetening. This aspect, in addition to the fact that it does not induce a glycemic response after its consumption, turns it into a good option for diabetics.
  • this plant has other beneficial properties such as: antihypertensive, digestive, antibacterial, hypoglycemic, anti-inflammatory, anti- carcinogenic, antioxidant and detoxifying effects, and it is abundantly rich in iron, manganese and cobalt.
  • Nanoencapsulation in biocompatible inorganic materials with human cell activity is an horrgarde technology to control the releasing process of the drug in the target place.
  • sol-gel process has reappeared as a promising platform for immobilization, stabilization and encapsulation of biological molecules such as enzymes, antibodies, microorganisms and a great variety of drugs.
  • the matrices obtained by this method are chemically inert, hydrophilic and in a single step of the synthesis the desirable products are obtained, and furthermore possess high mechanical strength, thermal stability in wide temperature ranges and negligibly adsorb organic solvents in comparison with other organic polymers.
  • An additional advantage is that it provides for viability to the encapsulated molecules, as these matrices act as water reservoirs, thereby helping to maintain the biological activity of the enzymes, antibodies, cells and, in the case of drugs, the hydration level required for the molecule.
  • the present invention addresses the issue of developing a process for the preparation of a hypoglycemic pharmaceutical composition based on T1O2 nanomaterials and Stevia Rebaudiana Bertoni (SrB), and to the delivery of SrB/Ti02 nanomatrices on hyperglycemia and hyperlipidemia in alloxan-induced diabetes mellitus (DM) and diabetes mellitus type 1 (DM1 ) models.
  • DM alloxan-induced diabetes mellitus
  • DM1 diabetes mellitus type 1
  • the complex comprising a compound of formula (I), or a vegetable extract comprising the compound or a fraction thereof and stevioside, or a vegetable extract comprising stevioside or a fraction thereof, thereby producing a virucidal effect and an effect of inhibiting cell degradation against an influenza virus, as well as the antiviral efficiency in a specific-pathogen-free (SPF) chicken, and therefore they can be employed in the prevention and processing of an infection by the influenza virus.
  • SPF specific-pathogen-free
  • MX 2014004817 A (MARKOSYAN) published on November 25 th , 2014, which corresponds to the document WO2013058870 A1 with international publication date of April 25 th , 2013, discloses: a process to produce a highly purified glycosyl stevia composition, characterized because it comprises the following stages: adding starch in water for form a starch suspension, adding a mixture of a-amylase and CGTase in the starch suspension and incubating from approximately 0.5-2 hours at approximately 75°C - 80° C, thereby resulting in a liquid starch suspension, inactivating ⁇ -amylase with a low pH heat, cooling the liquid starch suspension and adjusting pH to approximately 5.5-7.0, adding a freely soluble form of steviol glycosides in the liquid starch suspension, thereby resulting in a reaction mixture, adding a second batch CGTase in the reaction mixture and incubating for approximately 12-48 hours at approximately 55°C - 75° C, inactivating CGTase
  • An example of an objective of the present invention is to obtain the synthesis separately from T1O2 nanomatrices and T1O2 to 30% volume concentration from the Stevia rebaudiana Bertoni (SRB) extract by means of a reflux system with constant agitation.
  • SRB Stevia rebaudiana Bertoni
  • Another example of an objective of the present invention is to obtain T1O2 nanomatrices tagged as T1O2-70 through the preparation of a homogeneous solution, which contains butyl alcohol and deionized water.
  • This solution is added to a three-necked glass reactor (flask), which is placed on a grid with integrated heating blanket, with constant stirring and reflux at 70 S C. Subsequently, the solution is added with titanium n-butoxide (97%). Ultimately, the solution is submerged in an iced container and the solvent is removed with a rotary evaporator.
  • Another example of an objective of the present invention is to obtain SRB/T1O2 nanomatrices with 30% by volume, labeled as SrB/TiO 2 -30-70 and proceeding in a similar manner for obtaining a synthesis of TiO2-70 nanomatrices.
  • a variant is that the homogeneous solution is added with a 30% volume of SRB extract, and performing the same procedure mentioned above.
  • Yet another example of an objective of the present invention is to characterize the nanomatrices with the following techniques: IR spectroscopy with Fourier Transforms, UV-VIS spectroscopy, x-ray diffraction (XRD) and SEM. Furthermore, another example of an objective of the present invention is to develop a hypoglycemic pharmaceutical composition based on T1O2 nanomaterials and Stevia rebaudiana Bertoni (SRB) to evaluate the hypoglycemic effect of SRB/TiO2-30-70 nanomatrices with alloxan.
  • SRB Stevia rebaudiana Bertoni
  • an objective of the present invention is to encapsulate the Stevia Rebaudiana Bertoni (SrB) extract in T1O2 nanomaterials for evaluating the hypoglycemic effect of SRB/TiO2-30-70 nanomatrices with alloxan.
  • SrB Stevia Rebaudiana Bertoni
  • the above objects are realized by a process to prepare Stevia Rebaudiana Bertoni (SrB) extract nanocapsules in T1O2 nanomaterials, wherein it comprises the steps of: a) obtaining the separate synthesis of T1O2 and T1O2 nanomatrices to 30% volume concentration of the Stevia Rebaudiana Bertoni (SrB) extract by: b) preparing an homogeneous solution with a reflux system with constant stirring to obtain T1O2 nanomatrices, labeled as TiO2-70; and c) preparing an homogeneous solution with a reflux system with constant stirring by adding 30% by volume of the SrB extract to the homogeneous solution to obtain the SrB/Ti0 2 nanomatrices, labeled as SrB/TiO 2 -30-70.
  • Figure 1 graphically shows IR spectra of the SrB extract and of " ⁇ 2-70 and SrB/TiO2-30-70 nanomatrices in accordance with an embodiment of the present invention
  • Figure 2 graphically shows IR spectra of the 200 to 800 nm UV.VIS spectra of the SrB extract and of " ⁇ 2-70 and SrB/TiO2-30-70 nanomatrices in accordance with an embodiment of the present invention
  • Figure 3 graphically shows IR spectra of the 600 to 800 nm UV.VIS spectra of the SrB extract and of " ⁇ 2-70 and SrB/TiO2-30-70 nanomatrices in accordance with an embodiment of the present invention
  • Figure 4 graphically shows the diffractograms of the " ⁇ 2-70 and SrB/Ti02-
  • Figure 5 shows a micrograph of " ⁇ 2-70 nanomatrices in accordance with an embodiment of the present invention.
  • Figure 6 shows a micrograph of the " ⁇ 2-30-70 nanomatrix in accordance with an embodiment of the present invention
  • Figures 7A and 7B graphically show the effect of the delivery of the SRB/TiO2-10-70 and SrB/TiO2-30-70 nanomatrices on the temporary course of the glucose concentration with alloxan-induced DM1 in accordance with an embodiment of the present invention
  • Figure 8 graphically shows the effect of the delivery of the SRB/T1O2 nanomatrices on weight reduction in rats with alloxan-induced DM, in accordance with an embodiment of the present invention
  • FIG. 9A graphically shows the effect of the delivery of the SRB/T1O2 nanomatrices on glucose concentration (mg/dL) in plasma delivered with alloxan, in accordance with an embodiment of the present invention
  • Figure 9B graphically shows the effect of the delivery of the SRB/T1O2 nanomatrices on glycosylated hemoglobin concentration (%) delivered with alloxan, in accordance with an embodiment of the present invention
  • Figure 9C graphically shows the effect of the delivery of SRB/T1O2 nanomatrices on the concentration of insulin ( ⁇ /mL) delivered with alloxan;
  • FIG. 10A graphically shows the effect of the delivery of the SRB/T1O2 nanomatrices on cholesterol concentration (mg/dL) delivered with alloxan, in accordance with an embodiment of the present invention
  • Figure 10B graphically shows the effect of the delivery of the SRB/T1O2 nanomatrices on triglyceride concentration (mg/dL) delivered with alloxan, in accordance with an embodiment of the present invention.
  • FIG. 10C graphically shows the effect of the delivery of the SRB/T1O2 nanomatrices on HDL concentration (mg/dL) delivered with alloxan, in accordance with an embodiment of the present invention
  • the present invention refers to a hypoglycemic pharmaceutical composition based on T1O2 nanomaterials and Stevia Rebaudiana Bertoni (SrB), produced through the synthesis of T1O2 and T1O2 to 30% volume concentration of the SrB extract.
  • SrB Stevia Rebaudiana Bertoni
  • the SrB extract in T1O2 nanomatrices was encapsulated, which help to obtain quicker therapeutic effects with a single delivery, for evaluating the hypoglycemic effect of SrB/TiO2-30-70 nanomatrices.
  • T1O2 nanomatrices A homogeneous solution is prepared containing butyl alcohol and deionized water. This solution is added to a three-necked glass reactor (flask), which is placed on a grid with integrated heating blanket, with constant stirring and reflux at 70 S C. Subsequently, the solution is added with titanium n-butoxide (97%). Afterwards, the solution is submerged in an iced container and the solvent is removed with a rotary evaporator. Therefore, the synthesis of T1O2 nanomatrices, labeled as T1O2-70, are obtained.
  • flask three-necked glass reactor
  • a similar process is followed for obtaining the synthesis of TiO2-70 nanomatrices.
  • the variant is that the homogeneous solution is added 30 vol % of the SrB extract, and the same procedure is performed as above, to obtain the nanoreservoirs of SRB/TiOi0 2 with 30% by volume, labeled as SrB/TiO 2 -30-70.
  • the nanomatrices are characterized by the following techniques: IR with Fourier transforms, UV-VIS, DRX and SEM.
  • DM1 induced diabetes mellitus type 1
  • Alloxan induced diabetes mellitus type 1
  • the weight of the experimental subjects are is recorded at the beginning of the study. Rats are weighted on days 5, 10, 15 and 30 in order to watch the development of the DM1 clinical picture.
  • rats display glycaemia of between 160-200 mg/dL
  • Group B is delivered a dose of 45 mg/kg by weight of alloxan in citrate buffer pH 4.5 and then a dose of 1 g/kg by weight intraperitoneal ⁇ (i.p.) of SRB/T1O2-3O- 70 nanomatrices in accordance with Gregersen 2004.
  • Group C is delivered a dose of 45 mg/kg by weight of alloxan in citrate buffer pH 4.5 and then a dose of 1 g/kg by weight i.p. of SRB/TiO2-30-70 nanomatrices.
  • Determination of glucose Blood glucose determination is performed using a Roche digital glucometer, based on the glucose oxidase reaction, said reaction occurring between blood glucose and glucose oxidase. Measurements of blood glucose concentrations for rodents are made in the short term (0, 4, 8 and 24 hours) and long term (5, 10, 15 and 30 days), after i.p. delivery of nanomatrices 1 g/kg by weight, when they are fasted for 6 hours.
  • FIG. 1 graphically shows FTIR spectra of T1O2 and SrB/TiO2-30 nanocatalysts.
  • the IR spectrum of the T1O2 nanoreservoir that displays an absorption band at 3339.1 cm 1 , thereby corresponding to the enlargement vibration mode of an VO-H type, which identifies hydroxyl groups (OH ), water(H- OH), of the solvent (butanol, R-OH) and of the hydroxylated matrix (Ti-OH).
  • OH hydroxyl groups
  • water(H- OH) of the solvent
  • Ti-OH hydroxylated matrix
  • the asymmetrical enlargement vibration modes VC-H are located at 2939.2 cm 1 , which correspond to chemical species C-H of methyl (Ti- O-CH3) and ethoxy groups ( ⁇ Ti-OCH2CH3) which did not react during the T1O2 synthesis.
  • the flexural vibration modes (VOH) of hydroxyl groups of water present on the surface of the T1O2 nanomaterial are presented. It is mainly associated with the humidity of the nanomaterial, of the solvent and with the deformation 6HOH of coordinated water.
  • the flexural vibration modes of OH groups from ethoxide in the form of unreacted chemical species ⁇ Ti-OEt are located at 1448 cm "1 .
  • the symmetrical flexural vibrations vcoo, asymmetrical deformation VC-H and scissors-like deformation 6CH3 are found.
  • Wave numbers from 1 1 18.7 cm 1 to 1006.5 cm “1 absorption correspond to the flexural vibration modes of C-C symmetrical groups (vc-c), CH2 (VCH2) and C-0 (vc-o), which correspond to methoxy-bridging species, as well as to solvents, products and byproducts of the synthesis reaction of the material.
  • vc-c C-C symmetrical groups
  • CH2 VCH2
  • vc-o C-0
  • Nanomaterials with SrB to 30% volume of the extract have the same enlargement vibration modes: (VO-H) and (VC-H) and flexural mode: (VO-H) , (6HOH) , (vcoo ), (VC-H) , (6CH3), (VC-C) , (VC-O) and (vn-o) as those observed in the T1O2 nanomatrix. More pronounced and wide vibration peaks are observed, these tend to move slightly to farther regions of IR.
  • FIG. 2 graphically shows UV-VIS spectra of TiO 2 -70 and SrB/TiO 2 -30-70 nanoreservoirs and of the SrB extract.
  • UV-VIS spectrum of T1O2 presents a forbidden band energy of 376.5 nm.
  • the curve of the SrB/Ti02 nanomatrix gradually moves towards lower energy regions of the electromagnetic spectrum; from a wavelength of 376.5 nm (for TiO 2 -70) up to 406.2 nm (for SrB/TiO 2 -30-70), as shown in table 1 .
  • Table 1 shows the optical and electronic properties from UV- VIS spectra of (TiO2-70 and SrB/TiO2-30-70) nanomatrices obtained from fine chemical synthesis, from where:
  • Table 1 Data of optical and electronic properties of TiO2-70 and SrB/TiO2-30-70 nanomatrices.
  • Figure 3 graphically shows the nanoreservoirs with a concentration greater than 1 ⁇ _ of stevioside (SrB/TiO 2 -3-70, SrB/TiO 2 -10-70, SrB/TiO 2 -20-70 and SrB/TiO2-30-70), and an absorption curve at 670 nm, in the visible region, can be observed.
  • This absorption may correspond to ⁇ * transitions of ⁇ , ⁇ insaturated ketones and to the presence of cyclic oxypolyene groups of steviol.
  • the greatest intensity band located in the UV-VIS spectrum of the Stevia extract corresponds to the electronic transitions of ⁇ * from the stevioside.
  • FIG 4 x-ray diffractograms from TiO2-70 and SrB/TiO2-30-70 nanomatrices are graphically shown. Atomic dispersion factors from International Tables for X-Ray Crystallography were used for the analysis. According to the diffractograms presented in figure 4, all the nanomatrices obtained (TiO2-70 y SrB/TiO 2 -30-70) are amorphous.
  • Figure 5 shows the micrograph of TiO2-70 nanomatrices, with a traced area of 25 000X to 100 000X.
  • TiO2-70 presents a form of agglomerate particles with an average particle diameter of 100nm.
  • Figure 6 shows the micrograph of the SrB-TiO2-30-70 nanomatrix.
  • the T1O2 nanomatrix with 30 ⁇ _ SrB presents a sweep area of 1000X to 5000X, the average particle area being 50 nm. Evaluation of the biological activity of SrB/TiO2-30-70 nanomatrices in rats with DM1.
  • Figures 7A y 7B show the micrograph of the effect of delivery of SrB/Ti02- 10-70 and SrB/TiO2-30-70 nanomatrices on the temporary course (in hours and days) of glucose concentration in rats with alloxan-induced DM1 .
  • Rats were delivered alloxan (150 mg/kg) and later the SrB/TiO 2 -10-70 and SrB/TiO 2 -30-70 nanomatrices.
  • the plotted data represent mean ⁇ SEM (standard error of the mean). (One/way variance analysis (ANOVA), post test Bonferroni), ** p ⁇ 0.01 ; *** p ⁇ 0.001 (control vs. alloxan) # p ⁇ 0.05; ### p ⁇ 0.001 (alloxan vs. SrB (10 and 30 ⁇ _).
  • the results indicate that the group treated with alloxan reports a decreased weight when compared with the groups treated with alloxan + SrB / TiO 2 -10-70 of 14% (fifth day), 46% (tenth day), 94% (fifteenth day) and 187% (thirtieth day).
  • the group treated with alloxan + SrB/TiO 2 -30-70 was 22% (fifth day), 50% (tenth day), 88% (fifteenth day) and 144% (thirtieth day).
  • the comparative analysis of the results revealed a significant difference (see figure 8).
  • Figure 8 graphically shows the effect of the delivery of SRB/T1O2 nanomatrices on the weight reduction in rats with alloxan-induced diabetes mellitus (DM). Rats were delivered alloxan (150 mg/kg) and later the SrB/Ti02- 10-70 and SrB/TiO2-30-70 nanomatrices. The plotted data represent mean ⁇ SEM (one-way ANOVA, post test Bonferroni,) # p ⁇ 0.05; ### p ⁇ 0.001 (alloxan vs. SrB/Ti0 2 - 10-70 and SrB/TiO 2 -30-70).
  • the concentration of glucose and glycosylated hemoglobin of alloxan treated groups + SrB/TiO2-10-70 in respect of the group with alloxan + T1O2 have a lower concentration of glucose of 28% and 40% glycosylated hemoglobin; whereas the group treated with alloxan + SrB/TiO2-30-70 has 28% glucose and 40% glycated hemoglobin 30 days after starting the treatment (See Figures 9A and 9B).
  • the concentration of insulin in the group treated with alloxan + SrB/Ti0 2 - 10-70 and alloxan + SrB/TiO 2 -30-70 were increased between 137% and 645% respectively, when compared to the alloxan+Ti02 group. (See Figure 9C).
  • Figures 9A, 9B and 9C show the effect of the delivery of SRB/T1O2 nanomatrices on the concentration of glucose, glycosylated hemoglobin and insulin in rats delivered alloxan. Quantification was performed with plasma 30 days after the delivery of SRB/TiO 2 -10-70 and SrB/TiO 2 -30-70 nanomatrices (1 g/kg) in rats treated with alloxan (150 mg/kg).
  • glucose concentration (mg/dl) in plasma is shown
  • the graph of Figure 9B shows the percentage of glycated hemoglobin
  • the graph of Figure 9C shows the concentration of insulin ( ⁇ /mL).
  • the plotted data represent the mean ⁇ SEM.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé permettant de préparer des nanocapsules d'extrait de Stevia Rebaudiana Bertoni (SrB) dans des nanomatériaux de TiO2, ledit procédé comprenant les étapes consistant à : a) obtenir la synthèse séparée de TiO2 et de nanomatrices de TiO2 à une concentration en volume de 30 % de l'extrait de Stevia Rebaudiana Bertoni (SrB) ; b) préparer une solution homogène avec un système de reflux avec une agitation constante pour obtenir des nanomatrices de TiO2, étiquetées sous la forme TiO2-70 ; et c) préparer une solution homogène avec un système de reflux avec une agitation constante par l'ajout de 30 % en volume de l'extrait de SrB à la solution homogène afin d'obtenir les nanomatrices de SrB/TiO2, étiquetées sous la forme SrB/TiO2-30-70.
PCT/IB2015/054094 2015-05-29 2015-05-29 Procédé permettant d'obtenir une composition pharmaceutique hypoglycémique à base de nanomatériaux de tio2 et de stevia rebaudiana bertoni WO2016193780A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/IB2015/054094 WO2016193780A1 (fr) 2015-05-29 2015-05-29 Procédé permettant d'obtenir une composition pharmaceutique hypoglycémique à base de nanomatériaux de tio2 et de stevia rebaudiana bertoni

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2015/054094 WO2016193780A1 (fr) 2015-05-29 2015-05-29 Procédé permettant d'obtenir une composition pharmaceutique hypoglycémique à base de nanomatériaux de tio2 et de stevia rebaudiana bertoni

Publications (1)

Publication Number Publication Date
WO2016193780A1 true WO2016193780A1 (fr) 2016-12-08

Family

ID=57440541

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2015/054094 WO2016193780A1 (fr) 2015-05-29 2015-05-29 Procédé permettant d'obtenir une composition pharmaceutique hypoglycémique à base de nanomatériaux de tio2 et de stevia rebaudiana bertoni

Country Status (1)

Country Link
WO (1) WO2016193780A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2691952C1 (ru) * 2018-08-07 2019-06-19 Александр Александрович Кролевец Способ получения нанокапсул сухого экстракта стевии
RU2695618C2 (ru) * 2018-01-10 2019-07-24 Частное образовательное учреждение высшего образования "Региональный открытый социальный институт" ЧОУ ВО "РОСИ" Способ получения нанокапсул сухого экстракта стевии

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006116815A1 (fr) * 2005-05-02 2006-11-09 Vanadis Bioscience Ltd Composition pour le contrôle des niveaux de cholestérol
CN101156883A (zh) * 2007-10-24 2008-04-09 石任兵 甜叶菊有效部位及其活性和应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006116815A1 (fr) * 2005-05-02 2006-11-09 Vanadis Bioscience Ltd Composition pour le contrôle des niveaux de cholestérol
CN101156883A (zh) * 2007-10-24 2008-04-09 石任兵 甜叶菊有效部位及其活性和应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Database accession no. 2008-M65308 *
DIAZ A ET AL.: "Hypoglucemic and antihyperlipidemic activity of Ti02 nanostructured-conjugated Stevia rebaudiana bertoni in a model of diabetes mellitus in rats.", REVISTA MEXICAN A OF CIENCIAS FARMACEUTICAS 2013 ASOCIACION FARMACEUTICA MEXICAN A A.C. MEX, vol. 44, no. 4, pages 36, ISSN: 1027-3956 *
LANGLEA A ET AL.: "Stevia rebaudiana loaded titanium oxide nanomaterials as an antidiabetic agent in rats.", BRAZILIAN JOURNAL OF PHARMACOGNOSY 30/03/2015 SOCIEDADE BRASILEIRA OF FARMACOGNOSIA BRA, vol. 25, no. 2, March 2015 (2015-03-01), pages 145 - 151, XP055332793, ISSN: 0102-695X *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2695618C2 (ru) * 2018-01-10 2019-07-24 Частное образовательное учреждение высшего образования "Региональный открытый социальный институт" ЧОУ ВО "РОСИ" Способ получения нанокапсул сухого экстракта стевии
RU2691952C1 (ru) * 2018-08-07 2019-06-19 Александр Александрович Кролевец Способ получения нанокапсул сухого экстракта стевии

Similar Documents

Publication Publication Date Title
EP1676908B1 (fr) Procede de fermentation et de culture, extrait de plante fermente, poudre d'extrait de plante fermente et composition contenant ledit extrait de plante fermente
Wojdyło et al. Polyphenol compounds and biological activity of caper (Capparis spinosa L.) flowers buds
Chen et al. Synergistic hypoglycemic effects of pumpkin polysaccharides and puerarin on type II diabetes mellitus mice
Sabu et al. Effect of Cassia auriculata Linn. on serum glucose level, glucose utilization by isolated rat hemidiaphragm
Ding et al. Hypoglycaemic effect of comatin, an antidiabetic substance separated from Coprinus comatus broth, on alloxan-induced-diabetic rats
CN109303922B (zh) 一种刺梨多糖功能化纳米硒复合物及其制备方法与在降糖药物中的应用
CN106634978B (zh) 以甘蔗废糖蜜为原料合成荧光碳点的制备方法及其应用
WO2010140409A1 (fr) Agent favorisant l'élongation des neurites, agent améliorant la mémoire et agent anti-alzheimer comprenant la 4'-déméthylnobilétine ou la 4'-déméthyltangerétine comme principe actif, et procédé de production du composé
CN113004432B (zh) 一种铁皮石斛寡糖、铁皮石斛寡糖衍生物及其制备方法和应用
US20140288334A1 (en) Novel resveratrol polymerization compound or pharmaceutically acceptable salt thereof
Gómez-López et al. Characterization, stability, and bioaccessibility of betalain and phenolic compounds from Opuntia stricta var. Dillenii fruits and products of their industrialization
CN107922452A (zh) 一种氧化型β‑1,4‑寡聚葡萄糖醛酸及其制备方法和用途
Myo et al. Changes in bioactive compounds of coffee pulp through fermentation-based biotransformation using Lactobacillus plantarum TISTR 543 and its antioxidant activities
Gevrenova et al. UHPLC-MS Characterization and biological insights of different solvent extracts of two Achillea species (A. aleppica and A. santolinoides) from Turkey
WO2016193780A1 (fr) Procédé permettant d'obtenir une composition pharmaceutique hypoglycémique à base de nanomatériaux de tio2 et de stevia rebaudiana bertoni
Nikolova et al. Drug-delivery silver nanoparticles: a new perspective for phenindione as an anticoagulant
CN109232760A (zh) 桑黄护肝多糖ppb-2及其制备方法
Langle et al. Stevia rebaudiana loaded titanium oxide nanomaterials as an antidiabetic agent in rats
EP2324840A1 (fr) Production d'acides cafféoylquiniques à partir de cultures de cellules végétales d'Echinacea angustifolia
Lu et al. Maltase and sucrase inhibitory activities and hypoglycemic effects of carbon dots derived from charred Fructus crataegi
Dias et al. Recent technological advances in phenolic compounds recovery and applications: source of nutraceuticals for the management of diabetes
CN109535280A (zh) 一种抗坏血酸壳寡糖复合盐及其制备方法和应用
CN107987179A (zh) 一种低硫酸化岩藻半乳聚糖在制备免疫增强剂中的应用
CN110218263B (zh) 一种猴头菇菌糠多糖、制备方法及应用
JP4522624B2 (ja) レモン発酵物及びその製造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15894043

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 21/03/2018)

122 Ep: pct application non-entry in european phase

Ref document number: 15894043

Country of ref document: EP

Kind code of ref document: A1