JP5204578B2 - Joint pain improving composition, joint pain improving agent, or food - Google Patents

Description

  The present invention relates to a novel composition for improving joint pain, a joint pain improving agent, or a food that can reduce, treat, or prevent symptoms of joint pain such as arthritis.

  Joint pain such as arthritis, and arthropathy due to knee joint deformation, which is a problem particularly in elderly people, has become very frequent in recent years, increasing pain and gait disturbance as the disease progresses This has contributed to lowering the quality of daily life. Conventionally, steroids and non-steroidal drugs (NSAIDs) have been widely used to alleviate such symptoms, but there are concerns about side effects such as immune disorders and gastrointestinal disorders, which are safer and more effective. There is a need for treatment and prevention.

  Many food ingredients have been studied for this purpose. Of particular interest is glucosamine. Glucosamine is widely distributed in connective tissue and cartilage tissue, and combined with collagen, moisture, etc., contributes to the strength, flexibility and elasticity of each organ, but the ability to synthesize in vivo decreases with age. To do. Therefore, an attempt has been made to regenerate cartilage tissue by supplementing it, and many effective examples have been reported. In addition, it has been clarified that the combination with chondroitin is very effective for enhancing the cartilage regeneration ability of glucosamine (Non-patent Document 1). Patent Literature 1 discloses a composition for improving joint pain by using a composition of glycosaminoglycan such as creatine, glucosamine and chondroitin, or a composition obtained by adding MSM or collagen thereto.

  On the other hand, for collagen, although it has been reported that joint pain has been improved when each is continuously taken alone, there is no report clearly showing the interaction with glucosamine hydrochloride or chondroitin for collagen II, Effectiveness and safety have not been sufficiently studied scientifically (Non-Patent Document 2). Patent Document 2 discloses an anti-inflammatory and analgesic action by a composition containing MSM, chondroitin, collagen and an antioxidant.

  Patent Literature 3 discloses an oral pain relieving oral composition containing cat's claw, glucosamine, chondroitin sulfate and collagen. Non-Patent Document 1 reports the effect of a food containing glucosamine hydrochloride, chondroitin and collagen II on osteoarthritis of the knee.

JP2007-91662A JP2005-13123 JP2003-155250A New drugs and clinical studies, 54, 255-265, 2005. Collagen safety and functionality, Food component effectiveness assessment and health impact assessment project commentary, 2004.

  According to the above patent publication, it is recognized that MSM, glucosamine, chondroitin, and collagen have been conventionally used to relieve joint pain such as arthritis. However, no research has been reported yet on the effect of a composition comprising a combination of collagen, MSM, glucosamine and chondroitin on the improvement of joint pain, particularly regarding the amount (ratio).

  Therefore, the present invention examines a combination of collagen, MSM, glucosamine, and chondroitin, focusing on the preferred compounding amount (ratio), and is particularly effective for alleviating joint pain. It is an object of the present invention to provide a composition for improving joint pain, an agent for improving joint pain, or a food.

  In order to solve the above-mentioned problems, the present inventors have paid particular attention to collagen and MSM, and as a result of diligent research, as a result, joint pain containing collagen, MSM, glucosamine, and chondroitin at a suitable blending amount (ratio). The improvement composition was found and the present invention was completed.

  That is, according to the present invention, there is provided a composition for improving arthralgia comprising collagen, MSM, glucosamine, and chondroitin, and a composition containing collagen in an amount of 2000 mg or more per day. Since this composition contains a large amount of collagen in a suitable blending amount together with MSM, glucosamine, and chondroitin, it has an effect of improving joint pain.

  In addition, according to the present invention, there is provided an arthralgia improving agent containing collagen, MSM, glucosamine and chondroitin, which contains 2000 mg or more of collagen per day. This joint pain ameliorating agent is effective as a drug for improving joint pain because it contains a large amount of collagen in a suitable blending amount together with MSM, glucosamine, and chondroitin.

  Moreover, according to this invention, the foodstuff containing MSM, glucosamine, chondroitin, and the collagen of the intake of 2000 mg or more per day is provided. This food contains MSM, glucosamine, chondroitin and a large amount of collagen in a suitable blending amount, and is an effective food for improving joint pain.

  The present invention is effective in improving joint pain, particularly in reducing pain of joint pain.

[Explanation of terms]
“Collagen” in the present embodiment is a fibrous protein that exists in skin, blood vessels, teeth, cartilage tissue, connective tissue, etc. and occupies about 30% of the total protein amount, and most of them have a helix structure 3. It consists of a helical structure (tropocollagen) composed of polypeptide chains. Collagen is present in tissues such as skin (scale), cartilage, bone, organ, and tendon of mammals such as cattle and pigs, birds such as chickens, fish such as sharks and rays, and molluscs such as squid. Collagen to be extracted can be used, and these can be mixed and used. In addition to purified collagen, any collagen containing components can be used in the present invention. Instead of the above animal (marine) collagen, plant-derived collagen-like substances (plant collagen: extensin, etc.) such as soybeans and carrots are used alone or in combination with the above animal (marine) collagen. You may use together.

  In this embodiment, collagen can be further distinguished from type I collagen, type II collagen, and other collagens by their molecular structures. Type I collagen is present in the skin (dermis), human body, tendon, bone, etc., and is the most abundant collagen in the body, and type II collagen is present in articular cartilage, intervertebral disc, vitreous body, etc. It is collagen. These can be obtained by a conventional method, and can be obtained, for example, by extraction from a tissue or sample having a large content, separation or purification from a mixture, or the like. Further, in addition to purified collagen, any collagen can be used in the present invention as long as it contains each collagen as a component.

  In this embodiment, the collagen after the extraction may be further subjected to a treatment such as partial hydrolysis. For example, a partially degraded and reduced molecular form collagen, a collagen peptide treated with an enzyme (protease), a fermented collagen fermented with bacteria / yeast, or a fermentation treated with a combination of enzyme treatment and fermentation treatment Collagen peptides can also be used. This fermented collagen peptide is more suitable for oral intake because of its higher absorbability in oral intake than collagen, less bitterness and odor, and less thickness.

In addition, “MSM” in the present embodiment is an abbreviation for methylsulfonylmethane (chemical formula: (CH ₃ ) ₂ SO ₂ ). MSM is a sulfur compound that is also present in natural animals and plants, and is usually absorbed from foods and used as a sulfur source in most animals and plants. The MSM in this embodiment may be a natural product or a synthetic product. MSM derived from natural products is extracted directly from plants such as animal milk such as milk, pine (eg, pine leaves), green-yellow vegetables, tomatoes, coffee, tea (eg, tea leaves), apples, cabbage, or the like, or It is obtained by synthesizing the components extracted from these as raw materials. For example, MSM can also be obtained by reacting lignin isolated from pine needles with sulfur. In addition to purified MSM, any component containing MSM as a component can be used in the present invention. In the case of a synthetic product, it can be obtained, for example, by oxidation of dimethyl sulfoxide.

  In addition, “glucosamine” in the present embodiment refers to glucosamine (2-amino-2-deoxyglucose) and physiologically acceptable salts thereof (for example, hydrochloride, sulfate, phosphate, etc.), N-acetylglucosamine and the like. Is a generic name including glucosamine derivatives of and the physiologically acceptable salts thereof. Glucosamine is obtained by replacing the hydroxyl group of glucose with an amino group, and is biosynthesized from glucose and glutamine in vivo. Glucosamine is contained in polysaccharides, mucopolysaccharides, glycoproteins, glycolipids, bacterial cell wall peptidoglycans, and lipopolysaccharides of animals, plants, and microorganisms. Especially in animals, glucosamine is a component of sugar chain added to glycoproteins as cartilage / tendon.・ Distributed in connective tissues such as ligaments. Glucosamine can be obtained industrially, for example, by hydrolysis using chitin as a raw material, but chemically synthesized products or mixtures thereof can also be used. In addition to purified glucosamine, any component containing glucosamine as a component can be used in the present invention.

  The “chondroitin” in this embodiment is chondroitin sulfate, which is a sulfate ester thereof, in addition to chondroitin, which is a kind of mucopolysaccharide consisting of hexosamine and uronic acid, and physiologically acceptable salts thereof (for example, sodium salt). Is a generic name including Since chondroitin is contained in a large amount in a state of being bound to protein in the cornea, lens, ciliary muscle, vitreous body, cartilage, bone, tendon, blood vessel wall, skin, etc., this chondroitin-protein complex is included in the present invention. It can also be used. Chondroitin can be obtained from animal cartilage or the like, but chemically synthesized or a mixture thereof may be used. In addition to purified chondroitin, for example, cartilage powder or cartilage extract can also be used in the present invention as long as it contains chondroitin as a component.

  In addition, the “daily intake amount” in the present embodiment refers to the amount that an adult takes per day. The composition, the joint pain ameliorating agent, the food, etc. in the present embodiment are adjusted with the blending amount containing the target component so that the daily intake is within a defined range by taking 1 to several times. . Therefore, there is no restriction | limiting in particular in content, such as a composition ingested once, a joint pain improving agent, and a foodstuff.

  Further, “improvement of joint pain” in the present embodiment refers to, for example, osteoarthritis such as osteoarthritis of the hip, osteoarthritis of the knee, and rheumatoid arthritis, etc. It refers to reducing (relaxing), treating or preventing (preventing recurrence) the symptoms of joint pain for rheumatoid arthritis or arthritis with joint pain (such as sports disorders).

  In addition, the “functional food” in the present embodiment refers to, for example, health foods, health supplements, sick foods, nutritional supplements, or health functional foods specified by the Ministry of Health, Labor and Welfare (specific health foods, nutritional functional foods) ) Such as foods having superior physiological characteristics compared to ordinary foods. Furthermore, the label attached to the functional food includes, for example, a label recognized for a health functional food defined by the Ministry of Health, Labor and Welfare, or a label that the composition is used for the treatment of knee joint pain. Specifically, these indications are attached to, for example, a packaging container for functional food. Here, “food” includes all forms that are used orally exclusively for eating and drinking (including beverages, for example), and even those in the form of tablets are used exclusively for eating and drinking. As far as possible, it is included in the food in this embodiment.

Embodiment
In order to solve the above-mentioned problems, the present inventors focused on collagen and MSM in particular, and as a result of intensive research, they improved joint pain containing collagen, MSM, glucosamine, and chondroitin at a suitable blending amount (ratio). A composition was found.
Hereinafter, embodiments of the present invention will be described.

  One embodiment of the present invention is a composition for improving arthralgia comprising collagen, MSM, glucosamine, and chondroitin, and a composition containing collagen of 2000 mg or more per day. This composition is effective in improving joint pain because it contains a large amount of collagen in a suitable blending amount together with MSM, glucosamine, and chondroitin. In particular, many of the conventional arthralgia improving compositions (foods) had the problem of once again suffering from arthralgia once they were ingested, whereas the compositions (foods) of the present invention ) Improves the joint pain through synergism with MSM, glucosamine, chondroitin, etc., because it contains a large amount of collagen at a suitable blending amount. Can be prevented. In addition, it has a feature that the effect is shown more reliably (with fewer individual differences) in a shorter period of time than the conventional product.

  The content of MSM, glucosamine and chondroitin contained in the composition of the present embodiment is not particularly limited, and the content of collagen is not particularly limited as long as it is an intake of 2000 mg or more per day, preferably The intake is 2200 mg or more per day, more preferably 2500 mg or more per day, or 2500 mg per day. In addition, the upper limit of the collagen content can be determined in consideration of the saturation tendency of the joint pain improvement effect dependent on the collagen content, ease of ingestion, and cost. More specifically, for example, 20000 mg per day The following intake is preferable, more preferably 15000 mg or less per day, further preferably 10,000 mg or less per day, still more preferably 8000 mg or less per day, and still more preferably 5000 mg or less per day.

  Yet another embodiment is the aforementioned composition comprising 800 mg or more daily intake of type I collagen and 400 mg or more daily intake of type II collagen. Combining type I collagen and type II collagen enhances the joint pain improving effect. The content of type I collagen is not particularly limited, but may be an intake of 800 mg or more per day, preferably 1000 mg or more per day, more preferably 1200 mg or more per day, more preferably 1600 mg or more per day, The intake is preferably 2000 mg or more per day, or 2000 mg per day. The content of type II collagen is not particularly limited, but is preferably 400 mg or more per day, more preferably 500 mg or more per day, or 500 mg per day. Further, it is more preferable that the mixing ratio of type I collagen and type II collagen is 4: 1.

  Yet another embodiment is the aforementioned composition, wherein at least a portion of the collagen is a collagen peptide. Since the composition of the present invention contains a large amount of collagen as one of its characteristics, it is required to have low absorbability of collagen and elimination of difficulty in drinking. Therefore, these points can be improved by using a collagen peptide.

  Yet another embodiment is the above composition comprising an intake of MSM of 500 mg or more per day. In the composition of the present invention, MSM works synergistically with a suitable amount of collagen, glucosamine and chondroitin to bring about analgesic / anti-inflammatory action on the joint part, but contains MSM at an intake of 500 mg or more per day. The effect is stronger. The MSM content is not particularly limited, but is preferably 600 mg or more per day, more preferably 700 mg or more, most preferably 750 mg or more per day, or 750 mg per day. The upper limit is not particularly limited, but since MSM is a bitter component, it is preferable to have an intake of 2000 mg or less per day, more preferably 1500 mg or less per day, from the viewpoint of easy intake. More preferably, the intake is 1000 mg or less per day.

  Yet another embodiment is the above composition comprising an intake of glucosamine of 800 mg or more per day. In the composition of the present invention, glucosamine works synergistically with suitable amounts of collagen, MSM, chondroitin, and promotes the production of cartilage, thereby improving the function of cartilage and reducing pain of joint pain. By including glucosamine in an intake amount of 800 mg or more per day, the effect is exerted more strongly. The content of glucosamine is not particularly limited, but is preferably 900 mg or more per day, more preferably 1000 mg or more per day, or 1000 mg per day. Although there is no restriction | limiting in particular about the upper limit, From a viewpoint of easy ingestion, it is preferable that it is an intake of 2000 mg or less per day, More preferably, it is an intake of 1500 mg or less per day.

  Yet a further embodiment is the above composition comprising an intake of 500 mg or more per day of chondroitin. In the composition of the present invention, chondroitin works synergistically with a suitable amount of collagen, MSM, and glucosamine to relieve pain in the inflamed part and provides a lubricating effect, but contains chondroitin at a dose of 500 mg or more per day. And the effect is demonstrated more strongly. The chondroitin content is not particularly limited, but is preferably 600 mg or more per day, more preferably 700 mg or more, more preferably 800 mg or more per day, or 800 mg per day. The upper limit is not particularly limited, but from the viewpoint of ease of intake, the intake is preferably 2000 mg or less per day, more preferably 1500 mg or less, and even more preferably 1000 mg or less per day. .

  Glucosamine and chondroitin work synergistically between these two components for the formation of cartilage and other joint tissues. Therefore, when the ratio of glucosamine and chondroitin is 5: 4, the effect of improving joint pain is stronger. . In addition, collagen and glucosamine and collagen and chondroitin are synergistically involved in the formation of connective tissue in cartilage and joints, and the respective mixing ratios are 5: 2 and 25: 8, respectively. And more preferred.

  Yet a further embodiment is the aforementioned composition, provided in granular form. Since the composition of this embodiment is granular, it is easy to ingest a large amount of collagen, and can also be dissolved in water and drunk. Of course, the form of the composition of the present invention is not limited to this, and various forms or agents such as tablet (tablet), chewable, capsule, liquid (syrup, drink), cream, powder, jelly, etc. Can be shaped. These preparations can be produced by using a formulation technique or the like that is usually used in the field of foods and pharmaceuticals.

  Yet another embodiment is the above-described composition, characterized in that it is prepared as a functional food. For example, health foods, health supplements, sick foods, nutritional supplements, or health function foods (specific health foods, nutrient function foods) defined by the Ministry of Health, Labor and Welfare It means that it is prepared as a food having superior physiological characteristics as compared with ordinary food. In addition, for example, indications approved for functional health foods established by the Ministry of Health, Labor and Welfare and indications that the composition is used for the treatment of knee joint pain are provided on functional food packaging containers. May be.

  Yet another embodiment is a joint pain ameliorating agent comprising collagen, MSM, glucosamine and chondroitin, wherein the joint pain ameliorating agent comprises 2000 mg or more of collagen per day. This joint pain improving agent can also be used as a pharmaceutical or a quasi drug.

  Yet another embodiment is a food comprising MSM, glucosamine, chondroitin sulfate, and a daily intake of 2000 mg or more of collagen. The above food may be provided in any form as a food, and as a seasoning, for example, stevia powder, matcha powder, lemon powder, honey, sorbidol, reduced maltose, lactose, sugar solution, etc. may be used. . In addition to the various shapes or dosage forms described above, specific food products such as juices, yogurts, shortenings, spreads, mayonnaises, chocolate cream, sesame tofu, rice cakes, and powdered beverages are processed. It may be.

  In addition to the collagen, MSM, glucosamine, and chondroitin, the above-described composition, joint pain ameliorating agent, and food contain physiologically active substances, (food) raw materials, (food) additives, and the like as necessary. May be. Here, examples of the physiologically active substance include components that are particularly effective for improving joint pain. Specifically, for example, S-adenosylmethionine, vitamin B1, creatine, cat's claw, amino acid, vitamin C, and hyaluron. Examples include, but are not limited to acids. Examples of other additives / raw materials include those used by addition / mixing / infiltration and other methods in the production / processing / storage of foods, etc., for example, excipients, extenders, thickeners, Examples include binders, lubricants, stabilizers, colorants, emulsifiers, solubilizers, colorants, flavoring agents, seasonings, spices, sweeteners, preservatives, and flavorings that are commonly used. .

  In this embodiment, vitamin C is particularly effective as the active ingredient. Since vitamin C is essential for biosynthesis of hydroxyproline in the process of biosynthesis of collagen, the biosynthesis of collagen in vivo is promoted by including vitamin C, and the joint pain of the composition of the present invention The improvement effect is further enhanced.

  Furthermore, the inclusion of a fragrance helps to eliminate the bitter taste of MSM and the odor of collagen contained in the composition of the present invention, and is effective in eliminating difficulty ingesting (increasing compliance). As the fragrance, a citrus fragrance is particularly desirable.

  It is preferable to take the composition of the present invention continuously for 4 weeks or longer, preferably 8 weeks or longer, and most preferably 12 weeks or longer. The composition of the present invention can exhibit a more reliable effect when continuously ingested for 4 weeks or more, and can exhibit a higher and more reliable effect as continuous intake continues for 8 weeks and 12 weeks.

  In addition, the composition, the joint pain ameliorating agent, and the food described in the above embodiment are not intended to limit the present invention, but are disclosed for the purpose of illustration. The technical scope of the present invention is defined by the description of the scope of claims, and those skilled in the art can make various design changes within the technical scope of the invention described in the scope of claims.

  EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, these are each examples, and this invention is not limited to these. In addition, unless otherwise indicated, the commercially available reagent mentioned in the Example was used in accordance with the manufacturer's instruction or standard method.

[Example 1]
The comparative example is a food containing three components of collagen, glucosamine, and chondroitin, and the sample 1 according to the present invention increases the amount of type I collagen, which is an important component of cartilage formation, and is said to have an analgesic effect. This is a new blend of sulfonylmethane (MSM). A randomized, double-blind, placebo-controlled, parallel-group comparative study with a 4-week follow-up period was conducted after humans with mild joint pain in the knee for 12 weeks. The effect was investigated.

1. Subjects Subjects were 39 adult men and women aged 20 to under 75 years of age who had mild knee pain etc. who had sustained knee pain for more than 1 month and had not been hospitalized or treated for knee osteoarthritis. The composition of the subjects is shown in Table 1.

2. Sample and Intake Method Table 2 shows the component composition of the sample used in this test. Subjects took one of the samples three times a day, one before and after each meal in the morning, noon, and evening, with a glass of water. When it was difficult to drink, it was dissolved in a small amount (appropriate amount) of water and ingested.

3. Study schedule This study was a randomized, double-blind, placebo-controlled, parallel group comparison study. The test period was set to 12 weeks for the sample intake period, and further set to 4 weeks as the post-observation period after completion of the intake.

4). Inspection method (Subjective questionnaire survey)
The knee pain assessment method was applied to food with reference to the Japanese version of the Knee Osteoarthritis Measure (JKOM) and was revised as described below (items listed in Table 3, specific questionnaire form) (Shown in FIGS. 1a-g).

  I. Regarding the degree of knee pain by visual analogue scale (hereinafter referred to as VAS), the highest score was revised from "most severe pain experienced so far" to "severely painful (needs treatment)" II. The highest score for knee pain and stiffness has been revised from "severely painful" to "severely painful (needs treatment)". In addition, about I and II, it investigated according to the right and left knees, and the evaluation score was added together. Evaluation points are 0.5 to 10 points for I using VAS, II is 0 to 8 points for 0.5 units for each item, daily life status of III, normal activities of IV and V The health status was evaluated as 0 to 8 points for each item by 2 points. In addition, for the shoulders, elbows and limbs, the “investigation sheet” was used to observe the effects of test food intake.

  As an example of score calculation, `` stiffness '' is a state of resistance and abnormality that is different from usual when moving the knee joint, and the score of `` knee pain and stiffness '' is a stiffness immediately after waking up in the morning, Eight items, such as climbing stairs and pain when walking on a flat surface, were scored to determine the difference from the start of the test, and the average value was calculated and compared. The score for “status of daily life” is calculated by averaging 10 items such as climbing stairs, crouching, crouching, standing up, changing trousers and skirts, difficulty in going out, and the difference from the start of the test. Were calculated and compared.

5. Result 5-1. JKOM Food Variant Score Some results (II (knee of the knee) at each observation period (at the start of the study (week 0), 4 weeks, 8 weeks, 12 weeks and 4 weeks after the end of intake (post observation period)) Pain and stiffness) and III (status of daily life)) are shown in Table 4, and the whole is shown in FIG.

  (FIG. 2-A) With respect to “total of left and right knee scores of I (degree of knee pain)”, a significant improvement (p <0.01) after 4 weeks in the sample 1 group in comparison with before ingestion, In the comparative group, significant improvement (p <0.05) was observed after 4 weeks.

    (FIG. 2-B) Regarding “II (total of knee pain and stiffness) of left and right knee scores”, compared to the placebo group, the specimen 1 group was significant in the post-observation period after 8 weeks (p <0.05). In the comparative group, a significant improvement (p <0.05) was observed in the post observation period. In comparison with the pre-intake, the sample 1 group improved significantly (p <0.05) in the later observation period after 4 weeks, and the comparative example group was significant in the later observation period (p <0. 01) improvement was observed.

  (FIG. 2-C) With respect to “Total score of III (status of daily life)”, the improvement was significantly (p <0.05) in the specimen 1 group after 8 weeks in the post observation period compared with the placebo group. In the comparative group, significant improvement (p <0.05) was observed at 12 weeks and in the post observation period. In comparison with before ingestion, the sample 1 group significantly improved (p <0.05) after 4 weeks, the comparative example group after 8 weeks, and the post observation period.

  (Fig. 2-D) Regarding “IV (ordinary activity) total score”, a significant improvement (p <0.01) was observed in the sample 1 group after 4 weeks and in the later observation period in comparison with before intake. In the comparative group, significant improvement (p <0.05) was observed at 12 weeks and in the post observation period.

  (FIG. 2-E) Regarding “V (health state) total score”, a significant improvement (p <0.05) was observed in the specimen 1 group after 8 weeks in the post-observation period compared to the placebo group. . Even in comparison with before ingestion, significant improvement (p <0.05) was observed in the specimen 1 group in the post-observation period after 8 weeks.

  (FIG. 2-F) Regarding “total score from I to V”, compared with the placebo group, the specimen 1 group improved significantly (p <0.05) in the post observation period after 8 weeks, and compared In the example group, a significant improvement (p <0.05) was observed in the post observation period. In comparison with the pre-intake, the specimen 1 group showed a significant (p <0.01) improvement in the subsequent observation period after 4 weeks, and the comparative group was significant in the subsequent observation period after 8 weeks (p <0.01). 0.01) improvement was observed.

5-2. Pain in shoulders, elbows and limbs For each observation period (at the start of the study (week 0), 4 weeks, 8 weeks, 12 weeks and 4 weeks after the end of intake (16 weeks after the intake of the test food)), Compared to the group, the sample 1 group showed an improvement trend (p <0.1) throughout the sample intake period, and the comparison by observation period showed an improvement trend (p <0) in the 12th week and the subsequent observation period. .1) was observed.

6). Summary This time, for subjects with mild knee joint pain, a sample containing collagen, glucosamine and chondroitin as the main components (comparative example), and a sample containing sample MSM (specimen 1) with different mixing ratios We examined the pain-reducing effect on joint pain and safety, and also examined the pain-reducing effect on shoulder, elbow and limb pain. JKOM Food Variant Score (I: Knee Pain, II: Knee Pain and Stiffness, III: Daily Life Status, IV: Normal Activity, V: Health Status, Overall IV) Compared with the placebo group, the specimen 1 group showed significant improvements (p <0.05) in the II, III, V and overall in the post observation period from the 8th week onwards. Even when discontinued, the effect was confirmed to be persistent. In the comparative group, significant improvement (p <0.05) was observed in III at 12 weeks, and significant improvement (p <0.05) was observed in II, III, and overall in the later observation period. However, the sustainability of the effect was confirmed. In comparison with pre-ingestion, sample 1 group showed significant (p <0.05) improvement after 4 weeks of ingestion in I-IV and overall, and significant in I-IV and overall (p <0.01) was confirmed, and the sustainability of the effect was confirmed during the intake period and even when the intake was stopped. In the comparative example group, significant improvement (p <0.05) was observed in I after 4 weeks, and significant improvement (p <0.05) was observed in I to III and overall after 8 weeks. In addition, significant improvements (p <0.01) were observed in I to IV and overall in the post-observation period, and the sustainability of the effect was confirmed even when the intake was stopped.
Of the pains in the shoulders, elbows and limbs examined secondary, foot pain at 12 weeks showed a trend of improvement (p <0.1) in the sample 1 group compared to the placebo group.

  On the other hand, when the effects on physical examination, physical examination, hematology examination, and blood biochemistry examination were examined, it was clear in the specimen 1 group and the comparative example group in all examination items compared with the placebo group No significant variation was observed, indicating that Sample 1 and the Comparative Example did not adversely affect these items.

  Based on the above results, Specimen 1, which is a composition of the present invention containing collagen, MSM, glucosamine, and chondroitin in the appropriate blending amounts thereof, and 5 components thereof has an excellent pain reducing effect on knee joint pain. In addition, it has been confirmed that it has high safety, and is useful for further improvement of the quality of life for those suffering from knee pain, which increases with the arrival of an aging society. In particular, compared to conventional compositions with different compounding ratios (amounts), the certainty of the effect that the effect can be achieved with fewer individual differences and the persistence of the effect that the effect persists even after withdrawal of intake Had the characteristics.

[Example 2]
In the treatment of joint pain, if the tissue blood flow rate can be increased, it is considered that the metabolism in the arthritis affected tissue can be promoted and the prescribed active ingredient can be effectively reached. Thus, the tissue blood flow increasing effect of the composition of the present invention was examined by experiments using rat tail tissue blood flow.

1. Experiment 1-1. Experimental Method Eight-week-old IGS (Sprague-Dawley strain) male rats (body weight 254 to 360 g) were fasted the day before the test (fasted for about 16 to 20 hours). On the test day, after depilation, the rat was fixed using a fixator, and a joint fiber (Omega Wave Co., Ltd.) was attached and fixed on the skin on the caudal dorsal side at a position of about 2 cm from the ridge. The joint fiber was connected to a GJ probe (Omega Wave Co., Ltd.), and the tissue blood flow in the tail was measured with a laser tissue blood flow meter (Omega Flow FLO-N1, Omega Wave Co., Ltd.) via the GJ probe. After confirming that the rat was sedated in the fixator and the value of the blood flow of the tail tissue was stable, the measurement was started, and the average value for 10 minutes before administration was defined as the value before administration. Immediately after measurement of the pre-dose value, the rat was taken out of the fixator, and the test substance was forcibly administered orally using an oral sonde (Fuchigami instrument). Immediately after the administration, the rat was returned to the fixator and the measurement was resumed. The tissue blood flow was measured up to 70 minutes after administration of the test substance, and 10-minute intervals (0-10 minutes, 10-20 minutes, 20-30 minutes, 30 -40 minutes, 40-50 minutes, 50-60 minutes and 60-70 minutes), the average tissue blood flow at each measurement point was determined.

1-2. Group composition and test substance preparation Rats were divided into groups I and II. In accordance with the mixing ratio of the five main components of specimen 1 (Table 5), in the group I, a sample prepared so that the collagen dosage is 1 g / kg, 2.02 g / kg (about 20 times the daily dose of human being as specimen 1, (Converted as 50 kg body weight). In group II, 1.02 g / kg of a sample prepared with three components without collagen was administered (Table 6). Samples used in Group I and Group II were suspended in distilled water and prepared to have a dose volume of 5 mL / kg.

1-3. Statistical processing Numerical values were expressed as mean ± standard error (Mean ± SE). Statistical analysis performed a variance ratio test. When no significant difference was observed, Student'-t test was performed, and when significant difference was observed, Welch's-t test was performed. In all tests, the significance level was 5%.

2. Results No difference between groups I and II was observed in pre-dose values in rat tail tissue blood flow (Table 6). In group I, the blood flow of the tail tissue suddenly increases around 10 to 20 minutes after administration of the five main components of specimen 1, reaches a peak at 20 to 30 minutes after administration, and peaks until around 40 to 50 minutes after administration. Persisted (FIG. 3). In group II, it shows a gradual increase in tail tissue blood flow from about 20 to 30 minutes after administration of components excluding type I and type II collagen in the main 5 components, and reaches a peak at about 40 to 50 minutes after administration. It lasted from 60 to 70 minutes after administration (FIG. 3). Thus, both I and II groups showed an increase in the blood flow of the tail tissue, but the degree was stronger in group I containing collagen, and significant tail compared to group II 20 to 50 minutes after administration. An increase in tissue blood flow was observed (FIG. 3).

  As a result of the above experiment, as a result of oral administration at 1 g / kg as collagen in the awake rat according to the mixing ratio of the five main components of specimen 1, an increase in blood flow of the tail tissue was observed. In addition, an increase in tissue blood flow was also observed when 3 components were extracted from type I and type II collagen from the main 5 components, but the level was weaker than when I type and type II collagen were added. . From this result, it was confirmed that the specimen 1 has a particularly strong tissue blood flow increasing effect.

  The increase in tissue blood flow by the composition of the present invention contributes to the promotion of metabolism to the arthritis affected tissue and the effective arrival of the five main components prescribed in the specimen 1, and is particularly effective as an arthritis improving agent or food. it is conceivable that.

Example 3
For the purpose of investigating the tissue stabilizing effect important in joint pain, the stabilizing effect on cells possessed by the composition of the present invention was examined using blood cells in vitro. Specifically, the effect of a composition comprising type I collagen, type II collagen, MSM, glucosamine and chondroitin on thermal hemolysis of rat erythrocytes was examined. The blending amount / ratio of each component in the specimen 1 is shown in Table 5 above.

1. experimental method
Heparinized blood was collected from Wistar male rat abdominal vena cava, and the blood was centrifuged (2000 rpm, 5 minutes) to remove the supernatant. To the residue (erythrocytes), 0.15 M phosphate buffer (pH 7.4) was added to wash the erythrocytes four times (2000 rpm, 5 minutes). A 5% erythrocyte suspension was prepared with 0.15 M phosphate buffer. 3 ml of 5% erythrocyte suspension was added to 3 ml of 0.015 M phosphate buffer (pH 7.4) in which each specimen was dissolved, and incubated for 20 minutes in a water bath heated to 53 ° C. After completion of the reaction, the mixture was ice-cooled for 3 minutes and centrifuged (3000 rpm, 10 minutes), and the absorbance of the supernatant was measured at a wavelength of 540 nm. (Note: Since the absorbance of the supernatant solution was shaken out, the measurement was performed using a diluted solution diluted 4-fold with distilled water.)

2. Result 2-1. Specimen 1 Effects of Concentration Changes in the Main 5 Component Normal Formulation Formulation The formulation components of the present invention are formulated according to the table, and the effects on rat erythrocyte heat hemolysis are examined at concentrations of 2.5, 5, 10 and 20 mg / ml in the test solution As a result, it showed a concentration-dependent hemolysis suppressing effect (Table 7 and FIG. 4).

2-2. Effect of Presence / absence of Type I and Type II Collagen in Five Major Components of Specimen 1 The effect on thermal hemolysis by the presence / absence of type I and type II collagen in the formulation component of the present invention was examined (Table 8). The test solution concentration of the sample containing both type I and type II collagen was 10 mg / ml.
Even in the absence of both type I and type II collagen, that is, only three components of MSM, glucosamine and chondroitin, an inhibitory effect on hot hemolysis was observed. However, the inhibitory effect was enhanced by the additional formulation of type I or type II collagen, and further enhanced by the formulation of both collagens (Table 9, FIG. 5). The degree of this enhancement was dependent on the blending ratio of type I (5 / 50.5) or type II (20 / 50.5) collagen.

2-3. Influence by change in blending ratio of type I and type II collagen in five main components of specimen 1 The blending ratio of type I and type II collagen in the blending component of the present invention is 0, 50, 75, 100, The effect on thermal hemolysis at 125, 150 and 200% was examined (Table 10). The test solution concentration of a sample having a 100% composition was 10 mg / ml.
The inhibitory effect on hot hemolysis was enhanced as the blending ratio of both collagens was increased (Table 11, FIG. 6).

Example 4
For the purpose of investigating the tissue stabilizing action by the antioxidant action, the action of the composition of the present invention on the cells was examined in vitro. Specifically, the effects of a composition comprising type I collagen, type II collagen, MSM, glucosamine and chondroitin on free radical-induced hemolysis of rat erythrocytes and the free radicals themselves were examined. The blending amount / ratio of each component in the specimen 1 is shown in Table 5 above.

1. Experimental method 1-1. Radical-induced hemolysis test Wistar male rats (240-280 g) were opened under ether anesthesia, and heparinized blood was collected from the abdominal vena cava. The blood was centrifuged at 2000 rpm for 10 minutes, the supernatant was removed, and isotonic phosphate buffer (PBS (-), Nissui Pharmaceutical Co., Ltd.) was added to the residue (erythrocytes) in an amount of about 3 times, followed by centrifugation. . The same operation was repeated three times, and a 20% red blood cell suspension was prepared with PBS (−). 0.5 ml of 225 mM 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH, Wako Pure Chemical Industries, Ltd.) solution prepared with PBS (−) and 0.5 ml of this erythrocyte suspension and PBS 0.5 ml of the test substance prepared in (−) was mixed (the final concentration of AAPH was 75 mM), and incubated for 90 minutes at 37 ° C. under light shielding at a shaking rate of 160 times / minute. After completion of the incubation, the mixture was left in running water for 5 minutes, 3 ml of cold PBS (−) was added, mixed and centrifuged, and the absorbance of the supernatant was measured at 540 nm. Note that uric acid, which is a known antioxidant, was used as a positive control substance.

1-2. Radical scavenging test 1 mM 1,1-diphenyl-2-picrylhydrazyl (DPPH, Wako Pure Chemical Industries, Ltd.) dissolved in ethanol in 600 μl of a test substance prepared with PBS (−) (control is PBS (−) only) Strain)) 6 μl was mixed and allowed to stand at room temperature for 10 minutes, and the absorbance at 517 nm was measured. As a positive control substance, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) was used. Since Trolox is hardly soluble in water, 1 μl of Trolox dissolved in DMSO (control is DMSO only) was mixed with 1 ml of 10 μM DPPH dissolved in ethanol and allowed to stand at room temperature for 10 minutes, and then the absorbance at 517 nm was measured.

2. Result 2-1. Results of radical-induced hemolysis test In a free radical-induced hemolysis test using AAPH, it was confirmed that uric acid, which has an antioxidant action, suppresses hemolysis in a concentration-dependent manner. Since it did not suppress, it was confirmed that this membrane stabilization effect is based on an antioxidant action (FIG. 7). When the influence of the presence or absence of the combination of type I and type II collagen in the five main components of specimen 1 was examined, three components (I (-) II (-)) in the absence of both collagens and the presence of type II collagen (I (−) II (+)) did not suppress hemolysis, but hemolysis was suppressed in the presence of type I collagen (I (+) II (−)), and both collagens existed (I (+) II). In (+)), the inhibitory action was further enhanced (FIG. 8). Next, when the concentration-dependent effects on free radical-induced hemolysis of the main five components of specimen 1 and collagen (I: II = 4: 1) were examined, collagen (I: II = 4: 1) and collagen (I : II = 4: 1), a concentration-dependent inhibitory effect was observed in specimen 1 (FIG. 9). Thus, when the hemolytic effect was examined by changing the blending ratio of collagen type I and type II, I: II = 4: 1 showed the strongest inhibitory effect in comparison of the average value at each 0.25 mg / ml. . (FIG. 10, Table 12).

2-2. Result of radical scavenging test As a result of radical scavenging test using DPPH, concentration-dependent radical scavenging action was observed in collagen (I: II = 4: 1) (FIG. 11), and concentrations of 2.5 and 5 mg / ml , A stronger effect was observed than each of type I and type II collagen alone (FIG. 12). In addition, the experimental result at the time of using Trolox which is a positive control substance was shown in FIG. Next, when the radical scavenging rate was examined by changing the blending ratio of collagen type I and type II, I: II = 4: 1 was strong in the comparison of the average value at 2.5 mg / ml as in the hemolysis test. The inhibitory action was shown (FIG. 14, Table 13).

  From the above Examples 3 and 4, it is suggested that the composition based on the formulation of the present invention has an antioxidant / stabilizing effect on tissues / cells, and one of the joint pain improving effects of the composition of the present invention. It was thought to be the cause. This antioxidant action / stabilizing action is particularly strong when collagen is present at the blending ratio of the present invention, and is particularly greatly enhanced when type I collagen and type II collagen are used together in a composition suitable for the present invention.

  From the results of the above examples, compositions containing collagen, MSM, glucosamine, and chondroitin at the blending ratio (amount) of the present invention lacked any of these components / or differed in the blending ratio (amount). Compared with the conventional composition, it was shown to have a particularly excellent joint pain improving effect.

The questionnaire used for the test of Example 1 is shown. The questionnaire used for the test of Example 1 is shown. The questionnaire used for the test of Example 1 is shown. The questionnaire used for the test of Example 1 is shown. The questionnaire used for the test of Example 1 is shown. The questionnaire used for the test of Example 1 is shown. The questionnaire used for the test of Example 1 is shown. The transition of the evaluation point in the JKOM food modified method of the test of Example 1 is shown. Each graph shows the degree of knee pain according to the VAS method (A), knee pain and stiffness (B), state of daily life (C), daily life (D), health state (E), total (F ) Shows the test results, and each point shows an average value. ▲: Placebo diet group (n = 12), ○: Comparative diet group (n = 13), ●: Sample 1 diet group (n = 14). *, **; p <0.05, 0.01: Comparison with the placebo group (Bonferroni). #, ##; p <0.05, 0.01: Comparison with before ingestion (t-test). In the test of Example 2, the effect of the composition of the present invention (main 5 components) on the blood flow of the tail tissue of awake rats was quantified and expressed as an average value ± standard error (n = 7). * P <0.05, ** p <0.01: pair II group (Student's-t test). It is a graph of the rat erythrocyte hemolysis inhibitory effect which the composition of this invention shows. The composition of the present invention (main 5 components) was adjusted with the compounding ratio shown in Table 5. Figures in parentheses indicate suppression rates. It is the graph which showed the relationship between the presence or absence of type I / type II collagen and the rat erythrocyte hemolysis inhibitory effect in the composition of the present invention. Table 8 shows the blending amount of each sample depending on the presence or absence of blending of type I and type II collagen. Figures in parentheses indicate suppression rates. It is the graph which showed the relationship between the collagen compounding ratio and the rat erythrocyte hemolysis inhibitory effect in the composition of this invention. Table 10 shows the blending amount of each sample according to the change in the blending ratio of type I and type II collagen. Figures in parentheses indicate suppression rates. It is a graph of the experimental result of Example 4 which investigated the influence of uric acid and indomethacin with respect to free radical induction hemolysis using AAPH as a radical generating agent. n = 3. It is a graph of the experimental result of Example 4 which investigated the influence of the presence or absence of type I / II collagen of the composition (main 5 components) of this invention with respect to free radical induction hemolysis. The concentration of the composition of the present invention in the complete composition (I (+), II (+)) was 0.5 mg / ml. n = 3. It is a graph of the experimental result of Example 4 which investigated the influence of the composition of this invention and collagen (I type: II type = 4: 1) with respect to free radical induced hemolysis. n = 3. *, **: p <0.05, 0.01; vs control (Dunnet multiple comparison). It is a graph of the experimental result of Example 4 which investigated the influence by the difference in each ratio of collagen (type I: type II) with respect to free radical induced hemolysis. n = 6. It is a graph of the experimental result of Example 4 which investigated the DPPH radical scavenging action of collagen (I type: II type = 4: 1). **: p <0.01; vs control (Dunnet multiple comparison). It is a graph of the experimental result of Example 4 which investigated the influence of collagen type I, type II, and type I: type II = 4: 1 on the DPPH radical scavenging test. n = 3. +, ++: p <0.05, 0.01; vs type I: type II = 4: 1 (Dunnet multiple comparison). It is a graph of the experimental result of Example 4 which investigated the effect of the positive control substance Trolox in a DPPH radical elimination test. n = 3. **: p <0.01; vs control (Dunnet multiple comparison). It is a graph of the experimental result of Example 4 which investigated the influence by the difference of each ratio of collagen (type I: type II) with respect to a DPPH radical elimination test. n = 3.

Claims (9)

Collagen, and methylsulfonylmethane, a glucosamine and joint pain improvement composition comprising a chondroitin, collagen type I collagen and type II collagen 4: 1 to 1: Ri mixture der of 2 ratio, A composition that is used so that 2000 mg or more of collagen is ingested per day . The composition according to claim 1, which is used so that 800 mg or more of type I collagen per day and 400 mg or more of type II collagen per day are ingested .   The composition according to claim 1 or 2, wherein at least a part of the collagen is a collagen peptide. Wherein the daily 500mg or more methylation sulfonyl methane is used as ingestion composition according to claim 1. Wherein the daily 800mg or more glucosamine is used as ingestion composition according to claim 1. Wherein the daily 500mg or more chondroitin is used as ingestion composition according to claim 1.   The composition according to any one of claims 1 to 6, which is provided in a granular form.   The composition according to any one of claims 1 to 7, wherein the composition is prepared as a functional food. And collagen, a joint pain improvement agent comprising a methylsulfonylmethane, glucosamine, and chondroitin, collagen type I collagen and type II collagen 4: 1 to 1: mixture der of 2 ratio is, per day A joint pain ameliorating agent which is used so that 2000 mg or more of collagen is ingested .

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