JP2018090552A - Arthralgia improver - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an arthralgia improver having high efficacy.SOLUTION: An arthralgia improver contains as active ingredients nondenaturing proteoglycan and nondenaturing collagen of 3:10-7:10 in mass ratio.SELECTED DRAWING: Figure 7

Description

  The present invention relates to an agent for improving arthralgia.

  Joint pain and arthropathy caused by knee deformation, which is a problem in the elderly, have a significant impact on the quality of daily life. Conventionally, steroids and non-steroids have been widely used to relieve such symptoms, but there are concerns about side effects due to excessive immunosuppressive action.

  By the way, various substances having an action to improve joint pain such as chondroitin, vitamin B1 class, N-acetylglucosamine (NAG), and glucosamine have been reported (Patent Documents 1 and 2).

  And the joint pain improvement effect by proteoglycan has also been reported. As a joint pain improving effect by proteoglycan, a knee joint pain improving effect and a low back pain improving effect are known (Patent Documents 3 and 4).

  In addition to the joint pain improvement effect, proteoglycan normalizes the musculoskeletal system, prevents / recovers / improves functional deterioration, prevents / restores / improves skin sagging, elasticity, wrinkles, and pigmentation in the beauty system, and normalizes keratin Such effects are known (Patent Document 3).

  Furthermore, it has also been reported that non-denatured proteoglycans having a large molecular weight are highly effective in improving inflammatory bowel disease, skin barrier function, etc. (Patent Documents 5 and 6). It has also been reported that non-denatured proteoglycans have skin fibroblast proliferation activity and hyaluronic acid binding activity (Patent Documents 5 and 6).

  It has also been reported that therapeutic agents containing collagen have an effect of improving joint pain (Patent Documents 7 and 8).

Japanese Patent Laying-Open No. 2015-20959 Japanese Patent Laying-Open No. 2015-180687 Japanese Patent Laid-Open No. 2006-138060 Japanese Patent Application Laid-Open No. 2015-13845 JP 2011-219449 A Japanese Patent Laid-Open No. 2006-128467 JP 2003-155250 A JP 2014-114232 A

  As described above, a plurality of types of substances having an action of improving joint pain have been reported, but few studies have been made on combinations thereof.

  Among them, since the mechanism of action of proteoglycan is not clear, little is known about the usefulness of the interaction between proteoglycan and other substances having an action to improve joint pain.

  This invention made | formed in view of the said situation makes it a subject to find the usefulness by interaction of the substance which has the effect | action which improves the proteoglycan and other joint pain. In addition, an object of the present invention is to provide a joint pain ameliorating agent, a composition for improving joint pain, or a food that is extremely effective in alleviating joint pain by examining the blending ratio.

  As a result of diligent research to solve the above problems, the present inventors have found that a joint pain improving agent containing a non-modified proteoglycan and a non-modified collagen at a specific mass ratio has a high joint pain improving effect, The present invention has been completed.

That is, the joint pain improving agent of the present invention is a joint pain improving agent containing non-denatured proteoglycan and non-denatured collagen as active ingredients, and comprises non-denatured proteoglycan and non-denatured collagen in a mass ratio of 3:10 to 7:10. It is characterized by that.
Since the joint pain improving agent of the present invention contains non-denatured proteoglycan and non-denatured collagen at a specific mass ratio, it exhibits a high joint pain improving effect.

  In a preferred form of the invention, the unmodified proteoglycan has an average molecular weight of 900,000 Da or more.

  Any non-denatured collagen can be used for the joint pain improving agent of the present invention. Among these, a form using non-denatured type II collagen is preferable. According to such a form, a higher joint pain improving effect is exhibited.

  The present invention also relates to a composition for improving joint pain comprising the above-mentioned agent for improving joint pain as an active ingredient.

  In a preferred form of the present invention, the composition for improving joint pain is a food composition.

  The joint pain improving agent and the joint pain improving composition of the present invention are excellent in the action of reducing joint pain and arthropathy.

It is a graph which shows the relationship between the mass ratio of a non-denatured proteoglycan and a non-denatured collagen, and the improvement effect of "the pain of the left knee at rest" by the VAS test as described in an Example. It is a graph which shows the relationship between the mass ratio of a non-denatured proteoglycan and a non-denatured collagen, and the improvement effect of "the pain of the right knee at rest" by the VAS test as described in an Example. It is a graph which shows the relationship between the mass ratio of a non-denatured proteoglycan and a non-denatured collagen, and the improvement effect of "the pain of the left knee at the time of normal walking" by the VAS test as described in an Example. It is a graph which shows the relationship between the mass ratio of a non-denatured proteoglycan and a non-denatured collagen, and the improvement effect of "the pain of the right knee at the time of normal walking" by the VAS test as described in an Example. It is a graph which shows the relationship between the mass ratio of a non-denatured proteoglycan and a non-denatured collagen, and the "left knee pain at the time of stair climbing" improvement effect by the VAS test as described in an Example. It is a graph which shows the relationship between the mass ratio of a non-denatured proteoglycan and a non-denatured collagen, and the improvement effect of "the pain of the right knee at the time of stair climbing" by the VAS test as described in an Example. It is a graph which shows the relationship of the "total evaluation" of the mass ratio of non-denatured proteoglycan and non-denatured collagen, and the joint pain improvement effect by the VAS test as described in an Example.

  The joint pain improving agent of the present invention contains non-denatured proteoglycan and non-denatured collagen as active ingredients.

  Non-denatured proteoglycans are proteoglycans that can be used for formulation while substantially maintaining the molecular weight of the proteoglycans in the organism from which they are derived.

  It should be noted that the molecular weight composition of non-denatured proteoglycan is not necessarily the same as the molecular weight composition of proteoglycan in the organism from which it originates, and the proteoglycan in the organism from which the proteoglycan made available for formulation can be used. Proteoglycans contained in the joint pain ameliorating agent of the present invention can be said to be “non-denatured proteoglycans” if they have the same characteristics as the molecular weight composition.

  Non-denatured proteoglycans are also proteoglycans that have not been subjected to denaturation treatment in the process of extraction or formulation.

  In the present invention, “denaturation treatment” means an operation of actively denaturing proteoglycans. That is, the operation of extraction or formulation without substantially decomposing or destroying proteoglycan and the natural denaturation of proteoglycan over time are not included in the “denaturation treatment”.

  Even if a modified proteoglycan is produced in the production process of the joint pain ameliorating agent of the present invention, the joint of the present invention can be used as long as the main proteoglycan is within the range of the molecular weight composition of the proteoglycan in the organism from which it originated. Proteoglycans contained in pain ameliorating agents can be said to be “non-denatured proteoglycans”. Specifically, for example, the composition of the molecular weight of the proteoglycan in the organism originated from 80% by mass or more, preferably 90% by mass or more, more preferably 99% by mass or more of the proteoglycan contained in the joint pain improving agent of the present invention. If the proteoglycan is within the range, the proteoglycan contained in the joint pain ameliorating agent of the present invention can be evaluated as a non-denatured proteoglycan.

  The origin of the non-denatured proteoglycan contained in the joint pain ameliorating agent of the present invention is not particularly limited. For example, fish-derived cartilage tissue such as salmon nasal cartilage tissue, ray cartilage tissue, shark cartilage tissue, Non-denatured proteoglycans extracted from avian cartilage tissues such as chicken cartilage tissues, and from mammalian cartilage tissues such as bovine throat cartilage, bronchial cartilage, and whale cartilage.

  Among them, the non-denatured proteoglycan is preferably extracted from the tissue of one or more organisms of cartilage tissues such as salmon nasal cartilage tissue, shark cartilage tissue and chicken. The non-denatured proteoglycan is more preferably extracted from salmon nasal cartilage tissue.

  In the case where non-modified proteoglycan is prepared from a natural product, the preparation method is not particularly limited as long as it does not denature the proteoglycan. For example, salmon nasal cartilage is used as a raw material and extracted using an alkaline solution. The method of preparing and the method of immersing in the solution containing peracetic acid and recovering the solution after immersion can be selected.

  The unmodified proteoglycan may be a commercially available pharmaceutical raw material or food raw material.

  In the joint pain ameliorating agent of the present invention, it is preferable to use a non-modified proteoglycan having an average molecular weight of preferably 900,000 Da or more, more preferably 1,200,000 Da or more, and further preferably 1,500,000 Da or more.

  The method for calculating the average molecular weight of the non-denatured proteoglycan is not particularly limited as long as the average molecular weight can be calculated from the composition of the molecular weight of the proteoglycan in the product. For example, a high performance liquid chromatography apparatus was used. Examples thereof include a method for calculating an average molecular weight by quantitative analysis, and a method for calculating an average molecular weight by performing electrophoresis treatment after quantification using an ELISA method.

  Non-denatured collagen is collagen that can be used for formulation while substantially maintaining the molecular weight of the collagen in the organism that is the origin.

  Note that the molecular weight composition of non-denatured collagen does not necessarily have to be the same as the molecular weight composition of the collagen in the organism from which it originates, and the collagen in a state where it can be used for formulation is the source of the collagen in the organism from which it originates. If it has the same characteristics as the composition of molecular weight, the collagen contained in the joint pain improving agent of the present invention can be said to be “non-denatured collagen”.

  Non-denatured collagen is collagen that has not been subjected to denaturation treatment in the process of extraction or formulation.

  In the present invention, “denaturation treatment” means an operation of actively denaturing collagen. That is, the operation of extraction or formulation without substantially degrading or destroying the collagen and the natural denaturation of the collagen over time are not included in the “denaturation treatment”.

  In the process for producing the joint pain improving agent of the present invention, even if denatured collagen is produced, the joint of the present invention is not limited as long as the main collagen is within the range of the molecular weight composition of the collagen in the organism from which it originated. Collagen contained in the pain ameliorating agent can be said to be “non-denatured collagen”. Specifically, for example, the composition of the molecular weight of collagen in an organism originating from 80% by mass or more, preferably 90% by mass or more, more preferably 99% by mass or more of the collagen contained in the joint pain improving agent of the present invention. If the collagen is within the range, it can be evaluated that the collagen contained in the joint pain ameliorating agent of the present invention is non-denatured collagen.

  The origin of the non-denatured collagen contained in the joint pain ameliorating agent of the present invention is not particularly limited. For example, fish-derived cartilage tissues such as salmon nasal cartilage tissue, ray cartilage tissue, shark cartilage tissue, Non-denatured collagen extracted from avian cartilage tissues such as chicken cartilage tissues and further from cartilage tissues derived from mammals such as bovine throat cartilage, bronchial cartilage and whale cartilage.

  Among these, non-denatured collagen is preferably extracted from tissue of one or more organisms among cartilage tissues such as salmon nasal cartilage tissue, shark cartilage tissue, and chicken. The non-denatured collagen is more preferably extracted from salmon nasal cartilage tissue.

  In the case of preparing non-denatured collagen from a natural product, the preparation method is not particularly limited as long as it does not denature the collagen, and a method of preparing from a natural product by a conventional method can be adopted. .

  The non-denatured collagen may be a commercially available pharmaceutical material or food material.

The non-denatured collagen is preferably non-denatured type II collagen.
When the non-denatured collagen contained in the joint pain ameliorating agent of the present invention is non-denatured type II collagen, a higher joint pain improving effect is exhibited.

  And it is preferable to use the undenatured collagen whose average molecular weight becomes like this. Preferably it is 300,000 Da to 400,000 Da for the joint pain improving agent of this invention.

  The method for calculating the average molecular weight of non-denatured collagen is not particularly limited as long as the average molecular weight can be calculated from the composition of the molecular weight of collagen in the product. For example, a high performance liquid chromatography apparatus was used. Examples thereof include a method for calculating an average molecular weight by quantitative analysis, and a method for calculating an average molecular weight by performing electrophoresis treatment after quantification using an ELISA method.

  The arthralgia improving agent of the present invention is preferably non-denatured proteoglycan and non-denatured collagen, preferably 3:10 to 7:10, more preferably 4:10 to 6:10, and even more preferably 4.5: 10 to 5.5. : It is included at a mass ratio of 10.

The present invention also relates to a composition for improving joint pain comprising the above-mentioned agent for improving joint pain as an active ingredient.
The present composition can be in the form of a food composition or a pharmaceutical composition. Further, the joint pain improving agent of the present invention is preferably in the form of an oral composition.

  Examples of food compositions include general foods such as confectionery, bread, and noodles, drink preparations, food groups with the purpose of promoting health in the form of capsules and tablets (for example, foods for specified health use, nutritional functional foods, etc.) it can. Examples of the pharmaceutical composition include granules, powders, capsules, orally-administered drugs in the form of tablets. Particularly preferred is a form as a food composition.

  Moreover, these food compositions and pharmaceutical compositions can contain acceptable optional ingredients. As such optional ingredients, if it is a food composition, seasoning ingredients such as salt, sugar, sodium glutamate, sodium inosinate, vinegar, coloring ingredients, flavoring ingredients such as flavors, thickeners, emulsifying / dispersing agents, Preservatives, stabilizers, various vitamins and the like can be suitably exemplified, and plants such as cat's claw extract, white willow extract, boswellia serrata resin extract can be used as long as they are food groups and pharmaceutical compositions with the purpose of promoting health. Origin components, excipients such as crystalline cellulose, lactose, binders such as arabic gum and hydroxypropyl cellulose, disintegrants such as croscarmellose sodium and starch, lubricants such as magnesium stearate, calcium stearate, fine silicon oxide, Flavoring, flavoring, coloring, vitamin B1, vitamin B6, vitamin D3, vitamin B12, extracted vitamin E, etc. These various vitamins can be preferably exemplified. By treating these according to a conventional method, the composition of the present invention can be produced.

  The total content of non-denatured proteoglycan and non-denatured collagen in the composition for improving joint pain of the present invention is 0.05 to 90% by mass, more preferably 0.5 to 30% by mass, and still more preferably 5 to 10% by mass. More preferably, it can be 7-8 mass%.

  Proteoglycan is contained in an amount of 0.02 to 30% by mass, more preferably 0.2 to 10% by mass, and still more preferably 1 to 5% by mass with respect to the total amount of the composition for improving joint pain of the present invention. . This is because the joint pain improving effect of the joint pain ameliorating agent of the present invention is exhibited to a higher degree if it is at least the lower limit, and the joint pain improving effect is more efficiently exhibited if it is below the upper limit.

  Further, collagen is contained in an amount of 0.04 to 60% by mass, more preferably 0.4 to 20% by mass, and still more preferably 2 to 10% by mass with respect to the total amount of the composition for improving joint pain of the present invention. Is preferred. This is because the joint pain improving effect of the joint pain ameliorating agent of the present invention is exhibited to a higher degree if it is at least the lower limit, and the joint pain improving effect is more efficiently exhibited if it is below the upper limit.

  The composition for improving joint pain of the present invention is a form in which 1 to 15 mg of non-modified proteoglycan and non-modified collagen, which are active ingredients in the composition for improving joint pain, are taken once or in several divided doses per day. It is preferable that

  Hereinafter, the present invention will be specifically described by way of examples.

  In the examples, the correlation between the mass ratio of non-denatured proteoglycan and non-denatured collagen and the joint pain improving effect was examined.

1. Subjects: 25 adults aged 40 to under 75 years of age who have mild knee pain, etc. who have sustained mild knee pain, etc. and have not undergone hospitalization or medication for osteoarthritis, a total of 50 Targeted.

2. Manufacture of the product The nasal cartilage was extracted from raw salmon and stored frozen, and an alkali extraction solvent was added, and the obtained intermediate product was separated into non-denatured proteoglycan and non-denatured type II collagen by a centrifuge.
Then, the filter process which removes an impurity was performed, and the non-denaturing proteoglycan powder and the non-denaturing type II collagen powder were obtained by performing a spray-drying process after that.

  By adding excipients such as crystalline cellulose, calcium stearate, and fine silicon oxide to the non-modified proteoglycan powder and non-modified type II collagen powder, granulation is performed, and the resulting granules are processed into capsules to give 200 mg per tablet. Capsule-type products 1 to 4 were produced.

Table 1 shows the component composition of non-denatured proteoglycan and non-denatured type II collagen (total 15 mg) contained in the products 1 to 4 (one tablet 200 mg).
Product P is a placebo product (one tablet 200 mg) that does not contain non-denatured proteoglycan and non-denatured type II collagen.

  The non-denatured proteoglycan in the product was quantified using a high performance liquid chromatography apparatus (Shimadzu Corporation, column TSK-GEL G4000PWXL). Moreover, from the quantitative value of the peak indicating the non-modified proteoglycan in the product, it was confirmed that the average molecular weight of the non-modified proteoglycan in the product was 900,000 Da or more.

  In addition, non-denatured type II collagen in the product was quantified using the ELISA method. Further, it was separately subjected to an agarose electrophoresis treatment, and it was confirmed that the molecular weight of collagen in the product was in the range of 300,000 Da to 400,000 Da, which is the molecular weight of non-denatured type II collagen.

3. Examination method The test subject is divided into 5 test subject groups, each consisting of 5 men and women of 10 people, and each test subject group is one of products 1-4 or product P once a day, one tablet before going to bed. Ingested with a glass of water.

(Subjective questionnaire survey)
Regarding the knee joint pain evaluation method, regarding the degree of knee pain according to the visual analogue scale (hereinafter referred to as VAS), the pain at the start of the test was defined as the highest score portion (100%), and the lowest score portion (0%) as “no pain at all”. Set to “No”, “Pain in the left knee during rest”, “Pain in the right knee during rest”, “Pain in the left knee during normal walking”, “Pain in the right knee during normal walking”, “Stairs” A questionnaire survey was conducted on seven items: pain in the left knee during ascending / descending, pain in the right knee during ascending / descending stairs, and comprehensive evaluation, and the effects of test product intake were observed.

4). Results The results are shown in FIGS.
The group of subjects who took the product 1 showed a marked improvement in joint pain at the end of 6 weeks compared with the group of subjects who took other products. The group of subjects who took the products 2 and 3 showed a significant improvement in joint pain at the end of 6 weeks compared with the group of subjects who took other products. Moreover, it is recognized that the products 2 and 3 have the same joint pain improving effect.

5. Discussion Based on the above results, the joint pain improving agent of the present invention containing non-denatured proteoglycan and non-denatured type II collagen at a specific mass ratio has an excellent knee joint pain improving effect. In particular, a product (product 1) containing non-denatured proteoglycan and non-denatured type II collagen at a mass ratio of 5:10 had an excellent knee joint pain improving effect. Furthermore, product 1 had a repeated continuity of effect that the effect did not fade even if it was administered for a long time.

  In addition, the effect of improving joint pain of a product (product 2) containing non-denatured proteoglycan and non-denatured type II collagen in a mass ratio of 6:10 (product 2) and a product containing a mass ratio of 4:10 (product 3) is equivalent. Therefore, it can be said that the joint pain improving agent containing the non-denatured proteoglycan and the non-denatured type II collagen in a certain range ratio has a significant joint pain improving effect, with the joint pain improving effect of the product 1 being maximized. That is, a significant joint pain improving effect can be expected from a joint pain improving agent containing non-modified proteoglycan and non-modified type II collagen in a mass ratio of 3:10 to 7:10.

The present invention can be applied to supplements.

Claims (5)

A joint pain ameliorating agent comprising non-denatured proteoglycan and non-denatured collagen as active ingredients,
An arthralgia improving agent comprising non-denatured proteoglycan and non-denatured collagen in a mass ratio of 3:10 to 7:10.   The joint pain improving agent according to claim 1, wherein the non-denatured proteoglycan has an average molecular weight of 900,000 Da or more.   The joint pain improving agent according to claim 1 or 2, wherein the non-denatured collagen is non-denatured type II collagen.   The composition for joint pain improvement containing the joint pain improving agent of any one of Claims 1-3 as an active ingredient. The composition for improving joint pain according to claim 4, which is a food composition.