JPH05262793A - New peptide, inhibitor of gastric acid secretion-antiulcer agent and food and drink comprising the same peptide as active ingredient - Google Patents

Abstract

PURPOSE:To obtain an economically advantageous new peptide, having a specific amino acid sequence, capable of exhibiting inhibiting action on gastric acid secretion without any side effect, useful as an inhibitor of the gastric acid secretion, an antiulcer agent or a food and drink for preventing ulcer and derived from a mammalian milk or its processed product. CONSTITUTION:A whey concentrate is dissolved in water at 50 deg.C and regulated to pH 7.3. The regulated solution is then subjected to ultrafiltration through an ultrafiltration membrane having 20000 fractionation molecular weight. The resultant permeation liquid is then regulated to pH 7.0 and resubjected to ultrafiltration under the same conditions, desalted and concentrated. Water is subsequently added to dilute the concentrate. Thereby, diafiltration is carried out and the diluted concentrate is then concentrated and freeze-dried to provide a kappa-casein glycomacropeptide (GMP) crude fraction. The obtained fraction is subsequently passed through an anion exchange resin column and eluted with a 20mM tris-phosphoric acid buffer solution (pH 8.7) containing 0.3M common salt. The obtained eluted fraction is purified by a reversed phase high-performance liquid chromatography to afford the objective new peptide having an amino acid sequence expressed by the formula [(P) is phosphate group] and inhibiting action on gastric acid secretion.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel peptide derived from human or mammalian milk or a processed product thereof and having a physiologically active action. Further, the present invention relates to a gastric acid secretion inhibitory and anti-ulcer agent containing this peptide as an active ingredient, and foods and drinks having such an action.

[0002]

2. Description of the Related Art Antiulcer agents include antacids that suppress the digestive action of gastric juice, anticholinergics, antigastrin agents, and histamine receptor antagonists that suppress gastric juice secretion itself. However, antacids such as sodium hydrogen carbonate have a short duration of action, although they are fast-acting, and induce alkalosis by long-term administration in large doses. The calcium carbonate preparation causes hypercalcemia that causes urinary tract stones, and the magnesium preparation has a drawback that diarrhea is likely to occur. In addition, anticholinergic drugs also have side effects such as dry mouth, constipation, and palpitations, so they cannot always be said to be satisfactory antiulcer drugs.
Furthermore, the mainstream peptide formulations of anti-gastrin agents are:
Since it has to be purified from animal urine and organs like urogastrone and secretin, the manufacturing cost is high,
Moreover, there is a limit to the production amount. In addition, although a histamine receptor antagonist has been recently developed, it has a problem that ulcer is likely to recur when administration is stopped. Especially in modern society where stress is high, the lifetime prevalence of gastric ulcer is said to be 20%, and the probability of recurrence is very high at 80% or more, and in the case of recurrence, the administration of the anti-ulcer drug must be restarted. That is, a patient who once suffers from gastric ulcer must continue to take an antiulcer drug, which is a pharmaceutical, on a regular basis, and even if a drug with few side effects is used, it cannot be said that there is no effect on the human body.

Under these circumstances, the gastric juice secretion inhibitory effect is high, and there is no risk of side effects, and an anti-ulcer drug that can be manufactured relatively inexpensively, or the onset and recurrence of ulcer which can be said to be a chronic disease are prevented. There is a strong demand for foods that have the functionality to do so.

[0004]

DISCLOSURE OF THE INVENTION The present invention has been made to solve the problems found in the conventional anti-ulcer agents as described above. That is, in consideration of the characteristic that ulcer is a chronic disease, it was made for the purpose of providing a medicine or a food or drink effective for the treatment and prevention thereof. This is obtained from relatively inexpensive raw materials, good gastric secretion inhibitory effect, is used as an anti-ulcer agent for treating ulcer, further, functional food for preventing the onset and recurrence of ulcer 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 a peptide derived from milk has the above physiologically active action.

The physiologically active peptides in milk include, in addition to growth hormone, cell differentiation / growth factor, etc., calcium absorption promoting peptide, opioid peptide, angiotensin converting enzyme-damaging peptide and the like.

In addition, Vasilevskaya et al. [Vopr. Pitaniya,
4, P21-24 (1977)] reported that a κ-casein glycomacropeptide (hereinafter abbreviated as GMP) obtained by enzymatically decomposing κ-casein suppressed gastric acid secretion.
Guilloteau et al. (Reprod. Nutr. Develop., 27, P287-288
(1987)] reported that the intravenous administration of GMP to calves did not change the secretion of gastric juice. As described above, the present situation is that no clear conclusion has yet been reached on the gastric juice secretion inhibitory effect of GMP.

The inventors of the present invention have the following background.
Whey produced during cheese production, whey protein concentrate,
As a result of extensive studies using rats on the gastric juice secretion inhibitory effect of GMP obtained from a whey protein-containing solution such as deproteinized cheese whey, it was found that GMP itself does not have a gastric acid secretion inhibitory effect. It was found that a specific peptide sometimes mixed in the GMP fraction shows a remarkable gastric acid secretion inhibitory effect or an antiulcer effect, and the present invention has been completed.

[0008] That is, an object of the present invention is to provide a novel physiologically active peptide having a gastric acid secretion inhibitory effect and an anti-ulcer activity and having few side effects. A further object of the present invention is to provide a gastric acid secretion inhibitory and anti-ulcer agent or a food or drink containing such a physiologically active peptide as an active ingredient.

[0009]

The present invention is a peptide having the following amino acid sequence. Lys-Asn-Thr-Met-Glu-Hi
s-Val-Ser (P) -Ser (P) -Ser (P) -Glu-Glu-Ser-Ile-Ile-Ser
(P) -Gln-Glu-Thr-Tyr-Lys-Gln-Glu-Lys [(P) represents a phosphate group] Further, the present invention is a gastric acid secretion inhibitory agent containing such a physiologically active peptide as an active ingredient. Agent and antiulcer agent. Furthermore, the present invention relates to a food or drink containing such a physiologically active peptide as an active ingredient and having gastric acid secretion suppression and antiulcer activity. The bioactive peptide of the present invention can be collected from a glycomacropeptide (GMP) fraction.
It has long been known that GMP is released into whey during cheese production. As this raw material, cheese whey or whey protein concentrate produced by ultrafiltration of cheese whey, or cheese whey or lactose mother liquor obtained by precipitating and removing whey protein by a method such as heating can be used. In order to industrially produce the GMP fraction,
The method disclosed in JP-B-59-27358, the method described in JP-A-2-276542, or the method described in Japanese Patent Application No. 2-95686 may be used. Further, a GMP fraction can be obtained from the residual liquid produced from rennet casein card by the method disclosed in JP-A-63-284199. From the GMP fraction thus obtained, the ion exchange method and the reverse phase HPL
By C, an active center peptide having a gastric acid secretion inhibitory effect is isolated. In addition, the peptide of the present invention may be synthesized from constituent amino acids as a raw material by a peptide synthesizer or a usual organic chemical synthesis method, or may be obtained by a genetic engineering method.

That is, the physiologically active peptide of the present invention is
Raw milk, skim milk, whey or whey protein concentrate of humans or mammals such as cows, sheep and goats (WP
It is prepared using C) as a raw material.

As an example of this preparation method, as disclosed in, for example, Japanese Patent Application Laid-Open No. 2-276542, cheese whey obtained from these raw materials, WP
After obtaining C, deproteinized cheese whey, etc., and adjusting the pH to less than 4, it is subjected to ultrafiltration using a membrane having a molecular weight cutoff of 10,000 to 50,000 to obtain a permeate. And
Next, the permeate was adjusted to pH 4 or higher and the molecular weight cutoff was adjusted to 5
The GMP crude fraction is obtained by desalting and concentrating with a membrane of less than 10,000.

Further, the crude GMP fraction thus obtained was dissolved in a buffer solution containing 0.25 M sodium chloride at pH 8.7 and adsorbed on an anion exchange resin at pH 8.7. To elute the non-adsorbed portion. Next, the adsorbed portion is eluted with a buffer solution of pH 8.7 containing 0.3 M sodium chloride 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, the physiologically active peptide was analyzed by using an amino acid sequencer and found to have the above amino acid sequence (see Example 1).

As described above, many physiologically active peptides in milk are known, such as growth hormone, cell differentiation / growth factor, calcium absorption promoting peptide, opioid peptide and angiotensin converting peptide. Although the amino acid sequences of these peptides have already been clarified, peptides containing the amino acid sequence of the present invention are not included, and all are different from the peptides of the present invention.
The peptide according to the present invention is 1 to 2 on the N-terminal side of α _s2 casein.
Although it corresponds to the 4th, no physiological effects involving this peptide have been reported to date. Moreover, there is no report that this peptide was isolated. Regarding the antiulcer substance in milk, there is JP-A-62-277327, but the specific structure is not clarified. Moreover, from the viewpoint of the separation method, it is considered that the physiologically active peptide of the present invention has a different structure and characteristics. That is, while the peptide of the present invention has the property of binding to an anion exchange resin, the substance described in JP-A-62-277327 is
It is a substance that is collected by being adsorbed on a cation exchange resin.

From the above points, the peptide of the present invention was judged to be a novel peptide. Animal tests were carried out 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 has a gastric acid secretion inhibitory action and an antiulcer effect. I found that there is.

The novel peptide of the present invention means, in principle, a peptide having the above-mentioned amino acid sequence. Even if a peptide has several amino acids added, deleted or substituted, it has the same physiological activity as the above-mentioned peptide. As long as it is included in the novel peptide of the present invention.

The physiologically active peptide of the present invention can be used as an injection, or as an oral preparation as a sugar-coated tablet, tablet, capsule or the like to be used as a gastric acid secretion inhibitor or antiulcer agent. Furthermore, it may 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, jelly and ice cream, and also added to sweets such as gums and candies. can do.

The peptide of the present invention is a peptide derived from a milk component, and when it is taken orally, it has no adverse effect on the human body, and its intake amount is not particularly limited. However, when actually ingested as an anti-ulcer agent or ulcer-preventive food, 0.001 mg / kg body weight / day or more, preferably 0.01 to 1 mg / kg body weight / day is appropriate. That is, 0.001 mg / kg body weight /
The effect is not significantly increased in less than one day.

The peptide obtained as described above is
Although it is a milk-derived peptide, it has almost no antigenicity,
Less likely to cause allergic symptoms. The dose of the injection solution is 0.1 μg / kg body weight / day or more, and preferably 1 to 100 μg / kg body weight / day.
That is, if it is less than 0.1 μg / kg body weight / day, there is no effect, and if it is 100 μg / kg body weight / day or more, there is no disorder, but no particular increase in effect is observed.

These may be administered once a day or may be administered in several divided doses. The effective amount in the present invention refers to that which is added to a drug or a food or drink at such a dose to produce gastric acid secretion inhibitory action and antiulcer action.

[0021]

INDUSTRIAL APPLICABILITY The present invention provides a novel gastric acid secretion inhibitor and a peptide having an antiulcer action. further,
The physiologically active peptide of the present invention has the following actions and effects. (1) Since it is a peptide derived from milk which is usually taken as a food, there are no side effects even when administered. (2) Since the raw material is milk, which is a food, the manufacturing cost is lower than that of conventional antiulcer agents. (3) Since it can be prepared in a larger amount than conventional anti-ulcer agents,
It can be widely used not only as a medicine but also as a food material.

The present invention will be specifically described below based on examples.

[Example 1] Separation and purification of physiologically active peptides Whey protein concentrate (Taiyo Kagaku, trade name Sanlacto 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 is cut off molecular weight 2
Using a 10,000 ultrafiltration membrane (GR61PP manufactured by DDS), 50 ° C., pressure 0.4 MPa, average permeate flow rate 5
Ultrafiltration was performed at 2.4 liter / m ² · h. When the amount of permeated liquid reached 40 liters, 40 liters of water at 50 ° C. was added to the concentrated liquid, and ultrafiltration was continuously performed. Continuous operation was carried out as described above to obtain a total amount of permeated liquid of 160 liters. 25% caustic soda was added to the obtained permeated liquid to adjust the pH to 7.0, and ultrafiltration was performed again under the same conditions and the same ultrafiltration membrane until the concentrated liquid reached 5 liters, and desalted and concentrated. Subsequently, water at 50 ° C. was added, and diafiltration was performed under the same conditions and the same ultrafiltration membrane as before, while maintaining the concentrated liquid amount at 10 liters, and desalting was further performed. When the permeated liquid amount reached 80 liters by this diafiltration, stop adding water to the concentrated liquid, concentrated by ultrafiltration until the concentrated liquid amount became 2 liters, and frozen this concentrated liquid. After drying, 54 g of a GMP crude fraction containing κ-casein glycomacropeptide was obtained. The product was analyzed by urea SDS electrophoresis and found to have a purity of 82%.

1 g of the obtained crude GMP fraction was added to 0.25
20 mM Tris / HCl buffer (pH 8.
7) It was dissolved in 50 ml and passed through anion exchange resin DE-52 equilibrated with the same buffer solution. After elution of the non-adsorbed fraction with the same buffer solution at 800 ml, 20 mM containing 0.3 M sodium chloride
100 mg of the crude physiologically active peptide fraction was eluted with 200 ml of Tris / hydrochloric acid buffer (pH 8.7) and collected. 100 mg of the crude peptide fraction thus obtained was used as CAPCELL.
Fractionation was carried out by reverse phase HPLC using PAK C-18 AG120 (Shiseido Co., Ltd.) to obtain 40 mg of a physiologically active peptide that was eluted at a concentration of 5 to 7% acetonitrile. The eluate is
0.1M NaClO ₄ /0.05MH ₃ PO ₄ (N
aOH) (pH 9) and 100% acetonitrile were used. This elution pattern is shown in FIG. The physiologically active peptide fraction was No. It is 1.

The obtained peptide was used as an amino acid sequencer (470A type) manufactured by Applied Biosystems.
As a result, it was found to be two peptides having the following amino acid sequences. Lys-Asn-Thr-Met-Glu-His-Val-Ser (P) -S
er (P) -Ser (P) -Glu-Glu-Ser-Ile-Ile-Ser (P) -Gln-Glu-Th
r-Tyr-Lys-Gln-Glu-Lys

Example 2 Peptide Synthesis of Amino Acid Sequence Based on the amino acid sequence obtained in Example 1, a peptide synthesizer (43) from Applied Biosystems was used.
0A type) was used to synthesize the peptide having the sequence described above by the t-Boc method. That is, 0.5 mmol of Boc-L
-Cln-O-CH ₂ -PAM resin and each 2mmol
The constituent amino acids of (1) were packed in a peptide synthesizer and synthesis was carried out to obtain the resin bound with the peptide described in Example 1. The peptide bound to 1.63 g of resin was cleaved with trifluoromethanesulfonic acid in the presence of thioanisole and ethanedithiol, precipitated with diethyl ether, dissolved with 10% acetic acid, and replaced with 10% acetic acid. Basic anion exchange resin Bio
Purification by passing through -Rex MSZ 1-X8 yielded 150 mg of peptide. This peptide is further added to Aquapa
c RP-300 (Applied Biosystems)
Purified by reverse phase HPLC using 0.1% trifluoroacetic acid / water and 0.1% trifluoroacetic acid / acetonitrile as eluents, and 34 mg of white powder of bioactive peptide was obtained from the fraction eluted with 20% acetonitrile. Obtained.

[Example 3] Confirmation of gastric juice secretion inhibitory effect by intravenous injection Wistar rats (male, 7 months old, 8 animals in each group) that had been fasted for 16 hours and had a limited water supply for 2 hours were dissolved in physiological saline. The peptide obtained according to Example 1 was
1,1,10,100,1000 μg / kg body weight, β-
Lactoglobulin was intravenously injected at 1 mg / kg body weight or physiological saline alone, and the gastric pyloric region was immediately ligated. Four hours later, the gastric cardia was also ligated to remove the stomach, and the gastric juice accumulated in the stomach was collected and the volume was measured, and the acidity was measured by titration. The results are shown in Table 1. As shown in the table, gastric acid secretion was significantly reduced in the group to which the peptide of the present invention was administered at 1 μg / kg body weight or more.

[0025]

[Table 1] ──────────────────────────────────── Sample gastric acid secretion (mEq / 4 hr) ──────────────────────────────────── Peptide (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 0.058 ± 0.049 β-lactoglobulin (1 mg / kg body weight) 0.291 ± 0.070 saline solution 0.327 ± 0.089 ────────────────── ─────────────────── (mean ± standard deviation (n = 8))

[0026]

[Example 4] Confirmation of gastric secretion inhibitory effect by oral administration 0.2 ml was added to Wistar rats (male, 7 months old, 8 animals in each group) which were fasted for 16 hours and water supply was restricted for 2 hours.
0.001, 0.01, 0.1, 1, 10 mg / kg body weight of the peptide obtained in Example 1 dissolved in water, or water alone was orally administered, and 1 hour later, the gastric antrum was ligated. .. After 4 hours, the gastric cardia was also ligated to remove the stomach, and the volume of the collected gastric juice in the stomach was measured and the acidity was measured by titration. The measurement results are shown in Table 2. As shown in the table, the peptide of the present invention is 0.01 mg /
In the group administered with kg body weight or more, the gastric acid secretion inhibitory amount was significantly decreased.

[0027]

[Table 2] ──────────────────────────────────── Sample gastric acid secretion (mEq / 4 hr) ──────────────────────────────────── Peptide (0.001 mg / kg body weight) 0.276 ± 0.105 (0.01 mg / 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 kg body weight) 0.089 ± 0.054 Water 0.287 ± 0.094 ────────────────────────────────── ──── (mean ± standard deviation (n = 8))

[0028]

Example 5 Therapeutic effect of gastric ulcer by intravenous injection Wistar rats fasted for 16 hours (male, 8 weeks old,
0.5 ml of 70% ethanol was orally administered to 6 animals in each group, and the peptide according to Example 1 immediately separated from WPC, the peptide according to Example 2 synthesized with a peptide synthesizer, or β-lactoglobulin was added to physiological saline. Then, the solution was dissolved in E. coli and then administered intravenously at a dose of 0.01 mg / kg body weight. Five hours later, the stomach was removed, a large incision was made, the mucosal surface was washed with physiological saline, and the ulcer degree was observed. The ulcer degree was divided into 6 stages according to the degree of mucosal hemorrhage lesions. The results are shown in Table 3.
Shown in. As shown in the table, clear reduction of ulcer was observed in the group administered with the peptide of the present invention.

[0029]

[Table 3] ─────────────────────────────────── Sample ulcer degree ──────── ─────────────────────────── Peptide (from WPC) 1.57 ± 1.30 Peptide (synthetic) 1.26 ± 1. 19 β-lactoglobulin 3.11 ± 1.48 Water 3.67 ± 1.38 ─────────────────────────────── ───── Ulcer degree: 0 = No ulcer is found in the gastric mucosa. 1 = Redness only. 2 = 1 bleeding erosion. 3 = 2-5 bleeding sores. 4 = 6-9 bleeding sores. 5 = 10 or more bleeding sores. (Average value ± standard deviation (n = 6))

[0030]

[Example 6] Examples of ulcer-preventing food (1) Production of ulcer-preventing milk beverage Using the peptide of the present invention obtained in Example 1, an ulcer-preventing milk beverage was prepared according to the following formulation. ────────────────────────────────── Component blending ratio (wt%) ──────── ────────────────────────── Skim milk powder 7.7 Glucose 5.0 Safflower oil 2.0 Sugar ester 0.1 Vitamin 0. 02 yogurt flavor 0.18 peptide 0.01 water 84.99 ─────────────────────────────────── 23.1g skim milk, 1 glucose based on the proportion
5 g, vitamins 0.06 g, yogurt flavor 0.54 g, and bioactive peptide 0.03 g separated from the milk of the present invention were heated to 60 ° C. in 100 ml of warm water.
A mixture of 6 g of safflower oil and 0.3 g of sugar ester (trade name DKF160) at 60 ° C. was gradually added dropwise to the liquid dissolved in (1) while stirring with a TK homomixer to emulsify. Heat sterilize this at 90 ℃ for 5 minutes, then 10 ℃
The product was cooled to. In addition, a milk drink obtained by removing only the peptide from the above formulation table was produced in the same manner.

Next, these milk drinks were fed to rats,
The anti-ulcer effect was investigated. Wistar rats (male, 8 weeks old, 6 animals in each group) freely fed with a milk drink containing the above peptide or a milk drink produced without the peptide at the same time as fasting, 70% alcohol after 16 hours 0.
5 ml each was administered. Further, after 5 hours, the stomach was removed and a large incision was made. The mucosal surface was washed with physiological saline, and then the ulcer degree was observed. The observation results are shown in Table 4. As shown in the table, clear reduction of ulcers was observed in the group administered with the milk drink containing the peptide of the present invention.

[0032]

[Table 4] ─────────────────────────────────── Sample Ulcer Degree ──────── ─────────────────────────── 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 ──────────────────────────────────── Ulcer degree: 0 = no ulcer is found in the gastric mucosa. 1 = Redness only. 2 = 1 bleeding erosion. 3 = 2-5 bleeding sores. 4 = 6-9 bleeding sores. 5 = 10 or more bleeding sores. (Average value ± standard deviation (n = 6))

(2) Production of Jelly for Preventing Gastric Ulcer The peptide of the present invention obtained in Example 1 was used to produce a jelly for preventing ulcer with the following formulation.

────────────────────────────────── Component blending amount (wt%) ───── ───────────────────────────── Sand sugar 15.0 Prune extract 4.0 Gelatin 0.5 Peptide 0.05 Water 80. 45 ────────────────────────────────── Sugar, gelatin, and peptides were added to water 5
It was added to 0 ml and heated at 80 ° C. to dissolve it. Prune extract was added to this and stirred, then, transferred to a container and cooled.
Also, a jelly containing no peptide of the present invention was produced in the same manner.

Next, these jellies were given to the rats,
The ulcer prevention effect was investigated. Wistar rats (male, 8 weeks old, 6 animals in each group) that had been fasted for 16 hours were fed with the above-mentioned peptide-containing jelly or peptide-free jelly.
Each g was administered. 1 hour later 70% alcohol 0.5m
Each 5 minutes later, the stomach was extracted 5 hours later, the stomach was incised, the mucosal surface was washed with physiological saline, and the ulcer degree was observed. The observation results are shown in Table 4. As shown in this table, clear reduction of ulcer was observed in the group to which the jelly containing the peptide of the present invention was administered.

[0036]

Example 7 Ulcer Treatment Formulation (1) Capsule A 60 mg peptide of the present invention was filled in a soft capsule made of gelatin to obtain an ulcer treatment capsule. (2) Intravenous preparation 600 μg of the peptide of the present invention was dissolved in 1 ml of sterilized physiological saline, and this was filled under aseptic into an ampoule to obtain an intravenous injection.

[0037]

[Sequence list]

 SEQ ID NO: 1 Sequence length: 24 Sequence type: Amino acid Topology: Linear Sequence type: Peptide Sequence Lys-Asn-Thr-Met-Glu-His-Val-Ser (P) -Ser (P)- Ser (P) -Glu-Glu-Ser-Ile-Ile 1 5 10 15 -Ser (P) -Gln-Glu-Thr-Tyr-Lys-Gln-Glu-Lys 20 24 ((P) is a phosphate group Show]

[Brief description of drawings]

1 shows the elution pattern of the physiologically active peptide of the present invention in reverse phase HPLC of Example 1. FIG.

[Explanation of symbols]

 1 Bioactive peptide of the present invention

Claims (3)

[Claims] 1. A peptide having the following amino acid sequence: Ly
s-Asn-Thr-Met-Glu-His-Val-Ser (P) -Ser (P) -Ser (P) -Glu
-Glu-Ser-Ile-Ile-Ser (P) -Gln-Glu-Thr-Tyr-Lys-Gln-Gl
u-Lys [(P) represents a phosphate group] 2. A gastric acid secretion inhibitory and anti-ulcer agent comprising the peptide according to claim 1 as an active ingredient. 3. A food or drink which comprises the peptide according to claim 1 as an active ingredient and has gastric acid secretion inhibitory and antiulcer activity.