JPH0881371A - Hematopoietic function promoter - Google Patents

Abstract

PURPOSE: To obtain a hematopoietic function promoter containing imidazole compound(s), having preventive and recovery-promotive effect on hematopoietic hypofunction due to medicines such as carcinostatics or radiation, and presenting hematopoietic function-promotive effect in case of hematozemia. CONSTITUTION: This hematopoietic function promoter contains at least one kind of imidazole compound selected from among anserine, balenine, π- methylhistidine, and τ-methylhistidine, or an extract consisting mainly of one or more of them. This promoter can be subjected to pharmaceutical manufacturing process into a medicinal agent for oral or parenteral administration, or can be given to relevant patients in the form of food. The dose of this promoter, for oral administration, is 50mg-5g a day in terms of the total amount of the imidazole compounds, 50mg-5g a day in terms of anserine or balenine, or 75mg-7.5g a day in terms of π-methylhistidine or τ-methylhistidine; for parenteral administration, 5-500mg a day in terms of the total amount of the imidazole compounds, 5-500mg a day in terms of anserine or balenine, or 7.5-750mg a day in terms of π-methylhistidine or τ-methylhistidine.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a hematopoietic function-enhancing agent containing anserine, valenin, π-methylhistidine, τ-methylhistidine or an extract containing these as the main components, and foods and drinks having a hematopoietic function-enhancing action. And a manufacturing method thereof.

[0002]

2. Description of the Related Art In recent years, drug therapy such as anti-cancer agents and radiation therapy suppress the hematopoietic function, which causes a decrease in the number of white blood cells, which makes it impossible to continue drug administration or radiation therapy. It's a big problem. There is a method of transplanting bone marrow cells for such a hematopoietic function-inhibiting disorder, but there is a limit to the supply of fresh bone marrow cells, and there is also the risk of virus contamination, so safe oral administration It has been desired to develop a hematopoietic function-enhancing agent that can

On the other hand, anserine (β-alanyl-π-methyl-L-histidine) and valenin (β-alanyl-τ)
-Methyl-L-histidine) is a dipeptide that is present in muscle tissues of mammals, birds, reptiles, amphibians and the like, and is a known substance. Further, π-methylhistidine and τ-methylhistidine are known as biosynthetic intermediates of anserine and valenin, respectively. Many studies have been conducted since the discovery of these dipeptides early this century, and it has been reported that anserine and valenin are present in skeletal muscles of vertebrates in a concentration range of 1-20 mM.

It is known that its content changes with the type of muscle and the age of the animal, but its physiological action has not been completely clarified yet. However, in recent years, research on the action and effect has been carried out, and it has been disclosed in JP-A-61-161
Japanese Patent No. 246218 discloses that L-anserin has an action of recovering an abnormal decrease in immune response and suppressing excessive hyperactivity to maintain a normal function of the immune system. Further, Japanese Unexamined Patent Publication No. 4-16166 discloses carnosine, anserine, and varenin to suppress blood pressure increase, and Japanese Unexamined Patent Publication No. 4-187610 discloses carnosine, anserine, and varenin to increase skin elasticity and flexibility. There is.

On the other hand, homocarnosine is effective in suppressing leukopenia due to side effects of chemotherapeutic agents and radiation therapy that inhibit the growth of cancer and viruses, and JP-A-1-93526 discloses that L- It is disclosed in Japanese Patent Publication No. 5-13928 that carnosine is effective. There is also a report that when carnosine is administered to mice when irradiated, the survival rate is increased and the hematopoietic stem cell colony formation rate is increased (Bull. Exp. Bio.
l. Med. 112 (7) 966-968 (199
1)).

Further, in Japanese Patent Laid-Open No. 187067/1989, it is disclosed that carnosine, anserine and valenin have an antioxidant effect on protein foods.
In JP-A-35-35, carnosine, anserine, and valenin are added so that the product content is 0.1% or more, and the pH is
It is disclosed that the taste of the product is improved by setting the ratio to 6.5 or more.

However, anserine, valenin, π-
It has not been known at all that methylhistidine and τ-methylhistidine have a hematopoietic function enhancing action.

[0008]

Therefore, the present invention is intended to provide a highly safe hematopoietic function-enhancing agent and foods and drinks having a hematopoietic function-enhancing effect.

[0009]

Means for Solving the Problems As a result of earnest research to solve the above problems, the present inventors have found that anserine,
Valenin, π-methylhistidine, τ-methylhistidine has a prophylactic effect and a recovery-promoting effect on a decrease in hematopoietic function due to drugs such as anticancer agents and irradiation, and an effect of promoting hematopoietic function at blood loss. The inventors have found what is shown and completed the present invention.

Therefore, the present invention is intended to provide a hematopoietic function-enhancing agent comprising one or more imidazole compounds selected from the group of anserine, valenin, π-methylhistidine and τ-methylhistidine. .
The present invention also includes anserine, barenin, π-methylhistidine, and τ-methylhistidine in food and drink substantially free of anserine, valenin, π-methylhistidine, and one selected from the group of τ-methylhistidine. The present invention relates to a food or drink having an action of enhancing hematopoietic function, which is obtained by adding the imidazole compound or an extract containing the imidazole compound as a main component.

Furthermore, in foods and drinks that do not substantially contain anserine, valenin, π-methylhistidine, and τ-methylhistidine, anserine, valenin, π-methylhistidine, and τ-methylhistidine or the main component thereof are The present invention relates to a method for producing a food or drink having a hematopoietic function-enhancing action, which comprises adding the extract described above.

[0012]

[Specific Description] Anserine, Valenin, π-of the present invention
Methylhistidine and τ-methylhistidine are natural products,
For example, the broth discharged during the production of bonito flakes or dried sardines, the broth of marine products such as the broth discharged during the production of canned tuna, or the one extracted, separated, or purified from livestock meat such as abandoned chicken, The enzyme may be enzymatically synthesized or may be produced by a microorganism. The anserine, varenin, π-methylhistidine and τ-methylhistidine of the present invention are D-form, L-form,
It may be any of DL bodies. Since naturally occurring anserine, valenin, π-methylhistidine and τ-methylhistidine are all L-forms, the L-form is preferable when used as a food or drink.

The anserine, valenin, π-methylhistidine and τ-methylhistidine of the present invention may be in the form of a salt, and as the anserine salt, the varenin salt, the π-methylhistidine salt and the τ-methylhistidine salt,
There are acid addition salts based on carboxylic acid groups and pharmacologically acceptable acids based on amino groups, and also salts based on both carboxylic acid groups and amino groups.

Salts based on carboxylic acid groups include sodium,
There are salts with metals such as potassium, calcium, magnesium, zinc and aluminum, ammonium salts and substituted ammonium salts, for example salts with trialkylamines such as triethylamine or other amines, and salts based on amino groups include hydrochloric acid. There are salts with inorganic acids and organic acids such as sulfuric acid, phosphoric acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, succinic acid, maleic acid, benzenesulfonic acid and toluenesulfonic acid, but these are themselves. It can be produced by a known method by reacting free anserine, valenin, π-methylhistidine, τ-methylhistidine with a stoichiometrically calculated amount of the selected acid or base.

These may be used alone or in combination. In the present invention, anserine, valenin, π-methylhistidine and τ-methylhistidine of the present invention are not necessarily limited to high-purity purified products, and an extract containing the imidazole compound of the present invention as a main component may be used. You can also Here, the extract containing the imidazole compound of the present invention as a main component is, for example, aquatic juice broth such as broth discharged during the production of bonito flakes or dried sardines, or broth discharged during the production of canned tuna, and waste chicken meat and the like. An extract extracted from livestock meat according to a conventional method, or an ionic juice resin, etc. according to a conventional method from marine product broth or meat such as broth discharged during the production of skipjack tuna or dried sardines or broth discharged during the production of canned tuna And the fractions containing the imidazole compound of the present invention separated by using. An example of the preparative separation / purification method is JP-A-63-132878, "Method for preparative separation / purification of dipeptide from bonito broth".

Particularly, the dipeptide fraction separated and purified from the broth discharged during the production of canned tuna is preferable because it contains abundant anserine. The imidazole compound content of the imidazole compound-based extract of the present invention is 2% or more, preferably 10% or more, more preferably 50% or more, and particularly the anserine content is 1% or more, preferably 5% or more. % Or more, more preferably 20% or more.

The anserine, valenin, π-methylhistidine and τ-methylhistidine of the present invention have the action of reducing the decrease in hematopoietic function due to drugs, radiation irradiation, stress, etc., or promoting the recovery of the decreased hematopoietic function. Therefore, the compound of the present invention is useful as a drug or a medical supplement for preventing or ameliorating hematopoietic dysfunction caused by drugs, irradiation, stress and the like.

Examples of hematopoietic dysfunction include agranulocytosis, leukopenia, erythrocytopenia, aplastic anemia, hemolytic anemia, giant erythroblastic anemia, pancytopenia, thrombocytopenia and the like. , Among them agranulocytosis, sulfa drugs,
It is caused by many drugs such as antithyroid drugs, chloramphenicol, chlorothiazide, cimetidine, methyldopa and phenylbutazone. In addition, leukopenia, thrombocytopenia, and erythopenia are associated with nitrogen mustard, psulfan, chlorambucil, cyclophosphamide, methotrexate, 6-mercaptopurine, 5-fluorouracil, actinomycin D, adriamycin, mitomycin C, procarbazine, cisplatin. It is caused by anti-cancer drugs such as and radiation.

Particularly, the compounds of the present invention are leukopenia, thrombocytopenia, anemia caused by side effects of chemotherapeutic agents (anticancer drugs, anti-AIDS drugs, etc.) which inhibit the growth of cancer and viruses, and leukopenia caused by side effects of irradiation. It is effective against illness, thrombocytopenia, and anemia. In addition, the anserine of the present invention,
Valenin, π-methylhistidine and τ-methylhistidine have an action of promoting the hematopoietic function, and therefore the compound of the present invention is a drug for promoting the hematopoietic function after surgery with bleeding, after delivery, or after blood donation. It is also useful as a medical supplement. Particularly, the compound of the present invention is effective for promoting recovery of white blood cell count, red blood cell count, and platelet after surgery with bleeding, after delivery, or after blood donation.

When the hematopoietic function-enhancing agent of the present invention is used as a medicine, the dosage form may be any dosage form as long as oral or parenteral administration is conveniently carried out, for example, injection solution. , Infusion, powder, granules, tablets,
Capsules, enteric solutions, suppositories, ointments, inhalants, troches and the like can be mentioned, and these can be used alone or in combination according to the symptoms. These various preparations are prepared according to a conventional method by using a known auxiliary agent which can be usually used in the technical field of pharmaceutical preparation such as an excipient, a binder, a disintegrating agent, a lubricant, a corrigent and the like as a main drug according to the purpose. Can be converted.

The dose of the hematopoietic function-enhancing agent of the present invention varies depending on the route of administration, dosage form, symptoms, age, body weight and the like. Normally, when administered orally to an adult, the total amount of the imidazole compound of the present invention is 50 mg. ~ 5 g / day, preferably 1
00 mg to 2 g / day, more preferably 50 mg to 2 g / day,
More preferably 50 mg to 500 mg / day, even more preferably 50 mg to 180 mg / day, even more preferably 50 mg to 1
It is 00 mg / day.

Also, as anserine or valenin, 50
mg-5 g / day, preferably 100 mg-2 g / day, more preferably 50 mg-2 g / day, more preferably 50 mg-5
00 mg / day, more preferably 50 mg to 180 mg / day,
More preferably, it is 50 mg to 100 mg / day. Also π
7 as -methylhistidine or τ-methylhistidine
5 mg to 7.5 g / day, preferably 150 mg to 3 g / day,
More preferably 75 mg to 3 g / day, more preferably 75
mg-150 mg / day.

For parenteral administration, the total amount of the imidazole compound of the present invention is 5 mg to 500 mg / day, preferably 1
0 mg to 200 mg / day, more preferably 5 mg to 200 mg /
Day, more preferably 5 mg to 50 mg / day, even more preferably 5 mg to 18 mg / day, still more preferably 5 mg to 10 mg / day.
Is the day. Also, as anserine or valenin, 5 mg ~
500 mg / day, preferably 10 mg-200 mg / day, more preferably 5 mg-200 mg / day, more preferably 5 mg-
The dose is 50 mg / day, more preferably 5 mg to 18 mg / day, further preferably 5 mg to 10 mg / day. Also, as π-methylhistidine or τ-methylhistidine, 7.5 mg-
The dose is 750 mg / day, preferably 15 mg to 300 mg / day, more preferably 7.5 mg to 300 mg / day, more preferably 7.5 mg to 15 mg / day.

Since the anserine, valenin, π-methylhistidine and τ-methylhistidine of the present invention are substances originally existing in the body, they are low in toxicity and highly safe, and therefore have great significance as hematopoietic function enhancers. . When the hematopoietic function-enhancing agent of the present invention is used in the form of food or drink, it may be in the form of the above-mentioned formulation, but a required amount of the anserine of the present invention,
Valenin, π-methylhistidine, τ-methylhistidine or an extract containing these as the main ingredients is used as a raw material for food and drink, particularly anserine, valenin, π-methylhistidine or τ.
-It can be processed and manufactured by a general manufacturing method in addition to a raw material for food and drink which does not substantially contain methylhistidine. The blending amount varies depending on the dosage form and the morphological characteristics of the food, but is generally preferably 0.001 to 50%, but is not particularly limited.

In the present invention, anserine, valenin,
Examples of foods and drinks that do not substantially contain π-methylhistidine and τ-methylhistidine, such as foods and drinks that do not contain meat such as beef, pork, chicken, fish, whale, and snake meat, beef, pork, chicken, Foods and drinks that do not use meat extracts such as fish meat, whale meat and snake meat can be mentioned, but even foods and drinks made from meat such as beef, pork, chicken, fish, whale meat and snake meat can be used. , The amount of anserine, valenin, π-methylhistidine, τ-methylhistidine is very small, so the total amount of anserine, valenin, π-methylhistidine, τ-methylhistidine per meal is 50 mg.
Less than 5 or anserine content of 5 per serving
Less than 0 mg is anserine, valenin, π of the present invention.
-Methylhistidine and τ-Methylhistidine are included in foods and drinks that do not substantially contain them.

As the form of the food, anserine, valenin, π-methylhistidine or τ-methylhistidine, alone or in combination, or an extract containing an imidazole compound as a main component is used as a protein (a protein source having a balanced amino acid balance). In addition to nutritious milk protein, soy protein, egg white oligopeptide, soy hydrolyzate, etc.,
(A mixture of amino acids alone is also used), sugars, fats, etc., along with trace elements, vitamins, emulsifiers, flavors, etc. to make a natural liquid food, semi-digested nutritional food and component nutritional food, or solid, Or liquid foods or luxury items such as bread, noodles, rice, confectionery (biscuits, cakes, candy, chocolate, Japanese sweets), agricultural products such as tofu and its processed products, sake, fermented foods such as medicinal sake, mirin, Vinegar, soy sauce, miso, dressing, livestock foods such as yogurt, ham, bacon, sausage, mayonnaise, fish products such as kamaboko, fried tempura, and hanpen, fruit juice drinks, soft drinks, alcoholic drinks, beverages such as tea And the like.

In addition, preventive and improvement of hematopoietic dysfunction such as leukopenia and thrombocytopenia caused by drugs such as anti-cancer agents and radiation therapy, and promotion of hematopoietic function after surgery or after donation of blood (promotion of recovery of white blood cell count, for example) For the purpose of), under the control of a dietitian based on a doctor's meal, the powder of the imidazole compound of the present invention is added to any food at the time of cooking of a hospital meal, and the functional food is prepared in the form of the food. It can also be given to patients. In addition, vitamins, hormones and other nutritional supplements, trace elements and iron compounds may be mixed into the food and drink of the present invention.

In addition, the food and drink of the present invention having a hematopoietic function-enhancing action improves and prevents various symptoms caused by insufficient hematopoietic function, and promotes hematopoietic function after surgery or after donation of blood (for example, recovery of white blood cell count). (Acceleration), the total amount of the imidazole compound of the present invention is 50 mg or more, preferably 100 mg or more, more preferably 50 mg or more per day.
5 g, more preferably 100 mg to 2 g, more preferably 50 mg to 2 g, more preferably 50 mg to 500 mg, further preferably 50 mg to 180 mg, further preferably 50
It is desirable to be ingested orally in the range of 100 mg to 100 mg.

As anserine or valenin, 50 mg or more, preferably 100 mg or more, more preferably 50 mg to 5 g, more preferably 100 mg to 2 g, more preferably 50 mg to 2 g, more preferably 50 mg to 5 per day as anserine or varenin.
It is desirable to be orally ingested in an amount of 00 mg, more preferably 50 mg to 180 mg, and further preferably 50 mg to 100 mg. Further, as π-methylhistidine or τ-methylhistidine, 75 mg or more per day, preferably 1
50 mg or more, more preferably 75 mg to 7.5 g, more preferably 150 mg to 3 g, more preferably 75 mg to 3
g, more preferably in the range of 75 mg to 150 mg is preferably orally ingested.

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

[0031]

EXAMPLES Example 1 Effect of enhancing spontaneous proliferation ability of bone marrow cells Cyclophosphamide (CY) was intravenously injected into 7-week-old ICR mice at a dose of 300 mg / kg. L-anserin (Ans) was subcutaneously administered at a dose of 100 mg / kg every day from the day of cyclophosphamide administration. After administration of cyclophosphamide, the femurs of the mice were aseptically taken out on days 1, 3, 5, 7, 9 (L-anserin administration group was on days 5, 5 and 7) and both end bones were excised, From the stump, 20% fetal bovine serum-added RPMI1640 medium was injected to collect bone marrow cells. After calculating the number of cells per femur of each individual mouse, the bone marrow cells (2 × 100,000 cells / well) of each experimental group were seeded on a 96-well microplate, and at the same time ³
H-thymidine (0.5 μCi / well) was added and the mixture was cultured for 5 hours, and the radioactivity (CPM) was measured using a liquid scintillation counter. The experiment was carried out with 3 animals per group, and the results are shown as the average value ± standard error. In the parentheses, the spontaneous growth potential of bone marrow when the spontaneous growth potential of bone marrow on day 0 was defined as 100% was expressed in%.

In the CY alone administration group (control group), the spontaneous proliferative ability of bone marrow cells, which is an index of hematopoietic function, was remarkably suppressed on the 1st to 3rd day of administration, and the proliferative ability once recovered to the normal on the 5th day. However, on the 7th to 9th days, the tendency of suppression was recognized again. On the other hand, the group administered with L-anserin together with CY showed significantly higher spontaneous bone marrow cell proliferative ability than the control group on the 3rd to 7th day of administration, and particularly on the 3rd and 7th days, compared with the control group. It showed that L-anserin has a spontaneous proliferation-promoting action on bone marrow cells and enhances hematopoietic function.

[0033]

[Table 1]

Example 2 Effect of enhancing colony forming ability in serum
To ICR mice results 7 weeks old at a dose of 300 mg / kg cyclophosphamide a (CY) was injected intravenously. L-anserin (Ans) was subcutaneously administered at a dose of 100 mg / kg every day from the day of cyclophosphamide administration. After administration of cyclophosphamide, mouse serum was collected on days 1, 3, 5, 7, and 9 (L-anserin administration group on days 3, 5 and 7) to measure Colony Stimulating Activity (CSA). I served. Serum CSA assay was performed on bone marrow cells (1.5 × 10 5) aseptically collected from the femur of normal female ICR mice.
⁶ cells / ml) 50 μl, and FCS 200 μl,
50 μl of CSA assay serum was added to a medium containing 450 μl of 0.6% agar and 300 μl of × 2 DMEM, and the mixture was stirred well and cultured at 37 ° C. in 5% CO _{2 for} 10 days. Three
A cell population of 0 or more was calculated as a colony, and the number of colonies was used as CSA of serum. The experiment was carried out with 3 animals per group, and the results are shown as mean value ± standard deviation.

In the CY single administration group (control group), the colony forming ability (CSA) in the serum, which is an index of the hematopoietic function, was suppressed on the first day of administration, and CSA was compensated for on the third day and thereafter to compensate for this. Was observed. On the other hand, C
In the group administered with L-anserin together with Y, administration was 3 to 7
The CSA was higher than that of the control group on the day 3, and the C was 1.8 times or more that of the control group on the third day.
Since SA was shown, it was shown that L-anserin has a colony-forming ability enhancing action in serum and enhances hematopoietic function.

[0036]

[Table 2]

Embodiment 3 FIG. Anticancer drug cyclophosphamai
Hemopoietic function-enhancing effect in spleen of mouse treated with cyclophosphamide (CY) was intravenously injected into 7-week-old ICR mice at a dose of 300 mg / kg. The L-anserin (Ans) administration group was subcutaneously administered at a dose of 100 mg / kg every day from the day of cyclophosphamide administration. 3, 5 and 7 days after the administration of cyclophosphamide, the mouse splenocytes (5 × 10 ⁶ cells / ml) were concanavalin A2μ.
24 in 10% FCS RPMI1640 medium supplemented with g / ml
The supernatant after time culturing was used as a sample for IL-3 activity measurement. IL-3 activity is IL-3-dependent FDCP-2 cells 1 × 10 ⁴ cells / well were seeded on a 96-well microplate, the above sample was added in a 2-fold serial dilution, and after culturing for 24 hours, 3 (4 5-dimethylthyazol -2yl) 2,5
The FDCP-2 cell viability was measured by the MTT assay using -diphenyl tetrazolium bromide. WEHI
IL that supports 50% of the maximum growth of FDCP-2 cells cultured with the cell culture supernatant as the IL-3 standard
The IL-3 activity of the sample was
The sample dilution ratio including the absorption value of 50% maximum growth of d curve was calculated and obtained. The experiment was carried out with 3 animals per group, and the results are shown as the average value ± standard error.

In the CY single administration group (control group), on the first to third days after administration, I of splenocytes, which is an index of hematopoietic function, was measured.
The L-3 productivity was suppressed, and after 5 days, the IL-3 productivity was increased to more than twice the normal level in order to compensate for this. On the other hand, the group administered with L-anserin together with CY showed higher splenocyte IL-3 producing ability than the control group on the 3rd to 7th day of administration, and particularly on the 5th and 7th days, the control group was compared with the control group. Since L-anserin showed the ability to produce IL-3 more than 1.5 times,
3 It has been shown to have a productivity enhancing action and enhance a hematopoietic function.

[0039]

[Table 3]

Example 4 In the spleen of X-irradiated mice
Using hematopoietic hyperactive effect transplant method, the mouse bone marrow cells in the X-ray irradiated mice Colony Forming Unit in Spleen (C
FU-s) was measured. X-ray irradiation is Hitachi Medical's M
A BR-1520R type X-ray irradiation device was used. Dose rate is 1.16 Gy / min (150 kV, 20 mA, Filt)
er: 0.5mmAl + 0.1mmCu) and the dose is 6G
The whole body of X-ray irradiation of y was performed once. Irradiated recipient
5 × 10 ⁴ cells in the tail vein of female C57BL / 6 mice
Bone marrow cells of normal C57BL / 6 mice were injected. 8
After a day, the spleen of the mouse was removed, fixed with Bouin's solution, and the cell colonies formed on the surface of the spleen were counted. L-anserin administration group is 100 mg daily from the day of X-ray irradiation to the 7th day
In the chicken extract-administered group containing 2 mg / ml of L-anserin, the oral administration was performed at a dose of 0.5 ml / head every day from the day of X-ray irradiation to the 7th day. The experiment was conducted with 8 animals per group, and the results are shown as the average value ± standard error.

No colony was formed in the spleen of the X-ray non-irradiation group (normal mouse), and a colony was formed in the X-ray irradiation group (control group), which is an index of hematopoietic function.
-S activity was observed. On the other hand, the L-anserin administration group and the chicken meat extract administration group showed higher CFU-s activity than the control group, and particularly the L-anserin administration group showed significantly higher CFU-s activity. It was shown to enhance the hematopoietic function.

[0042]

[Table 4]

Example 5 Anticancer drug cyclophosphamai
White blood cell number recovery-promoting effect in mouse treated with cyclophosphamide (CY) was intravenously injected to 7-week-old C57BL / mouse at a dose of 300 mg / kg. L-anserin (Ans) was subcutaneously administered at a dose of 100 mg / kg every day from the day of cyclophosphamide administration. Blood was sampled from the orbital venous plexus of mice on the 7th, 8th and 9th days after administration of cyclophosphamide (7th, 8th and 9th days in the L-anserin administration group), and the white blood cell count was measured by an automatic hemocytometer. The experiment was carried out with 5 animals per group, and the results are shown as the average value ± standard error.

In the CY alone administration group (control group), the number of white blood cells, which is an index of hematopoietic function, decreased immediately after the administration,
~ Gradually recovered by day 9. On the other hand, the group administered with L-anserin together with CY showed a higher white blood cell count than the control group on the 7th to 9th day of administration, and especially on the 8th and 9th day, the control group had 1.5 times the white blood cell count. Since the white blood cell count was close to that of L., it was shown that L-anserin has a white blood cell number recovery promoting action and enhances the hematopoietic function.

[0045]

[Table 5]

Example 6 The bonito broth concentrate has a molecular weight of 1
It was treated with an ultrafiltration membrane fractionated at 0000 to obtain a clear solution of a low molecular weight fraction. After the pH of the clarified liquid was adjusted to 2.2 with dilute hydrochloric acid, the liquid was poured into a column packed with MM81 type ion exchange resin, manufactured by Beckman, and anserine, π-
Methylhistidine was adsorbed. Then the column is 57 ℃
A 0.4 N sodium citrate solution was allowed to flow while being kept warm to obtain a fraction containing anserine and π-methylhistidine. This was freeze-dried to obtain a dried product. The content of anserine or π-methylhistidine in the dried product was measured by an amino acid analyzer and found to be 56% and 8%, respectively. Example 7 . Lactose (50 parts), sucrose (39.8 parts), tragacanth gum (5 parts) and peppermint (0.2 parts) were mixed, and a solution prepared by dissolving 5 parts of anserine and 0.002 part of cupric chloride in 3.5 parts of distilled water was added thereto. , Kneaded well. Next, the above kneaded product was spread on a glass plate on which starch was sprayed with a rolling pin to form a sheet having a thickness of about 5 mm, which was punched out with a mold and dried to obtain a troche. Example 8 . 100 parts of flour to 2 parts of anserine, 0.001 part of manganese chloride, 4 parts of sucrose, 1.1 parts of salt, 2 parts of skimmed milk powder, 3 parts of yeast, 0.8 parts of yeast food, 6 parts of water
After adding 7.2 parts and kneading, 5 parts of fats and oils were further added and kneaded well. Primary fermentation was carried out at 28 ° C. for 90 minutes. Then, punching was performed, and after 28 minutes at 28 ° C., the mixture was packed in a mold and baked at 190 ° C. for 30 minutes to manufacture. Regarding the physical properties of the bread after baking, as a result of comparison with a product produced without adding carnosine, no difference was found in flavor and texture. Example 9 80 parts pork, 1 part anserine, 1 part π-methylhistidine, 0.001 part cupric chloride, 0.02 part sodium nitrite, 2 parts salt, 0.3 parts sodium pyrophosphate, 0.06 sodium ascorbate Parts and 1 part of sucrose were added, and the mixture was salted at 10 ° C. for 72 hours, then seasonings and spices were added and cut to prepare a ground meat. After filling this kneaded meat in a casing, a sausage was produced according to a conventional method. As a result of a sensory test of this sausage, no difference in color tone, texture or flavor was observed as compared with sausage produced without adding anserine or π-methylhistidine. Example 10 . Granules were produced according to the following formulation using the synthesized anserine.

Anserine 0.2 g Cupric chloride 0.02 mg Lactose 0.34 g Corn starch 0.45 g Hydroxypropyl methylcellulose 0.01 g Example 11 . To 20 g of vitamin C, 10 g of ferrous sulfate, 40 g of granulated sugar, and 30 g of an equal mixture of corn starch and lactose, 50 g of the extract obtained in Example 2 was added and mixed. The mixture is divided into 100 equal parts, packed in a bag, and 1.5 g of a stick-shaped functional food having a hematopoietic function-increasing action 10
0 bags were produced.

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Claims (4)

[Claims] 1. A compound selected from the group consisting of anserine, valenin, π-methylhistidine, and τ-methylhistidine.
A hematopoietic function enhancer comprising one or more imidazole compounds. 2. A food or drink substantially free of anserine, valenin, π-methylhistidine, and τ-methylhistidine, and one selected from the group of anserine, valenin, π-methylhistidine, and τ-methylhistidine. A food or drink having an action of promoting hematopoietic function, which is obtained by adding the above-mentioned imidazole compound or an extract containing this as a main component. 3. The food or drink according to claim 2, which is 50 mg to 5 g.
A food / drink having a hematopoietic function-enhancing action, which is characterized in that it can be taken with anserine per day. 4. A method for producing a food or drink having a hematopoietic function-enhancing effect, which comprises adding anserine, valenin or π-methyl to a food or drink substantially free of anserine, varenin, π-methylhistidine and τ-methylhistidine. A method comprising adding one or more imidazole compounds selected from the group of histidine and τ-methylhistidine, or an extract containing the same as a main component.