TWI528904B - Prenatal milk-derived composition for preventing the risk of low birthweight of newborns - Google Patents

Description

Prenatal milk-derived composition for preventing the risk of low birth weight in newborns

The present invention relates to the technical field of healthy foods and more particularly to the technical field of food compositions for preventing the risk of low birth weight in newborns.

By 1975, the problem of newborns having a low birth weight of 2,500 g or less (ie, low birth weight infants) at birth has improved in Japan. However, since 1980, the proportion of low birth weight infants in all newborns has increased in Japan. The reason for this phenomenon is as follows. Until then, it was still recommended to get enough nutrients during pregnancy, but since 1975-1980, even in the general public in Japan, it has been pointed out that excessive energy intake can cause obesity or different metabolic problems. Pregnant women are warned that excessive intake of nutrients during pregnancy can cause abnormal childbirth or pregnancy complications. In addition, it also includes the beauty requirements of pregnant women. Similarly, other suggested reasons are philosophical changes in obstetric agents, increased number of newborns born early during pregnancy, increased incidence of smoking in women at 20 years of age or younger, increased effects of multiple pregnancies, and similar reasons (non- Patent Document 1).

It is said that a newborn born with a low birth weight is associated with diseases such as diabetes, hypertension, and coronary artery disease (Non-Patent Document 2) and is also said to be associated with metabolic syndrome. Similarly, the respiratory function of a low birth weight infant is usually immature, such as about 25% of these infants develop into a primary apnea in preterm infants. It has raised the risk of developing disease in the brain or other organs.

As mentioned above, low birth weight at birth can cause different burdens, diseases or risks to newborns, so it is important to prevent low birth weight at birth. In order to avoid such problems, it is considered to be important to have good eating habits (to eat breakfast and similar habits according to a regular schedule) (Non-Patent Document 3). Also, for example, a method for predicting and diagnosing a newborn born at a low birth rate is reported in Patent Document 1.

In addition, for more than 40 years, in the nutritional necessities, such as the demand for vitamins during pregnancy, it has been specifically recommended to take folic acid during pregnancy. The relationship between folate deficiency and inhibition of central nervous system formation has been suggested. It is recommended to start taking folic acid before pregnancy because it reduces the risk of neural tube defects (NTD) (Non-Patent Document 4). In addition, the relationship between vitamin B12 or folic acid deficiency in pregnant women and low birth weight at birth is also suggested (Non-Patent Document 5).

Citation list Patent literature

PTL 1: JP Patent Publication (Kohyo) No. 2002-512047 A

Non-patent literature

NPL 1:http://www.aiiku.or.jp/aiiku/jigyo/contents/kaisetsu/ks0207/ks0207.htm

NPL 2: Lancet 1999, Vol. 353, No. 9166, p. 1789-1792

NPL 3: http://www.asagumi.jp/asagohan/txt/1-6

NPL 4: Report Concerning Reduction in the Risk of the Onset of Neural Tube Defects (December 2000) Conference concerning Risk of the Onset of Inborn Error

NPL 5: Asia Pac Journal of Clinical Nutrition 2006, Vol. 15, p. 538-543

A first object of the present invention is to develop a pharmaceutical composition or food composition for improving neonatal birth weight to prevent birth weight loss to below the average birth weight of a newborn by improving nutrition during pregnancy (post Also known as neonatal birth weight is low.

Similarly, a second object of the present invention is to develop a pharmaceutical or food composition for preventing neonatal birth weight, which is intended to be used for lack of nutritional balance due to snack intake as a staple food and vitamin deficiency (considered to be the recent birth weight) Pregnant women who are at increased risk of birth weight and low birth weight increase the background condition of the increase in the number of low infants.

Folic acid, which has been defined as a nutrient for pregnant women during pregnancy, is a water-soluble vitamin and is known to be weakly resistant to light, acids, bases, heat and the like. A problem with beverages such as milk containing folic acid and the like is known to be that a decrease in folic acid concentration is observed under long-term storage, for example (Nihon Chikusan Gakkaiho 2009, Vol. 80, pp. 41-45). Therefore, it is desirable to provide a pharmaceutical product, a prenatal food for a particular dietary use, or a prenatal nutritional supplement other than folic acid that provides safety and ensures nutrition and is easy to preserve.

Milk phospholipids (yeast phospholipids or phospholipids derived from milk) are safe food ingredients with excellent thermal stability and preservation qualities. Successful prevention of neonatal birth weight by ingesting lactophospholipids is very helpful for the health of pregnant women and newborns.

The present inventors have administered lecithin to vitamin B-deficient gestational rats, and subsequently evaluated the vitamin B group against pregnant rats based on the weight (length), body length, and organ weight of the rat (infant) measured immediately after birth. The effect and effects of vitamin B group on fetal rats. Therefore, the present inventors have found that a pregnant rat having a low birth weight can be born in the absence of vitamin B in a pregnant rat, but can be prevented from being born in a pregnant rat (pregnant female) which is administered with a lecithin to a vitamin B deficiency. Lower weight rat babies. Accordingly, the inventors have completed the present invention.

The present specification includes some or all of the contents disclosed in the specification and/or the drawings of Japanese Patent Application No. 2009-143615, which is a priority file of the present application.

The present invention has an excellent effect, and thus it is possible to prevent a low birth weight of a newborn by using a safe ingredient (yeast phospholipid) which is ingested as a food. In addition, in general, fat-soluble vitamins are more difficult to decompose than water-soluble vitamins. Therefore, it should be understood that the fat-soluble milk phospholipid has a rather excellent long-term storage quality (will not decompose).

The present invention includes a preparation for preventing low birth weight, which comprises as an active ingredient a milk phospholipid, thereby preventing a low birth weight of a newborn. The present invention further includes a preparation for reducing the risk of low birth weight of a newborn comprising as an active ingredient a milk phospholipid to reduce the risk of low birth weight of the newborn. The present invention further comprises a preparation for preventing low birth weight, which comprises as an active ingredient a milk phospholipid, thereby preventing birth weight loss of a newborn due to vitamin B deficiency in a pregnant woman. Also, the present invention includes a preparation for reducing the risk of low birth weight, which comprises as an active ingredient a milk phospholipid, thereby reducing the risk of low birth weight due to a vitamin B deficiency in a pregnant woman.

Similarly, the present invention encompasses a prenatal agent which is administered to a mother of a newborn by administering the agent to reduce diabetes, hypertension, or coronary artery disease associated with a low birth weight of the newborn after growth. Risk.

1. Prevention of low birth weight in newborns

Insufficient intake of vitamin B during pregnancy (vitamin B deficiency) is likely to result in low birth weight in newborns of pregnant women. Surprisingly, the inventors have found that a pregnant woman who has been administered with milk phospholipids to a dietary intake of vitamin B is significantly inhibited or prevented from having a low birth weight.

The composition for preventing neonatal birth weight of the present invention comprises as an active ingredient a milk phospholipid and comprises:

(1) A preparation for preventing birth weight and low birth weight to prevent neonatal birth weight;

(2) A preparation for reducing the risk of low birth weight to reduce the risk of low birth weight in newborns;

(3) A preparation for preventing birth weight in order to prevent low birth weight of a newborn due to vitamin B deficiency;

(4) A preparation for reducing the risk of low birth weight to reduce the risk of low birth weight due to vitamin B deficiency.

1-1. Composition for preventing neonatal birth weight

In the present invention, an example of an active ingredient for use in a composition for preventing neonatal birth weight is milk phospholipid. An example of a milk phospholipid is obtained by extracting a lipid component from milk using ethanol or the like, followed by extraction of milk phospholipid with acetone.

For example, a milk-derived phospholipid can be prepared by a known method disclosed in Japanese Patent Publication (Kokai) No. 2002-226394 A. Specifically, the milk-derived phospholipid can be obtained according to a known method {"Lipid Chemistry (Shishitsu no Kagaku) (Seikagaku Jikken Koza (Biochemical Experimental Lecture Series) 3)", Ed., The Japanese Biochemical Society, page 23, TOKYO KAGAKU DOZIN CO., LTD, 1974; "lipid II phospholipid (New Seikagaku Jikken Koza (New Biochemical Experimental Lecture Series) 4)", Ed., The Japanese Biochemical Society, p. 7, TOKYO KAGAKU DOZIN CO., LTD, 1991}, using solvent extraction cream (by-product of butter making); whey (by-product of cheese making); or skim milk to prepare. Alternatively, the phospholipid derived from milk can be prepared by using different types of chromatography, separating the extract (obtained by solvent extraction as described above). For example, phospholipids derived from milk may also be obtained from milk fat or cream, or butter whey, which is a by-product of the manufacture of butter, as an insoluble portion of acetone (solvent). Butter whey can also be used in the field of commercially available dairy products and is therefore available from (eg New Zealand, Tatua). Cream whey has a high content of MFGM, which contains phospholipids, and is therefore suitable as a raw material for extracting phospholipids.

When separating phospholipids from butter whey, the phospholipids should be utilized insoluble in acetone. The acetone-soluble fraction containing the neutral lipid is removed via multiple acetone extractions and the acetone-insoluble fraction containing the concentrated phospholipid is subsequently obtained. The acetone-insoluble portion was subjected to vacuum concentration to remove acetone, and then the concentrate was freeze-dried after sterilization. The dried product is milled to obtain a phospholipid fraction derived from milk. For example, the composition of the phospholipid fraction thus obtained contains 85% by weight of phospholipids. In the phospholipid fraction, a component comprising choline (such as phospholipid choline) and sphingomyelin are present.

In addition, for milk phospholipids, a dairy product containing lactophospholipid may also be used: "milk phospholipid concentrate" (containing about 5% by weight choline; 85% by weight lipid, 10% by weight ash content, 4% by weight carbohydrate, and 1 Weight % moisture).

Prenatal medication

The agent of the present invention is:

(1) A prenatal agent for preventing birth weight in newborns (for the prevention of low birth weight) or (2) a prenatal agent for reducing the risk of low birth weight in newborns (for reducing birth) a preparation for the risk of low weight); or

(3) A prenatal agent for reducing the risk of a newborn suffering from a disease associated with a low birth weight of a newborn, which is a pregnant woman who is administered the prenatal agent to a newborn mother.

Examples of the agent of the present invention comprising a milk phospholipid as an active ingredient include (1) a prenatal agent for preventing birth weight of a newborn (a preparation for preventing birth weight), and (2) a method for reducing birth of a newborn a prenatal agent at a low risk of weight (a preparation for reducing the risk of low birth weight), and (3) a prenatal agent for reducing the risk of a newborn having a low birth weight-related disease after growth It is a pregnant woman who is administered the prenatal medication to the newborn mother.

The agents of the invention may be formulated into suitable dosage forms such as powders, granules, lozenges, capsules and solutions. Once formulated, adjuvants such as excipients, adhesives, disintegrants, and lubricants, which are typically used in the formulation, are added. Examples of excipients include starch, lactose, sucrose, methylcellulose, carboxymethylcellulose, sodium alginate, calcium hydrogen phosphate, synthetic aluminum citrate, microcrystalline cellulose, polyvinylpyrrolidone (PVP), and Hydroxypropyl starch (HPS). Also, examples of the adhesive include starch, microcrystalline cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), powdered gum arabic, gel, aqueous solution of dextrose and sucrose, or the like, or an aqueous solution thereof Or ethanol solution. Examples of the disintegrant include starch, carboxymethylcellulose, carboxymethylcellulose calcium, microcrystalline cellulose, hydroxypropyl starch, and calcium phosphate. Further, examples of the lubricant include carnauba wax, light anhydrous citric acid, synthetic aluminum silicate, natural aluminum citrate, synthetic magnesium citrate, hardened oil, derivative of hydrogenated vegetable oil (Sterotex HM), sesame oil , white beeswax, titanium oxide, dried aluminum hydroxide-gel stearic acid, calcium stearate, magnesium stearate, talc, calcium hydrogen phosphate and sodium lauryl sulfate.

2-1. Formulation of the medicament of the present invention

Agent of the invention

The agent of the present invention is, in particular, (1) a prenatal agent for preventing low birth weight of a newborn, (2) a prenatal agent for reducing the risk of low birth weight of a newborn, or (3) a use A prenatal agent for reducing the risk of a neonatal growth-related disease associated with a low birth weight of a newborn, which is administered to a pregnant woman who is administered the neonatal mother to the newborn mother and may be administered orally or parenterally. Preferably, it is administered orally.

Similarly, with regard to the oral dosage form of the agent of the present invention, for example, the dose of choline is desirably in the range of 60 mg/day to 3.5 g/day, preferably in the range of 100 mg/day to 3.5 g/day. More preferably, it is in the range of 200 mg/day to 3.5 g/day, and more preferably in the range of 350 mg/day to 3.5 g/day. The dose of "breast phospholipid concentrate" (containing about 5% by weight choline; 85% by weight lipid, 10% by weight ash content, 4% by weight carbohydrate, and 1% by weight moisture) is desirably from 1.4 g/day to 75 g/ Within the range of days, preferably in the range of 2.4 g/day to 75 g/day, more preferably in the range of 4.8 g/day to 75 g/day, and also preferably in the range of 7.5 g/day to 75 g/ Within the scope of the day (for example, American Journal of Clinical Nutrition 2005, 82, pp. 111-117; American Journal of Clinical Nutrition 2006, vol. 83, pp. 905-911; European Journal of Nutrition, 2007, Vol. 46, Pages 300-306, Dietary Reference Intakes, p. 411).

In the present invention, it is desirable to start ingesting a prenatal agent for preventing birth weight of a newborn before pregnancy. It is desirable to ingest the prenatal agent at least once throughout the pregnancy, and preferably such ingestion throughout the pregnancy (eg, daily).

2-2. Subject to the agent of the present invention

The agent of the present invention, which is specifically described as (1) a prenatal agent for preventing birth weight of a newborn (for preventing a low birth weight), and (2) a method for reducing the birth weight of a newborn a prenatal agent for risk (a preparation for reducing the risk of low birth weight), or (3) a prenatal agent for reducing the risk of a newborn having a low birth weight-related disease after growth, which is via A pregnant woman who is administered this prenatal medication to a newborn mother and can be administered to all pregnant women. The agent of the present invention can be specifically administered to pregnant women who have an imbalance in nutritional intake. Specific examples of such pregnant women include pregnant women with insufficient vitamins and further clear examples thereof include vegetarian pregnant women and pregnant women with insufficient vitamin B. Here, the term "deficiency of vitamin B" means insufficient folic acid, insufficient vitamin B2, insufficient vitamin B6, and insufficient vitamin B12.

3. Prenatal food or prenatal nutritional supplements for special dietary purposes

The food or nutritional supplement food for special dietary use of the present invention (1) a prenatal food or a prenatal nutritional supplement for preventing a newborn having a low birth weight for a particular dietary use, and (2) one for Reduce the risk of low birth weight in newborns for prenatal or prenatal nutritional supplements for special dietary use, or (3) a risk of reducing the risk of neonatal growth-related diseases associated with low birth weight Prenatal food or prenatal nutritional supplements for special dietary use are administered to pregnant women who have given the prenatal medication to the newborn mother.

The food or nutritional supplement food for the special dietary use of the present invention comprises milk phospholipid as an active ingredient, and may be in any form of a solid (for example, a powder and a granule), a paste, a liquid or a suspension. For example, when the food is formulated into a drinkable formulation, additives such as sweeteners, acidulants, vitamin formulations, and other additives commonly used in the manufacture of drinkable formulations may also be added.

The food or nutritional supplement food of the present invention for special dietary use may be formulated as a supplement in a suitable dosage form such as a powder, granule, lozenge, capsule or solution.

Further, the food or nutritional supplement food of the present invention for special dietary use may be in the form of a food additive comprising phospholipid as an active ingredient for preparing prenatal food or prenatal nutritional supplement food for special dietary use.

For the ingestion of the food or nutritional supplement for the special dietary use of the present invention, it is desirable to take choline in the range of 60 mg/day to 3.5 g/day, preferably 100 mg/day to 3.5 g/day. In the range of 200 mg/day to 3.5 g/day, and preferably in the range of 350 mg/day to 3.5 g/day, and the desired "milk phospholipid concentrate" (including About 5% by weight of choline, 85% by weight of lipid, 10% by weight of ash content, 4% by weight of carbohydrate, and 1% by weight of water) are in the range of 1.4 g/day to 75 g/day, preferably 2.4 g. /day to 75 g / day, more preferably in the range of 4.8 g / day to 75 g / day, and also preferably in the range of 7.5 g / day to 75 g / day (for example, American Journal of Clinical Nutrition 2005, 82, pp. 111-117; American Journal of Clinical Nutrition 2006, Vol. 83, pp. 905-911; European Journal of Nutrition, 2007, Vol. 46, pp. 300-306, Dietary Reference Intakes, Page 411).

Instance

Example 1: Effect of ingesting lactose during pregnancy

experiment method

The rats were divided into 4 groups for experiments, and 8 rats in each group were used for feeding examples, and a total of 4 feeding examples were performed. The rat body weight ranged from 155 g to 165 g at the start of the experiment and ranged from 240 g to 290 g at the completion of the test (during pregnancy). At this time, there was no significant difference between the weights of each group.

(1) Feeding a 9-week-old female Wistar with a low-vitamin diet (low-vitamin diet: prepared by removing vitamin B2, folic acid, vitamin B12, and choline bitartrate from the AIN93G vitamin mixture) or a control diet (control group: AIN93G) Rats were given a free week of feeding. (Table 1)

(2) Female Wistar rats of 10 weeks old were mated.

(3) The day on which the mating (mating plug) is determined is recorded as day 0 of pregnancy. Feed the groups with a test diet (AIN93G, low-vitamin diet, low-vitamin diet + lactose (2.6% by weight; choline content of about 40 mg/g), low-vitamin diet + choline bitartrate (0.25% by weight) (free access to food). Feed on a test diet (free access) until the 20th day of pregnancy. In addition, the low-vitamin diet + lactose, low-vitamin diet + choline bitartrate and choline in AIN93G had a concentration of 0.1% by weight.

(4) On the 20th day of pregnancy, about 0.3 ml of blood was collected intravenously, laparotomy was performed, the fetus was taken out, and then the body weight was measured. In addition, the number of siblings is generally set at 12 +/- 3 (excluding the number of rats) and the groups are then compared to each other. For statistical analysis, the Statview differential one-way analysis (SAS) was used to perform the multiple comparison (Post-hoc: Scheffe) test.

test results

Fetal weight is reduced due to low vitamin intake (Figure 1). However, due to the intake of low vitamin supplements containing milk phospholipids, fetal weight is improved and therefore increased (Figure 1 and Table 2).

It has been confirmed by this test that the intake of vitamin-based infants is necessary. It further confirms that the intake of milk phospholipids can improve infants that are not fully developed due to vitamin deficiency.

Industrial application

The prenatal agent of the present invention, food for special dietary use, or nutritional supplement food has an excellent effect on preventing neonatal birth weight. Therefore, prenatal medications, foods for special dietary uses, or nutritional supplements can be used in the pharmaceutical or food manufacturing industries.

All publications, patents and patent applications cited herein are hereby incorporated by reference.

Figure 1 shows the results of opening the abdominal cavity on the 20th day of pregnancy, extracting the fetus and subsequently measuring its quantity and body weight.

(no component symbol description)

Claims (8)

A use of a milk-derived phospholipid for the manufacture of a prenatal agent that prevents the risk of vitamin B and folate intake in pregnant women who are born with low birth weight. The use of claim 1, wherein the latex derived from the milk comprises sphingomyelin and/or phospholipid choline. The use of claim 1 or 2, wherein the choline content is at least 60 mg/day. Use of a phospholipid derived from milk as a prenatal food or prenatal nutritional supplement for special dietary uses to prevent pregnancy risk of vitamin B and folate deficiency in producing low birth weight newborns . The use of claim 4, wherein the milk-derived phospholipid comprises sphingomyelin and/or phospholipid choline. The use of claim 4, wherein the milk-derived phospholipid comprises sphingomyelin and/or phospholipid choline. The use of any one of claims 4 to 6, wherein the choline content is at least 60 mg/day. A use of a milk-derived phospholipid for use as a food additive for the preparation of pre-natal foods or prenatal nutritional supplements for special dietary uses for the prevention of low birth weight in newborns.