WO2021123131A1 - Composition pour le traitement de l'hypertension et/ou de morbidités associées - Google Patents

Composition pour le traitement de l'hypertension et/ou de morbidités associées Download PDF

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Publication number
WO2021123131A1
WO2021123131A1 PCT/EP2020/086978 EP2020086978W WO2021123131A1 WO 2021123131 A1 WO2021123131 A1 WO 2021123131A1 EP 2020086978 W EP2020086978 W EP 2020086978W WO 2021123131 A1 WO2021123131 A1 WO 2021123131A1
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composition
hypertension
derivative
present
vitamin
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PCT/EP2020/086978
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English (en)
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Ute Obermueller-Jevic
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Basf Se
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof

Definitions

  • the present invention relates to compositions and methods of treatment and/or prevention of hypertension and/or associated morbidities thereto.
  • the present invention relates to compositions comprising at least two components selected from at least one human milk oligosaccharide (HMO), at least one C3-C4-alkane carboxylic acid, and at least one vitamin K2 compound.
  • HMO human milk oligosaccharide
  • C3-C4-alkane carboxylic acid at least one vitamin K2 compound.
  • Hypertension is a medical condition of a subject which is characterized by an abnormal and/or excessive increase of blood pressure of said subject.
  • a commonly used method for diagnosing hypertension is measuring the systolic and diastolic pressures, which are the maximum and minimum pressures, respectively.
  • the American Heart Association recommends at least three resting measurements on at least two separate health care visits.
  • normal blood pressure is in a range of 90-119 mmHg (systolic) and 60-79 mmHg (diastolic).
  • Prehypertension ranges from 120-129 mmHg (systolic) and 60-79 mmHg (diastolic).
  • Hypertension stage 1 ranges from 130-139 mmHg (systolic) and 80-89 mmHg (diastolic) while hypertension stage 2 is above 140 mmHg (systolic) and above 90 mmHg (diastolic).
  • Hypertensive crisis is defined as a blood pressure above 180 mmHg (systolic) and above 120 mmHg (diastolic).
  • Isolated systolic hypertension refers to elevated systolic blood pressure above 160 mmHg at normal diastolic pressure.
  • Isolated diastolic hypertension refers to a diastolic blood pressure above 90 mmHg at normal systolic pressure.
  • Other authorities have published slightly different cut off values. Hypertension is considered resistant if medications do not reduce blood pressure to normal levels.
  • Hypertension results when cardiac output increases due to elevated stroke volume or elevated heart rate. Hypertension also results from increased peripheral resistance due to increased vascular tone, modified vascular structure, vascular narrowing or vascular occlusion.
  • the underlying mechanisms may include abnormal hormonal regulation of the renin-angiotensin system, arterial calcification, atherosclerosis, vascular inflammation leading, endothelial dysfunction.
  • Essential hypertension is a form for which no underlying cause can be found. Secondary hypertension occurs due to another disorder and/or due to lifestyle. High blood pressure typically results from genetic or environmental risk factors or a combination of both. Lifestyle choices including diet (high salt intake), lack of physical exercise, tobacco smoking raise the blood pressure. Additional factors that impact blood pressures include a person's age and health problems such as insulin resistance, obesity, sleep apnea, coarctation of the aorta, kidney disease and endocrine conditions such as Cushing’s syndrome, hyperthyroidism, hypothyroidism, acromegaly, Conn’s syndrome, hyperaldosteronism, renal artery stenosis, hyperparathyroidism and pheochromocytoma. Other causes of hypertension are low birth weight, maternal smoking and lack of breastfeeding.
  • Pregnancy can also be a cause of hypertension.
  • I medications such as angiogenesis inhibitors (e.g. tyrosine kinase inhibitors, monoclonal antibodies), antidepressants (e.g. venlafaxine, bupropion, desipramine), asthma medications, caffeine, corticosteroids, cyclosporine, estrogens (e.g. anticontrazeptiva), immunosuppressants, migraine medications, nasal decongestants, nonsteroidal anti-inflammatory drugs, testosterone and other anabolic steroids increase blood pressure.
  • angiogenesis inhibitors e.g. tyrosine kinase inhibitors, monoclonal antibodies
  • antidepressants e.g. venlafaxine, bupropion, desipramine
  • asthma medications e.g. venlafaxine, bupropion, desipramine
  • asthma medications e.g. venlafaxine, bupropion, desipramine
  • steroids e.g. anticontrazeptiva
  • immunosuppressants e.g. anticontraz
  • hypertension A small percentage of all people with hypertension have an inherited form of hypertension. The most common causes of inherited hypertension result from familial hyperaldosteronism, pseudohypoaldosteronism type 2, Liddle syndrome, Bartter syndrome, Gitelman syndrome, and paragangliomas.
  • Hypertension itself is asymptomatic. Chronic hypertension over a period of decades contributes to heart failure and stroke. Hypertension is often linked with a number of conditions and/or diseases of the cardiovascular system, the renal system, the brain and nerve system, and the eyes (see Table 1) ⁇
  • the present invention provides in a first aspect a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound; or a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof; or a composition III comprising i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and ii) at least one vitamin K2 compound, and optionally iii) at least one HMO.
  • compositions I, II or III for use in the treatment or prevention of hypertension and/or associated morbidities thereto.
  • Another aspect of the present invention relates to said compositions I, II, or III for use in the treatment or prevention of hypertension.
  • compositions I, II or III for use in the treatment or prevention of morbidities associated to hypertension.
  • the present invention relates to methods for treating a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities.
  • present invention relates to methods for treating a subject having, being suspected of having or being at risk of developing hypertension.
  • the present invention relates to methods for treating a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • a nutritional supplement or a functional food comprising said compositions I, II or III.
  • Another aspect of the present invention is related to the use of said compositions I, II or III as a nutritional supplement or a functional food, in particular in the dietary management of hypertension and/or associated morbidities.
  • Another aspect of the present invention is related to the use of said compositions I, II or III as a nutritional supplement or a functional food, in particular in the dietary management of hypertension.
  • composition I, II or III is related to the use of said composition I, II or III as a nutritional supplement or a functional food, in particular in the dietary management of morbidities associated to hypertension.
  • the present invention relates to a kit for the pharmaceutical use or dietary management use comprising individually the components of said compositions I, II or III, respectively.
  • HMOs can be combined with C3-C4-alkane carboxylic acids or derivatives thereof, and optionally with at least one vitamin K2 compound. Such compositions provide beneficial effects as described herein.
  • composition I comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • HMO refers to human milk oligosaccharide(s). These carbohydrates are resistant to enzymatic hydrolysis by digestive enzymes (e.g. pancreatic and/or brush border).
  • digestive enzymes e.g. pancreatic and/or brush border.
  • HMOs are found in the human breast milk. Each individual HMO is based on a combination of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose and/or N-acetylglucosamine with many and varied linkages between them. So far over 130 such structures have been identified in human milk.
  • the HMOs can be acidic (e.g. charged sialic acid containing oligosaccharide) or neutral (e.g. fucosylated oligosaccharide).
  • the HMO is selected from the group of fucosylated oligosaccharides, N-acetylated oligosaccharides and sialylated oligosaccharides.
  • the HMO is a "fucosylated oligosaccharide". These are HMOs having a fucose residue. It has a neutral nature. Some examples are 2'-FL (2'-fucosyllactose), 3-FL (3-fucosyllactose), difucosyllactose, lacto-N-fucopentaose (e.g.
  • lacto-N- fucopentaose I lacto- N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V)
  • lacto-N-fucohexaose lacto-N- difucohexaose I, fucosyllacto-N-hexaose, fucosyllacto- N-neohexaose, difucosyllacto-N-hexaose I, difucosyllacto-N-neohexaose II and any combination thereof.
  • the fucosylated oligosaccharide is selected from the group comprising 2’-FL, 3-FL and difucosyllactose (e.g. 2’,2”-DiFL and/or 3, 2’-DiFL).
  • the fucosylated oligosaccharide is 2’-FL.
  • the HMO is a ”N-acetylated oligosaccharide”.
  • the term ”N-acetylated oligosaccharide(s)” encompasses both "N-acetyl-lactosamine” and "oligosaccharide(s) containing N-acetyl-lactosamine".
  • LNT lacto-N-tetraose
  • para-lacto-N- neohexaose para-LNnH
  • LNnT lacto-N-neotetraose
  • N-acetylated oligosaccharide is selected from the group of LNT and LNnT.
  • the HMO is a ’’sialylated oligosaccharide.
  • the term ’’sialylated oligosaccharide encompasses an oligosaccharide having a sialic acid residue. It has an acidic nature. Some examples are 3’-SL (3'-sialyllactose) and 6’-SL (6'-sialyllactose). In a preferred embodiment the sialylated oligosaccharide is 6’-SL.
  • the HMO is selected from the group comprising 2’-FL, 3-FL, difucosyllactose (e.g. 2’,2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL and/or any combination thereof.
  • the HMO is selected from the group comprising 2’-FL, difucosyllactose (e.g. 2’,2”-DiFL and/or 3,2’-DiFL), LNT, LNnT and 6’-SL and/or any combination thereof.
  • the HMO is selected from the group comprising 2’-FL, LNT, LNnT and 6'-SL and/or any combination thereof.
  • C3-C4-alkane carboxylic acid or derivative thereof encompasses propionic acid, n-butyric acid and iso-butyric acid (2-methyl propionic acid) as well as derivatives thereof and/or any mixture thereof.
  • Suitable derivatives are salts, esters and amides, in particular physiologically acceptable ones.
  • physiologically acceptable salts are alkali salts, like sodium or potassium salts, or alkaline-earth salts, like magnesium or calcium salts, or choline salts.
  • physiologically acceptable salts are alkali salts, in particular sodium salts or potassium salts, especially sodium salts.
  • physiologically acceptable esters are those derived from C1-C6 alcohols, in particular those derived from monohydric C1-C6 alcohols, e.g. those derived from methanol or ethanol, or dihydric C1-C6 alcohols, like those derived from 1 ,2-ethandiol, or C1-C4 alkoxy substituted monohydric alcohols, like those derived from 2-methoxyethanol, 2-ethoxyethanol or 2-butoxyethanol.
  • Other examples for physiologically acceptable esters are glycerides, like mono-, di-, or triglycerides, in particular mono- or diglycerides.
  • the physiologically acceptable esters are those derived from monohydric C1-C6 alcohols, e.g. those derived from methanol or ethanol, or mono- or diglycerides.
  • physiologically acceptable amides are those derived from mono- or di-C1-C6-alkyl amines.
  • the C3-C4 alkane carboxylic acid is provided as physiologically acceptable derivative thereof; in particular the derivative is a physiologically acceptable salt, e.g. a sodium salt or potassium salt, or a mixture thereof, or a physiologically acceptable ester, e.g. said ester is derived from C1 -C6 alcohols, in particular a mono-or a dihydric C1 -C6 alcohol, or said ester is a mono- or diglyceride, or a mixture thereof.
  • a physiologically acceptable salt e.g. a sodium salt or potassium salt, or a mixture thereof
  • a physiologically acceptable ester e.g. said ester is derived from C1 -C6 alcohols, in particular a mono-or a dihydric C1 -C6 alcohol, or said ester is a mono- or diglyceride, or a mixture thereof.
  • the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate or sodium butyrate or potassium butyrate or a mixture thereof. Especially, it is sodium propionate or sodium butyrate or a mixture thereof.
  • the C3-C4-alkane carboxylic acid or derivative thereof is propionic acid or a derivative thereof, in particular it is a physiologically acceptable salt of propionic acid, especially it is sodium propionate or potassium propionate, or a physiologically acceptable ester of propionic acid, especially methyl propionate or ethyl propionate or propionic acid monoglyceride or propionic acid diglyceride, particularly ethyl propionate or propionic acid monoglyceride.
  • the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate.
  • the C3-C4-alkane carboxylic acid or derivative thereof is butyric acid or a derivative thereof, in particular it is a physiologically acceptable salt of butyric acid, especially it is sodium butyrate or potassium butyrate, or a physiologically acceptable ester of butyric acid, especially methyl butyrate or ethyl butyrate or butyric acid monoglyceride or butyric acid diglyceride, particularly ethyl butyrate or butyric acid monoglyceride.
  • the C3-C4- alkane carboxylic acid or derivative thereof is sodium butyrate or potassium butyrate.
  • the at least one C3-C4-alkane carboxylic acid or derivative thereof is a mixture of propionic acid and butyric acid or derivatives thereof, in particular it is a mixture of physiologically acceptable salts of propionic acid and butyric acid, especially it is a mixture of sodium propionate and sodium butyrate or a mixture of potassium propionate and potassium butyrate, or a mixture of physiologically acceptable esters of propionic acid and butyric acid, especially a mixture of methyl propionate and methyl butyrate, or a mixture of ethyl propionate and ethyl butyrate, or a mixture of propionic acid monoglyceride and butyric acid monoglyceride, or a mixture of propionic acid diglyceride and butyric acid diglyceride, particularly a mixture of ethyl propionate and ethyl butyrate or a mixture of propionic acid monoglyceride and butyric acid monoglyceride.
  • vitamin K2 compound relates to a menaquinone-n (abbreviated MK-n), wherein n represents the number of the isoprenyl units in the side chain which is linked to the 3 position of 2-methyl- 1 ,4-naphtochinone.
  • n can be from 2 to 14, preferably from 4 to 14, in particular n is 6 or 7, even more particular n is 7 (MK-7).
  • MK-7 menaquinone-n
  • the vitamin K2 compound is in all-trans form.
  • n is preferably 4 (MK-4), and in particular MK-4 is in all- trans form.
  • the at least one vitamin K2 compound is a mixture of two or more MK-n, preferably of MK-6 and MK-7. Preferably these are in all-trans form.
  • composition I comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition I comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound.
  • composition I comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the composition I comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound, wherein the ratio of the at least one HMO (component A) and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) is from 100 : 1 to 1 : 100, preferably from 20:1 to 1 :20, more preferably 10:1 to 1 :10, even more preferably from 3: 1 to 1 :3, in particular2:1 to 1 :2.
  • the composition I comprises as at least one C3-C4- alkane carboxylic acid or derivative(s) thereof a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof, in a ratio of from 100 : 1 to 1 : 100, preferably from 20:1 to 1 : 20, more preferably from 10:1 to 1 :15, even more preferably from 2: 1 to 1 :8.
  • the at least one HMO and the at least one C3-C4- alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.
  • composition I does not comprise one or more vitamin K2 compounds.
  • the composition I comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound, wherein the ratio of the at least one HMO (component A) and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) is from 100 :1 to 1 : 100, preferably from 20:1 to 1 :20, more preferably 10:1 to 1 :10, even more preferably from 3: 1 to 1 :3, in particular 2:1 to 1 :2, and/or wherein the ratio of the at least one HMO (component A) and the at least one vitamin K2 compound (component C) is from 1000:1 to 1000000:1 , and/or wherein the ratio of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) and the at least one vitamin K2 compound (
  • said composition I comprises as at least one C3-C4- alkane carboxylic acid or derivative(s) thereof a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof, in a ratio of from 100 : 1 to 1 : 100, preferably from 20:1 to 1 : 20, more preferably from 10:1 to 1 :15, even more preferably from 2:1 to 1 :8.
  • the at least one HMO and the at least one C3-C4- alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.
  • the at least one HMO and the at least one the vitamin K2 compound are present in synergistic amounts.
  • the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound are present in synergistic amounts.
  • the at least one HMO, the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound are present in synergistic amounts.
  • the total amount of the at least one HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally the at least one vitamin K2 compound is from 1 to 100 wt% of the total composition I, preferably from 10 to 100 wt%.
  • the total amount of the at least one HMO is from 10 to 90 wt% of the total composition I, preferably from 20 to 80 wt%, more preferably from 30 to 70 wt%, even more preferably from 40 to 60 wt%. In yet another embodiment the total amount of the at least one HMO is from 5 to 50 wt% of the total composition I, preferably from 8 to 40 wt%, more preferably from 10 to 35 wt%, even more preferably from 15 to 30 wt%. In yet another embodiment the total amount of the at least one HMO is from 50 to 95 wt% of the total composition I, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 90 wt% of the total composition I, preferably from 15 to 85 wt%, more preferably from 20 to 75 wt%, even more preferably from 25 to 60 wt%. In yet another embodiment the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 50 wt% of the total composition I, preferably from 15 to 45 wt%, more preferably from 20 to 35 wt%.
  • the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 50 to 90 wt% of the total composition I, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • the total amount of the at least one vitamin K2 compound is from 0.00001 to 1 wt% of the total composition I, preferably from 0.0001 to 0.1 wt%.
  • the composition I can further comprise one or more vitamins or related compounds thereto, other than a vitamin K2 compound.
  • vitamins and related compounds thereto include vitamin A (e.g. retinol, retinyl acetate, retinyl palmitate, retinyl stearate, retinyl esters with other long-chain unsaturated fatty acids, retinal, retinoic acid and the like), vitamin B1 (e.g. thiamine, thiamine pyrophosphate, TPP, thiamine triphosphate, TTP, thiamine hydrochloride, thiamine mononitrate and the like), vitamin B2 (e.g.
  • vitamin B3 e.g. nicotinic acid, nicotinamide, nicotinamide adenine dinucleotide (NAD), nicotinic acid mononucleotide (NicMN), pyridine-3-carboxylic acid and the like, as well as the vitamin B3-precursor tryptophan
  • pantothenic acid e.g. pantothenate, panthenol and the like
  • vitamin B6 e.g.
  • pyridoxine pyridoxal, pyridoxamine, pyridoxine hydrochloride and the like
  • biotin folic acid (e.g. folate, folacin, pteroylglutamic acid and the like)
  • vitamin B12 e.g. cobalamin, methylcobalamin. deoxyadenosylcobalamin, cyanocobalamin, hydroxycobalamin, adenosylcobalamin and the like
  • vitamin E e.g.
  • alpha-, beta-, gamma- and/or delta-tocopherol alpha-, beta-, gamma- and/or delta- tocopherol acetate, alpha-, beta-, gamma- and/or delta-tocopherol succinate, alpha-, beta-, gamma- and/or delta-tocopherol nicotinate, alpha-, beta-, gamma- and/or delta tocotrienol and the like), vitamin K (e.g. vitamin K1 , phylloquinone, naphthoquinone, vitamin K3, menadione, and the like ), vitamin C (ascorbic acid), vitamin D (e.g. calciferol, cholecalciferol, 1 ,25-dihydroxyvitamin D, ergocaliferol and the like), and the like and/or mixtures thereof.
  • vitamin K e.g. vitamin K1 , phylloquinone, naphthoquinon
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more vitamins or related compounds thereto, other than at least one vitamin K2 compound.
  • composition does not comprise one or more vitamins or related compounds thereto.
  • composition I can further comprise one or more carotenoids.
  • carotenoids include astaxanthin, alpha-carotene, beta-carotene, beta- cryptoxanthin, lutein, lycopene, meso-zeaxanthin, zeaxanthin and the like (including cis/trans isomers) and/or mixtures thereof.
  • the presence and amounts of specific carotenoids will vary depending on the intended use.
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more carotenoids.
  • the composition I can further comprise one or more medium-chain fatty acids.
  • These medium-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or alkyl esters.
  • Examples of medium-chain fatty acids include caproic acid, caprylic acid, capric acid, lauric acid and the like and /or mixtures thereof.
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more medium-chain fatty acids.
  • composition I can further comprise one or more long-chain fatty acids.
  • long-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or as alkyl esters.
  • long chain fatty acids include saturated long chain fatty acids (e.g.
  • linoleic acid linoelaidic acid, alpha-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentenoic acid, docosahexaenoic acid and the like and/or mixtures thereof) and/or mixtures thereof.
  • These long chain fatty acids are comprised for example in vegetable oils, single cell oils and marine oils, e.g. fish oil, krill oil and the like.
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more long-chain fatty acids.
  • composition I can further comprise one or more prebiotics.
  • prebiotics include water-insoluble fibers (e.g. lignin, cellulose, hemi- cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof), water-soluble fibers (e.g.
  • arabinoxylan arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof
  • other oligosaccharides like xylooligosaccharides, fructooligosaccharides, galactooligosaccharides, isomalto-oligosaccharides and the like and/or mixtures thereof
  • water-insoluble fibers e.g. lignin, cellulose, hemi- cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof
  • water-soluble fibers e.g.
  • arabinoxylan arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof) and the like and/or mixtures thereof.
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more prebiotics.
  • composition I can further comprise one or more probiotics.
  • probiotics optionally present in the composition I of the present invention include microorganisms or parts thereof of the family Lactobacillaceae, e.g. of the genus Lactobacillus (e.g. the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii (like lactobacillus delbrueckii spp. bulgaricus, lactobacillus delbrueckii spp. delbrueckii, lactobacillus delbrueckii spp.
  • the family Lactobacillaceae e.g. of the genus Lactobacillus (e.g. the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii (like lactobacillus delbrueckii spp. bulg
  • lactis lactobacillus helveticus, lactobacillus plantarum, lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus salivarius and the like), of the genus Bifidobacterium (e.g. the species bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium lactis, bifidobacterium longum and the like), of the genus Pediococcus (e.g.
  • Lactococcus e.g. the species lactococcus lactis (like lactococcus latis spp. cremoris, lactococcus lactis spp. lactic and the like
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more probiotics.
  • composition I can further comprise one or more phenolic compounds.
  • phenolic compounds include monophenols (e.g. apiole, carnosol, carvacrol, dillapiole, rosemarinol and the like), flavonoids (e.g.
  • quercetin kaempferol, myricetin, fisetin, rutin, isorhamnetin, hesperidin, naringenin, silybin, eriodyctiol, acacetin, apigenin, chrysin, diosmetin, tangeritin, luteolin, catechins like epigallocatechin gallate, theaflavin, thearubigins, proanthocyanidins, pelargonidin, peonidin, cyanidin, delphinidin, malvidin, petunidin and the like), isoflavonoids (e.g.
  • daidzein genistein, glycitein and the like
  • aurones chalconoids
  • flavonolignans lignans
  • phytoestrogens stilbenoids (e.g. resveratrol, pterostilbene, piceatannol and the like)
  • curcuminoids e.g. curcumin and the like
  • tannins aromatic acids (e.g. salicylic acid, vanillic acid, gallic acid, ellagic acid, tannic acid, caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumarin and the like), phenylethanoids (e.g. tyrosol, hydroxytyrosol, oleocanthal, oleuropein and the like ), capsaicin, gingerol, alkylresorcinol and the like and/or mixtures thereof.
  • aromatic acids e.g. salicylic acid, vanillic acid, gallic acid
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more phenolic compounds.
  • composition I can further comprise one or more herbals, e.g. known from Chinese diets, Indian diets, Mediterranean diets and the like. These herbals can be provided as powders obtained from the plant and/or fungus or parts thereof or as extracts thereof.
  • herbals known from Chinese diets include extracts or powders of hawthorn fruit, wolfberry, spatholobus stem, caterpillar fungus, cloud mushroom, crysanthemum, honeysuckle flower, mulberry leaf, glossy privet fruit, malaytea scurfpea fruit, cherokee rose fruit, palmleaf raspberry fruit, Chinese magnoliavine fruit, reishi mushroom, ephedra, epimedium, Angelica root, Astragalus root, rhubarb, licorice, morinda root, notoginseng, white peony root, American ginseng, fleeceflower root, kudzu root, rehmannia root, salvia root, Chinese yam, wild buckwheat rhizome, tall gastrodia tuber, golden root, Cassia seed, Coix seed, Dodder seed and the like and/or mixtures thereof.
  • herbals known from Indian diets include extracts or powders of Amalaki (Indian gooseberry), Haritaki (chebulic myrobalan), Bibhitaki (beleric), Haldi (turmeric), Tulsi (holy basil), Shigru (moringa), Twak (cinnamon), Yashtimadhu (licorice root), Dhanyaka (coriander), Ashwagandha (winter cherry), Kumkuma (saffron), Manjistha (Indian madder), Brahmi (bacopa), Neem (margosa), Ajwain (Bishop’s weed), Elaichi (cardamom), Shikakai (Acacia concinna), Shatavari (wild asparagus), Jeera (cumin), Guduchi (tinospora) and the like and/or mixtures thereof.
  • Examples for herbals known from Mediterranean diets include extracts or powders of rosemary, basil, parsley, saffron, thyme, oregano, sage, cilantro, lemon, orange, grape, grapeseed, fig, blueberry, raspberry, strawberry, cherry, fennel, sesame seeds, pine seeds, garlic, onion, ginger root, pepper, chili and the like, olive oil and/or mixtures thereof.
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more herbals.
  • composition I can further comprise one or more minerals.
  • minerals include such ones comprising calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum and the like and/or mixtures thereof. Minerals are usually added in salt form.
  • composition I does not comprise one or more vitamin K2 compounds.
  • composition I does comprise one or more vitamin K2 compounds.
  • composition I does not comprise one or more minerals. In a further embodiment of the present invention the composition I does not comprise a mineral comprising iron.
  • composition I does not comprise one or more antibodies.
  • compositions I of the present invention can be prepared by mixing the at least one HMO, and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, optionally the at least one vitamin K2 compound, and optionally further components e.g. vitamins and related compounds thereto, carotenoids, medium chain fatty acids, long chain fatty acids, prebiotics, probiotics, phenolic compounds, herbals, minerals and the like and/or mixtures thereof, as known in the art.
  • the composition I does not comprise more than 80 wt% water.
  • the present invention provides a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound, for use as a medicament, preferably as a medicament for mammals, birds and/or fishes, in particular as a medicament for mammals.
  • the term ’’mammals encompasses humans and nonhuman mammals.
  • non-human mammals are livestock, e.g. sheep, goats, pigs, cattles, horses, camels, llamas and the like, and pets, e.g. cats, dogs and the like.
  • composition I is for use as a medicament for humans. In another preferred embodiment of the present invention the composition I is for use as a medicament for livestock and/or pets.
  • composition I is for use as a medicament for birds, e.g. poultry (like chickens, ducks, geese, turkeys and the like) and ornamental birds (like canaries and the like).
  • birds e.g. poultry (like chickens, ducks, geese, turkeys and the like) and ornamental birds (like canaries and the like).
  • composition I is for use as a medicament for fishes, e.g. fishes used for consumption (like salmon, tuna, sardines, cod, trout, and the like) and ornamental fishes (like kois and the like).
  • fishes e.g. fishes used for consumption (like salmon, tuna, sardines, cod, trout, and the like) and ornamental fishes (like kois and the like).
  • compositions I of the present invention for use as a medicament can be administered orally, enterally or parenterally, preferably orally.
  • composition I for use as a medicament is an orally administrable composition.
  • composition I comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and optionally iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for use as a medicament, preferably as a medicament for humans.
  • composition I shall be applicable for the compositions I for use as a medicament and the specific embodiments thereto.
  • the present invention provides a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound, for the use in the treatment and/or prevention of hypertension and/or associated morbidities thereto, preferably of mammals, more preferably of humans.
  • the term ’’’treatment” in the context of hypertension and/or associated morbidities thereto means using an effective therapy or management to alleviate, reduce or cure the condition and/or disease (hypertension and/or associated morbidities thereto) and/or symptoms thereof, as the case may be, in addition it also includes the stabilization of the condition and/or disease, as the case may be, in order not to worsen in the course of the respective condition and/or disease.
  • treatment is understood as using an effective therapy or management to stabilize, alleviate or reduce the condition and/or disease and/or symptoms thereof, as the case may be.
  • the term ’’prevention” in the context of hypertension and/or associated morbidities thereto means an effective therapy or management so that the condition and/or disease (hypertension and/or associated morbidities thereto) does not de novo develop, manifest and/or symptoms thereof do not occur.
  • composition I is for use in the treatment of hypertension and/or associated morbidities thereto.
  • composition I is for use in the prevention of hypertension and/or associated morbidities thereto.
  • hypotension refers to a condition and/or disease, as the case may be, which is characterized by an increased blood pressure compared to a normal blood pressure, which is defined by the American Heart Association as being in the range of 90-119 mmHg (systolic) and 60-79 mmHg (diastolic) of a respective subject.
  • a person with hypertension has pre-hypertension, hypertension stage 1 , hypertension stage 2, a hypertensive crisis, isolated systolic hypertension or isolated diastolic hypertension.
  • pre-hypertension refers to a blood pressure from 120-129 mmHg systolic and 60-79 mmHg diastolic of a respective subject
  • hypertension stage 1 refers to a pressure from 130-139 mmHg systolic and 80-89 mmHg diastolic of a respective subject
  • the term “hypertension stage 2” from a pressure above 140 mmHg systolic and above 90 mmHg diastolic of a respective subject
  • hypertensive crisis refers to a blood pressure of above 180 mmHg systolic and above 120 mmHg diastolic of a respective subject
  • isolatedated systolic refers to a blood pressure of above 180 mmHg s
  • the composition I is for use in the treatment or prevention of hypertension of a human.
  • the composition I is for use in the treatment or prevention of pre-hypertension of a human, or in another embodiment of hypertension stage 1 of a human, or in another embodiment of hypertension stage 2 of a human, or in another embodiment of hypertensive crisis of a human, or in another embodiment of isolated systolic hypertension of a human, or in another embodiment of isolated diastolic hypertension of a human.
  • associated morbidities as well as the term ’’morbidities associated to” mean one or more conditions and/or diseases which are co-occurring to the primary condition or disease (hypertension), or which are occurring later in the life of the subject who had earlier in his or her life said primary condition and/or disease (hypertension).
  • the composition I is for use in the treatment or prevention of an associated morbidity, e.g. an associated morbidity of the cardiovascular system, which includes atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms, peripheral vascular disease etc., an associated morbidity of the renal system, which includes hypertensive nephropathy, chronic renal failure etc., an associated morbidity of the nervous system, which includes headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia, convulsion etc., an associated morbidity of the vision system, which includes hypertensive retinopathy, vision loss etc., and the like, in particular of a human.
  • an associated morbidity e.g. an associated morbidity of the cardiovascular system, which includes atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms
  • composition I is for use in the treatment or prevention of an associated morbidity of the cardiovascular system, in particular of a human subject having hypertension.
  • composition I is for use in the treatment or prevention of atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms and/or peripheral vascular disease, in particular of a human subject having hypertension.
  • composition I is for use in the treatment or prevention of an associated morbidity of the renal system, in particular of a human subject having hypertension.
  • composition I is for use in the treatment or prevention of hypertensive nephropathy and/or chronic renal failure, in particular of a human subject having hypertension.
  • composition I is for use in the treatment or prevention of an associated morbidity of the nervous system, in particular of a human subject having hypertension.
  • composition I is for use in the treatment or prevention of headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia and/or convulsion, in particular of a human subject having hypertension.
  • composition I is for use in the treatment or prevention of an associated morbidity of the vision system, in particular of a human subject having hypertension.
  • composition I is for use in the treatment or prevention of hypertensive retinopathy and/or vision loss, in particular of a human subject having hypertension.
  • composition I for use in the treatment or prevention of hypertension is an orally administrable composition, in particular for a human subject.
  • composition I for use in the treatment or prevention of morbidities associated to hypertension is an orally administrable composition, in particular for a human subject.
  • the composition I comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for use in the treatment or prevention of hypertension and/or associated morbidities thereto, in particular of a mammal, especially of hypertension of a human or especially of morbidities associated to hypertension.
  • the composition I comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for use in the treatment or prevention of hypertension and/or associated morbidities thereto of a mammal, in particular of hypertension of a human, or in particular of morbidities associated to hypertension of a human.
  • the composition I for use in the treatment or prevention of hypertension and/or associated morbidities thereto, in particular of a mammal, especially of hypertension of a human or especially of morbidities associated to hypertension of a human does not comprise one or more vitamin K2 compounds.
  • composition I comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound, for use in the treatment or prevention of hypertension and/or associated morbidities thereto of a mammal, in particular of hypertension of a human, or in particular of morbidities associated to hypertension of a human.
  • the composition I comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for use in the treatment or prevention of hypertension and/or associated morbidities thereto of a mammal, in particular of hypertension of a human, or in particular of morbidities associated to hypertension of a human.
  • composition I shall be applicable for the compositions I for use in the treatment or prevention of hypertension and/or associated morbidities thereto and the specific embodiments thereto.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • the composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • said method is for treating a subject having hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • said method is for treating a subject having morbidities associated to hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing morbidities associated to hypertension, in particular a human.
  • said human subject is in the age of 12 years or older, preferably 18 years or older, more preferably 35 years or older, in particular 50 years or older, even more particular 60 years or older.
  • composition I can be administered, preferably orally, or that any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional the “at least one vitamin K2 compound” and optional further components can be administered separately, preferably orally.
  • composition I comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the composition I comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that these can be administered separately, preferably orally, and in case the composition I comprises as at least one vitamin K2 compound two or more vitamin K2 compounds that these can be administered separately, preferably orally.
  • the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.
  • the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g.
  • the propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1 .0 to 4.0 g/day.
  • the butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1 .0 to 5.0 g/day.
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 1 .5 to 4.0 g.
  • the daily application rate of the at least one vitamin K2 compound is from 1 to 1000 meg, preferably from 10 to 200 meg, in particular from 20 to 150 meg, especially from 30 to 100 meg.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of said composition I which does not comprise one or more vitamin K2 compounds.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound.
  • the composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4,
  • composition I shall be applicable for the use of the composition I in this method accordingly and in the specific embodiments thereto.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I, which does not comprise one or more vitamin K2 compounds, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the medicament manufactured as mentioned above is for treating a subject having hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • the medicament manufactured as mentioned above is for treating a subject having morbidities associated to hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing morbidities associated to hypertension, in particular a human.
  • composition I shall be applicable for the use of the composition I in this use accordingly and in the specific embodiments thereto.
  • the present invention provides a nutritional supplement comprising a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • the term “nutritional supplement” means a manufactured product intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of hypertension and/or associated morbidities thereto.
  • nutritional supplements include “dietary supplements” and “medical foods”.
  • a dietary supplement is intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, however it needs not to be used under medical supervision.
  • a medical food is also intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, but it is under medical supervision.
  • the terms “medical foods” and “food for special medical purpose” are interchangeable.
  • the nutritional supplement can comprise said composition I or that the nutritional supplement can comprise any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional the “at least one vitamin K2 compound” and optional further components in separate form.
  • the nutritional supplement is a dietary supplement.
  • the nutritional supplement is a medical food.
  • the nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension.
  • the nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.
  • the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g.
  • propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1.0 to 4.0 g/day.
  • butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day.
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g.
  • said subject is a human, preferably in the age of 12 years or older, more preferably 18 years or older, even more preferably 35 years or older, in particular 50 years or older, even more in particular 60 years or older.
  • the daily application rate of the at least one vitamin K2 compound is from 1 to 1000 meg, preferably from 10 to 200 meg, in particular from 20 to 150 meg, especially from 30 to 100 meg.
  • the nutritional supplement can be administered, preferably orally, or that any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and the optional “at least one vitamin K2 compound” and optional further components can be administered separately, preferably orally.
  • the nutritional supplement comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the nutritional supplement comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that these can be administered separately, preferably orally, and in case the nutritional supplement comprises as at least one vitamin K2 compounds two or more vitamin K2 compounds that these can be administered separately, preferably orally.
  • the present invention provides a nutritional supplement comprising a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • a composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition I which does not comprise one or more vitamin K2 compounds, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • said nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension.
  • said nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the nutritional supplement can comprise said composition I or that the nutritional supplement can comprise any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional the “at least one vitamin K2 compound” and optional further components in separate form.
  • composition I comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the composition I comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that these can be administered separately, preferably orally, and in case the composition I comprises as at least one vitamin K2 compound two or more vitamin K2 compounds that these can be administered separately, preferably orally.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition I, which does not comprise one or more vitamin K2 compounds.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound.
  • a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I, which does not comprise one or more vitamin K2 compounds, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the nutritional supplement manufactured as mentioned above is for the dietary management of a subject having hypertension, in particular a human, or a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • the nutritional supplement manufactured as mentioned above is for the dietary management of a subject having hypertension, in particular a human, or a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • composition I shall be applicable for the use of the composition I in this use accordingly and in the specific embodiments thereto.
  • Both, the medicament (in general and for the respective specific use) and the nutritional supplement (in general and for the respective specific use) of the present invention can be delivered in any suitable format.
  • Formulations suitable for oral administration may be in the form of capsules, tablets, pills, dragees, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth), powders, granules, and the like or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia), each comprising a predetermined amount of the at least one HMO, the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, optional the at least one vitamin K2 compound and optional further components.
  • the medicament in general and for the
  • active ingredients of said medicament and nutritional supplement can be delivered together in a respective suitable format or that each of component A and component B and optionally component C can be delivered in a respective format or that each of the active ingredients can be delivered in a respective format, or any combination thereof.
  • the desired components of the composition I may be mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar- agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as acetriglyceride
  • powders and/or granules can be reconstituted with water or another aqueous liquid prior to consumption.
  • the so obtained liquid does not comprise more than 80 wt% water.
  • liquid formulations do not comprise more than 80 wt% water.
  • the present invention provides a functional food comprising a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • the term “functional food” means a food which is fortified with the composition I according to the present invention and intended to be used in a diet, in particular of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the terms “functional food” and “fortified food” are interchangeable.
  • Examples for foods being suitable for the preparation of functional foods are (1) dairy products e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof; (2) bakery products e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof; (3) candy products e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof; (4) beverage products e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof.
  • dairy products e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof
  • bakery products e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof
  • candy products e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof
  • beverage products e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof.
  • the functional food can comprise said composition I or that the functional food can comprise any of the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional the “at least one vitamin K2 compound” and optional further components in separate form.
  • composition I comprises as the at least one HMO two or more HMOs these can be comprised separately in the functional food or together as composition
  • composition I comprises as the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof these can be comprised separately in the functional food or together as composition
  • composition I comprises as the at least one vitamin K2 compound two or more vitamin K2 compounds these can be comprised separately in the functional food or together as composition.
  • the functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.
  • the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g.
  • propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1 .0 to 4.0 g/day.
  • butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day.
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g.
  • said subject is a human, preferably in the age of 12 years or older, more preferably 18 years or older, even more preferably 35 years or older, in particular 50 years or older, even more in particular 60 years and older.
  • the daily application rate of the at least one vitamin K2 compound is from 1 to 1000 meg, preferably from 10 to 200 meg, in particular from 20 to 150 meg, especially from 30 to 100 meg.
  • the present invention provides a functional food comprising a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a functional food comprising a composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • a composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a functional food comprising a composition I which does not comprise one or more vitamin K2 compounds, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a functional food comprising a composition I which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound.
  • the present invention provides a functional food comprising a composition I which comprises i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • said functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension. In another embodiment of the present invention said functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides a method for the dietary management of a subject having, being suspected to have or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the “at least one HMO” and the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional the “at least one vitamin K2 compound” and optional further components can be comprised separately in the functional food or together as composition.
  • composition I comprises as at least one HMO two or more HMOs that these can be comprised separately in the functional food or together as composition
  • composition I comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that these can be comprised separately in the functional food or together as composition
  • composition I comprises as at least one vitamin K2 compound two or more vitamin K2 compounds that these can be comprised separately in the functional food or together as composition.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of a functional food which comprises a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • a functional food which comprises a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition I, which does not comprise one or more vitamin K2 compounds.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension. In another embodiment of the present invention said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I, which does not comprise one or more vitamin K2 compounds, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and iii) at least one vitamin K2 compound, for the manufacture of afunctional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition I comprising i) as component A 2’-FL, and ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the functional food manufactured as mentioned above is for the dietary management of a subject having hypertension, in particular a human, or a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • the nutritional supplement manufactured as mentioned above is for the dietary management of a subject having morbidities associated to hypertension, in particular a human, or a subject being suspected of having or being at risk of developing morbidities associated to hypertension, in particular a human.
  • composition I shall be applicable for the use of the composition I in this use accordingly and in the specific embodiments thereto.
  • the functional food of the present invention can be prepared by known techniques and it can have any suitable type of format such as (1) a dairy product e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof; (2) a bakery product e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof; (3) a candy product e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof; (4) a beverage product e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof.
  • a dairy product e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof
  • a bakery product e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof
  • a candy product e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof
  • (4) a beverage product e.g. fruit juice, vegetable juice, lemonade
  • composition I the composition I for use as a medicament, the composition I for use in the treatment or prevention of hypertension and/or associated morbidities thereto, the nutritional supplement and the functional food, in particular for use in the dietary management of hypertension and/or associated morbidities thereto, respectively, as disclosed herein, can be co-administered to subjects receiving at least one pharmaceutical against said hypertension and/or associated morbidities thereto.
  • pharmaceuticals used in the treatment of hypertension are thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan.
  • the present invention provides a method to treat a subject having hypertension and/or associated morbidities thereto, by administering to the subject a) an effective amount of a composition I, a composition I for use as a medicament, a composition I for use in the treatment or prevention of hypertension and/or associated morbidities thereto, a nutritional supplement or a functional food, in particular for use in the dietary management of hypertension and/or associated morbidities thereto, which comprises i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally iii) at least one vitamin K2 compound; and b) an effective amount of at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto, in particular, wherein the application rate of the at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto is reduced compared to a treatment with the at least one pharmaceutical alone.
  • the hypertension and/or associated morbidities thereto is hypertension and the pharmaceutical is a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g. verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors (e.g.
  • captopril enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan.
  • the present invention provides a composition
  • a composition comprising a) i) at least one HMO, and/or ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and/or iii) at least one vitamin K2 compound; and b) an effective amount of at least one pharmaceutical, in particular for use as a medicament, especially for use in the treatment of hypertension and/or associated morbidities thereto.
  • the present invention provides a composition
  • a composition comprising a) i) as component A 2’-FL, and/or ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and/or sodium butyrate, and/or iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4; and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the present invention provides a composition
  • a composition comprising a) as component A at least one HMO, preferably 2’-FL, and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the present invention provides a composition
  • a composition comprising a) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and/or sodium butyrate, and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the present invention provides a composition
  • a composition comprising a) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the composition I, the composition I for use as a medicament, the composition I for use in the treatment or prevention of hypertension, the nutritional supplement or a functional food, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension, especially of subjects having hypertension, used in said method comprises 2’-FL, and/or propionic acid and/or butyric acid or derivative(s) thereof, and/or MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably 2’-FL, sodium propionate and sodium butyrate, and/or optionally preferably MK-7 or MK-4.
  • composition I in another embodiment the composition I, the composition I for use as a medicament, the composition I for use in the treatment or prevention of a morbidity associated to hypertension, the nutritional supplement or a functional food, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing a morbidity associated to hypertension, especially e of subjects having morbidity associated to hypertension used in said method comprises 2’-FL and/or propionic acid and/or butyric acid or derivative(s) thereof and/or optionally MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably 2’-FL, sodium propionate and sodium butyrate, and/or optionally preferably MK-7 or MK-4.
  • the nutritional supplement or the functional food is for use in the dietary management of hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of a morbidity associated to hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the cardiovascular system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms and/or peripheral vascular disease, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the renal system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of hypertensive nephropathy and/or chronic renal failure, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the nervous system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia and/or convulsion, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the vision system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of hypertensive retinopathy and/or vision loss, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • kits for the pharmaceutical use or dietary management use comprising a first component comprising at least one HMO and a second component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and optionally a third component comprising at least one vitamin K2 compound.
  • the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL, and a second component comprising propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and optionally a third component comprising MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL, a second component comprising propionic acid or derivative(s) thereof, preferably sodium propionate, and a third component comprising butyric acid or derivative(s) thereof, preferably sodium butyrate, and optionally a forth component comprising MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the present invention provides said kit for the pharmaceutical use for the treatment or prevention of hypertension and/or associated morbidities thereto or dietary management use for the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, in particular of subjects having hypertension and/or associated morbidities thereto.
  • the present invention provides said kit for the pharmaceutical use or dietary management use for the treatment or prevention of hypertension or dietary management use for the dietary management of subjects having, being suspected of having or being at risk of developing hypertension, in particular of subjects having hypertension.
  • the present invention provides said kit for the pharmaceutical use or dietary management use for the treatment or prevention of morbidities associated to hypertension or dietary management use for the dietary management of subjects having, being suspected of having or being at risk of developing associated morbidities to hypertension, in particular of subjects having associated morbidities to hypertension.
  • kits for the pharmaceutical use comprising a first component comprising at least one HMO, and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and optionally a third component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is 2’-FL, a second component comprising a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g. verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors (e.g.
  • captopril enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril) and/or an angiotensin receptor blockers (e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan) in a pharmaceutical effective amount, and optionally a third component which is propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • an angiotensin receptor blockers e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan
  • the present invention provides a kit for the pharmaceutical use comprising a first component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and optionally a third component comprising at least one HMO.
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is propionic acid and/or butyric acid or derivative(s) thereof, a second component comprising a a thiazide-diuretics (e.g.
  • hydrochlorothiazide hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide
  • a calcium channel blockers e.g. verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin
  • an angiotensin converting enzyme inhibitors e.g.
  • captopril enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril) and/or an angiotensin receptor blockers (e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan) in a pharmaceutical effective amount, and optionally a third component which is 2’-FL.
  • angiotensin receptor blockers e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan
  • the present invention provides a kit for the pharmaceutical use comprising a first component comprising at least one vitamin K2 compound and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and optionally a third component comprising at least one HMO and/or at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, a second component comprising a a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • a pharmaceutical effective amount in a pharmaceutical effective amount
  • a third component 2’-FL and/or optionally a third component which is propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the present invention provides a kit for the pharmaceutical use comprising a first component comprising at least one HMO and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and a third component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and a forth component comprising at least one vitamin K2 compound.
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is 2’-FL, a second component comprising a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g. verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors (e.g.
  • captopril enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril) and/or an angiotensin receptor blockers (e.g.
  • a pharmaceutical effective amount in a pharmaceutical effective amount
  • a third component which is propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate
  • a forth component which is MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • butyric acid denotes n-butyric acid and the term “butyrate” denotes n-butyrate.
  • the term ”at least one HMO” is interchangeable with the term ’’component A
  • the term ”at least one C3-C4-alkane carboxylic acid or a derivative thereof’ is interchangeable with the term “component B”
  • the term “at least one vitamin K2 compound” is interchangeable with the term “component C”.
  • composition comprises several components that these can also be administered separately.
  • these components can be administered together or separately, as the case may be.
  • compositions of the present invention can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise depending on the needs.
  • the terminology as set forth herein is for description of the embodiments only and should not be construed as limiting the disclosure as a whole. In a particular embodiment the compositions of the invention consist essentially of the essential elements, and even more particular consist of the essential elements.
  • a composition I comprising i) at least one HMO, and ii) at least one C3-C4-alkane carboxylic acid or a derivative thereof, and optionally iii) at least one vitamin K2 compound.
  • composition I according to any one of embodiments 1-1 to 3-1, wherein one of the at least one HMO’s is a sialylated oligosaccharide.
  • composition I according to any one of embodiments embodiment 1-1 to 4-1, wherein one of the at least one HMO is 6’-sialyllactose (6’-SL).
  • composition I according to any one of embodiments 1-1 to 5-1, wherein one of the at least one HMO’s is a N-acetylated oligosaccharide.
  • composition I according to any one of embodiments 1-1 to 6-1, wherein one of the at least one HMO is lacto-N-tetraose (LNT).
  • LNT lacto-N-tetraose
  • composition I according to any one of embodiments 1-1 to 7-1, wherein the at least one
  • HMO is one or more HMOs selected from the group consisting of 2’-FL, 3-FL, difucosyllactose (in particular 2’,2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL.
  • composition I according to any one of embodiments 1-1 to 8-1, wherein the at least one
  • HMO is one, two or three HMOs selected from the group consisting of 2’-FL, 3-FL, difucosyllactose (in particular 2’, 2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL.
  • composition I according to any one of embodiments 1-1 to 9-1, wherein the at least one
  • HMO is one, two or three HMOs selected from the group consisting of 2’-FL, LNT, LNnT, 3’-SL and 6’-SL. 11-1.
  • the composition I according to any one of embodiments 1-1 to 9-1, wherein the at least one
  • HMO is one, two or three HMOs selected from the group consisting of 2’-FL, 2’,2”-DiFL and 3,2’-DiFL.
  • composition I according to any one of embodiments 1-1 to 11-1 wherein the at least one
  • HMO is 2’-FL.
  • composition I according to any one of embodiments 1-1 to 12-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof.
  • composition I according to any one of embodiments 1-1 to 13-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt or ester of propionic acid.
  • composition I according to any one of embodiments 1-1 to 14-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of propionic acid.
  • composition I according to any one of embodiments 1-1 to 15-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium salt of propionic acid.
  • composition I according to any one of embodiments 1-1 to 16-1 wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium propionate.
  • composition I according to any one of embodiments 1-1 to 14-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of propionic acid.
  • composition I according to any one of embodiments 1-1 to 18-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is butyric acid or a derivative thereof.
  • one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of butyric acid.
  • composition I according to any one of embodiments 1-1 to 21-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium salt of butyric acid.
  • composition I according to any one of embodiments 1-1 to 22-1 wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium butyrate.
  • composition I according to any one of embodiments 1-1 to 20-1, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of butyric acid.
  • composition I according to any one of embodiments 1-1 to 24-1, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof and butyric acid or a derivative thereof.
  • composition I according to any one of embodiments 1-1 to 25-1, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt of propionic acid and physiologically acceptable salt of butyric acid.
  • composition I according to any one of embodiments 1-1 to 26-1, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of propionic acid and an alkali salt or an alkaline earth salt of butyric acid.
  • composition I according to any one of embodiments 1-1 to 27-1, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium salt of propionic acid and a sodium or potassium salt of butyric acid.
  • composition I according to any one of embodiments 1-1 to 28-1 wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium propionate and sodium or potassium butyrate.
  • composition I according to any one of embodiments 1-1 to 25-1, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable ester of propionic acid and a physiologically acceptable ester of butyric acid.
  • 31-1 The composition I according to any one of embodiments 1-1 to 30-1, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of propionic acid and a C1 -C6 alkyl ester or a mono- or diglyceride of butyric acid.
  • composition I according to any one of embodiments 1-1 to 31-1 which does not comprise one or more vitamin K2 compounds.
  • composition I according to any one of embodiments 1-1 to 31-1 which comprise at least one vitamin K2 compounds.
  • composition I according to any one of embodiments 1-1 to 35-1, wherein the at least on vitamin K2 compound is MK-4, MK-6, MK-7 or any mixture thereof.
  • composition I according to any one of embodiments 1-1 to 36-1, wherein the at least on vitamin K2 compound is MK-4, MK-7 or a mixture of MK-6 and MK-7.
  • composition I according to any one of embodiments 1-1 to 37-1, wherein the weight to weight ratio of the at least one HMO (component A) : the at least one C3-C4 alkane carboxylic acid or a derivative thereof (component B) is from 100:1 to 1 :100.
  • composition I according to any one of embodiments 1-1 to 38-1, wherein the weight to weight ratio of (component A) : (component B) is from 20:1 to 1 :20, preferably from 10:1 to 1 :10, more preferably from 3:1 to 1 :3, in particular from 2:1 to 1 :2.
  • composition I according to any one of embodiments 25-I to 39-I, wherein the weight to weight ratio of the propionic acid or a derivative thereof : butyric acid or a derivative thereof is from 100:1 to 1 : 100.
  • composition I according to any one of embodiments 25-1 to 40-1 wherein the weight to weight ratio of the propionic acid or a derivative thereof : butyric acid or a derivative thereof is from 20:1 to 1 :20, preferably from 10:1 to 1 :15, more preferably from 2:1 to 1 :8. 42-I.
  • composition I according to any one of embodiments 1-1 to 42-1, wherein the weight to weight ratio of (component B) : (component C) is from 1000: 1 to 1000000: 1.
  • composition I according to any one of embodiments 1-1 to 43-1, wherein the at least one
  • HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.
  • composition I according to any one of embodiments 1-1 to 44-1, wherein the at least one
  • HMO and the at least one vitamin K2 compound are present in synergistic amounts.
  • composition I according to any one of embodiments 1-1 to 45-1, wherein the at least one
  • C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound are present in synergistic amounts.
  • composition I according to any one of embodiments 1-1 to 46-1, wherein the at least one
  • HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound are present in synergistic amounts.
  • composition I according to any one of embodiments 1-1 to 47-1, wherein the total amount of the at least one HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and optionally the at least one vitamin K2 compound is from 1 to 100 wt% of the total composition I, preferably from 10 to 100 wt%.
  • composition I according to any one of embodiments 1-1 to 48-1, wherein the total amount of the at least one HMO is from 10 to 90 wt% of the total composition I, preferably from 20 to 80 wt%, more preferably from 30 to 70 wt%, even more preferably from 40 to 60 wt%.
  • composition I according to any one of embodiments 1-1 to 48-1, wherein the total amount of the at least one HMO is from 5 to 50 wt% of the total composition I, preferably from 8 to 40 wt%, more preferably from 10 to 35 wt%, even more preferably from 15 to 30 wt%.
  • 52-I The composition I according to any one of embodiments 1-1 to 51-1, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 90 wt% of the total composition I, preferably from 15 to 85 wt%, more preferably from 20 to 75 wt%, even more preferably from 25 to 60 wt%.
  • composition I according to any one of embodiments 1-1 to 52-1, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 50 wt% of the total composition I, preferably from 15 to 45 wt%, more preferably from 20 to 35 wt%.
  • composition I according to any one of embodiments 1-1 to 52-1, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 50 to 90 wt% of the total composition I, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • composition I according to any one of embodiments 1-1 to 54-1, wherein the total amount of the at least one vitamin K2 compound is from 0.00001 to 1 wt% of the total composition I, preferably from 0.0001 to 0.1 wt%.
  • composition I according to any one of embodiments 1-1 to 55-1, wherein the composition I further comprises one or more vitamins or related compounds thereto, other than a vitamin K2 compound.
  • composition I according to embodiment 56-1 wherein the one or more vitamins or related compounds thereto are selected from the group of vitamin A, vitamin B1 , vitamin B2, vitamin B3, pantothenic acid, vitamin B6, biotin, folic acid, vitamin B12, vitamin E, vitamin K, vitamin C and vitamin D, or related compounds thereto and/or mixtures thereof.
  • composition I according to any one of embodiments 1-1 to 57-1, wherein the composition I further comprises one or more carotenoids.
  • composition I according to embodiment 58-1 wherein the one or more carotenoids are selected from the group of astaxanthin, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, meso-zeaxanthin, zeaxanthin (including cis/trans isomers) and/or mixtures thereof.
  • composition I according to any one of embodiments 1-1 to 59-1, wherein the composition I further comprises one or more medium-chain fatty acids, in free form, as glyceride, phospholipid, alkyl ester and/or mixtures thereof.
  • the one or more medium chain fatty acids are selected from the group of caproic acid, caprylic acid, capric acid, lauric acid and/or mixtures.
  • composition I according to any one of embodiments 1-1 to 61-1, wherein the composition I further comprises one or more long-chain fatty acids, in free form, as glyceride, phospholipid, alkyl ester and/or mixtures thereof.
  • composition I according to embodiment 62-1 wherein the one or more long chain fatty acids are selected from the group of saturated long chain fatty acids, mono-unsaturated long chain fatty acids, polyunsaturated long chain fatty acids and/or mixtures thereof.
  • composition I according to any one of embodiments 1-1 to 63-1, wherein the composition I further comprises one or more prebiotics.
  • composition I according to embodiment 64-1 wherein the one or more prebiotics are selected from the group of water-insoluble fibers, water-soluble fibers, other oligosaccharides and/or mixtures thereof, preferably water-insoluble fibers, water-soluble fibers and/or mixtures thereof.
  • composition I according to any one of embodiments 1-1 to 65-1, wherein the composition I further comprises one or more probiotics.
  • composition I according to embodiment 66-1, wherein the one or more probiotics are selected from the group of the family Lactobacilaceae, preferably of the genus Lactobacillus, in particular of the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii, lactobacillus helveticus, lactobacillus plantarum, lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus salivarius, of the genus Bifidobacterium, in particular of the species bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium lactis, bifidobacterium longum, of the genus Pediococcus, in particualar of the group of the family
  • composition I according to embodiment 68-1 wherein the one or more phenolic compounds are selected from the group of monophenols, flavonoids, isoflavonoids, aurones, chalconoids, flavonolignans, lignans, phytoestrogens, stilbenoids, piceatannol, curcuminoids, tannins, aromatic acids, phenylethanoids, capsaicin, gingerol, alkylresorcinol and/or mixtures thereof.
  • composition I according to any one of embodiments 1-1 to 69-1, wherein the composition I further comprises one or more herbals.
  • composition I according to embodiment 70-1 wherein the one or more herbals are selected from herbals known from Chinese diets, Indian diets, Mediterranean diets and/or mixtures thereof.
  • composition I according to any one of embodiments 1-1 to 71-1, wherein the composition I further comprises one or more minerals.
  • composition I according to any one of embodiments 1-1 to 72-1, wherein the composition does not comprise an antibody.
  • composition I according to embodiment 75-1, wherein the hypertension and/or associated morbidities thereto is hypertension, in particular of a human.
  • composition I according to embodiment 76-1 wherein the hypertension is prehypertension, or hypertension stage 1 or hypertension stage 2 or hypertensive crisis or isolated systolic hypertension or isolated diastolic hypertension, in particular of a human.
  • 78-I The composition I according to embodiment 75-I, wherein the hypertension and/or associated morbidities thereto is an associated morbidity, in particular of a human.
  • composition I according to any one of embodiments 74-1 to 83-1, wherein the composition
  • I is an orally administrable composition.
  • a method for treating a subject having, suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto comprising administering to the subject an effective amount of a composition I according to any one of embodiments 1-1 to 73-1.
  • 86-1 The method according to embodiment 85-1, wherein the subject, in particular a human, has, is suspected of having or being at risk of developing hypertension.
  • -I The method according to embodiment 85-I, wherein the subject, in particular a human, has, is suspected of having or being at risk of developing morbidities associated to hypertension.
  • -I The method according to any one of embodiments 85-I to 87-I, wherein the application rate of the at least one HMO is from 0.1 to 20.0 g/day, preferably from 1.0 to 15.0 g/day, more preferably from 2.0 to 10.0 g/day, in particular from 2.5 to 5.0 g/day. -I.
  • C3-C4-alkane carboxylic acid or derivative(s) thereof is propionic acid or a derivative thereof and is applied at a rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1.0 to 4.0 g/day. -1.
  • C3-C4-alkane carboxylic acid or derivative(s) thereof is butyric acid and/or a derivative thereof and is applied at a rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day.
  • -I The method according to any one of embodiments 85-I to 91-1, wherein the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is butyric acid and/or a derivative thereof and is applied at a rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day.
  • -I The method according to any one of embodiments 85-I to 91-1, wherein the at least one C3-
  • C4-alkane carboxylic acid or derivative(s) thereof is a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof and the application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g/day and the application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g/day, preferably the application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g/day, more preferably the application rate of propionic acid and/or a derivative thereof is from 1 .0 to 3.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g/day.
  • the nutritional supplement or the functional food according to embodiment 95-1 for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, preferably of mammals, birds and/or fishes, more preferably of mammals, even more preferably of humans.
  • the nutritional supplement or functional food according to embodiment 96-1 for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension, preferably of mammals, birds and/or fishes, more preferably of mammals, even more preferably of humans.
  • the nutritional supplement or functional food according to embodiment 96-1 for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension, preferably of mammals, birds and/or fishes, more preferably of mammals, even more preferably of humans.
  • the nutritional supplement or functional food according to embodiment 98-1 for use in the dietary management of subjects having, being suspected of having or being at risk of developing an associated morbidity of the cardiovascular system, an associated morbidity of the renal system, an associated morbidity of the nervous system or an associated morbidity of the vision system, in particular of a human, even more particular of a human having hypertension.
  • the nutritional supplement or functional food according to embodiment 99-1 for use in the dietary management of subjects having, being suspected of having or being at risk of developing atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms and/or peripheral vascular disease, in particular of a human, even more particular of a human having hypertension.
  • the nutritional supplement or functional food according to embodiment 99-1 for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertensive nephropathy and/or chronic renal failure, in particular of a human, even more particular of a human having hypertension.
  • the nutritional supplement or functional food according to embodiment 99-1 for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertensive retinopathy and/or vision loss, in particular of a human, even more particular of a human having hypertension.
  • -I A method for the dietary management of a subject having, suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, comprising administering to the subject an effective amount of a composition I according to any one of embodiments 1 -I to 73-I or a nutritional supplement according to any one of embodiments 95-I to 103-1 or a functional food according to any one of embodiments 95-1 to 103-1. -1.
  • the method according to claim 104-1 wherein the subject, in particular a human, has, is suspected of having or being at risk of developing hypertension. -1.
  • the method according to any one of embodiments 104-1 to 106-1, wherein the application rate of the at least one HMO is from 0.1 to 20.0 g/day, preferably from 1.0 to 15.0 g/day, more preferably from 2.0 to 10.0 g/day, in particular from 2.5 to 5.0 g/day. -1.
  • the application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g/day, preferably from 1.0 to 9.0 g/day, more preferably from 1.2 to 9.0 g/day, in particular from 2.0 to 8.0 g/day, especially from 2.5 to 6.0 g/day. -1.
  • C4-alkane carboxylic acid or derivative(s) thereof is a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof and the application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g/day and the application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g/day, preferably the application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g/day, more preferably the application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 1 .5 to 4.0 g/day.
  • a method to treat a subject having hypertension and/or associated morbidities thereto by administering to the subject a) an effective amount of a composition I according to any one of embodiments 1-1 to 73-1, a composition I for use as a medicament according to embodiment 74-1, a composition I for use in the treatment or prevention of hypertension and/or associated morbidities thereto according to any one of embodiments 75-1 to 84-1, a nutritional supplement or a functional food according to any one of embodiments 95-1 to 104-1, or with one of components A, B and C, or with two of components A, B and C as described in any one of embodiments 1 -I to 73-I, and b) an effective amount of at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto, wherein the application rate of the at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto is reduced compared to a treatment with the at least one pharmaceutical alone.
  • a composition comprising a) i) at least one HMO, and/or ii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and/or iii) at least one vitamin K2 compound; and b) an effective amount of at least one pharmaceutical, especially being suitable for the treatment or prevention of hypertension and/or associated morbidities thereto, in particular for use as a medicament, especially for use in the treatment or prevention of hypertension and/or associated morbidities thereto.
  • a composition comprising a) i) as component A 2’-FL, and/or ii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and/or sodium butyrate, and/or iii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4; and b) a thiazide-diuretics (especially hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (especially verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors
  • a composition I for use as a medicament according to embodiment 74-1 a composition I for use in the treatment or prevention of hypertension and/or associated morbidities thereto according to any one of embodiments 75-1 to 84-1, a nutritional supplement or a functional food according to any one of embodiments 95-1 to 103-1, a composition according to any one of embodiments 119-1 to 120-1, wherein the subject is a human, preferably in the age of 12 years or older, more preferably 18 years or older, even more preferably 35 years or older, in particular 50 years or older, even more in particular 60 years or older.
  • the subject is a human, preferably in the age of 12 years or older, more preferably 18 years or older, even more preferably 35 years or older, in particular 50 years or older even more in particular 60 years or older.
  • a kit for the pharmaceutical use or dietary management use comprising a first component A being at least one HMO, preferably as described in any one of embodiments 1-1 to 73-1, and a second component B being at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, preferably as described in any of embodiments 1-1 to 73-1 , and optionally a third component C being at least one vitamin K2 compound as described in any embodiments 1-1 to 73-1 for the treatment or prevention or dietary management use of hypertension and/or associated morbidities thereto.
  • kit according to embodiment 124-1 wherein the kit is forthe pharmaceutical use forthe treatment or prevention of hypertension or dietary management use of hypertension.
  • kits according to embodiment 124-1 wherein the kit is forthe pharmaceutical use forthe treatment or prevention of morbidities associated to hypertension or dietary management use of morbidities associated to hypertension.
  • a kit for the pharmaceutical use or dietary management use comprising a) a first component A being at least one HMO, preferably as described in any one of embodiments 1-1 to 73-1, and/or a second component B being at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, preferably as described in any of embodiments 1-1 to 73-1 , and/or a third component C being at least one vitamin K2 compound as described in any embodiments 1-1 to 73-1; and b) an effective amount of at least one pharmaceutical, especially being suitable for the treatment or prevention of hypertension and/or associated morbidities thereto, for use in the treatment or prevention of hypertension and/or associated morbidities thereto.
  • kits for the pharmaceutical use or dietary management use according to embodiment 127-1, wherein the at least one pharmaceutical is a thiazide-diuretics (especially hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (especially verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors (especially captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril) and/
  • HMOs can be combined with at least one vitamin K2 compound, and optionally with C3-C4-alkane carboxylic acids or derivatives thereof. Such compositions provide beneficial effects as described herein.
  • composition II comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • HMO refers to human milk oligosaccharide(s). These carbohydrates are resistant to enzymatic hydrolysis by digestive enzymes (e.g. pancreatic and/or brush border).
  • digestive enzymes e.g. pancreatic and/or brush border.
  • HMOs are found in the human breast milk. Each individual HMO is based on a combination of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose and/or N-acetylglucosamine with many and varied linkages between them. So far over 130 such structures have been identified in human milk.
  • the HMOs can be acidic (e.g. charged sialic acid containing oligosaccharide) or neutral (e.g. fucosylated oligosaccharide).
  • the HMO is selected from the group of fucosylated oligosaccharides, N-acetylated oligosaccharides and sialylated oligosaccharides.
  • the HMO is a "fucosylated oligosaccharide". These are HMOs having a fucose residue. It has a neutral nature. Some examples are 2'-FL (2'-fucosyllactose), 3-FL (3-fucosyllactose), difucosyllactose, lacto-N-fucopentaose (e.g.
  • lacto-N- fucopentaose I lacto- N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V)
  • lacto-N-fucohexaose lacto-N- difucohexaose I, fucosyllacto-N-hexaose, fucosyllacto- N-neohexaose, difucosyllacto-N-hexaose I, difucosyllacto-N-neohexaose II and any combination thereof.
  • the fucosylated oligosaccharide is selected from the group comprising 2’-FL, 3-FL and difucosyllactose (e.g. 2’,2”-DiFL and/or 3, 2’-DiFL).
  • the fucosylated oligosaccharide is 2’-FL.
  • the HMO is a ”N-acetylated oligosaccharide.
  • the term ”N-acetylated oligosaccharide(s)” encompasses both "N-acetyl-lactosamine” and "oligosaccharide(s) containing N-acetyl-lactosamine". They are neutral oligosaccharides having an N-acetyl-lactosamine residue. Suitable examples are LNT (lacto-N-tetraose), para-lacto-N- neohexaose (para-LNnH), LNnT (lacto-N-neotetraose) or any combination thereof.
  • N-acetylated oligosaccharide is selected from the group of LNT and LNnT.
  • the HMO is a ’’sialylated oligosaccharide.
  • the term ’’sialylated oligosaccharide encompasses an oligosaccharide having a sialic acid residue. It has an acidic nature. Some examples are 3’-SL (3'-sialyllactose) and 6’-SL (6'-sialyllactose). In a preferred embodiment the sialylated oligosaccharide is 6’-SL.
  • the HMO is selected from the group comprising 2’-FL, 3-FL, difucosyllactose (e.g. 2’,2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL and/or any combination thereof.
  • the HMO is selected from the group comprising 2’-FL, difucosyllactose (e.g. 2’,2”-DiFL and/or 3,2’-DiFL), LNT, LNnT and 6’-SL and/or any combination thereof.
  • the HMO is selected from the group comprising 2’-FL, LNT, LNnT and 6'-SL and/or any combination thereof.
  • C3-C4-alkane carboxylic acid or derivative thereof encompasses propionic acid, n-butyric acid and iso-butyric acid (2-methyl propionic acid) as well as derivatives thereof and/or any mixture thereof.
  • Suitable derivatives are salts, esters and amides, in particular physiologically acceptable ones.
  • physiologically acceptable salts are alkali salts, like sodium or potassium salts, or alkaline-earth salts, like magnesium or calcium salts, or choline salts.
  • physiologically acceptable salts are alkali salts, in particular sodium salts or potassium salts, especially sodium salts.
  • physiologically acceptable esters are those derived from C1-C6 alcohols, in particular those derived from monohydric C1-C6 alcohols, e.g.
  • physiologically acceptable esters are glycerides, like mono-, di-, or triglycerides, in particular mono- or diglycerides.
  • physiologically acceptable esters are those derived from monohydric C1-C6 alcohols, e.g. those derived from methanol or ethanol, or mono- or diglycerides.
  • physiologically acceptable amides are those derived from mono- or di-C1-C6-alkyl amines.
  • the C3-C4 alkane carboxylic acid is provided as physiologically acceptable derivative thereof; in particular the derivative is a physiologically acceptable salt, e.g. a sodium salt or potassium salt, or a mixture thereof, or a physiologically acceptable ester, e.g. said ester is derived from C1-C6 alcohols, in particular a mono-or a dihydric C1-C6 alcohol, or said ester is a mono- or diglyceride, or a mixture thereof.
  • a physiologically acceptable salt e.g. a sodium salt or potassium salt, or a mixture thereof
  • a physiologically acceptable ester e.g. said ester is derived from C1-C6 alcohols, in particular a mono-or a dihydric C1-C6 alcohol, or said ester is a mono- or diglyceride, or a mixture thereof.
  • the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate or sodium butyrate or potassium butyrate or a mixture thereof. Especially, it is sodium propionate or sodium butyrate or a mixture thereof.
  • the C3-C4-alkane carboxylic acid or derivative thereof is propionic acid or a derivative thereof, in particular it is a physiologically acceptable salt of propionic acid, especially it is sodium propionate or potassium propionate, or a physiologically acceptable ester of propionic acid, especially methyl propionate or ethyl propionate or propionic acid monoglyceride or propionic acid diglyceride, particularly ethyl propionate or propionic acid monoglyceride.
  • the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate.
  • the C3-C4-alkane carboxylic acid or derivative thereof is butyric acid or a derivative thereof, in particular it is a physiologically acceptable salt of butyric acid, especially it is sodium butyrate or potassium butyrate, or a physiologically acceptable ester of butyric acid, especially methyl butyrate or ethyl butyrate or butyric acid monoglyceride or butyric acid diglyceride, particularly ethyl butyrate or butyric acid monoglyceride.
  • the C3-C4- alkane carboxylic acid or derivative thereof is sodium butyrate or potassium butyrate.
  • the at least one C3-C4-alkane carboxylic acid or derivative thereof is a mixture of propionic acid and butyric acid or derivatives thereof, in particular it is a mixture of physiologically acceptable salts of propionic acid and butyric acid, especially it is a mixture of sodium propionate and sodium butyrate or a mixture of potassium propionate and potassium butyrate, or a mixture of physiologically acceptable esters of propionic acid and butyric acid, especially a mixture of methyl propionate and methyl butyrate, or a mixture of ethyl propionate and ethyl butyrate, or a mixture of propionic acid monoglyceride and butyric acid monoglyceride, or a mixture of propionic acid diglyceride and butyric acid diglyceride, particularly a mixture of ethyl propionate and ethyl butyrate or a mixture of propionic acid monoglyceride and butyric acid monoglyceride.
  • vitamin K2 compound relates to a menaquinone-n (abbreviated MK-n), wherein n represents the number of the isoprenyl units in the side chain which is linked to the 3 position of 2-methyl- 1 ,4-naphtochinone.
  • n can be from 2 to 14, preferably from 4 to 14, in particular n is 6 or 7, even more particular n is 7 (MK-7).
  • MK-7 menaquinone-n
  • the vitamin K2 compound is in all-trans form.
  • n is preferably 4 (MK-4), and in particular MK-4 is in all- trans form.
  • the at least one vitamin K2 compound is a mixture of two or more MK-n, preferably of MK-6 and MK-7. Preferably these are in all-trans form.
  • composition II comprises i) at least one HMO, and ii) at least one vitamin K2 compound.
  • composition II comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • composition II does not comprise one or more C3-C4- alkane carboxylic acid or derivative(s) thereof.
  • composition II comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii)as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the composition II comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, wherein the ratio of the at least one HMO (component A) and the at least one vitamin K2 compound (component C) is from 1000:1 to 1000000:1.
  • the at least one HMO and the at least one vitamin K2 compound are present in synergistic amounts.
  • composition II does not comprise one or more C3- C4-alkane carboxylic acid or derivative(s) thereof.
  • the composition II comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, wherein the ratio of the at least one HMO (component A) and the at least one vitamin K2 compound (component C) is from 1000:1 to 1000000:1 , and/or wherein the ratio of the at least one HMO (component A) and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) is from 100 : 1 to 1 : 100, preferably from 20:1 to 1 :20, more preferably 10:1 to 1 :10, even more preferably from 3: 1 to 1 :3, in particular2:1 to 1 :2, and/or wherein the ratio of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) and the at least one vitamin K2
  • said composition II comprises as at least one C3- C4-alkane carboxylic acid or derivative(s) thereof a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof, in a ratio of from 100 : 1 to 1 : 100, preferably from 20:1 to 1 : 20, more preferably from 10:1 to 1 :15, even more preferably from 2:1 to 1 :8.
  • the at least one HMO and the at least one the vitamin K2 compound are present in synergistic amounts.
  • the at least one HMO and the at least one C3-C4- alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.
  • the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound are present in synergistic amounts.
  • the at least one HMO, the at least one vitamin K2 compound and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.
  • the total amount of the at least one HMO and the at least one vitamin K2 compound, and optionally the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 1 to 100 wt% of the total composition II, preferably from 10 to 100 wt%.
  • the total amount of the at least one HMO is from 10 to 99.99999 wt% of the total composition II, preferably from 20 to 99.9999 wt%, more preferably from 30 to 99.999 wt%, even more preferably from 40 to 99.9 wt%. In yet another embodiment the total amount of the at least one HMO is from 5 to 50 wt% of the total composition II, preferably from 8 to 40 wt%, more preferably from 10 to 35 wt%, even more preferably from 15 to 30 wt%. In yet another embodiment the total amount of the at least one HMO is from 50 to 95 wt% of the total composition II, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • the total amount of the at least one vitamin K2 compound is from 0.00001 to 1 wt% of the total composition II, preferably from 0.0001 to 0.1 wt%.
  • the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 90 wt% of the total composition II, preferably from 15 to 85 wt%, more preferably from 20 to 75 wt%, even more preferably from 25 to 60 wt%. In yet another embodiment the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 50 wt% of the total composition II, preferably from 15 to 45 wt%, more preferably from 20 to 35 wt%.
  • the total amount of the at least one C3-C4- alkane carboxylic acid or derivative(s) thereof is from 50 to 90 wt% of the total composition II, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • the composition II can further comprise one or more vitamins or related compounds thereto, other than a vitamin K2 compound.
  • vitamins and related compounds thereto include vitamin A (e.g. retinol, retinyl acetate, retinyl palmitate, retinyl stearate, retinyl esters with other long-chain unsaturated fatty acids, retinal, retinoic acid and the like), vitamin B1 (e.g. thiamine, thiamine pyrophosphate, TPP, thiamine triphosphate, TTP, thiamine hydrochloride, thiamine mononitrate and the like), vitamin B2 (e.g.
  • vitamin B3 e.g. nicotinic acid, nicotinamide, nicotinamide adenine dinucleotide (NAD), nicotinic acid mononucleotide (NicMN), pyridine-3-carboxylic acid and the like, as well as the vitamin B3-precursor tryptophan
  • pantothenic acid e.g. pantothenate, panthenol and the like
  • vitamin B6 e.g.
  • pyridoxine pyridoxal, pyridoxamine, pyridoxine hydrochloride and the like
  • biotin folic acid (e.g. folate, folacin, pteroylglutamic acid and the like)
  • vitamin B12 e.g. cobalamin, methylcobalamin. deoxyadenosylcobalamin, cyanocobalamin, hydroxycobalamin, adenosylcobalamin and the like
  • vitamin E e.g.
  • alpha-, beta-, gamma- and/or delta-tocopherol alpha-, beta-, gamma- and/or delta- tocopherol acetate, alpha-, beta-, gamma- and/or delta-tocopherol succinate, alpha-, beta-, gamma- and/or delta-tocopherol nicotinate, alpha-, beta-, gamma- and/or delta tocotrienol and the like), vitamin K (e.g. vitamin K1 , phylloquinone, naphthoquinone, vitamin K3, menadione, and the like ), vitamin C (ascorbic acid), vitamin D (e.g. calciferol, cholecalciferol, 1 ,25-dihydroxyvitamin D, ergocaliferol and the like), and the like and/or mixtures thereof.
  • vitamin K e.g. vitamin K1 , phylloquinone, naphthoquinon
  • composition II does not comprise one or C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more vitamins or related compounds thereto, other than at least one vitamin K2 compound.
  • composition II does comprise one or more vitamins or related compounds thereto.
  • composition II can further comprise one or more carotenoids.
  • carotenoids include astaxanthin, alpha-carotene, beta-carotene, beta- cryptoxanthin, lutein, lycopene, meso-zeaxanthin, zeaxanthin and the like (including cis/trans isomers) and/or mixtures thereof. The presence and amounts of specific carotenoids will vary depending on the intended use.
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more carotenoids.
  • the composition II can further comprise one or more medium-chain fatty acids.
  • These medium-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or alkyl esters.
  • Examples of medium-chain fatty acids include caproic acid, caprylic acid, capric acid, lauric acid and the like and /or mixtures thereof.
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more medium-chain fatty acids.
  • composition II can further comprise one or more long-chain fatty acids.
  • long-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or as alkyl esters.
  • long chain fatty acids include saturated long chain fatty acids (e.g.
  • linoleic acid linoelaidic acid, alpha-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentenoic acid, docosahexaenoic acid and the like and/or mixtures thereof) and/or mixtures thereof.
  • These long chain fatty acids are comprised for example in vegetable oils, single cell oils and marine oils, e.g. fish oil, krill oil and the like.
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more long-chain fatty acids.
  • composition II can further comprise one or more prebiotics.
  • prebiotics include water-insoluble fibers (e.g. lignin, cellulose, hemi- cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof), water-soluble fibers (e.g.
  • arabinoxylan arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof
  • other oligosaccharides like xylooligosaccharides, fructooligosaccharides, galactooligosaccharides, isomalto-oligosaccharides and the like and/or mixtures thereof
  • water-insoluble fibers e.g. lignin, cellulose, hemi- cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof
  • water-soluble fibers e.g.
  • arabinoxylan arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof) and the like and/or mixtures thereof.
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof. In a specific embodiment composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more prebiotics.
  • composition II can further comprise one or more probiotics.
  • probiotics optionally present in the composition II of the present invention include microorganisms or parts thereof of the family Lactobacillaceae, e.g. of the genus Lactobacillus (e.g. the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii (like lactobacillus delbrueckii spp. bulgaricus, lactobacillus delbrueckii spp. delbrueckii, lactobacillus delbrueckii spp.
  • the family Lactobacillaceae e.g. of the genus Lactobacillus (e.g. the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii (like lactobacillus delbrueckii spp. bulg
  • lactis lactobacillus helveticus, lactobacillus plantarum, lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus salivarius and the like), of the genus Bifidobacterium (e.g. the species bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium lactis, bifidobacterium longum and the like), of the genus Pediococcus (e.g.
  • Lactococcus e.g. the species lactococcus lactis (like lactococcus latis spp. cremoris, lactococcus lactis spp. lactic and the like
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more probiotics.
  • composition II can further comprise one or more phenolic compounds.
  • phenolic compounds include monophenols (e.g. apiole, carnosol, carvacrol, dillapiole, rosemarinol and the like), flavonoids (e.g.
  • quercetin kaempferol, myricetin, fisetin, rutin, isorhamnetin, hesperidin, naringenin, silybin, eriodyctiol, acacetin, apigenin, chrysin, diosmetin, tangeritin, luteolin, catechins like epigallocatechin gallate, theaflavin, thearubigins, proanthocyanidins, pelargonidin, peonidin, cyanidin, delphinidin, malvidin, petunidin and the like), isoflavonoids (e.g.
  • daidzein genistein, glycitein and the like
  • aurones chalconoids
  • flavonolignans lignans
  • phytoestrogens stilbenoids (e.g. resveratrol, pterostilbene, piceatannol and the like)
  • curcuminoids e.g. curcumin and the like
  • tannins aromatic acids (e.g. salicylic acid, vanillic acid, gallic acid, ellagic acid, tannic acid, caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumarin and the like), phenylethanoids (e.g. tyrosol, hydroxytyrosol, oleocanthal, oleuropein and the like ), capsaicin, gingerol, alkylresorcinol and the like and/or mixtures thereof.
  • aromatic acids e.g. salicylic acid, vanillic acid, gallic acid
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more phenolic compounds.
  • composition II can further comprise one or more herbals, e.g. known from Chinese diets, Indian diets, Mediterranean diets and the like. These herbals can be provided as powders obtained from the plant and/or fungus or parts thereof or as extracts thereof.
  • herbals e.g. known from Chinese diets, Indian diets, Mediterranean diets and the like. These herbals can be provided as powders obtained from the plant and/or fungus or parts thereof or as extracts thereof.
  • herbals known from Chinese diets include extracts or powders of hawthorn fruit, wolfberry, spatholobus stem, caterpillar fungus, cloud mushroom, crysanthemum, honeysuckle flower, mulberry leaf, glossy privet fruit, malaytea scurfpea fruit, cherokee rose fruit, palmleaf raspberry fruit, Chinese magnoliavine fruit, reishi mushroom, ephedra, epimedium, Angelica root, Astragalus root, rhubarb, licorice, morinda root, notoginseng, white peony root, American ginseng, fleeceflower root, kudzu root, rehmannia root, salvia root, Chinese yam, wild buckwheat rhizome, tall gastrodia tuber, golden root, Cassia seed, Coix seed, Dodder seed and the like and/or mixtures thereof.
  • herbals known from Indian diets include extracts or powders of Amalaki (Indian gooseberry), Haritaki (chebulic myrobalan), Bibhitaki (beleric), Haldi (turmeric), Tulsi (holy basil), Shigru (moringa), Twak (cinnamon), Yashtimadhu (licorice root), Dhanyaka (coriander), Ashwagandha (winter cherry), Kumkuma (saffron), Manjistha (Indian madder), Brahmi (bacopa), Neem (margosa), Ajwain (Bishop’s weed), Elaichi (cardamom), Shikakai (Acacia concinna), Shatavari (wild asparagus), Jeera (cumin), Guduchi (tinospora) and the like and/or mixtures thereof.
  • Examples for herbals known from Mediterranean diets include extracts or powders of rosemary, basil, parsley, saffron, thyme, oregano, sage, cilantro, lemon, orange, grape, grapeseed, fig, blueberry, raspberry, strawberry, cherry, fennel, sesame seeds, pine seeds, garlic, onion, ginger root, pepper, chili and the like, olive oil and/or mixtures thereof.
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more herbals.
  • composition II can further comprise one or more minerals.
  • minerals include such ones comprising calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum and the like and/or mixtures thereof. Minerals are usually added in salt form.
  • composition II does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II does not comprise one or more minerals. In a further embodiment of the present invention the composition II does not comprise a mineral comprising iron.
  • composition II does not comprise one or more antibodies.
  • the compositions II of the present invention can be prepared by mixing the at least one HMO, and the at least one vitamin K2 compound, optionally the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally further components e.g. vitamins and related compounds thereto, carotenoids, medium chain fatty acids, long chain fatty acids, prebiotics, probiotics, phenolic compounds, herbals, minerals and the like and/or mixtures thereof, as known in the art.
  • the composition II does not comprise more than 80 wt% water.
  • the present invention provides a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for use as a medicament, preferably as a medicament for mammals, birds and/or fishes, in particular as a medicament for mammals.
  • the term ’’mammals encompasses humans and nonhuman mammals.
  • non-human mammals are livestock, e.g. sheep, goats, pigs, cattles, horses, camels, llamas and the like, and pets, e.g. cats, dogs and the like.
  • composition II is for use as a medicament for humans.
  • composition II is for use as a medicament for livestock and/or pets.
  • composition II is for use as a medicament for birds, e.g. poultry (like chickens, ducks, geese, turkeys and the like) and ornamental birds (like canaries and the like).
  • birds e.g. poultry (like chickens, ducks, geese, turkeys and the like) and ornamental birds (like canaries and the like).
  • composition II is for use as a medicament for fishes, e.g. fishes used for consumption (like salmon, tuna, sardines, cod, trout, and the like) and ornamental fishes (like kois and the like).
  • fishes e.g. fishes used for consumption (like salmon, tuna, sardines, cod, trout, and the like) and ornamental fishes (like kois and the like).
  • compositions II of the present invention for use as a medicament can be administered orally, enterally or parenterally, preferably orally.
  • the composition II for use as a medicament is an orally administrable composition.
  • composition II comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4-, and optionally iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for use as a medicament, preferably as a medicament for humans.
  • composition II shall be applicable for the compositions II for use as a medicament and the specific embodiments thereto.
  • the present invention provides a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the use in the treatment and/or prevention of hypertension and/or associated morbidities thereto, preferably of mammals, more preferably of humans.
  • the term ’’’treatment” in the context of hypertension and/or associated morbidities thereto means using an effective therapy or management to alleviate, reduce or cure the condition and/or disease (hypertension and/or associated morbidities thereto) and/or symptoms thereof, as the case may be, in addition it also includes the stabilization of the condition and/or disease, as the case may be, in order not to worsen in the course of the respective condition and/or disease.
  • treatment is understood as using an effective therapy or management to stabilize, alleviate or reduce the condition and/or disease and/or symptoms thereof, as the case may be.
  • the term ’’prevention” in the context of hypertension and/or associated morbidities thereto means an effective therapy or management so that the condition and/or disease (hypertension and/or associated morbidities thereto) does not de novo develop, manifest and/or symptoms thereof do not occur.
  • composition II is for use in the treatment of hypertension and/or associated morbidities thereto. In another embodiment of the present invention the composition II is for use in the prevention of hypertension and/or associated morbidities thereto.
  • hypotension refers to a condition and/or disease, as the case may be, which is characterized by an increased blood pressure compared to a normal blood pressure, which is defined by the American Heart Association as being in the range of 90-119 mmHg (systolic) and 60-79 mmHg (diastolic) of a respective subject.
  • hypertension stage 1 hypertension stage 2
  • hypertensive crisis refers to a blood pressure of above 180 mmHg systolic and above 120 mmHg diastolic of a respective subject
  • isolated systolic hypertension refers to a blood pressure from 120-129 mmHg systolic and 60-79 mmHg diastolic of a respective subject
  • hypertension stage 1 refers to a pressure from 130-139 mmHg systolic and 80-89 mmHg diastolic of a respective subject
  • hypertension stage 2 from a pressure above 140 mmHg systolic and above 90 mmHg diastolic of a respective subject
  • hypertensive crisis refers to a blood pressure of above 180 mmHg systolic and above 120 mmHg diastolic of a respective subject
  • isolated sysystolic refers to a blood pressure from 120 mmHg
  • composition II is for use in the treatment or prevention of hypertension of a human.
  • composition II is for use in the treatment or prevention of pre-hypertension of a human, or in another embodiment of hypertension stage 1 of a human, or in another embodiment of hypertension stage 2 of a human, or in another embodiment of hypertensive crisis of a human, or in another embodiment of isolated systolic hypertension of a human, or in another embodiment of isolated diastolic hypertension of a human.
  • associated morbidities as well as the term ’’morbidities associated to” mean one or more conditions and/or diseases which are co-occurring to the primary condition or disease (hypertension), or which are occurring later in the life of the subject who had earlier in his or her life said primary condition and/or disease (hypertension).
  • the composition II is for use in the treatment or prevention of an associated morbidity, e.g. an associated morbidity of the cardiovascular system, which includes atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms, peripheral vascular disease etc., an associated morbidity of the renal system, which includes hypertensive nephropathy, chronic renal failure etc., an associated morbidity of the nervous system, which includes headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia, convulsion etc., an associated morbidity of the vision system, which includes hypertensive retinopathy, vision loss etc., and the like, in particular of a human.
  • an associated morbidity e.g. an associated morbidity of the cardiovascular system, which includes atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms
  • composition II is for use in the treatment or prevention of an associated morbidity of the cardiovascular system, in particular of a human subject having hypertension.
  • composition II is for use in the treatment or prevention of atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms and/or peripheral vascular disease, in particular of a human subject having hypertension.
  • composition II is for use in the treatment or prevention of an associated morbidity of the renal system, in particular of a human subject having hypertension.
  • composition II is for use in the treatment or prevention of hypertensive nephropathy and/or chronic renal failure, in particular of a human subject having hypertension.
  • composition II is for use in the treatment or prevention of an associated morbidity of the nervous system, in particular of a human subject having hypertension.
  • composition II is for use in the treatment or prevention of headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia and/or convulsion, in particular of a human subject having hypertension.
  • composition II is for use in the treatment or prevention of an associated morbidity of the vision system, in particular of a human subject having hypertension.
  • composition II is for use in the treatment or prevention of hypertensive retinopathy and/or vision loss, in particular of a human subject having hypertension.
  • composition II for use in the treatment or prevention of hypertension is an orally administrable composition, in particular for a human subject.
  • composition II for use in the treatment or prevention of morbidities associated to hypertension is an orally administrable composition, in particular for a human subject.
  • the composition II comprises i) at least one HMO, and ii) at least one vitamin K2 compound, for use in the treatment or prevention of hypertension and/or associated morbidities thereto, in particular of a mammal, especially of hypertension of a human or especially of morbidities associated to hypertension.
  • composition II comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for use in the treatment or prevention of hypertension and/or associated morbidities thereto of a mammal, in particular of hypertension of a human, or in particular of morbidities associated to hypertension of a human.
  • composition II for use in the treatment or prevention of hypertension and/or associated morbidities thereto, in particular of a mammal, especially of hypertension of a human or especially of morbidities associated to hypertension of a human does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the composition II comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for use in the treatment or prevention of hypertension and/or associated morbidities thereto of a mammal, in particular of hypertension of a human, or in particular of morbidities associated to hypertension of a human.
  • the composition II comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for use in the treatment or prevention of hypertension and/or associated morbidities thereto of a mammal, in particular of hypertension of a human, or in particular of morbidities associated to hypertension of a human.
  • composition II shall be applicable for the compositions II for use in the treatment or prevention of hypertension and/or associated morbidities thereto and the specific embodiments thereto.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • said method is for treating a subject having hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • said method is for treating a subject having morbidities associated to hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing morbidities associated to hypertension, in particular a human.
  • said human subject is in the age of 12 years or older, preferably 18 years or older, more preferably 35 years or older, in particular 50 years or older, even more particular 60 years or older.
  • composition II can be administered, preferably orally, or that any of the “at least one HMO” and the “at least one K2 compound” and optional the “at least one C3- C4-alkane carboxylic acid or derivative(s) thereof’ and optional further components can be administered separately, preferably orally.
  • composition II comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the composition II comprises as at least one vitamin K2 compound two or more vitamin K2 compounds that these can be administered separately, preferably orally, and in case the composition II comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that these can be administered separately, preferably orally.
  • the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.
  • the daily application rate of the at least one vitamin K2 compound is from 1 to 1000 meg, preferably from 10 to 200 meg, in particular from 20 to 150 meg, especially from 30 to 100 meg.
  • the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g.
  • the propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1 .0 to 4.0 g/day.
  • the butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1 .0 to 5.0 g/day.
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition II which comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of said composition II which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method to treat a subject having a disease, in particular hypertension and/or associated morbidities thereto, or to prevent a subject being suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the composition II which comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the embodiments mentioned for the composition II shall be applicable for the use of the composition II in this method accordingly and in the specific embodiments thereto.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II, which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for the manufacture of a medicament, preferably for the treatment or prevention of hypertension and/or associated morbidities thereto.
  • the medicament manufactured as mentioned above is for treating a subject having hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • the medicament manufactured as mentioned above is for treating a subject having morbidities associated to hypertension, in particular a human, or preventing a subject being suspected of having or being at risk of developing morbidities associated to hypertension, in particular a human.
  • composition II shall be applicable for the use of the composition II in this use accordingly and in the specific embodiments thereto.
  • the present invention provides a nutritional supplement comprising a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the term “nutritional supplement” means a manufactured product intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of hypertension and/or associated morbidities thereto.
  • nutritional supplements include “dietary supplements” and “medical foods”.
  • a dietary supplement is intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, however it needs not to be used under medical supervision.
  • a medical food is also intended to supplement a diet, in particular of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, but it is under medical supervision.
  • the terms “medical foods” and “food for special medical purpose” are interchangeable.
  • the nutritional supplement can comprise said composition II or that the nutritional supplement can comprise any of the “at least one HMO” and the “at least one vitamin K2 compound” and optional the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional further components in separate form.
  • the nutritional supplement is a dietary supplement.
  • the nutritional supplement is a medical food.
  • the nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension.
  • the nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.
  • the daily application rate of the at least one vitamin K2 compound is from 1 to 1000 meg, preferably from 10 to 200 meg, in particular from 20 to 150 meg, especially from 30 to 100 meg.
  • the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g.
  • propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1 .0 to 4.0 g/day.
  • butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day.
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 1 .0 to 3.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 1 .5 to 4.0 g.
  • said subject is a human, preferably in the age of 12 years or older, more
  • the nutritional supplement can be administered, preferably orally, or that any of the “at least one HMO” and the “at least one vitamin K2 compound” and the optional “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional further components can be administered separately, preferably orally.
  • the nutritional supplement comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the nutritional supplement comprises as at least one vitamin K2 compounds two or more vitamin K2 compounds that these can be administered separately, preferably orally, and in case the nutritional supplement comprises as at least one C3- C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that these can be administered separately, preferably orally.
  • the present invention provides a nutritional supplement comprising a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition II which comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition II which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • a nutritional supplement comprising a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a nutritional supplement comprising a composition II which comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • a composition II which comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • said nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension.
  • said nutritional supplement is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the nutritional supplement which comprises a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the nutritional supplement can comprise said composition II or that the nutritional supplement can comprise any of the “at least one HMO” and the “at least one vitamin K2 compound” and optional the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional further components in separate form.
  • composition II comprises as at least one HMO two or more HMOs that these can be administered separately, preferably orally, and in case the composition II comprises as at least one vitamin K2 compound two or more vitamin K2 compounds that these can be administered separately, preferably orally, and in case the composition II comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that these can be administered separately, preferably orally.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition II, which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the nutritional supplement which comprises a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II, which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for the manufacture of a nutritional supplement, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the nutritional supplement manufactured as mentioned above is for the dietary management of a subject having hypertension, in particular a human, or a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • the nutritional supplement manufactured as mentioned above is for the dietary management of a subject having hypertension, in particular a human, or a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • composition II shall be applicable for the use of the composition II in this use accordingly and in the specific embodiments thereto.
  • Both, the medicament (in general and for the respective specific use) and the nutritional supplement (in general and for the respective specific use) of the present invention can be delivered in any suitable format.
  • Formulations suitable for oral administration may be in the form of capsules, tablets, pills, dragees, lozenges (using a flavored basis, usually sucrose and acacia ortragacanth), powders, granules, and the like or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as pastilles (using an inert base, such as gelatin and glycerin, or sucrose and acacia), each comprising a predetermined amount of the at least one HMO, the at least one vitamin K2 compound, optional the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and optional further components.
  • active ingredients of said medicament and nutritional supplement can be delivered together in a respective suitable format or that each of component A and component C and optionally component B can be delivered in a respective format or that each of the active ingredients can be delivered in a respective format, or any combination thereof.
  • the desired components of the composition II may be mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar- agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as acetriglyceride
  • powders and/or granules can be reconstituted with water or another aqueous liquid prior to consumption.
  • the so obtained liquid does not comprise more than 80 wt% water.
  • liquid formulations do not comprise more than 80 wt% water.
  • the present invention provides a functional food comprising a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the term “functional food” means a food which is fortified with the composition II according to the present invention and intended to be used in a diet, in particular of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the terms “functional food” and “fortified food” are interchangeable.
  • Examples for foods being suitable for the preparation of functional foods are (1) dairy products e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof; (2) bakery products e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof; (3) candy products e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof; (4) beverage products e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof.
  • dairy products e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof
  • bakery products e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof
  • candy products e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof
  • beverage products e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof.
  • the functional food can comprise said composition II or that the functional food can comprise any of the “at least one HMO” and the “at least one vitamin K2 compound” and optional the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional further components in separate form.
  • composition II comprises as the at least one HMO two or more HMOs these can be comprised separately in the functional food or together as composition
  • composition II comprises as the at least one vitamin K2 compound two or more vitamin K2 compounds these can be comprised separately in the functional food or together as composition
  • composition II comprises as the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof these can be comprised separately in the functional food or together as composition.
  • the functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the daily application rate of the at least one HMO is from 0.1 to 20.0 g, preferably from 1.0 to 15.0 g, more preferably from 2.0 to 10.0 g, in particular from 2.5 to 5.0 g.
  • the daily application rate of the at least one vitamin K2 compound is from 1 to 1000 meg, preferably from 10 to 200 meg, in particular from 20 to 150 meg, especially from 30 to 100 meg.
  • the daily application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is 0.1 to 10.0 g, preferably from 1.0 to 9.0 g, more preferably from 1.2 to 9.0 g, in particular from 2.0 to 8.0 g, especially from 2.5 to 6.0 g.
  • propionic acid and/or a derivative thereof can be administered in an application rate from 0.1 to 6.0 g/day, preferably from 0.5 to 5.0 g/day, more preferably from 1 .0 to 4.0 g/day.
  • butyric acid and/or a derivative thereof can be administered in an application rate from 0.1 to 9.0 g/day, preferably from 0.5 to 7.0 g/day, more preferably from 1.0 to 5.0 g/day.
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g
  • the daily application rate of propionic acid and/or a derivative thereof is from 1 .0 to 3.0 g
  • the daily application rate of butyric acid and/or a derivative thereof is from 1 .5 to 4.0 g.
  • said subject is a human, preferably in the age of 12 years or older, more preferably 18 years or older, even more preferably 35 years or older, in particular 50 years or older, even more in particular 60 years and older.
  • the present invention provides a functional food comprising a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a functional food comprising a composition II which comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • a functional food comprising a composition II which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto.
  • the present invention provides a functional food comprising a composition II which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a functional food comprising a composition II which comprises i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4 B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • said functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension.
  • said functional food is for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides a method for the dietary management of a subject having, being suspected to have or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the “at least one HMO” and the “at least one vitamin K2 compound” and optional the “at least one C3-C4-alkane carboxylic acid or derivative(s) thereof’ and optional further components can be comprised separately in the functional food or together as composition.
  • composition II comprises as at least one HMO two or more HMOs that these can be comprised separately in the functional food or together as composition
  • composition II comprises as at least one vitamin K2 compound two or more vitamin K2 compounds that also these can be comprised separately in the functional food or together as composition
  • composition II comprises as at least one C3-C4-alkane carboxylic acid or derivative(s) thereof two or more C3-C4-alkane carboxylic acid or derivative(s) thereof that also these can be comprised separately in the functional food or together as composition.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of a functional food which comprises a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • a functional food which comprises a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition II, which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a method for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, by administering to the subject an effective amount of the functional food which comprises a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing hypertension.
  • said method is for the dietary management of a subject having, being suspected of having or being at risk of developing morbidities associated to hypertension.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II, which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, for the manufacture of afunctional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the present invention provides the use of a composition II comprising i) as component A 2’-FL, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, for the manufacture of a functional food, preferably for the dietary management of subjects having, being at risk or developing hypertension and/or associated morbidities thereto.
  • the functional food manufactured as mentioned above is for the dietary management of a subject having hypertension, in particular a human, or a subject being suspected of having or being at risk of developing hypertension, in particular a human.
  • the nutritional supplement manufactured as mentioned above is for the dietary management of a subject having morbidities associated to hypertension, in particular a human, or a subject being suspected of having or being at risk of developing morbidities associated to hypertension, in particular a human.
  • composition II shall be applicable for the use of the composition II in this use accordingly and in the specific embodiments thereto.
  • the functional food of the present invention can be prepared by known techniques and it can have any suitable type of format such as (1) a dairy product e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof; (2) a bakery product e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof; (3) a candy product e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof; (4) a beverage product e.g. fruit juice, vegetable juice, lemonade, water and the like or mixtures thereof.
  • a dairy product e.g. yogurt, dessert, smoothie, milk and the like or mixtures thereof
  • a bakery product e.g. bread, rolls, pasta, cookie, cake, cereal bar and the like or mixtures thereof
  • a candy product e.g. candies, gummies, chewing gum, chocolate, pudding, cookie and the like or mixtures thereof
  • (4) a beverage product e.g. fruit juice, vegetable juice, lemonade
  • composition II the composition II for use as a medicament, the composition II for use in the treatment or prevention of hypertension and/or associated morbidities thereto, the nutritional supplement and the functional food, in particular for use in the dietary management of hypertension and/or associated morbidities thereto, respectively, as disclosed herein, can be co-administered to subjects receiving at least one pharmaceutical against said hypertension and/or associated morbidities thereto.
  • pharmaceuticals used in the treatment of hypertension are thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan.
  • the present invention provides a method to treat a subject having hypertension and/or associated morbidities thereto, by administering to the subject a) an effective amount of a composition II, a composition II for use as a medicament, a composition II for use in the treatment or prevention of hypertension and/or associated morbidities thereto, a nutritional supplement or a functional food, in particular for use in the dietary management of hypertension and/or associated morbidities thereto, which comprises i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof; and b) an effective amount of at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto, in particular, wherein the application rate of the at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto is reduced compared to a treatment with the at least one pharmaceutical alone.
  • the hypertension and/or associated morbidities thereto is hypertension and the pharmaceutical is a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g. verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors (e.g.
  • captopril enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g. azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan.
  • the present invention provides a composition
  • a composition comprising a) i) at least one HMO, and/or ii) at least one vitamin K2 compound, and/or iii) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof; and b) an effective amount of at least one pharmaceutical, in particular for use as a medicament, especially for use in the treatment of hypertension and/or associated morbidities thereto.
  • the present invention provides a composition
  • a composition comprising a) i) as component A 2’-FL, and/or ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and/or iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and/or sodium butyrate; and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the present invention provides a composition
  • a composition comprising a) as component A at least one HMO, preferably 2’-FL, and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the present invention provides a composition
  • a composition comprising a) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the present invention provides a composition
  • a composition comprising a) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and/or sodium butyrate and b) a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • the composition II, the composition II for use as a medicament, the composition II for use in the treatment or prevention of hypertension, the nutritional supplement or a functional food, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension, especially of subjects having hypertension, used in said method comprises 2’-FL, and/or MK-7 or a mixture of MK-6 and MK-7 or MK-4, and/or propionic acid and/or butyric acid or derivative(s) thereof, preferably 2’-FL, MK-7 or MK-4, and/or optionally preferably sodium propionate and sodium butyrate.
  • composition II in another embodiment, the composition II for use as a medicament, the composition II for use in the treatment or prevention of a morbidity associated to hypertension, the nutritional supplement or a functional food, in particular for use in the dietary management of subjects having, being suspected of having or being at risk of developing a morbidity associated to hypertension, especially of subjects having morbidity associated to hypertension, used in said method comprises 2’-FL, and/or MK-7 or a mixture of MK-6 and MK-7 or MK-4, and/or optionally propionic acid and/or butyric acid or derivative(s) thereof, preferably 2’-FL, MK-7 or MK-4, and/or optionally preferably sodium propionate and sodium butyrate.
  • the nutritional supplement or the functional food is for use in the dietary management of hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of a morbidity associated to hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the cardiovascular system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms and/or peripheral vascular disease, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the renal system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of hypertensive nephropathy and/or chronic renal failure, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the nervous system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia and/or convulsion, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of an associated morbidity of the vision system, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the nutritional supplement or the functional food is for use in the in the dietary management of hypertensive retinopathy and/or vision loss, in particular of a human subject having or being suspected of having or at risk of developing hypertension.
  • the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising at least one HMO and a second component comprising at least one vitamin K2 compound and optionally a third component comprising at least one C3-C4- alkane carboxylic acid or derivative(s) thereof.
  • the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL, and a second component comprising MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and optionally a third component comprising propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • the present invention provides a kit for the pharmaceutical use or dietary management use comprising a first component comprising 2’-FL, a second component comprising MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and a third component comprising propionic acid or derivative(s) thereof, preferably sodium propionate and a forth component comprising butyric acid or derivative(s) thereof, preferably sodium butyrate.
  • the present invention provides said kit for the pharmaceutical use for the treatment or prevention of hypertension and/or associated morbidities thereto or for the dietary management use of the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, in particular of subjects having hypertension and/or associated morbidities thereto.
  • the present invention provides said kit for the pharmaceutical use for the treatment or prevention of hypertension or for the dietary management use of the dietary management of subjects having, being suspected of having or being at risk of developing hypertension, in particular of subjects having hypertension.
  • the present invention provides said kit for the pharmaceutical use for the treatment or prevention of morbidities associated to hypertension or for the dietary management use of the dietary management of subjects having, being suspected of having or being at risk of developing associated morbidities to hypertension, in particular of subjects having associated morbidities to hypertension.
  • the present invention provides a kit for the pharmaceutical use comprising a first component comprising at least one HMO, and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and optionally a third component comprising at least one vitamin K2 compound.
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is 2’-FL, a second component comprising a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • a pharmaceutical effective amount in a pharmaceutical effective amount
  • kits for the pharmaceutical use comprising a first component comprising at least one vitamin K2 compound, and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and optionally a third component comprising at least one HMO.
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, a second component comprising a a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • kits for the pharmaceutical use comprising a first component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and optionally a third component comprising at least one HMO and/or at least one vitamin K2 compound.
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, a second component comprising a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g.
  • a thiazide-diuretics e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide
  • a calcium channel blockers e.g.
  • angiotensin converting enzyme inhibitors e.g. captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril
  • angiotensin receptor blockers e.g.
  • a pharmaceutical effective amount in a pharmaceutical effective amount
  • a third component which is 2’-FL and/or optionally a third component which is MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • the present invention provides a kit for the pharmaceutical use comprising a first component comprising at least one HMO and a second component comprising a pharmaceutical, preferably a pharmaceutical for use in the treatment or prevention of hypertension and/or associated morbidities thereto, and a third component comprising at least one vitamin K2 compound. and a forth component comprising at least one C3-C4-alkane carboxylic acid or derivative(s) thereof
  • the present invention provides a kit for the pharmaceutical use comprising a first component which is 2’-FL, a second component comprising a thiazide-diuretics (e.g. hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (e.g. verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors (e.g.
  • captopril enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril) and/or an angiotensin receptor blockers (e.g.
  • a pharmaceutical effective amount in a pharmaceutical effective amount
  • a third component which is MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4
  • a forth component which is propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate.
  • butyric acid denotes n-butyric acid and the term “butyrate” denotes n-butyrate.
  • the term ”at least one HMO” is interchangeable with the term ’’component A”
  • the term ”at least one C3-C4-alkane carboxylic acid or a derivative thereof” is interchangeable with the term “component B”
  • the term “at least one vitamin K2 compound” is interchangeable with the term “component C”.
  • compositions comprising several components that these can also be administered separately. However, this means that such components can be administered together or separately, as the case may be. Also, within the context of the present invention, ratios given are weight to weight ratios unless stated otherwise. The weight unit “meg” stands for micro gram. In addition, in the context of the invention, the terms “comprising” or “comprises” do not exclude other possible elements.
  • the composition of the present invention including the embodiments described herein, can comprise, consist of, or consist essentially of the essential elements and limitations of the invention described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise depending on the needs.
  • compositions of the invention consist essentially of the essential elements, and even more particular consist of the essential elements.
  • the singular forms "a”, “an”, and “the” are inclusive of their plural forms, and the other way around, unless the context clearly indicates otherwise. It is to be understood that the embodiments of the subject matter of the invention can be applied in the specific context but also in other combinations, without leaving the scope of the invention. E.g. it is understood that the embodiments mentioned for the composition of the present invention also apply for composition for use as a medicament, etc. The same applies for the respective conditions and/or diseases.
  • composition II comprising i) at least one HMO, and ii) at least one vitamin K2 compound, and optionally iii) at least one C3-C4-alkane carboxylic acid or a derivative thereof.
  • composition II according to any one of embodiments 1-11 to 3-11, wherein one of the at least one HMO’s is a sialylated oligosaccharide.
  • composition II according to any one of embodiments embodiment 1-11 to 4-11, wherein one of the at least one HMO is 6’-sialyllactose (6’-SL).
  • LNT lacto-N-tetraose
  • composition II according to any one of embodiments 1-11 to 7-11, wherein the at least one
  • HMO is one or more HMOs selected from the group consisting of 2’-FL, 3-FL, difucosyllactose (in particular 2’,2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL.
  • composition II according to any one of embodiments 1-11 to 8-11, wherein the at least one
  • HMO is one, two or three HMOs selected from the group consisting of 2’-FL, 3-FL, difucosyllactose (in particular 2’, 2”-DiFL and/or 3, 2’-DiFL), LNT, LNnT, 3’-SL and 6’-SL.
  • composition II according to any one of embodiments 1-11 to 9-11, wherein the at least one
  • HMO is one, two or three HMOs selected from the group consisting of 2’-FL, LNT, LNnT, 3’-SL and 6’-SL.
  • composition II according to any one of embodiments 1-11 to 9-11, wherein the at least one
  • HMO is one, two or three HMOs selected from the group consisting of 2’-FL, 2’,2”-DiFL and 3,2’-DiFL.
  • composition II according to any one of embodiments 1-11 to 11-11 wherein the at least one
  • HMO is 2’-FL.
  • composition II according to any one of embodiments 1-11 to 14-11, wherein the at least on vitamin K2 compound is MK-4, MK-6, MK-7 or any mixture thereof.
  • composition II according to any one of embodiments 1-11 to 15-11, wherein the at least on vitamin K2 compound is MK-4, MK-7 or a mixture of MK-6 and MK-7.
  • composition II according to any one of embodiments 1-11 to 16-11 which does not comprise one or more C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II according to any one of embodiments 1-11 to 16-11 which comprise at least one C3-C4-alkane carboxylic acid or derivative(s) thereof.
  • composition II according to any one of embodiments 1-11 to 18-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof.
  • composition II according to any one of embodiments 1-11 to 19-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt or ester of propionic acid.
  • composition II according to any one of embodiments 1-11 to 20-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of propionic acid.
  • composition II according to any one of embodiments 1-11 to 21-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium salt of propionic acid.
  • composition II according to any one of embodiments 1-11 to 22-11 wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium propionate.
  • composition II according to any one of embodiments 1-11 to 20-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of propionic acid.
  • composition II according to any one of embodiments 1-11 to 24-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is butyric acid or a derivative thereof.
  • composition II according to any one of embodiments 1-11 to 25-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt or ester of butyric acid.
  • composition II according to any one of embodiments 1-11 to 28-11 wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium butyrate.
  • composition II according to any one of embodiments 1-11 to 26-11, wherein one of the at least one C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of butyric acid.
  • composition II according to any one of embodiments 1-11 to 30-11, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is propionic acid or a derivative thereof and butyric acid or a derivative thereof.
  • composition II according to any one of embodiments 1-11 to 31-11, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable salt of propionic acid and physiologically acceptable salt of butyric acid.
  • composition II according to any one of embodiments 1-11 to 32-11, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is an alkali salt or an alkaline earth salt of propionic acid and an alkali salt or an alkaline earth salt of butyric acid.
  • composition II according to any one of embodiments 1-11 to 33-11, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a sodium or potassium salt of propionic acid and a sodium or potassium salt of butyric acid.
  • composition II according to any one of embodiments 1-11 to 34-11 wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is sodium or potassium propionate and sodium or potassium butyrate.
  • composition II according to any one of embodiments 1-11 to 31-11, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a physiologically acceptable ester of propionic acid and a physiologically acceptable ester of butyric acid.
  • composition II according to any one of embodiments 1-11 to 36-11, wherein the at least one
  • C3-C4-alkane carboxylic acid or a derivative thereof is a C1-C6 alkyl ester or a mono- or diglyceride of propionic acid and a C1 -C6 alkyl ester or a mono- or diglyceride of butyric acid.
  • 38-II The composition II according to any one of embodiments 1-11 to 37-11, wherein the weight to weight ratio of the at least one HMO (component A) : the at least one vitamin K2 compound (component C) is from 1000:1 to 1000000:1.
  • composition II according to any one of embodiments 1-11 to 38-11, wherein the weight to weight ratio of the at least one HMO (component A) : the at least one C3-C4 alkane carboxylic acid or a derivative thereof (component B) is from 100:1 to 1 :100.
  • composition II according to any one of embodiments 1-11 to 39-11, wherein the weight to weight ratio of (component A) : (component B) is from 20:1 to 1 :20, preferably from 10:1 to 1 :10, more preferably from 3:1 to 1 :3, in particular from 2:1 to 1 :2.
  • composition II according to any one of embodiments 31-11 to 40-11, wherein the weight to weight ratio of the propionic acid or a derivative thereof : butyric acid or a derivative thereof is from 100:1 to 1 : 100.
  • composition II according to any one of embodiments 31-11 to 41-11 , wherein the weight to weight ratio of the propionic acid or a derivative thereof : butyric acid or a derivative thereof is from 20:1 to 1 :20, preferably from 10:1 to 1 :15, more preferably from 2:1 to 1 :8.
  • composition II according to any one of embodiments 1-11 to 42-11, wherein the weight to weight ratio of (component B) : (component C) is from 1000: 1 to 1000000: 1.
  • composition I according to any one of embodiments 1-11 to 43-11, wherein the at least one
  • HMO and the at least one vitamin K2 compound are present in synergistic amounts.
  • composition II according to any one of embodiments 1-11 to 44-11, wherein the at least one
  • HMO and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.
  • composition II according to any one of embodiments 1-11 to 45-11, wherein the at least one vitamin K2 compound and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof are present in synergistic amounts.
  • composition II according to any one of embodiments 1-11 to 46-11, wherein the at least one
  • composition II according to any one of embodiments 1-11 to 47-11, wherein the total amount of the at least one HMO and the at least one vitamin K2 compound and optionally the at least oneC3-C4-alkane carboxylic acid or derivative(s) thereof is from 1 to 100 wt% of the total composition II, preferably from 10 to 100 wt%.
  • composition II according to any one of embodiments 1-11 to 48-11, wherein the total amount of the at least one HMO is from 10 to 99.99999 wt% of the total composition II, preferably from 20 to 99.9999 wt%, more preferably from 30 to 99.999 wt%, even more preferably from 40 to 99.9 wt%.
  • composition II according to any one of embodiments 1-11 to 48-11, wherein the total amount of the at least one HMO is from 5 to 50 wt% of the total composition II, preferably from 8 to 40 wt%, more preferably from 10 to 35 wt%, even more preferably from 15 to 30 wt%.
  • composition II according to any one of embodiments 1-11 to 49-11, wherein the total amount of the at least one HMO is from 50 to 95 wt% of the total composition II, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • composition II according to any one of embodiments 1-11 to 51-11, wherein the total amount of the at least one vitamin K2 compound is from 0.00001 to 1 wt% of the total composition II, preferably from 0.0001 to 0.1 wt%.
  • composition II according to any one of embodiments 1-11 to 52-11, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 90 wt% of the total composition II, preferably from 15 to 85 wt%, more preferably from 20 to 75 wt%, even more preferably from 25 to 60 wt%.
  • composition II according to any one of embodiments 1-11 to 52-11, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 50 wt% of the total composition II, preferably from 15 to 45 wt%, more preferably from 20 to 35 wt%.
  • composition II according to any one of embodiments 1 to 52-II, wherein the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 50 to 90 wt% of the total composition II, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • 56-II The composition II according to any one of embodiments 1-11 to 55-11, wherein the composition
  • vitamin II further comprises one or more vitamins or related compounds thereto, other than a vitamin K2 compound.
  • composition II according to embodiment 56-11 wherein the one or more vitamins or related compounds thereto are selected from the group of vitamin A, vitamin B1 , vitamin B2, vitamin B3, pantothenic acid, vitamin B6, biotin, folic acid, vitamin B12, vitamin E, vitamin K, vitamin C and vitamin D, or related compounds thereto and/or mixtures thereof.
  • composition II according to any one of embodiments 1-11 to 57-11, wherein the composition
  • composition II according to embodiment 58-11 wherein the one or more carotenoids are selected from the group of astaxanthin, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, meso-zeaxanthin, zeaxanthin (including cis/trans isomers) and/or mixtures thereof.
  • composition II according to any one of embodiments 1-11 to 59-11, wherein the composition
  • II further comprises one or more medium-chain fatty acids, in free form, as glyceride, phospholipid, alkyl ester and/or mixtures thereof.
  • composition II according to embodiment 60-11, wherein the one or more medium chain fatty acids are selected from the group of caproic acid, caprylic acid, capric acid, lauric acid and/or mixtures.
  • composition II according to any one of embodiments 1-11 to 61-11, wherein the composition
  • II further comprises one or more long-chain fatty acids, in free form, as glyceride, phospholipid, alkyl ester and/or mixtures thereof.
  • composition II according to embodiment 62-11, wherein the one or more long chain fatty acids are selected from the group of saturated long chain fatty acids, mono-unsaturated long chain fatty acids, polyunsaturated long chain fatty acids and/or mixtures thereof.
  • composition II according to any one of embodiments 1-11 to 63-11, wherein the composition
  • II further comprises one or more prebiotics.
  • composition II according to embodiment 64-11 wherein the one or more prebiotics are selected from the group of water-insoluble fibers, water-soluble fibers, other oligosaccharides and/or mixtures thereof, preferably water-insoluble fibers, water-soluble fibers and/or mixtures thereof.
  • composition II according to any one of embodiments 1-11 to 65-11, wherein the composition
  • II further comprises one or more probiotics.
  • composition II according to embodiment 66-11, wherein the one or more probiotics are selected from the group of the family Lactobacilaceae, preferably of the genus Lactobacillus, in particular of the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii, lactobacillus helveticus, lactobacillus plantarum, lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus salivarius, of the genus Bifidobacterium, in particular of the species bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium lactis, bifidobacterium longum, of the genus Pediococcus, in particualar of the group of the family
  • composition II according to any one of embodiments 1-11 to 67-11, wherein the composition
  • composition II according to embodiment 68-11 wherein the one or more phenolic compounds are selected from the group of monophenols, flavonoids, isoflavonoids, aurones, chalconoids, flavonolignans, lignans, phytoestrogens, stilbenoids, piceatannol, curcuminoids, tannins, aromatic acids, phenylethanoids, capsaicin, gingerol, alkylresorcinol and/or mixtures thereof.
  • composition II according to any one of embodiments 1-11 to 69-11, wherein the composition
  • II further comprises one or more herbals.
  • composition II according to embodiment 70-11 wherein the one or more herbals are selected from herbals known from Chinese diets, Indian diets, Mediterranean diets and/or mixtures thereof.
  • composition II according to any one of embodiments 1-11 to 71-11, wherein the composition
  • composition II further comprises one or more minerals.
  • 73-I The composition II according to any one of embodiments 1-11 to 72-11, wherein the composition does not comprise an antibody.
  • composition II as described in any one of the embodiments 1-11 to 73-11 for use as a medicament preferably as a medicament for mammals, birds and/or fishes, more preferably for mammals, even more preferably for humans.
  • composition II according to embodiment 75-11, wherein the hypertension and/or associated morbidities thereto is hypertension, in particular of a human.
  • composition II according to embodiment 76-11 wherein the hypertension is prehypertension, or hypertension stage 1 or hypertension stage 2 or hypertensive crisis or isolated systolic hypertension or isolated diastolic hypertension, in particular of a human.
  • composition II according to embodiment 75-II, wherein the hypertension and/or associated morbidities thereto is an associated morbidity, in particular of a human.
  • composition II as described in any one of embodiments 1-11 to 79-11, wherein the associated morbidity is hypertensive nephropathy and/or chronic renal failure of a subject, in particular a human, even more particular a human having hypertension.
  • composition II as described in any one of embodiments 1-11 to 79-11, wherein the associated morbidity ishypertensive retinopathy and/or vision loss of a subject, in particular a human, even more particular a human having hypertension.
  • composition II according to any one of embodiments 74-11 to 83-11, wherein the composition II is an orally administrable composition.
  • a method for treating a subject having, suspected of having or being at risk of developing a disease, in particular hypertension and/or associated morbidities thereto comprising administering to the subject an effective amount of a composition II according to any one of embodiments 1-11 to 73-11.
  • the method according to any one of embodiments 85-II to 89-II, wherein the application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g/day, preferably from 1.0 to 9.0 g/day, more preferably from 1.2 to 9.0 g/day, in particular from 2.0 to 8.0 g/day, especially from 2.5 to 6.0 g/day.
  • C4-alkane carboxylic acid or derivative(s) thereof is a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof and the application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g/day and the application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g/day, preferably the application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g/day, more preferably the application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g/day.
  • a nutritional supplement or a functional food comprising a composition II according to any one of embodiments 1-11 to 73-11.
  • the nutritional supplement or the functional food according to embodiment 95-11 for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension and/or associated morbidities thereto, preferably of mammals, birds and/or fishes, more preferably of mammals, even more preferably of humans.
  • the nutritional supplement or functional food according to embodiment 96-11 for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertension, preferably of mammals, birds and/or fishes, more preferably of mammals, even more preferably of humans.
  • the nutritional supplement or functional food according to embodiment 96-11 for use in the dietary management of subjects having, being suspected of having or being at risk of developing morbidities associated to hypertension, preferably of mammals, birds and/or fishes, more preferably of mammals, even more preferably of humans. 99-II.
  • the nutritional supplement or functional food according to embodiment 98-II for use in the dietary management of subjects having, being suspected of having or being at risk of developing an associated morbidity of the cardiovascular system, an associated morbidity of the renal system, an associated morbidity of the nervous system or an associated morbidity of the vision system, in particular of a human, even more particular of a human having hypertension.
  • the nutritional supplement or functional food according to embodiment 99-11 for use in the dietary management of subjects having, being suspected of having or being at risk of developing atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms and/or peripheral vascular disease, in particular of a human, even more particular of a human having hypertension.
  • the nutritional supplement or functional food according to embodiment 99-11 for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertensive nephropathy and/or chronic renal failure, in particular of a human, even more particular of a human having hypertension.
  • the nutritional supplement or functional food according to embodiment 99-II for use in the dietary management of subjects having, being suspected of having or being at risk of developing headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia and/or convulsion, in particular of a human, even more particular of a human having hypertension.
  • the nutritional supplement or functional food according to embodiment 99-II for use in the dietary management of subjects having, being suspected of having or being at risk of developing hypertensive retinopathy and/or vision loss, in particular of a human, even more particular of a human having hypertension.
  • a method for the dietary management of a subject having, suspected of having or being at risk of developing hypertension and/or associated morbidities thereto comprising administering to the subject an effective amount of a composition II according to any one of embodiments 1-11 to 73-11 or a nutritional supplement according to any one of embodiments 95-11 to 103-11 or a functional food according to any one of embodiments 95-11 to 103-11.
  • the method according to any one of embodiments 104-11 to 106-11, wherein the application rate of the at least one HMO is from 0.1 to 20.0 g/day, preferably from 1.0 to 15.0 g/day, more preferably from 2.0 to 10.0 g/day, in particular from 2.5 to 5.0 g/day. -11.
  • the method according to any one of embodiments 104-11 to 108-11, wherein the application rate of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 0.1 to 10.0 g/day, preferably from 1.0 to 9.0 g/day, more preferably from 1.2 to 9.0 g/day, in particular from 2.0 to 8.0 g/day, especially from 2.5 to 6.0 g/day. -11.
  • C3-C4-alkane carboxylic acid or derivative(s) thereof is a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof and the application rate of propionic acid and/or a derivative thereof is from 0.1 to 4.0 g/day and the application rate of butyric acid and/or a derivative thereof is from 0.1 to 6.0 g/day, preferably the application rate of propionic acid and/or a derivative thereof is from 0.5 to 4.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 0.5 to 5.0 g/day, more preferably the application rate of propionic acid and/or a derivative thereof is from 1.0 to 3.0 g/day, and the application rate of butyric acid and/or a derivative thereof is from 1.5 to 4.0 g/day.
  • a method to treat a subject having hypertension and/or associated morbidities thereto by administering to the subject a) an effective amount of a composition II according to any one of embodiments 1-11 to 73-11, a composition II for use as a medicament according to embodiment 74-11, a composition II for use in the treatment or prevention of hypertension and/or associated morbidities thereto according to any one of embodiments 75-11 to 84-11, a nutritional supplement or a functional food according to any one of embodiments 95-11 to 104-11, or with one of components A, B and C, or with two of components A, B and C as described in any one of embodiments 1-11 to 73-11, and b) an effective amount of at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto, wherein the application rate of the at least one pharmaceutical suitable to treat said hypertension and/or associated morbidities thereto is reduced compared to a treatment with the at least one pharmaceutical alone.
  • a composition comprising a) i) at least one HMO, and/or ii) at least one vitamin K2 compound or derivative(s) thereof, and/or iii) at least one C3-C4-alkane carboxylic acid; and b) an effective amount of at least one pharmaceutical, especially being suitable for the treatment or prevention of hypertension and/or associated morbidities thereto, in particular for use as a medicament, especially for use in the treatment or prevention of hypertension and/or associated morbidities thereto.
  • a composition comprising a) i) as component A 2’-FL, and/or ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and/or iii) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and/or sodium butyrate; and b) a thiazide-diuretics (especially hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (especially verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors
  • composition II as defined in any one of embodiments 1-11 to 73-11 as a nutritional supplement for the dietary management of hypertension and/or associated morbidities thereto.
  • a composition II for use as a medicament according to embodiment 74-11 a composition II for use in the treatment or prevention of hypertension and/or associated morbidities thereto according to any one of embodiments 75-11 to 84-11, a nutritional supplement or a functional food according to any one of embodiments 95-11 to 103-11, a composition according to any one of embodiments 119-11 to 120-11, wherein the subject is a human, preferably in the age of 12 years or older, more preferably 18 years or older, even more preferably 35 years or older, in particular 50 years or older, even more in particular 60 years or older.
  • the subject is a human, preferably in the age of 12 years or older, more preferably 18 years or older, even more preferably 35 years or older, in particular 50 years or older even more in particular 60 years or older.
  • a kit for the pharmaceutical use or dietary management use comprising a first component A being at least one HMO, preferably as described in any one of embodiments 1-11 to 73-11, and a second component C being at least one vitamin K2 compound as described in any embodiments 1-11 to 73-11, and optionally a third component B being at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, preferably as described in any of embodiments 1-11 to 73-II for the treatment or prevention or dietary management use of hypertension and/or associated morbidities thereto.
  • kit according to embodiment 124-11 wherein the kit is for the pharmaceutical use forthe treatment or prevention of hypertension or dietary management use of hypertension.
  • kit according to embodiment 124-11 wherein the kit is for the pharmaceutical use for the treatment or prevention of morbidities associated to hypertension or dietary management use of morbidities associated to hypertension.
  • a kit for the pharmaceutical use or dietary management use comprising a) a first component A being at least one HMO, preferably as described in any one of embodiments 1-11 to 73-11, and/or a second component C being at least one vitamin K2 compound as described in any embodiments 1-11 to 73-11 and/or a third component B being at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, preferably as described in any of embodiments 1-11 to 73-11; and b) an effective amount of at least one pharmaceutical, especially being suitable for the treatment or prevention of hypertension and/or associated morbidities thereto, for use in the treatment or prevention of hypertension and/or associated morbidities thereto.
  • kits forthe pharmaceutical use or dietary management use according to embodiment 127-11, wherein the at least one pharmaceutical is a thiazide-diuretics (especially hydrochlorothiazide, chlorthiazid, chlortalidone, indapamide, xipamide), a calcium channel blockers (especially verapamil, gallopamil, ditiazem, nitrendipine, felodipin, amlodipin, nifedipin, lercanidipin, nimodipine, isradipin, nisoldipin, nilvadipin, clevidipin), an angiotensin converting enzyme inhibitors (especially captopril, enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril) and/or
  • C3-C4-alkane carboxylic acids or derivatives thereof can be combined with at least one vitamin K2 compound, and optionally with HMOs. Such compositions provide beneficial effects as described herein.
  • the present invention provides composition III.
  • the composition III comprises i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and ii) at least one vitamin K2 compound, and optionally iii) at least one HMO.
  • ⁇ MO refers to human milk oligosaccharide(s). These carbohydrates are resistant to enzymatic hydrolysis by digestive enzymes (e.g. pancreatic and/or brush border). In the human breast milk many different kinds of HMOs are found.
  • Each individual HMO is based on a combination of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose and/or N-acetylglucosamine with many and varied linkages between them. So far over 130 such structures have been identified in human milk. Almost all of them have a lactose moiety at their reducing end while sialic acid and/or fucose (when present) occupy terminal positions at the non-reducing ends.
  • the HMOs can be acidic (e.g. charged sialic acid containing oligosaccharide) or neutral (e.g. fucosylated oligosaccharide).
  • the HMO is selected from the group of fucosylated oligosaccharides, N-acetylated oligosaccharides and sialylated oligosaccharides.
  • the HMO is a "fucosylated oligosaccharide". These are HMOs having a fucose residue. It has a neutral nature. Some examples are 2'-FL (2'-fucosyllactose), 3-FL (3-fucosyllactose), difucosyllactose, lacto-N-fucopentaose (e.g.
  • lacto-N- fucopentaose I lacto- N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V)
  • lacto-N-fucohexaose lacto-N- difucohexaose I, fucosyllacto-N-hexaose, fucosyllacto- N-neohexaose, difucosyllacto-N-hexaose I, difucosyllacto-N-neohexaose II and any combination thereof.
  • the fucosylated oligosaccharide is selected from the group comprising 2’-FL, 3-FL and difucosyllactose (e.g. 2’,2”-DiFL and/or 3, 2’-DiFL).
  • the fucosylated oligosaccharide is 2’-FL.
  • the HMO is a ”N-acetylated oligosaccharide.
  • the term ”N-acetylated oligosaccharide(s)” encompasses both "N-acetyl-lactosamine” and "oligosaccharide(s) containing N-acetyl-lactosamine". They are neutral oligosaccharides having an N-acetyl-lactosamine residue. Suitable examples are LNT (lacto-N-tetraose), para-lacto-N- neohexaose (para-LNnH), LNnT (lacto-N-neotetraose) or any combination thereof.
  • N-acetylated oligosaccharide is selected from the group of LNT and LNnT.
  • the HMO is a ’’sialylated oligosaccharide.
  • the term ’’sialylated oligosaccharide encompasses an oligosaccharide having a sialic acid residue. It has an acidic nature. Some examples are 3’-SL (3'-sialyllactose) and 6’-SL (6'-sialyllactose).
  • the sialylated oligosaccharide is 6’-SL.
  • the HMO is selected from the group comprising 2’-FL, 3-FL, difucosyllactose (e.g.
  • the HMO is selected from the group comprising 2’-FL, difucosyllactose (e.g. 2’,2”-DiFL and/or 3,2’-DiFL), LNT, LNnT and 6’-SL and/or any combination thereof.
  • the HMO is selected from the group comprising 2’-FL, LNT, LNnT and 6'-SL and/or any combination thereof.
  • C3-C4-alkane carboxylic acid or derivative thereof encompasses propionic acid, n-butyric acid and iso-butyric acid (2-methyl propionic acid) as well as derivatives thereof and/or any mixture thereof.
  • Suitable derivatives are salts, esters and amides, in particular physiologically acceptable ones.
  • physiologically acceptable salts are alkali salts, like sodium or potassium salts, or alkaline-earth salts, like magnesium or calcium salts, or choline salts.
  • physiologically acceptable salts are alkali salts, in particular sodium salts or potassium salts, especially sodium salts.
  • physiologically acceptable esters are those derived from C1-C6 alcohols, in particular those derived from monohydric C1-C6 alcohols, e.g. those derived from methanol or ethanol, or dihydric C1-C6 alcohols, like those derived from 1 ,2-ethandiol, or C1-C4 alkoxy substituted monohydric alcohols, like those derived from 2-methoxyethanol, 2-ethoxyethanol or 2-butoxyethanol.
  • Other examples for physiologically acceptable esters are glycerides, like mono-, di-, or triglycerides, in particular mono- or diglycerides.
  • the physiologically acceptable esters are those derived from monohydric C1-C6 alcohols, e.g. those derived from methanol or ethanol, or mono- or diglycerides.
  • physiologically acceptable amides are those derived from mono- or di-C1-C6-alkyl amines.
  • the C3-C4 alkane carboxylic acid is provided as physiologically acceptable derivative thereof; in particular the derivative is a physiologically acceptable salt, e.g. a sodium salt or potassium salt, or a mixture thereof, or a physiologically acceptable ester, e.g. said ester is derived from C1 -C6 alcohols, in particular a mono-or a dihydric C1 -C6 alcohol, or said ester is a mono- or diglyceride, or a mixture thereof.
  • the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate or sodium butyrate or potassium butyrate or a mixture thereof. Especially, it is sodium propionate or sodium butyrate or a mixture thereof.
  • the C3-C4-alkane carboxylic acid or derivative thereof is propionic acid or a derivative thereof, in particular it is a physiologically acceptable salt of propionic acid, especially it is sodium propionate or potassium propionate, or a physiologically acceptable ester of propionic acid, especially methyl propionate or ethyl propionate or propionic acid monoglyceride or propionic acid diglyceride, particularly ethyl propionate or propionic acid monoglyceride.
  • the C3-C4-alkane carboxylic acid or derivative thereof is sodium propionate or potassium propionate.
  • the C3-C4-alkane carboxylic acid or derivative thereof is butyric acid or a derivative thereof, in particular it is a physiologically acceptable salt of butyric acid, especially it is sodium butyrate or potassium butyrate, or a physiologically acceptable ester of butyric acid, especially methyl butyrate or ethyl butyrate or butyric acid monoglyceride or butyric acid diglyceride, particularly ethyl butyrate or butyric acid monoglyceride.
  • the C3-C4- alkane carboxylic acid or derivative thereof is sodium butyrate or potassium butyrate.
  • the at least one C3-C4-alkane carboxylic acid or derivative thereof is a mixture of propionic acid and butyric acid or derivatives thereof, in particular it is a mixture of physiologically acceptable salts of propionic acid and butyric acid, especially it is a mixture of sodium propionate and sodium butyrate or a mixture of potassium propionate and potassium butyrate, or a mixture of physiologically acceptable esters of propionic acid and butyric acid, especially a mixture of methyl propionate and methyl butyrate, or a mixture of ethyl propionate and ethyl butyrate, or a mixture of propionic acid monoglyceride and butyric acid monoglyceride, or a mixture of propionic acid diglyceride and butyric acid diglyceride, particularly a mixture of ethyl propionate and ethyl butyrate or a mixture of propionic acid monoglyceride and butyric acid monoglyceride.
  • vitamin K2 compound relates to a menaquinone-n (abbreviated MK-n), wherein n represents the number of the isoprenyl units in the side chain which is linked to the 3 position of 2-methyl- 1 ,4-naphtochinone.
  • n can be from 2 to 14, preferably from 4 to 14, in particular n is 6 or 7, even more particular n is 7 (MK-7).
  • the vitamin K2 compound is in all-trans form.
  • n is preferably 4 (MK-4), and in particular MK-4 is in all- trans form.
  • the at least one vitamin K2 compound is a mixture of two or more MK-n, preferably of MK-6 and MK-7. Preferably these are in all-trans form.
  • composition III comprises i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and ii) at least one vitamin K2 compound.
  • composition III comprises i) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4.
  • composition III does not comprise one or more HMO.
  • composition III comprises i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and ii) at least one vitamin K2 compound, and iii) at least one HMO.
  • composition III comprises i) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and iii) as component A 2’-FL.
  • the composition III comprises i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and ii) at least one vitamin K2 compound, and optionally iii) at least one HMO, wherein the ratio of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) and the at least one vitamin K2 compound (component C) is from 1000:1 to 1000000:1.
  • the composition III comprises as at least one C3-C4- alkane carboxylic acid or derivative(s) thereof a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof, in a ratio of from 100 : 1 to 1 : 100, preferably from 20:1 to 1 : 20, more preferably from 10:1 to 1 :15, even more preferably from 2: 1 to 1 :8.
  • the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound (component C) are present in synergistic amounts.
  • composition III does not comprise one or more HMO.
  • the composition III comprises i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and ii) at least one vitamin K2 compound, and iii) at least one HMO, wherein the ratio of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) and the at least one vitamin K2 compound (component C) is from 1000:1 to 1000000:1 , and/or wherein the ratio of the at least one HMO (component A) and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof (component B) is from 100 : 1 to 1 : 100, preferably from 20: 1 to 1 :20, more preferably 10:1 to 1 :10, even more preferably from 3: 1 to 1 :3, in particular2:1 to 1 :2, and/or wherein the ratio of the at least one HMO (component A) and the at least one vitamin K2
  • said composition III comprises as at least one C3- C4-alkane carboxylic acid or derivative(s) thereof a mixture of propionic acid or a derivative thereof and butyric acid or a derivative thereof, in a ratio of from 100 : 1 to 1 : 100, preferably from 20:1 to 1 : 20, more preferably from 10:1 to 1 :15, even more preferably from 2:1 to 1 :8.
  • the at the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound are present in synergistic amounts.
  • the at least one HMO and the at least one the vitamin K2 compound are present in synergistic amounts.
  • the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one HMO are present in synergistic amounts.
  • the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, the at least one vitamin K2 compound and the at least one HMO are present in synergistic amounts.
  • the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof and the at least one vitamin K2 compound, and optionally the at least one HMO is from 1 to 100 wt% of the total composition III, preferably from 10 to 100 wt%.
  • the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 99,99999 wt% of the total composition III, preferably from 15 to 99,9999 wt%, more preferably from 20 to 99,999 wt%, even more preferably from 25 to 99,999 wt%. In yet another embodiment the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 10 to 50 wt% of the total composition III, preferably from 15 to 45 wt%, more preferably from 20 to 35 wt%.
  • the total amount of the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof is from 50 to 90 wt% of the total composition III, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • the total amount of the at least one vitamin K2 compound is from 0.00001 to 1 wt% of the total composition III, preferably from 0.0001 to 0.1 wt%.
  • the total amount of the at least one HMO is from 10 to 90 wt% of the total composition III, preferably from 20 to 80 wt%, more preferably from 30 to 70 wt%, even more preferably from 40 to 60 wt%. In yet another embodiment the total amount of the at least one HMO is from 5 to 50 wt% of the total composition III, preferably from 8 to 40 wt%, more preferably from 10 to 35 wt%, even more preferably from 15 to 30 wt%. In yet another embodiment the total amount of the at least one HMO is from 50 to 95 wt% of the total composition III, preferably from 55 to 80 wt%, more preferably from 60 to 75 wt%.
  • the composition III can further comprise one or more vitamins or related compounds thereto, other than a vitamin K2 compound.
  • vitamins and related compounds thereto include vitamin A (e.g. retinol, retinyl acetate, retinyl palmitate, retinyl stearate, retinyl esters with other long-chain unsaturated fatty acids, retinal, retinoic acid and the like), vitamin B1 (e.g. thiamine, thiamine pyrophosphate, TPP, thiamine triphosphate, TTP, thiamine hydrochloride, thiamine mononitrate and the like), vitamin B2 (e.g.
  • vitamin B3 e.g. nicotinic acid, nicotinamide, nicotinamide adenine dinucleotide (NAD), nicotinic acid mononucleotide (NicMN), pyridine-3-carboxylic acid and the like, as well as the vitamin B3-precursor tryptophan
  • pantothenic acid e.g. pantothenate, panthenol and the like
  • vitamin B6 e.g.
  • pyridoxine pyridoxal, pyridoxamine, pyridoxine hydrochloride and the like
  • biotin folic acid (e.g. folate, folacin, pteroylglutamic acid and the like)
  • vitamin B12 e.g. cobalamin, methylcobalamin. deoxyadenosylcobalamin, cyanocobalamin, hydroxycobalamin, adenosylcobalamin and the like
  • vitamin E e.g.
  • alpha-, beta-, gamma- and/or delta-tocopherol alpha-, beta-, gamma- and/or delta- tocopherol acetate, alpha-, beta-, gamma- and/or delta-tocopherol succinate, alpha-, beta-, gamma- and/or delta-tocopherol nicotinate, alpha-, beta-, gamma- and/or delta tocotrienol and the like), vitamin K (e.g. vitamin K1 , phylloquinone, naphthoquinone, vitamin K3, menadione, and the like ), vitamin C (ascorbic acid), vitamin D (e.g. calciferol, cholecalciferol, 1 ,25-dihydroxyvitamin D, ergocaliferol and the like), and the like and/or mixtures thereof.
  • vitamin K e.g. vitamin K1 , phylloquinone, naphthoquinon
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more vitamins or related compounds thereto, other than at least one vitamin K2 compound.
  • composition III does comprise one or more vitamins or related compounds thereto.
  • composition III can further comprise one or more carotenoids.
  • carotenoids include astaxanthin, alpha-carotene, beta-carotene, beta- cryptoxanthin, lutein, lycopene, meso-zeaxanthin, zeaxanthin and the like (including cis/trans isomers) and/or mixtures thereof.
  • the presence and amounts of specific carotenoids will vary depending on the intended use.
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more carotenoids.
  • the composition III can further comprise one or more medium-chain fatty acids.
  • These medium-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or alkyl esters.
  • Examples of medium-chain fatty acids include caproic acid, caprylic acid, capric acid, lauric acid and the like and /or mixtures thereof.
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more medium-chain fatty acids.
  • composition III can further comprise one or more long-chain fatty acids.
  • long-chain fatty acids may be provided as free fatty acids, as glycerides (e.g. as monoglycerides, diglycerides or triglycerides and/or as mixtures thereof), as phospholipids, as alkyl esters and/or as mixtures thereof, preferably as glycerides, more preferably as triglycerides or as alkyl esters.
  • long chain fatty acids include saturated long chain fatty acids (e.g.
  • linoleic acid linoelaidic acid, alpha-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentenoic acid, docosahexaenoic acid and the like and/or mixtures thereof) and/or mixtures thereof.
  • These long chain fatty acids are comprised for example in vegetable oils, single cell oils and marine oils, e.g. fish oil, krill oil and the like.
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more long-chain fatty acids.
  • composition III can further comprise one or more prebiotics.
  • prebiotics include water-insoluble fibers (e.g. lignin, cellulose, hemi- cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof), water-soluble fibers (e.g.
  • arabinoxylan arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof
  • other oligosaccharides like xylooligosaccharides, fructooligosaccharides, galactooligosaccharides, isomalto-oligosaccharides and the like and/or mixtures thereof
  • water-insoluble fibers e.g. lignin, cellulose, hemi- cellulose, resistant starch, xanthum gum and the like and/or mixtures thereof
  • water-soluble fibers e.g.
  • arabinoxylan arabinoxylan, inulin, pectin, alginic acid and derivatives thereof, agar, carrageen, raffinose, xylose, polydextrose, lactulose and the like and/or mixtures thereof) and the like and/or mixtures thereof.
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more prebiotics.
  • composition III can further comprise one or more probiotics.
  • probiotics optionally present in the composition III of the present invention include microorganisms or parts thereof of the family Lactobacillaceae, e.g. of the genus Lactobacillus (e.g. the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii (like lactobacillus delbrueckii spp. bulgaricus, lactobacillus delbrueckii spp. delbrueckii, lactobacillus delbrueckii spp.
  • the family Lactobacillaceae e.g. of the genus Lactobacillus (e.g. the species lactobacillus acidophilus, lactobacillus alimentarius, lactobacillus casei, lactobacillus delbrueckii (like lactobacillus delbrueckii spp. bulg
  • lactis lactobacillus helveticus, lactobacillus plantarum, lactobacillus reuteri, lactobacillus rhamnosus, lactobacillus salivarius and the like), of the genus Bifidobacterium (e.g. the species bifidobacterium animalis, bifidobacterium bifidum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium lactis, bifidobacterium longum and the like), of the genus Pediococcus (e.g.
  • Lactococcus e.g. the species lactococcus lactis (like lactococcus latis spp. cremoris, lactococcus lactis spp. lactic and the like
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more probiotics.
  • composition III can further comprise one or more phenolic compounds.
  • phenolic compounds include monophenols (e.g. apiole, carnosol, carvacrol, dillapiole, rosemarinol and the like), flavonoids (e.g.
  • quercetin kaempferol, myricetin, fisetin, rutin, isorhamnetin, hesperidin, naringenin, silybin, eriodyctiol, acacetin, apigenin, chrysin, diosmetin, tangeritin, luteolin, catechins like epigallocatechin gallate, theaflavin, thearubigins, proanthocyanidins, pelargonidin, peonidin, cyanidin, delphinidin, malvidin, petunidin and the like), isoflavonoids (e.g.
  • daidzein genistein, glycitein and the like
  • aurones chalconoids
  • flavonolignans lignans
  • phytoestrogens stilbenoids (e.g. resveratrol, pterostilbene, piceatannol and the like)
  • curcuminoids e.g. curcumin and the like
  • tannins aromatic acids (e.g. salicylic acid, vanillic acid, gallic acid, ellagic acid, tannic acid, caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumarin and the like), phenylethanoids (e.g. tyrosol, hydroxytyrosol, oleocanthal, oleuropein and the like ), capsaicin, gingerol, alkylresorcinol and the like and/or mixtures thereof.
  • aromatic acids e.g. salicylic acid, vanillic acid, gallic acid
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more phenolic compounds.
  • composition III can further comprise one or more herbals, e.g. known from Chinese diets, Indian diets, Mediterranean diets and the like. These herbals can be provided as powders obtained from the plant and/or fungus or parts thereof or as extracts thereof.
  • herbals e.g. known from Chinese diets, Indian diets, Mediterranean diets and the like. These herbals can be provided as powders obtained from the plant and/or fungus or parts thereof or as extracts thereof.
  • herbals known from Chinese diets include extracts or powders of hawthorn fruit, wolfberry, spatholobus stem, caterpillar fungus, cloud mushroom, crysanthemum, honeysuckle flower, mulberry leaf, glossy privet fruit, malaytea scurfpea fruit, cherokee rose fruit, palmleaf raspberry fruit, Chinese magnoliavine fruit, reishi mushroom, ephedra, epimedium, Angelica root, Astragalus root, rhubarb, licorice, morinda root, notoginseng, white peony root, American ginseng, fleeceflower root, kudzu root, rehmannia root, salvia root, Chinese yam, wild buckwheat rhizome, tall gastrodia tuber, golden root, Cassia seed, Coix seed, Dodder seed and the like and/or mixtures thereof.
  • herbals known from Indian diets include extracts or powders of Amalaki (Indian gooseberry), Haritaki (chebulic myrobalan), Bibhitaki (beleric), Haldi (turmeric), Tulsi (holy basil), Shigru (moringa), Twak (cinnamon), Yashtimadhu (licorice root), Dhanyaka (coriander), Ashwagandha (winter cherry), Kumkuma (saffron), Manjistha (Indian madder), Brahmi (bacopa), Neem (margosa), Ajwain (Bishop’s weed), Elaichi (cardamom), Shikakai (Acacia concinna), Shatavari (wild asparagus), Jeera (cumin), Guduchi (tinospora) and the like and/or mixtures thereof.
  • Examples for herbals known from Mediterranean diets include extracts or powders of rosemary, basil, parsley, saffron, thyme, oregano, sage, cilantro, lemon, orange, grape, grapeseed, fig, blueberry, raspberry, strawberry, cherry, fennel, sesame seeds, pine seeds, garlic, onion, ginger root, pepper, chili and the like, olive oil and/or mixtures thereof.
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO.
  • composition III does not comprise one or more herbals.
  • composition III can further comprise one or more minerals.
  • minerals include such ones comprising calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum and the like and/or mixtures thereof. Minerals are usually added in salt form.
  • composition III does not comprise one or more HMO.
  • composition III does comprise one or more HMO. In another embodiment of the present invention the composition III does not comprise one or more minerals. In a further embodiment of the present invention the composition III does not comprise a mineral comprising iron.
  • composition III does not comprise one or more antibodies.
  • compositions III of the present invention can be prepared by mixing the at least one vitamin K2 compound, and the at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and optionally the at least one HMO, and optionally further components e.g. vitamins and related compounds thereto, carotenoids, medium chain fatty acids, long chain fatty acids, prebiotics, probiotics, phenolic compounds, herbals, minerals and the like and/or mixtures thereof, as known in the art.
  • the composition III does not comprise more than 80 wt% water.
  • composition III which comprises i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, ii) at least one vitamin K2 compound, and optionally iii) at least one HMO, for use as a medicament, preferably as a medicament for mammals, birds and/or fishes, in particular as a medicament for mammals.
  • the term ’’mammals encompasses humans and nonhuman mammals.
  • non-human mammals are livestock, e.g. sheep, goats, pigs, cattles, horses, camels, llamas and the like, and pets, e.g. cats, dogs and the like.
  • composition III is for use as a medicament for humans.
  • composition III is for use as a medicament for livestock and/or pets.
  • composition III is for use as a medicament for birds, e.g. poultry (like chickens, ducks, geese, turkeys and the like) and ornamental birds (like canaries and the like).
  • birds e.g. poultry (like chickens, ducks, geese, turkeys and the like) and ornamental birds (like canaries and the like).
  • composition III is for use as a medicament for fishes, e.g. fishes used for consumption (like salmon, tuna, sardines, cod, trout, and the like) and ornamental fishes (like kois and the like).
  • fishes e.g. fishes used for consumption (like salmon, tuna, sardines, cod, trout, and the like) and ornamental fishes (like kois and the like).
  • the compositions III of the present invention for use as a medicament can be administered orally, enterally or parenterally, preferably orally.
  • composition III for use as a medicament is an orally administrable composition.
  • composition III comprises i) as component B propionic acid and/or butyric acid or derivative(s) thereof, preferably sodium propionate and sodium butyrate, and ii) as component C MK-7 or a mixture of MK-6 and MK-7 or MK-4, preferably MK-7 or MK-4, and optionally iii) as component A 2’-FL, for use as a medicament, preferably as a medicament for humans.
  • composition III shall be applicable for the compositions III for use as a medicament and the specific embodiments thereto.
  • composition III which comprises i) at least one C3-C4-alkane carboxylic acid or derivative(s) thereof, and ii) at least one vitamin K2 compound, and optionally iii) at least one HMO, for the use in the treatment and/or prevention of hypertension and/or associated morbidities thereto, preferably of mammals, more preferably of humans.
  • the term ’’’treatment” in the context of hypertension and/or associated morbidities thereto means using an effective therapy or management to alleviate, reduce or cure the condition and/or disease (hypertension and/or associated morbidities thereto) and/or symptoms thereof, as the case may be, in addition it also includes the stabilization of the condition and/or disease, as the case may be, in order not to worsen in the course of the respective condition and/or disease.
  • treatment is understood as using an effective therapy or management to stabilize, alleviate or reduce the condition and/or disease and/or symptoms thereof, as the case may be.
  • the term ’’prevention” in the context of hypertension and/or associated morbidities thereto means an effective therapy or management so that the condition and/or disease (hypertension and/or associated morbidities thereto) does not de novo develop, manifest and/or symptoms thereof do not occur.
  • the composition III is for use in the treatment of hypertension and/or associated morbidities thereto.
  • composition III is for use in the prevention of hypertension and/or associated morbidities thereto.
  • hypotension refers to a condition and/or disease, as the case may be, which is characterized by an increased blood pressure compared to a normal blood pressure, which is defined by the American Heart Association as being in the range of 90-119 mmHg (systolic) and 60-79 mmHg (diastolic) of a respective subject.
  • hypertension stage 1 hypertension stage 2
  • hypertensive crisis refers to a blood pressure of above 180 mmHg systolic and above 120 mmHg diastolic of a respective subject
  • isolated systolic hypertension refers to a blood pressure from 120-129 mmHg systolic and 60-79 mmHg diastolic of a respective subject
  • hypertension stage 1 refers to a pressure from 130-139 mmHg systolic and 80-89 mmHg diastolic of a respective subject
  • hypertension stage 2 from a pressure above 140 mmHg systolic and above 90 mmHg diastolic of a respective subject
  • hypertensive crisis refers to a blood pressure of above 180 mmHg systolic and above 120 mmHg diastolic of a respective subject
  • isolated sysystolic refers to a blood pressure from 120 mmHg
  • composition III is for use in the treatment or prevention of hypertension of a human.
  • composition III is for use in the treatment or prevention of pre-hypertension of a human, or in another embodiment of hypertension stage 1 of a human, or in another embodiment of hypertension stage 2 of a human, or in another embodiment of hypertensive crisis of a human, or in another embodiment of isolated systolic hypertension of a human, or in another embodiment of isolated diastolic hypertension of a human.
  • associated morbidities as well as the term ’’morbidities associated to” mean one or more conditions and/or diseases which are co-occurring to the primary condition or disease (hypertension), or which are occurring later in the life of the subject who had earlier in his or her life said primary condition and/or disease (hypertension).
  • composition III is for use in the treatment or prevention of an associated morbidity, e.g.
  • an associated morbidity of the cardiovascular system which includes atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms, peripheral vascular disease etc.
  • an associated morbidity of the renal system which includes hypertensive nephropathy, chronic renal failure etc.
  • an associated morbidity of the nervous system which includes headache, stroke, hypertensive encephalopathy, confusion, cognitive impairment, dementia, convulsion etc.
  • an associated morbidity of the vision system which includes hypertensive retinopathy, vision loss etc., and the like, in particular of a human.
  • composition III is for use in the treatment or prevention of an associated morbidity of the cardiovascular system, in particular of a human subject having hypertension.
  • composition III is for use in the treatment or prevention of atherosclerosis, ischemic heart disease, atrial fibrillation, myocardial infarction, cardiomyopathy, heart failure, aortic aneurysms and/or peripheral vascular disease, in particular of a human subject having hypertension.
  • composition III is for use in the treatment or prevention of an associated morbidity of the renal system, in particular of a human subject having hypertension.

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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne des compositions et des méthodes pour le traitement et/ou la prévention de l'hypertension et/ou de morbidités associées d'un sujet. En particulier, la présente invention concerne des compositions comprenant au moins un oligosaccharide du lait humain (HMO) et au moins un acide carboxylique d'alcane en C3-C4 et éventuellement au moins un composé de vitamine K2.
PCT/EP2020/086978 2019-12-18 2020-12-18 Composition pour le traitement de l'hypertension et/ou de morbidités associées WO2021123131A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017129639A1 (fr) * 2016-01-26 2017-08-03 Nestec S.A. Compositions comprenant des oligosaccharides du lait humain destinés à être utilisées chez des nourrissons ou de jeunes enfants pour prévenir ou traiter un trouble de santé par augmentation de la sécrétion de glp-1
WO2017129650A1 (fr) * 2016-01-26 2017-08-03 Nestec S.A. Compositions comprenant 2 fl et lnnt pour utilisation chez des nourrissons ou de jeunes enfants pour prévenir ultérieurement dans la vie l'obésité ou des comorbidités associées

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017129639A1 (fr) * 2016-01-26 2017-08-03 Nestec S.A. Compositions comprenant des oligosaccharides du lait humain destinés à être utilisées chez des nourrissons ou de jeunes enfants pour prévenir ou traiter un trouble de santé par augmentation de la sécrétion de glp-1
WO2017129650A1 (fr) * 2016-01-26 2017-08-03 Nestec S.A. Compositions comprenant 2 fl et lnnt pour utilisation chez des nourrissons ou de jeunes enfants pour prévenir ultérieurement dans la vie l'obésité ou des comorbidités associées

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* Cited by examiner, † Cited by third party
Title
GALIÈ NAZZARENO ET AL: "Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2", CIRCULATION, AMERICAN HEART ASSOCIATION, INC, US, vol. 117, no. 23, 10 June 2008 (2008-06-10), pages 3010 - 3019, XP009526306, ISSN: 1524-4539, DOI: 10.1161/CIRCULATIONAHA.107.742510 *

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