JPH11116498A - Macrophage activator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject activator which increases both of the number of macrophages and the rate of macrophages when the phagocytosis is used as the indicator, possesses the sustainability and is useful as a functional food and the like by blending crude drugs of pumpkin seed and safflower. SOLUTION: This activator is obtained by blending two kinds of crude drugs of pumpkin seed and safflower with preferably either Plantago asiatica L. or Lonicera japonica Thunb. or the both. For example, the pumpkin seed and the safflower are contained in amounts of 5-95 wt.%, respectively, based on the total weight of the combination crude drugs, and the Plantago asiatica L. and the Lonicera japonica Thunb. are contained in amounts of 0-80 wt.%, respectively. These crude drugs are used as the raw powder or the extract extracted with water or an organic solvent such as ethanol. The daily dose of 10 mg-5 g per an adult as the total weight of the crude drugs may be orally taken.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel macrophage activator.

[0002]

2. Description of the Related Art Research on macrophages has recently become very active, and new knowledge has been rapidly accumulating in various fields, and accordingly, the biological concept of macrophages has been widely diversified. Macrophages are originally defined as cells with a strong phagocytic ability, but they are not limited to primitive phagocytes, but also present antigens to T cells, produce inflammatory cytokines, effectors of antitumor immunity, regulate immune responses, etc. It has become clear that cells play important roles in many aspects of a very wide range of biological defenses. Furthermore, functional changes that play an important role in many aspects of the molecular mechanism of intracellular sterilization that have been known for a long time have been elucidated. In recent years, enhanced intracellular sterilization and expression of antitumor activity found in activated macrophages have been elucidated. As a mechanism, the production of nitric oxide (NO) and its mechanism are in the spotlight.

[0003] Macrophages have three major roles. The first is the disposal of waste generated in the body. It processes old and dead cells and plays an important role in tissue metabolism and wound repair. It is also considered to be involved in the reconstitution of various tissues in the process of fetal formation. The second is a protective function against microorganisms and tumor cells. Monocytes and macrophages
Together with granulocytes and neutrophils in the blood, it is a first-line host defense. In addition, they play an important role in the effector function of the immune response through the action of antibodies and lymphokines produced by lymphocytes. Third is lymphocytes, especially T
It functions as an accessory cell for the immune response through presentation of antigen to cells and production of interleukin 1. In addition, macrophages are involved in hematopoiesis, production of complement components, and the like. That is, the functions are extremely diverse as follows.

Phagocytosis The primary task of macrophages is to take in senescent cells and foreign substances, digest them and process them. In addition, the defense of bacteria and fungi resistant to phagocytic bactericidal action of neutrophils is left to macrophage phagocytic bactericidal action, and activated macrophages protect virus by inactivating virus. Also plays a role. Inflammation and tissue repair Macrophages are proteases such as plasminogen activator, collagenase and elastase, acid hydrolases such as cathepsins B, C and D, polysaccharide degrading enzymes such as β-glucuronidase, hyaluronidase, lysozyme and α-glucosidase. , C1-C5 classical pathway and complement components of alternative pathways such as factor B, D, β ₁ H, C3bINA, prostaglandin E1, leukotriene B
Arachidonic acid metabolite, active enzyme, interleukin 1, interferon α, TNFα, TGFβ, FG
It produces and releases various secretions as needed, such as mediators such as F and platelet activating factor. These secretions are greatly involved in inflammation and tissue repair and regeneration. In acute inflammation, resident macrophages remove the cause by phagocytosis and secretory functions, and then monocyte-derived exuding macrophages accumulate. These macrophages produce various degrading enzymes, complement components, mediators and the like to amplify and expand inflammation. In chronic inflammation, macrophages become epithelioid cells or multinucleated giant cells and surround the remaining foreign bodies to form granulation tissue. Epithelioid cells secrete lysosomal enzymes and cytokines, and b-FGF and TGF
-Promote fibroblasts and angiogenesis via β and the like to repair damaged tissues.

Antitumor activity Macrophages also have the effect of destroying tumor cells by secretions such as lysosomal enzymes, activated oxygen and cytotoxin. This includes macrophages attaching or attacking the tumor, either directly or via antibodies bound to the tumor cells, or releasing TNF. In addition to its function as a phagocytic cell, macrophages also take up and digest antigenic substances and, if not completely digested, deliver the appropriately sized remaining antigen to antigen-presenting cells. There is. Also, macrophages themselves often act as antigen presenting cells. In addition, macrophages support the lymphatic response besides presenting antigen to lymphocytes. Interleukin 1 (IL-1) produced by macrophages assists in the proliferation of T cells and B cells that have reacted with the antigen, and assists in the production of lymphokines, differentiation into killer cells, and differentiation into antibody-producing cells. It also has the effect of enhancing the proliferation of thymic lymphocytes. Macrophages also produce interferon, thereby enhancing the activation of killer T cells and NK cells.

Immunosuppression While macrophages support lymphocyte reactions in this way, they also have a function of suppressing them. Prostaglandin E2 produced thereby suppresses lymphocyte proliferation and functional expression. Complement Production Macrophages are also the major producers of complement components (C1-C5, factor B, factor D, etc.) that are important substances in the immune response. Fibronectin production Fibronectin, which acts as an opsonin, is also produced from macrophages. I produced by macrophages
L-1 is CRP from liver via the IL-6 (C-reactive protein), the production of acute phase reactants, such as alpha ₁ antitrypsin, but enhances the release, these substances are useful for infection defense .

[0007] Activation of macrophages is necessary for the expression of the above functions. Examples of the substance that activates macrophages include lymphokines produced by T cells, so-called macrophage activating factor (MAF), bacterial components such as Mycobacterium tuberculosis, BCG, corynebacterium, nocardia, and propionobacterium, and bacterial lipopolysaccharide. And muramyl-dipeptides are known.

[0008] Regarding the macrophage activating action of crude drugs, screening using the stimulating action of nitric oxide production as an index revealed that among 200 kinds of crude drugs, tiger cane root, yellow wax, snakebed, malt, mulberry, mulberry, black rice, There is a report that 13 kinds of activity were recognized in Sansho, Floating hail, Jiang Huang, Yanhu cord, Oyster, Eggplant and Ginseng (Fukuda, 117th Annual Meeting of the Pharmaceutical Society of Japan, 1997)
Year).

[0009] WO 95/34218 discloses the addition of one or more (in particular three herbal medicines) of pumpkin, plantain and honeysuckle to feed to reduce particularly natural infections of parasites, bacterial and viral diseases. It is disclosed that the meat quality and egg quality are improved while preventing and enhancing the biological defense power. Furthermore, it discloses the health condition, survival rate, egg quality, and anti-leukocytozone disease effect of laying hens on feed containing four types of crude drugs, such as pumpkin, plantain, honeysuckle and safflower.

JP-A-56-92820 discloses that an interferon-inducing agent is extracted from Cucurbitaceae plants such as Japanese squash, and is disclosed in JP-A-56-79623 and JP-A-56-79623.
No. 97232 describes that an interferon-inducing agent is extracted from gold and silver blossoms, bolls and the like, and is useful for the prevention and treatment of viral infections in humans and animals.
JP-A-57-32222 discloses the antiviral activity and antitumor activity of an interferon-inducing agent extracted from safflower, and describes that it is useful as an antitumor agent, a physiological action improving agent, and a health promoting agent. I have.

[0011]

DISCLOSURE OF THE INVENTION The present inventors have eagerly sought to elucidate the physiological functions of crude drugs such as pumpkin, psyllium, honeysuckle and the like, which have excellent effects as animal feed components, and to find further uses. We have been studying. As a result, it has been found that a strong and persistent macrophage activating effect can be obtained by combining two crude drugs, pumpkin and safflower, as essential components, and further adding any or both of plantain and honeysuckle as optional components. .

[0012]

Means for Solving the Problems The present invention relates to a novel macrophage activator, which enhances both the phagocytosis number and the phagocytosis rate when the phagocytic activity is used as an index. Characterized by unsustainable sustained action. The present invention is a macrophage activator comprising a mixture of two kinds of crude drugs, pumpkin and safflower. Further, the present invention is a macrophage activator comprising a mixture of two kinds of crude drugs, pumpkin and safflower, and either or both of plantain and honeysuckle. Preferably, it is a macrophage activator comprising a mixture of four types of crude drugs, such as pumpkin, safflower, plantain, and honeysuckle. Further, the present invention relates to the third aspect.
It is a long-acting macrophage activator consisting of combining one or four crude drugs. The present invention also relates to a macrophage activator wherein these macrophage activators are added to functional foods and health foods.
It is a food or drink having a macrophage activating action, comprising a mixture of various crude drugs.

The above publications disclose the interferon-inducing effect of each crude drug as the active ingredient of the present invention, but do not disclose or suggest the macrophage activating effect. In addition, the aforementioned International Publication No. 95
No./34218 discloses the effect of a feed containing the four crude drugs of the present invention as a protective agent against infection with animal parasites, bacteria and viruses, but does not disclose or suggest a macrophage activating effect. Absent. In the present invention, based on the macrophage activating effect, anti-inflammatory agents against parasites, fungi, bacteria and viruses, anti-inflammatory agents as well as anti-inflammatory agents against dermatitis, arthritis, mastitis, pyometra, or lymphatic It is expected to be useful as a prophylactic or therapeutic agent for various diseases associated with insufficiency of bulb function or low production of complement or fibronectin.

Furthermore, since the macrophage activator of the present invention exhibits an unprecedented sustained action, the possibility of intermittent administration or periodic administration is expected. Moreover,
Since it is a combination of crude drugs that have been used in folk medicine since ancient times and whose safety has been confirmed, it is not only a therapeutic drug for humans or animals, but also as a preventive drug, functional food, and health food for a long time. Suitable for regular use. In the present invention, functional foods, health foods, or foods and drinks are limited to foods consumed by humans.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail.
You. First, the crude drug used in the present invention will be described.
I do. Pumpkin is a plant of the family Cucurbitaceae (Japanese name: Japanese pumpkin)
Cucurbita moschata Duch.) Seeds of the present invention
In the above, the seed of the related plant which achieves the object of the present invention
Including. Pumpkin may be used raw, but dried
Is preferable for preservation as a medicine or health food.
You may use only skin. Cucurbitin, Tan as an ingredient
Parkin, Vitamin A, B₁, B₂, C, and calo
Chin is also included. Safflower (Carthamus tinctorius
L.) is a dried tubular flower of the Asteraceae plant. Success
Minutes include Calsamine, Saffler Yellow, Lignan,
Contains sterols. Gynecological disorders, chills, menopause
Used for the treatment of impaired circulation.

[0016] Plantain (Plantago asiatica L.)
Seeds matured by bacteric plants (forehead) or whole plants (for car)
Front) is used. Ingredients are polysaccharides, planttenolic
acid., succinic acid, adenine, Aucubin, Plantaginin and
Vitamin A, B₁And so on. In humans as crude drugs
It is used as an anti-inflammatory, diuretic, and antiemetic. Watermelon
La (Lonicera japonica Thunb.) Is a young flower of the honeysuckle family
Or buds (gold and silver flowers), leaves, stems or whole plants (Shinobi)
Can be Ingredients include waxy substances, inositol, tanni
, Saponin, loniserin and the like. As crude drugs,
It is used as a fever, detox, diuresis and anti-inflammatory.

[0017] Formulated with the macrophage activator of the present invention
Pumpkin and safflower in the range of 5-95% each of the total amount of crude drugs
Including plantain, honeysuckle in the range of 0-80% each
Including. In the present invention, these crude drugs are used in bulk or water or organic form.
It can be used as a solvent extraction extract. That is, Hara
Powders, solvent preparations, powders, molding agents, leaching agents, etc.
Ethanol, acetone, etc. are used as organic solvents,
These can be used by mixing with water or two or more organic solvents.
Is also good. For extraction, add several times the amount of solvent to the crude drug
Perform extraction or leaching while heating. In addition, crude drug
When used in fresh, shaded or dried
It is used as a shred or powder.

The macrophage activator of the present invention, that is, a combination of the above crude drugs, can be widely used as various food materials, and any food can be used as long as it can be used as a food material. The crude powder of the crude drug of the present invention or an extract extracted with water or an organic solvent can be used as it is or in various forms by a method known per se, as a health food, a functional food (supplement), or a medicine.

For example, medicines or functional foods (supplements) can be converted into oral tablets, powders,
It is provided as fine granules, capsules, pills, and syrups. For formulation, excipients, binders, disintegrants, lubricants,
Buffers, flavoring agents, stabilizers and the like can be added as needed. It is mixed with at least one inert diluent such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, magnesium aluminate metasilicate. The composition is prepared according to a conventional method, with additives other than an inert diluent, for example, a lubricant such as magnesium stearate, starch, talc or a disintegrant such as calcium cellulose glycolate, a stabilizer such as lactose, A solubilizing agent such as glutamic acid or aspartic acid may be contained. Tablets or pills can be sucrose, gelatin, agar, pectin, hydroxypropyl cellulose,
It may be coated with a sugar coating such as hydroxypropylmethylcellulose phthalate or a film of a gastric or enteric substance.

In addition, caffeine, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, biotin, carnitine, pantothenic acid, and caffeine do not affect the crude drug as an active ingredient of the present invention. Water-soluble vitamins such as nicotinic acid and its derivatives, fat-soluble vitamins such as vitamin A and vitamin E and its derivatives, amino acids such as taurine and arginine, and crude drugs (licorice, gambo, fish ginkgo, chrysanthemum, carrot, cinnamon, etc.) Can be blended.
Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like, and commonly used inert diluents such as purified Contains water and ethanol. This composition contains, in addition to the inert diluent, humectants, adjuvants such as suspending agents, sweetening agents, flavoring agents,
A fragrance may be contained.

The health food can be provided in the form of a beverage or a confectionery such as jelly, biscuit, cookie, candy and the like. The crude drug of the present invention is appropriately determined depending on the individual case in consideration of the age, sex, and the like of the administration subject.
By ingesting g to 5 g, preferably 50 mg to 3 g, a desired macrophage activating effect can be exerted without fear of serious side effects.

[0022]

The following examples illustrate the invention. Example 1 Chicken intraperitoneal macrophage activation test Broiler-specific species (chunky) were grouped into 10 birds.
To the test administration group, a crude drug mixture of each composition was added to the feed at a 0.05% addition amount, and the feed was freely taken by constant feeding.
On the 28th day after the start of the test, the phagocytosis rate and the phagocytosis number of the intraperitoneal macrophages were measured, and the percentage relative to the value of the control group was determined. As a result, as shown in Table 1, in Test Group 1: Pumpkin, honeysuckle, plantain, and safflower added group, both the phagocytosis number and the phagocytosis rate were significantly increased. Further, the test group 2: pumpkin, honeysuckle and safflower added group, and the test group 3: pumpkin, plantain, safflower added group also significantly increased both the phagocytosis number and the phagocytosis rate. On the other hand, the phagocytosis rate was increased in the test group 4: the group to which the pumpkin alone was added, but the phagocytosis number was not changed. From the above, it was found that pumpkin and safflower are essential components for increasing both the phagocytosis number and the phagocytosis rate of macrophages. Furthermore, it was found that desired macrophage activation was achieved even when psyllium and honeysuckle were added as optional components.

[0023] Example 2 Effect test on the phagocytosis rate of adult cattle macrophages Four healthy lactating cows of Holstein weighing 596 to 650 kg were divided into a control group and a test group, each of which was divided into two cows. %, Safflower 10%, plantain 25
%, And 20% of a mixed crude drug having a component composition of honeysuckle 15% were mixed with the feed at the time of feeding in the morning and continuously administered for 28 days, and blood was collected over time to measure the phagocytic activity of blood macrophages. As a result, as shown in FIG. 1, the blood macrophage phagocytosis rate of the test group increased after the start of the test, and after 4 weeks of administration, surprisingly, the effect was maintained until 4 weeks after the discontinuation of the administration.

Example 3 Granules 5.0 g of watermelon pumpkin, 3.0 g of safflower, 1.0 g of psyllium, 3.0 g of honeysuckle, 67 g of lactose and 16 g of starch were uniformly mixed with a hard mixer, and hydroxypropyl was first mixed. 2 g of cellulose and 5 g of capric triglyceride in 8
A kneading solvent dissolved in 40 g of 5% ethanol is used as a kneading solvent, and after kneading, a basket type granulator (screen diameter 1 mm)
, And then pass through a 14-mesh sieve to be dried to obtain columnar granules. The above components and mannitol, hydroxypropylcellulose, magnesium aluminate metasilicate, aspartame and fragrance were uniformly mixed to give 12 granules.

[0025]

According to the present invention, a potent and persistent macrophage activator is provided. Based on the macrophage activating effect of the present invention, parasites, fungi, anti-infection agents against bacteria and viruses, arthritis as well as antitumor agents,
It is expected to be useful as an anti-inflammatory agent such as dermatitis, mastitis and pyometra, or as a preventive or therapeutic agent for various diseases associated with assisting lymphocyte function, producing complement, and producing fibronectin. In addition, to use crude drugs as the active ingredient,
There is no fear of side effects, and it can be used for a long time as a functional food and a health food as well as a medicine for humans and animals.

[Brief description of the drawings]

FIG. 1 shows the effect of the macrophage activator of the present invention on the phagocytosis rate of adult cattle macrophages.

Claims (6)

[Claims] A macrophage activator comprising a mixture of two herbs, pumpkin and safflower. 2. The activator for macrophages according to claim 1, wherein one or both of psyllium and honeysuckle are blended with two kinds of crude drugs, pumpkin and safflower. 3. A pumpkin, a safflower, a plantain, and a honeysuckle.
The macrophage activator according to any one of claims 1 to 3, comprising a crude drug of any kind. 4. The persistent macrophage activating agent according to claim 1, wherein 5. The macrophage activator according to claim 1, wherein said macrophage activator is added to functional foods and health foods. 6. A food or drink having a macrophage activating effect, comprising a mixture of two types of crude drugs, pumpkin and safflower.