JP3018305B2 - Gastric acid secretion inhibitor, anti-ulcer agent and food and beverage containing proteose peptone component 8F as active ingredient - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION The present invention relates to a medicament or a pharmaceutical composition having proteose peptone component 8F or an analog thereof derived from human or mammalian milk, or a processed product thereof, having an inhibitory effect on gastric acid secretion or an anti-ulcer effect. Food and drink.

[0002]

2. Description of the Related Art Antiulcer agents include antacids for suppressing gastric juice digestion, anticholinergic agents for suppressing gastric secretion itself, antigastrin agents, and histamine receptor antagonists. However, antacids, such as sodium bicarbonate, are quick-acting but have a short duration of action, and induce alkalosis by long-term large dose administration. Calcium carbonate preparations cause hypercalcemia causing urinary calculi, and magnesium preparations have a drawback that diarrhea is likely to occur. In addition, anticholinergic agents also have side effects such as dry mouth, constipation, and palpitations, and cannot always be said to be satisfactory antiulcer agents.
Furthermore, the mainstream peptide preparations of anti-gastrin agents are:
Since it must be purified from animal urine and organs, like urogastron and secretin, production costs are high,
There is also a limit on the amount of production. Recently, histamine receptor antagonists have been developed, but there is a problem that ulcers are likely to recur when administration is stopped. Particularly in a stressful modern society, the lifetime morbidity of gastric ulcer is said to be 20%, the probability of recurrence is extremely high at 80% or more, and when recurrence occurs, administration of the anti-ulcer drug must be started again. In other words, a patient once suffering from gastric ulcer must regularly take an antiulcer drug, which is a pharmaceutical, and even if a drug with few side effects is used, it cannot be said that there is no effect on the human body.

[0003] Under these circumstances, gastric juice secretion is highly effective, and there is no danger of side effects. In addition, an antiulcer agent which can be produced relatively inexpensively, or the onset or recurrence of ulcer, which can be regarded as a chronic disease, is prevented. There is a strong demand for food materials having the functionality to perform.

[0004]

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems of the conventional anti-ulcer drug. That is, the present invention has been made for the purpose of providing a medicament or a food or drink which is effective for the treatment and prevention of ulcers in consideration of the characteristics of the disease as a chronic disease. This is obtained from relatively inexpensive raw materials, has a good gastric secretion inhibitory effect, is used as an anti-ulcer agent for treating ulcers, and is a functional food for preventing the onset and recurrence of ulcers. Alternatively, it is intended to provide an active ingredient that can be used as a pathological diet. The present inventors have searched for an active ingredient having the above characteristics, and found that proteose peptone component 8F, which is a peptide derived from milk, has the above-mentioned action.

The proteose peptone component 8F corresponding to the N-terminal 1-228 positions of β-casein has already been reported by Andrew, AT [Eur.
Biochem., 90 , 67-71 (1978)]. There are several other types of proteose peptone in milk, but their physiological significance has not yet been elucidated.
Recently, Colbert, LB and Decker, EA reported that the filtrate separated by ultrafiltration using acid whey as a raw material has antioxidant activity [J. FoodSci., 56, 1248-1250 (199
1)]. In this, they state that the active ingredient is proteose peptone component 8F, but this activity is distinctly different from the gastric acid secretion inhibitory effect described in the present invention.

Further, Vasilevskaya et al. [Vopr. Pitaniya,
4, 21-24 (1977)] reported that κ-casein glycomacropeptide (hereinafter abbreviated as GMP), obtained by enzymatically degrading κ-casein, suppressed gastric acid secretion.
Guilloteau et al. [Reprod. Nutr. Develop., 27 , 287-288
(1987)] reported that intravenous administration of GMP to calves did not alter gastric juice secretion. Thus, GM
At present, no clear conclusions have been made as to the effect of P on gastric secretion suppression.

[0007] In this background, the present inventors have
Whey produced during cheese production, whey protein concentrate,
GMP obtained from a solution containing whey protein such as deproteinized cheese whey as a raw material was used to study the gastric secretion inhibitory effect of rats, and it was found that GMP itself did not have the effect of inhibiting gastric acid secretion. Proteose peptone component 8F mixed in GMP fraction
However, the present inventors have found that they exhibit a remarkable gastric acid secretion inhibitory effect or an anti-ulcer effect, and have accomplished the present invention. Furthermore, the present inventors have examined the physiological activity of analogs of the proteose peptone component and found that they have the same gastric acid secretion inhibitory effect or antiulcer effect as the proteose peptone component.

[0008] That is, an object of the present invention is to provide a gastric acid secretion suppressing or anti-ulcer agent, or a food or drink, comprising as an active ingredient proteose peptone component 8F isolated from milk or an analog thereof.

[0009]

As described above, the present invention relates to a gastric acid secretion inhibitor or an anti-ulcer agent containing proteose peptone component 8F or an analog thereof as an active ingredient. In addition, the present invention relates to a food or drink having a gastric acid secretion inhibitory or anti-ulcer effect, comprising proteose peptone component 8F or an analog thereof as an active ingredient.

[0010] The proteose peptone component 8F of the present invention can be collected from a GMP fraction. GMP
It has long been known that whey is released into whey during cheese production. As this raw material, cheese whey or a whey protein concentrate produced by ultrafiltration of cheese whey, or cheese whey or lactose mother liquor from which whey protein has been precipitated and removed by heating or the like can be used. For industrial production of GMP fractions,
The method disclosed in JP-A-27358, the method described in JP-A-2-276542, or the method described in JP-A-2-95686 may be used. Also, a GMP fraction can be obtained from the remaining liquid from the production of the rennet casein card by the method disclosed in JP-A-63-284199. From the GMP fraction thus obtained, an active center proteose peptone component 8F having a gastric acid secretion inhibitory effect is isolated by ion exchange or reverse phase HPLC.

That is, the proteose peptone component 8F of the present invention is prepared using raw milk, skim milk, whey or whey protein concentrate (WPC) of human or mammals such as cows, sheep, and goats as raw materials.

As an example of this preparation method, for example, as disclosed in JP-A-2-276542, first, cheese whey, WPC, deproteinized cheese whey and the like obtained from these raw materials are obtained. , After adjusting this to below pH 4,
Using a membrane having a molecular weight cut-off of 10,000 to 50,000, ultrafiltration is performed to obtain a permeate. Then, the permeated solution is adjusted to pH 4 or higher, desalted using a membrane having a molecular weight cut-off of 50,000 or less, and concentrated to obtain a GMP fraction.

Further, the GMP fraction thus obtained is dissolved in a buffer solution of pH 8.7 containing 0.2 M salt, adsorbed on an anion exchange resin at pH 8.7, and purified using the same buffer solution. Elute the adsorbed part. Next, the adsorbed portion is eluted with a buffer solution of pH 8.7 containing 0.25 to 1 M salt to obtain a crude peptide fraction. The crude peptide fraction is fractionated by reverse phase HPLC to obtain a purified bioactive peptide (see Example 1). In the present invention, when this bioactive peptide was analyzed using an amino acid sequencer, it was found to be proteose peptone component 8F.

The proteose peptone component 8F of the present invention is obtained by adding trypsin to raw milk, skim milk, acid casein solution or sodium caseinate solution, enzymatically decomposing casein at pH 7 to 8 for about 3 hours and then ethanol precipitation. It can be separated and recovered by ultrafiltration or ion exchange.

For example, a 1% sodium caseinate solution
Add 5 g of trypsin to 50 liters and add 3 at pH 8
After stirring for a time, the permeate obtained by ultrafiltration using a membrane having a molecular weight cut off of 10,000 is adsorbed on an anion exchange resin. Then, after the non-adsorbed fraction is eluted with a pH 6 to 9 buffer containing 0.2 M sodium chloride, the proteose peptone component 8F is eluted with a pH 6 to 9 buffer containing 0.25 to 1 M sodium chloride. In place of the ultrafiltration treatment, hydrochloric acid may be added to precipitate the casein at the isoelectric point, and the supernatant obtained may be subjected to anion exchange treatment. Or,
Proteose peptone component 8F can also be obtained from the fraction precipitated by adding ethanol at a concentration of 20 to 40% (see Example 2).

The proteose peptone component 8F is a peptide composed of 28 amino acids represented by the following formula. Arg-Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly-Glu-Ile-Va
l-Glu-Ser-Leu-Ser-Ser-Ser-Glu-Glu-Ser-Ile-Thr-Arg-
As described above, many peptides such as growth hormone, cell differentiation / growth factor, opioid peptide, and angiotensin converting peptide are known as physiologically active peptides in Ile-Asn-Lys milk.

Although the amino acid sequences of these peptides have already been elucidated, peptides containing the amino acid sequence of the present invention are not included, and all are different from the peptides of the present invention. Japanese Patent Application Laid-Open No. 62-277327 discloses an anti-ulcer substance in milk, but no specific structure has been disclosed. Moreover, from the viewpoint of the separation method, it is considered that the structure and properties are different from those of the physiologically active peptide of the present invention. That is, although the peptide of the present invention has a property of binding to an anion exchange resin, it is disclosed in JP-A-62-27732.
The substances described in Japanese Patent Publication No. 7 are substances which are adsorbed and recovered on a cation exchange resin.

An animal test was conducted on the physiological activity of this peptide. As shown in Examples 3 to 6, not only intravenous injection (hereinafter abbreviated as intravenous injection) but also oral administration gave an inhibitory effect on gastric acid secretion. It was found that it had an ulcer effect.

The proteose peptone component 8F of the present invention means a peptide having the above amino acid sequence in principle. However, it may be a peptide in which several amino acids are added, deleted, or substituted. Also,
Ser (serine) at positions 15, 17, 18, and 19 on the amino acid sequence of proteose peptone component 8F may be phosphorylated to form phosphoserine. As long as they have the same physiological activity as the above-mentioned peptide, they are included in the proteose peptone component 8F of the present invention. In the present invention, such a peptide is referred to as a proteose peptone component 8F analog. For example, casein phosphopeptide (CPP), which is known as a calcium absorption promoting peptide, is a peptide represented by the following formula lacking the three amino acids at the C-terminal side of the amino acid sequence of the proteose peptone component 8F of the present invention. . Examination of this physiological activity revealed that it had a gastric acid secretion inhibitory effect similar to that of proteose peptone component 8F and had an antiulcer effect. Therefore, CPP is an analog of the proteose peptone component 8F in the present invention. Arg-Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly-Glu-Ile-Va
l-Glu-Ser-Leu-Ser-Ser-Ser-Glu-Glu-Ser-Ile-Thr-Arg

The physiologically active peptide of the present invention can be used as an injection, or administered as an oral preparation as a sugar-coated tablet, tablet, or capsule, etc., and used as a drug having a gastric acid secretion inhibitory or anti-ulcer effect. Furthermore, it can be used as an anti-ulcer food material by adding it to various foods and drinks, such as soft drinks, fruit juice drinks, fermented drinks, and jelly and ice cream, and also to confectionery such as gum and candy. can do. The peptide of the present invention is a peptide derived from a milk component, has no adverse effect on the human body when taken orally, and there is no particular limitation on its intake. However, when it is actually taken orally as an anti-ulcer agent or as an anti-ulcer food, 0.001 mg /
The body weight is at least kg body weight / day, preferably 0.01 to 1 mg / kg body weight / day. That is, when the amount is less than 0.001 mg / kg body weight / day, almost no effect is observed. When the amount is 1 mg / kg body weight / day or more, there is no obstacle, but no remarkable increase in the effect is observed.

The peptide of the present invention has little antigenicity even though it is a milk-derived peptide, and is less likely to cause allergic symptoms. The dose of the injection solution is more than 0.1 μg / kg body weight / day for an adult male, preferably 1 to 100 μg / kg body weight / day. That is, 0.
No effect at less than 1 μg / kg body weight / day, 100 μg / kg
Above body weight / day, there is no obstacle, but there is no particular increase in efficacy.

Therefore, the effective amount in the present invention means a dose which is added to a medicine or a food or drink in such an amount as to give a gastric acid secretion inhibiting effect or an anti-ulcer effect.

[0023]

Industrial Applicability The present invention provides a medicament, a food or a drink, comprising as an active ingredient a proteose peptone component 8F and its analogs, which have a gastric acid secretion inhibitory and anti-ulcer action. Furthermore, the physiologically active peptide of the present invention has the following effects. (1) Since it is a peptide derived from milk which is usually taken as food, there is no side effect even if administered. (2) Since milk, which is a food, is used as a raw material, the production cost is lower than that of a conventional anti-ulcer agent. (3) Because it can be prepared in a larger amount than conventional anti-ulcer drugs,
It can be widely used not only as a pharmaceutical but also as a food material.

Hereinafter, the present invention will be specifically described based on examples.

Example 1 Separation and purification of a physiologically active peptide Whey protein concentrate (manufactured by Taiyo Kagaku, trade name Sunlac N-
2) 1 kg was dissolved in 50 liters of water at 50 ° C. and adjusted to pH 3.5 with concentrated hydrochloric acid. This was subjected to ultrafiltration using an ultrafiltration membrane having a molecular weight cut-off of 20,000 (DDS GR61PP) at 50 ° C., a pressure of 0.4 MPa, and an average permeate flow rate of 52.41 / m ² · h. When the amount of the permeate reached 40 liters, 40 liters of water at 50 ° C. was added to the concentrate, and ultrafiltration was further continuously performed. Continuous operation was performed as described above, and a total of 160 liters of permeate was obtained.

To the obtained permeate, 25% caustic soda was added to adjust the pH to 7.0. The same ultrafiltration membrane was again used, and ultrafiltration was performed under the same conditions until the concentrated solution became 5 liters. did. Subsequently, water at 50 ° C. was added, and diafiltration was carried out with the same ultrafiltration membrane under the same conditions as before, while keeping the amount of the concentrated solution at 10 liters, and further desalting was performed. This diafiltration allows the permeate volume to be
When the volume reached 1 liter, the addition of water to the concentrate was stopped, and the concentrate was concentrated by ultrafiltration until the volume of the concentrate reached 2 liters. The concentrate was lyophilized, and κ-casein glycomacropeptide (GMP 54 g). This one is Urea
As a result of analysis by SDS electrophoresis, the purity was 82%.

1 g of the obtained GMP fraction contains 0.2 M salt
It was dissolved in 50 ml of 20 mM Tris / hydrochloric acid buffer (pH 8.7) and passed through an anion exchange resin Q-Sepharose equilibrated with the same buffer. After the non-adsorbed fraction was eluted with 800 ml of the same buffer, 100 mg of the crude bioactive peptide fraction was eluted and collected with 200 ml of 20 mM Tris / HCl buffer (pH 8.7) containing 0.3 M salt. 100 mg of the crude bioactive peptide fraction thus obtained was added to CAPCELL
The fraction was separated by reverse phase HPLC using PAK C-18 AG120 (Shiseido) to obtain 40 mg of proteose peptone component 8F eluted with 15% acetonitrile. The eluate is 0.1 MN
aClO ₄ /0.05MH ₃ PO ₄ (NaOH) (pH 9) and 100% acetonitrile were used. This elution pattern is shown in FIG. The bioactive peptide fraction is No. 2.

The obtained peptide was analyzed using an amino acid sequencer (type 473A) manufactured by Applied Biosystems, and the amino acid sequence described above was determined.

[0028]

Example 2 5 g of trypsin was added to 50 liters of a 1% soda casein solution, and the mixture was stirred at 40 ° C. for 1 hour, and then adjusted to pH 4 to 5 with 2N hydrochloric acid to cause isoelectric precipitation of casein. Then, the supernatant was recovered, and after adding 50 g of calcium chloride, ethanol was added to a concentration of 40%, and the generated precipitate was recovered. The recovered precipitate is lyophilized and
g of casein phosphopeptide was obtained. In addition, it was confirmed in the same manner as in Example 1 that this precipitate was a casein phosphopeptide.

[0029]

Example 3 Confirmation of Gastric Acid Secretion Inhibitory Effect by Intravenous Injection Wistar rats (male, 7 months old, 8 rats in each group), which had been fasted for 16 hours and restricted for 2 hours, were dissolved in saline. 0.1, 1, 10, 100, 1000 μg / kg body weight of β-lactoglobulin or 1 mg / kg body weight of β-lactoglobulin or physiological saline alone was injected into the stomach pylorus immediately. Ligated. Four hours later, the gastric cardia was also ligated, and the stomach was removed. The gastric juice collected in the stomach was collected, the volume was measured, and the acidity was measured by titration. Table 1 shows the results. As shown in the table, in the group to which the peptide of the present invention was administered at 1 μg / kg body weight or more, the amount of gastric acid secretion was significantly suppressed.

[0030]

[Table 1] ───────────────────────────────── Sample Gastric acid secretion (mEq / 4hr) ──── ───────────────────────────── Proteose peptone 8F (0.1 μg / kg body weight) 0.281 ± 0.105 (1 μg / kg body weight) 0.108 ± 0.088 (10 μg / kg body weight) 0.096 ± 0.052 (100 μg / kg body weight) 0.066 ± 0.092 (1 mg / kg body weight) 0.058 ± 0.049 β-lactoglobulin (1 mg / kg body weight) 0.291 ± 0.070 Physiological saline 0.327 ± 0.089 ─ ──────────────────────────────── (mean ± standard deviation (n = 8))

[0031]

Example 4 Confirmation of Gastric Acid Secretion Inhibitory Effect by Oral Administration Wistar rats (male, 7 months old, 8 rats in each group), which had been fasted for 16 hours and restricted for 2 hours, were dissolved in 0.2 ml of water. Proteose peptone 8 of Example 1 of the present invention
F was orally administered with 0.001, 0.01, 0.1, 1, 10 mg / kg body weight or water alone, and one hour later, the gastric pylorus was ligated. 4
After a lapse of time, the stomach cardia was also ligated to remove the stomach, the gastric juice collected in the stomach was collected, the volume was measured, and the acidity was measured by titration. Table 2 shows the measurement results. As shown in the table,
0.01 mg of proteose peptone 8F of Example 1 of the present invention
In the group administered more than / kg body weight, gastric acid secretion was significantly suppressed.

[0032]

[Table 2] ───────────────────────────────── Sample Gastric acid secretion (mEq / 4hr) ──── ───────────────────────────── Proteose peptone 8F (0.001mg / kg body weight) 0.276 ± 0.105 (0.01mg / kg body weight) 0.132 ± 0.096 (0.1 mg / kg body weight) 0.106 ± 0.081 (1 mg / kg body weight) 0.071 ± 0.046 (10 mg / kg body weight) 0.089 ± 0.054 Water 0.287 ± 0.094 ─────────────── ────────────────── (mean ± standard deviation (n = 8))

[0033]

Example 5 Therapeutic Effect of Gastric Ulcer by Intravenous Injection 0.5% of 70% ethanol was orally administered to Wistar rats (male, 8 weeks old, 6 rats in each group) which had been fasted for 16 hours and immediately separated from WPC. The proteose peptone 8F according to Example 1 of the present invention, the proteose peptone 8F of the present invention synthesized by a peptide synthesizer, or β-lactoglobulin are dissolved in physiological saline, and then intravenously administered at a dose of 0.01 mg / kg body weight. did. Five hours later, the stomach was removed and an incision was made on the stomach. The mucosal surface was washed with physiological saline, and the degree of ulcer was observed. The ulcer degree was divided into six stages according to the degree of mucosal hemorrhagic lesion. Table 3 shows the results. As shown in the table, in the group to which the proteose peptone 8F of the present invention was administered, clear reduction of ulcer was observed.

[0034]

[Table 3] ─────────────────────────── Sample ulcer degree ──────────────── ─────────── Proteose peptone 8F (derived from WPC) 1.57 ± 1.30 Proteose peptone 8F (synthetic product) 1.26 ± 1.19 β-lactoglobulin 3.11 ± 1.48 Water 3.67 ± 1.38 ──────度 Degree of ulcer: 0 = No ulcer was found in the gastric mucosa. 1 = Redness only. 2 = 1 bleeding erosion. 3 = 2-5 bleeding erosions. 4 = 6-9 bleeding erosions. 5 = 10 or more bleeding erosions. (Average value ± standard deviation (n = 6))

[0035]

Example 6 Gastric acid secretion when casein phosphopeptide is orally administered
Confirmation of inhibitory effect Casein phos-peptide dissolved in 0.2 ml of water was added to Wistar rats (male, 7 months old, 8 rats in each group) which had been fasted for 16 hours and water supply was restricted for 2 hours. 10, 10
0 mg / kg body weight or water alone was orally administered, and one hour later, the gastric pylorus was ligated. Four hours later, the gastric cardia was also ligated, and the stomach was removed. The gastric juice collected in the stomach was collected, the volume was measured, and the acidity was measured by titration. As shown in Table 4, gastric acid secretion was significantly suppressed in the group to which casein phosphopeptide was administered at 0.1 mg / kg body weight or more.

[0036]

[Table 4] ──────────────────────────────── Sample Gastric acid secretion (mEq / 4hr) ───── ─────────────────────────── Casein phosphopeptide (0.01mg / kg body weight) 0.279 ± 0.109 (0.1mg / kg body weight) 0.120 ± 0.062 (1 mg / kg body weight) 0.082 ± 0.037 (10 mg / kg body weight) 0.089 ± 0.056 (100 mg / kg body weight) 0.061 ± 0.021 Water 0.268 ± 0.089 ─────────────────── ───────────── (mean ± standard deviation (n = 8))

[0037]

Example 7 Example of Food for Preventing Ulcer (1) Production of Milk Drink for Preventing Ulcer Using Proteose Peptone 8F of Example 1 of the present invention,
A milk beverage for ulcer prevention was prepared according to the following formulation. ───────────────────────── Ingredients Compounding ratio (wt%) ───────────────── ──────── skim milk powder 7.7 glucose 5.0 safflower oil 2.0 sugar esters 0.1 vitamins 0.02 yogurt flavor 0.18 peptide 0.01 water 84.99 ──────── ─────

Based on the above mixing ratio, 23.1 g of skim milk, 15 g of glucose, 0.06 g of vitamins, yogurt flavor
0.54 g and 0.03 g of the physiologically active peptide separated from milk of the present invention were dissolved in 100 ml of warm water heated to 60 ° C., and 6 g of safflower oil and sugar ester (trade name: DKF1)
60) A mixture obtained by mixing 0.3 g at 60 ° C. was gradually added dropwise while stirring with a TK homomixer to emulsify the mixture. This was sterilized by heating at 90 ° C for 5 minutes, and then cooled to 10 ° C to obtain a product. In addition, a milk beverage in which only the peptide was removed from the above composition table was produced in the same manner.

Next, these milk drinks were given to rats,
The anti-ulcer effect was examined. Wistar rats (male, 8 weeks old, 6 rats in each group) were allowed to freely drink the milk drink containing the above peptide or the milk drink prepared without the peptide at the same time as the start of fasting, and after 16 hours, 70% alcohol Was administered in 0.5 ml portions. Five more hours later, the stomach was removed and an incision was made in the bay, and the mucosal surface was washed with physiological saline, and the degree of ulcer was observed. Table 4 shows the observation results. As shown in the table, in the group to which the milk drink containing proteose peptone 8F of Example 1 of the present invention was administered, clear reduction of ulcer was observed.

[0040]

[Table 5] ───────────────────────── Sample ulcer degree ──────────────────乳 Peptide-containing milk drink 1.43 ± 1.21 Milk drink 2.98 ± 1.45 Peptide-containing jelly 1.87 ± 1.54 Jelly 3.01 ± 1.55 ─────────────────────度 Degree of ulcer: 0 = No ulcer was found in the gastric mucosa. 1 = Redness only. 2 = 1 bleeding erosion. 3 = 2-5 bleeding erosions. 4 = 6-9 bleeding erosions. 5 = 10 or more bleeding erosions. (Average value ± standard deviation (n = 6))

(2) Production of Jelly for Preventing Gastric Ulcer A jelly for preventing ulcer was produced from Proteose Peptone 8F of Example 1 of the present invention by the following formulation.

──────────────────────── Component content (wt%) ─────────────── ───────── Sugar 15.0 Prue extract 4.0 Gelatin 0.5 Peptone 0.05 Water 80.45 ────────────────────────

According to the above mixing ratio, sugar, gelatin and peptide were added to 50 ml of water, dissolved by heating at 80 ° C., pruned extract was added thereto, stirred, transferred to a container and cooled. Jelly containing no peptide of the present invention was similarly produced.

Next, these jellies were given to rats,
The effect of preventing gastric ulcer was examined. Wistar rats (male, 8 weeks old, 6 rats in each group), which had been fasted for 16 hours, were given jelly containing the above peptide or jelly containing no peptide.
g was administered. One hour later, 0.5 ml of 70% alcohol was administered, and 5 hours later, the stomach was excised and incised into the bay, and the mucosal surface was washed with physiological saline, and the ulcer degree was observed. Table 4 shows the observation results. As shown in this table, in the group to which the jelly containing proteose peptone 8F of Example 1 of the present invention was administered, clear reduction of ulcer was observed.

[0045]

Example 8 Preparation for Ulcer Treatment (1) Capsule A capsule for treating ulcer was obtained by filling 60 mg of proteose peptone 8F of Example 1 of the present invention into a soft capsule made of gelatin. (2) Intravenous Injection Proteose Peptone 8F 600 μgx of Example 1 of the present invention
Was dissolved in 1 ml of sterile physiological saline, and this was filled into an ampoule under aseptic conditions to obtain an intravenous solution.

[0046]

[Sequence list]

 SEQ ID NO: 1 Sequence length: 28 Sequence type: amino acid Topology: Linear Sequence type: Peptide Sequence: Arg Glu Leu Glu Glu Leu Asn Val Pro Gly Glu Ile Val Glu Ser Leu Ser Ser 1 5 10 15 Ser Glu Glu Ser Ile Thr Arg Ile Asn Lys 20 25

SEQ ID NO: 2 Sequence length: 25 Sequence type: amino acid Topology: linear Sequence type: peptide Sequence: Arg-Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly- Glu-Ile-Va
l-Glu-Ser-Leu-Ser-Ser-Ser-Glu-Glu-Ser-Ile-Thr-Arg

[Brief description of the drawings]

FIG. 1 shows the elution pattern of proteose peptone component 8F of the present invention by reversed-phase HPLC of Example 1.

[Explanation of symbols]

 2: Proteose peptone component 8F

────────────────────────────────────────────────── ─── Continuation of front page (56) References JP-A-5-65295 (JP, A) JP-A-4-210647 (JP, A) JP-A-2-276542 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) A61K 38/00 A23L 1/30 C07K 14/00

Claims (4)

(57) [Claims] 1. Proteose peptone component 8
Gastric acid secretion inhibiting addition is F or active ingredient its analog
Is an anti-ulcer agent. 2. The agent according to claim 1, wherein the active ingredient is proteose peptone component 8F represented by the following amino acid sequence. Arg-Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly-Glu-Ile-Val-Glu-Ser-Leu-Ser-Ser- Ser-Glu-Glu-Ser-Ile-Thr-Arg- Ile-Asn-Lys 3. The agent according to claim 1, wherein the active ingredient is a casein phosphopeptide represented by the following amino acid sequence. Arg-Glu-Leu-Glu-Glu-Leu-Asn-Val-Pro-Gly-Glu-Ile-Val-Glu-Ser-Leu-Ser-Ser- Ser-Glu-Glu-Ser-Ile-Thr-Arg 4. Proteose peptone component 8
Gastric acid secretion inhibiting addition is F or active ingredient its analog
Is a food or drink with anti-ulcer action.