JP2016138062A - High molecular sugar chain compound in which specific molecular binding unit is present at terminal portion in molecule, and use thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a safe useful substance excellent in stability which sufficiently and sustainably functions in normalization of the motor system and prevention/recovery/amelioration of hypofunction, as well as prevention/recovery/amelioration of skin sagging, elasticity, wrinkles and pigmentation and normalization of keratin in a cosmetic system, and to provide applications and means thereof.SOLUTION: Provided are a cartilaginous precursor cell proliferation promoter, a cartilage differentiation promoter, a cartilage calcification inhibitor, a knee joint ameliorating agent, a skin sagging ameliorating agent, a skin elastic ameliorating agent, an ameliorating agent for skin wrinkles, a skin keratin ameliorating agent, a skin pigmentation inhibitor and a humectant, in which three kinds of molecular binding units obtained by binding, in the order of a certain sequence, five sugars including sulfate group or phosphate group partially and at a specific position are present at a terminal site in the molecule, as a main active molecular part, and whose active ingredient is a high molecular sugar chain compound obtained by hydrolyzing a glycoprotein substance extracted from cartilage tissues. Provided are also a health food, a health drink, a pharmaceutical composition or a cosmetic composition comprising these agents.SELECTED DRAWING: None

Description

（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される一般式２で示される分子結合単位

（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される一般式３で示される分子結合単位

The present invention relates to a polymer sugar chain compound in which a specific molecular binding unit is present at a terminal site in the molecule, which provides various useful effects in musculoskeletal and cosmetic systems, and use thereof. More specifically, it is extracted from the cartilage tissue of fish, mollusks, birds, and mammals in which any of the molecular binding units of (1) to (3) below is present at the terminal site in the molecule as the main active molecule portion. Cartilage progenitor cell growth promoter, cartilage differentiation promoter, cartilage calcification inhibitor, knee joint improver, skin sagging improver, comprising as an active ingredient a high molecular weight sugar chain compound obtained by hydrolyzing a glycoprotein substance. The present invention relates to a skin elasticity improving agent, a skin wrinkle improving agent, a skin keratin improving agent, a skin pigmentation inhibitor, a moisturizing agent, and a health food or health drink, a pharmaceutical composition, and a cosmetic composition containing them.
(1) A molecular binding unit represented by the general formula 1 composed of the sequence of N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose

(2) Molecular binding unit represented by the general formula 2 composed of the sequence of N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate

(3) Molecular binding unit represented by the general formula 3 composed of the sequence of N-acetylgalactosamine-6-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose

  Fish, mollusks, birds, and mammals' soft tissues are soft and wettable substances composed mainly of biopolymers (proteins, sugar chains, etc.) and water. In particular, articular cartilage is composed of chondrocytes and a supporting tissue in which approximately 65 to 80% of water is contained in a gap in a matrix formed from a polymer such as collagen, hyaluronic acid, and a glucosaminoglycan-core protein conjugate. Constructed, these exert flexible and sufficient cushioning performance against the strong force applied to the articular cartilage and play an important function in the musculoskeletal system.

  However, even in healthy adults, it is known that aging causes a decrease in chondrocytes, a modification of components constituting the cartilage supporting tissue, and a decrease in the water content of the cartilage matrix (Non-Patent Documents 1 and 2). ). There is also a concern that if the calcification of the cartilage proceeds excessively, osteophytes are formed, and inflammation and minor fractures are repeated, leading to abnormal ossification.

  In recent years, the number of people who suffer from joint pain has been increasing. For example, in the 2007 National Life Survey by the Ministry of Health, Labor and Welfare, the rate of complained persons (the proportion of people with subjective symptoms due to illness or injury) is high. Results such as “back pain” and “joint pain of limbs” within the top 5 are reported as subjective symptoms. Among arthropathy, osteoarthritis, which can be said to be a reserve arm for severe arthritis, is attracting attention, and its incidence is about 75% in women over 50 years old and about 54% in men. Yes.

  In order to maintain the function of the musculoskeletal system in the living body, especially the cartilage tissue, it is known to repeat not only the repair of the damage but also the decomposition and regeneration of the tissue. It is generally considered to be effective to improve hyaluronic acid, D-glucuronic acid and N-acetyl-D-, which are polysaccharides in which disaccharide units of collagen, N-acetylglucosamine and glucuronic acid are linked. Interest in cartilage-related substances such as chondroitin sulfate, glucosamine, etc. that have sulfate groups bound to a polysaccharide chain that repeats the disaccharide of galactosamine, and that can be supplementarily consumed. ing.

  Such conventional applied techniques include, for example, arthritis alleviation and treatment composition containing hydrolyzed collagen having an average molecular weight of 10,000 to 80,000 (patent document 1), rheumatism containing type I, II and III collagen as active ingredients. Drugs for treating osteoarthritis (Patent Document 2), therapeutic agents for rheumatoid arthritis (Patent Document 3) containing type II collagen as an active ingredient, and drugs for treating degenerative joint diseases that are injection suspensions containing collagen (Patent Document) 4) Thermally denatured type II collagen for the treatment of rheumatoid arthritis (Patent Document 5), intraarticular perfusate containing hyaluronic acid having a molecular weight of 200,000 to 2.5 million and capable of reducing damage to cartilage matrix or chondrocytes (Patent document 6), therapeutic agent for arthritic diseases comprising a complex of hyaluronic acid and zinc (patent document 7), osteoarthritis composed of crosslinked hyaluronic acid, chronic Injections for treatment of various arthropathy such as rheumatoid arthritis (Patent Document 8), Collagen, chondroitin sulfate, chondroitin, N-acetylglucosamine-containing cartilage formation promoter (Patent Document 9), black vinegar, glucosamine, chondroitin sulfate And health food (Patent Document 10) having an excellent effect on anti-joint disorders including hyaluronic acid, for the treatment of cartilage or connective tissue containing chondroitin and glucosamine, or for the treatment of arthritis or to maintain their healing state Composition (Patent Document 11) and the like.

  On the other hand, proteins such as collagen, and sugars such as hyaluronic acid, chondroitin sulfate, and other biological macromolecules such as mucopolysaccharides derived from living organisms are moisturized, provided with lubricity, and proliferated, activated, and prevented aging of skin cells. Various usefulness in cosmetics such as action and repair of damaged tissue is also known, and it has been used for a long time as a medical material as well as an external preparation for skin and hair such as cosmetics.

  As a conventional application technique in such a field, for example, a skin protective agent containing soluble natural (untreated) collagen having an unchanged collagen structure as an ingredient for improving skin elasticity, enhancing skin hydration ability, and skin rejuvenation (Patent Document 12) , Hyaluronic acid, chondroitin sulfate, soluble cosmetics containing soluble collagen, skin cosmetics effective for skin cell activation, increased skin flexibility and elasticity (Patent Document 13), rough blend of water-soluble collagen and mucin Skin cosmetics that improve skin, keratin, and moisturizing effect (Patent Document 14), moisturizing cosmetics containing hyaluronic acid with a molecular weight of 2 million or more (Patent Document 15), hyaluronic acid, chondroitin sulfate, mucoic acid, keratan sulfate, etc. There is a hair dye composition (Patent Document 16) that is excellent in preventing hair damage and the like, which is formulated with the above mucopolysaccharide.

  In addition, as a conventional technique related to an extract from cartilage tissue or use thereof, for example, cartilage extract extracted with water added to bovine or porcine cartilage at 40 to 50 ° C. and its cosmetic use (Patent Document 17), Examples include shark cartilage extract having body hypertensive factor (PHF) activity and its drug use (Patent Document 18).

JP-A 63-39821 WO92 / 6708 JP-A-9-59176 WO93 / 02699 JP-A-9-255581 JP-A-5-279244 WO00 / 53194 JP 61-210034 JP2007-161688 JP 2004-166616 A WO94 / 22453 JP 47-14341 JP 54-52733 A JP-A-62-249911 JP 63-156707 A JP-A-1-56611 JP-A-6-345636 WO99 / 02548

Sei Tanaka, Glucosamine Research 4 (Aid Publishing), P89-100 (2008) Geihan Rizkalla et al. Clin. Invest. 90, P2268-2277 (1992)

  Collagen, hyaluronic acid, chondroitin sulfate, glucosamine, etc. have been conventionally expected as cartilage-related substances for the purpose of maintaining the health of the musculoskeletal system mainly composed of cartilage tissue, and ingestion as food and drink has been promoted. However, it is difficult for the ingested component to be re-synthesized as a biological component as it is, and in many explanations, it is considered as an auxiliary factor for suppressing cartilage degradation.

  In addition, these cartilage-related substances such as collagen have some recognized cosmetic effectiveness, but are not sufficient or transient, light, heat, etc. There were many problems such as denaturation, alteration, discoloration, and instability in the prescription system.

  The present invention is sufficient and continuous for normalization of the musculoskeletal system, prevention / recovery / improvement of functional deterioration, prevention / recovery / improvement of skin sagging, elasticity, wrinkles and pigmentation in the cosmetic system, and normalization of keratin. It is an object of the present invention to provide a useful substance that functions safely and has good stability and a means for its use.

  In the process leading up to the present invention, the present inventors have described the above-mentioned normalization of the musculoskeletal system, prevention / recovery / improvement of functional deterioration, and prevention / recovery / improvement of skin sagging, elasticity, wrinkles, and pigmentation in the cosmetic system. As a safe and stable useful substance that functions satisfactorily and sustainably for normalization of keratin, five sugars including a sugar having a sulfate group or a phosphate group extracted from cartilage partially and at specific positions; We have already found a glycoprotein substance containing 5-15% of molecular binding units in the molecule in which serine in the protein is bound in a certain sequence order.

  If it is possible to more precisely elucidate what molecular structural units that make up this glycoprotein substance exert this excellent effect, heat resistance is improved by reducing the molecular weight of the glycoprotein substance. It is also possible to provide it as an active ingredient material that can be used industrially while maintaining its effectiveness and functionality.

（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される一般式２で示される分子結合単位

（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される一般式３で示される分子結合単位

［２］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする軟骨分化促進剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［３］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする軟骨石灰化抑制剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［４］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とするひざ関節改善剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［５］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする皮膚たるみ改善剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［６］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする皮膚弾力改善剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［７］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする皮膚しわ改善剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［８］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする皮膚角質改善剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［９］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする皮膚色素沈着抑制剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［１０］主要な活性分子部分として、下記（１）〜（３）の何れかの分子結合単位が分子内の末端部位に存在する、魚類，軟体動物，鳥類，哺乳類の軟骨組織より抽出された糖蛋白質物質を加水分解することによって得られる高分子糖鎖化合物を有効成分とする保湿剤。
（１）Ｎ−アセチルガラクトサミン−４−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式１で示される分子結合単位
（２）Ｎ−アセチルガラクトサミン, Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロース−２−フォスフェートの配列順で構成される前記一般式２で示される分子結合単位
（３）Ｎ−アセチルガラクトサミン−６−サルフェート，Ｄ−グルクロン酸，Ｄ−ガラクトース，Ｄ−ガラクトース，Ｄ−キシロースの配列順で構成される前記一般式３で示される分子結合単位
［１１］請求項１〜１０記載の軟骨前駆細胞増殖促進剤，軟骨分化促進剤，軟骨石灰化抑制剤，ひざ関節改善剤、皮膚たるみ改善剤，皮膚弾力改善剤，皮膚しわ改善剤，皮膚角質改善剤，皮膚色素沈着抑制剤，保湿剤の何れかを配合した健康食品又は健康飲料，医薬品組成物。
［１２］請求項５〜１０記載の皮膚たるみ改善剤，皮膚弾力改善剤，皮膚しわ改善剤，皮膚角質改善剤，皮膚色素沈着抑制剤，保湿剤の何れかを配合した化粧料組成物。 That is, the present invention includes the following items.
[1] Extracted from cartilage tissues of fish, mollusks, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal site in the molecule as the main active molecule portion A cartilage progenitor cell growth promoter comprising as an active ingredient a macromolecular sugar chain compound obtained by hydrolyzing a glycoprotein substance.
(1) A molecular binding unit represented by the general formula 1 composed of the sequence of N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose

(2) Molecular binding unit represented by the general formula 2 composed of the sequence of N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate

(3) Molecular binding unit represented by the general formula 3 composed of the sequence of N-acetylgalactosamine-6-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose

[2] Extracted from cartilage tissues of fish, mollusks, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal site in the molecule as the main active molecule portion A cartilage differentiation promoting agent comprising a high-molecular sugar chain compound obtained by hydrolyzing a glycoprotein substance as an active ingredient.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed in the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose [3] The following (1) Fish, mollusc, avian, or mammalian cartilage tissue in which any of the molecular binding units (3) to (3) is present at the terminal site in the molecule. Cartilage calcification inhibitor as an active ingredient a polymer sugar chain compounds obtained by the extracted glycoprotein substances hydrolysis.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed in the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose [4] The following (1) Fish, mollusc, avian, or mammalian cartilage tissue in which any of the molecular binding units (3) to (3) is present at the terminal site in the molecule. Knee joint improving agent comprising as an active ingredient the high-molecular sugar chain compounds obtained by the extracted glycoprotein substances hydrolysis.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed in the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose [5] The following (1) Fish, mollusc, avian, or mammalian cartilage tissue in which any of the molecular binding units (3) to (3) is present at the terminal site in the molecule. Skin sagging improving agent comprising as an active ingredient the high-molecular sugar chain compounds obtained by the extracted glycoprotein substances hydrolysis.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed in the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose [6] Fish, mollusc, avian, or mammalian cartilage tissue in which any of the molecular binding units (3) to (3) is present at the terminal site in the molecule. Skin elasticity improving agent comprising as an active ingredient a polymer sugar chain compounds obtained by the extracted glycoprotein substances hydrolysis.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed in the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose [7] As the main active molecular moiety, the following (1) Fish, mollusc, avian, or mammalian cartilage tissue in which any of the molecular binding units (3) to (3) is present at the terminal site in the molecule. Wrinkle agent containing, as an active ingredient, polymer sugar chain compounds obtained by the extracted glycoprotein substances hydrolysis.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose [8] Fish, mollusc, avian, or mammalian cartilage tissue in which any of the molecular binding units (3) to (3) is present at the terminal site in the molecule. Skin keratin improving agent comprising as an active ingredient the high-molecular sugar chain compounds obtained by the extracted glycoprotein substances hydrolysis.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed in the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose [9] The following (1) Fish, mollusc, avian, or mammalian cartilage tissue in which any of the molecular binding units (3) to (3) is present at the terminal site in the molecule. Skin pigmentation inhibitor comprising as an active ingredient a polymer sugar chain compounds obtained by the extracted glycoprotein substances hydrolysis.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit [10] represented by the general formula 3 composed in the order of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose. Fish, mollusc, avian, mammalian cartilage tissue in which any of the molecular binding units of (3) is present at the terminal site in the molecule Moisturizing agent comprising, as an active ingredient, a polymer sugar chain compounds obtained by hydrolyzing the extracted glycoproteins material Ri.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Cartilage progenitor cell proliferation according to claim 11 wherein the molecular binding unit represented by the general formula 3 is composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose. Accelerator, cartilage differentiation promoter, cartilage calcification inhibitor, knee joint improver, skin sag improver, skin elasticity improver, skin Improving agents, skin keratin improving agents, skin pigmentation inhibitors, health food or a health drink formulated with either humectants, pharmaceutical compositions.
[12] A cosmetic composition comprising any one of the skin sagging improving agent, skin elasticity improving agent, skin wrinkle improving agent, skin keratin improving agent, skin pigmentation inhibitor, and moisturizer according to claims 5 to 10.

(Active ingredient)
According to the present invention, cartilage progenitor cell proliferation promoter, cartilage differentiation promoter, cartilage mineralization inhibitor, knee joint improver, skin sag improver, skin elasticity improver, skin wrinkle improver, skin keratin improver, skin pigmentation Inhibitors and moisturizers are extracted from cartilage tissues of fish, molluscs, birds, and mammals, where molecular binding units (Chemical Formula 1 to Chemical Formula 3) having certain common molecular structural features are present at the end of the molecule. A high-molecular sugar chain compound obtained by hydrolyzing the produced glycoprotein substance is used as an active ingredient.

  A molecular binding unit having a common molecular structure characteristic is a unit in which five sugars including a sugar having a sulfate group or a phosphate group at a specific position are bound in a certain sequence order. It consists of three types. The present inventor has found that a sugar chain compound having these three types of molecular bonding units is a main active molecular moiety that brings about various useful effects in the musculoskeletal system and the cosmetic system of the present invention.

  The polymer sugar chain compound obtained by hydrolyzing the glycoprotein substance extracted from the cartilage tissue of the present invention has the above five sugars including a sugar having a sulfate group or a phosphate group at a specific and specific position. Three types of molecular binding units linked in a certain sequence order are present at the molecular ends. In addition, a high-molecular sugar chain compound in which a molecular bond unit in which five similar sugars not containing a sulfate group or a phosphate group are bonded in a certain sequence order is present at the molecular end may also be included. However, when viewed as a whole of the polymer sugar chain compound, the polymer sugar chain compound according to the present invention (Chemical Formula 1 to Chemical Formula 3): the same five sugars that do not contain a sulfate group or a phosphate group are bound in a certain sequence order. The polymer sugar chain compound in which the molecular binding unit is present at the molecular end is preferably contained at a ratio of about 1: 5 to 1:20.

(Effective intake)
When the polymer sugar chain compound according to the present invention is used for orally ingested pharmaceuticals, quasi drugs, health foods, health drinks, etc., the standard is about 1 to 200 mg / day. It is considered that it is preferable to set an amount that is preferably taken at 3 mg / day or more.

(Recommended prescription amount for external use)
Moreover, when using in the form of external preparations, such as a quasi-drug and a cosmetic composition, it is preferable to formulate in the range of about 0.0001 to 0.005% by weight.

  The polymer sugar chain compound according to the present invention has excellent effects for maintaining the health of the musculoskeletal system such as promotion of cartilage progenitor cell proliferation, promotion of cartilage differentiation, suppression of cartilage calcification, and improvement of knee joint, It has excellent effects on beauty systems such as skin elasticity improvement, skin wrinkle improvement, skin keratin improvement, skin pigmentation suppression, and moisturizing. Moreover, it is safe and has good stability. Therefore, it is possible to produce health foods and health drinks that are useful for maintaining the health of the musculoskeletal system, pharmaceutical compositions, and cosmetic compositions that are useful for the beauty system by blending a small amount.

1 represents an HPLC chart of a glycoprotein substance hydrolyzate obtained for elucidating the structural characteristics of a polymer sugar chain compound according to the present invention. The evaluation result regarding the proliferative action of a cartilage progenitor cell about each sugar chain compound from which the main active molecule part of the polymeric sugar chain compound by this invention differs, and its density | concentration dependence effect are represented. The evaluation result regarding the chondrocyte progenitor cell proliferation action and its concentration-dependent effect of the macromolecular sugar chain compound according to the present invention is shown. The evaluation result regarding the cartilage differentiation action and its density | concentration dependence effect about each sugar_chain | carbohydrate compound from which the main active molecule part of the polymeric sugar_chain | carbohydrate compound by this invention differs is represented. The evaluation result regarding the cartilage differentiation effect | action and its density | concentration dependence effect about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the cartilage mineralization inhibitory effect about each sugar chain compound from which the main active molecule part of the polymeric sugar chain compound by this invention differs and its density | concentration dependence effect are represented. The evaluation result regarding the cartilage calcification inhibitory effect about the polymeric sugar chain compound by this invention and its density | concentration dependence effect is represented. The evaluation result regarding the knee joint improvement effect about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the skin sagging improvement effect about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the collagen production effect | action about each sugar_chain | carbohydrate compound from which the macromolecular sugar_chain | carbohydrate compound by this invention differs in a main active molecule part is represented. The evaluation result regarding the skin elasticity improvement effect about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the skin elasticity improvement effect about each sugar_chain | carbohydrate compound from which the main active molecule part differs from the polymeric sugar_chain | carbohydrate compound by this invention is represented. The evaluation result regarding the skin wrinkle improvement effect about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the skin keratin improvement effect about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the stain score about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the skin pigmentation inhibitory effect about each sugar_chain | carbohydrate compound from which the macromolecular sugar_chain | carbohydrate compound by this invention differs in a main active molecule part is represented. The evaluation result regarding the moisturizing effect about the polymeric sugar chain compound by this invention is represented. The evaluation result regarding the moisturizing effect about each sugar chain compound from which the main active molecule part differs from the polymeric sugar chain compound by this invention is represented.

  The polymer sugar chain compound according to the present invention can be obtained by hydrolyzing a glycoprotein substance extracted from fish, mollusk, bird, or mammalian cartilage tissue. In the present invention, since the polymer sugar chain compound is used as a food or drink or cosmetic, the solvent used for the extraction of the glycoprotein substance avoids toxic and harmful solvents, such as water or a low concentration aqueous acetic acid solution of 6% or less. It is desirable to use

  The cartilage is added with a solvent of about 5 to 10 times (w / v) and gently extracted. The extraction temperature is preferably a low temperature of 10 ° C. or lower (preferably 5 ° C. or lower), but extraction can be performed at 10 ° C. to 50 ° C. depending on the solvent conditions. Subsequently, after filtering and removing an insoluble matter, an extract is refine | purified using a 0.1 micrometer film | membrane. When the material obtained here is treated with an alkaline solution such as 0.5 M lithium hydroxide at 4 ° C. for 1 day, an active polymer sugar chain compound is obtained. The permeating substance is purified using an ultrafiltration membrane having a molecular sieve of 100,000 to 300,000. Thereby, active polymer sugar chain compounds (1) to (3) are obtained.

  The polymer sugar chain compound serving as an active ingredient can be prepared in an optimum shape as necessary for carrying out the present invention, such as a solution (liquid), paste, powder, granule and the like.

  Specific examples of the health food or health drink and the pharmaceutical composition according to the present invention are not limited to those mainly intended to improve the musculoskeletal system, but include nutritional supplementation, nutrition tonic, fatigue recovery, constitution improvement, beauty and slimming, etc. General-purpose foods or beverages such as sprinkles, herb salt, sauces, dressings and other seasonings, jelly, gum, candy, yogurt, tablets, soft drinks, etc. , Injection drugs, medications to be taken.

  Specific examples of the cosmetic composition according to the present invention are as follows: 1) topical or systemic external pharmaceutical preparations, skin cleansers, skin cosmetics, 2) medicinal or cosmetic preparations applied to the scalp / hair, 3 ) Medicinal or cosmetic bathing agent used in bath water 4) deodorant / deodorant for human body 5) medicinal or cosmetic oral agent such as dentifrice, mouthwash, mouthwash, 6 ) It can be used by appropriately blending in skin patch sheets, cosmetic sheets, cosmetic cotton, sanitary products, sanitary cotton, wet tissue and the like. Ampules, capsules, powders, granules, solids, solutions, gels, bubbles, emulsions, sheets, mists, sprays, etc.

  Such external preparations include basic cosmetics such as creams, gels, ointments, liquid external preparations, lotions, emulsions, creams, ointments, gels, lotions, oils, packs, mists, facial cosmetic sheets, etc. , Shaving agents, facial cleansers, skin cleansers (including soaps), shampoos, rinses, hair treatments, hair styling agents, permanents, hair nickings, hair dyes, hair restorers Makeup cosmetics such as foundation, lipstick, blusher, eye shadow, eyeliner, mascara, perfume, skin deodorant, antiperspirant, bathing agent, mouthwash, toothpaste, mouth freshener, etc. .

  In addition to essential drugs, the components and additives exemplified below can be arbitrarily selected and blended in the health food or health drink, pharmaceutical composition, and cosmetic composition according to the present invention.

(1) Various fats and oils Avocado oil, almond oil, fennel oil, sesame oil, olive oil, orange oil, orange rafa oil, sesame oil, cacao oil, chamomile oil, carrot oil, cucumber oil, beef fat fatty acid, cucumber oil, safflower oil , Shea fat, liquid shea fat, soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, owl, palm Oil, beef tallow, pork tallow, squalene, squalane, pristane or hydrogenated products of these oils (hardened oil, etc.).

(2) Waxes Beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, rice wax and the like.

(3) Mineral oils Liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microcrystalline wax, etc.

(4) Fatty acids Lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid Synthetic fatty acids such as natural fatty acids such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid and isopentanoic acid.

(5) Alcohols: natural alcohols such as ethanol, isopyropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, phenoxyethanol, and synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, 2-octyldodecanol .

(6) Polyhydric alcohols Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol 1,3-butylene glycol, pentyl glycol, glycerin, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol and the like.

(7) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, Diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, and the like.

(8) Metal soaps Aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate and the like.

(9) gum, sugar or water-soluble polymer compound gum arabic, benzoin rubber, dammar gum, guaiac oil, Irish moss, karaya gum, tragacanth gum, carob gum, quinseed, agar, casein, lactose, fructose, sucrose or ester thereof, Trehalose or derivatives thereof, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan to which alkylene (C2-C4) oxide such as ethylene oxide is added, low molecular chitin Or chitosan, chitosan salt, sulfated chitin or chitosan, phosphorylated chitin or chitosan, alginic acid or salt thereof, hyaluronic acid or salt thereof, chondroitin sulfate or salt thereof, heparin, ethylcellulose, methylcellulose, carboxy Polyalkylene such as methyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyethylene oxide and polypropylene oxide Oxide or its crosslinked polymer, carboxyvinyl polymer, polyethyleneimine and the like.

(10) Surfactant Anionic surfactant (alkyl carboxylate, alkyl sulfonate, alkyl sulfate ester salt, alkyl phosphate ester salt), cationic surfactant (alkyl amine salt, alkyl quaternary ammonium salt), amphoteric Surfactant: Carboxylic acid type amphoteric surfactant (amino type, betaine type), sulfate ester type amphoteric surfactant, sulfonic acid type amphoteric surfactant, phosphate ester type amphoteric surfactant, nonionic surfactant ( Ether type nonionic surfactant, ether ester type nonionic surfactant, ester type nonionic surfactant, block polymer type nonionic surfactant, nitrogen-containing type nonionic surfactant), other surfactants ( Natural surfactants, protein hydrolyzate derivatives, polymer surfactants, surfactants containing titanium and silicon, fluorocarbons System surfactant), and the like.

(11) Various vitamins Vitamin A group: retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B group: thiamine hydrochloride, thiamine sulfate (vitamin B1), Riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, vitamin C group: vitamin C acid or derivatives thereof, vitamin D group: Ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotaxosterol, vitamin E group: vitamin E or derivatives thereof, ubiquinones, vitamin K group: phytonadione (vitamin K1), menaquinone (vitamin K2), me Dione (vitamin K3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carnitine, ferulic acid, .gamma.-oryzanol, orotic acid, vitamin P such (rutin, eriocitrin, hesperidin), vitamin U and the like.

(12) Various amino acids Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine , Arginine, ornithine, histidine and the like, and their amino acid derivatives such as sulfate, phosphate, nitrate, citrate or pyrrolidone carboxylic acid.

(13) Various additives derived from plant or animal raw materials These are processed in a conventional manner according to the type and form of the product to be added (for example, grinding, milling, washing, hydrolysis, fermentation, purification) , Compression, extraction, fractionation, filtration, drying, pulverization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc., arbitrarily selected and combined), arbitrarily selected from various materials You can use it.

  In obtaining an additive derived from a plant or animal material, the solvent used for extraction may be selected in consideration of the intended purpose, type, or subsequent processing of the product to be provided. Water, methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, isobutanol and other lower alcohols or hydrous lower alcohols, propylene glycol, 1,3-butylene glycol, glycerin and other polyhydric alcohols or hydrous polyhydric alcohols, acetone, It is desirable to use one or a mixture of two or more selected from various organic solvents such as ethyl acetate. However, when it is not preferable to contain an organic solvent depending on the application, it is sufficient to use only water or ethanol that can be easily removed after extraction, and it may be used alone or in any mixture with water. The thing extracted and extracted may be sufficient.

  When using additives derived from plant or animal-based ingredients for systemic or topical external preparations and cosmetics, it not only protects skin and hair, but also moisturizes, improves touch and texture, imparts flexibility, and reduces irritation , Aroma stress relief, cell activation (cell aging prevention), inflammation suppression, skin and hair quality improvement, rough skin prevention and improvement, hair growth, hair growth, hair loss prevention, glossiness, cleansing effect, fatigue In addition to cosmetic effects such as relaxation, blood flow promotion, and bathing effects, effects such as flavoring, deodorization, thickening, antiseptic, and buffering can also be expected.

  In foods and drinks, nutritional supplementation, fatigue recovery, tonicity, cell activation (cell aging prevention) and other healthy and cosmetic effects, as well as taste improvement, color tone, aroma, gloss, stabilization, thickening, antiseptic, etc. Can be used for the purpose. In addition to this, we expect various cosmetic and pharmaceutical effects of each of the raw materials known so far, and by combining these, we aim to enhance the target effect or to have a multifunctional effect It is also possible to make a product that expects

Specific plants (herbal medicines) as raw materials include, for example, almonds (toen), ai (indigo leaves), aokazura (Keifu Fuji), Aoki (Aoki), Aogiri or Kenashia Ogiri (Ao Tung), Aotsu Samurai (wooden candy) , Aotenma, acacia, red ginseng, red spruce `` fruit '', red clover, red grapes, red ginseng (logwood), red wrinkles (red buds), red crested or red crested or reddish (root), red crested or reddish (ground yellow), Agi (Aki), Aki larch, Akinire (crusted skin), Aguay Guassou, Aguahe (Omiten coconut palm), Akebi (Kitsu), Asa (Asakojin), Maruba morning glory or morning glory (Chicken), Hydrangea (hydrangea), Ashitaba (Tomorrow), Azuki (Red Azuki), Asunaro, Acerola, Asenyaku (Asenyaku), Athira (Shokuyokanna), Anise, Abiyu, A Biurana, oilseed rape, Abemaki `` fruit '', avocado, ama, achacha (Amacha), Achacharu, Amadokoro (Jade bamboo), Amana (a light-hearted), amaranth (Hyuyu, Hagatetou, Himogeito, Senninkoku, Sugimorigateto, Hosoaogeito, Hasoagoito Aozulan, Amaranthus hypochondriacus), Amigasayuri or Baimo (shellfish mother), Aristolomeria (Yurizuisen), Arcana (Alcanna), Algarrobo (Cabe), Altea, Arnica, Alpinia or Katsumadai (Suzukuku), Aloe (蘆薈), Aloe vera, angelica, apricot or honanzu (Anzujin), Ansokkou (benzoic incense), yellow support, igakozolina (geo-biliary head), licorice or gecko licorice (indian oyster), rush (light heart grass), itadori (tiger cane root), yew (one Place), Strawberry, fig (no flower `` fruit, leaf ''), Ichihatsu (first), Ichibi (winter lion), Ichiyakusou (one medicinal herb), ginkgo (Ginkgo `` seed, leaves ''), Japanese yellow peas (distant), carob, Japanese beetle ( Taillexi), Inubiyu (Honagainubiyu), Rice `` Seeds, Seed coat '', Inondo `` Seeds '', Ibuki-so-sou, Nettle, Ylang-ylang, Iwa-tobacco (Iwabuchi), Iwahiba or Iwamatsu (rolling mushroom), kidney beans, oolong tea, fennel (mustard) , Wheat (Chibusanoki), Ukiyara (Sanryo), Uguisukagura `` Fruit '', Himewikyo, Turmeric (Urban), Duckweed, Usubasaishin or Keirinsaishin or Oshusaishin (spicy), Usvenia Oy, Usbeni Hollyhock, phalaenopsis, weevil (summer hay), udo or shishiudo (gung, alone, tangy), unyadegato (unkari) A, Cat's Claw), Uba tea, Ume (Japanese apricot `` seed, pulp ''), Japanese white beetle, Uwaurushi (Kusako-kemomo), Unshuumika (Chen), Unboku, Estragon, Ezoukogi (Tomogoka), Ezo-suzuran, Echinashi (Hosobamurasaki Barengiku) , Enishida, Enokitake (榎 茸), Ebisugusa or Cassia Tora (Keiko), El Campre, Elderberry “fruit”, Elemi, Elingi or Pre-Lotus Elinji, Enju (Safflower, Camellia rice), Pea, Ogi or Kibanaogi (Yellow Twilight), Naruko Yuri or Kagura-mabanaru Koyuri (Yellow), Ohisasa Yuki or Sasano Yuki, Ouren (Yo Ren), Ogata Houken, Okarasuri (Karokon), Oguruma (Civil Works Incense), Otsu Samurai (Prevention), Psyllium , Car forage), toucan thistle (Zhengzhou leakage, bald eagle), toucan Mi (coconut palm), Toucan cactus, Ovana okera or okera (white moth), Osara squirrel (Banaba), Ooyabaya shabushi "fruit", Oohashigusa (cereal sperm), Omia catechu, Oomihasa or hawthorn (Mountain vegetation), Omiyashi, Omiji Barley), Oka, Okazeri (snake bed), Okra `` fruit '', Oguruma (overturn), Oguri higotai (Zhengzhou leakage, indigo head), Panax ginseng or Tochibaninjin (Ginseng), Hypericum pertussis or Pterotus pertussis or Hypericum perforatum (Brother cut grass), Odorikosou (continuous), Onamomi (Circle ear), Onigomi, Onikoro or Tokoro or Nagadokoro (Hikai), Oninoyara (Tempa), Onyuri or Sasayuri or Hakatayuri (Yuri), Onoelan, Ononis, Halibut楡), Ominae (losing sauce), Yuuko, Dutch mustard (watercress), Ora Dazelli, Dutch beech, Dutch bees, olives `` fruit, seeds, leaves '', oregano, orange `` fruits, peels '', silkworm (ripe yellow), cacao `` fruits, peels, seeds '', oysters (bamboo `` leaves ''), Kagi-Kazura (Katsufuji), Kakidooshi or Kantorisou (Lotus), Kakiran, Gaku Hydrangea, Cassia, Casinoki (fruit berries), Gadju (Kashiwa), Kashiwa (Kashiwagi, Kashiwa), Cascarilla, Cascala Sagrada, gypsophila, gypsophila, cynomolgus (Kinshato), kaniwa, carnation, valerian (valerian), hippopotamus, birch or fern birch (white birch), gerbera, pumpkin, kapokoki `` seed '', kahoku salamander (蜀椒), gama Yellow), chamomile or roman chamomile, chamomile (weed), cam cam (camo duck), collar, chrysanthemum, calla or cinnamon , Oat biscak (half summer), oats, guarana `` seed '', carahoo (kokubaku), karaya, galyu, karin (garden), garcinia, kawamidori, kawara-saiko (reeled rape, white millet), kawajisha, kawaratake, kawaranadeshiko ( (Stone bamboo) or Ezokawaranadeshiko (buckwheat noodles, buckwheat), Chinese carrot (blue potatoes), Chinese mugwort (bamboo chin mackerel), kansui (kansui), licorice (licorice), kantarasa, candelilla, kanto, canna, kanran, raspberry (ezo strawberry) , Dutch Strawberry, Shrimp Strawberry, Nawashiro Strawberry, Momiji Strawberry, European Raspberry Strawberry), Kiwi `` Fruits, Leaves '', Kikarasuuri (Gurone), Chrysanthemum (Kikyo, Kikyo-root), Chrysanthemum (Chrysanthemum, Chrysanthemum, Datura), Kikutanigiku, Kisage (Salmon), Gigigishi (sheep hooves), pheasant (salmon), Kizuta, Kidachi aloe, Kidachi mint , Quina, linden (shinkona, red linden), quinoa (quinoa), yellowfin (yellow tuna), bean, gymnema sylvester, kimenkaku, cabbage, cabbage `` unripe fruit '', caraway, cucumber, gyory (Nishikawa willow, tail willow), Kiraja saponaria, Kiraya, Kiransou (Kinza small grass), Kumquat `` fruit '', Kinkiju, Ginseikai, Kimbusen, Kinma, Kinkihiki (Sentsukusa), Kinlan, Ginlan, Ginryohen, Guapeba Vermela, Guava `` Fruit '', Guayule, Quercus・ Infectria (garlic pods), kukui nuts, kugenumaran, wolfberry (bamboo shoots, coconut palm leaves, cocoon leaves, ground bone skin), cedar casserole (Tenmon winter), kudu (kudzu), camphor tree, gooseberry `` fruit '', ginseng (yellow flower candy) ), Kutiti River, Gardenia (Yamako), Kunigi (Kusou), Kupu , Kubeba, Kumazasa, Kuma-tsutsura (horse whip grass), Clara (bitter), cranberry `` fruit '', chestnut `` seed, fruit, astringent skin '', curcumigo latifolia `` fruit '', grapefruit `` fruit and leaf '', buckthorn, kuroganemochi ( Rescue), Kamehiba Kokoshi or Kurobana Hikikoshi or Hikiokoshi (prolonging grass), Clove (clove, clove), Gumbai Tuna (Sekimei, Sekimeishi), Keigai (Kashiwa, Hakuho), Celosia (Chicken flower, Chicken crown), Gekkavidin, Gecko (Laurel Tree), Kenashi Sartoribaira (Dogo, Mountain Return), Gentiana, Gennoshouko (Old Grass), Kemponashi (Kigushi), Kokisekoku, Kishimizukan (Koji, Tachibana, Obenimikan, Fukurimikan, Sagamikouji, Ponkan, Santara Skin) ), Koshinbara (monthly flower), Koiusui mint, Kozo `` Fruit '', kocha (tea), kohone (river bone), koh hong (Tsubakimoto, Karamotomoto), Kouriang, Kouryokyo (Koryo), cilantro `` fruit '', Koouren (Huo Ren), Koganebana (Yellow Gon), cowberry (Etsu) Tachibana), Coco `` fruit '', Goshuyu (Kurei), Gosho strawberry (Golden bonsai), Pepper (Pepper), Cosmos, Copaiba balsam, Coffee `` Seeds, leaves '', Kobushi or magnolia (hot pepper), Burdock (Beef bowl, Gyudon) ), Coconut lees, sesame (sesame seeds), sesame seeds (genus ginseng), trash (goji), saneka or binankazura or pine bush, wheat (wheat), rice or rice bran `` red potato, white birch '', rice oil, cola acminata `` seed '' , Cola Bella "Seeds", Colony Lilla, Koroha "Fruits", Colombo, Conzurango, Kombu, Konjac, Comfrey (Chang Zhang grass), Sisal (Sisal Asa), Cy Hailan Sakaneran (Ezosakaneran), Sasima button eel or Sina button eel or Cinnamon ginseng (weikensen), Sakura (Ooshima cherry, Yamazakura, Oyamazakura, Edhigashi, Mamezakura, Miyazakura, Someiyoshino, Takanezakura, Kasamikan, Sakura, Sakura, Sakura Fruit, bark (cherry bark) ''), cherry, pomegranate, sasa, sababagin orchid, sasanqua, sardine sardine (salmon), sweet potato, sugar cane, sugar beet, sunflower jujube (saccharin), saffron (bancho flower, west safflower), sapodilla, sapotea mariyo , Pomelo `` fruit '', savonso, salmon berry `` fruit '', salamander (sasma), salamander (sand indigo sashimi), salvia (sage), scallops (bamboo rape), sawagurumi (wild walnuts), sankaku cactus, sangre Degrad ( Loton), Salamander, Sansino Ginseng (37 ginseng), Sanshuyu (Yamamuro), Sansho (Yamamuro), Sandskon (Yamazune), Shea (Kalite), Cyano `` fruit '', Shiitake mushroom (Shitake), Sion (Purple spider), winged bean, jikitarisu, shikunshi (messenger), perilla or ajizo or chimmentiso or catamenzo (purple leaf, shisoko), rosewood, linden tree, red-faced syringae, renilla (ream), shimeji (hinshimeji, shakashimeji, hatake-shimeji Shimeji, beech shimeji, honjimeshi, shirotamogitake, shimokren (hot pepper), shimotsuso, potato, shajin (shasan), jasmine (matsurika), janohi (barley winter), jury scorpion, shrimp swordfish, sand , Shredded sand), juzudama, palm "fruit", shung lan, jujuu palm, show (Ginger), Zodiac hydrangea (Tsuneyama), Shobu (bamboo shoot, Sone), Shozu `` fruit '', Shirakashi `` Seeds '', Silane (Bikkyu), Shirogori `` Seeds '', White clover (Clover), White clover (chicken bone grass) , White squirrels (smoke squirrels), Shirobanatsuta "flowers", Shirobana Lupine, Shirominanten (southern Tenmi), Cinconacylbra, Ginkgo biloba (Mizuka, Suzuka, Senncho), Cinnamon, Cinnamomum cassia (Kaishin), Suika , Honeysuckle (gold and silver flowers, Shinobu winter), sorrel (acid model), swim berry `` fruit '', star apple, stevia, strawberry `` fruit '', succulent (Xu Longan), sugina (question), purslane (horse tooth soap, horse tooth soap Child), plum "fruit", sulgaran (oran), Japanese red pine "ball cone", Japanese larch, Japanese kizuta, Japanese seiyo Walnut, hawthorn, cypress, dandelion, horse chestnut (maronier), pear `` fruit '', sunflower, elder, scallop (juniper, pine), yarrow (milfoil), rose, antelope Japanese butterfly, Japanese mistletoe, American mint or Atlantic mint Sarcophagus), cedron (Boushuboku), mallow, hirohasenega, senega, seri, celery, nematode (river cucumber), senshinren (pure ream), sendan, sennin cactus, Nanna `` fruit, leaf '', ginseng (daikon), sea bream (medicated), senboku, soka (grass), elephant chrysanthemum, prawns, buckwheat `` seed '', potato monogram, broad bean, daiou (daihuang), radish, soybean, daidai (Orange peel, fruit), Takasago Gurihigotai (Southeast Indigo Sashimi), Takasaburo (Cirrus Lotus), Takatodai (Oyodo), Takarabi (Cirrus spine), Dark Sweet Cherry `` Fruit '', Japanese hollyhock, Tachikoso (Time, Hundred incense), Tachidokoro (Hikai), Tachiyanagi, Tamarind `` Seeds '', Onion, Tamshiba (hot pepper), Taranoki `` Fruits, leaves, root bark '', Tarayo (Large winter blue, Ichiha tea, bitter tea, bitter tea), Dahlia (Tenjiku button), Tarwi, Tankimi, Tanshiwiwa, Tanjin (Tanjin), Dandelion (Shinko), Shirobana Dandelion or Mouko Dandelion, Danmaru, Cherry , Imperata "fruit, roots, buds", the district Seth carrot (Takefushi carrots), chicory, chunker Piedra
(Kidachi Kumiso), Tulip, Chono Stay, Datura Thistle (Artichoke), Datura (Dark Yellow), Datura (Amber), Datura Worm, Choreimaitake (Amber), Chorogi, Azalea, Azalea, Tsukuritake (mushrooms), Tsuchiakebi, camellia, camellia, clover (lacquered grass), camellia (duck-weed), Tsuruzuki (red bean), Tsurutsukikibi, Tsurudokudami (what neck rice cake), Tsuruna (Apricot apricot), Tsuruninjin (four leaf ginseng), Tsuruma, Tsuwabuki, Deiko, Teuchigurumi, Duberry `` Fruit '', Tengusa, Tencha (bamboo tea), Tendai-yaku (glaze), Toga (winter coconut), Tokagi quail, Capsicum (banban), Toki (toll), Tokinsenka (Tokinsenka) Marigold), red croaker, touna bena (river cut), corn or corn hair (Southern lashes), horned potato (Sadako), Torindo or Ginseng (Dragon gall), Tokusa (wood band), Dokudami (10 medicines), Tokushi (Nippaku), Toshishi or Mamedaoshi or Nekazura, Tochu (bark, bark, Leaves, roots ''), ash (crusts), tomatoes, tragacanth, triacanthos `` seed '', Turkish almonds, tormentilla, dronoki, troro mallow, tonka bean, nigerian berries `` fruit '', Chinese yam or wild yam (wild boar), nagii kada (butcher bloom) ), Naginata Koju, Nazuna, Rapeseed, Natsume or Vertical Spider (Sword Bean), Natsumikan, Jujube (Otsugi), Naniwaibara (Golden Cherry), Navena (Suspended), Nameko, Nankin Bean (Peanut), Nanten (Southern Fruit), Namban Karamushi (Sesame), Niosumire, Nigaki (Nakiki), Nigamugi (Sweetness), Nikuzuku, Kei or Nikkei or Seika Ronnikei or Yabunikei (Cinnamon) or Keishi (Keishi branch), Flying tiger plover, leek (lion), elderberry (bone, `` fruit, flower, stem, leaf ''), garlic (large persimmon), Nurde (penta), leek, nemonoki Or Nebu or Nebi or Nemurino or Digokubana (community), Noazami (Daisetsu), Nobara (fruit), Nozenkazura (Lingen flower), Nogateto, Yarrow, Nodake (former cucumber), Novara, Peach, Pineapple `` fruit '', Hibiscus (Busouge) , Fulinbussouge, Roselle), Hailindo, Hauchiwa, Pau Dorse, Hakama Labosi (osteostomy), Hakukayumatou, Chinese cabbage, Chinese cabbage (white tinea), Hakulberry `` fruit '', Japanese crocodile (breeding), Habami (coconut), Hasidorokoro (Roof root), basil, lotus (lotus, lotus meat, lotus), parsley (holland jellies), hadakamugi, batata, bee or maize Ke (bamboo shoots), patchouli, mint (thin-load, thin-leaves), yellow peas, pearl barley (Yokuinin), Hanasuge (my mother), bananas, hanahakka, Hanabishi (Sitoshiri, Shitsutsuri), vanilla bins, papaya, scallop , Pahalobobo, hub `` whole grass, stem, leaf '', paprika, oysters, hamago or honey bee (Vulgaris), hamasge (Katsukiko), Hamabishi (Shitsuko), Hamanasu (Maikai flower), hamabofu (hamafufu), Hamamelis, palm, rose (rose), balata, balata rubber tree, agaric (agaric, white-faced agaric, quince) (Skin, maple leaves), Barbasco, Harlindow, Handaikai (Taiho Sea), breadfruit, hinoki Sea urchin (hiboshi), lizard carrot (participant), pecan nuts, ganbanana (stone urchin, vine pearl shahua), higurmadaria, higotai, hishi (hishimi), pistachio, beet, human lizard (hisarium), human winged fern, daisies (Daisy), Hinata Taikozuchi (cow knee), chickweed, cypress, hiba, castor, sunflower, bell pepper, Himezu (Tengu), Himamatsu (Kaori), Himematsutake (Kawariharatake, Hiromatsutake), Himemuyoran, Pimenta `` fruit '', Beakshi, beakkyu, jade "fruit", chickpea, lentil, bellowed oyster, hirohaokinagusa (bald eagle), loquat "fruit, leaf, stem", betel nut (large clothes skin, coconut), puer tea (common tea), sweet pod (Southern rattan), Japanese cypress, Japanese cypress poppo (Japanese winter flower, Japanese winter leaf), Fujibakama (Orchid), Japanese bean (Japanese peas), Japanese red bean (Chujizakura, strawberry) ), Grapes `` fruit, pericarp, seeds, leaves '', beech, Fuyumushinatsusatake (Cycium Cordyceps), Brazilian licorice, Brazilian carrot, Brazilian palm, Brazilian elephant coconut, black currant `` fruit '', blackberry, Branjen, plum `` Fruit '', Fruceraria, Blueberry (Prunus serrata), Prunes, Floral Blanca, Blond Psyllium, Bundow (Mung Bean), Hazelnut, Loofah, Hetsukaran, Safflower (Safflower), Heneken, Belladonna, Berry `` Fruits '', Percea, Pervianberg , Pereschia grandifolia, red beetle or squirrel (scenic sky), boysenberry `` fruit '', scallop or narcissus or nendo or hahagigi kokia (silk), horsiran, scallop (saccharus, acute pupa, pelagic grass), pouteria・ Supporters, Po Terrier Lucuma, Spinach, Bow Fu (Windproof), Spinach, Japanese physalis (Torune), Japanese cypress (Japanese folk magnolia, Park), Bokeh (Kiso), Hosoba-Aragiku (Kayoyoku), Hosoba-oguruma, Hosobanaokera (Samurai), Hosobakirinso (Keitenzochi), Hosobabarengiku, Bodaiju (bamboo tree), button (peony `` flowers, leaves, stems, bark ''), button pi (peony skin), hop, jojoba, borage (Lurichisha), Bordeaux, howtle berry `` `` Fruit '', Hononiku (meat jutsu, large art), Honsecek (iron skin stone shark, sparrow mountain stone shark), myzurutennansho (Tennan star), Maitake (maiko), maou (mao), maca, macadamia nut, margaret (mok) (Shungiku), Makri (marine grass), Magwa (mulberry bark `` bark, leaf ''), Magnolia splengeri, Mazaran euba, Masalanzuba de Searer, Masheira de Boi Mashua (Tamanowenhalen, Kyukonkinrenka), Matatabi (wood tengu), Matsukasa, pine `` leaves, bark, root '', Matta Orillo, Matsuhodo (茯苓), Matico (Cordon sillo), Mayoram (Hanahakka), Malvano jardin (Bitter), Mulberry `` Fruit '', Quince, Malene (Biloud Mouse Squid), Mango, Mangosteen, Manzanya (Andesuka Mitsuru), Manshugurumi, Mandarin `` Fruit '', Mannentake (Ganoderma biloba), Pheasant (fruit berry `` Fruit '') , Mishimasaiko (Saihu), Mizusobako or Mizuasagao (Dongweed), Mizokakushi (Half-sided lotus), Misohagi (Chinese green), Japanese willow or Japanese willow (Henpo), Mitsugasiwa, Mitsuba, Midorisapote, Mirimaza, Mimosa, Myoga, Miracle fruit “fruit”, myrrh, mirobalan, wheat straw, mugweed (mushroom), muk Japanese cypress, mugwort (life-prolonging skin), munya, purple (purple), purple or yellow purple corn, purple corn, purple corn (Kunming chicken blood), megakansa opuntika, pheasant (maranthus), mebougi, melaroika, Melissa, Melilot, Melon `` Fruit '', Moukomomogi, Mosouchiku, Mokkirin, Mogi (Pepper), Mochinoki, Mokko (woody incense), Momijidaio, Peach (peach `` leaves, seeds, flowers, fruit ''), coconut, Morello Cherry `` fruit '', Morohaya (burlap), Yakawamura potato, Yakuchi (Michichi), cornflower (cornflower), cornflower mint, yacon, Yashabushi (Yagari) or Himeyashabushi `` Fruit, pericarp, fruit ear '', Yachiyanagi, Millet (octagonal gold plate), mistletoe (willow infestation), willow (kawayanagi, tachiyana) , Weeping willow, red willow, cat willow, dog willow, gold willow, koryanagi, unryu willow, miyagi willow, palm, willow, beech, goldfish, beef, stalk (Crane, Tenmeisei), pokeweed (commercial land), Japanese alder (Yamamuro), Japanese yam (Plum skin), Japanese mugwort, eucalyptus, Yukinoshita (tiger ear grass), yucca or flevifolia, yuzu `` fruit '', lily, yorogusa, Mugwort (Leaf), Ligan (Raimaru), Lime `` fruit '', Rye, Lacanca `` Fruit '', Raspberry `` Leaf, fruit '', Latania (Klamelia), Lackey or Shallot (Lady), Lavender, Longan (long-eyed meat), Agave (Aono Agave, Fuclin Agave) Ryokucha (green tea), apple `` fruits, seeds, leaves, roots '', gentian, lubas or suabishimusu (Suzu Ryo), Ruritama thistle (bladder tiger tai, Xinjiang indigo sashimi), litchi (toothpick, toothpick core), lettuce (chisha) , Red currant `` fruit '', red pitaya, lemon `` fruit '', lemongrass, forsythia or Chinese forsythia (ream), forsythia, wintersweet, wax palm, locon (reed, root), loganberry `` fruit '', rose Examples thereof include marie (mannenrou), rose hips (nobara), wasabi, cotton wisteria (Ming Mongolia), and bituminous (ground).

  As seaweeds, seaweed [Green algae: Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoidia, Aonori (Usba aonori, Sugiaonori, Hiraaoori, Boaonori, Hosoeda Aonori), Anaaoosa (Aosa)] (Macombu, Resilibu, Hosocome, Mitsuishi Kombu), Wakame, Hirome, Aowakame, Giant Kelp (Macrocystis Integrifolia, Neocitus Ruetkeana), Hijiki, Hibamata, Umiuchiwa, Usubaumiuchiwa Umiuchiwa, Akaba Umiuchiwa, Konami Uchiwa, Okinawa Uchiwa, Usuki Uchiwa, Etsumi Uchiwa], seaweed [Red algae: Hijirimen, Maca (Tengusa), Hiraksa, Syria, Oaxa Caterpillar, Yatabegusa, Yuukiri, Shimatengusa, Tosakanori, Togekirinsai, Amakusakirinsai, Giraffe, Juniper ginkgo rhinoceros, Tsunomata, Totsuka (Yahazutsu notamata), Ezotsunotamata, Togetu no Takita , Yaleus banori, Kagius banori, Susius banori, Haius banori, Akamo mizunori] and the like.

  Other algae, for example, green algae (Chlamydomonas: Chlamydomonas, Akayukimo, Dunaliella: Dunaliella, Chlorococcus: Chlorococcus, Kuwanomimo: Kuwanomimo, Volbox: Dandelion, Volbox, Palmera, Yotsumeo, Himidori Aoumiduro, Tsurugidomiro, Hibidoro: Hibidoro, Aosa: Anaaaosa, Amiaosa, Nagaaosa, Kawanori: Kawanori, Friccella, Shiogusa : Magatama, Dioscorea: Pheasantata, Surichogita, Heraiwata, Kurokita, Hanemo, Genus: Mill, Chromel, Sakibutimil, Nagamil, Hiramil Casanori: Casanori, Jusmo: Jujusmo, Tamajusmo, Mizojusmo, Mika ヅ kimo, Korekaete, Tsutsumimo, Kikkogusa, Humanexa : Sumiremo, Hosimidro, Fuchinashimidro etc.).

  Cyanobacteria (Suizenjinori: Suizinori, Aoko, Nenju: Kawatake, Ishijelly, Hassai, Yuremo, Rasenmo (Spirulina): Spirulina, Trichodesmium (Iaciasio), etc.

  Brown alga Sanadagusa: Sanadagusa, Fukurimamiji, Commongusa: Commongusa, Yahazugusa: Ezoyahaz, Yahazugusa, Uraboshiyahaz, Jigamusa: Jigmygusa, Umichiwagusa, Umamisakugakua, Hakusou : Navarimo, Chasomen genus: Motsuki Chasomen, Matsumo genus: Matsumo, Nagamatsumo genus: Nagamatsumo, Okinawa mozuku: Okinawa mozuku, fake Tomozuku: Niseft Mozuku, Futomozuku: Futomozuku, Ishimozuku: Ishimozuku, Kuromo: Kuromo, Nisemozuku: Nisemozuku, Mozuku: Mozuku, Ishige: Ishige, Iroro, Ichimegasa: Ichimegasa Umibosu, Urushigusu: Urushigusa, Keurushigusa, Tobaccogusa, Composita: Composita, Haberodomo: Haberodoki, Havanori: Habanori, Habanori: Habanori, Commonbukuro, Ezobukuro, Ezobukuro Chishima fukuronori genus: Chishima fukuronori, Kagomenori genus: Kagomenori, Muraridori genus: Murachidori, shark genus: shark zusa, genus genus: lobster, genus genus: yokojimamanori, Ganoderma genus: cynomolgus, fennel spider: fennel spider, vine genus: turmo, turtle genus: sea turtle, scorpion genus: sujime, misji kumbu genus: misji kumbu, atsuba misji kumbu, kumbu genus: tsutsugara kumbu, oyster kumbu, onikombu, gakonbubu Barracuda, Trollocombu: Trollocombu, Antokume: Antokume, Kajime: Kajime, Tsuruarame, Kurome, Kikuishikombu: Kikuishicombu, Nejikcombu: Nejicombu, Kuroshiome: Kuroshiome, Nekoshikonbu, Aramei Genus: Ainuwakame, Chigaiso, Oniwakame Ezoi Shige: Ezoi Shige, Yabane Moku: Yabane Moku, Rappa Moku: Rappa Moku, Joromoku: Ugano Moku, Jo Lomoku, Hiemoku, Honda Walla: Tamanashimoku, Isomoku, Nagashimamoku, Akamoku, Shidamoku, Honda Walla, Nejimoku, Narasamo, Mametawala, Tatsukuri, Yatsumata Moku, Umitora no Moku, Fushishimoku, Mohmokumoku, Hahamokumoku , Ukimo: Ouokimo, Burukimo: Burukimo, Kayamonori: Kayamonori, etc.).

  Red algae Genus: Sea urchins, Tsukumonori, Anemone crickets, Astragalus, Amaranthus, Amaranthus, Agaricata Genus: Tamaitadaki, Kaikekenori Genus: Kaginori, Kaikekenori, Tengusa: Himetengususa, Hytengususa, Oobusa, Nambugu , Kohira, Yohira, Kinukusa, Hibirodo: Hibirodo, Himebiro, Isomumedo: Isommedo, Aedes: Rhizome, Ryumons: Ryumon, Ranunculaceae, Nisekare Naminohana: Hosobanaminohana, Naminohana, Sangomodoki: Ragaramomodoki, Shiogusagoromo: Shiogusagoromo, Iwanokawa: Etsukiiwanawa, Kinokawa: Kinokawa, Kanonote, Sangori Kyono Shiro, Sakuranori, Nikumukade, Tambanori, Tsurutsuru, Fudarak, Marubahdarak, Isonohana: Nurakusa, Ronulaksa, Oomkadenori, Hirakintoki: Hirakintoki, Matabou: Matabou, Kintoki: Chabokintoki, Kintoki, Matsunori, Rice, Tokamatsu, Hitomatsu, Fushikintoki, Tsunomude, Nagakinito, Crayfish Nagaobane: Naganobane, Funori genus: Hanafonori, Fukurofunori, Mafunori, Karekigusa: Karekigusa, Tosakamodoki: Hosobanatosakamodoki, Hironotosakamodoki, Yatsudegatatosakamodoki, Kurotosakamodokisane, Zotosofomoza Tosakamodoki, Nankaitosakamodoki, Himetosakamodoki, Kinuhada: Kinuhada, Ezotosaka: Ezotosaka, Tsukasanori: Enashikarimenia, Otsukasanori, Hana Tacarimenia, Hoonoo: Honoo, Hikagenoit: Hikagenoit, Usuginu, Nikuhounoo: Nikuhounoo, Venus nago, Venus nago, Susca veni: Suscabeni, Okarugusa: Yamadagusa, Mirin: Mirin, Hosokamiso , Isomocca genus: Isomocca, Yukari genus: Yukari, Hosoyukari, Ibaranori genus: Ibaranori, Saidaibara, Tachiibara, Kagibaranori, Kojinoo: Kizino-o, Isodantsu: Isodantsu, Atsubanori: Atsubanori, Ogonori, Ogonori, Ogori Mizo-okonori, birch, beniogonori, fukureshinori, purple birch, shinkaibanori, spruce birch, kataogonori, ryukyuogono Li, Atlantic scorpion, Ivy genus, Yumigataonori, Kubireogonori, Mosagogonori, Kinubanori, Amanita genus: Hachijotensamodoki, Fushikenori genus: Fushikenori, Namiiwatake, Nymphalanthus Itagususa, Saimi, Hari, Lotus Jigusa: Lotus Jigusa, Sugi nori: Ikanoashi, Hosoibonori, Nobonori, Black Haginansou Genus: gourd, cherries, octopus: octopus, sedge, genus: genus, genus: goat, dals : Dulse, Scorpionus, Anadalus, Weibusa: Uebusca, Benifronori: Benifuronori, Fusunagi: Futsutsunagi, Himefusunagi, Hirohafushitsugi, Otsunagisou, Hirawatagigi, Usuwasugi , Egonori: Egonori, Futogigi, Saeda: Saeda, Chirimomiji: Chirimomiji, Konohori family: Habutaenori, Konohori, Suzuronori, Usubeni: Genus: Kagios banori, Yareus banori, Susius banori, Heius banori, Usubanorimodoki: Usubanorimodoki, Ayanishiki genus: Ayani Genus: Aeginu, Dadia: Enasidadia, Shimadadia: Isohagi, Shimadadia, Dajimodoki: Dajimodoki, Euglena: Morayogusa, Fuyugusa, Makuri: Makri, Yanaginogi, Yuna, Yukinagina , Sasabayanaginori, Sozo genus: Kurosozo, Kobsozo, Hanesozo, Sozonohana, Hanegusa genus: Hananegusa, Hananegusa, Kozanemo genus: Kozanemo, Isomurasaki, Hosozozanemo, Himegoshigusu, Giant genus Isomagusa, Suginasugusa: Suginasusa, Isobashou: Isobasho, Fujimatsumo: Fujimatsumo, Sawweed: Haeshinosakiba, Kawamoku : Kawamoke, Aokawa Mozuku, Himekawa Mozuku, Ideyugogome: Ideyugogome, Okichimozuku: Ochimodoku, Otosa, Chinorimo: Chinomo, Chisujinori, Chisujinori, etc.).

  Axial algae (Shajikumo, Shiratamamo, Hoshitsurimo: Hoshitsurimo, Rikunotumusu, Flaskmo: Himebumo, Chaboflasmo, Tripera, etc.), yellow algae (Hikarimo: Hikarimo, etc.), etc.

  Animal-derived materials include chicken crown extract, cow or pig, human placenta extract, cow or pig stomach, duodenum, intestine, spleen extract or degradation product thereof, cow or pig brain tissue extraction Collagen hydrolysates (acids, alkalis, enzymes, etc.) of products, cattle / pigs or fish, collagen derivatives such as water-soluble collagens or acylated collagens, elastin or elastin hydrolysates of cattle or pigs (acids, alkalis, enzymes, etc.) ) Or water-soluble elastin derivative, keratin and its degradation product or their derivatives, silk protein and its degradation product or their derivatives, pig or cow blood cell protein degradation product (globin peptide), cow or pig hemoglobin degradation product (hemin) Hematin, heme, protoheme, heme iron, etc.), milk, casein and degradation products thereof or derivatives thereof, skim milk powder and degradation products thereof or derivatives thereof Lactoferrin or decomposed product thereof, egg ingredients, fish hydrolyzate, nucleic acid-related substance (ribonucleic acid, deoxyribonucleic acid), or the like.

  As a material derived from these plant or animal-based materials, any site, cell, tissue, organ, metabolite, etc. derived from a gene recombinant or a cell fusion can also be used. Furthermore, for example, an undifferentiated cell group, a cell group in the middle of differentiation, or the like obtained by culturing an arbitrary site, cell, tissue, organ or the like can also be used.

(14) Marine components Seawater such as deep seawater, for example, sea salt, dried seawater, inorganic salt (sodium chloride, magnesium chloride, potassium chloride, etc.), sea mud or mud (from the Dead Sea or Atlantic Ocean) Fango), for example, Italian mud, German fungo, Eifelfango, Freiburg fungo, etc. Sea mud or mud from various locations (containing components: silicon dioxide, titanium dioxide, aluminum oxide, iron oxide, manganese oxide, sodium oxide, potassium oxide, Magnesium oxide, calcium oxide, strontium oxide, sodium, potassium, magnesium, calcium, chromium, iron, copper, nickel, zinc, lead, manganese, arsenic, water), saintoku stone, etc.

(15) Microbial culture metabolite Yeast metabolite, yeast extract, bacterial metabolite, bacterial extract, mold or actinomycete metabolite, mold or actinomycete extract, natto metabolite, natto extract, rice fermentation extract , Fermented rice bran (red rice bran, white birch) extract, Euglena extract or decomposition product thereof or water-soluble derivative thereof, trehalose or derivative thereof, lactic acid fermentation product of raw milk or skim milk powder, fermented lactic acid bacteria of legumes, coconut plant Lactic acid bacteria fermented products.

(16) α-hydroxy acids Glycolic acid, citric acid, malic acid, tartaric acid, lactic acid and the like.

(17) Inorganic pigments Silicic anhydride, magnesium silicate, talc, kaolin, bentonite, mica, titanium mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide, Bengala, black iron oxide, gunjo, chromium oxide, chromium hydroxide, carbon black, calamine, etc.

(18) UV absorber / blocker benzophenone derivatives (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, dihydroxy Dimethoxybenzophenone, dihydroxydimethoxybenzophenone-sodium sulfonate, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, etc.), paraaminobenzoic acid derivatives (paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, Octyl paradimethylaminobenzoate), methoxycinnamate derivatives (ethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2-ethoxycinnamic acid cinnamate) Til, sodium paramethoxycinnamate, potassium paramethoxycinnamate, diparamethoxycinnamate mono-2-ethylhexanoate glyceryl, etc.), salicylic acid derivatives (octyl salicylate, phenyl salicylate, homomenthyl salicylate, dipropylene glycol salicylate, ethylene glycol salicylate, myristyl salicylate, Methyl salicylate, etc.), anthranilic acid derivatives (methyl anthranilate, etc.), urocanic acid derivatives (urocanic acid, ethyl urocanate, etc.), coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives , Camphor derivative, furan derivative, pyrone derivative, nucleic acid derivative, allantoin derivative, nicotinic acid derivative, vitamin B6 derivative Body, umbelliferone, esculin, benzyl cinnamate, sinoxate, oxybenzone, dioxybenzone, octabenzone, thrisobenzone, benzoresorcinol, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, neoheliopan, escalol, zinc oxide, talc, kaolin etc.

(19) Whitening agent Paraaminobenzoic acid derivative, salicylic acid derivative, anthranilic acid derivative, coumarin derivative, amino acid compound, benzotriazole derivative, tetrazole derivative, imidazoline derivative, pyrimidine derivative, dioxane derivative, camphor derivative, furan derivative, pyrone derivative, Nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin C or derivatives thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), vitamin E or derivatives thereof, kojic acid or derivatives thereof, oxybenzone, benzophenone, arbutin, guaiazulene, Shikonin, baicalin, baicalein, berberine, placenta extract, ellagic acid, lucinol, etc.

(20) Tyrosinase activity inhibitor Vitamin C or a derivative thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), hydroquinone or a derivative thereof (hydroquinone benzyl ether, etc.), kojic acid or a derivative thereof, vitamin E or a derivative thereof, N-acetyltyrosine or derivatives thereof, glutathione, hydrogen peroxide, zinc peroxide, placenta extract, ellagic acid, arbutin, lucinol, silk extract, plant extract (camille, mulberry, gardenia, pearl oyster, clam, clam, mugwort, honeysuckle) , Kihada, dokudami, matsuhod, pearl barley, mussel, hops, hawthorn, eucalyptus, yarrow, altea, keihi, mankaishi, hamamelis, yamagwa, lifelong grass, bellflower, toshishi, zetsugo, gyu, mao, senkyu, dod Tsu, Psycho, storm, littoralis, Scutellaria, peony bark, cranesbill, kudzu root, licorice, Fushi aloe, Cimicifuga, safflower, green tea, black tea, Ali elixir), and the like.

(21) Melanin pigment reduction / decomposition substance Phenylmercury hexachlorophene, mercuric oxide, mercuric chloride, hydrogen peroxide, zinc peroxide, hydroquinone or its derivative (hydroquinone benzyl ether).

(22) Turnover promoting action / cell activator hydroquinone, lactic acid bacteria extract, placenta extract, ganoderma extract, vitamin A, vitamin E, allantoin, spleen extract, thymus extract, yeast extract, fermented milk extract, plant extract (aloe, Ogon, Japanese horsetail, Gentian, Burdock, Shikon, Carrot, Camelis, Hop, Yokuinin, Odori, Semburi, Japanese cypress, Japanese red snapper, Achacha, Hypericum, Cucumber, Necklace, Rosemary, Parsley).

(23) Astringents Succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc paraphenolsulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannic acid (including catechin compounds) and the like.

(24) Active oxygen scavenger SOD, catalase, glutathione peroxidase and the like.

(25) Antioxidant Vitamin C or a derivative thereof or a salt thereof, stearic acid ester, vitamin E or a derivative thereof, nordihydrogua cetelenic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol , Parahydroxyanisole, propyl gallate, sesamol, sesamorin, gossypol, propolis, etc.

(26) Lipid peroxide production inhibitor β-carotene, plant extract (sesame culture cell, hamcha, hypericum, hamamelis, clove, melissa, birch, birch, salvia, rosemary, minamitenji, jitsu, ginkgo, green tea).

(27) Anti-inflammatory agent Ictamol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid or its Salt, glycyrrhetinic acid or a salt thereof, licorice extract, sicon extract, age extract, propolis, etc.

(28) Antibacterial / bactericidal / disinfectant Acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or hydrolyzate thereof, alkyldiaminoethylglycine chloride solution, triclosan, sodium hypochlorite, chloramine T, Sarashi powder, iodine compound, iodoform, sorbic acid or its salt, propionic acid or its salt, salicylic acid, dehydroacetic acid, parahydroxybenzoic acid esters, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p -Chlorophenol, p-chloro-m-xylenol, p-chloro-m-cresol, thymol, phenethyl alcohol, O-phenylphenol, Irgasan CH3565, halocarban, hexachlorophene, chlorohexidine, ester Tanol, methanol, isopropyl alcohol, benzyl alcohol, ethylene glycol, propylene glycol, 2-phenoxyethanol, 1,2-pentanediol, zinc pyridione, chlorobutanol, isopropylmethylphenol, nonionic surfactant (polyoxyethylene lauryl ether, Polyoxyethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, etc.), amphoteric surfactant, anionic surfactant (sodium lauryl sulfate, lauroyl sarcosine potassium, etc.), cationic surfactant (cetyltrimethylammonium bromide, benzalkco chloride) Nium, benzethonium chloride, methyl rosaniline chloride), formaldehyde, hexamine, brilliant green, malachite green, crystal bio Tsu DOO, Jamaru photosensitive No. 101-containing, photosensitizer No. 201, photosensitizer No. 401, N- long chain acyl basic amino acid derivative and its acid shark salts, zinc oxide, hinokitiol, Sophora root, propolis, and the like.

(29) Moisturizer Glycerin, propylene glycol, 1,3-butylene glycol, hyaluronic acid or its salt, polyethylene glycol, chondroitin sulfate or its salt, water-soluble chitin or its derivative or chitosan derivative, pyrrolidone carboxylic acid or its salt, lactic acid Sodium, mini Sasanishiki extract, natto metabolite, natto extract, loofah water, birch (white birch) or red pine sap

(30) Elastase activity inhibitor diisopropyl fluorophosphate, plant extract (eg, gongoid, hypericum, clara, mulberry leaves, keihi, genokosho, comfrey, salvia, elderberry, bodaiju, button pie), seaweed extract and the like.

(31) Hair preparations Selenium disulfide, alkylisoquinolinium bromide solution, zinc pyrithione, biphenamine, thianthol, castari tincture, pepper tincture, pepper tincture, quinine hydrochloride, strong ammonia water, potassium bromate, sodium bromate, thio Glycolic acid and the like.

(32) Antiandrogens Follicular hormones (estrone, estradiol, ethinyl estradiol, etc.), isoflavones, oxendrone, etc.

(33) Peripheral vascular blood flow promoter Vitamin E or derivatives thereof, assembly extract, garlic extract, carrot extract, aloe extract, gentian extract, toki extract, cephalanthin, carpronium chloride, minoxidil and the like.

(34) Stimulants Pepper tincture, nonyl acid vanillamide, cantalis tincture, ginger tincture, peppermint oil, l-menthol, camphor, benzyl nicotinate and the like.

(35) Metabolic activator Photosensitive element 301, hinokitiol, pantothenic acid or derivatives thereof, allantoin, placenta extract, biotin, pentadecanoic acid glyceride and the like.

(36) Antiseborrheic agent Pyridoxine or a derivative thereof, sulfur, vitamin B6 and the like.

(37) Keratolytic agent Resorcin, salicylic acid, lactic acid, urea and the like.

(38) Oxidizing agent Hydrogen peroxide water, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium tripolyphosphate, sodium bromate, potassium bromate, sodium pyrophosphate, Sodium orthophosphate, sodium silicate hydrogen peroxide adduct, sodium sulfate hydrogen peroxide adduct, sodium chloride hydrogen peroxide adduct, β-tyrosinase enzyme solution, mushroom extract, etc.

(39) Hair remover Inorganic reducing agents such as strontium sulfate, sodium sulfide, barium sulfide, calcium sulfide, thioglycolic acid or its salts (calcium thioglycolate, sodium thioglycolate, lithium thioglycolate, magnesium thioglycolate) Strontium thioglycolate) and the like.

(40) Hair swelling agents such as ethanolamine, urea and guanidine.

(41) Dye agent
5-aminoorthocresol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, 3,3'-iminodiphenol, 2,4-diaminophenoxyethanol hydrochloride 2,4-diaminophenol hydrochloride, toluene-2,5-diamine hydrochloride, nitroparaphenylenediamine hydrochloride, paraphenylenediamine hydrochloride, N-phenylparaphenylenediamine hydrochloride, metaphenylenediamine hydrochloride, orthoaminophenol, N-phenyl acetate Paraphenylenediamine, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, toluene-2,5-diamine, toluene-3,4-diamine, nitroparaphenylenediamine, paraaminophenol, para Nitroorthophenylenediamine, paraphenylenediamine, paramethylamino Phenol, picramic acid, sodium picramate, N, N'-bis (4-aminophenyl) -2,5-diamino-1,4-quinonediimine, 5- (2-hydroxyethylamino) -2-methylphenol, N -Phenylparaphenylenediamine, metaaminophenol, metaphenylenediamine, 5-aminoorthocresol sulfate, 2-amino-5-nitrophenol sulfate, orthoaminophenol sulfate, orthochloroparaphenylenediamine sulfate, 4,4'-diamino sulfate Diphenylamine, 2,4-diaminophenol sulfate, toluene-2,5-diamine sulfate, nitroparaphenylenediamine sulfate, paraaminophenol sulfate, paranitroorthophenylenediamine sulfate, paranitrometaphenylenediamine sulfate, paraphenylenediamine sulfate, parasulfate sulfate Methylaminophenol, metaaminosulfate Diol, metaphenylenediamine sulfate, catechol, diphenylamine, α-naphthol, hydroquinone, pyrogallol, phloroglucin, gallic acid, resorcin, tannic acid, 2-hydroxy-5-nitro-2 ', 4'-diaminoazobenzene-5'-sulfone Sodium acid, hematein, etc.

(42) Fragrance Natural animal fragrance such as musk, civet, castorium, ambergris, anise essential oil, angelica essential oil, ylang ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guayakwood essential oil, Cumin essential oil, black letter essential oil, cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriandel essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil, Otsuka perfume essential oil, tuberose essential oil, clove essential oil, orange flower essential oil, winter green essential oil, trout balsam essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, persimmon essential oil, hiba essential oil, sandalwood essential oil, petit gren essential oil, bay essential oil, vetiva essential oil, bergamot Spirit , Peru balsam essential oil, boad rose essential oil, melamine essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lavender essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary essential oil, Japanese mint essential oil, and other synthetic flavors Fragrance etc.

(43) Dye and Colorant Red Cabbage Dye, Red Rice Dye, Akane Dye, Anato Dye, Ikumi Dye, Turmeric Dye, Enju Dye, Krill Dye, Amber Dye, Caramel, Gold, Silver, Gardenia Dye, Corn Dye, Onion Dye , Tamarind pigment, spirulina pigment, buckwheat whole plant pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple potato pigment, purple yam pigment, lac pigment, rutin etc.

(44) Sweeteners Sugar, sweet tea, fructose, arabinose, galactose, xylose, stevia, mannose, maltose, honey, glucose, miraculin, monelin, licorice extract and the like.

(45) Nutrient enhancer Shell calcined calcium, cyanocobalamin, yeast, wheat germ, egg yolk powder, hemicellulose, heme iron and the like.

(46) Dairy products Milk, cheese, fresh cream, butter, margarine, powdered milk, whey, condensed milk, etc.

(47) Others Hormones, sequestering agents, pH adjusters, chelating agents, antiseptic and antifungal agents, cooling agents, stabilizers, emulsifiers, animal and vegetable proteins and their degradation products, animal and vegetable polysaccharides And its degradation products, animal and plant glycoproteins and their degradation products, blood flow promoters, anti-inflammatory agents, anti-inflammatory agents, anti-allergic agents, wound treatment agents, foam increasing agents, thickeners, enzymes, purified water (electronic Water, small clustering, etc.), oral preparations, deodorants / deodorants, bittering agents, seasonings, etc. are raised, and in combination with these, the effects of the present invention or other cosmetic effects are added Or a synergistic improvement can be expected.

(Production of polymer sugar chain compound 1)
6% acetic acid to 0% acetic acid (water) (5 times volume (w / v)) is added to nasal cartilage (1 part) of salmon and extracted at a low temperature of 5 ° C. or lower for 24 to 48 hours. Got. The extract was subjected to molecular weight fractionation to obtain a glycoprotein substance having a molecular weight of 50,000 to 1,000,000. Subsequently, 0.5M lithium hydroxide (LiOH) solution was added thereto, and incubated at 4 ° C. for 1 day. After the reaction, acetic acid was added to stop the reaction, and 1M-NH ₄ HCO ₃ was added through a cation exchange resin: AG 50W-X2 Resin to neutralize to obtain a polymer sugar chain compound (A).

(Production of polymer sugar chain compound 2)
About 5 to 10 times (w / v) of the solvent was added to the cartilage and gently extracted. The extraction temperature is preferably a low temperature of 10 ° C. or lower (preferably 5 ° C. or lower), but extraction can be performed at 10 ° C. to 50 ° C. depending on the solvent conditions. Subsequently, after filtering and removing insoluble matter, the extract is purified using a 0.1 μm membrane. The obtained substance is treated with an alkaline solution such as 0.5M lithium hydroxide at 4 ° C. for 1 day, and the permeated substance is purified by using an ultrafiltration membrane having a molecular sieve of 100,000 to 300,000 to obtain a polymer. A sugar chain compound was obtained.

(Analysis of structural features of useful components)
The polymer sugar chain compound (A) was fluorescently labeled with 2-aminobenzamide (2AB) and purified by paper chromatography to obtain a 2AB reaction product. This reaction product was digested with chondroitinase ABC (CSaseABC) and chondroitinase AC-II (CSaseAC-II). As a result of analyzing this digested product by HPLC with respect to the disaccharide / oligosaccharide fraction, from the peak (FIG. 1) showing a coincidence with the standard substance,
(A-1) N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, sugar chain compound composed of D-xylose in sequence order (A-2) N-acetylgalactosamine, Sugar chain compound (A-3) N-acetylgalactosamine-6-sulfate, D-glucuronic acid composed of D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate Glycan compounds composed of D-galactose, D-galactose, D-xylose sequence (A-4) N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose sequence Was detected.

(HPLC conditions)
Column: YMC-Pack PA-G (anion exchange column)
Solvent: (A) 1M-NaH ₂ PO ₄ Flow rate: 0.5 mL / min
(B) 16 mM NaH ₂ PO ₄
Gradient: B Conc. 100% → 47%? (0 → 60 min) Linear gradient Detection: Fluorescence (Ex. 330 nm, Em. 420 nm)
HPLC system: manufactured by JASCO

  In this analysis, (A-4) occupies about 80 to 90% of the constituent ratio of the sugar chain compounds configured in the sequence order of the molecular binding units (A-1) to (A-4), The total of three types of sugar chain compounds (A-1) to (A-3) in which five sugars containing a sulfate group or a phosphate group at a specific position are bonded in a certain sequence order is 5 to 15% It turned out to be.

  Using the polymer sugar chain compounds (A) and (A-1) to (A-4) produced in the above-mentioned examples as samples, and evaluating them in safety tests and various test systems, the musculoskeletal system and beauty The usefulness was evaluated.

(Safety test: primary skin irritation test)
Japanese white rabbits (female, 3 per group, weight 2. (Approx. 2 kg). Evaluation was performed using erythema and edema as an index based on the criteria for Draise 24, 48, and 72 hours after application. As a result, in all animals, no erythema and edema were observed, and it was judged that there was no problem with primary skin irritation.

(Safety test: Cumulative skin irritation test)
A polymer sugar chain compound was prepared in purified water so that the dry solid content concentration was 1.0% by weight, and the skin of a Hartley guinea pig (female, 3 mice per group, weight of about 320 g) shaved on the back was applied. 0.5 mL / animal was applied once a day, 5 times a week. Application was performed over 2 weeks and shaving was performed on the last application day of each week. Evaluation was performed using erythema and edema as indices based on the criteria for Draise on the day after each application and the day after the last application. As a result, in all animals, no erythema and edema were observed for 2 weeks, and it was judged that there was no problem with respect to cumulative skin irritation.

(Safety test: acute toxicity test)
2,000 mg / kg was orally administered to ddy mice (male and female, 5 mice per group, 5 weeks old) fasted for 4 hours before the test, and the occurrence and degree of toxicity symptoms were observed. Observed over time. As a result, no abnormality was observed in all mice for 14 days, and no abnormalities were found in the anatomy. Therefore, LD50 was 2,000 mg / kg or more, which was judged to be safe.

(Evaluation of proliferative action of cartilage precursor cells)
It is known that the cartilage matrix is denatured by aging, and the number of cartilage cells is reduced in the cartilage tissue that has developed osteoarthritis, and accordingly, the cartilage matrix cannot be produced and the cartilage is worn. The effect on cartilage progenitor cell proliferation was evaluated using ATDC5, a multi-stage cartilage differentiation model.
[sample]
A: High molecular sugar chain compound A-1: N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-2: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate, a sugar chain compound A-3: N-acetylgalactosamine-6-sulfate, D -Glycolic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-4: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose The sugar chain compound samples composed in the order of the sequences were prepared and added so as to have a final medium addition concentration.
As comparative controls, B: glucosamine hydrochloride, C: sodium chondroitin sulfate, D: collagen, E: hyaluronic acid were used for the test. The control was not added.
[Test method]
ATDC5 (RIKEN) was seeded in a 96-well culture plate at 1200 cells / well, replaced 24 hours later with 0.5% serum and DMEM / F12 (added transferrin, sodium selenite), added sample, 5% CO ₂ , 37 ° C Culture was performed for 7 days under the conditions described above. After culturing, the number of cells was measured by the MTT method, and the chondrocyte proliferation promoting action of each sample was analyzed based on the relative value when the control was 100.
[result]
The test results are shown in FIGS. For sample (A) and samples (A-1) to (A-3), significant cartilage progenitor cell proliferation promoting action was observed in a concentration-dependent manner. In addition, (E) hyaluronic acid, which was used as a comparative control, had some effects, but no significant effects were observed in the other comparative controls (B) to (D). From these results, it was found that the main active molecular parts of the chondrocyte progenitor cell growth promoting action are (A-1) to (A-3), and any of these molecular binding units is located at the terminal site in the molecule. The existing polymer sugar chain compound (A) was considered useful as an excellent cartilage precursor cell proliferation promoter.

(Evaluation of cartilage differentiation promoting effect)
Using ATDC5, a multi-stage cartilage differentiation model, the effect on cartilage differentiation promotion was evaluated.
[sample]
A: High molecular sugar chain compound A-1: N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-2: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate, a sugar chain compound A-3: N-acetylgalactosamine-6-sulfate, D -Glycolic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-4: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose The sugar chain compound samples composed in the order of the sequences were prepared and added so as to have a final medium addition concentration.
As comparative controls, B: glucosamine hydrochloride, C: sodium chondroitin sulfate, D: collagen, E: hyaluronic acid were used for the test. In addition, the control was not added, and insulin was used for the positive control in the test.
[Test method]
ATDC5 (RIKEN) was seeded on a 12-well culture plate at 5 × 10 ⁴ cells / well, replaced with 5% serum and DMEM / F12 (added transferrin, sodium selenite), and 5% CO ₂ at 37 ° C. The cells were cultured for 7 days to be confluent. Thereafter, each sample was added and cultured for 21 days. After culturing, the cartilage differentiation ability was evaluated by quantitative analysis with WinROOF of the images obtained by staining with Alcian blue.
[result]
The test results are shown in FIGS. With respect to the sample (A) and the samples (A-1) to (A-3), a significant cartilage differentiation promoting effect was recognized in an insulin-independent manner. In addition, (E) hyaluronic acid, which was used as a comparative control, had some effects, but no significant effects were observed in the other comparative controls (B) to (D). From these results, it is found that the main active molecular parts of the cartilage differentiation promoting action are (A-1) to (A-3), and any one of these molecular binding units is present at the terminal site in the molecule. The polymer sugar chain compound (A) was thought to be useful as an excellent cartilage differentiation promoter.

(Evaluation of inhibitory effect on cartilage calcification)
The cartilage matrix degenerates with aging, and in cartilage tissue that has developed osteoarthritis, the number of chondrocytes is reduced, and as a result, the cartilage matrix cannot be produced and the cartilage is worn. It is also known that bones rub against each other due to ectopic calcification of cartilage, and symptoms progress. Using ATDC5, a multi-stage cartilage differentiation model, the effect on calcification inhibition was evaluated.
[sample]
A: High molecular sugar chain compound A-1: N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-2: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate, a sugar chain compound A-3: N-acetylgalactosamine-6-sulfate, D -Glycolic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-4: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose The sugar chain compound samples composed in the order of the sequences were prepared and added so as to have a final medium addition concentration.
As comparative controls, B: glucosamine hydrochloride, C: sodium chondroitin sulfate, D: collagen, E: hyaluronic acid were used for the test. In addition, the control was not added, and insulin was used for the positive control in the test.
[Test method]
ATDC5 (RIKEN) was seeded on a 12-well culture plate at 5 × 10 ⁴ cells / well, and 5% serum and DMEM / F12 (transferrin, sodium selenite added) were used under conditions of 5% CO ₂ and 37 ° C. The cells were cultured for 7 days to be confluent. Thereafter, the cells were further cultured for 21 days under the condition of adding insulin to form cartilage. Thereafter, each sample was added, and further cultured for 24 days under conditions of 3% CO ₂ and 37 ° C using 5% serum and α-MEM (transferrin, sodium selenite, insulin added). The calcification site was stained with, and the acquired image was quantitatively analyzed with WinROOF to evaluate the ability to inhibit cartilage calcification. Furthermore, the cartilage state on the 52nd day of culture was evaluated by Alcian blue staining.
[result]
The test results are shown in FIGS. For sample (A) and samples (A-1) to (A-3), significant suppression of cartilage calcification was observed. However, no significant effect was observed in the other comparative controls (B) to (E). From these results, it was found that the main active molecular parts of the cartilage mineralization inhibitory action are (A-1) to (A-3), and any one of these molecular binding units is present at the terminal site in the molecule. It was considered that the polymer sugar chain compound (A) is useful as an excellent cartilage calcification inhibitor.

  The macromolecular sugar chain compound (A) according to the present invention was recognized to have two functions, namely, promotion of cartilage regeneration and normal maintenance of cartilage. From these results, it was suggested that the prevention and improvement effect of osteoarthritis can be expected.

(Evaluation of knee joint improvement effect)
With the aging society in recent years, osteoarthritis (OA) is increasing, but OA is a disease that causes dysfunction due to decrease or degeneration of cartilage due to aging or mechanical load on joints. The effect of knee joint improvement was evaluated on humans with pain in the knee joint, which is considered to be the initial stage of OA.
[sample]
A: A sample obtained by adding dextrin to 5 mg of a polymer sugar chain compound sample was used in a capsule.
[Test method]
Twelve males and females in their 40s to 70s who had pain in the knee joint, with which consent was obtained in writing, were subjects (average 58.8 years), and sample (A) 10 mg / day was orally ingested for 12 weeks. Knee pain was evaluated before and 12 weeks after ingestion. Evaluation was performed using the Japanese Orthopedic Association Knee OA Treatment Judgment Criteria (JOA score) method of objective findings.
[result]
The test results are shown in FIG. From the 4th week, knee joint pain was significantly improved and all of the knee joints were improved.

(Evaluation of skin sagging improvement effect 1)
When collagen or elastin in the skin matrix is decomposed or denatured by ultraviolet rays or stress, it becomes impossible to maintain the structure of the skin, and eventually the skin becomes sagging. The effect of improving skin sagging was evaluated by observing facial deformation due to temporary changes in the direction of gravity.
[sample]
A: High molecular sugar chain compound B: Sodium chondroitin sulfate C: Hyaluronic acid placebo: Dextrin only 5 mg sample added with dextrin was used in a capsule.
[Test method]
Twenty healthy men and women in their 20s to 40s who obtained consent in writing were subjects. Sample (A) capsule group 5 (average age 39.6 years), sample (B) capsule group 5 (average age 40.8 years) ), 5 samples (C) capsule group (average age 44.0 years) and 5 placebo capsule groups (average age 40.0 years) were subjected to a double-blind parallel group test. One capsule per day was orally ingested for 2 weeks, and sagging of the facial skin was evaluated by the stamp method (Wakamatsu et al., 130th Annual Meeting of the Pharmaceutical Society of Japan (Okayama) 30P-pm135) before and after ingestion. Then, the elliptical long / short axis ratio of the downward stamp was analyzed.
(Stamp method)
The face is fixed in two directions, vertical and horizontal (downward) with respect to the floor, with a cheek at a certain distance from the nose, and a round ring stamp of blue when vertical and red when horizontal. Two weeks after the start of the capsule pre-intake test, the entire face is photographed with a Robo Skin Analyzer (RSA-50, manufactured by Inforward), and the elliptical long / short axis ratio of the red ring when horizontal (downward) is calculated from the image analysis. The measurement was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%).
[result]
The test results are shown in FIG. As the ellipse major axis minor axis ratio is closer to 1 (perfect circle), the sagging is improved. The sample (A) ingestion group showed an improvement in sagging in which the ellipse major axis ratio decreased compared to that before ingestion, but the sample (B), sample (C), and placebo ingestion groups showed a marked improvement. There wasn't. Therefore, the polymer sugar chain compound (A) was considered useful as a skin sag reducing agent.

(Evaluation of skin sagging improving action 2)
Skin collagen is a major structure that accounts for about 70% of human dermis and plays an important role in maintaining the structure of the skin. Most of the collagen of the dermis is type I collagen, and it is thought that when its production ability decreases due to aging or the like, it leads to wrinkles and sagging of the skin. Using human normal dermal fibroblasts, the effect on the production ability of type I collagen (type I collagen production promoting action) was analyzed, and the skin sagging improvement action was evaluated.
[sample]
A: High molecular sugar chain compound A-1: N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-2: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate, a sugar chain compound A-3: N-acetylgalactosamine-6-sulfate, D -Glycolic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-4: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose Sugar chain compound B: sodium chondroitin sulfate C: hyaluronic acid sample Final medium addition concentration was added was prepared so as to 0.001%.
[Test method]
Human normal dermal fibroblasts (Kurabo Co., Ltd.) were seeded in a 24-well culture plate at a concentration of 2 × 10 ⁴ cells / mL using 5% fetal bovine serum (Thermo Trace) -containing DMEM medium (Sigma). After 72 hours of pre-culture under conditions of% CO ₂ and 37 ° C., the culture medium was replaced with 0.25% fetal calf serum (Thermo Trace) -containing DMEM medium (Sigma) to which each sample was added, and further cultured for 72 hours. After cultivation, the amount of type I collagen was measured with Procollagen Type I C-Peptide (PIP) EIA Kit (manufactured by Takara Bio Inc.). At the same time, the number of cells was measured with Cell Counting Kit-8 (manufactured by Dojin Chemical Co., Ltd.), the amount of type I collagen was calculated. Analyzed.
[result]
The test results are shown in FIG. With respect to sample (A) and samples (A-1) to (A-3), a remarkable type I collagen production promoting action was observed. From these results, it was found that the main active molecular parts of the type I collagen production promoting action are (A-1) to (A-3), and any of these molecular binding units is located at the terminal site in the molecule. It was considered that the existing polymer sugar chain compound (A) is useful as an excellent skin sagging improvement.

(Evaluation of skin elasticity improvement effect 1)
The decrease in skin elasticity is thought to be due to a decrease in new-kind metabolic functions of skin components such as collagen, elastin, and basement membrane, and eventually leads to skin aging symptoms such as wrinkles and sagging. The skin elasticity improving effect was evaluated using a skin viscoelasticity measuring device.
[sample]
A: High molecular sugar chain compound B: Sodium chondroitin sulfate C: Hyaluronic acid placebo: Dextrin only 5 mg sample added with dextrin was used in a capsule.
[Test method]
Twenty healthy men and women in their 20s to 40s who obtained consent in writing were subjects. Sample (A) capsule group 5 (average age 39.6 years), sample (B) capsule group 5 (average age 40.8 years) ), 5 samples (C) capsule group (average age 44.0 years) and 5 placebo capsule groups (average age 40.0 years) were subjected to a double-blind parallel group test. Ingestion of 1 capsule per day for 2 weeks between meals, elasticity and plasticity of face skin (apply force) before and after intake with skin viscoelasticity measuring device (CUTOMETER SEM 575, COURAGE + KHAZAKA Electronic GmbH) And the skin elasticity improving effect after 2 weeks was analyzed by a relative value with the value before ingestion being 100. The measurement method forms a waveform of how the skin changes when a negative pressure of 500 mb is applied from a hole with a diameter of about 1 mm, the skin is sucked for 5 seconds, and then the negative pressure is suddenly released twice. It was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%) in advance.
[result]
The test results are shown in FIG. In the sample (A) ingestion group, the elasticity of the skin was significantly improved as compared with that before the ingestion, and a significant improvement in the plasticity was observed (the lower the plasticity, the better the elasticity improvement effect). Therefore, the polymer sugar chain compound (A) was considered useful as a skin elasticity improving agent.

(Evaluation of skin elasticity improvement effect 2)
[sample]
A: High molecular sugar chain compound A-1: N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-2: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate, a sugar chain compound A-3: N-acetylgalactosamine-6-sulfate, D -Glycolic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-4: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose Sugar chain compound B: sodium chondroitin sulfate C: hyaluronic acid sample It was adjusted to a solid concentration of 0.001% aqueous solution.
[Test method]
18 female subjects (average age 34.0 years) who obtained consent in writing were divided into 6 groups, Sample A and Sample A-1 (1G), Sample A and Sample A-2 (2G), ... , Sample A and sample A-4 (4G), sample A and sample B (5G), sample A and sample C (6G), applied to the left and right sides of the face twice a day for 4 weeks, before application 4 weeks after the start of the test, the skin elasticity (Ur / Uf) was measured with a skin viscoelasticity measuring device (CUTOMETER SEM 575, manufactured by COURAGE + KHAZAKA Electronic GmbH). The measurement method forms a waveform of how the skin changes when a negative pressure of 500 mb is applied from a hole with a diameter of about 1 mm, the skin is sucked for 5 seconds, and then the negative pressure is suddenly released twice. It was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%) in advance.
[result]
The test results are shown in FIG. From 1G to 3G, the elasticity of the skin was significantly improved on both the left and right sides, but similar improvements were not observed in the 4G sample A-4 application part, 5G sample B application part, and 6G sample C application part. .

(Evaluation of skin wrinkle improvement effect)
[sample]
A: High molecular sugar chain compound B: Sodium chondroitin sulfate C: Hyaluronic acid placebo: Dextrin only 5 mg sample added with dextrin was used in a capsule.
[Test method]
Twenty healthy men and women in their 20s to 40s who obtained consent in writing were subjects. Sample (A) capsule group 5 (average age 39.6 years), sample (B) capsule group 5 (average age 40.8 years) ), 5 samples (C) capsule group (average age 44.0 years) and 5 placebo capsule groups (average age 40.0 years) were subjected to a double-blind parallel group test. One capsule per day was orally ingested for two weeks between meals, and the number of wrinkles at present was analyzed by Robo Skin Analyzer (RSA-50 Inforward) before and after ingestion. The measurement was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%) in advance.
[result]
The test results are shown in FIG. In the sample (A) intake group, the number of wrinkles decreased compared to before the intake. In addition, it was confirmed from the photographed image that the wrinkles were shallow. In the sample (B) ingestion group and the sample (C) ingestion group, a slight decreasing tendency was observed. Therefore, the polymer sugar chain compound (A) was considered useful as a skin wrinkle improving agent.

(Evaluation of skin keratin improvement effect)
When skin turnover is disturbed by external stress such as dryness or ultraviolet rays, the shape of keratinocytes changes and the barrier function decreases. In such a skin state, since stratification exfoliation is observed in the horny cells originally exfoliated in a single layer, the skin keratin improvement effect was evaluated by observing it.
[sample]
A: High molecular sugar chain compound B: Sodium chondroitin sulfate C: Hyaluronic acid placebo: Dextrin only 5 mg sample added with dextrin was used in a capsule.
[Test method]
Twenty healthy men and women in their 20s to 40s who obtained consent in writing were subjects. Sample (A) capsule group 5 (average age 39.6 years), sample (B) capsule group 5 (average age 40.8 years) ), 5 samples (C) capsule group (average age 44.0 years) and 5 placebo capsule groups (average age 40.0 years) were subjected to a double-blind parallel group test. 1 capsule per day is orally ingested for 2 weeks between meals, and after ingestion and after 2 weeks, the stratum corneum is collected from the cheeks with a keratin checker (Asahi Biomed H), and after staining, observed with an optical microscope. The degree of delamination where keratinocytes overlap and peel off was scored. The score was evaluated as “2” to “4”, with “1” indicating a bad state where the delamination was the most and “5” indicating no delamination at all. The measurement was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%).
[result]
The test results are shown in FIG. In the sample (A) ingestion group, a significant improvement in skin keratin was observed as compared with that before ingestion. Therefore, the polymer sugar chain compound (A) was considered useful as a skin keratin improving agent.

(Evaluation of skin pigmentation inhibitory effect 1)
[sample]
A: High molecular sugar chain compound B: Sodium chondroitin sulfate C: Hyaluronic acid placebo: Dextrin only 5 mg sample added with dextrin was used in a capsule.
[Test method]
Twenty healthy men and women in their 20s to 40s who obtained consent in writing were subjects. Sample (A) capsule group 5 (average age 39.6 years), sample (B) capsule group 5 (average age 40.8 years) ), 5 samples (C) capsule group (average age 44.0 years) and 5 placebo capsule groups (average age 40.0 years) were subjected to a double-blind parallel group test. One capsule per day is orally ingested for two weeks between meals, and before and after two weeks, using a facial imaging analysis device: VISIA Evolution (manufactured by Canfield), a stain score on the left cheek (spots in the specified area) Ratio) was analyzed. The measurement was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%) in advance.
[result]
The test results are shown in FIG. In the sample (A) ingestion group, the scimi score decreased compared to before the ingestion. It was also confirmed that there were fewer noticeable spots from the captured images. Therefore, the polymer sugar chain compound (A) was considered useful as a skin pigmentation inhibitor.

(Evaluation of skin pigmentation inhibitory effect 2)
[sample]
A: High molecular sugar chain compound A-1: N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-2: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate, a sugar chain compound A-3: N-acetylgalactosamine-6-sulfate, D -Glycolic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-4: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose Sugar chain compound B: sodium chondroitin sulfate C: hyaluronic acid sample It was adjusted to 0.001% aqueous solution.
[Test method]
18 female subjects (average age 34.0 years) who obtained consent in writing were divided into 6 groups, Sample A and Sample A-1 (1G), Sample A and Sample A-2 (2G), ... , Sample A and sample A-4 (4G), sample A and sample B (5G), sample A and sample C (6G), applied to the left and right sides of the face twice a day for 4 weeks, before application And 4 weeks after the start of the test, the pigmentation (large) area portion (dark portion with a size exceeding 1.2 mm ² ) was analyzed using a Robo Skin Analyzer (RSA-50, manufactured by Inforward). The measurement was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%).
[result]
FIG. 16 shows changes in the pigmentation (large) area before and after the sample application. In 1G-3G, the tendency which both left and right decreased was seen. In the 4G A-4 coating part, the 5G sample B coating part, and the 6G sample C coating part, the decreasing tendency as the other coating parts was not recognized.

(Evaluation of moisturizing effect 1)
[sample]
A: High molecular sugar chain compound B: Sodium chondroitin sulfate C: Hyaluronic acid placebo: Dextrin only 5 mg sample added with dextrin was used in a capsule.
[Test method]
Twenty healthy men and women in their 20s to 40s who obtained consent in writing were subjects. Sample (A) capsule group 5 (average age 39.6 years), sample (B) capsule group 5 (average age 40.8 years) ), 5 samples (C) capsule group (average age 44.0 years) and 5 placebo capsule groups (average age 40.0 years) were subjected to a double-blind parallel group test. One capsule per day was orally ingested for 2 weeks between meals, and horny water content (conductance) was measured using an impedance meter (SKICON-200, manufactured by IBIS Co., Ltd.) before and after 2 weeks. The measurement was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%).
[result]
The test results are shown in FIG. In the sample (A) ingestion group, a significant increase in the amount of horny water was observed as compared with that before ingestion. Therefore, the polymer sugar chain compound (A) was considered useful as a humectant.

(Evaluation of moisturizing effect 2)
[sample]
A: High molecular sugar chain compound A-1: N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-2: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate, a sugar chain compound A-3: N-acetylgalactosamine-6-sulfate, D -Glycolic acid, D-galactose, D-galactose, D-xylose sugar chain compound A-4: N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose Sugar chain compound B: sodium chondroitin sulfate C: hyaluronic acid sample It was adjusted to 0.001% aqueous solution.
[Test method]
18 female subjects (average age 34.0 years) who obtained consent in writing were divided into 6 groups, Sample A and Sample A-1 (1G), Sample A and Sample A-2 (2G), ... , Sample A and sample A-4 (4G), sample A and sample B (5G), sample A and sample C (6G), applied to the left and right sides of the face twice a day for 4 weeks, before application And 4 weeks after the start of the test, the amount of horny water (conductance) was measured using an impedance meter (SKICON-200, manufactured by IBS). The measurement was performed after acclimatization for 20 minutes in a constant temperature and humidity chamber (20 ° C., humidity 50%).
[result]
FIG. 18 shows the change in the amount of keratin moisture (conductance) before and after application of the sample. In 1G to 3G, a significant tendency to increase keratin water content was observed on both the left and right sides. The 4G A-4 coating part, the 5G sample B coating part, and the 6G sample C coating part also showed a tendency to increase the amount of keratinous water, but it was smaller than the other sample coating parts (sample A). there were.

(Evaluation of stability)
[sample]
A: The polymer sugar chain compound sample was adjusted to a 1% aqueous solution.

(1) Stability over time [Test method]
Place the sample in a transparent borosilicate glass bottle, leave it at 4 ° C, room temperature, 50 ° C in a constant temperature bath, a window exposed to sunlight for a certain period of time, change in absorbance at 600nm, change in pH, turbidity or precipitation over time Was observed. The results are shown in Table 1.

(2) Thermal stability [Test method]
The sample was placed in a borosilicate glass transparent bottle and allowed to stand in a constant temperature bath at 90 ° C. for a certain period, and the change in absorbance at 600 nm, turbidity, or precipitation was observed over time. The results are shown in Table 2.

(3) pH stability [test method]
After adjusting the pH of the sample with hydrochloric acid and sodium hydroxide solution, the sample was allowed to stand for a certain period, and the change in absorbance at 600 nm, turbidity or precipitation was observed over time. The results are shown in Table 3. For this reason, it is desirable that the pH is adjusted to 9 or less in application means that are useful for maintaining the health of the musculoskeletal system according to the present invention in a solution system and for the beauty system.

[Manufacture of various health foods, health drinks, and cosmetic compositions]
Various cosmetic compositions according to the present invention were prepared. The prescription example is shown below. Ethanol is abbreviated as EtOH, and 1,3-butylene glycol is abbreviated as 1,3-BG.
(Beauty / health tablet)
The composition containing the following additives was compressed into tablets. weight%
1. Polymer sugar chain compound (A) powder 1
2. N-acetylglucosamine 5
3. Chondroitin sodium sulfate 1
4). Collagen powder for food 5
5. Guarana 50% EtOH extraction powder 5
6). Royal jelly powder 5
7). Sodium ascorbate 1
8). Lactose 35
9. Corn starch 25
10. Hydroxypropyl cellulose 4
11. Magnesium stearate 1
12 Dextrin 12

(Cosmetic food for beauty and health)
The following additives were filled into gelatin capsules to produce a capsule-type food (one package).
Weight g
1. Polymer sugar chain compound (A) powder 0.05
2. Collagen powder for food 0.1
3. Collagen tripeptide 0.05
4). Porcine placental water extraction powder (50% dextrin) 0.01
5. Soy peptide 0.02
6). Sodium ascorbate 0.03

(Natural supplements for beauty and health)
Granules (4 packs) containing the following additives were produced. Weight g
1. Collagen powder for food 5
2. Fat content 0.024
3. Sodium aspartate 0.01
4). Vitamin A 0.002
5. Vitamin B1 0.003
6). Vitamin B2 0.004
7). Vitamin B6 0.004
8). Vitamin B12 0.0006
9. Sodium ascorbate 0.03
10. Vitamin E 0.002
11. Niacin 0.004
12 Pantothenic acid 0.001
13. Arginine 0.6
14 Leucine 0.6
15. Valine 0.4
16. Eggshell calcium 0.01
17. Polymer sugar chain compound (A) powder 0.01
18. Hydroxypropyl cellulose 2
19. N-acetylglucosamine 5
20. Chondroitin sodium sulfate 1
21. Dextrin 2

(Beauty and health drinks)
weight%
1. Pomegranate water extract 20
2. Rose Hot Water Extract 20
3. Sodium ascorbate 0.1
4). Polymer sugar chain compound (A) powder 0.01
5. Porcine placental water extract 0.02
6). Honey 5
7). Citric acid 0.1
8). Water-soluble collagen for food 2
9. dl-malic acid 0.1
10. D-sorbitol solution (70%) 10
11. Sodium benzoate 0.03
12 Perfume appropriate amount13. Residue with 100 purified water

(Lactic acid bacteria fermented beverage for beauty and health)
weight%
1. Polymer sugar chain compound (A) solution (solid content: 1.0%) 2
2. Carrot juice lactic acid bacteria fermentation 40
3. Orange concentrated reduced juice 10
4). Sodium ascorbate 0.2
5. Lactulose syrup 1
6). Citric acid 0.1
7). Water-soluble collagen for food 2
8). Perfume appropriate amount 9. Residue with 100 purified water

(Ii) Weight Minamata 500g
2. 500g sugar
Is mixed and heated at 120 ° C. under reduced pressure (−500 mmHg), and then cooled to 90 ° C. to this,
3. Polymer sugar chain compound (A) solution concentrate 5g
4). 30g orange fruit ground
5. Stevia extract 20g
6). Citric acid 10g
7). Fragrance 1.5mL
Was added and kneaded sufficiently, and this was punched and molded into a circle having a diameter of 15 mm and a thickness of 8 mm to produce a bag.

(lotion)
weight%
1. Polymer sugar chain compound (A) solution (solid content: 1.0%) 1
2. Sorbit 2
3.1,3-BG 2
4). Polyoxyethylene oleyl ether (25 EO adduct) 2
5. EtOH 20
6). Ascorbic acid 2-glucoside 0.2
7). Green tea 30% EtOH extract 0.01
8). Chamomile 30% EtOH extract 1.0
9. pH adjuster appropriate amount10. Phenoxyethanol appropriate amount11. Residue with 100 purified water

(Milky lotion)
weight%
1. Polymer sugar chain compound (A) solution (solid content: 1.0%) 1
2. Squalane 3
3. Vaseline 1
4). Stearyl alcohol 0.3
5. Sorbitan monostearate 1.5
6). Polyoxyethylene (20) sorbitan monooleate 3
7.1,3-BG 10
8). Ascorbic acid phosphate magnesium salt 0.1
9. Acerola 30% 1,3-BG extract 1.0
10. Scarlet root 30% 1,3-BG extract 1.0
11. Sodium hyaluronate 0.005
12 Preservative (paraoxybenzoic acid ester) Residue with 100 purified water

(Milky lotion)
weight%
1. Polymer sugar chain compound (A) solution (solid content: 1.0%) 2.0
2. Squalane 8.0
3. Jojoba oil 7.0
4). Maltose 3.0
5. Ascorbic acid phosphate magnesium salt 0.1
6). Cetyl alcohol 1.5
7). Glycerol monostearate 2.0
8). Polyoxyethylene (20) cetyl ether 3.0
9. Polyoxyethylene (20) sorbitan monooleate 2.0
10. Yuzu 50% 1,3-BG extract (containing Yuzuceramide) 1.0
11. Porcine placenta extract 0.1
12.1, 3-BG 1.0
13. Glycerin 2.0
14 Sodium hyaluronate 0.001
15. Preservative (paraoxybenzoic acid ester) Residue with 100 purified water

(Cosmetic oil)
mass%
1. Polymer sugar chain compound (A) solution (solid content: 1.0%) 1.0
2. Liquid paraffin 30.0
3. Squalane 20.0
4). Olive oil 20.0
5. Isopropyl palmitate 10.0
6). Olive oil 1.0
7). Shea fat 1.0
8). Butylhydroxyanisole 0.1
9. DL-α-tocopherol derivative 0.1
10. Ascorbic acid phosphate magnesium salt 0.1
11. Bilberry 30% 1,3-BG extract 1.0
12 Indigo Luros 30% 1,3-BG extract 1.0
13. Preservative (paraoxybenzoic acid ester) Perfume appropriate amount 15. Residue with 100 purified water

(cream)
mass%
1. Polymer sugar chain compound (A) solution (solid content: 1.0%) 1.0
1. Sara honey bees 11.0
2. Liquid paraffin 22.0
3. Lanolin 10.0
4). Olive oil 5.0
5. Chamomile oil 5.0
6). Palm oil 5.0
7). Oat bark 30% 1,3-BG extract 2.0
8). Water-soluble collagen solution 3.0
10. Porcine placenta extract 0.1
11. Ascorbic acid phosphate magnesium salt 0.1
12 Liquid shea fat 1.0
13. Hydroxypropyl cellulose 2.0
14 Residue with 100 purified water

(Face washing cream)
mass%
1. Polymer sugar chain compound (A) solution (solid content: 1.0%) 2.0
2. Stearic acid 10.0
3. Palmitic acid 10.0
4). Myristic acid 12.0
5. Lauric acid 4.0
6). Oleyl alcohol 1.5
7). Lanolin derivative (EO adduct) 1.0
8). Glycerin 18.0
9. Potassium hydroxide 6.0
10. Glycyrrhizic acid 2-potassium 1.0
11. Soap nut (Rita) extracted saponin 0.1
12 Perfume appropriate amount13. Residue with 100 purified water

(Hair shampoo) Weight part 1. Lauryl sulfate triethanolamine 5
2. Sodium polyoxyethylene lauryl ether sulfate 12
3. 1,3-butylene glycol 4
4). Lauric acid diethanolamide 2
5. 2-Phenylchromone 0.01
6). Polymer sugar chain compound (A) solution (solid content: 1.0%) 1.0
7). Arginine or its salt 0.2
8). Preservative (ethyl paraben) Appropriate amount 9. Residue with 100 purified water

  According to the present invention, it is obtained by hydrolyzing a glycoprotein substance extracted from cartilage tissue of fish, mollusk, birds, and mammals, in which a specific molecular binding unit exists as a main active molecule part at the terminal site in the molecule. High molecular sugar chain compounds have excellent effects for maintaining the health of the musculoskeletal system, such as cartilage progenitor cell proliferation promotion, cartilage differentiation promotion, cartilage calcification inhibition, knee joint improving agent, skin sagging improvement, skin elasticity It has excellent cosmetic effects such as improvement, skin wrinkle improvement, skin keratin improvement, skin pigmentation suppression, and moisturizing. Therefore, it is possible to manufacture and provide health foods, health drinks, pharmaceutical compositions useful for maintaining the health of the musculoskeletal system, and cosmetic compositions useful for the beauty system. It can be used as various applied products in the beauty industry such as cosmetics.

Claims (12)

Glycoprotein substances extracted from cartilage tissues of fish, molluscs, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A cartilage progenitor cell growth promoter comprising a high-molecular sugar chain compound obtained by hydrolyzing sucrose as an active ingredient.
(1) A molecular binding unit represented by the general formula 1 composed of the sequence of N-acetylgalactosamine-4-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose

(2) Molecular binding unit represented by the general formula 2 composed of the sequence of N-acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate

(3) Molecular binding unit represented by the general formula 3 composed of the sequence of N-acetylgalactosamine-6-sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose

Glycoprotein substances extracted from cartilage tissues of fish, molluscs, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A cartilage differentiation promoter comprising a high-molecular weight sugar chain compound obtained by hydrolyzing sucrose as an active ingredient.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, molluscs, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A cartilage calcification inhibitor comprising, as an active ingredient, a macromolecular sugar chain compound obtained by hydrolyzing sucrose.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, mollusks, birds and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A knee joint improving agent comprising a high-molecular-weight sugar chain compound obtained by hydrolyzing a lipase as an active ingredient.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, mollusks, birds and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part An agent for improving skin sag, comprising as an active ingredient a high-molecular sugar chain compound obtained by hydrolyzing water.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, molluscs, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A skin elasticity improving agent comprising a high-molecular-weight sugar chain compound obtained by hydrolyzing as an active ingredient.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, molluscs, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A skin wrinkle-improving agent comprising a polymer sugar chain compound obtained by hydrolyzing sucrose as an active ingredient.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, molluscs, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A skin keratin improving agent comprising a high-molecular-weight sugar chain compound obtained by hydrolyzing as an active ingredient.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, molluscs, birds, and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A skin pigmentation inhibitor comprising, as an active ingredient, a macromolecular sugar chain compound obtained by hydrolyzing water.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Glycoprotein substances extracted from cartilage tissues of fish, mollusks, birds and mammals in which any of the following molecular binding units (1) to (3) is present at the terminal end in the molecule as the main active molecular part A moisturizer comprising a high-molecular weight sugar chain compound obtained by hydrolyzing the active ingredient.
(1) N-acetylgalactosamine-4-sulphate, D-glucuronic acid, D-galactose, D-galactose, D-xylose molecular binding unit represented by the general formula 1 (2) N- Molecular binding unit (3) N-acetylgalactosamine-6 represented by the above general formula 2 composed of the sequence of acetylgalactosamine, D-glucuronic acid, D-galactose, D-galactose, D-xylose-2-phosphate -Molecular binding unit represented by the above general formula 3 composed of the sequence of sulfate, D-glucuronic acid, D-galactose, D-galactose, D-xylose Cartilage progenitor cell growth promoter, cartilage differentiation promoter, cartilage mineralization inhibitor, knee joint improver, skin sagging improver, skin elasticity improver, skin wrinkle improver, skin keratin improver, A health food or health drink or a pharmaceutical composition containing either a skin pigmentation inhibitor or a moisturizer. A cosmetic composition comprising any one of the skin sagging improving agent, skin elasticity improving agent, skin wrinkle improving agent, skin keratin improving agent, skin pigmentation inhibitor, and moisturizer according to claim 5.

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