EP3883587A1 - Dietary supplement used to reduce the release of inflammatory agents and related use - Google Patents

Dietary supplement used to reduce the release of inflammatory agents and related use

Info

Publication number
EP3883587A1
EP3883587A1 EP19835836.8A EP19835836A EP3883587A1 EP 3883587 A1 EP3883587 A1 EP 3883587A1 EP 19835836 A EP19835836 A EP 19835836A EP 3883587 A1 EP3883587 A1 EP 3883587A1
Authority
EP
European Patent Office
Prior art keywords
titrated
boswellia
dietary supplement
cells
ananas
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
EP19835836.8A
Other languages
German (de)
English (en)
French (fr)
Inventor
Massimo Defilippi
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.)
MAYOLY ITALIA S.P.A.
Original Assignee
Biohealth Italia Srl
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 Biohealth Italia Srl filed Critical Biohealth Italia Srl
Publication of EP3883587A1 publication Critical patent/EP3883587A1/en
Pending legal-status Critical Current

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)
    • A61K36/30—Boraginaceae (Borage family), e.g. comfrey, lungwort or forget-me-not
    • 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)
    • A61K36/32—Burseraceae (Frankincense family)
    • A61K36/324—Boswellia, e.g. frankincense
    • 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)
    • A61K36/32—Burseraceae (Frankincense family)
    • A61K36/328—Commiphora, e.g. mecca myrrh or balm of Gilead
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)

Definitions

  • the present invention refers to a dietary supplement designed to drastically reduce the inflammatory effects in people affected by leukemia with infections from Gram-negative bacteria.
  • monocytes and macrophages synthetize and release in their environment a variety of cytokines and other proteins which perform a central role in the development of acute and chronic inflammations.
  • THP-1 is a human monocyte leukemic cell line; it is known from scientific literature that these cells are capable of producing pro- inflammatory cytokines (THE- 1 , THE-6 and TNF) and chemokines (THE-8 and MCP-1) in reply to a stimulation by
  • LPS Lipo-polysaccharides
  • LPS is a polysaccharide deemed as the main component of the external membrane of Gram-negative bacteria. Recent studies have clarified how LPS is recognized by monocytes and macrophages of the innate immune system; in particular, human monocytes are extremely sensitive to LPS and their response is translated into the expression and the release of many inflammatory cytokines.
  • WO-A1-2010/037213 disclose the various components which make the dietary supplement of the present invention; none of them, however, can be used individually to reduce a release of inflammatory cytokines in patients in whose organism there are leukemic cells of a TPH-1 type.
  • the main object of the present invention is reducing, till almost cancelling, the release of inflammatory cytokines, in patients in whose organism there are leukemic cells of the TPH-1 type, said release being a consequence of the response of said TPH-1 cells to a stimulation with
  • LPS Lipo-polysaccharides
  • Johnst titrated in essential fatty acids , preferably Omega 3 and Omega 6;
  • Ananas (Ananas comosus (L. MERR, stipites) dry extract titrated in bromeline;
  • Boswellia Boswellia sacra Flueck . (syn.
  • Boswellia carteri Birdw . rubber resin
  • fluid extract titrated 4% in acetyl - 11-keto-beta- boswellic acid (AKBA) ;
  • Myrrh (Commiphora myrra, oil-rubber resin) fluid extract , titrated 4% in furan-dienes .
  • said dietary supplement comprises the above four active ingredients, with the following relative concentrations :
  • Ananas (Ananas comosus, L. MERR, stipites) dry extract titrated in bromeline: 16%;
  • Boswellia Boswellia sacra Flueck . (syn. (Boswellia carteri Birdw. ) , rubber resin) fluid extract , titrated 4% in acetyl -11-keto-beta- boswellic acid (AKBA) : 30%;
  • Figure 1 shows the release of inflammatory cytokines TNF-a, due to the stimulation with LPS, of THP-1 cells as such and pre-treated with a formulation according to the invention
  • Figure 2 shows a Table with a formulation according to the invention subjected to experimentations ;
  • Figure 3 shows a Table with the results of experimentations performed on the formulation of
  • the invention therefore deals with a dietary supplement, to be used to reduce the release of inflammatory cytokines in patients in whose organism there are leukemic cells of the TPH-1 type, such release being a consequence of the response of said TPH-1 cells to a stimulation with Lipo-polysaccharides (LPS) ;
  • the dietary supplement of the invention comprises the following active ingredients :
  • Johnst titrated in essential fatty acids, preferably Omega 3 and Omega 6;
  • Ananas Ananas comosus (L. MERR, stipites) dry extract titrated in bromeline;
  • Boswellia Boswellia sacra Flueck. (syn.
  • Boswellia carter! Birdw . rubber resin) fluid extract , titrated 4% in acetyl-ll-keto-beta- boswellic acid (AKBA) ;
  • Myrrh (Commiphora myrra, oil -rubber resin) fluid extract, titrated 4% in furan-dienes.
  • the dietary supplement of the invention comprises the four above active ingredients, with the following relative concentratios :
  • Buglossoides arvensis seed oil (L. , I.M. Johnst) titrated in essential fatty acids, preferably Omega 3 and Omega 6: 14%;
  • Ananas (Ananas comosus, L. MERR, stipites) dry extract titrated in bromeline: 16%;
  • Boswellia (Boswellia sacra Flueck. (syn. (Boswellia carter! Birdw. ) , rubber resin) fluid extract , titrated 4% in acetyl- 11-keto-beta- boswellic acid (AKBA) : 30%;
  • extra-virgin olive oil (Olea europaea L., fructus) ;
  • titanium dioxide ,- oleic acid
  • the above described supplement can be packaged in capsules and have the following global composition:
  • Buglossoides arvensis seed oil (L., I.M. Johnst) titrated in essential fatty acids, preferably Omega 3 and Omega 6: 9.764%;
  • Ananas (Ananas comosus, L. MERR, stipites) dry extract titrated in bromeline: 11.159%;
  • Boswellia BosweIlia sacra Plueck. (syn. (Boswellia carteri Birdw.), rubber resin) fluid extract , titrated 4% in acetyl -11-keto-beta- boswellic acid (AKBA) : 20.923%;
  • Myrrh (Commiphora myrra, Engl., oil -rubber- resin) fluid extract , titrated 4% in furan-dienes : 28.456%;
  • hydroxyl -propyl-methylcellulose capsule ingredient: 12.554%;
  • ethyl cellulose 2.664%
  • medium-chain triglycerides 0.711%
  • titanium dioxide 0.349%
  • oleic acid 0.307%
  • the above described dietary supplement is then used as anti-inflammatory agent.
  • composition of the formulation subjected to experimentations is also included in the Table in Figure 2.
  • THP-1 cells have been kept in a RPMI-1640 ground free from endotoxins and containing: 5,5 mmol/1 glucose, 50 miho ⁇ / ⁇ mercapto-ethanol, 10* bovine fetal serum, 2 mmol/1 glutamine, 1 mmol/1 sodium pyruvate, 10 mmol/1 HEPES.
  • the stimulation in vitro has been performe through the addition of LPS [100 ⁇ g/l] for 4 hours to THP-1 cells seeded in a 12 -well plate ( ⁇ lxl0 6 cells/ml) and incubated at 37°C and 5* C0 2 grown in 75-mm 2 flasks in RPMI-1640 ground enriched with bovine fetal serum and taken to 70* of confluence.
  • the Tumor Necrosis Factor (TNF-a) is an inflammatory cytokine and is a 17-kDa polypeptide mainly produced by activated monocytes and macrophages. This polypeptide mediates some immune and inflammatory responses, including activation and differentiation of monocytes and macrophages, expression of MHC of classes I and II and expression of adhesion molecules on endothelial cells.
  • THP-1 cells (lxlO 6 cells/ml) stimulated with LPS
  • Step 1 the THP-1 cells (lxlO 6 cells/ml) have been pre-treated for 1 hour with two different formulation concentrations:
  • Step 2 The pre-treated TPH-1 cells have been stimulated with LPS [100 pg/l] for 4 hours .
  • the culture ground with the cells has been recovered at the end of the experimental time and the cells have been lysed by using a sonicator .
  • the thereby- obtained supernatant has then been used for the following qualitative and quantitative analyses .
  • Step 3 The supernatant has been used to quantify the TNF-or through ELISA test (Tumor Necrosis
  • Figure 1 shows the results of the stimulation of THP-l cells with LPS, as such and pre-treated with the formulation.
  • THP-l cells The maximum stimulation level of THP-l cells has been obtained by treating them with LPS [100 pg/l] after a 4 -hour incubation.
  • CTR- CTR-
  • columns (B) and (E) show the releases of cytokines from two samples of cells stimulated with LPS, namely the dosage of TNF-a detected on a first and on a second sample of TPH-1 cells, respectively.
  • TNF-a released by the not stimulated cells is greatly different from the concentration of TNF-a released from cells stimulated with LPS .
  • the columns designated as (C) and (F) include the TNF-a released after stimulation with LPS of the THP-1 cells pre-treated with the formulation at the concentration of [0.2 mg/ml] and [67 mg/ml] respectively .
  • D is the percentage variation computed between the sample of TPH-1 cells stimulated with LPS and
  • p is the p value , according to the Student's statistics, computed between sample stimulated with
  • CTR is the control only of the TPH-1 cells not treated with LPS.
  • the in vitro model which has been applied has allowed to test two different concentrations [0.2 mg/ml] and [67 mg/ml] of the formulation according to the invention.
  • TNF-a known mediator of several immune and inflammatory responses, suggesting an anti- inflammatory activity of the tested sample.
  • the Table in Figure 2 shows a composition comprising the above mentioned four active ingredients, plus various ingredients having other functions.
  • the formulation of the invention can be conveniently packaged in capsules, for a practical up-take by a patient.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Microbiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
EP19835836.8A 2018-11-19 2019-11-18 Dietary supplement used to reduce the release of inflammatory agents and related use Pending EP3883587A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT102018000010393A IT201800010393A1 (it) 2018-11-19 2018-11-19 Integratore alimentare atto a ridurre il rilascio di agenti infiammatori e relativo uso
PCT/IT2019/000106 WO2020105070A1 (en) 2018-11-19 2019-11-18 Dietary supplement used to reduce the release of inflammatory agents and related use

Publications (1)

Publication Number Publication Date
EP3883587A1 true EP3883587A1 (en) 2021-09-29

Family

ID=65861505

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19835836.8A Pending EP3883587A1 (en) 2018-11-19 2019-11-18 Dietary supplement used to reduce the release of inflammatory agents and related use

Country Status (3)

Country Link
EP (1) EP3883587A1 (it)
IT (1) IT201800010393A1 (it)
WO (1) WO2020105070A1 (it)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11357810B2 (en) * 2019-10-09 2022-06-14 Brain Health Holding Llc Compositions with purified Bombyx mori cocoon silk peptide fiber and refined Buglossoides arvensis seed oil having synergistic effects for improving memory, focus, and cognitive function, and related methods
IT202000018970A1 (it) 2020-08-03 2022-02-03 Asoltech Srl Composizione a base di mirra

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080213357A1 (en) * 2007-02-12 2008-09-04 Andrew Bruce Hebard Plant Derived Lipid Useful for Nutraceutical and Cosemeceutical Applications
EP2334312A4 (en) * 2008-10-02 2012-11-28 Nutriquine N V COMPOSITIONS WITH PLANT EXTRACTS AND ITS USE IN THE TREATMENT OF INFLAMMATION
ITUB20153066A1 (it) * 2015-08-11 2017-02-11 Graal S R L Composizione alimentare e/o nutraceutica contenente pea
ITUB20153171A1 (it) * 2015-08-20 2017-02-20 Aboca Spa Societa Agricola Composizione comprendente tannini

Also Published As

Publication number Publication date
WO2020105070A1 (en) 2020-05-28
IT201800010393A1 (it) 2019-02-19

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