JP2000050793A - Synthetic milk composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a synthetic milk composition capable of improving the function of pancreatic digestion (e.g. pancreatic amylase) in a living body through increasing insulin concentration in blood up to the same level as in breast nursing by being orally administered. SOLUTION: This synthetic milk composition is prepared by adding insulin to synthetic milk so as for insulin concentration to become <=104 times concentration in woman's milk, pref. (0.3-5) times concentration in woman's milk. The composition can increase insulin concentration in blood up to the same level as in breast nursing by being orally administered.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an artificial milk composition. More specifically, the present invention relates to an artificial milk composition characterized by changing the blood insulin concentration and pancreatic digestive function of a living body by oral administration from the birth to the weaning period, as in breastfeeding.

[0002]

2. Description of the Related Art Breast milk contains a high concentration of physiologically active substances such as various hormones, growth factors (growth factors) and enzyme inhibitors. These physiologically active substances are considered to be important as factors for assisting the physiological functions of infants and promoting and controlling the growth and development of infants. Among these physiologically active substances in breast milk, insulin-like gr
owth factor (IGF), epiderm
al growth factor (EGF), ner
It has been shown that the growth factor, prolactin and immunoglobulin G specifically pass through the intestinal tract. Apart from its specificity, it has been suggested that some biologically active substances in breast milk, including insulin, can be absorbed into the body. Therefore, biologically active substances in breast milk are not only responsible for the growth and maturation of small intestinal epithelial cells,
It may also play an important role in the development of tissues where breast milk is not in direct contact.

On the other hand, in the case of artificial milk, most of the bioactive substances derived from bovine breast milk are decomposed or removed in the process of purifying the milk protein as a raw material. It contains only very low concentrations of bioactive substances. Therefore, when nursing with artificial milk, the lack of a physiologically active substance in the milk may affect various growth and development processes of the infant. However, it has not been fully clarified which developmental processes and how infants are different from mothers. Given the differences, little has been done on the causal relationship between such developmental processes and bioactive substances in breast milk, so the physiological significance of bioactive substances in breast milk remains largely unknown. Remains.

[0004] In modern society, it is difficult to raise all infants solely from breast milk, and formula powder is required. In addition to formula being the only source of nutrition for formula infants, it is necessary to make better formulas, taking into account that breast milk is important as an inducer of the infant's developmental process. ing. However, physiologically active substances found in breast milk may not have clear physiological significance, and are not added to currently available infant formulas.

[0005] Of course, infant formula containing insulin is not commercially available, and it has been reported that administration of an insulin-added formula increases blood insulin levels and consequently pancreatic amylase. It has never been done before and is new.

[0006]

BACKGROUND OF THE INVENTION Many mammals, including humans, take polysaccharides, mainly starch, which have not been taken up as a major energy source by weaning. In humans and rats, the amylase content in the previously low pancreatic zymogen granules begins to increase during weaning. An increase in pancreatic amylase at this time is very important to secure a stable energy source. Also, since weaning is a period of development of various tissues, sufficient energy intake, which is thought to be enabled by increased pancreatic amylase, may be important for subsequent growth and body function.

The present invention has been made in view of the state of the art.
The purpose of the present invention is to newly develop an artificial milk composition capable of changing pancreatic digestive functions such as elevation of pancreatic amylase in a living body to the same level as in breastfeeding.

[0008]

DISCLOSURE OF THE INVENTION The present invention has been made to achieve the above-mentioned object, and focuses on the physiological importance of the increase in pancreatic amylase in the early stage of weaning, and explains the cause of the induction of pancreatic amylase activity increase The present inventors have conducted extensive research on. In the course of that study, they found that dietary changes did not affect the increase in pancreatic amylase activity in the early stages of weaning, and that the rats fed with artificial milk did not show an increase in amylase in the early stages of weaning. Obtained.

The present inventors have further studied and found that
Focusing on insulin for the first time and measuring blood insulin concentration, an increase in blood insulin concentration was observed in breast-fed rats, but not in artificially-fed rats. It was confirmed that the change was one day earlier, and it was strongly inferred that the change in blood insulin concentration in the early stage of weaning was related to absorption of insulin in breast milk.

In order to confirm this point, when an artificial milk supplemented with insulin was orally administered, a significant increase in blood insulin concentration was observed as inferred. The present inventors have obtained useful new findings that the increase in blood insulin concentration caused by the increase in blood insulin concentration, in other words, that the increase in blood insulin concentration is an inducer of pancreatic amylase increase.

The present invention has been made on the basis of these useful new findings, and has a basic technical idea of an artificial milk composition to which insulin has been added. It increases or regulates the insulin concentration and / or the expression of pancreatic amylase in a living body and other pancreatic digestive functions, and changes the same as in breastfeeding.

[0012] The artificial milk composition according to the present invention includes, for example, infant formula, premature infant formula, follow-up milk, special formula for pharmaceutical use, and other formulas for use in artificial nursing, It includes all liquid formulas prepared for the purpose of artificial nursing infants. And this artificial milk composition is not intended for administration only for newborns to infants from birth to weaning period, but also for infants and children after weaning period, adults, elderly people, sick people Is what you do.

[0013] The artificial milk composition according to the present invention usually contains insulin at a concentration that does not reduce the blood glucose level of a living body by oral administration. The concentration of insulin added to the formula in breast milk (approximately 20 ng / ml)
If the concentration is higher than 10 ⁴ times the blood sugar level, the insulin added to the formula should be less than 1% of the concentration in breast milk.
0 ^4-fold better to the following concentration ranges, preferably from 0.1 to 10 times the concentration in breast milk, and more preferably 0.3 to 5
It is good to set the concentration range to twice.

However, the same level as breast milk, and 5
Administration of the artificial milk supplemented with twice the concentration of insulin did not increase the blood insulin level to the same level as when breastfeeding. In addition, when nursing with insulin-added milk at the same level as breast milk, as shown later, it was found that an increase in pancreatic amylase in the weaning period equivalent to that in nursing was not induced, and there was room for further improvement. .

Insulin has various actions and essentials on various organs and tissues. Infancy is a time when the tissues of a living body change and develop dramatically, and blood insulin may be involved in many developmental processes other than pancreatic amylase. For example, it is conceivable that an increase in blood insulin concentration plays an important role in the formation and increase of adipose tissue, skeletal muscle, and liver, and expression of functions as tissues. In addition, the development of these tissues simultaneously increases the blood glucose processing ability, which is considered to lead to an improvement in blood glucose maintenance ability in addition to the blood glucose lowering promoting action of insulin. However, these developments may not occur sufficiently unless an increase in blood insulin concentration equivalent to that in breastfeeding occurs.

Therefore, the present inventors focused on the protease inhibitor activity contained in breast milk for the first time and made further studies in order to more efficiently increase the blood insulin concentration due to insulin intake. Breast milk contains high concentrations of several substances having protease inhibitor activity. Although their physiological roles and importance are not clear, the present inventors have inhibited pancreatic protease activity in the intestinal tract, thereby suppressing the degradation of bioactive substances in breast milk, and I got the idea that the absorption was efficient. The major protease inhibitor in breast milk is trypsin inhibitor (TI).

[0017] As a result of taking these factors into account, the present inventors suggest that TI activity in breast milk suppresses the decomposition of insulin in milk and efficiently increases blood insulin concentration. Obtained. On the other hand, no TI activity is detected in the artificial milk. Then, when TI was simultaneously added to insulin-supplemented milk so as to have the same level as the TI activity detected in breast milk, it was found that the increase in blood insulin concentration increased as predicted by the present inventors. .

Further, based on this finding, the present inventors:
New knowledge that nursing with an artificial milk supplemented with insulin and TI simultaneously induces an increase in blood insulin concentration and the development of pancreatic amylase in the early weaning period has been obtained. The invention described above, which is based on the point of raising the temperature, has been further improved. In addition, for inhibiting the decomposition of insulin in milk, in addition to TI, any substance that is a chymotrypsin inhibitor or any other protease inhibitor that can suppress the decomposition of insulin can be used. I also got recognition.

The present invention has been finally completed based on the above-mentioned useful new findings and further studied. The present invention relates to a case in which the blood insulin concentration and / or the pancreatic digestive function of a living body are breast-fed by oral administration. An artificial milk composition to be changed equivalently is a basic technical idea, and as one of its specific embodiments, the above-mentioned invention relating to an artificial milk composition containing insulin is further improved, and insulin and proteolytic enzyme inhibition The present invention relates to an artificial milk composition using an agent in combination.

In other words, the artificial milk composition according to the present invention, if necessary, should have the same level of blood insulin concentration and / or pancreatic digestive function as in breastfeeding when administered orally, For this purpose, necessary amounts of insulin and, if necessary, further a protease inhibitor are added. Therefore, it is not necessary to add both components to the artificial milk composition in combination, and if only a large amount of insulin is used or if the proteolytic enzyme inhibitory activity in the living body is high, only insulin is used as the artificial milk composition. It may be added to the composition.

Normally, the amount of insulin added to the artificial milk is in a concentration range of 10 ⁴ times or less, preferably 0.1 to 10 times, more preferably 0.3 to 5 times the insulin concentration in breast milk. It is better to set the concentration range.

However, the above-mentioned insulin concentration range is a guideline for administration to healthy children from birth to weaning, and is intended to reduce blood sugar levels and treat diabetic patients. In such a case, the concentration may be higher than the above concentration range, or conversely, a certain amount of insulin may be secreted, and in a case where the amount thereof may be further added, the concentration may be lower than the above concentration range. Good. In the latter case, the degradation of the added insulin in the intestinal tract need not be particularly suppressed without adding a protease inhibitor.

The amount of the protease inhibitor is not particularly limited as long as it can inhibit the decomposition of insulin. However, as a rough guide, the amount of insulin added is 20 ng / g.
In the case of ml, the TI is in the range of 0.1 to 10 U / ml, preferably 0.5 to 2 U / ml. However, this blending amount naturally varies depending on the amount of insulin added, the protease activity of the living body itself, and the like, and in some cases, may be outside the above range.

The method of compounding insulin and, if necessary, a protease inhibitor is as follows. In the case of producing a liquid formula, sterilized insulin (and the inhibitor) solution is added to a solution prepared by sterilizing the raw material,
Mix and cool as usual to make the product. In addition, when preparing milk powder, the raw materials are prepared and homogenized.
Sterilized solution, sterilized insulin (and its inhibitor)
Is added and mixed, and concentrated and dried according to a conventional method to obtain a product, or a sterilized concentrate containing insulin (and the inhibitor) is powdered by freeze-drying or the like,
It can also be mixed with a formula powder to form a product.

As the insulin used in the present invention, not only purified insulin but also compounds having the same function as insulin can be used. The latter compound refers to a compound obtained by performing substitution, deletion, insertion, transfer, or the like on a part of the amino acid sequence so that the insulin function is not changed. Still further, in the present invention, crude insulin, said compound, and
Can also be used.

Hereinafter, embodiments of the present invention will be described.

[0027]

Example 1 The effect of the intake of artificial milk supplemented with insulin on the blood insulin concentration in the early stage of weaning was investigated.
It was confirmed by the following.

The rats at the early stage of weaning were divided into two groups, one of which was breastfed with breast milk and the other with infant formula. For each group, plasma insulin concentration and pancreatic amylase activity were measured. The obtained results are shown in FIGS.

As a result, in the early weaning rats bred with breast milk, the age-dependent increase in blood insulin concentration occurred. As shown in FIG. 1A, the blood insulin concentration starts to increase at 14 days of age, peaks at 17 days of age, and then temporarily decreases. Infancy is the time when the tissues of a living body change and develop dramatically. Since insulin has various actions and essentials on various organs and tissues, the rise in blood insulin concentration in the early weaning may be involved in much of the developmental process at this time. On the other hand, in rats fed with artificial milk, no increase in blood insulin concentration was observed.

FIG. 1B shows the change of amylase activity in granules of pancreatic zymogen of early weaning rats. In breast-fed rats, pancreatic amylase activity begins to increase at 14 days of age, peaks at 18 days of age, and then decreases gradually. Thus, the change in pancreatic amylase activity moves according to the change in blood insulin concentration. These results support that pancreatic amylase increase in early weaning is induced by an increase in blood insulin concentration. On the other hand, in rats fed with artificial milk, no increase in pancreatic amylase was observed.

Therefore, an experiment was conducted on 17-day-old rats in which the increase in blood insulin concentration peaked when breast milk was continuously taken. To eliminate the effects of insulin from breast milk,
On the day before the experiment, the stomach of the pup rat (16 days old) was cannulated, and an artificial milk without added insulin was administered overnight. The artificial milk was administered every other hour for 5 minutes at 300 μl. The artificial milk used was composed of nutrient composition, osmotic pressure, p
H is approximated to rat breast milk (JP-A-09-322)
715). On the morning of the experiment, the rats were divided into two groups, each group consisting of 8 rats, and each group was administered with an artificial milk (20 ng / ml) supplemented with the same level of insulin as that of breast milk and an artificial milk not supplemented with insulin. . In addition, the insulin concentration of the artificial milk to which insulin was not added was the measurement limit (0.2 n
g / ml).

Blood was collected at 0, 1, 3, and 6 hours after the start of the administration of the milk supplemented with insulin, and the insulin concentration in the plasma was measured by radioimmunoassay. FIG. 2 shows the measurement results of the blood insulin concentration. As a result, in the group to which the artificial milk to which insulin was not added was administered, the plasma insulin concentration was at the same level as the blood insulin concentration at the age of 14 days, and was constant at about 0.7 ng / ml. On the other hand, in the group to which the insulin-added milk was administered, the blood insulin level significantly increased 3 hours after the start of the administration, and maintained the same level 6 hours later. In addition,
Although not shown in the figure, the blood glucose concentration was constant during the experiment, and no difference was observed between the groups. From the above results, it was shown that insulin-added milk at the same level as that of mother's milk had the effect of increasing blood insulin concentration in several hours without affecting blood glucose concentration.

[0033]

Example 2 The effect of increasing the concentration of insulin in blood by changing the concentration of insulin added to artificial milk was examined.

As in Example 1, the stomach of 16-day-old pups was cannulated, and an artificial milk without insulin was administered overnight. On the morning of the next day, the rats were divided into 4 groups, each group consisting of 8 rats.
Artificial milk supplemented with insulin at 5, 20, and 80 ng / ml was administered to each group. Six hours after the start of the administration of the milk supplemented with insulin, blood was collected, and the plasma insulin concentration was measured by a radioimmunoassay. The results are shown in FIG.

As a result, in the group to which the artificial milk to which insulin was not added was administered, the blood insulin concentration was about 0.5.
It was 7 ng / ml. In contrast, the administration of 5 ng / ml insulin-added milk showed an increase in blood insulin concentration, and the administration of 20 ng / ml insulin-added milk at the same level as in rat breast milk resulted in a significant increase in blood insulin concentration. Was. In addition, the administration of 80 ng / ml of the insulin-added milk further increased the blood insulin concentration, which was about 1.6 times that of the group to which the artificial milk without the addition of insulin was administered. Although not shown in the figure, there was no difference in blood glucose concentration between the groups. In addition, the blood concentration of C-peptide, which is produced when insulin is synthesized in pancreatic β cells and released into the blood together with insulin, is the same as that in the group to which 20 ng / ml insulin-supplemented milk was administered and that in the non-insulin-added artificial milk There was no difference from the group that received. From this, it was recognized that milk insulin did not promote insulin secretion from the pancreas, but milk insulin itself was absorbed into the body to increase blood insulin concentration.

[0036]

Example 3 The effect of adding TI to milk to increase the increase in blood insulin concentration due to milk insulin was examined.
It was confirmed by the following.

A 16 day old rat was gastrically cannulated,
To eliminate the effects of insulin from breast milk, normal artificial milk (STD) without added insulin was administered overnight. The administration of the artificial milk was performed at 300 μl for 5 minutes every hour. The formula used was composed of nutrients, osmotic pressure, pH
Is approximated to rat breast milk (Japanese Patent Laid-Open No. 09-3227).
15). The next morning, the rats were divided into 4 groups of 9 rats each, and STD milk and TI (soybean-derived) added milk (1 U / m
l), milk with insulin (20 ng / ml), milk with insulin and TI (TI, INS, INS / TI milk)
Was administered. The expected TI activity is detected in each artificial milk. Four hours after the start of administration of each artificial milk, blood was collected, and the plasma insulin concentration was measured by radioimmunoassay. FIG. 4 shows the obtained results.

As a result, in the INS group, the blood insulin concentration was significantly higher than the STD, but did not reach the level (about 1.5 ng / ml) of 17-day-old breast-fed rats. On the other hand, the blood insulin concentration of the INS / TI group showed a significantly higher rise than that of the INS group,
The level was the same as that of a day-old lactating rat. Administration of the artificial milk to which TI alone was added (TI group) did not change the blood insulin concentration. In addition, there was no difference in blood glucose concentration between the groups. In addition, the TI activity in blood did not differ between the groups, and was the same level in the breast-feeding rats. These results indicate that milk TI activity itself has no effect of increasing blood insulin concentration, but that it increases the absorption efficiency of milk insulin by inhibiting the degradation of milk insulin by pancreatic proteases. It was suggested. In addition, it was confirmed that the milk TI was not absorbed in the blood, but acted only in the intestinal tract.

[0039]

Example 4 A rat artificial lactation (AR) experiment was performed using an artificial milk supplemented with insulin and TI, and an increase in blood insulin concentration due to insulin and TI activity in milk induces an increase in pancreatic amylase in the early stage of weaning. Was considered.

[0040] Stomach cannula was applied to 13-day-old rat pups, and they were artificially reared with three types of artificial milk, STD, INS, and INS / TI, until they were 21 days old. The dose of artificial milk is 1
It was 4.8 ml / day at 3 days of age and increased gradually with increasing age (0.6 ml per day). In each group, body weight and pancreas weight increased with increasing age, and there was no effect of insulin and TI activity in milk. Although not shown, the blood sugar level did not change with age in each group, and the effect of milk insulin was not observed.
At each age, blood and pancreas were collected.

FIG. 5A shows the blood insulin concentration measured by the radioimmunoassay method. 18 in STD group
The blood insulin concentration was almost constant until the age of day, and no increase in the blood insulin concentration peaked at the age of 17 days was observed as in the breast milk group described above. After 18 days of age, blood insulin levels began to rise gradually. Although the blood insulin concentration in the INS group was not different from that in the STD group at 14 days of age,
It increased from the age of 16 days, and significantly increased with respect to the STD group at the age of 17 days. The blood insulin concentration of the INS group was 18
It gradually decreased on the day, and then increased gradually as in the STD group.
By the simultaneous addition of insulin and TI to the artificial milk, the increase in blood insulin concentration at the third week after birth became more remarkable than in the INS group, and the behavior was similar to the daily change of breast-fed rats. At 16, 17, and 18 days of age, INS / TI
The blood insulin concentration of the group was significantly higher than that of the STD group, and increased to twice that of the STD group at 17 days of age. At the age of 19 days, the blood insulin level in the INS / TI group decreased,
Thereafter, there was no difference with the blood insulin in the STD group. As described above, the addition of insulin and TI to the milk used for nursing induced an increase in the blood insulin concentration in the early stage of weaning without affecting the blood glucose level.

Next, the activity of amylase contained in pancreatic zymogen granules, which are storage organs for pancreatic digestive enzymes, was measured. The result is shown in FIG. 5B. In the STD group, the pancreatic amylase activity was almost constant until the age of 18 days, as shown above.
Then it began to increase slowly. The amylase activity of the INS group was not different from that of the STD group at 14 and 16 days of age, but showed a significant increase at 17 days of age. Thereafter, it remained constant until 21 days of age. Nursing with an artificial milk supplemented with insulin and TI induced an increase in pancreatic amylase activity at 3 weeks of age seen in breast-fed rats. Amylase activities at 17, 18, and 19 days of age were 1.4, 1.7, and 1.6 times that of the STD group, respectively. 21
The pancreatic amylase activity gradually decreased at the age of day, and reached the same level as the STD group and the INS group. This study also confirmed that daily changes in amylase activity in each group followed changes in blood insulin concentration, indicating that milk insulin increased pancreatic amylase through an increase in blood insulin concentration. Was. In other words, it was shown that increasing the blood insulin concentration can induce an increase in pancreatic amylase in the early weaning period observed in breast-fed rats. In addition, pancreatic amylase activity (27.3 ± 3.2 U / mg proteini) of rats bred to 18 days of age with artificial milk to which only TI was added.
Since n) was at the same level as the STD group, it was suggested that the TI activity itself did not have the effect of increasing pancreatic amylase activity.

[0043]

Example 5 The following raw materials were prepared. (Per 100 g of product) skim milk powder 28 g mixed oil 25 g lactose 40 g skim whey powder 5 g vitamins and minerals 2 g insulin 10 μg

A predetermined amount of the above-mentioned raw materials (mixed oil of fractionated oil of lard, fractionated oil of palm, mixed oil of soybean oil, coconut oil and fish oil) was weighed, blended and purified according to a conventional method. After sterilization, concentration, and homogenization, insulin was added aseptically and spray-dried to produce a powdered infant formula. After similarly sterilizing, insulin was aseptically added and sealed in the final step to produce a liquid infant formula containing insulin.

[0045]

Example 6 In Example 5, 750 units of a trypsin inhibitor were added in addition to insulin, to prepare infant formula and liquid infant formula.

[0046]

According to the present invention, the insulin concentration in blood can be increased to the same level as that of breastfeeding by orally administering the insulin-added artificial milk, and as a result, pancreatic amylase such as pancreatic amylase can be obtained. Digestion function can be enhanced.

In addition, according to the present invention, by raising a baby with artificial milk to which insulin and TI are added simultaneously, it is possible to increase the blood insulin concentration and further induce the development of pancreatic amylase in the early stage of weaning. In addition, by increasing the blood insulin level, it is possible to induce an increase in pancreatic amylase in the early stage of weaning, which occurs when breastfeeding.
Furthermore, by the induction of an increase in blood insulin concentration according to the present invention, the development process of each of the insulin-sensitive organs occurring during the infancy and the weaning period can proceed normally.

In recent years, attempts have been made to absorb orally taken insulin into the blood instead of administering insulin by injection, as a treatment for patients with insulin-dependent diabetes mellitus. Can also be used. According to the present invention, it is also possible to lower the blood glucose level by orally administering high-concentration insulin or a compound having the same action as insulin together with TI without special treatment in infants.

[Brief description of the drawings]

FIG. 1 shows the relationship between the age of rats (breastfeeding and artificial feeding) in early weaning, blood insulin concentration (A) and pancreatic amylase activity (B).

FIG. 2 shows the results of measuring the insulin concentration in plasma of rats to which artificial milk with or without insulin was administered.

FIG. 3 shows the relationship between the concentration of insulin added to artificial milk and the concentration of insulin in plasma.

FIG. 4 shows the relationship between administered artificial milk (without addition of insulin, addition of trypsin inhibitor, addition of insulin, addition of insulin + trypsin inhibitor) and insulin concentration in plasma.

FIG. 5: Artificial milk (control, insulin supplement, insulin +
2 shows the relationship between the age of each rat to which trypsin inhibitor was added and the plasma insulin concentration (A) and pancreatic amylase activity (B).

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4B001 AC05 EC06 4C084 AA02 AA17 AA20 BA44 DB34 MA02 MA52 NA10 NA14 ZC352 4H045 AA30 BA20 DA37 DA56 EA01 EA27

Claims (11)

[Claims] 1. An artificial milk composition characterized in that by oral administration, the blood insulin concentration is changed to the same level as in breastfeeding. 2. An artificial milk composition characterized in that by oral administration, the digestive function of the pancreas of a living body is changed to the same level as in breastfeeding. 3. The artificial milk composition according to claim 1, wherein the composition contains insulin or a compound having a function equivalent to insulin at a concentration that does not decrease the blood glucose level of a living body by oral administration. 4. The method according to claim 1, which further comprises a concentration of insulin or a compound having a function equivalent to insulin which does not decrease the blood glucose level of a living body by oral administration, and a protease inhibitor. The artificial milk composition according to the above. 5. The method according to claim 1, wherein the insulin added to the artificial milk is in a concentration range of 10 ⁴ times or less the concentration in breast milk, preferably 0.3 to 5 times the concentration in breast milk. The artificial milk composition according to any one of claims 1 to 4. 6. The compound according to claim 1, wherein the compound having a function equivalent to insulin added to the artificial milk has a concentration range having a function equivalent to insulin in the concentration range according to claim 5. The artificial milk composition according to any one of the preceding claims. 7. The artificial milk composition according to claim 4, wherein the protease inhibitor is an inhibitor that inhibits an enzyme that degrades insulin or a compound having a function equivalent to insulin. 8. The method according to claim 1, wherein the protease inhibitor added to the artificial milk together with insulin or a compound having the same function as insulin is a trypsin inhibitor or a protease inhibitor having a function equivalent to the trypsin inhibitor. The artificial milk composition according to claim 7, which is used. 9. The concentration of a trypsin inhibitor or a protease inhibitor having the same function as a trypsin inhibitor added to an artificial milk is not more than a concentration showing an activity to eliminate all trypsin activity in the small intestine, and is preferably The artificial milk composition according to claim 8, wherein the composition has the same activity as described above. 10. The method according to claim 1, wherein the compound is orally administered from birth to weaning period.
Item 4. The artificial milk composition according to Item. 11. The artificial milk composition for an insulin-dependent diabetic patient according to any one of claims 1 to 9, which is orally administered after the weaning period.