EP3829612A1 - Extrait de pâquerette - Google Patents

Extrait de pâquerette

Info

Publication number
EP3829612A1
EP3829612A1 EP18752122.4A EP18752122A EP3829612A1 EP 3829612 A1 EP3829612 A1 EP 3829612A1 EP 18752122 A EP18752122 A EP 18752122A EP 3829612 A1 EP3829612 A1 EP 3829612A1
Authority
EP
European Patent Office
Prior art keywords
extract
extracted
guava
extraction
composition
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
EP18752122.4A
Other languages
German (de)
English (en)
Inventor
Rolf Sorg
Bettina SCHWARZINGER
Julian Weghuber
Tobias KÜHNE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PM International AG
Original Assignee
PM International AG
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 PM International AG filed Critical PM International AG
Publication of EP3829612A1 publication Critical patent/EP3829612A1/fr
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/06—Preparations for care of the skin for countering cellulitis
    • 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
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

Definitions

  • the present invention relates to a process for producing an extract from daisies (Bellis perennis) and an extract obtainable by this process. Furthermore, the invention relates to a composition containing the extract according to the invention and the use of
  • composition according to the invention as a dietary supplement and / or medicament.
  • the invention also relates to the production of a composition according to the invention, in particular a food supplement.
  • Diabetes mellitus is a group of metabolic diseases that lead to hyperglycemia. People with type 2 diabetes mellitus (T2DM) represent the main group of patients with diabetes (90%) worldwide. The global prevalence of diabetes has increased significantly in 2014 with more than 400 million people affected in 2014. Diabetes caused 1.5 million deaths in 2012 and another 2.2 million
  • T2DM The main features of T2DM are hyperglycemia, insulin resistance and
  • T2DM is also associated with hyperlipidemia and high blood pressure. This combination is called a metabolic syndrome, which is a high risk factor for cardiovascular diseases. For this reason, there is a great demand for approaches to prevent and treat the health problems associated with T2DM.
  • the previously known glucose lowering pharmaceuticals include
  • Insulin sensitizers such as glitazone, inhibitors of hepatic gluconeogenesis such as metformin, or kidney sodium glucose co-transporters (SGLT1 / 2) inhibitors such as dapagliflozin.
  • SGLT1 / 2 kidney sodium glucose co-transporters
  • dapagliflozin a kidney sodium glucose co-transporters
  • the object of the present invention is to provide a method for producing an extract from daisies (Bellis perennis), since it has surprisingly been found that extracts from daisies
  • Another object of the invention is to provide the extract obtainable by the method and a composition comprising the extract. It is also an object of the invention to use the composition as
  • composition according to the invention in particular one
  • the material to be extracted is the flowers, optionally including the stems, and / or the leaves of daisies.
  • the material to be extracted, made from daisies comprises the flowers of daisies.
  • the material to be extracted made from daisies, consists of the flowers of daisies.
  • the material to be extracted is dried before the extraction.
  • This drying can be carried out by merely drying at room temperature (about 20 ° C.), preferably drying at room temperature for 2 to 7 days. However, it is also possible to dry the material to be extracted, made from daisies, at a slightly elevated temperature of 30 to 50 ° C for a period of 10 to 24 hours.
  • the material to be extracted is preferably dried to a residual water content of 8 to 10% by weight before the extraction.
  • the material to be extracted is extracted with a suitable mill, for example one, before extraction
  • the at least one alcohol preferably comprises ethanol.
  • the aqueous solvent preferably comprises a mixture of water and at least one alcohol, preferably ethanol, in a volume ratio of 10 to 1 to 1 to 1.
  • Pure water or pure alcohol can also be used as solvents in the process according to the invention.
  • the weight ratio of material to be extracted, produced from daisies, to aqueous solvent is preferably from 1: 1 to 1:20, particularly preferably 1: 9.
  • the method according to the invention is also preferably thereby
  • the extraction of the material to be extracted, made from daisies is carried out for about 5 to 120 minutes, preferably for 15 to 45 minutes.
  • the method according to the invention is also preferably thereby
  • the treatment with ultrasound is preferably carried out over a period of 5 to 120 minutes, preferably about 20 minutes.
  • the method according to the invention is also preferably thereby
  • the solid and insoluble constituents are removed by centrifugation, preferably at 2500 to 3000 g, and / or filtration, preferably with a filter with a mesh size / pore size of 4 to 7.
  • the method according to the invention is also preferably thereby
  • aqueous solvent is removed after extraction of the material to be extracted, made from daisies to get dry extract.
  • the aqueous solvent can preferably be removed by blowing in nitrogen.
  • the method according to the invention is also preferably thereby
  • the extract obtained contains the compounds neochlorogenic acid, chloric acid, caffeic acid, rutin, hyperoside, isoquercitrin, guaijaverine,
  • Avicularin, quercitrin, kaempferol, luteolinapigenin-7-glucoside, apigenin-7-glucuronide and / or apigenin preferably in a concentration of 0.001 to 5 mg / ml.
  • the present invention further relates to an extract obtainable by the method described above.
  • the present invention also relates to a composition comprising the extract obtainable by the process according to the invention.
  • composition according to the invention containing the extract of daisies obtainable by the method according to the invention, also contains an extract from the fruits of the real guava
  • This extract from the fruits of the real guava is preferably obtainable by a process comprising the steps
  • fruit or fruit denotes pulp, optionally with skin or skin.
  • the term fruit or fruits preferably does not include the seeds, kernels and / or leaves or parts thereof.
  • Carbon dioxide is preferably used as the distraction agent for the process according to the invention. Instead of carbon dioxide, in a method according to the invention, for example, ethene, propane, ammonia, nitrous oxide, nitrous oxide and / or can also be used as the removal agent
  • Chlorotrifluoromethane can be used.
  • the high-pressure extraction system comprises at least one extractor.
  • the carbon dioxide is present in the supercritical state in the extractor and extracts the material to be extracted.
  • the high-pressure extraction system comprises at least one separator. There is a lower one in the separator
  • Destraction is preferably carried out by feeding carbon dioxide to an extractor and guiding carbon dioxide loaded with extract from the extractor into a separator in which extract from the carbon dioxide separates.
  • the extraction is preferably carried out in a continuous mode in which pure carbon dioxide is continuously fed to the extractor and carbon dioxide loaded with extract is continuously fed from the extractor to the separator in which extract from the carbon dioxide separates.
  • the material to be extracted comprises a puree from guava fruits or a solid obtained from
  • the material to be extracted comprises at least 60% by weight of puree from guava fruit or a solid obtained by drying puree from fruit of real guava.
  • the material to be extracted is a pulp from real guava fruit or a solid obtained by drying a pulp from real guava fruit.
  • the material to be extracted preferably contains no seeds, kernels and / or leaves of the real guava or parts thereof.
  • the musts from the real guava fruit or the solid obtained by drying a muse from the fruits of the real guava contains no seeds, kernels and / or leaves of the real guava or parts thereof.
  • the material to be extracted is preferably dried to a water content of from 3% by weight to 50% by weight, preferably from 5% by weight to 35% by weight, particularly preferably from 7% by weight to 30% by weight.
  • the material to be extracted is dried before removal to a solid with a water content of 7% by weight to 30% by weight.
  • the material to be extracted is dried by means of a drying cabinet or vacuum chamber before the extraction.
  • the material to be extracted is dried at 30 ° C. to 75 ° C., preferably at 35 ° C. to 65 ° C., for a period of 20 hours to 120 hours, preferably from 40 hours to 80 hours, before the extraction ,
  • the material to be extracted is dried in a vacuum chamber at 30 ° C. to 50 ° C. before the extraction.
  • the material to be extracted is a solid, obtained by drying a musts from the real guava fruit, or comprises this solid
  • the solid is preferably comminuted before the extraction.
  • the solid is preferably comminuted to a powder, preferably at least 80% by weight of the
  • Powder components have a diameter between 0.05 mm and 30 mm, preferably between 0.1 mm and 10 mm.
  • Water is preferably added as a cosolvent to the extraction material for the extraction, preferably 1% by weight to 30% by weight of water, particularly preferably 8% by weight to 20% by weight of water, based on the dry mass of the extract material. With water as the cosolvent, the yield of the extraction can be increased.
  • the pressure in an extractor is preferably
  • High pressure extraction system during the extraction 100 bar to 500 bar, preferably 200 bar to 400 bar, very particularly preferably 250 bar to 350 bar.
  • the temperature in an extractor is preferably
  • High pressure extraction system during the extraction 31 ° C to 80 ° C, preferably 31 ° C to 50 ° C.
  • the extraction takes place over 1 h to 8 h, preferably 2 h to 4 h.
  • the high-pressure extraction system comprises an extractor and a separator and the extractor is flowed through during the extraction by a continuous flow of carbon dioxide of 2 to 20, preferably 5 to 12, kg of carbon dioxide per hour per kg of material to be extracted, the continuous flow of carbon dioxide is fed to the separator.
  • the amount of carbon dioxide relates to the dry mass of the material to be extracted.
  • the water content of the is
  • % preferably set to 7% by weight to 30% by weight.
  • an extract obtained is dried after the extraction, the drying preferably taking place by means of a drying cabinet or vacuum chamber, and the water content after drying preferably being ⁇ 10% by weight.
  • the composition of the extract obtained in particular with regard to polyphenols, differs greatly from the composition of extracts of the real guava, obtainable by processes not according to the invention.
  • Polyphenols are preferably identified using an HPLC method mentioned in the examples.
  • Polyphenols are preferably identified using an HPLC method mentioned in the examples, and the polyphenols phloridzin, phloretin, quercetin, quercitrin, isoquercitrin, hyperoside, avicularin, guaijaverin, procyanidin B1 and B2, (+) - catechin, (-) - catechin , (-) - epicatechin, gallocatechin, epicatechin gallate, gallic acid and ellagic acid include or are.
  • Hyperoside avicularin, guaijaverin, procyanidin B1 and B2, (+) -catechin, (-) - catechin, (-) - epicatechin, gallocatechin, epicatechin gallate, gallic acid and ellagic acid each less than 0.8% by weight, preferably less than 0.3% by weight, based on the dry weight of the extract.
  • the composition of the extract obtained differs greatly from the composition of extracts of the real guava, obtainable by processes not according to the invention.
  • none of the polyphenols which are identified in extracts of the real guava, obtainable by alternative methods is identified in the extract obtained, the polyphenols preferably being identified using an HPLC method mentioned in the examples.
  • none of the polyphenols which are identified in extracts of the real guava, obtainable by alternative methods is identified in the extract obtained, the polyphenols preferably being identified by an HPLC method mentioned in the examples, and the polyphenols being phloridzin , Phloretin, Quercetin, Quercitrin, Isoquercitrin, Hyperosid, Avicularin, Guaijaverin, Procyanidin Bl and B2, (+) - Catechin, (-) - Catechin, (-) - Epicatechin, Gallocatechin, Epicatechingallat,
  • Gallic acid and ellagic acid include or are.
  • Hyperoside avicularin, guaijaverin, procyanidin B1 and B2, (+) - catechin, (-) - catechin, (-) - epicatechin, gallocatechin, epicatechin gallate, gallic acid and ellagic acid each less than 0.8% by weight, preferably less than 0.3% by weight, based on the dry weight of the extract.
  • the present invention further relates to compositions as described above for use as a dietary supplement and / or
  • composition for use to reduce blood sugar peaks and / or to inhibit intestinal glucose absorption and / or to reduce weight is to be specified.
  • compositions for use in the treatment or prevention of diabetes mellitus and / or hyperglycemia and / or obesity is also based on the idea of a method for producing a composition according to the invention, in particular one
  • composition according to the invention Dietary supplement containing the extract according to the invention, the extract being obtainable by the method according to the invention.
  • the process for producing a composition according to the invention comprises:
  • the extract is preferably applied in the form of a solution of the extract in aqueous ethanol or propanol.
  • the extract is preferably applied by spraying a solution of the extract onto a carrier substance, such as, for example, gum arabic.
  • the extract-containing carrier substance is preferred after the application of the
  • the carrier substance is preferably mixed during application.
  • the process ensures a particularly even distribution of
  • Extract in the composition Extract in the composition.
  • Water content 100 x mass (water) / mass (water +
  • Chlorogenic acid, neochlorogenic acid and caffeic acid were obtained from Sigma-Aldrich (Schnelldorf, Germany). Guaijaverin and Avicularin came from Glentham Life Sciences (Corsham, United Kingdom). Rutin, hyperoside, isoquercitrin and quercitrin were obtained from extra synthesis (Genay Cedex, France). For the production of stock solutions, the vegetable
  • a library with 2,300 water-soluble herbal extracts was provided by Frank Döring (Christian-Albrechts-University Kiel, Germany).
  • NovoRapid from Novo Nordisk was provided by Daniel Weghuber
  • CHO-Kl cells that stably express the human insulin receptor (hIR) and GLUT4-myc-GFP were developed by Manoj K. Bhat (National Center for Cell Science,
  • the cells were in Ham's F12 culture medium supplemented with 100 pg / ml penicillin, 100 pg / ml streptomycin, 1%
  • G418 and 10% fetal bovine serum (FBS) were maintained and cultured in a humidified atmosphere at 37 ° C and 5% C0 2 .
  • Fresh daisy plants were collected and dried at room temperature for 1 week. The dried material was in a
  • CHO-Kl hIR / GLUT4-myc-GFP cells were placed in 96-well plates (35,000
  • the cells were treated with insulin or in KRPFI buffer
  • the scanning of larger areas was supported by a laser-controlled automatic focus hold system (ZDC2).
  • ZDC2 laser-controlled automatic focus hold system
  • the 488 nm emission of the diode laser (Toptica Photonics, Kunststoff, Germany) was used to image the GFP fluorescence. After appropriate filtering that was
  • Fluorescence signal via an Orca-R2 CCD camera (Hamamatsu Photonics,
  • Haselgrubler R. et al. PloS one (2017) and Haselgrubler, R. et al. Journal of visualized experiments (2018).
  • the eggs were at 38 ° C with an average
  • the eggs were turned over automatically and continuously, checked for fertilization by fluoroscopy and the area of the air bubble marked.
  • the eggshell was pointed with a
  • the extracts were diluted with HBSS or water to a final concentration of ⁇ 300 mg / L, which was finally introduced into the air compartment of the egg using a syringe. After the incubation, the eggshell above the air bubble was carefully removed and the eggshell membrane was leveled with PBS. In the next step, the eggshell membrane was removed and the
  • Thermo Scientific Dionex Ultimate 3000 consisting of an LPG-3400SD pump with built-in degasser, a WPS-3000 U (T) SL cooled
  • the analyte was separated on an Accucore C18 column (150 mm x 3.0 mm inner diameter, 2.6 ⁇ m particle size; Thermo Scientific). The column temperature was set to 40 ° C and the injection volume was 1 ml.
  • the analytes were separated by gradient elution with mobile phase A with 0.1% formic acid (FA) in water and mobile phase B with 0.1% FA in acetonitrile at a flow rate of 0.5 mL / min.
  • the starting conditions of the elution gradient were 95% A and 5% B. After an equilibration time of 5 min, the proportion of B was increased to 20% at 8 min and to 40% at 12 min, followed by 60% B at 15 min and 80% B at 17 min for 3 min. B was reduced to 5% at 20 min to 25 min.
  • Polyphenols have been quantified against known standards, provided they are available at concentrations in a linear range of 1-1,000 mg / L.
  • the first image recordings were supported by the Olympus Xcellence RT software. For the calculation of the fluorescence intensity in individual cells and a quick comparison of the fluorescence signal in numerous cells in
  • the Spotty framework was used at different intervals.
  • Process according to the invention produced (homemade).
  • Fig. 1A shows the effect of the three extracts tested after 10 min incubation.
  • the ethanolic extracts 4404 and 4407 only led to a moderate increase in the GFP signal of ⁇ 8% and ⁇ 5%, respectively. 17
  • the effectiveness of the two PECKISH library extracts 4404 and 4407 was quantified by testing different concentrations from 0.1 mg / L to 10 mg / L.
  • the homemade extract and the two PECKISH extracts were dissolved in HBSS buffer (300 mg / L).
  • NovoRapid a fast-acting human insulin analog, was used as a positive control (3.3 U / ml) to demonstrate insulin sensitivity. After incubation with the extracts for 1 or 2 h, the blood sugar values were checked over a week
  • Caffeic acid (hydroxycinnamic acids).
  • kaempferol and luteolin were identified by HPLC-MS analysis, but due to the lack thereof
  • FIG. 3 A representative HPLC-DAD chromatogram giving retention times and maximum wavelengths of each compound is shown in Fig. 3.
  • Table 1 summarizes the content of identified polyphenols. The best known hydroxycinnamic acid was chlorogenic acid (2.69 mg / L), apigenin -7-glucoside and apigenin-7-glucuronide (overlapping retention times) were found to be very common flavones (0.42 mg / L), while quercitrin was found as

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

Abstract

La présente invention concerne un procédé pour la production d'un extrait de pâquerette (Bellis perennis), comprenant les étapes consistant à: a) fournir une matière à extraire, produite à partir de pâquerettes ; b) extraire la matière à extraire à l'aide d'un solvant aqueux, en vue d'obtenir un extrait. L'invention concerne également un extrait pouvant être obtenu au moyen dudit procédé, une composition comprenant un extrait pouvant être obtenu au moyen dudit procédé et l'utilisation dudit extrait en tant que complément alimentaire et/ou médicament, en particulier pour la réduction de pics de glycémie et/ou pour l'inhibition de la résorption de glucose intestinale et/ou pour la perte de poids, ainsi que pour l'utilisation lors du traitement ou de la prévention du diabète sucré et/ou de l'hyperglycémie et/ou de l'adiposité.
EP18752122.4A 2018-08-02 2018-08-02 Extrait de pâquerette Pending EP3829612A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2018/071034 WO2020025137A1 (fr) 2018-08-02 2018-08-02 Extrait de pâquerette

Publications (1)

Publication Number Publication Date
EP3829612A1 true EP3829612A1 (fr) 2021-06-09

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ID=63143126

Family Applications (1)

Application Number Title Priority Date Filing Date
EP18752122.4A Pending EP3829612A1 (fr) 2018-08-02 2018-08-02 Extrait de pâquerette

Country Status (2)

Country Link
EP (1) EP3829612A1 (fr)
WO (1) WO2020025137A1 (fr)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101145089B1 (ko) * 2003-12-23 2012-05-21 체엘에르-헤미쉐스 라보라토리움 독토르 쿠르트 리히터 게엠베하 벨리스 페레니스 추출물을 포함하는 국소 탈색소 제형
AT502717A1 (de) * 2005-11-09 2007-05-15 Omnica Gmbh Pharmazeutische verwendung einer verbindung

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