Oral composition containing proteoglycans

Abstract

The present invention provides an oral composition for improving joint pain, lower back pain, and / or walking, which does not contain collagen as an active ingredient and contains proteoglycan as an active ingredient. [Solution] An oral composition for improving joint pain, lower back pain, and / or walking, which does not contain collagen as an active ingredient and contains proteoglycan as an active ingredient.

Description

Technical Field

[0004] ,

[0005]

[0001] The present invention relates to a novel use of an oral composition containing proteoglycan for use in humans and the like.

Background Art

[0002] Many people, regardless of gender or age, are troubled by low back pain and the like. Oral compositions containing proteoglycan and collagen for reducing low back pain and the like are known (Patent Document 1). On the other hand, for example, the effects of proteoglycan alone on low back pain and the like have not always been fully verified. In addition, since collagen is insoluble in water, it can be difficult to handle when manufacturing a composition or the like (Non-Patent Document 1).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Non-Patent Documents

[0004]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] To provide an oral composition for improving joint pain, low back pain, and / or walking improvement, which does not contain collagen as an active ingredient and contains proteoglycan as an active ingredient.

Means for Solving the Problems

[0006] To solve the above problems, the present inventors conducted diligent research and found that an oral composition that does not contain collagen but contains proteoglycan as an active ingredient exhibits effects in improving joint pain, lower back pain, and / or walking. That is, the present invention includes the following embodiments.

[0007] [1] An oral composition for improving joint pain, lower back pain and / or walking, which does not contain collagen as an active ingredient and contains proteoglycan as an active ingredient. [2] The composition according to [1], wherein the active ingredient is proteoglycan in an amount of 5 mg to 50 mg per human daily intake. [3] The composition according to [1] or [2], wherein the proteoglycan is a proteoglycan derived from salmon nasal cartilage. [4] The composition according to [3], wherein the molecular weight of the peak top of the proteoglycan is 300,000 to 800,000. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide oral compositions for improving joint pain, lower back pain, and / or walking, which do not contain collagen as an active ingredient and contain proteoglycan as an active ingredient.

[0009] The following provides a detailed explanation of this disclosure, including examples. Unless otherwise specified, each disclosure may refer to the explanations of other disclosures.

[0010] <Definition> (derived from) In the specification of this application, the phrase "derived from" is used with the intention of encompassing (1) to (3) below. (1) It is purified, (2) Being isolated, and / or (3) Modification [this includes low molecular weight treatment and high molecular weight treatment (polymerization)] or alteration.

[0011] (Proteoglycan) "Proteoglycan" refers to a molecule (glycoprotein) in which a protein (core protein) and a glycosaminoglycan (GAG, also called "polysaccharide" or "sugar chain") are covalently bonded. Proteoglycans exist, for example, as extracellular matrix in skin, organs, and cartilage. Glycosaminoglycans are generally known as long-chain sugar chains that do not have a branched structure. Examples of the aforementioned proteoglycans include aggrecan, versican, decorin, testican, breakican, biglycan, serglycin, syndecan, perlecan, dystroglycan, agrin, claustrin, glypican, lumican, keratocan, and neurocan. These proteoglycans can be classified, for example, into chondroitin sulfate proteoglycans, dermatan sulfate proteoglycans, heparan sulfate proteoglycans, or keratan sulfate proteoglycans depending on the type of GAG bound to the protein.

[0012] Examples of the aforementioned GAGs include chondroitin, chondroitin sulfate, dermatan sulfate (chondroitin sulfate B), heparan sulfate, heparin, and keratan sulfate. Examples of the aforementioned chondroitin include O-type sugar chains whose main disaccharide structure is a disaccharide structure of glucuronic acid and acetylgalactosamine, and iO-type sugar chains whose main structure is a disaccharide structure of iduronic acid and acetylgalactosamine (hereinafter also referred to as "chondroitin sulfate O" and "chondroitin sulfate iO," respectively). The aforementioned chondroitin sulfate has a structure in which a sulfate group is added to a sugar chain in which the disaccharides of glucuronic acid and acetylgalactosamine are repeated. For example, the aforementioned chondroitin sulfate is gluc Examples include chondroitin sulfate A (type A), which has a disaccharide structure mainly consisting of iduronic acid and acetylgalactosamine 4-sulfate; chondroitin sulfate iA (type iA), which has a disaccharide structure mainly consisting of iduronic acid and acetylgalactosamine 4-sulfate; chondroitin sulfate C (type C), which has a disaccharide structure mainly consisting of glucuronic acid and acetylgalactosamine 6-sulfate; and chondroitin sulfate iC (type iC), which has a disaccharide structure mainly consisting of iduronic acid and acetylgalactosamine 6-sulfate.

[0013] Proteoglycans derived from salmon nasal cartilage are proteoglycans obtained by extraction from salmon nasal cartilage. Here, salmon refers to fish belonging to the genus Oncorhynchus, but preferably salmon with the scientific name "Oncorhynchus keta" is selected from the viewpoint of efficiently regulating the immune response. The proteoglycans contained in the composition of the present invention are prepared, for example, by the method described in the publication (Japanese Patent Publication No. 6317053). Furthermore, the amount of proteoglycans contained in the composition of the present invention is preferably such that it is 5 mg to 50 mg per human daily intake, for example, from the viewpoint of effectively exhibiting the desired effect. The molecular weight of the peak top of the proteoglycan is preferably 300,000 to 800,000.

[0014] The proteoglycans used in this invention, such as PG derived from salmon nasal cartilage, can be produced by methods described in, for example, Japanese Patent Publications (Japanese Patent No. 6875701, Japanese Patent No. 6317053, and Japanese Patent No. 7295572).

[0015] Commercially available proteoglycans include, for example, salmon nasal cartilage-derived proteoglycans such as Proteoglycan IPC (Ichimaru Pharcos) and Proteoglycan F (Ichimaru Pharcos).

[0016] (Do not include as an active ingredient) "Not contained as an active ingredient" means that it is not included in order to exert the desired effects (improvement of joint pain, improvement of lower back pain, and / or improvement of walking). The composition of the present invention may contain collagen, hyaluronic acid, etc., listed below, to an extent that does not exert the desired effects. The amounts of collagen, hyaluronic acid, etc., contained are less than 100 mg of collagen peptide, less than 10 mg of undenatured type II collagen, and less than 120 mg of sodium hyaluronate, based on the daily intake of a human.

[0017] Collagen has a helical structure composed of three polypeptide molecules, each with a molecular weight of approximately 100,000, in which amino acids are linked together in a chain. This structure forms fibrous or membranous structures. The types and number of amino acids that make up collagen are highly distinctive. One of its characteristics is that it contains amino acids such as hydroxyproline and hydroxylysine, which are not included in the 20 basic amino acids that make up typical proteins. These amino acids are special amino acids found only in collagen and a limited number of closely related proteins, and hydroxyproline in particular accounts for about 10% of all amino acids in collagen. Therefore, hydroxyproline can be considered an indicator of the amount of collagen. While there are no particular limitations on the type of collagen based on differences in amino acid composition, type II collagen is preferred as it is abundant in cartilage.

[0018] Hyaluronic acid is a mucopolysaccharide polymer compound having a chain structure in which disaccharide units, each consisting of N-acetylglucosamine and glucuronic acid linked together, are connected. Other cartilage components include laminin, fibronectin, elastin, and the like.

[0019] (Oral composition) The oral composition according to the present invention is, for example, foods and drinks (including functional display foods, foods for specified health use, supplements, etc.), pharmaceuticals, and the like.

[0020] For example, when the oral composition is a food or drink, the form of the food or drink includes various foods and drinks such as breads, cakes, noodles, confectioneries, jellies, frozen foods, ice creams, dairy products, beverages, etc., as well as forms similar to the above-described oral dosage forms (tablets, capsules, syrups, etc.). Foods in various forms can be prepared by combining the active ingredient of the present invention alone or in appropriate combination with other food materials, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, colorants, antioxidants, humectants, thickeners, and the like.

[0021] For example, when the oral composition is a pharmaceutical product, the pharmaceutical product generally can easily assemble a convenient once-daily dosing regimen that can be adjusted according to the degree of pain, and the form of the pharmaceutical product is, for example, in solid form or liquid form. Examples of the solid form include, for example, powders, tablets, pills, capsules, cachets, troches, suppositories, and dispersible granules. For example, in the case of a powder, the carrier is generally a micronized solid that is a mixture with the micronized active ingredient. For example, in the case of a tablet, the active ingredient is generally mixed with a carrier having the necessary binding ability in an appropriate ratio and formed into a desired shape and size. Suitable carriers may include, without limitation, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low melting point wax, cocoa butter, and the like. The pharmaceutical product may also contain components such as excipients, stabilizers, preservatives, binders, disintegrants, hydrocarbons, fatty acids, alcohols, esters, pH adjusters, preservatives, etc. as necessary within a range that does not impair the desired effect.

[0022] (Improvement of joint pain) Joint pain is the pain felt in the joints, and is the pain associated with joint diseases caused by wear of joint cartilage due to factors such as aging, excessive exercise, and injuries. Joint pain is, for example, a disease accompanied by inflammation, pain that occurs in the joints without even being accompanied by inflammation, and infectious arthritis. More specifically, joint pain (joint diseases) includes, for example, osteoarthritis, rheumatoid arthritis, joint pain associated with influenza infection, collagen diseases, spondyloarthritis, infectious arthritis, gout, and inflammatory joint pain caused by diseases such as rheumatoid arthritis. In the present invention, improvement includes not only improving pain but also, for example, preventing the occurrence of pain.

[0023] (Improvement of low back pain) Lower back pain is pain felt in the lower back. A large number of people, regardless of age or gender, have a history of lower back pain. It is thought that lower back pain can be caused by tension in the muscles of the lower back and spine due to unnatural postures or heavy labor, or by age-related conditions such as herniated discs, degenerative lumbar spondylosis, osteoporosis, spinal stenosis, spondylolysis, or menopausal symptoms, either individually or in combination. Except for lower back pain caused by typical bone deformities such as herniated discs, spinal stenosis, and spondylolysis, imaging studies of the affected area often reveal no abnormalities, making it difficult to pinpoint the cause of lower back pain. For patients with lower back pain who are not candidates for surgery, including those whose cause cannot be identified, treatment primarily focuses on symptomatic relief. Symptomatic treatments include physical therapy, thermotherapy, orthotic therapy, and drug therapy using anti-inflammatory and analgesic drugs, as well as muscle relaxants. While drug therapy, such as anti-inflammatory analgesics and muscle relaxants, is the most popular and first-line treatment for patients with lower back pain, it does not fundamentally resolve the cause of the pain. Furthermore, long-term use of these drugs raises concerns about side effects. Therefore, particularly among those with a history of lower back pain, there is a very high level of awareness regarding preventing severe lower back pain, i.e., preventing it. In addition to reviewing past lifestyle habits such as poor posture to prevent lower back pain, various agents have been proposed to address the desire to prevent and / or improve lower back pain by actively consuming foods effective in preventing it. In this invention, improvement includes not only alleviating pain but also, for example, preventing the onset of pain.

[0024] (Improved walking ability) Improving walking ability involves improving or maintaining reduced walking ability. While it is clear that walking ability and muscle strength are related, as a result of muscle training, Even if muscle strengthening effects are achieved, the improvement in walking performance may not be significant (Physical Therapy, Vol. 41, No. 8, pp. 567-572, 2014).

[0025] The present invention will now be described in more detail with reference to examples, but the present invention is not limited in any way to these examples. In the following examples, the unit % in the numerical values ​​indicating the amount of each component added means mass %. [Examples]

[0026] [Preparation of Example 1 and Comparative Example 1 (Placebo)] The following were prepared: Example 1 and Comparative Example 1. Example 1: An oral composition in capsule form containing 10 mg of water-soluble proteoglycan (average molecular weight at peak top: 450,000) and 190 mg of dextrin. Note that this oral composition of Example 1 does not contain collagen or hyaluronic acid. Comparative Example 1: An oral composition in capsule form containing 200 mg of dextrin. This oral composition of Comparative Example 1 does not contain water-soluble proteoglycan, collagen, or hyaluronic acid.

[0027] (Evaluation of Example 1, etc.) Human monitoring tests were conducted using Example 1 and Comparative Example 1 according to the following protocol.

[0028] (protocol) • Study design: Randomized, double-blind, placebo-controlled, parallel-group comparison. • Participants: Healthy men and women aged 40 to 74 who experience age-related joint discomfort, difficulty walking, or decreased muscle strength. • Number of participants in the study: 58 (29 participants x 2 groups). • Allocation Method: Allocation personnel created allocation tables using random numbers and assigned allocation numbers to the research foods. The allocation tables were sealed by the allocation personnel until the analysis participants and data were finalized. At the time of allocation, there were no significant differences among the subjects in terms of age, sex, height, weight, subjective symptoms of knee pain during pre-examination, or gait rate (steps per second). • Method of intake: Using the method from Example 1, participants were given 10 mg of proteoglycan per day. One tablet was taken orally once a day between breakfast and lunch. In parallel, a placebo group was also established and administered the same dosage as Comparative Example 1. In the following example 1, the group that administered Example 1 will be referred to as the "Group from Example 1," and the group that administered Comparative Example 1 will be referred to as the "Group from Comparative Example 1." • Intake period: 12 weeks (84 days).

[0029] (Test example 1, 6m walking test results) The analysis included individuals who did not experience lower back pain during the pre-examination (effective analysis subjects). A 3m preliminary walking path was set before and after a 6m walking measurement path, making a total of 12m of straight walking distance. Measurements were taken before intake and 12 weeks after intake, and the cadence (steps per unit time) was calculated from walking time and step count. The results are shown in Table 1. In the group of Example 1, the cadence was significantly higher at 12 weeks of intake compared to the group of Comparative Example 1. The results are shown in Table 1.

[0030] [Table 1]

[0031] (Test example 2: Subjective symptoms related to walking and running) The following questionnaire was administered to the test subjects (those included in the effective analysis) to evaluate the effectiveness related to walking. Question 1: How much pain do your knees experience when walking on a flat surface? Question 2: How difficult is it for you to climb stairs? Question 3: How difficult is it for you to stand? Question 4: How long can you walk without stopping?

[0032] Questions 1, 2, and 3 used the Knee Trauma and Osteoarthritis Assessment Score (JKOOS) and were answered using a 5-choice format. 1 point was awarded for selecting the option representing the best functional state, 5 points for selecting the option representing the most severe functional state, and 2, 3, and 4 points for intermediate options, in descending order of functional state. For tabulation, 1 point was considered 100%, 5 points 0%, 2 points 75%, 3 points 50%, and 4 points 25%, with higher scores indicating a greater tendency towards improvement.

[0033] Question 4 was evaluated using Locomo25, with 0 points for distances of 2-3km or more, 1 point for approximately 1km, 2 points for approximately 300m, 3 points for approximately 100m, and 4 points for approximately 10m. A lower score indicated a greater tendency towards improvement.

[0034] The results are shown in Table 2. In the responses to questions 1, 2, 3, and 4, no significant change was observed in the measured values ​​in the Comparative Example 1 group, whereas in the Example 1 group, the measured values ​​significantly improved at 6 weeks of intake compared to before intake.

[0035] [Table 2]

[0036] (Test example 3: Subjective symptoms related to walking and running) Furthermore, a questionnaire with the following questions was administered to evaluate the effectiveness of the vehicle during operation. • Additional question 1: How difficult is it for you to run?

[0037] For this additional question 1, JKOOS was used, and participants were asked to answer using a 5-choice format. 1 point was assigned to "feel no inconvenience at all," 5 points to "hardly able to do anything," and for intermediate answers, points were assigned in descending order of functional status: 2, 3, and 4. For tabulation, 1 point was set to 100%, 5 points to 0%, 2 points to 75%, 3 points to 50%, and 4 points to 25%, with higher scores indicating a greater tendency towards improvement. The results are shown in Table 3. While no significant change in measured values ​​was observed in the Comparative Example 1 group, the measured values ​​in the Example 1 group were significantly higher at 12 weeks of intake compared to before intake. Note that only individuals without lower back pain at the time of the pre-examination were included in the analysis (effective analysis subjects).

[0038] [Table 3]

[0039] (Test example 4, subjective symptoms of knee pain (Visual analog scale, VAS)) Participants were asked to rate the degree of knee pain using a 100mm VAS scale. The left end of the VAS line represented "no symptoms," and the right end represented "the most severe pain the participant had ever experienced." Participants were asked to rate their pain for the days prior to the test. The results are shown in Table 4. At 6 weeks (42 days) and 12 weeks (84 days) of intake, the group in Example 1 had significantly lower knee pain values ​​at rest and while sitting in a kneeling position compared to the group in Comparative Example 1 (confirming a reduction in pain).

[0040] [Table 4]

[0041] (Test example 5, subjective symptoms of lower back pain) The Japanese Low Back Pain Assessment Questionnaire (JLEQ) was used to evaluate the pain and condition of the lower back. For "the degree of lower back pain," the 100 mm VAS scale was used to assess the pain level. Participants were asked to record their lower back pain in the days prior to the examination, with the left end of the VAS line representing "no pain" and the right end representing "the most severe pain the participant has ever experienced." For "lower back pain," "problems in daily life," and "condition over the past month," a questionnaire consisting of 30 multiple-choice questions with 5 options each was used. The answer to the best functional state was scored at 0 points, the answer to the most severe functional state at 4 points, and for intermediate answers, points were assigned in order of best functional state: 1 point, 2 points, and 3 points respectively.

[0042] The results are shown in Table 5. Regarding "degree of lower back pain," "lower back pain," and "problems in daily life," no significant changes were observed in the Comparative Example 1 group, whereas in Example 1, these conditions significantly decreased at week 6 (42 days) and week 12 (84 days) compared to before intake.

[0043] [Table 5]

[0044] (Test example 6, subjective symptoms of lower back pain) We also conducted a survey using the following individual questions. Question 1: Have you experienced lower back pain in the mornings when you get up and start moving around over the past few days? Question 2: Have you experienced lower back pain when standing for the past few days? Question 3: Have you experienced lower back pain when bending forward in the past few days? Question 4: Have you experienced lower back pain when bending your back over the past few days? Question 5: How difficult has it been for you to maintain the same posture for the past few days? Question 6: Have you felt the need to lie down and rest due to back pain in the past few days?

[0045] The survey results are shown in Table 6. In questions 1, 2, 3, and 4, no significant changes were observed in the measured values ​​in the Comparative Example 1 group, whereas in the Example 1 group, the measured values ​​significantly decreased at week 12 compared to before intake. In questions 5 and 6, no significant changes were observed in the measured values ​​in the Comparative Example 1 group, whereas in the Example 1 group, the measured values ​​significantly decreased at week 6 and week 12 compared to before intake.

[0046] [Table 6]

[0047] Although embodiments of the present invention (including examples) have been described above with reference to the drawings, the specific configuration of the present invention is not limited thereto, and any design changes, etc., that do not depart from the spirit of the present invention are still included. [Industrial applicability]

[0048] We can now provide oral compositions for improving joint pain, lower back pain, and / or walking, which do not contain collagen as an active ingredient and contain proteoglycan as an active ingredient.

Claims

1. An oral composition for improving joint pain, lower back pain, and / or walking, which does not contain collagen as an active ingredient, but contains proteoglycan as an active ingredient.

2. The composition according to claim 1, wherein the proteoglycan is a proteoglycan derived from salmon nasal cartilage.

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