JP2003048850A - Therapeutic agent of arthropathy, and functional food - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral therapeutic agent of arthropathy and functional food, capable of treating the damage of the arthroidal cartilage and the bone. SOLUTION: The therapeutic agent of the arthropathy and the functional food contains at least one kind selected from a collagen and a collagen peptide, an amino sugar, and at least one kind selected from a mucopolysaccharide and uronic acid. The agent and the food can rapidly treat not only the damage of the arthrodial cartilage but also the damage of the bone. As a result, the agent and the food can exhibit particular effects of repairing the damage in the strength and brings to a cured state not only the damage of the arthrodial cartilage but also the damage of the bone is early repaired (recovered).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an oral joint injury therapeutic agent or functional food. More specifically, the present invention relates to an oral joint injury therapeutic agent or a functional food, which is used for healing damage and defects of cartilage and bones of joints that are difficult to treat, and can repair cartilage and bones of joints more quickly than usual. .

[0002]

Joints play a very important role in the movement of animals. The bones that are straight to each other can be bent at an arbitrary angle at a joint portion that is a joint portion between the bones. The existence of this flexible joint that can be freely bent is the most important thing for exercising, and bone and muscle alone cannot exercise. Knee joints, shoulder joints, elbow joints, wrists, ankles, and all other joints perform this function. At the joint,
The important thing is cartilage. Cartilage plays a role of a support mechanism of a living body together with bone and exists in various forms throughout the body. Especially what is called articular cartilage exists at both ends of the bone,
It is called hyaline cartilage because of its characteristics as a matrix. This surface is very smooth, allowing the joints to move as the surfaces slide well together. Therefore, when a part thereof is chipped or damaged, it causes a movement disorder. Cartilage also acts synergistically with the synovial fluid present in the joint cavity to form a cushion between bones. Without such action, vigorous exercise or jumping is impossible. Further, the joint is composed of a portion composed of cartilage and synovial fluid (hereinafter referred to as cartilage portion) and a bone portion that firmly supports the cartilage portion, and can withstand mechanical loads such as impact caused by weight and exercise. Only when the joints exert such a function sufficiently can the animal move.

When the articular cartilage is defective or damaged, if the glucosamine salt is not ingested at all, the healing becomes very bad or the healing does not occur. It has long been said that the cartilage of joints is difficult to heal or takes a very long time to heal. In contrast, it has been reported that administration of glucosamine salt repairs cartilage in the defect (Shouro et al., FOOD Style 21, Vol.4, N
o.6, p67-73 (2000)). Compared to the case where no glucosamine salt is given, the defect is repaired faster and the gap between the defect is filled with cartilage or fibrous tissue. Thus, the active intake of glucosamine salt accelerates the repair of the defect. However, since the joint is a structure composed of a cartilage part and a bone part, and the glucosamine salt does not exert any effect on the repair of the bone part, it is inferior in terms of the effect of repairing the strength of the joint. In order to avoid these problems, a composition for treating joints comprising a hydrolyzed collagen protein and glucosamine is also known (for example, WO98 / 44929). However, the therapeutic effect is not sufficient, and a better treatment method has been demanded.

[0004]

The cartilage of the joint allows smooth movement of the body by sliding on each other's smooth surfaces and by forming a cushion between the bones. Therefore, when the cartilage of the joint is injured, various movement disorders including a walking disorder occur. On the other hand, it is known that the cartilage itself is very hard to heal, and it takes a very long time to heal or does not completely heal. Joint injury may occur due to injury to cartilage or injury to the bone itself along with cartilage. Even when a joint part including cartilage and bone is damaged, the defect is only healed in a cartilage-filled state by conventional administration of glucosamine salt alone. Similarly, when only chondroitin sulfate, which is a cartilage component of the joint, is administered, the defective portion can be healed only when it is filled with cartilage. That is, it is possible to obtain only a cure for a state of low physical strength, in other words, an incomplete state. For example, any impact on the repaired cartilage will destroy it because it is less tolerant of mechanical loading than a normal bone-supported cartilage. Also, the destroyed fragments remain in the joint cavity, causing great pain to the patient. In order to prevent such a phenomenon and recover joint damage early, not only the cartilage but also the bone under the cartilage should be promptly corrected to quickly improve the resistance (physical strength) of the joint to mechanical load. It is necessary to restore it to a normal level. The present invention seeks to solve these problems.

The inventors of the present invention have conducted various studies to solve this problem, and found that collagen (or collagen peptide) and cartilage components, which are the main components of bone formation and are expected to contribute to bone formation. A glucosamine salt that is a kind of amino sugar that is a constituent component of a certain mucopolysaccharide and contributes to cartilage repair, and a mucopolysaccharide containing a component other than glucosamine that is a constituent component of cartilage and / or uronic acid that is a constituent component of mucopolysaccharide The present invention has been completed by discovering that the co-administration of the above-mentioned drug can form a normal amount of bone and cartilage, impart normal strength and smoothness, and repair joint damage. Thus, according to the present invention, due to the synergistic effect of the combined administration of the three components of collagen (or collagen peptide) and glucosamine salt and mucopolysaccharide (or uronic acid), it is not possible to cure to a nearly complete state so far. Alternatively, it allows the repair of joints, which were said to take a very long time to heal, in a shorter time, allowing the restoration of normal joint structure. That is, according to the present invention, not only the damaged part of the joint is promptly filled with cartilage, but also the part of the bone below which the original bone should be formed is repaired, and the joint structure becomes closer to normal. Repaired and damaged joints are repaired more quickly and to a more complete condition.

The social significance of this is extremely great. For example, playing sports may damage joints, and surgical operation may remove part or all of cartilage and bone. Further, in an aging society that is progressing more and more, it is feared that cartilage and bones of all joints such as knees, elbows and shoulders will be worn away, and the number of people lacking them will increase. To these people, it is very significant to restore the normal structure and function of joints by co-administering collagen (or collagen peptide), glucosamine salt and mucopolysaccharide (or uronic acid). deep. As described above, the present invention is capable of recovering joint damage earlier by co-administering three components of collagen (or collagen peptide), glucosamine salt, and mucopolysaccharide (or uronic acid). The present invention provides a therapeutic agent for joint injury and a functional food (that is, food, beverage, feed, etc.).

[0007]

Means for Solving the Problems The gist of the present invention made in order to solve the above-mentioned problems is (1) at least one selected from collagen and collagen peptide, an amino sugar, a mucopolysaccharide and urone. Oral joint injury therapeutic agent or functional food characterized by containing at least one selected from acids; (2) Collagen and / or collagen peptide, amino sugar, mucopolysaccharide and / or uronic acid , 1 each
Ratio of 0-100: 10 to 100: 5-40 (weight ratio,
The same shall apply hereinafter), the therapeutic agent or functional food for oral joint injury according to the above (1); (3) 1 each of collagen and / or collagen peptide, amino sugar, mucopolysaccharide and / or uronic acid.
A method for producing an oral joint injury therapeutic agent or a functional food, which comprises blending in a ratio of 0 to 100: 10 to 100: 5 to 40.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Regarding the collagen used in the present invention, the type (type I, type II, type III, etc.) and origin (animal species, site, etc.) are not particularly limited, and various types of collagen are used. be able to. Preferably, type I collagen derived from skins, bones, tendons, etc. of cattle, pigs, chickens, etc. is used because of its abundant raw materials. In addition, type II collagen derived from cartilage of cow, pig, chicken, etc. is used.

The collagen peptide used in the present invention is a peptide obtained by hydrolyzing the above collagen. For example, collagen hydrolyzed with a proteolytic enzyme such as collagenase or acid or alkali. Examples thereof include those obtained by heating or hydrolyzing collagen in the presence of. Such a hydrolysis method is already known, and a method for purifying and fractionating the obtained collagen peptide is also known, and is well known to those skilled in the art. Although the molecular weight of the collagen peptide is not particularly limited, those having an average molecular weight of about 10,000 or less, preferably about 4,000 or less are used in terms of absorbability into the living body.
Note that collagen and collagen peptide may be used in combination.

Examples of the amino sugar used in the present invention include glucosamine and galactosamine. These amino sugars may be salts, and examples thereof include hydrochlorides and sulfates. The amino sugar may be chemically modified, and may be, for example, an N-acylated or esterified amino sugar. More specifically, glucosamine, glucosamine hydrochloride, glucosamine sulfate, N-acetylglucosamine, galactosamine, N-acetylglucosamine-6-sulfate and the like are exemplified.

Examples of the mucopolysaccharides used in the present invention include acidic mucopolysaccharides (eg, hyaluronic acid, hyaluronosulfate, heparin, chondroitin sulfates, lysozyme substrates, etc.) and neutral mucopolysaccharides. . Hyaluronic acid, hyaluronosulfate and chondroitin sulfates (AC) are preferably used. The mucopolysaccharide capable of forming a salt may be in the form of a salt. Examples of the uronic acid used in the present invention include glucuronic acid and iduronic acid. The uronic acid may be a salt, and examples of such a salt include sodium salt, potassium salt, calcium salt and the like. In addition, you may use together mucopolysaccharide and uronic acid.

The mixing ratio of the above-mentioned collagen and / or collagen peptide, amino sugar, mucopolysaccharide and / or uronic acid is not particularly limited as long as the effect can be exhibited, but preferably collagen and / or collagen peptide , Amino sugar, and mucopolysaccharide and / or uronic acid,
The ratio is 10 to 100: 10 to 100: 5 to 40, respectively, and more preferably 10 to 50:10 to 100: 5 to 4.
It is blended at a ratio of 0.

The therapeutic agent for oral joint injury of the present invention comprises the above-mentioned three components of collagen and / or collagen peptide, amino sugar, mucopolysaccharide and / or uronic acid as active ingredients, and Oral administration (including nasal administration, enteral administration and transmucosal administration) for the purpose of treatment and prevention. Upon administration, the active ingredient is mixed with a solid or liquid non-toxic pharmaceutically acceptable carrier suitable for oral administration, and is administered in the form of a conventional pharmaceutical preparation. Examples of such a preparation include an oral preparation (for example, Solid agents such as tablets, granules, powders and capsules, liquid agents such as solutions, suspensions and emulsions,
Lyophilized preparations, etc.), inhalants, suppositories, enteral infusions, etc., and these preparations can be prepared by conventional means for preparation. Examples of the nontoxic carrier for pharmaceutical use include glucose, lactose, sucrose, starch, mannitol,
Examples include dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, albumin, water, physiological saline and the like.
If necessary, conventional additives such as stabilizers, lubricants, wetting agents, emulsifiers and binders can be added as appropriate. In the therapeutic agent for joint injury of the present invention, the dose of the active ingredient is appropriately selected and determined depending on the patient's age, body weight, symptoms, degree of disease, administration schedule, formulation form, etc. The dose may be about 10 g and may be administered in several divided doses per day.

The functional food of the present invention comprises the above-mentioned collagen and / or collagen peptide, an amino sugar, and
It is composed of three components of mucopolysaccharide and / or uronic acid. In this specification, the functional food is
It is a concept that includes ordinary foods, beverages, confectioneries, feeds, and the like. The functional food is eaten as a functional food (or food material) useful for treating and preventing joint injury, as it is, or after adding various nutrients or by containing it in foods and drinks. For example, after adding the suitable auxiliaries mentioned above, using a conventional means, an edible form, for example,
It may be formed into granules, granules, tablets, capsules, pastes, etc. for edible use, and various foods (eg, ham,
Processed meat products such as sausages, processed fish products such as kamaboko and chikuwa, confectionery such as snacks, dairy products such as breads, butter and milk powder, soy products such as tofu and fried foods)
It may be used by adding it to water, or by adding it to drinks such as water, fruit juice, milk, and soft drinks. In addition, for animal feed (including pet food), collagen and / or collagen peptide, amino sugar, mucopolysaccharide and / or
Alternatively, it may be in a form containing uronic acid. The amount of intake in the form of such functional food depends on age, weight, symptoms,
It is appropriately selected and determined depending on the degree of disease, the form of food, etc., and is, for example, about 0.1 g to 10 g per day, but even if ingested in large amounts, it has the advantage of not adversely affecting the living body, May be ingested.

[0015]

The therapeutic agent for oral joint injury and functional food of the present invention comprises at least one selected from collagen and collagen peptide, at least one selected from amino sugar, mucopolysaccharide and uronic acid. It is possible to cure not only the cartilage of the joint but also the damage to the bone by the synergistic action of the three. in this way,
Since not only the cartilage part but also the bone part is repaired (restored) at an early stage, the strength is stronger and the complete healing can be quickly restored.

[0016]

The present invention will be described in more detail based on the following examples, but the invention is not intended to be limited to these examples.

Test Example 1 The concept of joint injury treatment of the present invention is shown in FIGS. The figure shows that a defect is created by making a hole through the cartilage through the joint of the animal and leading to the bone, and water (control), glucosamine salt alone, collagen peptide alone,
1 is a schematic view showing a wound healing state when a composition comprising glucosamine salt + collagen peptide and collagen peptide + glucosamine salt + chondroitin sulfate is ingested. FIG. 1 shows the case of the control group to which water was administered, in which the tissue did not recover and the defect was not filled in many cases. On the other hand, even when buried, it is often occupied by a fibrous structure that should not exist. FIG. 2 shows the case where the glucosamine salt was administered alone, and the defect portion was filled with cartilage or cartilage and fibrous tissue, and the space was filled with some tissue for the time being as compared with the control group in which water was administered. Are better. However,
Since it is filled with cartilage or cartilage and fibrous tissue, sufficient physical strength is not obtained, and when mechanical load is continuously applied, repaired tissue is often detached or missing again, and complete repair It has not been repaired.

On the other hand, FIG. 3 shows that when collagen peptide was administered, a small amount of bone appeared under the cartilage even at the same time, which was slightly stronger than the repair of cartilage only when glucosamine was administered alone. Present a strong situation. However, its strength is considerably weaker than that of normal joints. On the other hand, FIG. 4 shows that when collagen peptide and glucosamine salt are administered, a large amount of bone is formed under the cartilage, but the amount is not sufficient, and its strength is higher than that of a normal joint. And still weak. On the other hand,
FIG. 5 shows the case where three components of collagen peptide, glucosamine salt and chondroitin sulfate are co-administered, and a large amount of bone is formed under the cartilage part and the structure is restored to a structure close to a normal part (non-defective part). As a result, the healed joint exerts the necessary and sufficient strength.

Test Example 2Rabbit joint defect healing test (1) Preparation of collagen peptide Prepare the collagen peptide used for the test as follows
However, the present invention is not limited to this. Raw chicken legs
(From broiler) in 10 times diluted hydrochloric acid for 24 hours or more
After stirring, deashing and acid swelling were performed. And flow enough
After washing with water, the mixture was extracted with about twice the amount of warm water and filtered. Filter
The liquid is treated with an ion exchange resin, and the extract content is 10% or more.
Concentrated until. This concentrated solution is treated with a protease.
The mixture was treated at 50 ° C. for 1-2 hours and heat-inactivated. Furthermore, the extract
Concentrate to 25-30% min and dry with a spray dryer.
It was dried to obtain a powdery collagen peptide.

(2) Test Method A test animal having a joint damage was prepared by drilling a hole through which the cartilage was passed through the knee joint of a rabbit and leading to the bone. Then, the experimental animals were made to drink 5 kinds of solutions having different compositions for 3 consecutive days. (A) water (control group), (B) aqueous solution containing glucosamine hydrochloride (1 g / day), (C) aqueous solution containing collagen peptide (1 g / day), (D) glucosamine hydrochloride (1 g / day) and An aqueous solution containing two components of collagen peptide (1 g / day). (E) Glucosamine hydrochloride (1 g / day) and collagen peptide (1 g / day)
And an aqueous solution containing 3 components of chondroitin sulfate (0.05 g / day). After 3 weeks, the knee joint of the rabbit was incised, and the degree of repair of the defect creation site was observed, and the tissue of the repair site was observed under a microscope. FIG. 6 schematically shows the repaired state. In order to distinguish the cartilage part from other tissues, in addition to normal HE staining, safranin-O staining and alcian blue staining are performed (safranin-O staining and alcian blue staining are
The proteoglycan and glycosaminoglycan peculiar to cartilage tissue were specifically stained), and the thickness of cartilage formed in the defective portion was measured. Then, as shown in FIG. 6, the ratio of the thickness of the cartilage at the normal portion (the portion that was not deleted) to the thickness of the cartilage generated at the defective portion was calculated and expressed as a joint healing coefficient. Therefore, the closer the joint healing coefficient is to 1, the more the damage to the joint is repaired to a state closer to the normal condition (1 when completely restored).

(3) Results (a) After 3 weeks, in the control group to which water was administered, the defective portion was not repaired much and remained as voids. As a result, he was not cured. (b) In the group administered with glucosamine salt alone, collagen peptide alone, glucosamine salt and collagen peptide in combination, and three components of glucosamine salt, collagen peptide and chondroitin sulfate in combination, the defective portion was repaired after 3 weeks . Glucosamine salt alone, collagen peptide alone, glucosamine salt and collagen peptide,
Table 1 shows the results of the measured joint healing index for the group in which the glucosamine salt, the collagen peptide, and the three components of chondroitin sulfate were jointly administered. No bone was formed in the glucosamine salt-administered group. In the collagen peptide alone administration group, the amount of bone formed was small, and conversely, the amount of generated cartilage was larger than in the normal and collagen / glucosamine combined administration group. The joint healing coefficient was 1.72, which was a larger value than the normal value 1. In the collagen and glucosamine administration group, the joint healing coefficient was 1.45, which was closer to 1 compared with the collagen peptide alone administration group, but it could not be said to be complete repair. However, it was confirmed that the joint damage in the combined administration group of three components of collagen, glucosamine and chondroitin sulfate restored the joint damage to a normal state with a joint healing coefficient of 1.11. In addition, in the combined administration group of collagen peptide, glucosamine salt and chondroitin sulfate, the amount of bone regenerated in the lower part of the repaired cartilage is similar to that of a normal joint, and the strength similar to that of a normal joint can be recovered early. It was considered.

[0022]

Test Example 3 By the same method as in the above example, the ratio of collagen peptide, glucosamine hydrochloride and chondroitin sulfate was set to 10:10.
Tests were also performed on the 0: 5 aqueous solution and the 100: 10: 5 aqueous solution, and it was confirmed that the joint damage was repaired in a more normal manner as in the case of the combined administration of Test Example 2. Was done.

Example 1 Collagen peptide 100 mg Glucosamine hydrochloride 100 mg Chondroitin sulfate 10 mg Magnesium stearate 5 mg Corn starch 20 mg Lactose 75 mg According to a conventional method, the mixture having the above composition was tableted to give tablets.

Example 2 Collagen peptide 100 mg Glucosamine hydrochloride 100 mg Hyaluronic acid 10 mg Magnesium stearate 5 mg Corn starch 20 mg Lactose 75 mg According to a conventional method, the mixture having the above composition was tableted to give tablets.

Example 3 Collagen peptide 150 mg Glucosamine hydrochloride 50 mg Chondroitin sulfate 10 mg Magnesium stearate 5 mg Lactose 95 mg According to a conventional method, a mixture having the above composition was filled in a gelatin hard capsule to obtain a capsule.

Example 4 Natural juice (concentrated juice reduction) was mixed with collagen peptide (500 mg), glucosamine hydrochloride (500 mg) and chondroitin sulfate (25 mg) per 200 ml of the juice, followed by sterilization according to a conventional method and aseptic packaging. , A fruit juice product was obtained.

Example 5 To a ground meat for wiener sausage, 200 mg of collagen peptide, 200 mg of glucosamine hydrochloride and 40 mg of chondroitin sulfate were mixed per 15 g of the meat, and the sausage casing was filled in a conventional manner and smoked. Then, it was sterilized and packaged after cooling to obtain a wiener sausage.

Example 6 A wiener sausage was obtained in the same manner as in Example 5, except that 250 mg of collagen peptide, 150 mg of glucosamine hydrochloride and 100 mg of chondroitin sulfate were mixed per 15 g of the kneaded meat.

Example 7 150 g of chicken sternal cartilage (commonly known as bevel cartilage) and 1 part of water
000 ml was added, flavored vegetables such as onion, carrot, parsley, celery, ginger, and grain pepper were added, and the mixture was simmered and heated on low heat for 3 hours. After cooling, it was filtered with a strainer and seasoned with salt and pepper to give a trisoup. Collagen peptide 3 per 200 ml of the soup
After mixing in a ratio of 00 mg, glucosamine hydrochloride 300 mg and chondroitin sulfate 30 mg, the mixture was sterilized according to a conventional method and aseptically packaged to obtain a soup product.

Example 8 Chicken (40 parts by weight per 100 parts by weight of the raw material mixture)
(Part) with a silent cutter into fine pieces of meat with a diameter of 5 mm or less, and ice (20 parts), sorbitol (9.1 parts), flour (10 parts), vegetable protein (5.
3 parts), bone meal (5 parts), salt (1 part), collagen (1 part)
Parts), glucosamine (7.5 parts), chondroitin sulfate (0.4 parts), seasoning (0.5 parts), polymerized phosphate (0.1 part).
2 parts) was added to prepare a dough. Next, this dough is formed into a plate with a thickness of 1 cm, cut into a size with a long side of 10 cm and a short side of 1.5 cm, baked in a convection oven (CM6, Rational) set at 120 ° C, and cooled. Thus, the feed was obtained.

[Brief description of drawings]

FIG. 1 is a schematic diagram showing the repair condition of joint cartilage and bone,
The case of the control group is shown.

FIG. 2 is a schematic diagram showing a repairing condition of joint cartilage and bone,
The case of glucosamine salt alone administration is shown.

FIG. 3 is a schematic diagram showing the repair condition of joint cartilage and bone,
The case of single administration of collagen peptide is shown.

FIG. 4 is a schematic diagram showing a repairing condition of joint cartilage and bone,
The case where a collagen peptide and a glucosamine salt were administered is shown.

FIG. 5 is a schematic diagram showing the repair condition of joint cartilage and bone,
The case where a collagen peptide, a glucosamine salt, and chondroitin sulfate are administered together is shown.

FIG. 6 is a view showing a repair state of joint cartilage and bone in Test Example 2.

Front page continued (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61P 19/02 A61K 37/12 (72) Inventor Yasuki Taguchi 3-3 Midorigahara, Tsukuba, Ibaraki Nippon Ham Co., Ltd. Company Central Research Laboratory (72) Inventor Fumitake Morimatsu 3-3 Midorigahara, Tsukuba City, Ibaraki Prefecture Nippon Ham Co., Ltd. Central Research Institute (72) Ryoji Yamada 3-3 Midorigahara, Tsukuba City, Ibaraki Prefecture Nippon Ham Central Research Institute Co., Ltd. (72) Inventor Minami Saburo 2-8-28 F-term, Wakabadai Minami, Tottori City, Tottori Prefecture (reference) 4B018 LE03 MD09 MD19 MD20 MD33 ME14 4C084 AA02 BA44 MA02 MA35 MA37 MA52 NA14 ZA96 4C086 AA01 AA02 EA22 EA25 MA02 MA03 MA04 MA52 NA14 ZA96

Claims (3)

[Claims] 1. A therapeutic agent or function for oral joint injury, comprising at least one selected from collagen and collagen peptide, amino sugar, and at least one selected from mucopolysaccharide and uronic acid. Sex food. 2. Collagen and / or collagen peptide, amino sugar, mucopolysaccharide and / or uronic acid are contained at a ratio (weight ratio) of 10 to 100: 10 to 100: 5 to 40, respectively. 2. The therapeutic agent for oral joint injury or the functional food according to 1. 3. Collagen and / or collagen peptide, amino sugar, mucopolysaccharide and / or uronic acid are blended at a ratio (weight ratio) of 10 to 100: 10 to 100: 5 to 40, respectively. A method for producing a therapeutic agent for oral joint injury or a functional food.