EP3200622A1 - Nutritional composition for use to treat or prevent pregnancy related conditions - Google Patents

Nutritional composition for use to treat or prevent pregnancy related conditions

Info

Publication number
EP3200622A1
EP3200622A1 EP15771931.1A EP15771931A EP3200622A1 EP 3200622 A1 EP3200622 A1 EP 3200622A1 EP 15771931 A EP15771931 A EP 15771931A EP 3200622 A1 EP3200622 A1 EP 3200622A1
Authority
EP
European Patent Office
Prior art keywords
acid
concentration
range
maternal
composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP15771931.1A
Other languages
German (de)
French (fr)
Inventor
Clara Lucia Garcia-Rodenas
Irma SILVA ZOLEZZI
Kim-Anne LE
Timothy James Wooster
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Societe des Produits Nestle SA
Original Assignee
Nestec SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nestec SA filed Critical Nestec SA
Publication of EP3200622A1 publication Critical patent/EP3200622A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a maternal compositions comprising, with respect to the total fatty acid concentration, more than 50wt% of long chain fatty acids and 50wt% or less of medium chain fatty acids, for use to treat or prevent acid reflux, nausea or vomiting, gestational diabetes mellitus, and/or a condition associated with any of the foregoing in a pregnant subject and/or its offspring.
  • Nausea and vomiting, acid reflux, and indigestion are all common gastrointestinal conditions affecting pregnant mammals.
  • the seriousness of these conditions can range from the somewhat benign and merely uncomfortable, to the severe and in rare cases life-threatening.
  • the aforementioned conditions may not only be a threat to the health and wellbeing of the pregnant mammal, they may even pose a threat to the healthy development of her offspring.
  • compositions that can improve gastric motility, and in particular accelerate gastric emptying rates are of great interest to the maternal health and wellness industry.
  • compositions that can accelerate gastric emptying rates and thereby may be used to treat or prevent the aforementioned conditions.
  • mothers and their physicians are generally against the use of pharmacological therapies during pregnancy.
  • non-pharmaceutical compositions that can accelerate gastric emptying rates and which may therefore be used to treat and/or prevent nausea and vomiting, acid reflux, and indigestion in a pregnant subject.
  • a maternal composition comprising, with respect to the total fatty acid concentration, more than 50 wt% of long chain fatty acids and 50 wt% or less of medium chain fatty acids, is emptied rapidly from the stomach and may be used to accelerate gastric emptying. This is particularly in comparison to a composition comprising more than 50 wt% of medium chain fatty acids and 50 wt% or less of long chain fatty acids.
  • a maternal composition comprising, with respect to the total fatty acid concentration, more than 50 wt% of long chain fatty acids and 50% or less of medium chain fatty acids, is emptied rapidly from the stomach and may be used to accelerate gastric emptying and to increase the expression of FGF19 in a subject, and accordingly, may be used to treat and/or prevent nausea or vomiting, acid reflux, indigestion and gestational diabetes in a pregnant subject e.g. a pregnant cat, dog or human.
  • a maternal composition in accordance with the invention comprising, with respect to the total fatty acid concentration, less than 5 wt% of medium chain fatty acids, may be particularly effective.
  • a maternal composition in accordance with the invention comprising long chain fatty acids selected from the groups consisting of; myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linoleic acid, arachidic acid, eicosenoic acid, and combinations thereof.
  • each type of long chain and/or medium chain fatty acid comprised in a maternal composition of the invention is mainly e.g. at least 98%, 99%, or 99.5%, in the form of triglycerides.
  • Palmitic acid in particular in the sn 1 or 3 triglyceride form, is known to cause and/or exacerbate constipation. Accordingly, a maternal composition of the invention having a low palmitic acid concentration, in particular in the sn 1 or 3 triglyceride form, of no more than 14%, more particularly no more than 7%, or those that are free from palmitic acid, in particular in the sn 1 or 3 triglyceride form, may also be used to treat or prevent constipation.
  • a maternal composition in accordance with the invention may be particularly effective at treating or preventing nausea or vomiting, acid reflux, indigestion, gestational diabetes, and/or constipation in a pregnant subject if used in conjunction or combination with ingredients known to be useful in the treatment or prevention of these conditions e.g. Vitamin B6 ginger or extracts thereof.
  • a maternal composition in accordance with the invention may be administered enterally to a pregnant subject before and/or during pregnancy and/or during lactation, administration may be at any time of the day or night and may be before eating.
  • a maternal composition in accordance with the invention may be administered in the form of a fat blend e.g. an encapsulated fat blend or alternatively it may be administered in the form of a powdered nutritional composition to be reconstituted in for example milk, juice or water, a food product, a drink, a nutritional supplement such as a powdered nutritional supplement to be sprinkled on food or mixed in an aqueous medium for example milk, juice or water, or a nutraceutical.
  • nausea or vomiting, acid reflux, indigestion and gestational diabetes are associated with a variety of conditions affecting a pregnant subject and/or their offspring e.g. dehydration, electrolyte imbalances, nutritional deficiencies, likelihood of having a small for gestational age baby, venous thromboembolism, pulmonary embolism and preeclampsia macrosomia, birth injury to the mother or infant, shoulder dystocia, premature delivery, and caesarian delivery (hereinafter C- section) developing type II diabetes immediately after pregnancy and later in life for the mother, infants developing an impaired glucose tolerance and/or suffering from excess weight/adiposity and associated metabolic disorders e.g.
  • composition of the invention may also be used to treat or prevent these associated conditions in said pregnant subject or their offspring.
  • Figure 1 shows an overview of the study described in Example 1.
  • FIG. 2 shows the results for measurements of gastric emptying.
  • Figure 3 shows the results for measurements of FGF 19 in blood samples taken during experiment described in Example 1.
  • Figure 4 shows the results for measurement of bile acids in blood samples taken during experiment described in Example 1.
  • a maternal composition comprising, with respect to the total fatty acid concentration, more than 50% of long chain fatty acids and 50% or less of medium chain fatty acids, is emptied rapidly from the stomach and may be used to accelerate the gastric emptying rate.
  • a composition is considered to be rapidly emptied from the stomach if 50% of the consumed composition is emptied within 350 to 550mins, more particularly 400 to 500mins.
  • T50meas The time when half of a composition is emptied from the stomach is referred to as T50meas.
  • the gastric emptying time of a composition can be measured by methods well known to the skilled person. One such method is laid out herein in example 1.
  • a further advantage of maternal compositions in accordance with the invention is that they were also found to increase the secretion of bile acid and the expression of FGF-19.
  • FGF-19 is an intestinal hormone that can exert beneficial effects on glucose metabolism by increasing insulin sensitivity and inducing glycogen synthesis. Circulating levels of FGF-19 have been found to be reduced in pregnant subjects suffering from Gestational Diabetes Mellitus (hereinafter GDM) and to be inversely correlated with insulin resistance in this population (Wang, 2013). Increasing circulating levels of FGF19 has been proven a useful mean to prevent and to treat insulin intolerance and type 2 diabetes (Shaap et al, 2012) A composition that increases circulating FGF-19 levels may therefore be used to treat or prevent GDM or a condition associated therewith in a pregnant subject and/or its offspring.
  • GDM Gestational Diabetes Mellitus
  • a maternal composition comprising, with respect to the total fatty acid concentration, 50 wt% or more of long chain fatty acids and less than 50 wt% of medium chain fatty acids, for use to treat or prevent acid reflux, nausea or vomiting, indigestion, and/or gestational diabetes mellitus, and/or a condition associated with any of the foregoing in a pregnant subject and/or its offspring.
  • subject refers to a mammal and more particularly a cat, a dog or a human.
  • HG Hyperemesis gravidarum
  • HG is the most severe form of nausea and vomiting in pregnancy and it effects between 0.5- 2% of of pregnant women. HG may be defined as severe and persistent nausea and vomiting, and may lead to weight loss greater than 5% of prepregnancy weight, dehydration, electrolyte imbalances, and nutritional deficiencies, typically requiring hospitalisation.
  • nausea or vomiting may lead to a reduction in maternal weight gain throughout pregnancy, which may result in suboptimal fetal outcomes.
  • women who suffer from extreme nausea and vomiting (such as HG) can be at higher risk of having small for gestational age babies and premature births.
  • Nausea or vomiting, in particular HG is also known to be a risk factor for venous thromboembolism, pulmonary embolism and preeclampsia.
  • in utero exposure to nausea or vomiting, in particular HG has been associated with an increased risk in the offspring for depression, bipolar disorder, and anxiety in adulthood.
  • the term "GDM" as used herein refers to any degree of glucose intolerance with onset or first recognition during pregnancy.
  • Whether or not a mammal has an impaired glucose tolerance may be determined by measuring its fasting glucose plasma concentration, or by carrying out an oral glucose tolerance test (OGTT).
  • OGTT oral glucose tolerance test
  • the skilled person will be familiar with these tests and the criteria for diagnosing an impaired glucose tolerance and hence GDM.
  • NACB National Academy of clinical biochemistry
  • AACC American Association for clinical chemistry
  • a pregnant human subject is considered as having an impaired glucose tolerance if their fasting plasma glucose concentration equates to 5.1mmol/L or more, or if their blood glucose concentration equates to less than 10 mmol/L lhour after a 75gram glucose drink, or less than 8.5 mmol/L 2 hours after a 75gram glucose drink.
  • GDM may increase the risk of a number of maternal-fetal conditions, including macrosomia, birth injury to the mother or infant, shoulder dystocia, premature delivery, and caesarian delivery
  • the term "acid reflux” as used refers to a condition wherein acid comes up from the stomach into the esophagus, it is also referred to a Gastroesophageal reflux (GE ) and in severe cases to a gastroesophageal reflux disease (GERD).
  • GE Gastroesophageal reflux
  • GERD gastroesophageal reflux disease
  • indigestion refers to a condition wherein digestion is impaired in a subject. It is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating, belching, nausea.
  • the term “Medium chain fatty acids” as used herein refers to n-carboxylic acids of saturated linear aliphatic chains comprising 6-12 carbon atoms, and derivatives thereof. Any reference to a specific medium chain fatty acid is also a reference to any derivative thereof.
  • Long chain fatty acids refers to n-carboxylic acids of saturated linear aliphatic chains comprised of 13 or more, more particularly 13 to 22, carbon atoms, and derivatives thereof. Any reference to a specific long chain fatty acid is also a reference to any derivative thereof.
  • Non limiting examples of derivatives of medium and/or long chain fatty acids include phospholipids, triglycerides, diglycerides, and monoglycerides.
  • the maternal composition of the invention may comprise long chain fatty acid in any concentration in the range of 50 to 100 wt% with respect to the total fatty acid content e.g.50 -60 wt%, 50-70 wt%, 60-80 wt%, 60-90 wt%, 95-100 wt%.
  • the maternal composition of the invention may comprise medium chain fatty acids in any concentration less than 50 wt%, with respect to the total fatty acids, e.g. in the range 0-49.99 wt%, 10-40 wt%, 5-30 wt%, 12-45 wt%.
  • the composition of the invention is free or substantially free from medium chain fatty acids. By substantially free is meant that the composition comprises up to 5%, up to 2% or up to 1% of medium chain fatty acids.
  • Any long chain fatty acid that is suitable for ingestion by the pregnant subject may be used in the composition of the invention.
  • Non limiting examples of suitable long chain fatty acids include; myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linoleic acid, arachidic acid, eicosenoic acid, and combinations thereof.
  • Any medium chain fatty acid that is suitable for ingestion by the pregnant subject may be used in the composition of the invention.
  • Non limiting examples of suitable medium chain fatty acids include; caproic acid, caprylic acid, decanoic acid, dodecanoic acid, and combinations thereof.
  • the long and/or medium chain fatty acids comprised in the maternal composition of the invention are mainly in the form of triglycerides.
  • triglycerides By mainly is meant at least 98 wt%, more particularly at least 99.5wt%, even more particularly more than 99.5 wt%.
  • the long and medium chain fatty acids comprised within the maternal compositions of the invention may be saturated, unsaturated or polyunsaturated.
  • unsaturated fatty acids include oleic acid, as well as polyunsaturated fatty acids (PUFAS), for example linoleic acid, alpha-linoleic, arachidonic acid, docohexaenoic acid, and/or eicosenoic acid
  • polyunsaturated fatty acids include alpha-linolenic acid (ALA) 18:3, stearidonic acid (SDA) 18:4, eicosatrienoic acid (ETE) 20:3, n-3 eicosatetraenoic acid (ETA) 20:4, eicosapentaenoic acid (EPA) 20:5, n-3 docosapentaenoic acid (DPA) 22:5, docosahexaenoic acid (DHA) 22:6, linoleic acid 18:2, gamma-linolenic acid (GLA) 18:3, n-6 eicosadienoic acid 20:2, dihomo-gamma-linolenic acid (DGLA) 20:3, arachidonic acid (AA or A A) 20:4, n-6 docosadienoic acid 22:2, and docosapentaenoic acid 22:5.
  • ALA alpha-linolenic acid
  • SDA
  • the composition of the invention comprises at least one unsaturated fatty acid, mainly in the form of triglycerides, in an amount of at least 15 wt%, at least 20 wt%, at least 35 wt%, at least 38 wt%, 40 wt % to 90 wt%, 50 wt% to 80 wt%, 50 wt% to 75 wt%, 50 wt% to 70 wt %, 55 wt% to 70 wt %, with respect to the total fatty acid concentration.
  • the maternal composition of the invention comprises at least one polyunsaturated fatty acid (PUFA), the PUFA(s) being present in an amount generally of at least 8 wt%, or 10 wt%, with respect to the total fatty acid concentration.
  • PUFA polyunsaturated fatty acid
  • the presence of PUFAs is especially advantageous for several key health benefits such as cognitive benefits, visual and cognitive development, anti-inflammatory properties, as it is known in the art.
  • the maternal composition of the invention comprise PUFAs selected from the group consisting of alpha-linolenic acid, and/or linoleic acid, which are essential fatty acids, and /or docosahexanoic acid (DHA, C22:6) and/or arachidonic acid (ARA, C20:4) which are known for their health benefits with respect to cognition for example.
  • PUFAs selected from the group consisting of alpha-linolenic acid, and/or linoleic acid, which are essential fatty acids, and /or docosahexanoic acid (DHA, C22:6) and/or arachidonic acid (ARA, C20:4) which are known for their health benefits with respect to cognition for example.
  • Essential fatty acids are fatty acids that must be ingest because the body requires them for good health but cannot synthesise them.
  • the maternal composition of the invention comprise linoleic and/or alpha linoleic acid, in particular in a total combined concentration, with respect to the total fatty acid concentration, in the range of 10 to 15 wt%, 12 to 14 wt%, 12.5 to 13.9 wt%.
  • the maternal composition of the invention comprises palmitic acid, more particularly in the sn 1 or 3 triglyceride form, in an amount in the range of not more than 14 wt%, more particularly not more than 7 wt%, 6 wt%, 5 wt%, 4 wt%, 3 wt%,
  • Palmitic acid in particular in the sn 1 or 3 triglyceride form, is released as a free fatty acid during digestion and can form soaps with calcium that are not digested. These are excreted and make the stool consistency harder. Thus, reducing the amounts of the palmitic acid, in particular in the sn 1 or 3 triglyceride form, is released as a free fatty acid during digestion and can form soaps with calcium that are not digested. These are excreted and make the stool consistency harder. Thus, reducing the amounts of the palmitic acid, in particular in the sn 1 or
  • 3 triglyceride form can help to prevent or alleviate constipation.
  • Constipation is described as infrequent bowel movements or difficult evacuation.
  • the maternal composition is free from palmitic acid, in particular the sn 1 or 3 triglyceride form.
  • the maternal composition comprises, with respect with the total fatty acid content, the following medium and/or long chain fatty acids:
  • caprioic acid hexanoic acid in a concentration in the range of 0 to 1 wt% e.g 0.05 to 0.5 wt%, 0.05 to 0.4 wt%, 0.06 to 0.4 wt%, or 0.07 to 0.3 wt%; and/or
  • caprylic acid in a concentration in the range of 0 to 10 wt% e.g. 2 to 8 wt%, 1.55 to 2 wt%, 1.6 to 2 wt%, 1.65 to 2 wt%, 1.7 to 2 wt%; and/or
  • decanoic acid in a concentration in the range of 0 to 10 wt% e.g. 0 to 1.8 wt%, 0.1 to 1.8 wt%, 1 to 1.7wt%, 1 to 1.5wt% or 1.2 to 1.8 wt%; and/or
  • dodecanoic acid in a concentration in the range of 0 to 12.0 wt% e.g. 0 to 10 wt%, 0 to 8 wt%, 0 to 6 wt%, 0 to 4 wt%, 1 to 12 wt%, 2 to 12 wt%. 4 to 12 wt%, 6 to 12 wt%, 8 to 12 wt%, 10 to 12 wt%.
  • myristic acid in a concentration in the range of 0 to wt% e.g 0.05 to 0.5 wt%, 0.05 to 0.4 wt%, 0.06 to 0.4 wt%, or 0.07 to 0.3 wt%; and/or
  • palmitic acid in a concentration in the range of 0 to 5 wt% e.g. 2 to 4 wt%, 2 to 3.5 wt%, 2.3 to 3.4 wt% and/or
  • palmitoleic acid in a concentration in the range of 0 to 1 wt% e.g 0.05 to 2 wt%, 0.05 to 1.5 wt%, 0.05 to 0.12 wt%; and/or
  • stearic acid in a concentration in the range of 0 to 3 wt% e.g. 1 to 3 wt%, 1 to 2.5 wt%, 2.51 to 1.04 wt%; and/or oleic acid in a concentration in the range of 0 to 70 wt% e.g. 10 to 70 wt%, 10 to 60 wt%, 10 to 50 wt%; and/or
  • linoleic acid in a concentration in the range of 9 to 11 wt%, 10 to 10.5wt%;
  • alpha-linoleic acid in a concentration in the range of 2 to 5 wt%, 2 to 3.5wt%, 2.2 to 3.2 wt%; and/or arachidic acid in a concentration in the range of 0.1 to 0.5 wt%, 0.1 to 0.5 wt%, 0.2 to 0.31wt%; and/or
  • the maternal composition of the invention may be employed in any effective dose that provides a benefit with respect to the treatment or prevention of, GDM and a condition associated therewith in a pregnant subject and/or its offspring.
  • An effective dose may be any dose that improves, by any degree, acid reflux, nausea or vomiting, indigestion, constipation and/or gestational diabetes mellitus i.e. an impaired glucose intolerance, in a pregnant subject.
  • an effective dose will depend on the type, age, size and health status of the subject, on the subject's lifestyle, as well as on its genetic heritage.
  • a particularly useful dose may be a dose equating to lOOmg to 500mg, 200 to 350mg, or 200mg to 300mg of the total fatty acids comprised in the maternal composition.
  • dose refers to a daily quantity of the maternal composition that is administered to a subject before pregnancy i.e. a subject intending to get pregnant, and/or during pregnancy i.e. to a pregnant subject, and/or during lactation.
  • the daily quantity or dose may be administered all at once or it may be spread out over several administrations throughout a day.
  • the dose may be by administered by any known method, in particular enterally e.g. orally.
  • the dose may be administered at any time of the day or night. However, depending on the condition to be treated, it may be beneficial to administer the dose at a particular time e.g. for nausea and/vomiting it may be beneficial to administer the dose in the morning or anytime during the day before eating, for acid reflux and indigestion it may be beneficial to administer the dose in the evening, before going to bed, or anytime during the day before eating, and for GDM it may be beneficial to administer the dose during the day before eating.
  • composition is administered before eating it may be administered 2 hours, 1 hour, 30mins, 20mins, lOmins or 5 mins before eating.
  • a maternal composition of the invention is administered to a subject desiring to get pregnant it may for example be administered during at least 1, 2, 3 or 4 months preceding the pregnancy or desired pregnancy. If administered to a pregnant subject, it may be administered throughout or partially throughout the pregnancy e.g. for at least 4, at least 8, at least 12, at least 16, at least 20, at least 24, at least 28, or at least 36 weeks depending on the gestational period of the subject. If administered during lactation it may be administered throughout or partially throughout the lactation period of said subject. Since nausea or vomiting is more prevalent in the first and second trimester of pregnancy, administration may be particularly beneficial in the first and/or second trimester of pregnancy to treat and/or prevent this condition.
  • administration may be particularly beneficial in the second and third trimester of pregnancy to treat and/or prevent one or more of these conditions.
  • administration may be particularly beneficial in the second and third trimester of pregnancy to treat and/or prevent this condition.
  • the maternal composition of the invention may be a fat blend that consists solely of fat.
  • the maternal composition may comprise other ingredients commonly used in maternal compositions e.g. the composition may further comprises a protein source e.g. dried milk or dried skimmed milk, and a carbohydrate source e.g. sucrose and/or maltodextrin, possibly together with lecithin, soya lecithin and/or a bulking agent.
  • the compositions of the invention may also comprise probiotics, prebiotics and vitamins and minerals. For example, vitamins and minerals recommended by a governmental body, such as US DA, for supplementation in pregnancy e.g.
  • vitamin A or retinol activity equivalent e.g. beta carotene or a mix of carotenoids, Vitamin C, Vitamin Bl, niacin, folic acid, biotin, Vitamin E.
  • RAE retinol activity equivalent
  • other possible ingredients include: other nutrients, for instance, selected from the group of lipids e.g.
  • conventional food additives such as anti-oxidants, stabilizers, emulsifiers, acidulants, thickeners, buffers or agents for pH adjustment, chelating agents, colorants, excipients, flavor agents, osmotic agents, pharmaceutically acceptable carriers, preservatives, sugars, sweeteners, texturizers, emulsifiers, water and any combination thereof.
  • the maternal composition may also alternatively or additionally contain glucose syrup, milk fat, magnesium citrate, choline salts and esters, prebiotic fibers, and/or ascorbyl palmitate.
  • Flavor compounds such as cocoa powder or honey, for example, may be added to provide taste variations.
  • the maternal composition includes other ingredients known to be useful in the treatment of nausea or vomiting, acid reflux, indigestion and/or GDM e.g. Vitamin B6 ginger or extracts thereof are known to be used to treat or prevent nausea and vomiting.
  • other ingredients known to be useful in the treatment of nausea or vomiting, acid reflux, indigestion and/or GDM e.g. Vitamin B6 ginger or extracts thereof are known to be used to treat or prevent nausea and vomiting.
  • the maternal compositions of the invention may be administered in any form suitable for ingestion by the subject e.g. it can be in the form of a powdered nutritional composition, a food product, a drink, a nutraceutical, a nutritional supplement e.g. a powdered nutritional supplement e.g. to be sprinkled on food or mixed in a medium e.g. water or juice, or milk.
  • a powdered nutritional composition e.g. a powdered nutritional supplement e.g. to be sprinkled on food or mixed in a medium e.g. water or juice, or milk.
  • Non limiting examples of food products include cereal-based products, yogurts or other milk-derived products and bars.
  • Nutritional supplements can for example be provided in the form of a pill, a tablet or a powder supplement that can for example be mixed in a medium e.g. water, milk or juice, or sprinkled on food.
  • Powdered nutritional supplements that can for example be sprinkled on food or mixed in a medium e.g. water, juice or milk, are currently well accepted by consumers.
  • a medium e.g. water, juice or milk
  • nausea and vomiting and/or acid reflux and/or indigestion and/or GDM are associated with a variety of conditions that may affect the pregnant subject and/or its offspring.
  • Nausea or vomiting, acid reflux, indigestion, and/or GDM is considered as being associated with a condition if it increases the risk of a subject having or developing that condition during pregnancy, during birth, after birth or later in the life of said pregnant subject or its offspring.
  • later in life may refer to up to 1 year after birth, up to 5 years after birth, up to 10 years after birth or 20years and beyond after birth.
  • Non limiting example of conditions effecting the pregnant subject that are associated with nausea and vomiting include; dehydration, electrolyte imbalances, nutritional deficiencies, venous thromboembolism, pulmonary embolism and preeclampsia, premature delivery, depression, bipolar disorder, and anxiety.
  • Non limiting example of conditions effecting the offspring of pregnant subjects that are associated with nausea and vomiting include; infants being small for their gestation age or suffering from depression, bipolar disorder, and anxiety later in life.
  • Non limiting example of conditions effecting the pregnant subject that are associated with GDM include; macrosomia, birth injury, premature delivery, caesarian delivery (hereinafter C-section), developing type II diabetes immediately after pregnancy and later in life.
  • Non limiting example of conditions effecting the offspring of pregnant subjects that are associated with GDM include; macrosomia, birth injury, shoulder dystocia, premature delivery, developing an impaired glucose tolerance and/or suffering from excess weight/adiposity and associated metabolic disorders e.g. type II diabetes and obesity later in life.
  • a nutritional composition in accordance with the invention for use in the manufacture of a medicament for use in the treatment or prevention of nausea or vomiting, acid reflux, indigestion, and/or GDM and a condition associated with any of the foregoing in a pregnant subject and/or its offspring, wherein said medicament is administered to said subject before and/or during pregnancy and/or during lactation
  • a method of treating and or preventing nausea or vomiting, acid reflux, indigestion, and/or GDM and a condition associated with any of the foregoing in a pregnant subject and/or its offspring comprising administering a maternal composition in accordance with the invention before and/or during pregnancy and/or during lactation.
  • the subjects were healthy males from 20 to 40 years old with a BMI of 19 to 24.9 kg m "2 , and which had a normal fasting glycemia.
  • the five study products contained the same amount of maltodextrins and whey protein, but differed in their fatty acid composition. All study products contain a third of each subject's daily energy requirement, as determined by the Harris Benedict equation multiplied by a factor 1.5 to account for physical activity.
  • TTI total energy intake
  • WP whey proteins
  • MUFA Monounstaturated fatty acids
  • PUFA Polyunsaturated fatty acids
  • MCT medium chain triglycerides
  • Meals are per-subject isocaloric, except for Ml which is the fat-free reference diet and has similar carbohydrate and protein content to the other meals, but no lipid. All other meals one third of each subject's daily energy requirement, M2 and M3 are dominated by oleic acid, M4 and M5 by MCT.
  • Soybean oil 40% emulsion incl. Citrem 22,50 5,14 lipids 18 8,1 9,00 2,06 emulsion water 12,60 2,88
  • Canola oil 40% emulsion incl. Citrem 18,75 4,29 lipids 15 6,75 7,50 1,71 emulsion water 10,50 2,40
  • Soybean oil 40% emulsion incl. Citrem 27,50 6,29 lipids 22 10 11,00 2,51 emulsion water 15,40 3,52
  • the beverage was served at room temperature in an opaque cup with a cover to be consumed orally within 5-10 minutes.
  • Blood samples were drawn time points starting from 1 hr before intake of the beverage, and during the 4 hours of the study (See further figure 1 for overview of study).
  • T50Meas is derived from these equations and represents the time in minutes when half of the stomach's content has been emptied.
  • FGF-19 fibroblast growth factor 19
  • Intestinal FGF19 can exert beneficial effects on glucose metabolism, by increasing insulin sensitivity and inducing glycogen synthesis. This hormone can also promote protein synthesis, and lead to growth of lean body mass
  • FGF19 was measured by ELISA using commercial kit from R&D Systems.
  • Meals 2 and 5 displayed no phase separation.
  • Meals 3 and 4 displayed modest creaming, which was due to fat particle aggregation. Such separation in the stomach will be relatively minor and have only a modest effect on gastric emptying. No effect on gastric empting is anticipated for Meals 2, 4, 5.
  • Palmitic Acid sn-2 (% of palmitic acid) 27.30
  • Palmitic Acid sn-1,3 (% of palmitic 72.70
  • Palmitic Acid sn-2 (% of total fat) 2.20
  • Palmitic Acid sn-1,3 (% of total fat) 5.90
  • Palmitic Acid (% of total fat) 7.80
  • Palmitic Acid sn-2 (% of palmitic acid) 20.30
  • Palmitic Acid sn-1,3 (% of palmitic 79.70
  • Palmitic Acid sn-2 (% of total fat) 1.60
  • Palmitic Acid sn-1,3 (% of total fat) 6.20

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Mycology (AREA)
  • Pediatric Medicine (AREA)
  • Otolaryngology (AREA)
  • Hospice & Palliative Care (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

A maternal composition comprising, with respect to the total fatty acid concentration, more than 50 wt% of long chain fatty acids and 50 wt% or less of medium chain fatty acids, for use to treat or prevent acid reflux, nausea or vomiting, gestational diabetes mellitus, and/or a condition associated with any of the foregoing in a pregnant subject and/or its offspring, wherein said maternal composition is administered to a mammal before and/or during pregnancy and/or during lactation.

Description

Nutritional composition for use to treat or prevent pregnancy related conditions Technical field of the invention
The present invention relates to a maternal compositions comprising, with respect to the total fatty acid concentration, more than 50wt% of long chain fatty acids and 50wt% or less of medium chain fatty acids, for use to treat or prevent acid reflux, nausea or vomiting, gestational diabetes mellitus, and/or a condition associated with any of the foregoing in a pregnant subject and/or its offspring.
Background of the invention
Nausea and vomiting, acid reflux, and indigestion are all common gastrointestinal conditions affecting pregnant mammals. The seriousness of these conditions can range from the somewhat benign and merely uncomfortable, to the severe and in rare cases life-threatening. Depending on the severity, the aforementioned conditions may not only be a threat to the health and wellbeing of the pregnant mammal, they may even pose a threat to the healthy development of her offspring.
During pregnancy a variety of physiological changes occur that are thought to contribute to the pathophysiology of the aforementioned conditions. However, changes leading to disturbances in gastric motility, and more particularly prolonged gastric emptying rates, are thought to be of particular relevance for these conditions (Prolonged gastric emptying rates increase the risk of GE (Omur O, Erdo an M, Ozkilic H, Yilmaz C, Mol Imaging Radionucl Ther. 2014), nausea and vomiting (Stein B1, Everhart KK, Lacy BE. Curr Treat Options Gastroenterol. 2014)). A fast emptying of the gastric contents after a meal can prevent or alleviate both acid reflux and nausea/vomiting.
Accordingly, compositions that can improve gastric motility, and in particular accelerate gastric emptying rates, are of great interest to the maternal health and wellness industry.
There are a variety of pharmacological compositions that can accelerate gastric emptying rates and thereby may be used to treat or prevent the aforementioned conditions. However, because of the fear of effecting the health of their offspring, mothers and their physicians are generally against the use of pharmacological therapies during pregnancy.
Accordingly, there is a need for non-pharmaceutical compositions that can accelerate gastric emptying rates and which may therefore be used to treat and/or prevent nausea and vomiting, acid reflux, and indigestion in a pregnant subject. The inventors have found that a maternal composition comprising, with respect to the total fatty acid concentration, more than 50 wt% of long chain fatty acids and 50 wt% or less of medium chain fatty acids, is emptied rapidly from the stomach and may be used to accelerate gastric emptying. This is particularly in comparison to a composition comprising more than 50 wt% of medium chain fatty acids and 50 wt% or less of long chain fatty acids. This is surprising given that the prior art teaches that long chain fatty acids slow gastric emptying whereas medium chain fatty acids have no effect on gastric emptying (Kossena GA, Charman WN, Wilson CG, O'Mahony B, Lindsay B, Hempenstall JM, Davison CL, Crowley PJ, Porter C. J.Pharm Res. 2007 Nov;24(ll):2084-96). The inventors have also found that a composition in accordance with the invention increases expression of fibroblast growth factor 19 (hereinafter FGF19) in subjects.
Summary of the invention
The invention is set out in the claims. A maternal composition comprising, with respect to the total fatty acid concentration, more than 50 wt% of long chain fatty acids and 50% or less of medium chain fatty acids, is emptied rapidly from the stomach and may be used to accelerate gastric emptying and to increase the expression of FGF19 in a subject, and accordingly, may be used to treat and/or prevent nausea or vomiting, acid reflux, indigestion and gestational diabetes in a pregnant subject e.g. a pregnant cat, dog or human.
A maternal composition in accordance with the invention comprising, with respect to the total fatty acid concentration, less than 5 wt% of medium chain fatty acids, may be particularly effective. As might a maternal composition in accordance with the invention comprising long chain fatty acids selected from the groups consisting of; myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linoleic acid, arachidic acid, eicosenoic acid, and combinations thereof. Because of the increased absorption of fatty acids when they are in the form of triglycerides, it may be preferable that each type of long chain and/or medium chain fatty acid comprised in a maternal composition of the invention is mainly e.g. at least 98%, 99%, or 99.5%, in the form of triglycerides.
Palmitic acid, in particular in the sn 1 or 3 triglyceride form, is known to cause and/or exacerbate constipation. Accordingly, a maternal composition of the invention having a low palmitic acid concentration, in particular in the sn 1 or 3 triglyceride form, of no more than 14%, more particularly no more than 7%, or those that are free from palmitic acid, in particular in the sn 1 or 3 triglyceride form, may also be used to treat or prevent constipation. A maternal composition in accordance with the invention may be particularly effective at treating or preventing nausea or vomiting, acid reflux, indigestion, gestational diabetes, and/or constipation in a pregnant subject if used in conjunction or combination with ingredients known to be useful in the treatment or prevention of these conditions e.g. Vitamin B6 ginger or extracts thereof.
A maternal composition in accordance with the invention may be administered enterally to a pregnant subject before and/or during pregnancy and/or during lactation, administration may be at any time of the day or night and may be before eating. A maternal composition in accordance with the invention may be administered in the form of a fat blend e.g. an encapsulated fat blend or alternatively it may be administered in the form of a powdered nutritional composition to be reconstituted in for example milk, juice or water, a food product, a drink, a nutritional supplement such as a powdered nutritional supplement to be sprinkled on food or mixed in an aqueous medium for example milk, juice or water, or a nutraceutical.
As stated herein, nausea or vomiting, acid reflux, indigestion and gestational diabetes are associated with a variety of conditions affecting a pregnant subject and/or their offspring e.g. dehydration, electrolyte imbalances, nutritional deficiencies, likelihood of having a small for gestational age baby, venous thromboembolism, pulmonary embolism and preeclampsia macrosomia, birth injury to the mother or infant, shoulder dystocia, premature delivery, and caesarian delivery (hereinafter C- section) developing type II diabetes immediately after pregnancy and later in life for the mother, infants developing an impaired glucose tolerance and/or suffering from excess weight/adiposity and associated metabolic disorders e.g. type II diabetes and obesity, depression, bipolar disorder, and anxiety immediately after birth or later in life. Accordingly, by treating or preventing nausea or vomiting, acid reflux, indigestion, constipation, and gestational diabetes in said pregnant subjects, the composition of the invention may also be used to treat or prevent these associated conditions in said pregnant subject or their offspring.
Brief description of the figures
Figure 1 shows an overview of the study described in Example 1.
Figure 2 shows the results for measurements of gastric emptying. M= Meal (see Table 1 and Tables 2 to 6 for composition); * indicates P<0.0001; ** indicates P=0.0003. half time (t50/min)
Figure 3 shows the results for measurements of FGF 19 in blood samples taken during experiment described in Example 1. M= Meal (see Table 1 and Tables 2 to 6 for composition); ** indicates P= 0.001. Area over baseline (AOB), (picogram/mL min). Figure 4 shows the results for measurement of bile acids in blood samples taken during experiment described in Example 1. Area over baseline (AOB), (micromole/L min). * indicates P=0.9; ** indicates P= 0.3; *** indicates P=0.0003; **** indicated P=0.0001. The present invention will now be described in more detail. Detailed Description
As stated herein above, the inventors have found that a maternal composition comprising, with respect to the total fatty acid concentration, more than 50% of long chain fatty acids and 50% or less of medium chain fatty acids, is emptied rapidly from the stomach and may be used to accelerate the gastric emptying rate.
Since, decreased gastric motility, and in particular prolonged gastric emptying, is thought to be a contributing factor for a variety of conditions affecting pregnant subjects i.e. acid reflux, nausea or vomiting, and indigestion. It follows that a composition that is rapidly emptied from the stomach and that may therefore stimulate and/or accelerate gastric emptying, may be used in the treatment or prevention of one or more of these aforementioned conditions and a condition associated therewith in a pregnant subject and/or its offspring.
A composition is considered to be rapidly emptied from the stomach if 50% of the consumed composition is emptied within 350 to 550mins, more particularly 400 to 500mins.
The time when half of a composition is emptied from the stomach is referred to as T50meas.
The gastric emptying time of a composition can be measured by methods well known to the skilled person. One such method is laid out herein in example 1.
A further advantage of maternal compositions in accordance with the invention is that they were also found to increase the secretion of bile acid and the expression of FGF-19.
FGF-19 is an intestinal hormone that can exert beneficial effects on glucose metabolism by increasing insulin sensitivity and inducing glycogen synthesis. Circulating levels of FGF-19 have been found to be reduced in pregnant subjects suffering from Gestational Diabetes Mellitus (hereinafter GDM) and to be inversely correlated with insulin resistance in this population (Wang, 2013). Increasing circulating levels of FGF19 has been proven a useful mean to prevent and to treat insulin intolerance and type 2 diabetes (Shaap et al, 2012) A composition that increases circulating FGF-19 levels may therefore be used to treat or prevent GDM or a condition associated therewith in a pregnant subject and/or its offspring.
Accordingly, in a first aspect of the present invention there is provided a maternal composition comprising, with respect to the total fatty acid concentration, 50 wt% or more of long chain fatty acids and less than 50 wt% of medium chain fatty acids, for use to treat or prevent acid reflux, nausea or vomiting, indigestion, and/or gestational diabetes mellitus, and/or a condition associated with any of the foregoing in a pregnant subject and/or its offspring. The term "subject" as used herein refers to a mammal and more particularly a cat, a dog or a human.
The term "treat" as used herein also encompasses amelioration and/or alleviation of a condition e.g. the symptoms of a condition. The term "nausea and vomiting" as used refers to any nausea and vomiting experienced in pregnancy. It includes Hyperemesis gravidarum (HG). HG is the most severe form of nausea and vomiting in pregnancy and it effects between 0.5- 2% of of pregnant women. HG may be defined as severe and persistent nausea and vomiting, and may lead to weight loss greater than 5% of prepregnancy weight, dehydration, electrolyte imbalances, and nutritional deficiencies, typically requiring hospitalisation.
Depending on the severity, nausea or vomiting may lead to a reduction in maternal weight gain throughout pregnancy, which may result in suboptimal fetal outcomes. Also, women who suffer from extreme nausea and vomiting (such as HG) can be at higher risk of having small for gestational age babies and premature births. Nausea or vomiting, in particular HG, is also known to be a risk factor for venous thromboembolism, pulmonary embolism and preeclampsia. Furthermore, in utero exposure to nausea or vomiting, in particular HG, has been associated with an increased risk in the offspring for depression, bipolar disorder, and anxiety in adulthood. The term "GDM" as used herein refers to any degree of glucose intolerance with onset or first recognition during pregnancy.
Whether or not a mammal has an impaired glucose tolerance may be determined by measuring its fasting glucose plasma concentration, or by carrying out an oral glucose tolerance test (OGTT). The skilled person will be familiar with these tests and the criteria for diagnosing an impaired glucose tolerance and hence GDM. According to the criteria set out in the National Academy of clinical biochemistry (NACB) guidelines, published by the American Association for clinical chemistry (AACC), a pregnant human subject is considered as having an impaired glucose tolerance if their fasting plasma glucose concentration equates to 5.1mmol/L or more, or if their blood glucose concentration equates to less than 10 mmol/L lhour after a 75gram glucose drink, or less than 8.5 mmol/L 2 hours after a 75gram glucose drink.
GDM may increase the risk of a number of maternal-fetal conditions, including macrosomia, birth injury to the mother or infant, shoulder dystocia, premature delivery, and caesarian delivery
(hereinafter C-section). Mothers suffering from GDM also have an increased risk of developing type II diabetes immediately after pregnancy and later in life, and the offspring of mothers suffering from GDM have an increased risk of developing an impaired glucose tolerance and/or suffering from excess weight/adiposity and associated metabolic disorders e.g. type II diabetes and obesity later in life.
The term "acid reflux" as used refers to a condition wherein acid comes up from the stomach into the esophagus, it is also referred to a Gastroesophageal reflux (GE ) and in severe cases to a gastroesophageal reflux disease (GERD). The term "indigestion" as used refers to a condition wherein digestion is impaired in a subject. It is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating, belching, nausea. The term "Medium chain fatty acids" as used herein refers to n-carboxylic acids of saturated linear aliphatic chains comprising 6-12 carbon atoms, and derivatives thereof. Any reference to a specific medium chain fatty acid is also a reference to any derivative thereof.
The term "Long chain fatty acids" as used herein refers to n-carboxylic acids of saturated linear aliphatic chains comprised of 13 or more, more particularly 13 to 22, carbon atoms, and derivatives thereof. Any reference to a specific long chain fatty acid is also a reference to any derivative thereof.
Non limiting examples of derivatives of medium and/or long chain fatty acids include phospholipids, triglycerides, diglycerides, and monoglycerides. The maternal composition of the invention may comprise long chain fatty acid in any concentration in the range of 50 to 100 wt% with respect to the total fatty acid content e.g.50 -60 wt%, 50-70 wt%, 60-80 wt%, 60-90 wt%, 95-100 wt%.
The maternal composition of the invention may comprise medium chain fatty acids in any concentration less than 50 wt%, with respect to the total fatty acids, e.g. in the range 0-49.99 wt%, 10-40 wt%, 5-30 wt%, 12-45 wt%. In an embodiment the composition of the invention is free or substantially free from medium chain fatty acids. By substantially free is meant that the composition comprises up to 5%, up to 2% or up to 1% of medium chain fatty acids.
Any long chain fatty acid that is suitable for ingestion by the pregnant subject may be used in the composition of the invention.
Non limiting examples of suitable long chain fatty acids include; myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linoleic acid, arachidic acid, eicosenoic acid, and combinations thereof.
Any medium chain fatty acid that is suitable for ingestion by the pregnant subject may be used in the composition of the invention.
Non limiting examples of suitable medium chain fatty acids include; caproic acid, caprylic acid, decanoic acid, dodecanoic acid, and combinations thereof.
In a particular embodiment of the invention the long and/or medium chain fatty acids comprised in the maternal composition of the invention are mainly in the form of triglycerides. By mainly is meant at least 98 wt%, more particularly at least 99.5wt%, even more particularly more than 99.5 wt%.
The long and medium chain fatty acids comprised within the maternal compositions of the invention may be saturated, unsaturated or polyunsaturated. Examples of unsaturated fatty acids include oleic acid, as well as polyunsaturated fatty acids (PUFAS), for example linoleic acid, alpha-linoleic, arachidonic acid, docohexaenoic acid, and/or eicosenoic acid
Examples of polyunsaturated fatty acids include alpha-linolenic acid (ALA) 18:3, stearidonic acid (SDA) 18:4, eicosatrienoic acid (ETE) 20:3, n-3 eicosatetraenoic acid (ETA) 20:4, eicosapentaenoic acid (EPA) 20:5, n-3 docosapentaenoic acid (DPA) 22:5, docosahexaenoic acid (DHA) 22:6, linoleic acid 18:2, gamma-linolenic acid (GLA) 18:3, n-6 eicosadienoic acid 20:2, dihomo-gamma-linolenic acid (DGLA) 20:3, arachidonic acid (AA or A A) 20:4, n-6 docosadienoic acid 22:2, and docosapentaenoic acid 22:5.
In a particular embodiment the composition of the invention comprises at least one unsaturated fatty acid, mainly in the form of triglycerides, in an amount of at least 15 wt%, at least 20 wt%, at least 35 wt%, at least 38 wt%, 40 wt % to 90 wt%, 50 wt% to 80 wt%, 50 wt% to 75 wt%, 50 wt% to 70 wt %, 55 wt% to 70 wt %, with respect to the total fatty acid concentration.
In another embodiment of the invention, the maternal composition of the invention comprises at least one polyunsaturated fatty acid (PUFA), the PUFA(s) being present in an amount generally of at least 8 wt%, or 10 wt%, with respect to the total fatty acid concentration. The presence of PUFAs is especially advantageous for several key health benefits such as cognitive benefits, visual and cognitive development, anti-inflammatory properties, as it is known in the art.
It may particularly beneficial if the maternal composition of the invention comprise PUFAs selected from the group consisting of alpha-linolenic acid, and/or linoleic acid, which are essential fatty acids, and /or docosahexanoic acid (DHA, C22:6) and/or arachidonic acid (ARA, C20:4) which are known for their health benefits with respect to cognition for example.
Essential fatty acids are fatty acids that must be ingest because the body requires them for good health but cannot synthesise them.
In a particular embodiment the maternal composition of the invention comprise linoleic and/or alpha linoleic acid, in particular in a total combined concentration, with respect to the total fatty acid concentration, in the range of 10 to 15 wt%, 12 to 14 wt%, 12.5 to 13.9 wt%. In another embodiment of the present invention the maternal composition of the invention comprises palmitic acid, more particularly in the sn 1 or 3 triglyceride form, in an amount in the range of not more than 14 wt%, more particularly not more than 7 wt%, 6 wt%, 5 wt%, 4 wt%, 3 wt%,
2 wt%, with respect to the total fatty acid content.
Palmitic acid, in particular in the sn 1 or 3 triglyceride form, is released as a free fatty acid during digestion and can form soaps with calcium that are not digested. These are excreted and make the stool consistency harder. Thus, reducing the amounts of the palmitic acid, in particular in the sn 1 or
3 triglyceride form, can help to prevent or alleviate constipation.
11%- 38% of pregnant women experience constipation. Constipation is described as infrequent bowel movements or difficult evacuation.
In another embodiment of the present invention the maternal composition is free from palmitic acid, in particular the sn 1 or 3 triglyceride form.
In further embodiments of the present invention the maternal composition comprises, with respect with the total fatty acid content, the following medium and/or long chain fatty acids:
caprioic acid (hexanoic acid) in a concentration in the range of 0 to 1 wt% e.g 0.05 to 0.5 wt%, 0.05 to 0.4 wt%, 0.06 to 0.4 wt%, or 0.07 to 0.3 wt%; and/or
caprylic acid (octanoic acid) in a concentration in the range of 0 to 10 wt% e.g. 2 to 8 wt%, 1.55 to 2 wt%, 1.6 to 2 wt%, 1.65 to 2 wt%, 1.7 to 2 wt%; and/or
decanoic acid in a concentration in the range of 0 to 10 wt% e.g. 0 to 1.8 wt%, 0.1 to 1.8 wt%, 1 to 1.7wt%, 1 to 1.5wt% or 1.2 to 1.8 wt%; and/or
dodecanoic acid in a concentration in the range of 0 to 12.0 wt% e.g. 0 to 10 wt%, 0 to 8 wt%, 0 to 6 wt%, 0 to 4 wt%, 1 to 12 wt%, 2 to 12 wt%. 4 to 12 wt%, 6 to 12 wt%, 8 to 12 wt%, 10 to 12 wt%. myristic acid in a concentration in the range of 0 to wt% e.g 0.05 to 0.5 wt%, 0.05 to 0.4 wt%, 0.06 to 0.4 wt%, or 0.07 to 0.3 wt%; and/or
palmitic acid in a concentration in the range of 0 to 5 wt% e.g. 2 to 4 wt%, 2 to 3.5 wt%, 2.3 to 3.4 wt% and/or
palmitoleic acid in a concentration in the range of 0 to 1 wt% e.g 0.05 to 2 wt%, 0.05 to 1.5 wt%, 0.05 to 0.12 wt%; and/or
stearic acid in a concentration in the range of 0 to 3 wt% e.g. 1 to 3 wt%, 1 to 2.5 wt%, 2.51 to 1.04 wt%; and/or oleic acid in a concentration in the range of 0 to 70 wt% e.g. 10 to 70 wt%, 10 to 60 wt%, 10 to 50 wt%; and/or
linoleic acid in a concentration in the range of 9 to 11 wt%, 10 to 10.5wt%; and/or
alpha-linoleic acid in a concentration in the range of 2 to 5 wt%, 2 to 3.5wt%, 2.2 to 3.2 wt%; and/or arachidic acid in a concentration in the range of 0.1 to 0.5 wt%, 0.1 to 0.5 wt%, 0.2 to 0.31wt%; and/or
eicosenoic acid in a concentration in the range of 0.5 to 1 wt%, 0.5 to 0.6wt%, 0.51 to 0.57wt%; and/or any combination thereof. The maternal composition of the invention may be employed in any effective dose that provides a benefit with respect to the treatment or prevention of, GDM and a condition associated therewith in a pregnant subject and/or its offspring.
An effective dose may be any dose that improves, by any degree, acid reflux, nausea or vomiting, indigestion, constipation and/or gestational diabetes mellitus i.e. an impaired glucose intolerance, in a pregnant subject.
It is well within the purview of the skilled person to determine an effective dose. Typically, an effective dose will depend on the type, age, size and health status of the subject, on the subject's lifestyle, as well as on its genetic heritage.
A particularly useful dose may be a dose equating to lOOmg to 500mg, 200 to 350mg, or 200mg to 300mg of the total fatty acids comprised in the maternal composition. The term "dose" as used herein refers to a daily quantity of the maternal composition that is administered to a subject before pregnancy i.e. a subject intending to get pregnant, and/or during pregnancy i.e. to a pregnant subject, and/or during lactation.
The daily quantity or dose may be administered all at once or it may be spread out over several administrations throughout a day. The dose may be by administered by any known method, in particular enterally e.g. orally.
The dose may be administered at any time of the day or night. However, depending on the condition to be treated, it may be beneficial to administer the dose at a particular time e.g. for nausea and/vomiting it may be beneficial to administer the dose in the morning or anytime during the day before eating, for acid reflux and indigestion it may be beneficial to administer the dose in the evening, before going to bed, or anytime during the day before eating, and for GDM it may be beneficial to administer the dose during the day before eating.
If a composition is administered before eating it may be administered 2 hours, 1 hour, 30mins, 20mins, lOmins or 5 mins before eating.
If a maternal composition of the invention is administered to a subject desiring to get pregnant it may for example be administered during at least 1, 2, 3 or 4 months preceding the pregnancy or desired pregnancy. If administered to a pregnant subject, it may be administered throughout or partially throughout the pregnancy e.g. for at least 4, at least 8, at least 12, at least 16, at least 20, at least 24, at least 28, or at least 36 weeks depending on the gestational period of the subject. If administered during lactation it may be administered throughout or partially throughout the lactation period of said subject. Since nausea or vomiting is more prevalent in the first and second trimester of pregnancy, administration may be particularly beneficial in the first and/or second trimester of pregnancy to treat and/or prevent this condition.
Since acid reflux and indigestion are more prevalent in second and third trimester of pregnancy, administration may be particularly beneficial in the second and third trimester of pregnancy to treat and/or prevent one or more of these conditions.
Since the risk of GDM increases in the second and third trimester of pregnancy, administration may be particularly beneficial in the second and third trimester of pregnancy to treat and/or prevent this condition.
The maternal composition of the invention may be a fat blend that consists solely of fat. Alternatively the maternal composition may comprise other ingredients commonly used in maternal compositions e.g. the composition may further comprises a protein source e.g. dried milk or dried skimmed milk, and a carbohydrate source e.g. sucrose and/or maltodextrin, possibly together with lecithin, soya lecithin and/or a bulking agent. The compositions of the invention may also comprise probiotics, prebiotics and vitamins and minerals. For example, vitamins and minerals recommended by a governmental body, such as US DA, for supplementation in pregnancy e.g. calcium, magnesium, phosphorus, iron, zinc, copper, iodine, selenium, vitamin A or retinol activity equivalent (RAE) e.g. beta carotene or a mix of carotenoids, Vitamin C, Vitamin Bl, niacin, folic acid, biotin, Vitamin E. Non limiting examples of other possible ingredients include: other nutrients, for instance, selected from the group of lipids e.g. Short chain fatty acids , carbohydrates, and protein, micronutrients (in addition to those set out above), or pharmaceutically active agents; conventional food additives such as anti-oxidants, stabilizers, emulsifiers, acidulants, thickeners, buffers or agents for pH adjustment, chelating agents, colorants, excipients, flavor agents, osmotic agents, pharmaceutically acceptable carriers, preservatives, sugars, sweeteners, texturizers, emulsifiers, water and any combination thereof.
The maternal composition may also alternatively or additionally contain glucose syrup, milk fat, magnesium citrate, choline salts and esters, prebiotic fibers, and/or ascorbyl palmitate. Flavor compounds, such as cocoa powder or honey, for example, may be added to provide taste variations.
It may be particularly beneficial if the maternal composition includes other ingredients known to be useful in the treatment of nausea or vomiting, acid reflux, indigestion and/or GDM e.g. Vitamin B6 ginger or extracts thereof are known to be used to treat or prevent nausea and vomiting.
The maternal compositions of the invention may be administered in any form suitable for ingestion by the subject e.g. it can be in the form of a powdered nutritional composition, a food product, a drink, a nutraceutical, a nutritional supplement e.g. a powdered nutritional supplement e.g. to be sprinkled on food or mixed in a medium e.g. water or juice, or milk.
Non limiting examples of food products include cereal-based products, yogurts or other milk-derived products and bars.
Nutritional supplements can for example be provided in the form of a pill, a tablet or a powder supplement that can for example be mixed in a medium e.g. water, milk or juice, or sprinkled on food.
Powdered nutritional supplements that can for example be sprinkled on food or mixed in a medium e.g. water, juice or milk, are currently well accepted by consumers. As stated hereinabove, nausea and vomiting and/or acid reflux and/or indigestion and/or GDM are associated with a variety of conditions that may affect the pregnant subject and/or its offspring.
Nausea or vomiting, acid reflux, indigestion, and/or GDM is considered as being associated with a condition if it increases the risk of a subject having or developing that condition during pregnancy, during birth, after birth or later in the life of said pregnant subject or its offspring.
As used herein later in life may refer to up to 1 year after birth, up to 5 years after birth, up to 10 years after birth or 20years and beyond after birth.
Non limiting example of conditions effecting the pregnant subject that are associated with nausea and vomiting include; dehydration, electrolyte imbalances, nutritional deficiencies, venous thromboembolism, pulmonary embolism and preeclampsia, premature delivery, depression, bipolar disorder, and anxiety.
Non limiting example of conditions effecting the offspring of pregnant subjects that are associated with nausea and vomiting include; infants being small for their gestation age or suffering from depression, bipolar disorder, and anxiety later in life.
Non limiting example of conditions effecting the pregnant subject that are associated with GDM include; macrosomia, birth injury, premature delivery, caesarian delivery (hereinafter C-section), developing type II diabetes immediately after pregnancy and later in life.
Non limiting example of conditions effecting the offspring of pregnant subjects that are associated with GDM include; macrosomia, birth injury, shoulder dystocia, premature delivery, developing an impaired glucose tolerance and/or suffering from excess weight/adiposity and associated metabolic disorders e.g. type II diabetes and obesity later in life.
In another aspect of the invention there is provided a nutritional composition in accordance with the invention for use in the manufacture of a medicament for use in the treatment or prevention of nausea or vomiting, acid reflux, indigestion, and/or GDM and a condition associated with any of the foregoing in a pregnant subject and/or its offspring, wherein said medicament is administered to said subject before and/or during pregnancy and/or during lactation
In another aspect there is provided a method of treating and or preventing nausea or vomiting, acid reflux, indigestion, and/or GDM and a condition associated with any of the foregoing in a pregnant subject and/or its offspring comprising administering a maternal composition in accordance with the invention before and/or during pregnancy and/or during lactation.
The present invention will now be described in further details by the way of the following examples.
Examples Example 1
A cross-over study was designed where each subject received all test meals. Subjects were randomly assigned to one of 10 possible randomized sequences of the 5 test products. Each subject received the 5 study products during 5 different visits, separated by at least 1-week washout, and at most 4 weeks. Each visit spread over two days (D-l and DO):
• Day -1 for getting standardized meals
• Day 0 for:
- Baseline plasma samples
- Study product intake
- Plasma samples - Breath samples
The subjects were healthy males from 20 to 40 years old with a BMI of 19 to 24.9 kg m"2, and which had a normal fasting glycemia.
Study description
The five study products contained the same amount of maltodextrins and whey protein, but differed in their fatty acid composition. All study products contain a third of each subject's daily energy requirement, as determined by the Harris Benedict equation multiplied by a factor 1.5 to account for physical activity.
1. Maltodextrin (43% TEI)+whey proteins (WP, 12% TEI)
2. Maltodextrin (43% TEI)+WP (12% TEI)+MUFA (39% TEI)+PUFA (6% TEI)
3. Maltodextrin (43% TEI)+WP (12% TEI)+MUFA (27% TEI)+MCT (12% TEI)+PUFA (6% TEI) 4. Maltodextrin (43% TEI)+ WP (12% TEI)+MUFA (12% TEI)+MCT (27% TEI)+PUFA (6% TEI)
5. Maltodextrin (43% TEI)+WP (12% TEI) + MCT(39% TEI)+PUFA (6% TEI).
(TEI= total energy intake; WP= whey proteins; MUFA= Monounstaturated fatty acids; PUFA=Polyunsaturated fatty acids; MCT=medium chain triglycerides) See also Table 1 for composition of meals.
100 mg of 13C-octanoate (Eurisotope, St Aubin, France) was added to each study product to monitor gastric emptying. Table 1: Fatty acid profile of study products
Meals are per-subject isocaloric, except for Ml which is the fat-free reference diet and has similar carbohydrate and protein content to the other meals, but no lipid. All other meals one third of each subject's daily energy requirement, M2 and M3 are dominated by oleic acid, M4 and M5 by MCT.
Table 1
Table 2 Composition of Meal 1 (Ml) maltodextrin (=3 wt% water) 43 107,50 24,57
Whey protein 12 30,00 6,86
Water to add 300,00 68,57
Total without additives (kg) 437,50 100,00
TS final beverage (% m/m) 31%
Masking LG 0,19
Stevia 0,01
Strawberry aroma 0,08
Table 3: Composition of Meal 2 (M2)
Table 4: Composition of Meal 3 (M3)
Table 5: Composition of Meal 4 (M4) mix) (m/m)
Meal 4
maltodextrin 43 107,50 24,57
Whey protein 12 30,00 6,86
MCT 40% emulsion incl. Citrem 83,75 19,14 lipids 67 30,15 33,50 7,66 emulsion water 46,90 10,72
Soybean oil 40% emulsion incl. Citrem 22,50 5,14 lipids 18 8,1 9,00 2,06 emulsion water 12,60 2,88
Canola oil 40% emulsion incl. Citrem 18,75 4,29 lipids 15 6,75 7,50 1,71 emulsion water 10,50 2,40
High oleic sunflower oil 40% emulsion incl. 0,00 0,00 Citrem
lipids 0 0 0,00 0,00 emulsion water 0,00 0,00
Total Citrem (4% m/m emulsion) 5,00 1,14
Water to add 175,00 40,00
Total without additives (kg) 437,50 100,00
TS final beverage (% m/m) 43%
Masking LG 0,19
Stevia 0,01
Strawberry aroma 0,08
Table 6: Composition of Meal 5 (M5)
Lipid % of TEI Amount Amount composition per diet per (% final oil (g) lOOg mix) (m/m)
Meal 5 maltodextrin 43 107,50 24,57
Whey protein 12 30,00 6,86
MCT 40% emulsion incl. Citrem 97,50 22,29 lipids 78 35,1 39,00 8,91 emulsion water 54,60 12,48
Soybean oil 40% emulsion incl. Citrem 27,50 6,29 lipids 22 10 11,00 2,51 emulsion water 15,40 3,52
Canola oil 40% emulsion incl. Citrem 0,00 0,00 lipids 0 0 0,00 0,00 emulsion water 0,00 0,00
High oleic sunflower oil 40% emulsion incl. 0,00 0,00 Citrem
lipids 0 0 0,00 0,00 emulsion water 0,00 0,00
Total Citrem (4% m/m emulsion) 5,00 1,14
Water to add 175,00 40,00
Total without additives (kg) 437,50 100,00
TS final beverage (% m/m) 43%
Masking LG 0,19
Stevia 0,01
Strawberry aroma 0,08
Study
On the day of the kinetic, the participants came fasted. There were no other diet restrictions.
The beverage was served at room temperature in an opaque cup with a cover to be consumed orally within 5-10 minutes.
Blood samples were drawn time points starting from 1 hr before intake of the beverage, and during the 4 hours of the study (See further figure 1 for overview of study).
Gastric emptying
In brief, 100 mg of 13C-octanoate was dissolved into the test meals on the evening preceding the test to ensure complete homogeneous dissolution of the tracer. On the day of the metabolic investigation, wwo baseline breath samples were collected in 3 glass vacutainers at times -30 and -15 min prior to the meal ingestion. All test meals were ingested in less than 10 minutes, and time zero was defined as the end of food ingestion. Breath samples were collected at times 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 and 240 minutes using Easy Sampler Device and Crimp Tubes from QuinTron (Milwaukee, Wisconsin, USA)
Breath 13C02 samples were analyzed for 13C enrichment using an isotope ratio mass spectrometer (IRMS, Delta V Advantage, Thermo, Bremen, Germany) device hyphenated to a gas chromatography system (GC Trace, Thermo, Bremen, Germany). The analyses were performed to assess the 13C02/12C02 ratio (expressed as 613C, %o). C02 standard gas was calibrated against international standard allowing 13C/12C ratio to be quoted against the Vienna Pee De Belemnite (VPDB).
Data were transformed using non linear equations according to Ghoos et al (2) using the R software to calculate non-linear curve fitting. The parameter T50Meas is derived from these equations and represents the time in minutes when half of the stomach's content has been emptied.
See also Figure 2 for results. FGF-19
FGF-19 (fibroblast growth factor 19) is an intestinal hormone which can reduce the risk of hepatic steatosis and cholestasis, and promote liver growth. Intestinal FGF19 can exert beneficial effects on glucose metabolism, by increasing insulin sensitivity and inducing glycogen synthesis. This hormone can also promote protein synthesis, and lead to growth of lean body mass
FGF19 was measured by ELISA using commercial kit from R&D Systems.
The results show FGF-19 is more stimulated in M3 and M2, i.e. those meals which are have low or no MCT content induce significantly higher levels of FGF_19 as compared to controls. The meals M4 and M5 were not significantly different from control.
See also Figure 3. Creaming experiments
Experiments were performed to validate the gastric emptying method.
Method: Samples of each test product (Ml- M5) were mixed in equal proportion with simulated gastric juice, which consisted of 2 mg/mL NaCI and 4.5 mg/mL pepsin at 37 °C and a pH of 1.9. The physical distribution of fat throughout each mixture was assessed by measuring optical turbidity as a function of sample height (every 30 um) over time at 37°C using a Turbiscan™ LAB.
The results are presented below in Table 7. Meal 3 was diluted to test how sstable it was (Meal 3 (-
10%)).
Table 7: In vitro meal coagulation test results
Conclusions: Meals 2 and 5 displayed no phase separation. Meals 3 and 4 displayed modest creaming, which was due to fat particle aggregation. Such separation in the stomach will be relatively minor and have only a modest effect on gastric emptying. No effect on gastric empting is anticipated for Meals 2, 4, 5.
Example 2A:
Table 8: Example of a lipid blend according to the invention
Palmitic Acid sn-2 (% of palmitic acid) 27.30
Palmitic Acid sn-1,3 (% of palmitic 72.70
acid)
Palmitic Acid sn-2 (% of total fat) 2.20
Palmitic Acid sn-1,3 (% of total fat) 5.90
Example 2B:
Table 9: Example of lipid blend according to the invention
Ingredients Variant 2: No Betapol-55
MCT Oil -
Palm Olein -
Milk Fat 15.00
Betapol-55 0.00
Coconut Oil 20.00
Canola Oil 22.87
Sunflower Oil 18.28
High Oleic Sunflower Oil 21.59
A ASCO/DHASCO 1:1 1.00
ARASCO/DHASCO 2:1 1.25
Palmitic Acid (% of total fat) 7.80
Palmitic Acid sn-2 (% of palmitic acid) 20.30
Palmitic Acid sn-1,3 (% of palmitic 79.70
acid)
Palmitic Acid sn-2 (% of total fat) 1.60
Palmitic Acid sn-1,3 (% of total fat) 6.20

Claims

Claims
1. A maternal composition comprising, with respect to the total fatty acid concentration, more than 50 wt% of long chain fatty acids and 50 wt% or less of medium chain fatty acids, for use to treat or prevent acid reflux, nausea or vomiting, indigestion, gestational diabetes mellitus, and/or a condition associated with any of the foregoing in a pregnant mammal and/or its offspring, wherein said maternal composition is administered to a mammal before and/or during pregnancy and/or during lactation.
2. The maternal composition according to claim 1 comprising, with respect to the total fatty acid concentration, up to 5 wt% of medium chain fatty acids.
3. The maternal composition of claim 1 or 2 wherein, the long chain fatty acids are selected from the group consisting of: myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alpha-linoleic acid, arachidic acid, eicosenoic acid, and combinations thereof.
4. The maternal composition of any one of claim 1 to 3 wherein, at least 98 wt% of long chain
and/or medium chain fatty acids comprised in said maternal composition are in the form of triglycerides.
5. The maternal composition of any one of claims 1 to 4 wherein, said maternal composition
comprises, with respect to the total fatty acid concentration, no more than 14 wt% of palmitic acid.
6. The maternal composition according to any one of the preceding claims, comprising, with respect to the total fatty acid concentration, caprioic acid in a concentration in the range of 0 to 1 wt%, and/or caprylic acid in a concentration in the range of 0 to 10 wt%; and/or decanoic acid in a concentration in the range of 0 to 10 wt%; and/or dodecanoic acid in a concentration in the range of 0 to 12.0 wt%; and/or myristic acid in a concentration in the range of 0 to 0.5wt% ; and/or palmitic acid in a concentration in the range of 0 to 5 wt%; and/or palmitoleic acid in a concentration in the range of 0 to 1 wt%; and/or stearic acid in a concentration in the range of 0 to 3 wt%; and/or oleic acid in a concentration in the range of 0 to 70 wt%; and/or linoleic acid in a concentration in the range of 9 to 11 wt%, and/or alpha-linoleic acid in a concentration in the range of 2 to 5 wt%; and/or arachidic acid in a concentration in the range of 0.1 to 0.5 wt%,and/or eicosenoic acid in a concentration in the range of 0.5 to 1 wt%; and/or any combination thereof.
7. The maternal composition according to any one of the preceding claims, further comprising vitamin B6, ginger or an extract of ginger.
8. The maternal composition according to any one of the preceding claims, wherein said composition is a fat blend.
9. The maternal composition according to any one of claims 1 to 7, wherein said composition is in the form of a powdered nutritional composition, a food product, a drink, a nutritional supplement such as a powdered nutritional supplement, or a nutraceutical.
10. The maternal composition according to any one of claims 5 to 9 for use to treat and/or prevent constipation.
11. The maternal composition according to any one of the preceding claims for use as defined in claim 1, wherein the mammal is a mammal selected from the group consisting of a cat, a dog, a human.
12. The maternal composition according to any one of the preceding claims for use as defined in claim 1 wherein said composition is administered before eating.
13. The maternal composition as defined in any one of claims 1 to 9 for use in the manufacture of a medicament for use in the treatment or prevention of acid reflux, nausea or vomiting, indigestion, gestational diabetes mellitus, and a condition associated with any of the foregoing in a pregnant mammal and/or its offspring.
14. The nutritional composition according to any one of claims 1 to 9 for use as defined in any one of claims 1 or claim 13, wherein the condition associated with acid reflux, gestational diabetes mellitus and/or nausea and vomiting, is selected from the group consisting of: dehydration, electrolyte imbalances, nutritional deficiencies, small for gestational age babies, venous thromboembolism, pulmonary embolism and preeclampsia macrosomia, birth injury to the mother or infant, shoulder dystocia, premature delivery, caesarian delivery (hereinafter C- section) , type II diabetes immediately after pregnancy and later in life of the pregnant mammal, offspring impaired glucose tolerance and/or excess weight/adiposity and associated metabolic disorders e.g. type II diabetes and obesity in the offspring, and depression, bipolar disorder, and anxiety later in the life of the offspring.
15. A method of treating and/or preventing indigestion, acid reflux, gestational diabetes mellitus, nausea or vomiting, and a condition associated with any of the foregoing in a pregnant mammal and/or its offspring, comprising administering a maternal composition as defined in any one of claims 1 to 9 to a mammal before and/or during pregnancy and/or during lactation.
EP15771931.1A 2014-09-30 2015-09-29 Nutritional composition for use to treat or prevent pregnancy related conditions Withdrawn EP3200622A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14187062 2014-09-30
PCT/EP2015/072396 WO2016050758A1 (en) 2014-09-30 2015-09-29 Nutritional composition for use to treat or prevent pregnancy related conditions

Publications (1)

Publication Number Publication Date
EP3200622A1 true EP3200622A1 (en) 2017-08-09

Family

ID=51655584

Family Applications (1)

Application Number Title Priority Date Filing Date
EP15771931.1A Withdrawn EP3200622A1 (en) 2014-09-30 2015-09-29 Nutritional composition for use to treat or prevent pregnancy related conditions

Country Status (7)

Country Link
EP (1) EP3200622A1 (en)
CN (1) CN106604651A (en)
BR (1) BR112017002553A2 (en)
CA (1) CA2952767A1 (en)
MX (1) MX2017004017A (en)
PH (1) PH12017500051A1 (en)
WO (1) WO2016050758A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107960656A (en) * 2018-01-19 2018-04-27 云南省第三人民医院 A kind of pregnant woman's prenatal nutrition composition
CA3090800C (en) * 2018-02-19 2023-10-03 Abbott Laboratories Lipid emulsion nutritional product
CN108872424A (en) * 2018-04-16 2018-11-23 南京医科大学 Dodecanoic acid and prostaglandin E2 combination are used as macrosomia's auxiliary diagnosis marker and its application
NZ769854A (en) * 2018-06-22 2024-03-22 Fonterra Cooperative Group Ltd Use of polar lipids to treat or prevent gestational diabetes mellitus

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5000975A (en) * 1988-12-29 1991-03-19 American Home Products Corporation Randomized palm oil fat composition for infant formulas
US20050037065A1 (en) * 1999-05-27 2005-02-17 Drugtech Corporation Nutritional formulations
US20040219188A1 (en) * 2003-05-02 2004-11-04 Comer Gail M. Composition and methods for nutritional management of patients with hepatic disease
AU2007227838B2 (en) * 2006-03-23 2012-10-25 N.V. Nutricia Preterm formula
EP2110027A1 (en) * 2008-04-01 2009-10-21 Nestec S.A. Long-chain polyunsaturated fatty acids (LC-PUFA) in maternal nutrition during pregnancy and lactation
RU2516782C2 (en) * 2010-01-29 2014-05-20 Н.В. Нютрисиа Liquid enteral nutrient composition suitable for enteral feeding, minimising upper and lower gastrointestinal complications
WO2013134482A1 (en) * 2012-03-07 2013-09-12 Children's Medical Center Corporation Methods for enhancing, improving, or increasing fertility or reproductive function
US9629820B2 (en) * 2012-12-24 2017-04-25 Qualitas Health, Ltd. Eicosapentaenoic acid (EPA) formulations

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
None *
See also references of WO2016050758A1 *

Also Published As

Publication number Publication date
PH12017500051A1 (en) 2017-05-22
WO2016050758A1 (en) 2016-04-07
CN106604651A (en) 2017-04-26
MX2017004017A (en) 2017-06-21
BR112017002553A2 (en) 2017-12-05
CA2952767A1 (en) 2016-04-07

Similar Documents

Publication Publication Date Title
EP2563167B9 (en) Methods and lipid compositions for promoting development of gut flora
Wu et al. Health consequences of nutrition in childhood and early infancy
EP1976397B1 (en) Infant immunological formula
PT2026791E (en) Maternal supplement
EP1874138A2 (en) Nutrition with lipids and non-digestible saccharides
WO2016050758A1 (en) Nutritional composition for use to treat or prevent pregnancy related conditions
AU2019280019A1 (en) Nutritional composition for use in promoting gut and/or liver maturation and/or repair
JP2023503401A (en) A mixture of HMOs to improve the microflora of pregnant women
US11554131B2 (en) Mixture of HMOs for treating autoimmune diseases
AU2015327029B2 (en) Nutritional composition with low content of medium-chain fatty acids in specific proportions, and its uses.
Hatem et al. Trans isomeric fatty acids in human milk and their role in infant health and development
US9149050B2 (en) Use of conjugated linoleic acid
RU2586150C2 (en) Additive for mother intended for reinforcing the immune system of a child
JP6902797B2 (en) Nutritional composition for diarrhea prevention
TW201628509A (en) Nutritional supplements containing a peptide component and uses thereof
BR112019028039A2 (en) nutritional composition, use of a combination of bifidobacterium breve and non-digestible oligosaccharides, and method to prevent and / or reduce the risk of hyperinsulinemia
TWI803459B (en) Composition for use in the prophylaxis of allergic disease
JPWO2015178492A1 (en) Antiallergic agent, allergic diarrhea ameliorating agent and pharmaceutical composition
EP4346448A1 (en) Infant formula comprising milk fat for reducing the risk of obesity in at risk infants
JP5258144B2 (en) Method for producing solid coenzyme Q10 oral preparation with improved absorbability

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20170502

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SOCIETE DES PRODUITS NESTLE S.A.

17Q First examination report despatched

Effective date: 20191119

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20200603