JP4875865B2 - NTx value reducing agent for prevention and treatment of osteoarthritis - Google Patents
NTx value reducing agent for prevention and treatment of osteoarthritis Download PDFInfo
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- 201000008482 osteoarthritis Diseases 0.000 title claims description 17
- 238000011282 treatment Methods 0.000 title claims description 11
- 230000002265 prevention Effects 0.000 title claims description 8
- 239000003638 chemical reducing agent Substances 0.000 title claims description 7
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 20
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 20
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 20
- 210000000845 cartilage Anatomy 0.000 claims description 16
- 241000972773 Aulopiformes Species 0.000 claims description 15
- 235000019515 salmon Nutrition 0.000 claims description 15
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 14
- 229920002674 hyaluronan Polymers 0.000 claims description 14
- 229960003160 hyaluronic acid Drugs 0.000 claims description 14
- 102000000503 Collagen Type II Human genes 0.000 claims description 12
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- 239000008280 blood Substances 0.000 claims description 7
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- 239000003795 chemical substances by application Substances 0.000 claims description 2
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- 229920001436 collagen Polymers 0.000 description 5
- 210000002997 osteoclast Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920001218 Pullulan Polymers 0.000 description 2
- 239000004373 Pullulan Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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- 235000019423 pullulan Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
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- 208000008930 Low Back Pain Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
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- 230000009245 menopause Effects 0.000 description 1
- 210000002184 nasal cartilage Anatomy 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000001599 osteoclastic effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
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- 239000000377 silicon dioxide Substances 0.000 description 1
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- 238000001694 spray drying Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- -1 sucrose fatty acid ester Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
本発明は、変形性関節症の予防及び治療に用いるＮＴｘ値低減剤に関するものである。 The present invention relates to an NTx value reducing agent used for prevention and treatment of osteoarthritis.
骨の組織では、破骨細胞により古くなった骨が溶かされる骨吸収が起きる一方、骨芽細胞により前記骨吸収が起きた部位に新しい骨を作って再生する骨形成が起きている。ところが、加齢により骨形成が不活発になると関節の軟骨が磨り減ったり、関節に負担がかかったりして、変形性関節症を起こすようになる。前記変形性関節症では、特に膝関節、股関節等の関節痛や腰痛を伴い、甚だしいときには歩行が困難になる。 In the bone tissue, osteoclastic cells cause bone resorption where old bones are dissolved, while osteoblasts cause bone formation in which new bone is created and regenerated at the site where the bone resorption occurs. However, when bone formation becomes inactive due to aging, the cartilage of the joint is worn down or a burden is applied to the joint, causing osteoarthritis. The osteoarthritis is accompanied by arthralgias such as knee joints and hip joints and back pain, and when it is severe, walking becomes difficult.
前記変形性関節症は、近年の高齢者人口の増加に伴い、増加する傾向にある。そこで、前記変形性関節症の予防及び治療に有効な組成物の開発が望まれる。
本発明は、かかる事情に鑑み、変形性関節症の予防及び治療に優れた効果を備えるＮＴｘ値低減剤を提供することを目的とする。 An object of this invention is to provide the NTx value reduction agent provided with the effect excellent in prevention and treatment of osteoarthritis in view of this situation.
かかる目的を達成するために、本発明の変形性関節症の予防及び治療用ＮＴｘ値低減剤は、コンドロイチン硫酸と、ヒアルロン酸と、ＩＩ型コラーゲンとを有効成分として含有する変形性関節症の予防及び治療用ＮＴｘ値低減剤であって、前記コンドロイチン硫酸と、ヒアルロン酸と、ＩＩ型コラーゲンとは、サケ軟骨から抽出された複合体であり、経口投与により血中のＮＴｘ値を低減させることを特徴とする。 To achieve this object, the NTx value reducing agent for prevention and treatment of osteoarthritis according to the present invention prevents osteoarthritis containing chondroitin sulfate, hyaluronic acid, and type II collagen as active ingredients. and a therapeutic NTx value reducing agent, and the chondroitin sulfate, and hyaluronic acid, and collagen type II, Ri complexes der extracted from salmon cartilage, reducing the NTx values in the blood by oral administration It is characterized by.
コンドロイチン硫酸はそれ自体生物の軟骨に多く見られる化合物であるが、ヒアルロン酸及びＩＩ型コラーゲンと同時に摂取することにより、血中のコンドロイチン硫酸濃度が上昇すると共に、ＮＴｘ値が低減する。この結果、骨形成に用いられるコンドロイチン硫酸が増加して、骨形成を促進すると共に、破骨細胞によって骨コラーゲンが分解されたときに産生される骨に特異性が高い物質であるＮＴｘ値が低減して破骨細胞による骨吸収が抑制されるので、変形性関節症の予防及び治療に優れた効果を得ることができる。 Chondroitin sulfate itself is a compound often found in the cartilage of living organisms, but when taken at the same time as hyaluronic acid and type II collagen, the chondroitin sulfate concentration in the blood increases and the NTx value decreases . As a result, chondroitin sulfate used for bone formation increases, promotes bone formation, and decreases the value of NTx, which is a bone-specific substance produced when bone collagen is degraded by osteoclasts. and bone resorption by osteoclasts is inhibited by Runode, it is possible to obtain an excellent effect in the prevention and treatment of osteoarthritis.
また、前記コンドロイチン硫酸、ヒアルロン酸、ＩＩ型コラーゲンは、サケ軟骨から抽出された複合体である。サケ軟骨の抽出物には、前記コンドロイチン硫酸、ヒアルロン酸、ＩＩ型コラーゲンが複合体として含まれているので、好都合である。サケ軟骨から、前記複合物を抽出する方法としては、例えば、サケ軟骨を酵素処理してタンパク質を抽出した溶液を、濾過し、得られた濾液を乾燥させる方法等を挙げることができる（特許文献１参照）。 Further, the chondroitin sulfate, hyaluronic acid, II type collagen, Ru complexes der extracted from salmon cartilage. The salmon cartilage extract is advantageous because it contains the chondroitin sulfate, hyaluronic acid, and type II collagen as a complex. Examples of the method for extracting the complex from salmon cartilage include a method of filtering a solution obtained by extracting salmon cartilage with an enzyme and extracting the protein, and drying the obtained filtrate (Patent Document). 1).
前記ＮＴｘ値低減剤は、前記コンドロイチン硫酸、ヒアルロン酸、ＩＩ型コラーゲンを合わせて１日当たり１０ｍｇ〜５ｇの範囲で摂取できるように製剤されたものであることが好ましい。１日当たりの摂取量が１０ｍｇ未満では、骨形成を促進する効果を得ることができないことがあり、５ｇを超えてもそれ以上の効果は期待できない。 The NTx value reducing agent is preferably formulated such that the chondroitin sulfate, hyaluronic acid and type II collagen can be ingested in a range of 10 mg to 5 g per day. If the daily intake is less than 10 mg, the effect of promoting bone formation may not be obtained, and if it exceeds 5 g, no further effect can be expected.
本実施形態の変形性関節症の予防及び治療用組成物は、コンドロイチン硫酸と、ヒアルロン酸と、ＩＩ型コラーゲンとを有効成分として含有するものである。前記コンドロイチン硫酸、ヒアルロン酸、ＩＩ型コラーゲンは複合体を形成しており、該複合体としてサケ軟骨からの抽出物を用いる。
The composition for prevention and treatment of osteoarthritis according to the present embodiment contains chondroitin sulfate, hyaluronic acid, and type II collagen as active ingredients. The chondroitin sulfate, hyaluronic acid, II collagen forms a complex, Ru using extracts from salmon cartilage as a complex.
前記サケ軟骨からの抽出物としての前記複合体は、例えば、サケ軟骨を酵素処理してタンパク質を抽出した溶液を、濾過し、得られた濾液を乾燥させる方法により得ることができる。 The complex as an extract from salmon cartilage can be obtained, for example, by a method of filtering a solution obtained by extracting salmon cartilage by enzyme treatment and drying the obtained filtrate.
前記方法では、具体的には、先ず、原料のサケ軟骨に同量の水を添加し、該サケ軟骨を９０℃の温水中で１時間撹拌して洗浄し、脱脂、脱臭する。次に、水温５０℃で原料のサケ軟骨に対して０．２重量％のタンパク分解酵素（アロアーゼ）を加え、２時間攪拌して酵素処理し、抽出溶液を得る。次いで、前記抽出溶液を９０℃で５分間加熱して酵素を失活させた後、水温６０℃で原料のサケ軟骨に対して２．５重量％の活性炭を添加し、３０分間攪拌し、脱脂、脱臭、脱色を行う。そして、濾過助剤を加えフィルタープレスで濾過することにより脱脂した後、スプレードライにて乾燥させることにより、前記複合体を得ることができる。 Specifically, in the above method, first, the same amount of water is added to the raw salmon cartilage, and the salmon cartilage is stirred and washed in warm water at 90 ° C. for 1 hour to degrease and deodorize. Next, 0.2% by weight of proteolytic enzyme (aroase) is added to the raw salmon cartilage at a water temperature of 50 ° C., and the mixture is stirred for 2 hours for enzyme treatment to obtain an extraction solution. Next, the extracted solution was heated at 90 ° C. for 5 minutes to inactivate the enzyme, and then 2.5% by weight of activated carbon was added to the raw salmon cartilage at a water temperature of 60 ° C., stirred for 30 minutes and degreased. , Deodorization and decolorization. And after adding a filter aid and filtering with a filter press and degreasing, the said composite_body | complex can be obtained by making it dry by spray drying.
前記サケ軟骨からの抽出物としての前記複合体は、例えば、全体の４０重量％以上のコンドロイチン硫酸、全体の１重量％以上のヒアルロン酸、全体の２３重量％以上のＩＩ型コラーゲンを含んでいる。 The complex as an extract from the salmon cartilage contains, for example, 40% by weight or more of chondroitin sulfate, 1% by weight or more of hyaluronic acid, and 23% by weight or more of type II collagen. .
本実施形態の組成物は、前記複合体を１日当たり１０ｍｇ〜５ｇの範囲で摂取できるように、例えばカプセル剤等の形に製剤されたものであることが好ましく、例えば健康食品等の食品としても服用することができる。本実施形態の組成物によれば、前述のようにして服用することにより、血中のコンドロイチン硫酸濃度を増加させ、骨形成を促進するので、変形性関節症を予防することができ、あるいは変形性関節症の症状を軽減することができる。 The composition of the present embodiment is preferably formulated in the form of a capsule or the like so that the complex can be ingested in a range of 10 mg to 5 g per day. Can be taken. According to the composition of the present embodiment, by taking as described above, the chondroitin sulfate concentration in the blood is increased and bone formation is promoted, so that osteoarthritis can be prevented or deformed. The symptoms of osteoarthritis can be reduced.
次に、本発明の実施例を示す。 Next, examples of the present invention will be described.
本実施例では、まず、サケの鼻軟骨から抽出された複合体を用いて、コンドロイチン硫酸、ヒアルロン酸、ＩＩ型コラーゲンを有効成分として含む健康食品をカプセル剤の形に製剤した。前記カプセル剤は、前記複合体２５０ｍｇ、結晶セルロース７１ｍｇ、ショ糖脂肪酸エステル１５ｍｇ、微粒二酸化ケイ素４ｍｇを、５３．８６ｍｇのプルランで包んだものであり、該プルランは９．１４ｍｇの水分を含んでいる。また、前記複合体は、全体の４０重量％のコンドロイチン硫酸、全体の１重量％のヒアルロン酸、全体の２３重量％のＩＩ型コラーゲンを含んでいる。 In this example, first, using a complex extracted from salmon nasal cartilage, a health food containing chondroitin sulfate, hyaluronic acid, and type II collagen as active ingredients was formulated into a capsule form. The capsule is obtained by wrapping 250 mg of the complex, 71 mg of crystalline cellulose, 15 mg of sucrose fatty acid ester and 4 mg of fine silicon dioxide in 53.86 mg of pullulan, and the pullulan contains 9.14 mg of water. . Further, the complex contains 40% by weight of chondroitin sulfate, 1% by weight of hyaluronic acid, and 23% by weight of type II collagen.
次に、４８歳、５１歳、６２歳の女性モニター３名、２８歳、４２歳、４８歳の男性モニター３名に、前記カプセル剤を１日当たり２錠、１ヶ月に亘って投与した。各モニターは、膝関節、股関節の痛み、腰痛等を訴えている。また、女性モニター３名はいずれも既に閉経している。 Next, 3 capsules of 48, 51, and 62 female monitors and 3 male monitors of 28, 42, and 48 years old were administered 2 capsules per day for 1 month. Each monitor complains of knee and hip pain, low back pain, etc. All three female monitors are already menopause.
次に、前記カプセル剤を投与し始める前（投与前）と、１ヶ月投与した後（投与後）とで、各モニターの血中のコンドロイチン硫酸濃度（ｎｍｏｌ／ｍｌ）、血中のＮＴｘ（Ｉ型コラーゲン架橋Ｎ−テロペプチド）値（ｎｍｏｌ／ｌ）を測定した。各モニターの測定値の平均値を表１に示す。 Next, before starting administration of the capsule (before administration) and after administration for 1 month (after administration), the blood chondroitin sulfate concentration (nmol / ml), NTx (I Type collagen cross-linked N-telopeptide) value (nmol / l) was measured. Table 1 shows the average value of the measured values of each monitor.
表１から、血中のコンドロイチン硫酸の濃度は、投与後には投与前に比べて上昇していることが明らかであり、ＮＴｘ値は投与後には投与前に比べて低減していることが明らかである。 From Table 1, it is clear that the concentration of chondroitin sulfate in the blood is increased after administration compared to before administration, and that the NTx value is decreased after administration compared with before administration. is there.
前記ＮＴｘ値は、破骨細胞によって骨コラーゲンが分解されたときに産生される骨に特異性が高い物質であり、ＮＴｘ値の低減は破骨細胞による骨吸収が抑制されていることを示している。従って、本実施例の組成物によれば、血中濃度が高くなったコンドロイチン硫酸が骨形成に使用される一方、破骨細胞による骨吸収が抑制されて、変形性関節症を予防し、あるいは治療する効果を得ることができることが明らかである。 The NTx value is a substance highly specific to bone produced when bone collagen is decomposed by osteoclasts, and a decrease in NTx value indicates that bone resorption by osteoclasts is suppressed. Yes. Therefore, according to the composition of this example, chondroitin sulfate having a high blood concentration is used for bone formation, while bone resorption by osteoclasts is suppressed to prevent osteoarthritis, or It is clear that a therapeutic effect can be obtained.
Claims (2)
前記コンドロイチン硫酸と、ヒアルロン酸と、ＩＩ型コラーゲンとは、サケ軟骨から抽出された複合体であり、
経口投与により血中のＮＴｘ値を低減させることを特徴とする変形性関節症の予防及び治療用ＮＴｘ値低減剤。 An NTx value reducing agent for preventing and treating osteoarthritis comprising chondroitin sulfate, hyaluronic acid, and type II collagen as active ingredients,
Said chondroitin sulfate, and hyaluronic acid, and collagen type II, Ri complexes der extracted from salmon cartilage,
An agent for reducing NTx value for prevention and treatment of osteoarthritis, characterized by reducing blood NTx value by oral administration .
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| ES2281265B1 (en) * | 2005-11-24 | 2008-08-16 | Bioiberica, S.A. | COMPOSITIONS FOR THE TREATMENT OF ARTROSIS. |
| JP2009257842A (en) * | 2008-04-14 | 2009-11-05 | Ttc:Kk | Examination method of osteoarthritis and diagnostic kit |
| CN102170905B (en) | 2008-08-01 | 2016-08-03 | 阿克西斯股份有限公司 | Osteoarthritis treatment agent and preventive |
| WO2011093083A1 (en) | 2010-01-29 | 2011-08-04 | Ａｘｉｓ株式会社 | Pharmaceutical composition for treatment or prevention of osteoarthritis, and method of production therefor |
| JP5792636B2 (en) | 2010-01-29 | 2015-10-14 | Ａｘｉｓ株式会社 | Injection containing a therapeutic agent for osteoarthritis |
| JP2012246222A (en) | 2010-01-29 | 2012-12-13 | Axis Inc | Use for production of therapeutic agent or prophylactic agent for osteoarthritis |
| CN108159015B (en) * | 2018-01-09 | 2020-09-29 | 成都通德药业有限公司 | Sodium chondroitin sulfate capsule and preparation method thereof |
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| US6025334A (en) * | 1994-04-28 | 2000-02-15 | Les Laboratoires Aeterna Inc. | Extracts of shark cartilage having anti-collagenolytic, anti-inflammatory, anti-angiogenic and anti-tumoral activities; process of making, methods of using and compositions thereof |
| US6162787A (en) * | 1999-04-02 | 2000-12-19 | Immudyne, Inc. | Methods for treating arthritis using collagen type II, glucosamine chondroitin sulfate, and compositions |
| US6607745B2 (en) * | 2001-05-18 | 2003-08-19 | Harry Leneau | Ingestion of hyaluronic acid for improved joint function and health |
| MXPA01011542A (en) * | 2001-11-13 | 2003-05-22 | Alcon Inc | Regeneration of articular cartilage damaged by osteoarthritis i and ii, by means of intra-articular application of sodium hyaluronate and chondroitin sulphate in a gel carrier. |
| JP2003155250A (en) * | 2001-11-15 | 2003-05-27 | Fancl Corp | Healthy hood for relieving arthrodynia |
| JP2004149736A (en) * | 2002-11-01 | 2004-05-27 | Nippon Barrier Free:Kk | Chondroitin sodium sulfate, chondroitin sulfate-containing substance, and method for producing them |
| JPWO2004083257A1 (en) * | 2003-03-20 | 2006-06-22 | ホソカワミクロン株式会社 | Proteoglycan isolated from cartilaginous fish and method for producing the same |
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