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WO2018134460A1 - Préparation à base d'oeuf à propriétés anti-inflammatoires et antioxydantes - Google Patents

Préparation à base d'oeuf à propriétés anti-inflammatoires et antioxydantes Download PDF

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Publication number
WO2018134460A1
WO2018134460A1 PCT/ES2018/070032 ES2018070032W WO2018134460A1 WO 2018134460 A1 WO2018134460 A1 WO 2018134460A1 ES 2018070032 W ES2018070032 W ES 2018070032W WO 2018134460 A1 WO2018134460 A1 WO 2018134460A1
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WIPO (PCT)
Prior art keywords
egg
preparation
temperature
amount
pressure
Prior art date
Application number
PCT/ES2018/070032
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English (en)
Spanish (es)
Inventor
Crisanto Palacios Gavilán
Christian Palacios Gazules
Original Assignee
Liofilizados Girona, Sl
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 Liofilizados Girona, Sl filed Critical Liofilizados Girona, Sl
Publication of WO2018134460A1 publication Critical patent/WO2018134460A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C50/00—Quinones
    • C07C50/02—Quinones with monocyclic quinoid structure
    • C07C50/04—Benzoquinones, i.e. C6H4O2

Definitions

  • the present invention relates to a fertilized egg preparation comprising coenzyme Q10 and one or more antioxidants, its preparation process, and its pharmaceutical, nutraceutical or cosmetic compositions. Additionally, it also refers to the use of said pharmaceutical, nutraceutical or cosmetic egg compositions for use as an anti-inflammatory, analgesic or cosmetic agent.
  • CFS chronic fatigue syndrome
  • Fibromyalgia is a syndrome characterized by widespread chronic pain and the presence of between 1 and 18 painful points of connection between muscle and tendon, which are known as "trigger points.”
  • the current therapeutic alternatives offer a wide range of treatments, without a largely significant response, which include a rheumatologic, neurological, psychiatric medical approach, treatment with anti-inflammatories or analgesics.
  • a syndrome of difficult diagnosis and treatment for which there is no clear etiology to date and there are enormous difficulties in the treatment of associated pain, which is often accompanied by depression and other psychiatric disorders derived from loss of mobility, chronic pain, and even social isolation in the most serious cases.
  • Inflammasomes which are macromolecules of the protein type, comprise NOD type receptors, an apoptosis-associated protein (ASC) and procaspase-1; such inflamasomes can be activated by the variation of different factors, including ionic concentration, intracellular or extracellular ATP, destabilization of phagolysosome, or for example, mechanisms of oxoreduction.
  • ASC apoptosis-associated protein
  • procaspase-1 procaspase-1
  • IL-1 ⁇ interleukin 1 ⁇
  • IL-18 interleukin 18
  • Zhou et al (2009) have also suggested the link between the inhibition of mitochondrial respiratory chain complexes I and III and the triggering of musculoskeletal syndromes, particularly fibromyalgia.
  • a lack of coenzyme Q10 was also observed (Villalba et al, 2000; Modi et al, 2006), as well as an increase in oxidative stress.
  • ROS reactive oxygen species
  • Coenzyme Q10 or CoQ10 is a 1,4-benzoquinone that can be found in three oxidation states known as ubiquinone (oxidized form), ubiquinol (reduced form) and semiquinone or ubisemiquinone (partially reduced form).
  • Coenzyme Q10 It is present in most eukaryotic cells, mainly in mitochondria, where it plays a key role in the oxidative phosphorylation chain responsible for the production of ATP (Mancini et al, 2011; Litarru et al, 2007).
  • CoQ10 can act as a carrier of 1 or 2 electrons, playing a central role in the electron transport chain, because it has iron-sulfur clusters that They can only accept one electron at a time, and because it acts as an antioxidant capable of capturing free radicals.
  • CoQ10 is currently classified as a lipophilic antioxidant, particularly in its reduced form, which represents more than 80% of the total CoQ10 in human plasma, and protects biological membranes and lipoproteins.
  • CoQ10 can also participate, in addition, in several aspects of redox control of cell signaling pathways, such as in the self-oxidation of semiquinone, which represents a primary source of hydrogen peroxide.
  • eggs represent one of the great pillars of human food, being a valuable source of protein;
  • egg preparations provide safe, non-toxic compositions, which in various studies have demonstrated their effectiveness in use as an anti-inflammatory and as an analgesic.
  • EP0904090 describes an anti-inflammatory composition obtained by separating a water soluble fraction from a whole egg, the white or the yolk, of an animal in a superimmunized state, from which an extract less than 3000 dalton is obtained. of average molecular weight with anti-inflammatory properties.
  • EP2765869 describes an egg preparation comprising a mixture of yolk and white with a ratio of yolk to white between 98%: 2% and 60%: 40%, respectively, both extracted from a fertilized egg incubated during a period between 18 and 36 hours.
  • the compositions described herein show certain expression patterns of growth factors suitable for the use of said compositions as analgesic, anti-inflammatory and regenerative agents.
  • CA2197050 describes the use of compositions derived from incubated fertilized eggs, comprising physiologically tolerable carriers and excipients, for the treatment or prevention of cancer.
  • An objective of the present invention is to provide an egg preparation comprising an egg product extracted from an incubated fertilized egg, coenzyme Q10, and one or more antioxidants.
  • stimulation phase is understood the stage of embryonic development that happens to the formation of the blastula, and which results in the formation of the three fundamental layers of the embryo, i.e. ectoderm, mesoderm and endoderm.
  • Neurostimulation phase means the stage of embryonic development that occurs in the final stages of gastrulation, and which includes the formation of the central nervous system.
  • Supercritical fluid extraction or SFE (ie supercritical fluid extractior ⁇ ) is known in the state of the art as the process of separating a component (ie extractant) with respect to another (ie matrix) using supercritical fluids as extracting solvents, such as carbon dioxide.
  • supercritical fluid refers to a gas subjected to high compression, under certain critical conditions of temperature and pressure, so that it has combined properties of gases and liquids.
  • supercritical carbon dioxide supercritical extraction conditions assume a critical temperature of 31 ° C and a critical pressure of 74 bar.
  • bitterry product or “nutraceutical composition” refers to products or compositions derived from foods intended to provide additional health benefits compared to the basic nutritional value of such foods. Usually, these products are highly regulated by the authorities, and are usually pharmaceutical grade nutrients.
  • acceptable pharmaceutical excipients or carriers refers to suitable excipients or carriers, from a medical point of view, for use in contact with human and animal tissues without excessive toxicity, irritation, allergic response, or any other problem or complication, commensurable with a reasonable benefit / risk ratio.
  • bitteretically acceptable excipients or carriers refers to suitable excipients or carriers, from the food point of view, for use in nutraceutical products or compositions.
  • cosmetically acceptable excipients or carriers refers to excipients or carriers suitable for use in contact with human or animal skin without excessive toxicity, incompatibility, instability, allergic response, among others.
  • the term "effective amount” refers to an amount sufficient to obtain an expected effect.
  • the present invention comprises an egg preparation comprising: a) an egg product that has been previously extracted from an incubated fertilized egg,
  • said egg product has been previously extracted from a fertilized egg incubated for a period of time between 0 and 17 hours, which makes it possible to control that the egg remains in the gastrulation phase, without the neurulation phase having yet begun. , thus ensuring that said egg preparation contains pluripotent cells.
  • 0 hours refers to the moment in which fertilization occurs and therefore the beginning of embryonic development.
  • the egg product has been previously extracted from a fertilized bird egg.
  • said bird is selected from hen, goose, duck, quail, turkey, ostrich, pheasant and dove; In an even more preferred embodiment, said bird is a chicken.
  • the egg preparation of the present invention comprises an amount of coenzyme Q10 comprised between 0.1% and 4.5% by weight with respect to the total weight of said preparation, more preferably an amount of coenzyme Q10 comprised between 0.2% and 2.2% by weight with respect to the total weight of said preparation, and even more preferably, an amount of coenzyme Q10 comprised between 0.4% and 0.7% by weight with respect to the total weight of said preparation.
  • the egg preparation of the invention comprises an amount of one or more antioxidants comprised between 2.2% and 6.7% by weight with respect to the total weight of said preparation; preferably, the egg preparation comprises an amount of one or more antioxidants comprised between 1.7% and 5.6% by weight with respect to the total weight of said preparation.
  • Said one or more antioxidants are selected from the group consisting of, but not limited to superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), ascorbic acid (ie vitamin C), ⁇ -tocopherol (ie vitamin E), retinol, ⁇ -carotene (ie vitamin A precursor), metallothionein, melatonin, taurine, selenium, resveratrol, methionine, polyphenols, isoflavonones, S-adenosyl-methionine, and any of its mixtures.
  • SOD superoxide dismutase
  • SOD comprises a cofactor, which is selected from the group consisting of copper, zinc, manganese and iron.
  • Another aspect of the present invention comprises a process for the preparation of the egg preparation described above, comprising: a) incubating a fertilized egg,
  • a fertilized egg is preferably incubated for a period of time between 0 and 17 hours, in order to control that the incubated fertilized egg is kept in gastrulation phase, without The neurulation phase has still begun, thus ensuring that the egg preparation obtained contains pluripotent cells. More preferably, the fertilized egg is incubated for a period of time between 0 and 17 hours, at a temperature between 34 ° C and 41 ° C, and a relative humidity between 30% and 75%; even more preferably, the fertilized egg is incubated for a period of time between 0 and 17 hours at a temperature of 38 ° C and a relative humidity between 55% and 60%.
  • Stage c) corresponds to a sterilization process to suppress bacteria, molds and other microorganisms potentially harmful to health, which is based on the optimization of a process known as high pressure processing or HPP ("high-pressure processing”), widely used in the food sector.
  • the pressure of step c) of the process described above is 6000 bar.
  • the temperature of step c) is 9 ° C; further, preferably, the duration of step c) is 5 minutes. More preferably, step c) is carried out at a pressure of 6000 bar and a temperature of 9 ° C, for 5 minutes.
  • stage d) The selection of the temperature of stage d) is important for the maintenance of the biological conditions suitable for the good preservation of the egg product and its properties.
  • the temperature when the drying of the egg product is carried out at atmospheric pressure, the temperature must be below 60 ° C, preferably, a temperature between 5 ° C and 50 ° C, to avoid the acceleration of embryonic development; more preferably, the drying of the egg product of step d) is carried out at a temperature between 25 ° C and 40 ° C.
  • the temperature may be equal to or greater than 60 ° C. It will be obvious to the person skilled in the art that when working under pressure conditions corresponding to vacuum pressure, it will be possible to work with a temperature equal to or greater than 60 ° C, although it will be necessary to adjust these conditions to preserve the properties of the egg product .
  • Said step d) of drying can be carried out by numerous methods known within the state of the art, such as lyophilization, spray-drying, microwave drying, spray drying, and mixer drying under vacuum conditions.
  • a mixer under vacuum conditions preferably a temperature of 30 ° C will be used.
  • Step f) of adding an amount of coenzyme Q10 and an amount of one or more antioxidants is preferably carried out in a mixer.
  • steps d) -f) can be carried out in a band mixer at a rotation speed equal to or greater than 5 turns per minute. The use of this type of mixer allows to carry out, simultaneously, the drying of the product, and a homogeneous micronization and mixing.
  • the egg product obtained through the present process of the invention is in the form of nanocapsules.
  • Said nanocapsules can be obtained by means of any of the methods of obtaining known in the state of the art, which will be obvious to the person skilled in the art.
  • This final egg product in the form of nanocapsules has an analgesic, anti-inflammatory or cosmetic activity 10 times higher than that obtained with the non-encapsulated egg product.
  • the method of obtaining the egg preparation described above further comprises a step of extracting cholesterol by means of supercritical fluid extraction (SFE) technology, which can be carried out after stage d), and prior to stage e).
  • Said additional extraction stage will be carried out at a pressure between 150 and 450 bar, and a temperature between 15 ° C and 70 ° C.
  • said additional stage of supercritical fluid extraction of growth factors and cholesterol can be carried out at a pressure of 275 bar and a temperature of 40 ° C.
  • the supercritical fluid extraction technique is a clean and safe, completely safe option, which allows components to be separated efficiently, while preserving their characteristics, which has led to its rapid implementation in the food sector.
  • examples of supercritical fluid applicable in step e) include carbon dioxide or SC-C0 2 , water, ethane, propane, methanol and ethanol, all in supercritical form, that is, handled under temperature conditions and Critical pressure suitable for each of them, as will be apparent to a person skilled in the art.
  • the method of obtaining the egg preparation described above comprises an additional step comprising the extraction of saturated and unsaturated fats and oils from said egg preparation by extraction with supercritical fluid; said additional stage can be carried out according to the conditions described above, and can be carried out after stage d) and prior to stage e).
  • SFC extraction it is possible to separate the saturated and unsaturated fats and oils, so that the subsequent grinding (stage e) and addition of a quantity of coenzyme Q10 and an amount of one or more antioxidants (stage f) and takes conducted only on an egg protein concentrate free of fats and oils.
  • This alternative embodiment also comprises a second additional stage, subsequent to step f), of re-incorporating saturated and unsaturated fats and oils in a whisk, in which the corresponding final emulsion is obtained. That is, according to this alternative embodiment, the method of obtaining the egg preparation described above comprises the following steps:
  • step d2) extract saturated and unsaturated fats and oils from the product obtained in step d) by extracting with supercritical fluid
  • step d2) grind the egg protein concentrate free of saturated and unsaturated fats and oils resulting from step d2).
  • step f) add an amount of coenzyme Q10 and an amount of one or more antioxidants, f2) reinstate the saturated and unsaturated fats and oils obtained in step d2), on the mixture obtained in step f.
  • the egg preparation of the present invention is administered to mammals, more preferably, to humans.
  • this third aspect of the invention relates to pharmaceutical, nutraceutical or cosmetic compositions comprising an effective amount of egg preparation described above, and one or more suitable pharmaceutical, nutraceutical or cosmetic excipients or carriers, respectively.
  • the present invention provides a new solution that in addition to providing the natural nutrients of the egg itself, provides antioxidants, with the consequent reduction of oxidative stress and coenzyme Q10, which in combination with said antioxidants, has demonstrated a significant effect. in the control of oxidative stress, and in the improvement of the efficiency of the mitochondrial respiratory chain.
  • Said pharmaceutical, nutraceutical or cosmetic compositions are preferably characterized by a dosage form selected from: a) a solid form selected from powder, tablet, coated tablet, capsule, coated capsule, granule, envelope, encapsulated nanoparticle, and
  • a liquid form selected from solution, spray, cream, emulsion, gel, paste, shampoo and serum.
  • these pharmaceutical, nutraceutical or cosmetic compositions are described which comprise an effective amount of egg preparation for use as an anti-inflammatory agent for the treatment of anti-inflammatory conditions.
  • this composition may be administered in combination with one or more known anti-inflammatory agents.
  • these pharmaceutical, nutraceutical or cosmetic compositions which comprise an effective amount of egg preparation for use as an analgesic agent for the treatment of acute or chronic pain under pain-related conditions.
  • this composition may be administered in combination with one or more known analgesic agents.
  • Conditions related to acute or chronic pain include, but are not limited to, chronic fatigue syndrome, fibromyalgia or adrenal fatigue.
  • Figure 1 shows the percentage of healthy cells (fibroblasts) after 17, 23 and 44 hours of treatment.
  • Figure 1 shows the percentage of tumor cells (HepG2) after 17, 23 and 44 hours of treatment.
  • Figure 3 Percentage of healthy cells (fibroblasts) at the time OH, 24 and 48 hours of treatment.
  • Figure 4 shows the protein study of the effect of egg extract treatment.
  • FIG. 5 shows the weight control in mice at the beginning and end of the different treatments.
  • Figure 6 shows the pain test as an effect of the different treatments.
  • Figure 7 shows the depression trial (forced swimming test for depression) as an effect of the different treatments.
  • Figure 8 shows the levels of the inflammatory marker IL-1 beta.
  • Figure 9 shows the weight control at the beginning and end of the different treatments.
  • Figure 10 shows the pain test as an effect of the different treatments.
  • Figure 11 shows the depression test as an effect of the different treatments.
  • Figure 12 shows the levels of the inflammatory marker IL-1 beta.
  • Figure 13 shows the protein study of the effect of treatment with egg extract and CoQ10.
  • Figure 14A shows the levels of ATP; 14B: shows the levels of lipid peroxidation determined in muscle and liver 14C.
  • Figure 15 shows the levels of MnSOD determined in muscle. Detailed description of the invention
  • the present invention relates to a fertilized egg preparation comprising coenzyme Q10 and one or more antioxidants, its preparation process and pharmaceutical, nutraceutical or cosmetic compositions comprising said egg preparation and the use thereof for use as an anti-inflammatory agent. , analgesic or cosmetic.
  • Example 1 In vitro study of the effects of egg extract.
  • Example 2 In vivo study of the effects of egg extract.
  • mice were subjected to different treatments, 5 to the treatment of para-minoabenzoic acid (PABA), an inhibitor of the Te CoQ10 synthesis that reproduces the symptoms of fibromyalgia, 5 to PABA plus Egg of 17 hours and 5 without Treatment as a negative control.
  • PABA para-minoabenzoic acid
  • FIG. 6 shows the results of the hot plate test in which the mice, subjected to a temperature of 56 degrees, assess the time it takes to react to pain and therefore the pain threshold. A lower threshold was observed in the PABA group, as well as a significant increase in the egg group which demonstrates the increase in analgesia.
  • Example 3 In vivo study of the effects of egg extract compared to CoQ10.
  • mice were subjected to different treatments, 5 to the treatment of para-minoabenzoic acid (PABA), a coQ10 synthesis inhibitor that reproduces the symptoms of fibromyalgia and that our group has patented, to 5 PABA plus Egg of h hours, 5 PABA plus CoQ10 30mg, 5 the combination of PABA, egg 0 hours and CoQ10 and 5 without treatment as a negative control.
  • PABA para-minoabenzoic acid
  • egg treatment induced high levels of ATP production, thus stimulating bioenergetic cells against the PABA-induced deficit.
  • fertilized egg extract induces changes both at the cellular level and in animal models that lead us to think of a beneficial effect from the point of view of oxidative stress and inflammation. It induces cell growth and moderates the effect of apoptosis in addition to stimulating the production of ATP. In addition, it shows beneficial effects in terms of analgesia and antidepressant effect in our model. patented mouse. It shows no toxicity effects in the parameters evaluated by us or in the metabolism.
  • the combination with the well-known antioxidant CoQ10 shows greater efficacy in depression, but not in pain where CoQ10 is most effective.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne une préparation à base d'oeuf fertilisé comprenant une coenzyme Q10 et un ou plusieurs antioxydants, ainsi que son procédé de préparation et ses compositions pharmaceutiques, nutraceutiques ou cosmétiques. L'invention concerne également l'utilisation desdites compositions pharmaceutiques, nutraceutiques ou cosmétiques à base d'oeuf en vue de son application comme agent anti-inflammatoire, analgésique ou cosmétique.
PCT/ES2018/070032 2017-01-19 2018-01-17 Préparation à base d'oeuf à propriétés anti-inflammatoires et antioxydantes WO2018134460A1 (fr)

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ES201730061A ES2604552B1 (es) 2017-01-19 2017-01-19 Preparado de huevo con propiedades antiinflamatorias y antioxidantes
ESP201730061 2017-01-19

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008156108A1 (fr) * 2007-06-21 2008-12-24 Kaneka Corporation Produit fonctionnel issu du bétail, et procédé pour la production de celui-ci
WO2009115429A1 (fr) * 2008-03-19 2009-09-24 Joan Cunill Aixela Préparation alimentaire et composition pharmaceutique contenant un extrait embryonnaire
WO2010130980A2 (fr) * 2009-05-11 2010-11-18 Med-Eq As Traitement du stress
WO2015160262A1 (fr) * 2014-04-16 2015-10-22 Amerikal Nutraceutical Corp Composition anti-vieillissement

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR086437A1 (es) * 2011-10-13 2013-12-11 Aixela Juan Cunill Preparado de huevo con propiedades regeneradoras, analgesicas y/o anti-inflamatorias
CN104855516A (zh) * 2015-06-17 2015-08-26 刘丽亭 一种适宜心脑血管患者调理的醋蛋牛奶饮品的制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008156108A1 (fr) * 2007-06-21 2008-12-24 Kaneka Corporation Produit fonctionnel issu du bétail, et procédé pour la production de celui-ci
WO2009115429A1 (fr) * 2008-03-19 2009-09-24 Joan Cunill Aixela Préparation alimentaire et composition pharmaceutique contenant un extrait embryonnaire
WO2010130980A2 (fr) * 2009-05-11 2010-11-18 Med-Eq As Traitement du stress
WO2015160262A1 (fr) * 2014-04-16 2015-10-22 Amerikal Nutraceutical Corp Composition anti-vieillissement

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GERWYN MORRIS ET AL: "Coenzyme Q10 Depletion in Medical and Neuropsychiatric Disorders: Potential Repercussions and Therapeutic Implications", MOLECULAR NEUROBIOLOGY, vol. 48, no. 3, 13 June 2013 (2013-06-13), US, pages 883 - 903, XP055481580, ISSN: 0893-7648, DOI: 10.1007/s12035-013-8477-8 *
HIROSHI KAMISOYAMA ET AL: "Transfer of Dietary Coenzyme Q10 into the Egg Yolk of Laying Hens", JOURNAL OF POULTRY SCIENCE, 25 January 2010 (2010-01-25), pages 28 - 33, XP055481533, Retrieved from the Internet <URL:https://www.jstage.jst.go.jp/article/jpsa/47/1/47_009037/_pdf/-char/en> [retrieved on 20180606], DOI: 10.2141/jpsa.009037 *

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