专利摘要:
Nutraceutical composition consisting of a polyphenol in glycolic solution, method of obtaining and its therapeutic use. The invention relates to a method of obtaining a nutraceutical composition consisting of glycerin and a polyphenol or a derivative thereof, which comprises: a) heating the glycerin to a temperature between 30ºC-35ºC; b) mixing the heated glycerin and the polyphenol in a ratio of polyphenol and glycerin comprised between 1:15 to 1:30 by weight: and c) dispersing the mixture by means of cavitation induced by 20 kHz ultrasound, for at least 10 minutes, to form Weak intermolecular interactions by hydrogen bonding between the hydroxyl groups of the components of the mixture. Likewise, another object of the invention is the nutraceutical composition obtainable from the described method, as well as its use for the treatment of diseases such as diabetes, cholesterolemia and neurodegenerative diseases, one of them being Alzheimer's. (Machine-translation by Google Translate, not legally binding)
公开号:ES2841474A1
申请号:ES202030007
申请日:2020-01-08
公开日:2021-07-08
发明作者:Gil Jesus Martin;Juan Celia Andres;Duran Laura Buzon;Lebena Eduardo Perez;Ramos Pablo Martin
申请人:Universidad de Valladolid;
IPC主号:
专利说明:

[0004] Technical sector of the invention
[0005] The invention presented is framed in the field of Biochemistry and finds its fundamental application in the food sector, specifically functional and nutraceutical foods. Specifically, it is a glycolic solution (that is, based on glycerin) of active compounds, which are specifically polyphenols, ingestible as it is prepared or in aqueous solution, and which is obtained by cavitation at low temperature, which significantly increases its solubility and, consequently, its bioavailability.
[0007] Background of the invention
[0008] Chemistry is a field of remarkable breadth and in continuous technological progress, applicable to the pharmaceutical, food, agricultural and cosmetic industries, which need to evolve in order to achieve an improvement in the effectiveness of the substances chosen for an intended use, providing solutions adapted to increasingly demanding needs.
[0010] One of these substances is functional or nutraceutical foods. Although they lack precise regulations, a nutraceutical compound can be defined as a natural substance made from one or more natural ingredients, which is used as a dietary supplement and is present in food although in a less concentrated form, that is, than in the nutraceutical is ingested in doses higher than those found in food. This type of natural substances are bioactive because they are assumed to have a favorable effect on health greater than that shown when ingested through food, being even capable of preventing and treating diseases.
[0012] The concept of bioavailability is essential to ensure that the active compound to be delivered is used by the body and is useful for its intended purpose. Unfortunately, the administration of many compounds often suffers from solubility problems and, therefore, their bioavailability is zero or very low.
[0013] Within the nutraceutical field, the bioactive substances or biologically active compounds (CBAs) that are commonly used are usually insoluble in water. This is the case, among others, of polyphenols, substances that are usually found in plants or in some fruits, whose solubility is practically nil and therefore, in their normal formulation, they are not usable inside organisms, since that its absorption occurs naturally through water.
[0015] The development of new techniques for solubilization, encapsulation or transport of these CBAs applicable in the food sector, for the purposes of their conversion into bioavailable substances, is one of the workhorses of current Chemistry and has a great future application.
[0017] Among these techniques, outside the field of food, the one described in Spanish patent ES2718225B2 can be highlighted, authored by the same inventors of the present technological innovation, where the solubilization of active compounds applicable to agriculture through the use of oligomers is analyzed. low molecular weight chitosan, a compound not accepted for human consumption, and steviol glycosides as encapsulating agents; This complex is formed by sonication. There are also techniques to improve the bioavailability of hydrophobic or partially insoluble compounds in water that are intended to be ingested, such as the use of glycerin as a vehicle for said substances, a use that has been analyzed in several scientific publications: Shehata, Emad & Grigorakis , Spyros & Loupassaki, Sofia & Makris, Dimitris (2015): Extraction optimization using water / glycerol for the efficient recovery of polyphenolic antioxidants from two Artemisia species; Separation and Purification Technology, 149 ( 10) .; Corneliu Tanase et al (2019): A Critical Review of Phenolic Compounds Extracted from the Bark of Woody Vascular Plants and Their Potential Biological Activity ;, Molecules, 24: 1182.
[0019] Thus, in patent application JP-A-2008-179547 a solution has been proposed in which a polyphenol is dissolved in a fatty acid triglyceride as a preparation that guarantees the storage stability of the active compound. Additionally, in the patent application JP-A-6-239716 it is revealed that the discoloration of a polyphenol, which usually experiences during the preparation of compositions, can be avoided with an aqueous solution to contain a compound that has two or more groups hydroxyl alcoholic or to further contain an organic reducing agent. However, in these polyphenol stabilization techniques an oily solvent, a fatty acid triglyceride, is used. Therefore, from a compatibility, security and storage stability point of view, it has been difficult to use this solution on an industrial level.
[0021] For its part, patent EP2646041 describes a method to extract propolis, characterized in that it comprises the complexation of the extractable components with hydroxypropyl-p-cyclodextrin as an inclusion agent during the extraction. After defining the particle size of the propolis with a mechanical device, in the second stage said particles are dispersed in a water / glycerol mixture, in whose aqueous phase the hydroxypropyl-p-cyclodextrin has previously been dissolved. The mixture of water and glycerol is carried out to reduce the viscosity of the medium, due to the glycerol, but the addition of cyclodextrins later hinders the release and bioavailability of the polyphenols contained in propolis.
[0023] On the other hand, the international patent application WO2008 / 096343A1 describes methods of preparing a liquid (alcoholic) pharmaceutical composition based on turmeric or curcumin and an alcohol, preferably ethanol, as an extractive compound, which can be dissolved in water to be ingested, its objective being medical treatment. The method describes the extraction by heating of the turmeric components and curcumin, and combining them to form the ethanolic composition. When using ethanol, the heating must be considerably high (above 60 ° C, in practice reaching its boiling temperature, 78 ° C), and if glycerin is added as a solvent to replace part of the ethanol, the mixture is heats up to about 100 ° C. Therefore, these compositions can also contain glycerin, but without dispensing with ethanol as an essential component, since glycerin is hardly used to replace a part of ethanol. The temperature referred to in this document is too high to preserve the chemical and organoleptic properties of the active component (in this case, curcumin), which affects its functionality and the beneficial results expected after ingestion. It has been verified that the dissolution carried out at high temperatures, similar to those indicated in the aforementioned patent application, produces a degradation in the chemical structure of the polyphenol, which implies the loss of its biochemical properties.
[0024] It should also be noted the international patent application WO2015 / 094479, which refers to a composition for oral care that comprises rutin as an active agent and a solvent that can be propylene glycol, glycerin or a mixture of both (although in reality only propylene glycol is used with glycerin or sorbitol, never glycerin alone), therefore a mixture of compounds with which it is intended to increase the solubility of the active agent. The composition of this mouthwash can be prepared simply by premixing both mentioned compounds and then combining the mixture with the rest of the ingredients of the final composition. Unfortunately, propylene glycol is not a substance allowed in the composition of nutraceutical compounds, since according to Regulation (EC) 1333/2008, in Annex III Part I, its use is limited to 1 gr per kg of final food, for so it is not feasible to use such a mixture in nutraceutical compositions. On the other hand, the text does not define the key conditions of the process (temperature, quantity to be solubilized ...), and that determine the success or failure of the process (it is unlikely to be achieved, in any condition, to achieve total solubility and to time to maintain the organoleptic properties of the active agent). Likewise, the effectiveness of an active agent such as polyphenol to be used as a mouthwash does not have the same requirements as those it must meet as a nutraceutical, specifically to be ingested and subsequently assimilated by the body.
[0026] In short, there are currently in the bibliography techniques for the transport of active compounds (CBAs) in general, and applied to food in particular, which increase their availability. However, at an industrial level, the known mechanisms suffer from serious problems, mainly because techniques are not used that favor the feasibility and acceleration of complex formation (they are complex and expensive reactions) and significantly reduce the effect of the method itself. in the properties of the compound; normally, a degradation of the organoleptic properties occurs due to the temperatures at which the active substances in question must be diluted.
[0028] From the aforementioned, it is deduced the need to develop new CBAs solubilization systems applicable to the sector of functional and nutraceutical foods, which overcome the aforementioned drawbacks and serve to convey these water-insoluble compounds, as is the case of polyphenols, and finally they are bioavailable and maintain their biochemical and organoleptic properties.
[0029] General description of the invention
[0030] The present invention, without previous treatments of the components or subsequent mixtures with other active substances or other additives (other than simply water), drastically improves the stability and bioavailability of polyphenols and their derivatives (from now on in the text we speak generally polyphenol or polyphenols to refer to the whole), originally insoluble, and facilitates its application directly as a nutraceutical, and even in aqueous solution. To do this, a very simple technique has been developed that is initially reduced from glycerin, as a carrier agent, and mixed with polyphenol, as an active agent, then carrying out an ultrasound-assisted cavitation by introducing the sonication head into the glycol solution, until the solubilization of the active compound is assured in a short period of time.
[0032] Specifically, the present invention refers to a method for obtaining a nutraceutical composition consisting of glycerin and an active agent that is a polyphenol or a derivative thereof, comprising:
[0033] a) preheating the glycerin to a temperature between 30 ° C-35 ° C, both limits included;
[0034] b) mixing the preheated glycerin and the polyphenol in a ratio of polyphenol and glycerin comprised between 1:15 to 1:30 by weight, including both limits; Y
[0035] c) dispersing the mixture by means of cavitation by direct sonication at 20 kHz for at least 10 minutes, until weak intermolecular interactions are formed by hydrogen bonding between the hydroxyl groups of the two components of the mixture.
[0037] Ultimately, the technique proposed in the present invention lies in the elaboration of a natural composition, without additives, from the use of glycerin, a harmless substance that can be ingested quantum satis. According to the provisions of article 3.2.h) of Regulation (EC) N ° 1333/2008 of the European Parliament and of the Council, of December 16, 2008, on food additives, the term "quantum satis" means that a maximum level and substances are thus used in accordance with good manufacturing practice, in an amount not exceeding that necessary to achieve the intended purpose and provided that the consumer is not misled.
[0038] In addition to the use of glycerin as a carrier agent, the main novelty of the proposed method resides in the application of ultrasonic cavitation or sonication (direct application of ultrasound on the solution) to obtain it, preferably using an ultrasound head that is immersed in the mixture. The advantage of using ultrasonic cavitation is twofold: on the one hand, they catalyze the formation of these bonds by hydrogen bonding between glycol and polyphenol and, on the other hand, they allow to maintain controlled temperatures that are considered low compared to usual. , in such a way that they reduce the temperature of the solution by 40 ° C-50 ° C with respect to other alternative methods (microwave, inductive, ...). Thus, starting from a temperature that oscillates between 30-35 ° C, it has been found that, when applying cavitation, this starting temperature of the first stage mixture is progressively increased to 40 ° C-60 ° C, but never above said temperature. In this way, it is ensured that the structure of the polyphenols is not degraded by the negative effect of the excessive heat applied to the molecule. This entails obvious energetic advantages, avoiding, among other things, the degradation of the biochemical properties of the compounds. This result is of vital importance so that the active agents maintain their beneficial biochemical and organoleptic properties intact when consumed as a nutraceutical.
[0040] We will call bioactive compounds (CBAs) those natural substances, usually insoluble in water, found in plants, as well as in the products derived from them (for example, in flour, in oil ...), in small amounts, and that have an effect (beneficial or harmful) on living organisms. More specifically, within the scope of the present invention, the term CBA refers to compounds permitted for use as a nutraceutical, and which are intended to be uniformly dispersed in a component selected for this purpose, finally forming an intimate solution, for the purpose of subsequent bioavailability. inside the organisms that ingest it. In a preferred embodiment, said polyphenol and its derivatives are selected from the group consisting of:
[0041] - a flavonoid, including chalcones, flavones, flavanols, flavandiols, anthocyanins, and condensed tannins. More specific examples of them are rutin, catechin, epicatechin, isoramnetin, kaempferol, myricetin, quercetin, among the most important; - resveratrol, hydroxytyrosol, curcumin, silymarin, silybin and other similar polyphenols; Y
[0042] - phenolic acids, such as hydroxycinnamic acid derivatives, ferulic acid derivatives and caffeic acid derivatives, among others.
[0044] During the process of preparing the nutraceutical composition, the pH is around 6-7, preferably 6. In turn, as explained, even when heating as a result of the cavitation stage, the temperature of the solution does not never rises above 60 ° C during the process, since, otherwise, there is a risk of altering and oxidizing the molecular structure of the polyphenols, inactivating their properties and negatively modifying their organic properties (darkening and oxidation of the product , bitter taste ...). Indeed, one of the special characteristics of the method developed is that the glycerin is preheated before adding the active agent, but only at a reduced temperature and always well below those normally used to mix these components (which usually oscillate around the 100 ° C), which favors that the properties of said agent are not modified by the procedure and, at the same time, that it is fully available for assimilation.
[0046] The solubility of the polyphenol increases with the concentration by weight of glycerin in the mixture, in such a way that the higher the concentration of glycerin, the greater the solubilization of the polyphenol. But this also implies a higher economic expense over the required theoretical concentrations, which is not necessary for its effectiveness. For this reason, the use of polyphenol: glycerin stoichiometry of 1:15 to 1:30 by weight, being more preferably 1:25 by weight, is recommended as essential in this invention (being more economical), until the formation of supramolecular structures in which the polyphenol is trapped between the hydroxyl groups of glycerol by weak or short-range electrostatic interactions, unlike the covalent bond, which has a much higher energy (and which would affect its bioavailability).
[0048] Thus, new bioproducts are obtained, which are binary complexes or macromolecules in liquid form (glycol), by means of weak electrostatic bonds, due to the generation of hydrogen bonds between hydroxyl groups present in glycerin and the hydroxyl groups present in polyphenol. . The formation of these links allows not only greater availability and effectiveness when ingested, but also its subsequent dilution in water without reducing the theoretical effectiveness of CBA.
[0050] Preferably, the cavitation step is carried out for 10 minutes.
[0052] The preheating temperature of the glycerin and, consequently, that which the mixture acquires in the cavitation stage, depends on the polyphenol or polyphenol derivative used. Thus, in a particular case of the invention, when the polyphenol is a flavonoid, such as rutin, the glycerin is heated in the first stage to 30 ° C; in this case, as a result of the second cavitation stage, the temperature is increased to 40 ° C. In another particular case, when the polyphenol is selected from curcumin or resveratrol, the glycerin is heated to 35 ° C, and the temperature in the second stage rises to 50 ° C as a consequence of the application of ultrasound. Also in another particular case, where the polyphenol is selected from silymarin or silybin, the glycerin is heated to 45 ° C, rising in the second stage to 60 ° C as a result of the cavitation induced by ultrasound.
[0054] The solubility and characterization studies of the polyphenols have been carried out with a UV-VIS spectrophotometer and / or an HPLC-Mass chromatograph, verifying in a surprising and unexpected way that the solubility in water of the polyphenols contained in the composition obtained is maintained even in successive aqueous dilutions. This result is key because it allows not only to formulate a concentrated product, but also to later be able to use it or market it diluted in water without altering its properties. Thus, the nutraceutical composition obtained maintains the water solubility of the polyphenols in subsequent dilution stages, from a composition: water weight ratio of up to 1:50, and even up to 1: 100 by weight, favoring their storage and commercialization. Thus, the method preferably comprises a subsequent stage in which the composition obtained is diluted in water in a ratio between 1: 1 to 1: 100 (composition: water).
[0056] It has been observed that, when the nutraceutical composition is diluted in water, the hydroxyl groups of the glycerin that remain free after forming the macromolecules or complexes with the polyphenol, are solvated with it, further increasing the solubility of the entire complex, which is an unexpected effect. Solvation is an interaction of a solute with a solvent that leads to the stabilization of the solute species in solution. We have verified that this phenomenon occurs in the complex formed within the nutraceutical composition, which unexpectedly leads to a drastic increase in the water solubility of the complex formed between glycerin and polyphenol.
[0058] Another object of the present invention is the nutraceutical composition obtainable from the method described above, in any of its variations. Said composition consists of a glycolic solution of an active compound that is polyphenol, where the solution comprises binary complexes or macromolecules formed by weak electrostatic interactions that are hydrogen bonds between hydroxyl groups present in glycerin and hydroxyl groups present in polyphenol. , said composition being composed of a ratio of polyphenol and glycerin comprised between 1:15 and 1:30 by weight.
[0060] All the limitations and variations described for the method also apply for the compound, as is for example the selection of the polyphenol. Similarly, a preferred ratio of polyphenol and glycerin is 1:25 by weight.
[0062] The chemical structure of the macromolecules or complexes that are formed in the nutraceutical composition object of protection when it is formed by curcumin and glycerol is represented below. Molecules are represented with electrostatic charges. Due to hydrogen bonds, the polyphenol molecule is folded. Two hydrogen bonds can form between the two oxygens of the primary alcohols of glycerin and the two phenolic hydrogens or a single hydrogen bridge, the first alternative being more stable:
[0063] In the case of resveratrol (that is, when this is the selected active compound), structures similar to the previous ones are produced, but in this case the second alternative (a single hydrogen bridge) is more stable:
[0068] The following shows the structure of the macromolecules that are formed in the composition, when glycerin complexes with silybin:
[0073] In the case of the composition with rutin, the first alternative is more stable (two hydrogen bonds between the two oxygens of the primary alcohols of glycerin and the two phenolic hydrogens), although both show the same effectiveness:
[0076] The nutraceutical composition described above in this specification is also an object of the present invention, regardless of the method by which it is obtained, in any of the variations defined herein. Said composition therefore consists of a glycolic solution (that is, based on glycerin) of the active compound, which is polyphenol, where said solution comprises binary complexes or macromolecules formed by weak interactions of the electrostatic type that are hydrogen bonds between hydroxyl groups. present in glycerin and hydroxyl groups present in polyphenol, said composition being composed of a ratio of polyphenol and glycerin between 1:15 and 1:30 by weight, preferably 1:25.
[0078] Likewise, another object of the invention is an aqueous solution of the nutraceutical compound described above, wherein said dilution has a composition: water ratio comprised in a range from 1: 1 to 1: 100 by weight, said ratio preferably being comprised between 1:50 and 1: 100 composition and water, respectively.
[0080] Another aspect of the present invention is the use of the compound as a nutraceutical, that is, a compound as described above for use as a nutraceutical. Specifically, an effect of the nutraceutical compound has been observed in the reduction of diabetes and low molecular weight LDL cholesterol, as well as in the treatment of neurodegenerative diseases, such as Alzheimer's disease, so that preferably the composition is used for such applications. The dose and frequency of intake for such uses is between 3 and 5 ml / day of the glycol composition object of protection. This beneficial effect is due to its anti-inflammatory, antioxidant, capillary strengthening and circulation improvement properties, among other observed results.
[0082] Examples
[0083] Example 1: Procedure for obtaining nutraceutical compounds according to the present invention
[0084] 1.1. A first process consisted in introducing 40 grams of the polyphenol, which was the routine flavonoid, in 1260 grams of glycerin (weight equivalent to 1 liter of glycerin) at 30 ° C. Subsequently, the high-power ultrasound head (20 kHz) was introduced and the dissolution process began, so that the pH of this gel was around 6 or 7.
[0086] Cavitation was applied for 10 minutes, producing a progressive rise in temperature to 40 ° C. At this time, the total solubilization of the flavonoid rutin in glycerin was verified, as well as the formation of weak electrostatic bonds through hydrogen bonds between the hydroxyl groups, giving rise to binary complexes or macromolecular structures.
[0088] 1.2. In a second process, the dispersion and dissolution by cavitation of a mixture prepared from 5 grams of curcumin, as polyphenol, in 150 grams of glycerin and in another separate process, from a mixture of 5 grams of resveratrol, as polyphenol , in 150 grams of glycerin; in both cases, the glycerin was previously heated to 35 ° C, before mixing. In these cases, there was a progressive rise in temperature during 10 minutes of application of sonochemistry up to 50 ° C.
[0090] 1.3. In another process, silymarin was used as the active agent, and in a last procedure, silybin was used as a polyphenol. In both cases, the cavitation mix consisted of 10 grams of the polyphenol in 150 grams of glycerin. Also in both cases, the initial temperature of the bath, that is, of the glycerine before mixing, was adjusted to 45 ° C, producing a progressive rise in temperature up to 60 ° C during the 10 minutes of cavitation.
[0091] Example 2: Preparation of an aqueous solution of the compounds obtained in Example 1
[0092] Once the compositions of the aforementioned complexes between polyphenol and glycerin were formed, water was added to form an aqueous solution thereof. The ratio of nutraceutical compound and water was 1:50 by weight. These polyphenols in glycerin solution surround themselves with a layer of solvent and are solvated with the water molecules. This is a protic solvent, since hydrogen is attached to a strongly electronegative atom (oxygen) and the bond is highly polarized.
[0094] The hydrogen bonding capacity is greater in the case of water than in alcohols, which is why they are appreciably soluble in water. The phenolic OH group and the OHs of glycerin are easily solvated.
[0096] In the case of curcumin, solvation takes place by the formation of hydrogen bonds between water and the primary hydroxyls of glycerin.
[0101] In the case of resveratrol, we would have the same solvation with the glycol and also with the remaining phenolic OH.
[0103] The same can be said for silybin.
[0106] In the rutin, solvation occurs with phenols, with glycerin and not with the OH of the rutinose disaccharide that the molecule possesses.
[0109] As a summary of the aforementioned results, it was observed that in the dissolution of polyphenols in glycerin and their subsequent dilution in water, two factors intervene that are responsible for the dramatic increase in their solubility: on the one hand, the formation of bonds by hydrogen bonding between the different hydroxyl groups present and, on the other, and no less important, the solvation of the complex obtained with the water molecules when it was diluted.
[0111] Example 3: Application of the prepared nutraceutical compounds, in the treatment of diabetes, cholesterol and in the treatment of Alzheimer's. Tests were carried out with the formulations described in this document, specifically with the nutraceutical compositions obtained in Example 1, in various groups people: a first group was under treatment for cholesterol, who also suffered from diabetes after prolonged treatment; a second group was under chemotherapy treatment; finally, a third group was on treatment for Alzheimer's. The following results were obtained:
[0113] 3.1. In the case of the nutraceutical composition that contains silymarin, making available 10 grams of silymarin in a 125 ml vial of glycerin, and taking a small 3 ml spoon (similar to coffee) as a daily dose. During a time between 2 and 3 months, a reduction in glucose, glycated hemoglobin and low molecular weight cholesterol (LDL) levels was observed by blood tests in 7 cases of the 10 tested (in each of them , an effect was seen in at least two of these parameters outlined).
[0115] Likewise, it was found that this nutraceutical composition acted as a hepatoprotector in the case of fatty liver (blood transaminases were reduced), not only for people with cholesterol treatment but also for people who are taking aggressive medication, such as chemotherapy; thus, a reduction in lipids accumulated in the liver due to the malfunction of the organ was confirmed.
[0117] 3.2. In the case of the rutin-based nutraceutical composition, dissolving 5 grams of rutin in 125 ml of glycerin, and orally administering a daily dose of 3 ml (spoon similar to those of coffee) for a period between 2 and 3 months, A significant improvement was observed in patients with neurodegenerative disorders, such as Alzheimer's, with memory improvement and recovery, probably due to an improvement in cardiovascular circulation and the reduction of associated brain inflammation.
[0119] In both case studies, the nutraceutical compositions based on silymarin and routine, no unfavorable consequences on the health of the people involved in the study have been observed. Clearly, it is confirmed that, even increasing their availability in higher doses than usual, these substances are considered safe and can be part of food supplements without causing significant negative alterations in your body.
权利要求:
Claims (12)
[1]
1. A method of obtaining a nutraceutical composition consisting of glycerin and an active agent that is a polyphenol or a derivative thereof, comprising:
a) preheating the glycerin to a temperature between 30 ° C-35 ° C; b) mixing the preheated glycerin and the polyphenol in a ratio of polyphenol and glycerin comprised between 1:15 to 1:30 by weight; Y
c) dispersing the mixture by means of cavitation induced by 20 kHz ultrasound for at least 10 minutes, until weak intermolecular interactions are formed by hydrogen bonding between the hydroxyl groups of the two components of the mixture.
[2]
2. The method according to claim 1, wherein the polyphenol or its derivative is selected from the group consisting of:
- a flavonoid, selected from the group consisting of: chalcones, flavones, flavanols, flavandiols, anthocyanins and condensed tannins;
- resveratrol, hydroxytyrosol, curcumin, silymarin and silybin; Y
- phenolic acids, selected from the group consisting of: derivatives of hydroxycinnamic acid, derivatives of ferulic acid and derivatives of caffeic acid, among others.
[3]
3. The method according to claim 2, wherein the polyphenol or its derivative is selected from the group consisting of: rutin, curcumin, resveratrol, silymarin and silybin.
[4]
4. The method according to any one of claims 1 to 3, wherein the ratio of polyphenol and glycerin is 1:25 by weight.
[5]
The method according to any one of the preceding claims, wherein the cavitation time is 10 minutes.
[6]
6. The method according to any one of the preceding claims, wherein the method comprises a subsequent step in which the nutraceutical composition obtained from step b) is diluted in water, in a composition / water ratio of between 1: 1 and 1 : 100.
[7]
7. A nutraceutical composition obtainable from the method described in any one of the preceding claims, characterized in that it consists of a glycolic solution of the polyphenol, in which a glycolic medium comprises macromolecules formed by weak interactions of the electrostatic type, which are bridges of hydrogen, between hydroxyl groups present in glycerin and hydroxyl groups present in polyphenol; said composition composed of a ratio of polyphenol and glycerin comprised between 1:15 and 1:30 by weight.
[8]
8. The nutraceutical composition according to claim 7, wherein the ratio of polyphenol and glycerin is 1:25 by weight.
[9]
Composition according to any one of claims 7 or 8, for use as a nutraceutical.
[10]
Composition according to the preceding claim for use in the treatment of one of the diseases selected from the group consisting of: diabetes, choleresterolemia and a neurodegenerative disease.
[11]
Composition according to the preceding claim for use in the treatment of Alzheimer's.
[12]
Composition according to any one of claims 9 to 11, wherein the daily dose to be ingested is 3 ml to 5 ml of the nutraceutical composition.
类似技术:
公开号 | 公开日 | 专利标题
ES2602107T3|2017-02-17|Nanoemulsion
Jain et al.2010|Phytosome: a novel drug delivery system for herbal medicine
KR100752990B1|2007-08-30|Compositions for preventing or treating skin diseases comprising nanoliposomes and natural extracts
ES2768323T3|2020-06-22|Cosmetic compositions containing at least one hydrotrope and at least one active compound
KR20050112080A|2005-11-29|Antioxidative composition and composition for external use
ES2641091T3|2017-11-07|Vitamin D Composition
JP5432470B2|2014-03-05|Ceramide solution and external preparation for skin
ES2324400T3|2009-08-06|PROCEDURE FOR THE PRODUCTION OF A CONCENTRATE OF ISOFLAVONAS.
Jose et al.2019|Role of solid lipid nanoparticles as photoprotective agents in cosmetics
ES2627403T3|2017-07-28|Transdermal phosphatidylcholine composition and method of producing it
RU2383356C1|2010-03-10|External preparation for local application with thermal effect |
BR112021007331A2|2021-07-20|high potency vitamin c topical formulations
ES2841474B2|2022-01-24|NUTRACEUTIC COMPOSITION CONSISTING OF A POLYPHENOL IN GLYCOL SOLUTION, METHOD OF OBTAINING AND ITS THERAPEUTIC USE
RU2475230C1|2013-02-20|Therapeutic sunburn product
Deshpande et al.2014|Phytosomes: A noval drug delivery system for phytoconstituents
KR102042453B1|2019-11-08|Soluble type idebenone stabilizing composition, manufacturing method thereof and cosmetic composition using the same
JP6352560B2|2018-07-04|External composition containing ascorbic acid and / or salt thereof
JP6907243B2|2021-07-21|Resveratrol solubilized products for pharmaceutical purposes
ES2861593A1|2021-10-06|PHARMACEUTICAL COMPOSITION INCLUDING A DISSOLUTION OF SILYMARIN IN A DEEP EUTECTIC SOLVENT OF NATURAL ORIGIN, METHODS OF OBTAINING AND USE IN MEDICINE |
CN103859395A|2014-06-18|Self-emulsifying drug release system of coenzyme Q10 with high absorptivity and preparation method and application thereof
JP2006062968A|2006-03-09|Dropsy-improving agent
NZ335473A|2001-02-23|Therapeutic and cosmetic compositions, their use and method for the preparation thereof
BR112015012491B1|2020-03-17|COMPOSITION OF MELATONIN OR ITS DERIVATIVES WITH COENZYME Q10 AND ITS USE AGAINST SKIN AGING
CN100998867A|2007-07-18|Anticancer Chinese medicine compound nanometer emulsion and its preparation method
ES2827999T3|2021-05-25|An oral drug formulation comprising silybin
同族专利:
公开号 | 公开日
ES2841474B2|2022-01-24|
引用文献:
公开号 | 申请日 | 公开日 | 申请人 | 专利标题
WO2008096343A1|2007-02-04|2008-08-14|Menachem Rabinovich|Turmeric compositions and methods for the preparation thereof|
FR2944794A1|2009-04-28|2010-10-29|Rocher Yves Biolog Vegetale|Preparing flavonoid glycoside oligomer comprises solubilizing flavonoid glycoside in mixture comprising glycerin, ethanol and aqueous solution to obtain solution having flavonoid and polymerizing solubilized flavonoid glycoside by laccase|
US20180369193A1|2010-12-22|2018-12-27|Laboratoires Expanscience|Avocado flesh and/or skin extract rich in polyphenols and cosmetic, dermatological and nutraceutical compositions comprising same|
US20130029905A1|2011-02-01|2013-01-31|M/S Akay Flavours & Aromatics Pvt Ltd|Formulation containing curcuminoids exhibiting enhanced bioavailability|
CN107049937A|2017-04-19|2017-08-18|李锐|A kind of composition and its application and curcumin composition for improving curcumin solubility|
法律状态:
2021-07-08| BA2A| Patent application published|Ref document number: 2841474 Country of ref document: ES Kind code of ref document: A1 Effective date: 20210708 |
2022-01-24| FG2A| Definitive protection|Ref document number: 2841474 Country of ref document: ES Kind code of ref document: B2 Effective date: 20220124 |
优先权:
申请号 | 申请日 | 专利标题
ES202030007A|ES2841474B2|2020-01-08|2020-01-08|NUTRACEUTIC COMPOSITION CONSISTING OF A POLYPHENOL IN GLYCOL SOLUTION, METHOD OF OBTAINING AND ITS THERAPEUTIC USE|ES202030007A| ES2841474B2|2020-01-08|2020-01-08|NUTRACEUTIC COMPOSITION CONSISTING OF A POLYPHENOL IN GLYCOL SOLUTION, METHOD OF OBTAINING AND ITS THERAPEUTIC USE|
[返回顶部]