TW201247112A - Infant formula for use in the prevention of cardiovascular diseases - Google Patents
Infant formula for use in the prevention of cardiovascular diseases Download PDFInfo
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201247112 六、發明說明: 【發明所屬之技術領域】 本發明係關於嬰兒配方、較佳新生兒配方,其用於尤其 在以後生命中預防心血管疾病及用於預防高血壓。 【先前技術】 血壓係當心臟泵出血液時血液推壓動脈壁之力。若此壓 力升高並隨時間而保持較高,則其可以多種方式損害身 體。 血壓數值包括收縮壓及舒張壓。收縮血壓係當心臟跳動 同時泵送血液時之壓力。舒張血壓係當心臟在跳動之間處 於靜息時之壓力。 高血壓係與較高風險之心血管疾病相關之嚴重病況,且 可導致(例如)冠狀動脈心臟病、心臟衰竭、中風、腎衰竭 及其他健康問題。在心血管疾病中,其症狀或原因中之一 者呈現高血壓者尤其引人關注。 咼血壓係由持續高血壓引起之疾病病況。高血壓係全身 動脈血壓超出正常範圍之心臟慢性醫學病況。高血壓範圍 通常係指收縮血壓為140 mmHg或更高或舒張血壓為9〇 _Hg或更高m。將高血|分類為原發性(_町, essential)或繼發性。約9〇%至95%之病例稱為「原發性高 血壓」,其係指尚未發現醫學原因之高血壓。剩餘5%至 10%之病例(繼發性高血壓)係由影響腎 '動脈、心臟或内 分泌系統之其他病況引起。 全世界高血壓發病率正在增加。此外,即使在未表現外 163923.doc 201247112201247112 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to infant formulas, preferably neonatal formulations, for the prevention of cardiovascular diseases and for the prevention of hypertension, especially in later life. [Prior Art] Blood pressure is the force by which blood pushes the arterial wall when the heart pumps blood. If this pressure rises and remains high over time, it can damage the body in a variety of ways. Blood pressure values include systolic and diastolic blood pressure. Systolic blood pressure is the pressure when the heart beats while pumping blood. Diastolic blood pressure is the pressure at rest when the heart is beating. Hypertension is a serious condition associated with higher-risk cardiovascular disease and can lead to, for example, coronary heart disease, heart failure, stroke, kidney failure, and other health problems. Among cardiovascular diseases, one of the symptoms or causes of hypertension is particularly interesting. Blood pressure is a disease condition caused by persistent high blood pressure. Hypertensive system is a chronic medical condition in which the heart's arterial blood pressure is outside the normal range. The range of hypertension usually means a systolic blood pressure of 140 mmHg or higher or a diastolic blood pressure of 9 〇 _Hg or higher. Classify high blood | as primary (_machi, essential) or secondary. About 9 to 95% of cases are called "primary hypertension", which refers to hypertension that has not been found for medical reasons. The remaining 5% to 10% of cases (secondary hypertension) are caused by other conditions affecting the kidney's arteries, heart or endocrine system. The incidence of hypertension worldwide is increasing. In addition, even in the absence of performance 163923.doc 201247112
部症狀之輕微或輕 症,例如,大腦中; 就嬰兒營養而言,人類母乳代表無可爭議之黃金標準。 然而在些情形下,由於醫學原因,或由於母親選擇不 餵養母乳,母乳餵養不足或不順利。已研發用於該等情況 之嬰兒配方。 WO 2010/070613 A2係關於嬰兒灌食配方及相關系統。 更特定而言,其揭示用於早產嬰兒之具有低蛋白含量(低 於1 g/100 mL)及低能量含量(低於50 kcal/100 mL)之嬰兒 配方。未提供與血壓相關之數據。 WO 2007/004878 A2係關於治療及/或預防兒童肥胖症之 方法’其包含投與含有脂肪、易消化碳水化合物及蛋白之 營養組合物’其中蛋白以蛋白乾重計包含至少25重量%之 键長為25個至30個胺基酸之肽。其揭示較低膜島素分泌。 WO 2006/069918 A1係關於具有經降低之蛋白含量之嬰 兒配方的用途,其用於在嬰兒生命之最初幾個月中不斷降 低IGF-1之循環量。 163923.doc • 4· 201247112 EP 1932437 A1係關於用於具有在以後生命中患肥胖症 之風險之嬰兒的嬰兒配方,該嬰兒配方具有低於650 kcal/ 升之能量密度及低於1.8 g/100 kcal之蛋白含量。其並未論 述血壓。 •才Tf; 7¾¾ 為 Fruhkindlichc ErnShrung und sp註teres Adipositasrisiko」(Bundesgesundheitsbl. 2010,53: 666-673)之綜述論文中’ Koletzko等人論述低蛋白含量配方用 於降低肥胖症風險之潛在益處。 因此,業内需要可用於通常在以後生命中預防心血管疾 病或高血壓之嬰兒配方。 【發明内容】 因此,本發明提供至少包含蛋白源、脂質源、碳水化合 物源之嬰兒配方,其中蛋白含量係低於2丨g/1〇〇 kcal,該 嬰兒配方用於尤其在以後生命中預防心血管疾病或高血 壓。 本發明之另一態樣係預防患者之心血管疾病之方法,其 包含在患者出生後至少三個月期間且在一年内用嬰兒配方 餵養該患者,纟中該嬰兒配方至少包含蛋白源、脂質源、 碳水化合物源’且其中該嬰兒配方之蛋白含量係、低於2.1 g/100 kcal 0 本發明之再-態樣係預防患者之高血壓之方法,其包含 在患者出生後至少二個月期間且在一年内用嬰兒配方餵養 該患者’彡中該嬰兒配方至少包含蛋白源、脂質源、碳水 化合物源’且其中該嬰兒配方之蛋白含量係低於2.1 g/100 kcal 0 163923.doc 201247112 本發明者已驚奇地發現,根據本發明使用之嬰兒配方尤 其有利於預防高血壓及潛在心血管疾病、具體而言彼等與 高血壓相關之心血管疾病。此涵蓋冠狀動脈心臟病、心臟 衰竭、周邊動脈疾病、高血壓性視網膜病變、高血壓性腦 病、中風及腎衰竭。儘管僅在患者為嬰兒時向其餵養嬰兒 配方,但可在相同患者之以後生命中(例如剛到3歲)觀察到 預防效果。 【實施方式】 本文所用以下術語具有以下含義。 術語「嬰兒」意指年齡未滿丨2個月之兒童。 術語「嬰兒配方」意指意欲用於在生命第一年期間之嬰 兒之具體營養用途且本身滿足此類人之營養要求的食品, 如在1991年5月14日之歐洲委員會指令91/321/EEC (Eur〇pean Commission Directive 91/321/EEC)中所定義。術語「嬰兒 配方」包括低致敏性嬰兒配方。術語「嬰兒配方」包括新 生兒配方及較大嬰兒配方(f〇U〇w 〇n 。 術"。新生兒配方」意指意欲用於在生命之最初4個月 至6個月期間之嬰兒之具體營養用途的食品。 術扣較大嬰兒配方」意指意欲用於年齡在4個月至ό個 月’最多12個月之嬰兒之具體營養用途且在此類人逐漸多 樣化之飲食中構成主要液體要素之食品。 術語「預防心血管疾病」意指通常在以後生命中預防心 i管疾病並降低心血管疾病之頻率及/或發生率及/或嚴重 程度及/或持續時間。發生率係指任何心血管疾病之次 I63923.doc 201247112 數。風險係指出現心血管疾病之可能性。頻率係指相同心 血管疾病之次數。持續時間係指心血管疾病之總持續時 間。心血管疾病具體而言係彼等與高血壓相關之疾病。心 血管疾病包括(例如)冠狀動脈心臟病、心臟衰竭、周邊動 脈疾病、高血壓性視網膜病變、高血壓性腦病、中風及腎 衰竭。基於群體估計,舒張血壓減少2 mmHg可使中風風 險降低15%且使冠狀動脈心臟病風險降低6% (c〇〇k nr、Mild or mild symptoms, such as in the brain; in terms of infant nutrition, human breast milk represents the undisputed gold standard. However, in some cases, breastfeeding is inadequate or unsatisfactory for medical reasons, or because the mother chooses not to breastfeed. Infant formulas have been developed for these situations. WO 2010/070613 A2 relates to infant feeding formulations and related systems. More specifically, it discloses infant formulas for premature infants with low protein content (less than 1 g/100 mL) and low energy content (less than 50 kcal/100 mL). No blood pressure related data was provided. WO 2007/004878 A2 relates to a method for the treatment and/or prevention of childhood obesity comprising the administration of a nutritional composition comprising fat, digestible carbohydrates and proteins, wherein the protein comprises at least 25% by weight of the protein by dry weight of protein A peptide of 25 to 30 amino acids in length. It reveals lower membrane secretion. WO 2006/069918 A1 relates to the use of an infant formula having a reduced protein content for continuously reducing the circulating amount of IGF-1 during the first few months of an infant's life. 163923.doc • 4· 201247112 EP 1932437 A1 relates to an infant formula for infants at risk of developing obesity in later life, having an energy density of less than 650 kcal/liter and less than 1.8 g/100 The protein content of kcal. It does not address blood pressure. • Tf; 73⁄43⁄4 is a review paper by Fruhkindlichc ErnShrung und sp note teres Adipositasrisiko” (Bundesgesundheitsbl. 2010, 53: 666-673). Koletzko et al. discuss the potential benefits of low protein content formulations for reducing the risk of obesity. Therefore, there is a need in the industry for infant formulas that are commonly used to prevent cardiovascular disease or hypertension in later life. SUMMARY OF THE INVENTION Accordingly, the present invention provides an infant formula comprising at least a protein source, a lipid source, a carbohydrate source, wherein the protein content is less than 2丨g/1〇〇kcal, and the infant formula is used to prevent especially in later life. Cardiovascular disease or high blood pressure. Another aspect of the present invention is a method of preventing cardiovascular disease in a patient, comprising: feeding the patient with an infant formula during at least three months after the birth of the patient and within one year, wherein the infant formula comprises at least a protein source, a lipid Source, carbohydrate source 'and wherein the infant formula has a protein content of less than 2.1 g/100 kcal 0. The re-state of the invention is a method for preventing hypertension in a patient, comprising at least two months after the patient is born The patient is fed with an infant formula during the period of one year, 'the infant formula contains at least a protein source, a lipid source, a carbohydrate source' and wherein the protein content of the infant formula is less than 2.1 g/100 kcal 0 163923.doc 201247112 The inventors have surprisingly found that infant formulas for use in accordance with the present invention are particularly advantageous for the prevention of hypertension and potential cardiovascular diseases, in particular, cardiovascular diseases associated with hypertension. This covers coronary heart disease, heart failure, peripheral arterial disease, hypertensive retinopathy, hypertensive encephalopathy, stroke, and kidney failure. Although the infant formula is fed only when the patient is an infant, a preventive effect can be observed in the later life of the same patient (e.g., just up to 3 years old). [Embodiment] The following terms as used herein have the following meanings. The term "baby" means a child who is under 2 months of age. The term "infant formula" means a food intended for the specific nutritional use of an infant during the first year of life and which meets the nutritional requirements of such a person, as in the European Commission Directive 91/321 of May 14, 1991. Defined in EEC (Eur〇pean Commission Directive 91/321/EEC). The term "infant formula" includes hypoallergenic infant formulas. The term "infant formula" includes neonatal formula and larger infant formula (f〇U〇w 〇n. surgery " neonatal formula" means an infant intended for use during the first 4 months to 6 months of life. A food for a specific nutritional use. A large infant formula means a specific nutritional use intended for infants aged 4 months to 9 months, up to 12 months, and in a diet in which such persons are increasingly diversified A food that constitutes a major liquid element. The term "preventing cardiovascular disease" means preventing the frequency and/or incidence and/or severity and/or duration of cardiovascular disease, usually in later life. Rate refers to the number of any cardiovascular disease I63923.doc 201247112. Risk refers to the possibility of cardiovascular disease. Frequency refers to the number of times of the same cardiovascular disease. Duration refers to the total duration of cardiovascular disease. Cardiovascular Diseases are specifically diseases related to hypertension. Cardiovascular diseases include, for example, coronary heart disease, heart failure, peripheral arterial disease, and hypertensive retinopathy. Change, hypertensive encephalopathy, stroke, and kidney failure. Based on population estimates, a 2 mmHg reduction in diastolic blood pressure can reduce the risk of stroke by 15% and reduce the risk of coronary heart disease by 6% (c〇〇k nr,
Cohen J ^ Hebert P > Taylor JO . Hennekens CH. Implications of small reductions in diastolic blood pressure for primary prevention. Arch Intern Med" 1995; 155: 701-709)。 術語「在以後生命中」涵蓋在介入終止後之影響。「在 以後生命中」之影響可在該介入終止後數月或數年。因 此’「以後生命」可意指在3歲時、在青少年期間或在成年 期間。在幼童之情況下,此係指2 5歲至1()歲之年齡。在 青少年之情況下,其係指10歲至20歲之年齡。在成人之情 ’兄下#係^ 1 8歲以上之年齡。更—般而,使用本發明 嬰兒配方之持續時間對「以後生命」之含義有影響。 除非另有說明’否則所有百分比均以重量計。 ,據本發明’嬰兒配方較佳用於預防與高血壓相關之心 血管疾病。換言之,高血壓可係該等心血管疾病之症狀或 原因之一。 較佳地„亥配方之蛋白含量係在16 g"⑼kcd至2」 g kCal範圍内。較佳地,蛋白含量係低於2.0 g/100 更佳低於1,9 g/100 kcal且甚至更佳低於1.85 g/100 163923.doc 201247112 kca卜舉例而言,蛋白含量係在丨6 g/1〇〇 kcai至2 〇 kcal範圍内,較佳在! 6 g/1〇〇 kca丨至1 9 g/i〇〇让㈡丨範圍 内,更佳在 1.6g/l〇〇kcal至 1.85g/l〇〇kcal範圍内。 乳蛋白可來源於牛乳、山羊乳、母羊乳、水牛乳、駱駝 乳、母馬乳及其混合物。 蛋白源較佳係在乳蛋白 '乳蛋白部分水解產物、低致敏 性乳蛋白水解產物及其混合物内選擇。該等蛋白可係完整 蛋白’或經水解蛋白,或完整蛋白與經水解蛋白之混合 物。較佳地’嬰兒配方之實施例包含未經水解之乳清蛋 白。 在實施例中,嬰兒配方之蛋白源可基於乳清、酪蛋白及 其混合物,以及基於大豆之蛋白源。因此,蛋白源較佳包 含乳清蛋白、赂蛋白或兩者之混合物,且蛋白源更佳僅係 乳清蛋白、酿·蛋白或兩者之混合物。在較佳實施例中,蛋 白源係乳清蛋白與酪蛋白之混合物,乳清/酪蛋白之比率 至少等於50/50,較佳至少等於6〇/4〇,更佳至少等於 70/30 〇 就乳清蛋白而言,蛋白源可基於酸乳清或甜乳清或其混 合物’且可以任何期望比例包括α·乳白蛋白及卜乳球蛋 白。當嬰兒配方包含乳清蛋白時,較佳地已自乳清蛋白去 除大部分路蛋白-糖-巨肽(CGMP),即,CGMP之含量較 低。較佳地,CGMP含量相對於天然乳清蛋白降低至少 80〇/〇。舉例而言’蛋白源可包含經水解甜乳清部分,其中 已去除超過85%之原本存在之CGmp,例如如在 163923.doc 201247112 EP1220620B1之實例1中所揭示。 可期望向(例如)據信具有患牛乳過敏症之風險之嬰兒提 供部分水解蛋白。部分水解蛋白係組合物,其中蛋白/肽 群體之60°/。至70%之分子量小於1000道爾頓(Dah〇n)。通常 認為部分水解蛋白具有低致敏性(HA)。乳蛋白水解產物之 水解程度可藉由NPN/TN%來描述^非蛋白氮對總氮廣泛 地用作酶水解產生之可溶性肽之量度。NPN/TN%意指非 蛋白氮除以總氮xlOO。可如Adler_Nisse n j_,1979,jCohen J ^ Hebert P > Taylor JO . Hennekens CH. Implications of small reductions in diastolic blood pressure for primary prevention. Arch Intern Med"1995; 155: 701-709). The term "in later life" covers the effects of termination of intervention. The effect of "in later life" may be months or years after the termination of the intervention. Therefore, "after life" can mean at the age of 3, during adolescence or during adulthood. In the case of young children, this refers to the age of 25 to 1 (). In the case of adolescents, it refers to the age of 10 to 20 years of age. In the adult's love ‘Brother’s #系^ 1 8 years old or older. More generally, the duration of use of the infant formula of the present invention has an effect on the meaning of "future life." All percentages are by weight unless otherwise stated. According to the present invention, the infant formula is preferably used for preventing cardiovascular diseases associated with hypertension. In other words, hypertension can be one of the symptoms or causes of these cardiovascular diseases. Preferably, the protein content of the formula is in the range of 16 g < (9) kcd to 2" g kCal. Preferably, the protein content is less than 2.0 g/100, more preferably less than 1,9 g/100 kcal and even more preferably less than 1.85 g/100 163923.doc 201247112 kca. For example, the protein content is in 丨6 G/1〇〇kcai to 2 〇kcal range, preferably! 6 g / 1 〇〇 kca 丨 to 1 9 g / i 〇〇 (2) 丨 range, more preferably in the range of 1.6g / l 〇〇 kcal to 1.85g / l 〇〇 kcal. Milk protein can be derived from cow's milk, goat's milk, ewe's milk, buffalo milk, camel milk, mare's milk and mixtures thereof. Preferably, the protein source is selected from the milk protein 'partial milk hydrolysate, hypoallergenic milk protein hydrolysate, and mixtures thereof. These proteins may be either intact proteins or hydrolyzed proteins, or a mixture of intact and hydrolyzed proteins. Preferably, the embodiment of the infant formula comprises unhydrolyzed whey protein. In embodiments, the protein source for the infant formula can be based on whey, casein, and mixtures thereof, as well as a soy-based protein source. Therefore, the protein source preferably comprises whey protein, albumin or a mixture of the two, and the protein source is preferably only whey protein, brewing protein or a mixture of the two. In a preferred embodiment, the protein source is a mixture of whey protein and casein, the ratio of whey/casein is at least equal to 50/50, preferably at least equal to 6〇/4〇, more preferably at least equal to 70/30〇 In the case of whey proteins, the protein source may be based on acid whey or sweet whey or a mixture thereof' and may include alpha-lactalbumin and galactoglobulin in any desired ratio. When the infant formula contains whey protein, most of the road protein-sugar-macropeptide (CGMP) has been removed from the whey protein, i.e., the CGMP content is low. Preferably, the CGMP content is reduced by at least 80 〇/〇 relative to the native whey protein. For example, the protein source may comprise a hydrolyzed sweet whey fraction wherein more than 85% of the originally present CGmp has been removed, for example as disclosed in Example 1 of 163, 923, doc 201247112 EP 1220620 B1. It may be desirable to provide a partially hydrolyzed protein to, for example, an infant believed to be at risk of having a cow's milk allergy. Partially hydrolyzed protein composition, wherein the protein/peptide population is 60°/. The molecular weight to 70% is less than 1000 Daltons (Dah〇n). Partially hydrolyzed proteins are generally considered to have low sensitization (HA). The degree of hydrolysis of the milk protein hydrolysate can be described by NPN/TN%. A measure of the soluble peptide produced by enzymatic hydrolysis of non-protein nitrogen to total nitrogen. NPN/TN% means non-protein nitrogen divided by total nitrogen x100. Can be like Adler_Nisse n j_, 1979, j
Agric. F〇〇d Chem.,27 (6),1256-1262所詳細說明量測 NPN/TN/〇。一般而s ,部分水解蛋白之特徵在於npn/ TN%在75%至85%範圍内^較佳地,蛋白水解產物之 NPN/TN%係在70%至90。/。、較佳75%至85%範圍内。 若需要經水解蛋白,則可視需要並如業内習知實施水解 過程。舉例而言,可藉由以一或多個步驟酶促水解乳清部 分來製備乳清蛋白水解產物。若用作起始材料之乳清部分 實質上不含乳糖’則發現,該蛋白在水解過程期間經受遠 遠較少之離胺酸阻滯。此使得能夠將離胺酸阻滯之程度自 約15重量%之總離胺酸降低至小於約1〇重量%之離胺酸; 例如,約7重量%之離胺酸,此會顯著改善蛋白源之營養 品質。可添加游離精胺酸、游離組胺酸、游離牛磺酸、游 離酪胺酸及富色胺酸乳蛋白、游離色胺酸或其混合物。亦 可在嬰兒配方中添加核苷酸以及肉鹼作為氮源。 因此’蛋白源可包含乳清蛋白、路蛋白、其水解產物及 163923.doc 201247112 適宜破水化合物源係乳糖、蔗糖、麥芽糊精、澱粉。可 使用其混合物。碳水化合物源較佳包含乳糖。較佳地,碳 水化合物源包含至少80〇/〇乳糖、宙从s 孔糖、更佳至少9〇%乳糖且甚至 更佳至少95%乳糖〇在較佳眘楠 貫施例中,碳水化合物源僅係 乳糖。通常’當嬰兒配方包含朝撼主 ,. 0 3孔糖時’礼糖係以在9 g/100 kcal至 13 g/1〇〇 Real、較佳 10 g/1〇〇 _12 gn〇〇 _範 圍内之量存在。 嬰兒配方通常含有脂質源。在此情形下,脂質源可係適 用於嬰兒配方之任何脂質或脂肪。較佳脂肪源包括乳脂、 紅花油、蛋黃脂質、芥花油、撖欖油、椰子油、棕櫚仁 油、大豆油、魚油、棕櫚油、高油酸葵花籽油及高油酸紅 钯油,以及含有長鏈多不飽和脂肪酸之微生物發酵油。脂 質源亦可呈源自該等油之部分之形式,例如棕櫚油精、中 鏈甘油三酯及諸如以下等脂肪酸之酯:花生四烯酸、亞油 酸、棕櫚酸、硬脂酸、二十二碳六烯酸、次亞麻油酸、油 酸、月桂酸、癸酸、辛酸、己酸及諸如此類。亦可添加少 量含有大量預形成之花生四烯酸及二十二碳六烯酸之油, 例如魚油或微生物油《脂肪源中脂肪酸與n_3脂肪酸之 比率較佳為約5:1至約1 5:1 ;例如約8:1至約1 〇: 1。 在實施例中’嬰兒配方之能量密度包含6〇〇 kcal/L至78〇 keal/L、較佳 630 keal/L至 700 keal/L。 嬰免配方較佳亦以營養有效量含有認為在日常飲食中所 必需之所有維生素及礦物。已確立對某些維生素及礦物之 最低要求。嬰兒配方令視情況存在之礦物、維生素及其他 163923.doc • 10· 201247112 營養素之實例包括維生素A、維生素B 1、維生素B2、維生 素B6、維生素B12、維生素E、維生素K、維生素C、維生 素D、葉酸、肌醇、菸鹼酸、生物素、泛酸、膽鹼、鈣、 填、磁、鐵、鎮、銅、鋅、猛、氣、钟、納、砸、鉻、 翻、牛磺酸及L-肉鹼。礦物通常以鹽形式添加。特定礦物 及其他維生素之存在及量將視既定群體而變化。 若需要’則嬰兒配方可含有乳化劑及穩定劑,例如大豆 卵磷脂、單-及二甘油酯之檸檬酸酯及諸如此類。 嬰兒配方亦可含有至少一種益生菌。較佳益生菌係彼等 το整時安全、係產生L(+)乳酸之培養物且對於諸如嬰兒配 方及較大嬰兒配方等產品而言具有可接受存架壽命者,該 等產品要求在長達36個月内保持穩定且有效。 嬰兒配方較佳具有與標準嬰兒配方及較大嬰兒配方相比 含量降低之電解質。舉例而言,NA/K比率(mm〇1)可係約 0.4 ’(Na+K)/Cl 比率(mm〇i)可係約 i 8,Na+K+C1可係約 34 (mmol) ’且(Na+K)-Cl可係約1 〇 (mm〇i)。嬰兒配方較佳具 有低磷酸鹽含量,且較佳具有小於40 mg/100 kcal之磷含 菫。較佳地,嬰兒配方之鈣含量係介於35 g/i〇〇爪1^與45 g/1〇〇mL之間,磷含量係介於15mg/mL與25mg/mL之間且 C a/P比率係介於1.4與3之間。 嬰兒配方亦可含有可能具有有益效應之其他物質,例如 乳鐵蛋白、纖維、核㈣、核#及諸如此類。 文闡述之所有用途尤其意欲用於尤其介於生命之〇個 月至36個月之間之嬰兒及幼童^具體而言,嬰兒配方及用 163923.doc 201247112 途適於具有心血管疾病風險之嬰兒,具體而言具有心血管 疾病家族史之嬰兒。更具體而言,嬰兒配方及用途適於具 有與高血壓相關之心血管疾病(換言之,高血壓係其症狀 或原因中之一者之心血管疾病)之風險的嬰兒。 嬰兒配方可係新生兒配方或較大嬰兒配方,且該組合物 較佳係新生兒配方。根據本發明使用之嬰兒配方係作為液 體組合物供嬰兒消費。然而,嬰兒配方可作為嬰兒配方粉 末提供,其可藉由將該嬰兒配方粉末與水混合以液體形式 重構。 嬰兒配方之劑量方案可基於三個參數來設計,該等參數 可組合在一起且將詳述如下: _嬰兒配方佔每日食物攝入之量, -方案之持續時間, -方案之起始曰期。 在本說明書中,食物攝入係按照能量攝入來評估。 較佳地,嬰兒配方應佔嬰兒之每日食物(或能量)攝入之 至少50% ’更佳佔嬰兒之每日食物(或能量)攝入之至少 _或甚至至少7〇%。在另—較佳實施例中,嬰兒配方佔 嬰兒之每日食物(或能量)攝入之至少8〇%。較佳地嬰兒 配方代表嬰兒之唯一食物(或能量)攝入。 此方案較佳應在嬰兒出生後—年内維持至少3個月。該 方案可維持3個月以上,例如至少6個月,且甚至只要嬰兒 配方係此年齡類別之適當食物。舉例而言,該方案可自出 生起維㈣達3個月至6個月之年齡,或甚至長達9個月或 163923.doc -12· 201247112 12個月之年齡。較佳地,該方案在嬰兒(包括早產兒)出生 時開始,且在出生後一年内結束。該方案可在嬰兒之生命 期間演變。在出生後最初4個月至6個月期間,嬰兒配方可 係新生兒配方,且可代表該期間嬰兒之 攝入。-旦食物多樣化開始,嬰兒配方可係較=量配) 方。然後其佔較低嬰兒之食物(或能量)攝入,例如每曰食 物(或能量)攝入之30%、40%或5〇%,多達9〇%、8〇%或 70。/。,視給予嬰兒之非配方食物量而定。通常,非配方食 物量隨時間增加。 舉例而言,在出生後至少3個月多至6個月期間且在一年 内’嬰兒配方佔每日食物(或能量)攝入之至少5〇%。較佳 地,在嬰兒生命之最初3個月多至最初6個月期間(即在出 生後3個月至6個月内),嬰兒配方佔嬰兒之每日食物(或能 量)攝入之至少50% ^甚至更佳地,在嬰兒生命之至少最初 3個月多至最初6個月期間,嬰兒配方佔嬰兒之每日食物 (或能量)攝入之至少在再一方案中’在嬰兒生命之 至少最初3個月期間,嬰兒配方代表嬰兒之唯一食物(或能 量)攝入。 " 本發明亦關於一種預防患者心血管疾病之方法或一種預 防患者高血壓之方法,該等方法包含在患者出生後至少3 個月期間且在一年内用嬰兒配方餵養該患者,其中該嬰兒 配方至少包含蛋白源、脂質源、碳水化合物源且其中該 嬰兒配方之蛋白含量係低於2_1 g/100 kcal。上文已揭示用 於該等方法中之嬰兒配方以及數種可實施之劑量方案。 I63923.doc •13· 201247112 此處應注意,患者在極小年齡、較佳在出生後3個月至6 個月,最多12個月之年齡期間,遵循特定方案。然而,可 在患者之以後生命中(例如,幼童時、青少年時或成年時) 觀察到預期的預防效果。 在上文方法之較佳實施例中,嬰兒配方佔患者之每曰食 物(或能量)攝入之至少50%。 現將以實例方式闡述可根據本發明使用之嬰兒配方。 可以任何適宜方式製備該配方。舉例而言,其可藉由將 蛋白源、碳水化合物源及脂肪源以適當比例摻和在一起來 製備。若使用,則此時可包括乳化劑。維生素及礦物可於 此時添加,但其通常在稍後添加以避免熱降解。可在摻和 前將任何親脂性維生素、乳化劑及諸如此類溶解於脂肪源 中。然後,可混入水(較佳已經受反滲透之水)以形成液體 混合物。水之溫度便利地係在介於約5〇〇c與約8〇〇c之間之 範圍内以幫助成份分散。可使用市售液化器來形成液體混 合物。然後’在(例如)兩個階段中將該液體混合物均質 化。 然後’可藉由(例如)以下方式熱處理液體混合物以降低 細菌載量:將液體混合物迅速加熱至介於約8(Γ(:與約 150 C之間之範圍内之溫度並保持介於約5秒與約5分鐘之 間之持續時間。此可藉助蒸汽注入、高壓釜或熱交換器 (例如’板式熱交換器)來實施。 然後’可藉由(例如)急驟冷卻將液體混合物冷卻至介於 約60°C與約851之間。然後,可在(例如)兩個階段中再次 163923.doc • 14 - 201247112 將液體混合物均質化’在第一階段中介於約丨〇 Mpa與約3〇 Mpa之間’且在第二階段中介於約2 Mpa與約ι〇 Μρ&之 間。然後,可進一步冷卻均質化混合物以添加任何熱敏感 性組份,例如維生素及礦物。此時,可便利地調整均質化 混合物之pH及固體含量。 將均質化混合物轉移至適宜乾燥裝置(例如,喷霧乾燥 器或冷凍乾燥器)中並轉化為粉末。粉末之水分含量應小 於約5重量%。 若液體嬰兒配方較佳,則可將均質化混合物滅菌,然後 以無菌方式填充至適宜容器中,或可首先將其填充至容器 中且然後殺菌。 藉由考慮附圖1將易於理解本發明技術,圖丨係展示使用 一種不同灌食嬰兒配方(母乳傲養,BF ;根據本發明使用 之嬰兒配方’ F1.8 ;比較嬰兒配方F2.7)時量測之血壓(BP) (收縮血壓’ SBP ;舒張血壓,DBP ;平均血壓,MBP)之 圖。 將在以下實例中解釋圖1。 藉由以下非限制性實例來進一步闡釋本發明,該等實例 僅用於閣釋性目的。 實例 下表1中(僅以閣釋方式)給出命名為F 1.8之根據本發明使 用之嬰兒配方的組成。 163923.doc 201247112 表1 營養素 /100 kcal /升 能量(kcal) 100 670 蛋白(g) 1.83 12.3 脂肪(g) 5.3 35.7 亞麻油酸(g) 0.79 5.3 α-次亞麻油酸(mg) 101 675 乳糖(g) 11.2 74.7 礦物(g) 0.37 2.5 Na (mg) 23 150 K(mg) 89 590 Cl (mg) 64 430 Ca (mg) 62 410 P(mg) 31 210 Mg (mg) 7 50 Mn(pg) 8 50 Se㈣ 2 13 維生素A (gg RE) 105 700 維生素D(pg) 1.5 10 維生素E(mgTE) 0.8 5.4 維生素ΚΙ (μ8) 8 54 維生素C (mg) 10 67 維生素B1 (mg) 0.07 0.47 維生素B2 (mg) 0.15 1.0 於驗酸(mg) 1 6.7 維生素B6 (mg) 0.075 0.50 163923.doc -16 - 201247112 葉酸㈣) 9 60 泛酸(mg) 0.45 3 維生素Β12(μ§) 0.3 2 生物素(pg) 2.2 15 膽鹼(mg) 10 67 Fe (mg) 1.2 8 ΐ(μ^ 15 100 Cu (mg) 0.06 0.4 Zn (mg) 0.75 5 利用含有2.7 g/100 kcal之蛋白且命名為F2.7之配方來實 施比較研究。兩種嬰兒配方F1.8及F2.7之能量均為670 kcal/L。嬰兒配方F1.8與F2.7之不同之處僅在於下表2中之 組份: 表2 營養素V组成/100 kCal F1.8 F2.7 碳水化合物(乳糖)(g) 11.16 10.38 蛋白(赂蛋白/乳清:30/70) (g) 1.83 2.70 納(mg) 23 26 調整碳水化合物含量以確保配方F1.8及F2.7兩者中之相 同能量攝入量。假設鈉含量之差異與蛋白含量之差異相關 聯。人們認為不同鈉含量之影響可忽略。 在隨機化研究中,本發明者已自3歲兒童量測舒張血 壓、收縮血壓及平均血壓,該等兒童在生命之最初4個月 期間僅餵養以下食物: 163923.doc 201247112 •餵養母乳(BF) (n=84);或 •用根據本發明使用之低蛋白配方(1.8 g蛋白/100 kcal) F1.8 餵養(n=74);或 •用高蛋白比較配方(2.7 g蛋白/100 kcal) F2.8餵養 (n=80)。 餵養母乳及餵養配方之嬰兒兩者均可在4個月時開始補 充性餵養。餵養配方之嬰兒維持其各別配方直至1歲,且 餵養母乳之群組接受低蛋白配方F1.8。配方可佔嬰兒之食 物攝入的30%至90%,此端視(例如)其年齡而定。 結果匯總於下表3中且展示於圖1中,圖1展示使用三種 不同嬰兒配方(母乳餵養,BF ;根據本發明使用之嬰兒配 方,F1.8 ;比較嬰兒配方F2.8)時量測之血壓(BP)(即收縮 血壓,SBP ;舒張血壓,DBP ;平均血壓,MBP)。 表3 血壓 收縮 舒張 平均血壓 (mmHg) SBP DBP MBP 餵養母乳 94.04±7.83 62.45±6.56 69.72±6.55 1.8 g蛋白/100 kcal 96.40±9.31 64.84±8.16 72.18±8.05 2.7§蛋白/1001«^1 96.70±12.53 65.98±10.67 74.05±11.01 對於收縮壓(SBP)而言,F1.8對BF,p=0.1849 ; F2.7對 BF,ρ=0.1377 對於舒張壓(DBP)而言,F1.8對BF,p = 0.0798 ; F2.7對 BF,ρ<0·04 163923.doc -18- 201247112 對於平均血壓(MBP)而言,F1.8對BF,ρ=0·0735 ; F2.7 對 BF,ρ<0.01 p值低於0.05意味著差異顯著。 因此,本發明者已展示,在生命之至少最初4個月期間 . 僅餵養低蛋白配方(1.8 g蛋白/100 kcal)之3歲兒童的血壓比 , 彼等僅餵養高蛋白配方(2.7 g蛋白/100 kcal)者更接近於僅 餵養母乳之兒童。 參考文獻The measurement of NPN/TN/〇 is detailed in Agric. F〇〇d Chem., 27 (6), 1256-1262. Typically, s, partially hydrolyzed protein is characterized by npn/TN% in the range of 75% to 85%. Preferably, the NPN/TN% of the protein hydrolysate is between 70% and 90%. /. Preferably, it is in the range of 75% to 85%. If hydrolyzed proteins are desired, the hydrolysis process can be carried out as needed and as known in the art. For example, the whey protein hydrolysate can be prepared by enzymatically hydrolyzing the whey fraction in one or more steps. If the whey fraction used as the starting material is substantially free of lactose, it is found that the protein undergoes much less peracid acid retardation during the hydrolysis process. This makes it possible to reduce the degree of amino acid retardation from about 15% by weight of total lysine to less than about 1% by weight of the amine acid; for example, about 7% by weight of the amino acid, which significantly improves the protein. The nutritional quality of the source. Free arginine, free histidine, free taurine, free tyrosine and leucine-containing milk protein, free tryptophan or mixtures thereof may be added. Nucleotides and carnitine can also be added to the infant formula as a nitrogen source. Thus, the protein source may comprise whey protein, passin, hydrolysate thereof and 163923.doc 201247112 Suitable sources of water-repellent compounds are lactose, sucrose, maltodextrin, starch. A mixture thereof can be used. The carbohydrate source preferably comprises lactose. Preferably, the carbohydrate source comprises at least 80 〇/〇 lactose, a sucrose from the shole, more preferably at least 9% lactose, and even more preferably at least 95% lactose 〇 in a preferred embodiment, a carbohydrate source It is only lactose. Usually 'when the infant formula contains the pilgrimage to the lord, the 0 3 hole sugar is used at 9 g/100 kcal to 13 g/1 〇〇 Real, preferably 10 g/1 〇〇 _12 gn 〇〇 _ The amount within the range exists. Infant formulas usually contain a source of lipids. In this case, the lipid source can be any lipid or fat suitable for use in an infant formula. Preferred fat sources include milk fat, safflower oil, egg yolk lipid, canola oil, eucalyptus oil, coconut oil, palm kernel oil, soybean oil, fish oil, palm oil, high oleic sunflower oil and high oleic red palladium oil. And microbial fermentation oils containing long chain polyunsaturated fatty acids. The lipid source may also be in the form of a portion derived from such oils, such as palm olein, medium chain triglycerides, and esters of fatty acids such as arachidonic acid, linoleic acid, palmitic acid, stearic acid, and the like. Dosahexaenoic acid, linoleic acid, oleic acid, lauric acid, capric acid, caprylic acid, caproic acid, and the like. A small amount of oil containing a large amount of pre-formed arachidonic acid and docosahexaenoic acid may also be added, such as fish oil or microbial oil. The ratio of fatty acid to n-3 fatty acid in the fat source is preferably from about 5:1 to about 15 :1 ; for example, about 8:1 to about 1 〇: 1. In the examples, the energy density of the infant formula comprises from 6 〇〇 kcal/L to 78 ke keal/L, preferably from 630 keal/L to 700 keal/L. The infant-free formula preferably also contains all of the vitamins and minerals deemed necessary in the daily diet in a nutritionally effective amount. Minimum requirements for certain vitamins and minerals have been established. Infant formula makes minerals, vitamins and other substances as appropriate 163923.doc • 10· 201247112 Examples of nutrients include vitamin A, vitamin B 1, vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D , folic acid, inositol, nicotinic acid, biotin, pantothenic acid, choline, calcium, filling, magnetic, iron, town, copper, zinc, fierce, gas, bell, sodium, strontium, chromium, turpent, taurine and L-carnitine. Minerals are usually added in the form of a salt. The presence and amount of specific minerals and other vitamins will vary depending on the established population. If desired, the infant formula may contain emulsifiers and stabilizers such as soy lecithin, citric acid esters of mono- and diglycerides, and the like. The infant formula may also contain at least one probiotic. Preferred probiotics are those that are safe at all times, produce L(+) lactic acid cultures, and have acceptable shelf life for products such as infant formulas and larger infant formulas, which are required to be long Stable and effective for 36 months. Infant formulations preferably have a reduced level of electrolyte compared to standard infant formulas and larger infant formulas. For example, the NA/K ratio (mm〇1) can be about 0.4 '(Na+K)/Cl ratio (mm〇i) can be about i 8, Na+K+C1 can be about 34 (mmol)' And (Na+K)-Cl can be about 1 〇 (mm〇i). The infant formula preferably has a low phosphate content and preferably has a phosphorus content of less than 40 mg/100 kcal. Preferably, the calcium content of the infant formula is between 35 g/i pawl 1^ and 45 g/1〇〇mL, and the phosphorus content is between 15 mg/mL and 25 mg/mL and Ca/ The P ratio is between 1.4 and 3. Infant formulas may also contain other substances that may have beneficial effects, such as lactoferrin, fiber, core (4), core #, and the like. All uses described herein are especially intended for infants and young children, especially between the months of life and 36 months. In particular, infant formula and 163923.doc 201247112 are suitable for cardiovascular risk. Infants, specifically infants with a family history of cardiovascular disease. More specifically, the infant formula and use are suitable for infants at risk of having a cardiovascular disease associated with hypertension (in other words, hypertension is one of the symptoms or causes of cardiovascular disease). The infant formula can be a neonatal formula or a larger infant formula, and the composition is preferably a neonatal formula. The infant formula used in accordance with the present invention is used as a liquid composition for infant consumption. However, the infant formula can be provided as an infant formula which can be reconstituted in liquid form by mixing the infant formula powder with water. The dosage regimen for infant formulas can be designed based on three parameters that can be combined and will be detailed as follows: _ Infant formula for daily food intake, - duration of program, - start of program 曰period. In this specification, food intake is assessed by energy intake. Preferably, the infant formula should comprise at least 50% of the infant's daily food (or energy) intake ‘more preferably at least _ or even at least 7% of the infant's daily food (or energy) intake. In another preferred embodiment, the infant formula comprises at least 8% of the infant's daily food (or energy) intake. Preferably, the infant formula represents the sole food (or energy) intake of the infant. This program should preferably be maintained for at least 3 months after the baby is born. The regimen can last for more than 3 months, for example at least 6 months, and even as long as the infant formula is the appropriate food for this age category. For example, the program can be aged from 3 months to 6 months, or even up to 9 months or 163923.doc -12· 201247112 12 months. Preferably, the regimen begins at the time of birth of the infant (including premature infants) and ends within one year of birth. The program can evolve during the life of the baby. During the first 4 months to 6 months after birth, the infant formula can be a neonatal formula and can represent the infant's intake during that period. - Once the food is diversified, the infant formula can be compared to the amount of the formula. It then takes up less than 9%, 40%, or 5% of the food (or energy) intake of the lower infant, for example, up to 9%, 8%, or 70% of the intake of food (or energy). /. Depending on the amount of non-formulated food given to the baby. Generally, the amount of unformulated food increases over time. For example, infant formula accounts for at least 5% of daily food (or energy) intake for at least 3 months to 6 months after birth and within one year. Preferably, the infant formula accounts for at least the daily food (or energy) intake of the infant during the first 3 months of the infant's life up to the first 6 months (ie within 3 months to 6 months after birth). 50% ^ or even better, during at least the first 3 months of the baby's life up to the first 6 months, the infant formula accounts for at least one of the baby's daily food (or energy) intake in the infant's life. For at least the first 3 months, the infant formula represents the only food (or energy) intake of the baby. " The present invention also relates to a method of preventing cardiovascular disease in a patient or a method of preventing hypertension in a patient, the method comprising feeding the patient with an infant formula for at least 3 months after the birth of the patient and within one year, wherein the infant The formulation comprises at least a protein source, a lipid source, a carbohydrate source and wherein the infant formula has a protein content of less than 2_1 g/100 kcal. The infant formulas used in these methods and several dosage regimens that can be implemented are disclosed above. I63923.doc •13· 201247112 It should be noted here that patients are following a specific schedule at a very young age, preferably between 3 months and 6 months after birth, and up to 12 months of age. However, the expected preventive effect can be observed in later life of the patient (e.g., at a young child, at adolescence, or at an adult age). In a preferred embodiment of the above method, the infant formula comprises at least 50% of the food intake per meal (or energy) of the patient. Infant formulations that can be used in accordance with the present invention will now be illustrated by way of example. The formulation can be prepared in any suitable manner. For example, it can be prepared by blending a protein source, a carbohydrate source, and a fat source together in an appropriate ratio. If used, an emulsifier can be included at this point. Vitamins and minerals can be added at this point, but they are usually added later to avoid thermal degradation. Any lipophilic vitamins, emulsifiers, and the like can be dissolved in the fat source prior to blending. Water (preferably already subjected to reverse osmosis water) can then be mixed to form a liquid mixture. The temperature of the water is conveniently in the range of between about 5 〇〇c and about 8 〇〇c to aid in the dispersion of the ingredients. Commercially available liquefiers can be used to form the liquid mixture. The liquid mixture is then homogenized in, for example, two stages. The liquid mixture can then be heat treated by, for example, the following method to reduce the bacterial load: the liquid mixture is rapidly heated to a temperature in the range of about 8 (Γ (with a range between about 150 C and maintained at about 5) The duration between seconds and about 5 minutes. This can be carried out by means of a steam injection, autoclave or heat exchanger (for example a 'plate heat exchanger). Then the liquid mixture can be cooled to a medium by, for example, rapid cooling. Between about 60 ° C and about 851. Then, in a (for example) two stages again 163923.doc • 14 - 201247112 homogenization of the liquid mixture 'in the first stage between about 丨〇Mpa and about 3 〇 Between Mpa' and between about 2 Mpa and about ι〇Μρ& in the second stage. The homogenized mixture can then be further cooled to add any heat sensitive components, such as vitamins and minerals. The pH and solids content of the homogenized mixture is adjusted. The homogenized mixture is transferred to a suitable drying device (for example, a spray dryer or a freeze dryer) and converted into a powder. The moisture content of the powder should be small. About 5% by weight. If the liquid infant formula is preferred, the homogenized mixture can be sterilized and then filled aseptically into a suitable container, or it can be first filled into a container and then sterilized. The technique of the present invention will be readily understood, and the figure shows the blood pressure measured using a different formula for infants (breast breastfeeding, BF; infant formula used according to the invention 'F1.8; comparing infant formula F2.7) BP) (systolic blood pressure 'SBP; diastolic blood pressure, DBP; mean blood pressure, MBP). Figure 1 will be explained in the following examples. The invention will be further elucidated by the following non-limiting examples, which are only for the cabinet For the purpose of release.Examples The composition of the infant formula used according to the invention, designated F 1.8, is given in Table 1 below. 163923.doc 201247112 Table 1 Nutrients / 100 kcal / liter of energy (kcal) 100 670 protein (g) 1.83 12.3 fat (g) 5.3 35.7 linoleic acid (g) 0.79 5.3 α-linolenic acid (mg) 101 675 lactose (g) 11.2 74.7 mineral (g) 0.37 2.5 Na (mg) 23 150 K(mg) 89 590 Cl (mg) 64 430 Ca (mg) 62 410 P(mg) 31 210 Mg (mg) 7 50 Mn(pg) 8 50 Se(iv) 2 13 Vitamin A (gg RE) 105 700 Vitamin D (pg) 1.5 10 Vitamin E (mgTE) 0.8 5.4 Vitamin ΚΙ (μ8) 8 54 Vitamin C (mg) 10 67 Vitamin B1 (mg) 0.07 0.47 Vitamin B2 (mg) 0.15 1.0 Acid test (mg) 1 6.7 Vitamin B6 (mg) 0.075 0.50 163923.doc -16 - 201247112 Folic acid (4) 9 60 Pantothenic acid (mg) 0.45 3 Vitamin Β12 (μ§) 0.3 2 Biotin (pg) 2.2 15 Choline (mg) 10 67 Fe (mg) 1.2 8 ΐ (μ^ 15 100 Cu (mg) 0.06 0.4 Zn (mg) 0.75 5 A comparative study was carried out using a formulation containing 2.7 g/100 kcal of protein and designated F2.7. The energy of both infant formulas F1.8 and F2.7 is 670 kcal/L. Infant formula F1.8 differs from F2.7 only in the components in Table 2 below: Table 2 Nutrient V composition / 100 kCal F1.8 F2.7 Carbohydrate (lactose) (g) 11.16 10.38 Protein Protein/Whey: 30/70) (g) 1.83 2.70 nano (mg) 23 26 Adjust the carbohydrate content to ensure the same energy intake in both formulations F1.8 and F2.7. It is assumed that the difference in sodium content is related to the difference in protein content. It is believed that the effects of different sodium levels are negligible. In a randomized study, the inventors have measured diastolic blood pressure, systolic blood pressure, and mean blood pressure from a 3-year-old child who was fed only the following food during the first 4 months of life: 163923.doc 201247112 • Breastfeeding (BF) (n=84); or • fed with a low protein formula (1.8 g protein/100 kcal) F1.8 (n=74) used according to the invention; or • a high protein comparison formula (2.7 g protein/100 kcal) F2.8 feeding (n=80). Both infants fed breast milk and feeding formulas can start supplemental feeding at 4 months. Infants fed the formula maintained their respective formulations until the age of 1 and the group fed the breast milk received the low protein formula F1.8. The formula may account for 30% to 90% of the infant's food intake, depending on, for example, the age of the infant. The results are summarized in Table 3 below and shown in Figure 1, which shows the measurement using three different infant formulas (breastfeeding, BF; infant formula used in accordance with the invention, F1.8; comparative infant formula F2.8). Blood pressure (BP) (ie, systolic blood pressure, SBP; diastolic blood pressure, DBP; mean blood pressure, MBP). Table 3 Blood pressure systolic diastolic mean blood pressure (mmHg) SBP DBP MBP Breastfeeding 94.04±7.83 62.45±6.56 69.72±6.55 1.8 g protein/100 kcal 96.40±9.31 64.84±8.16 72.18±8.05 2.7§ protein/1001«^1 96.70±12.53 65.98±10.67 74.05±11.01 For systolic blood pressure (SBP), F1.8 is BF, p=0.1849; F2.7 is BF, ρ=0.1377 For diastolic blood pressure (DBP), F1.8 is BF,p = 0.0798 ; F2.7 vs. BF,ρ<0·04 163923.doc -18- 201247112 For mean blood pressure (MBP), F1.8 vs. BF, ρ=0·0735; F2.7 vs. BF, ρ < A 0.01 p value below 0.05 means that the difference is significant. Thus, the inventors have shown that during the first 4 months of life, only the low blood protein formula (1.8 g protein / 100 kcal) of the 3-year-old children's blood pressure ratio, they only fed a high protein formula (2.7 g protein) /100 kcal) is closer to children who only breastfeed. references
Boubred 等人(2007). Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats. Am J Physiol Renal Physiol, 293: 1944-1949.Boubred et al. (2007). Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats. Am J Physiol Renal Physiol, 293: 1944-1949.
Jarvisalo 等人(2009). Breast feeding in infancy and arterial endothelial function later in life. European journal of clinical nutrition, 63(5): 640-645. 【圖式簡單說明】 圖1展示使用三種不同灌食嬰兒配方時量測之血壓。 I63923.doc •19·Jarvisalo et al. (2009). Breast feeding in infancy and arterial endothelial function later in life. European journal of clinical nutrition, 63(5): 640-645. [Simplified illustration] Figure 1 shows the use of three different feeding formulas The blood pressure is measured. I63923.doc •19·
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