JP2016520126A - Compositions and methods for protection of articular cartilage - Google Patents
Compositions and methods for protection of articular cartilage Download PDFInfo
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- JP2016520126A JP2016520126A JP2016516634A JP2016516634A JP2016520126A JP 2016520126 A JP2016520126 A JP 2016520126A JP 2016516634 A JP2016516634 A JP 2016516634A JP 2016516634 A JP2016516634 A JP 2016516634A JP 2016520126 A JP2016520126 A JP 2016520126A
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- 210000001188 articular cartilage Anatomy 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims description 8
- 239000000203 mixture Substances 0.000 title abstract description 7
- UYEWRTKHKAVRDI-UHFFFAOYSA-N Calebin A Natural products C1=C(O)C(OC)=CC(C=CC(=O)COC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 UYEWRTKHKAVRDI-UHFFFAOYSA-N 0.000 claims abstract description 16
- UYEWRTKHKAVRDI-ASVGJQBISA-N Calebin A Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)COC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 UYEWRTKHKAVRDI-ASVGJQBISA-N 0.000 claims abstract description 16
- 230000006378 damage Effects 0.000 claims abstract description 15
- 230000001575 pathological effect Effects 0.000 claims abstract description 14
- 241000124008 Mammalia Species 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 241000700159 Rattus Species 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 8
- 210000002683 foot Anatomy 0.000 description 6
- 210000005222 synovial tissue Anatomy 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 208000014674 injury Diseases 0.000 description 4
- 206010018691 Granuloma Diseases 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000000548 hind-foot Anatomy 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 244000158441 Pleurotus sajor caju Species 0.000 description 1
- 235000004116 Pleurotus sajor caju Nutrition 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000003237 epithelioid cell Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- Veterinary Medicine (AREA)
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Abstract
カレビンAおよびその組成物の哺乳類関節軟骨に対する病的損傷を阻止する新規な治療可能性を開示する。Disclosed is a novel therapeutic potential to prevent pathological damage to mammalian articular cartilage of Calebin A and compositions thereof.
Description
本発明は、一般に、関節軟骨のための保護組成物および保護方法に関する。特に、本発明は、カレビンAの関節軟骨に対する病的損傷を阻止する可能性に関する。 The present invention relates generally to protective compositions and methods for articular cartilage. In particular, the present invention relates to the possibility of preventing pathological damage to articular cartilage of Calebin A.
従来技術の説明
関節軟骨は、骨の関節表面を覆って滑膜関節を形成している特殊な結合組織である。関節軟骨は、滑膜関節に、低摩擦と比較的無痛の運動をもたらす能力を授与している。関節軟骨の構造および機能は、外傷(落下または事故)、擦傷および裂傷並びに基礎病的疾患症状の後に損傷する傾向を有する。関節軟骨組織は、通常、損傷または疾病後に再生(自己修復プロセス)せず、組織の喪失および欠損の形成をもたらす。そのような非再生に寄与する原因としては、(i) 少ない細胞成分、(ii) 貧弱な代謝および(iii) 生来の軟骨細胞の、濃密なマトリックス繊維故の組織内で分裂し移動する制限された能力がある。従って、関節軟骨を外傷および疾患による損傷から保護することのできる活性成分は、そのような外傷を受けやすい個々人の生活の質を改善する注目に値する範囲を提供する重要な技術的領域を構成する。
Description of the Prior Art Articular cartilage is a special connective tissue that forms a synovial joint over the articular surface of bone. Articular cartilage confers the ability to provide synovial joints with low friction and relatively painless movement. The structure and function of articular cartilage tends to be damaged after trauma (fall or accident), abrasions and lacerations and underlying pathological conditions. Articular cartilage tissue usually does not regenerate (self-repair process) after injury or disease, resulting in tissue loss and defect formation. The causes contributing to such non-regeneration include (i) limited cellular components, (ii) poor metabolism, and (iii) limited chondrocytes that divide and migrate within tissues due to dense matrix fibers. Have the ability. Thus, active ingredients capable of protecting articular cartilage from trauma and disease damage constitute an important technical area that provides a remarkable range of improvements in the quality of life of individuals susceptible to such trauma. .
本発明の本質は、カレビンAおよびその組成物の哺乳類関節軟骨に対する病的損傷を阻止する可能性を開示することである。
本発明は、上記の目的を満たし、さらに、関連する利点を提供する。
The essence of the present invention is to disclose the potential of Calebin A and its compositions to prevent pathological damage to mammalian articular cartilage.
The present invention fulfills the above objectives and further provides related advantages.
発明の要約
本発明は、カレビンAおよびその組成物の哺乳類関節軟骨に対する病的損傷を阻止する可能性に関する。
本発明は、以下の利点を提供する。
１．カレビンAおよびその組成物の哺乳類関節軟骨に対する病的損傷を阻止する新規な治療可能性の開示。
SUMMARY OF THE INVENTION The present invention relates to the potential to prevent pathological damage to mammalian articular cartilage of Calebin A and compositions thereof.
The present invention provides the following advantages.
1. Disclosure of novel therapeutic potential to prevent pathological damage to mammalian articular cartilage of Calebin A and its compositions.
本発明の他の特徴および利点は、本発明の本質を例として示す添付画像と併せた以下のより詳細な説明から明らかとなるであろう。 Other features and advantages of the present invention will become apparent from the following more detailed description, taken in conjunction with the accompanying images, illustrating by way of example the nature of the invention.
(図１、２および３)
最も好ましい実施態様において、本発明は、哺乳類の関節軟骨を病的損傷から保護するためのカレビンAの有効量での使用方法に関し、該方法は、上記保護を必要とする哺乳類に有効量のカレビンAを投与する処置を含むことを特徴とする。
(Figs. 1, 2 and 3)
In a most preferred embodiment, the present invention relates to the use of an effective amount of calebin A to protect mammalian articular cartilage from pathological damage, said method comprising an effective amount of calebine in a mammal in need of said protection. It includes a treatment for administering A.
もう１つの好ましい実施態様においては、本発明は、哺乳類の関節軟骨の病的損傷からの保護方法に関し、該方法は、上記保護を必要とする哺乳類に有効量のカレビンAを投与する処置を含むことを特徴とする。 In another preferred embodiment, the present invention relates to a method of protecting mammalian articular cartilage from pathological damage, comprising the step of administering an effective amount of Calebin A to a mammal in need of such protection. It is characterized by that.
カレビンAおよびその組成物の哺乳類関節軟骨に対する病的損傷を阻止する新規な治療可能性を、以下で説明する具体的な実施例において明確に説明する。 The novel therapeutic potential to prevent pathological damage to mammalian articular cartilage of Calebin A and its compositions is clearly illustrated in the specific examples described below.
病的損傷：
動物モデルにおけるアジュバント誘発関節炎
使用動物：
いずれか一方の性別のアルビノウィスター(Albino Wistar)ラット
動物の体重：
140〜180グラム
動物数/群：
05匹
Pathological damage :
Adjuvant-induced arthritis in animal models
Animals used :
Albino Wistar rats of either gender
Animal weight :
140-180g
Number of animals / group :
05 animals
方法：
慢性関節炎を、ラットにおいて、液体パラフィン中で均質化した不活化ヒト型結核菌(Mycobacterium tuberculosis)の(0.5%w/v)懸濁液の0.05mLを左後足に注入することによって誘発させた。
Method :
Chronic arthritis was induced in rats by injecting 0.05 mL of a (0.5% w / v) suspension of inactivated Mycobacterium tuberculosis homogenized in liquid paraffin into the left hind paw .
組織病理：
対照および処置群の動物の右足関節を後足から分離し、秤量し、10％緩衝ホルマリン中に24時間浸漬し、その後、10%EDTA中で脱灰処理した。その後、関節を脱水し、処理し、パラフィン(56C〜58C)ブロックを作成し、染色し(ヘマトキシリンおよびエオシン)、複合顕微鏡によって検査した(Patel P, Patel D, Patel N. Experimental investigation of anti-rheumatoid activity of Pleurotus sajorcaju in adjuvant-induced arthritic rats. Chinese Journal of Natural Medicines, 2012; 10 (4): 0269‐0274)。
Histopathology :
The right ankle joint of the control and treated animals was separated from the hind paw, weighed, soaked in 10% buffered formalin for 24 hours, and then decalcified in 10% EDTA. The joints were then dehydrated and processed to create paraffin (56C-58C) blocks, stained (hematoxylin and eosin), and examined by compound microscopy (Patel P, Patel D, Patel N. Experimental investigation of anti-rheumatoid activity of Pleurotus sajorcaju in adjuvant-induced arthritic rats. Chinese Journal of Natural Medicines, 2012; 10 (4): 0269-0274).
組織病理結果：
対照関節炎群のラット足組織(図１)は、滑膜組織によって局所的に損傷した関節軟骨(矢印)を示していた。関節軟骨と滑膜組織は、散在性類上皮細胞を含む大量の好酸性の乾酪壊死(caeseous necrosis)によって置換わっており、僅かな貧弱に形成されたはっきりしない肉芽腫が存在していた。
Histopathological results :
Rat foot tissue of the control arthritis group (FIG. 1) showed articular cartilage (arrow) locally damaged by synovial tissue. Articular cartilage and synovial tissue were replaced by a large amount of acidophilic caeseous necrosis, including scattered epithelioid cells, and there was a slight, poorly defined granulomas formed.
カレビンA (10mg/kg)で処置した群のラット足組織(図２)は、関節内で滑膜組織を含む損傷されていない関節軟骨を示していた。滑膜組織は、密集した脈管性間隙(長い矢印)、散在性リンパ球(短い矢印)および損傷されてない滑膜表層からなっていた。肉芽腫は観察されなかった。 The rat foot tissue of the group treated with calebine A (10 mg / kg) (FIG. 2) showed intact articular cartilage containing synovial tissue within the joint. The synovial tissue consisted of a dense vascular gap (long arrows), scattered lymphocytes (short arrows) and an intact synovial surface. Granulomas were not observed.
カレビンA (20mg/kg)で処置した群のラット足組織(図３)は、関節内で滑膜組織を含む損傷されていない関節軟骨を示していた。滑膜組織は、軽微な滑膜上皮過形成(短い矢印)、散在性リンパ球(長い矢印)および損傷されてない脈管性間隙からなっていた。肉芽腫は観察されなかった。 The rat foot tissue of the group treated with Calebin A (20 mg / kg) (FIG. 3) showed intact articular cartilage containing synovial tissue within the joint. The synovial tissue consisted of minor synovial epithelial hyperplasia (short arrows), scattered lymphocytes (long arrows) and undamaged vascular gaps. Granulomas were not observed.
関節炎ラットの組織病理試験は、カレビンAによる関節軟骨の投与量依存性保護を示している。 Histopathological studies of arthritic rats show dose-dependent protection of articular cartilage by calebin A.
本発明を好ましい実施態様に関連して説明してきたけれども、当業者であれば、明らかに、本発明はそのような実施態様に限定されないことを理解すべきである。むしろ、本発明の範囲は、特許請求の範囲に関連してのみ解釈すべきである。 Although the present invention has been described with reference to preferred embodiments, it should be appreciated by those skilled in the art that the present invention is not limited to such embodiments. Rather, the scope of the present invention should be construed only in connection with the claims.
本発明を好ましい実施態様に関連して説明してきたけれども、当業者であれば、明らかに、本発明はそのような実施態様に限定されないことを理解すべきである。むしろ、本発明の範囲は、特許請求の範囲に関連してのみ解釈すべきである。
本発明は、さらに、以下の態様であり得る。
［１］
哺乳類の関節軟骨を病的損傷から保護するためのカレビンAの有効量での使用方法であって、前記保護を必要とする哺乳類に有効量のカレビンAを投与する処置を含むことを特徴とする前記使用方法。
［２］
哺乳類の関節軟骨の病的損傷からの保護方法であって、前記保護を必要とする哺乳類に有効量のカレビンAを投与する処置を含むことを特徴とする前記保護方法。
Although the present invention has been described with reference to preferred embodiments, it should be appreciated by those skilled in the art that the present invention is not limited to such embodiments. Rather, the scope of the present invention should be construed only in connection with the claims.
The present invention may further be the following aspects.
[1]
Use of an effective amount of calebin A to protect mammalian articular cartilage from pathological damage, comprising the step of administering an effective amount of calebin A to a mammal in need of said protection Said usage.
[2]
A method for protecting mammalian articular cartilage from pathological damage, comprising the step of administering an effective amount of Calebin A to a mammal in need of said protection.
Claims (2)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2014/010993 WO2015105501A1 (en) | 2014-01-10 | 2014-01-10 | Composition and method for the protection of articular cartilage |
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| Publication Number | Publication Date |
|---|---|
| JP2016520126A true JP2016520126A (en) | 2016-07-11 |
| JP6142446B2 JP6142446B2 (en) | 2017-06-07 |
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| KR (2) | KR101685263B1 (en) |
| AU (1) | AU2014201769B2 (en) |
| CA (1) | CA2935898C (en) |
| EA (1) | EA027614B1 (en) |
| NZ (1) | NZ622909A (en) |
| PH (1) | PH12016501138B1 (en) |
| SG (1) | SG11201605336YA (en) |
| WO (1) | WO2015105501A1 (en) |
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| EP2040696B1 (en) * | 2006-07-14 | 2017-01-25 | DSM IP Assets B.V. | Compositions and use thereof for the treatment, co-treatment or prevention of inflammatory disorders |
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Non-Patent Citations (3)
| Title |
|---|
| INFLAMMATION, vol. 34, no. 4, JPN6016032059, 2011, pages 291 - 301 * |
| JOURNAL OF NATURAL PRODUCTS, vol. 65, no. 9, JPN6016032064, 2002, pages 1227 - 1231 * |
| メルクマニュアル第１８版日本語版, JPN6016032061, 2006, pages 2 - 9 * |
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| Publication number | Publication date |
|---|---|
| SG11201605336YA (en) | 2016-07-28 |
| KR20160087387A (en) | 2016-07-21 |
| AU2014201769A1 (en) | 2015-07-30 |
| EA027614B1 (en) | 2017-08-31 |
| PH12016501138A1 (en) | 2016-07-18 |
| KR101685333B1 (en) | 2016-12-09 |
| AU2014201769B2 (en) | 2018-05-24 |
| WO2015105501A1 (en) | 2015-07-16 |
| NZ622909A (en) | 2018-04-27 |
| CA2935898A1 (en) | 2015-07-16 |
| PH12016501138B1 (en) | 2016-07-18 |
| CA2935898C (en) | 2018-11-06 |
| KR20150105185A (en) | 2015-09-16 |
| EA201591212A1 (en) | 2015-10-30 |
| KR101685263B1 (en) | 2016-12-09 |
| JP6142446B2 (en) | 2017-06-07 |
| EA201591212A8 (en) | 2016-05-31 |
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