JP2018052890A - Nutritional composition for promoting wound healing of inflammation period in postoperative wound healing process - Google Patents
Nutritional composition for promoting wound healing of inflammation period in postoperative wound healing process Download PDFInfo
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- JP2018052890A JP2018052890A JP2016192773A JP2016192773A JP2018052890A JP 2018052890 A JP2018052890 A JP 2018052890A JP 2016192773 A JP2016192773 A JP 2016192773A JP 2016192773 A JP2016192773 A JP 2016192773A JP 2018052890 A JP2018052890 A JP 2018052890A
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Abstract
Description
本発明は、術後の創傷治癒過程における炎症期の創傷治癒を促進するための栄養組成物に関する。 The present invention relates to a nutritional composition for promoting wound healing in the inflammatory phase in the post-surgical wound healing process.
一般に、手術を受ける際には手術に先だって麻酔が投与され、その麻酔の作用で体温が低下する。この体温低下は細胞の活動低下等を伴い、患者の回復を遅らせる原因にもなる。また術後に残された創傷に対しては、抗生物質の投与や消毒剤の塗布などにより創感染を防御する措置は施されるが、創傷自体の治癒は患者が持つ自然治癒力に頼っている。 In general, when undergoing surgery, anesthesia is administered prior to surgery, and the body temperature is lowered by the action of the anesthesia. This decrease in body temperature is accompanied by a decrease in cell activity and the like, and also causes a delay in patient recovery. For wounds left after surgery, measures are taken to protect against wound infection by administering antibiotics or applying disinfectants, but the wound itself depends on the natural healing power of the patient. Yes.
従来では、周術期（手術の前後）における対応として栄養管理が重要であると言われている（非特許文献１：術前術後の栄養管理；東口高志, 伊藤彰博、藤田保健衛生大学医学部外科学・緩和ケア講座 MEDICAMENT NEWS (1912): 1-4, 2007.）。 Conventionally, it is said that nutrition management is important as a response in the perioperative period (before and after surgery) (Non-patent document 1: Preoperative and postoperative nutrition management; Takashi Higashiguchi, Akihiro Ito, School of Medicine, Fujita Health University) Surgery and palliative care course MEDICAMENT NEWS (1912): 1-4, 2007.).
その中でも免疫力を高めて、術後の早期回復を目指すためグルタミン、ω-3系脂肪酸、ビタミン、微量元素などの栄養素が必要であると報告されているが、コラーゲンペプチドについては報告されていない。 Among them, it has been reported that nutrients such as glutamine, omega-3 fatty acids, vitamins and trace elements are necessary to enhance immunity and aim for early recovery after surgery, but no collagen peptide has been reported. .
本発明は、術後の創傷治癒過程における炎症期の創傷治癒を促進するための栄養組成物を提供することを目的とする。 An object of the present invention is to provide a nutritional composition for promoting wound healing in the inflammatory phase in the wound healing process after surgery.
本発明者らは、コラーゲンペプチドを含有する栄養組成物を切創モデル動物に与えることにより、血清CRPにおいて6日摘出群で有意な低値が認められ，創傷部位のコラーゲンの生成の指標であるコラーゲンI及びIIIの遺伝子発現に高値傾向が認められることを見出した。このことは、コラーゲンペプチド摂取により炎症期が短縮する可能性を示唆している。 The present inventors gave a nutritional composition containing a collagen peptide to a cut model animal, and a significant low value was observed in the 6-day excised group in serum CRP, which is an index of collagen production at the wound site. It was found that a high tendency was observed in the gene expression of collagen I and III. This suggests the possibility of shortening the inflammatory phase by ingesting the collagen peptide.
創傷部では、コラーゲン合成を発現させることにより、組織の再構築が行われる。このコラーゲンの合成能を上げるために、コラーゲンペプチドを経口投与することにより、吸収されたコラーゲン分解物によりコラーゲン合成能が向上すると考えられる。 In the wound part, tissue reconstruction is performed by expressing collagen synthesis. In order to increase the ability to synthesize collagen, oral administration of a collagen peptide is considered to improve the ability to synthesize collagen by the absorbed collagen degradation product.
本発明の要旨は、以下の通りである。
（１）コラーゲンペプチドを含有する、術後の創傷治癒過程における炎症期の創傷治癒を促進するための栄養組成物。
（２）１日あたり、10±3 gのコラーゲンペプチドが投与されるように用いられる、（１）記載の組成物。
（３）１投与単位あたり、10±3 gのコラーゲンペプチドを含み、１日あたり１投与単位で投与されるように用いられる、（２）記載の組成物。
（４）さらに、微量元素も投与されるように用いられる、（１）〜（３）のいずれかに記載の組成物。
（５）微量元素が、鉄、亜鉛及びセレンからなる群より選択される少なくとも１種である、（４）記載の組成物。
（６）１日あたり、5.0±3.0mgの鉄、12±6mgの亜鉛及び50±25μgのセレンからなる群より選択される少なくとも１種の微量元素が投与されるように用いられる、（５）記載の組成物。
（７）１投与単位あたり、5.0±3.0mgの鉄、12±6mgの亜鉛及び50±25μgのセレンを含み、１日あたり１投与単位で投与されるように用いられる、（６）記載の組成物。
（８）さらに、ビタミン類も投与されるように用いられる、（１）〜（７）のいずれかに記載の組成物。
（９）ビタミン類が、ビタミンA及び/又はβ−カロテン、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、ナイアシン、葉酸、ビタミンＤ３、ビタミンＥ、ビオチン、並びにパントテン酸からなる群より選択される少なくとも１種である、（８）記載の組成物。
（１０）１日あたり、300±250μg（レチノール活性等量）のビタミンＡ及び/又はβ−カロテン、3.0±1.5mgのビタミンＢ１、3.0±1.5mgのビタミンＢ２、5.0±2.5mgのビタミンＢ６、10±5μgの-ビタミンＢ１２、500±250mgのビタミンＣ、15±7.5mgのナイアシン、550±275μgの葉酸、5.5±2.75μgのビタミンＤ３、20±10mgのビタミンＥ、50±25μgのビオチン、並びに10±5mgのパントテン酸からなる群より選択される少なくとも１種のビタミン類が投与されるように用いられる、（９）記載の組成物。
（１１）１投与単位あたり、300±250μg（レチノール活性等量）のビタミンＡ及び/又はβ−カロテン、3.0±1.5mgのビタミンＢ１、3.0±1.5mgのビタミンＢ２、5.0±2.5mgのビタミンＢ６、10±5μgの-ビタミンＢ１２、500±250mgのビタミンＣ、15±7.5mgのナイアシン、550±275μgの葉酸、5.5±2.75μgのビタミンＤ３、20±10mgのビタミンＥ、50±25μgのビオチン、並びに10±5mgのパントテン酸を含み、１日あたり１投与単位で投与されるように用いられる、（１０）記載の組成物。
（１２）剤形が、液状、ゲル状、粉末、顆粒又は錠剤であり、経口投与される、（１）〜（１１）のいずれかに記載の組成物。
The gist of the present invention is as follows.
(1) A nutritional composition for promoting wound healing in the inflammatory phase in the post-surgical wound healing process, comprising a collagen peptide.
(2) The composition according to (1), which is used so that 10 ± 3 g of collagen peptide is administered per day.
(3) The composition according to (2), which contains 10 ± 3 g of collagen peptide per dosage unit and is used to be administered at a dosage unit per day.
(4) The composition according to any one of (1) to (3), which is used so that a trace element is also administered.
(5) The composition according to (4), wherein the trace element is at least one selected from the group consisting of iron, zinc and selenium.
(6) It is used so that at least one trace element selected from the group consisting of 5.0 ± 3.0 mg iron, 12 ± 6 mg zinc and 50 ± 25 μg selenium is administered per day. (5) The composition as described.
(7) The composition according to (6), comprising 5.0 ± 3.0 mg of iron, 12 ± 6 mg of zinc and 50 ± 25 μg of selenium per dosage unit, and used to be administered in one dosage unit per day object.
(8) The composition according to any one of (1) to (7), which is further used to administer vitamins.
(9) The vitamins are vitamin A and / or β-carotene, vitamin B 1 , vitamin B 2 , vitamin B 6 , vitamin B 12 , vitamin C, niacin, folic acid, vitamin D 3 , vitamin E, biotin, and pantothene The composition according to (8), which is at least one selected from the group consisting of acids.
(10) 300 ± 250 μg (equivalent retinol activity) of vitamin A and / or β-carotene, 3.0 ± 1.5 mg of vitamin B 1 , 3.0 ± 1.5 mg of vitamin B 2 , 5.0 ± 2.5 mg of vitamin per day B 6 , 10 ± 5 μg-vitamin B 12 , 500 ± 250 mg vitamin C, 15 ± 7.5 mg niacin, 550 ± 275 μg folic acid, 5.5 ± 2.75 μg vitamin D 3 , 20 ± 10 mg vitamin E, 50 ± The composition according to (9), wherein 25 μg of biotin and at least one vitamin selected from the group consisting of 10 ± 5 mg of pantothenic acid are administered.
(11) per dosage unit, vitamin A and / or β- carotene 300 ± 250 [mu] g (retinol activity equivalent), vitamin B 1 of 3.0 ± 1.5mg, 3.0 ± 1.5mg of vitamin B 2, 5.0 ± 2.5 mg Vitamin B 6 , 10 ± 5 μg-vitamin B 12 , 500 ± 250 mg vitamin C, 15 ± 7.5 mg niacin, 550 ± 275 μg folic acid, 5.5 ± 2.75 μg vitamin D 3 , 20 ± 10 mg vitamin E, The composition according to (10), which contains 50 ± 25 μg of biotin and 10 ± 5 mg of pantothenic acid and is used to be administered at a dosage unit per day.
(12) The composition according to any one of (1) to (11), wherein the dosage form is liquid, gel, powder, granule, or tablet and is orally administered.
本発明の組成物により、術後の創傷治癒過程における炎症期の創傷治癒を促進することが可能となる。 The composition of the present invention makes it possible to promote wound healing in the inflammatory phase in the post-surgical wound healing process.
以下、本発明の実施の形態についてより詳細に説明する。 Hereinafter, embodiments of the present invention will be described in more detail.
本発明は、コラーゲンペプチドを含有する、術後の創傷治癒過程における炎症期の創傷治癒を促進するための栄養組成物を提供する。
コラーゲンペプチドは、吸収される際にジペプチドレベル（プロリルヒドロキシプロリン（以下、Pro-Hyp）、ヒドロキシプロリルグリシン（以下、Hyp-Gly））まで分解されて吸収される。
術後に皮膚、吻合部が損傷を受けた「炎症期」には、吸収されたPro-HypやHyp-Glyは損傷部位周辺の繊維芽細胞を刺激し、刺激を受けた繊維芽細胞は損傷部位へ遊走が促進される。損傷部位に集まった繊維芽細胞は細胞外マトリクス（コラーゲン、エラスチン、ヒアルロン酸）を形成する。
「増殖期」には同時に細胞外マトリクスの形成と同時に血管新生がもたらされ肉芽組織を形成し、組織の欠損部を充てんする。
「成熟期」になると一旦、形成されたコラーゲンは分解され、より抗張力の強いコラーゲンへと再構築されていき、損傷部位の組織は修復される。
The present invention provides a nutritional composition for promoting inflammatory stage wound healing in the post-surgical wound healing process, comprising a collagen peptide.
When the collagen peptide is absorbed, it is broken down to the dipeptide level (prolylhydroxyproline (hereinafter, Pro-Hyp), hydroxyprolylglycine (hereinafter, Hyp-Gly)) and absorbed.
In the “inflammatory phase” when the skin and anastomosis are damaged after surgery, absorbed Pro-Hyp and Hyp-Gly stimulate fibroblasts around the damaged area, and the stimulated fibroblasts are damaged. Migration is promoted to the site. Fibroblasts that collect at the site of injury form an extracellular matrix (collagen, elastin, hyaluronic acid).
In the “proliferation phase”, angiogenesis is brought about at the same time as the formation of the extracellular matrix, forming granulation tissue and filling the defective part of the tissue.
Once in the “mature stage”, the formed collagen is decomposed and reconstructed into a stronger collagen, and the tissue at the damaged site is repaired.
コラーゲンペプチドは、ゼラチンを加水分解し低分子化することにより得られるが、ゼラチンと比べ水分に溶解した際にゲル化する作用は低く、水溶性に優れ冷水にも容易に溶解する特性を持っている。また、コラーゲンペプチドの素となるコラーゲンは、ブタ、ウシ、トリ、魚の皮や骨などから抽出することが出来る。 Collagen peptides can be obtained by hydrolyzing gelatin to lower its molecular weight, but it has a low gelling effect when dissolved in water compared to gelatin, and it has excellent water solubility and easily dissolves in cold water. Yes. Collagen which is a source of collagen peptide can be extracted from pigs, cows, birds, fish skins and bones.
本発明の組成物を用いてコラーゲンペプチドを投与する場合、一日あたりの投与量として、コラーゲンペプチドは、3〜20 gが適当であり、5〜15 gが好ましく、例えば、１日あたりの投与量を１投与単位として含む組成物を１日１回投与するように用いるとよい。本発明の組成物の好ましい使用態様では、１日あたり、10±3 gのコラーゲンペプチドが投与されるように用いられ、例えば、１投与単位あたり、10±3 gのコラーゲンペプチドを含む組成物が、１日あたり１投与単位で投与されるように用いられるとよい。 When the collagen peptide is administered using the composition of the present invention, the collagen peptide is suitably 3 to 20 g, preferably 5 to 15 g, for example, administered per day. A composition containing the amount as one dosage unit may be used to be administered once a day. In a preferred embodiment of the composition of the present invention, 10 ± 3 g of collagen peptide is used per day, for example, a composition comprising 10 ± 3 g of collagen peptide per dosage unit. It may be used so that it is administered in one dosage unit per day.
本発明の組成物は、さらに、微量元素も投与されるように用いられるとよい。微量元素は、鉄、亜鉛及びセレンからなる群より選択される少なくとも１種であるとよい。術後患者では、鉄欠乏などが生じることもあるので、組成物に鉄を添加するとよい。術後患者の創傷部及び/又は吻合部の回復を促進するためには、核酸・タンパク質合成補助因子、例えば、亜鉛を添加することが好ましい。亜鉛は、体内では、アルブミンやグロブリンなどと結合し、生体をくまなく流通する。低亜鉛血症では、皮膚や消化管などの上皮細胞、骨などから亜鉛が肝臓に動員され、これら上皮組織への欠乏がいち早く起こることが知られている。また、細胞の分化、増殖を促し得る細胞成長促進因子として、亜鉛を添加してもよい。亜鉛を用いる場合には、食品添加物として許可され又生物学的利用率の高い酵母が産生する亜鉛成分（ジンクイースト）を用いることが好ましい。また硫酸亜鉛を用いても良い。亜鉛は抗酸化酵素であるスーパーオキシドジスムターゼの構成物質であり、セレンは、抗酸化酵素であるグルタチオンペルオキシダーゼの構成物質であるので、これらの微量元素の抗酸化剤としての作用を期待して、組成物に添加してもよい。抗酸化剤は、手術に伴う酸化的ストレスに対して強力な還元作用を有する。 The composition of the present invention may be used so that trace elements are also administered. The trace element may be at least one selected from the group consisting of iron, zinc, and selenium. In patients after surgery, iron deficiency may occur, so it is recommended to add iron to the composition. In order to promote recovery of the wound and / or anastomosis of the patient after surgery, it is preferable to add a nucleic acid / protein synthesis cofactor, such as zinc. Zinc binds to albumin and globulin in the body and circulates throughout the living body. In hypozincemia, it is known that zinc is mobilized to the liver from epithelial cells such as the skin and digestive tract, bones, and the like, and deficiencies in these epithelial tissues occur quickly. Further, zinc may be added as a cell growth promoting factor that can promote cell differentiation and proliferation. When using zinc, it is preferable to use a zinc component (zinc yeast) which is permitted as a food additive and produced by yeast having a high bioavailability. Zinc sulfate may also be used. Zinc is a constituent of superoxide dismutase, an antioxidant enzyme, and selenium is a constituent of glutathione peroxidase, an antioxidative enzyme, so the composition of these trace elements is expected to act as an antioxidant. It may be added to the product. Antioxidants have a strong reducing action against oxidative stress associated with surgery.
本発明の組成物を用いて微量元素を投与する場合、１日あたりの投与量として、鉄は、1.0〜50.0 mgが適当であり、2.0〜10.0 mgが好ましく、亜鉛は、1.0〜45.0 mgが適当であり、1.5〜20.0 mgが好ましく、セレンは、5.0〜440 μgが適当であり、10〜120μgが好ましく、例えば、１日あたりの投与量を１投与単位として含む組成物を１日１回投与するように用いるとよい。本発明の組成物の好ましい使用態様では、１日あたり、5.0±3.0 mgの鉄、12±6 mgの亜鉛及び50±25μgのセレンからなる群より選択される少なくとも１種の微量元素が投与されるように用いられ、例えば、１投与単位あたり、5.0±3.0 mgの鉄、12±6 mgの亜鉛及び50±25μgのセレンを含む組成物が、１日あたり１投与単位で投与されるように用いられるとよい。 When a trace element is administered using the composition of the present invention, the appropriate daily dose of iron is 1.0 to 50.0 mg, preferably 2.0 to 10.0 mg, and zinc is 1.0 to 45.0 mg. 1.5 to 20.0 mg is preferable, and selenium is preferably 5.0 to 440 μg, preferably 10 to 120 μg. For example, a composition containing a dose per day as one dosage unit is once a day. It may be used as an administration. In a preferred embodiment of the composition of the present invention, at least one trace element selected from the group consisting of 5.0 ± 3.0 mg iron, 12 ± 6 mg zinc and 50 ± 25 μg selenium is administered per day. For example, so that a composition containing 5.0 ± 3.0 mg iron, 12 ± 6 mg zinc and 50 ± 25 μg selenium per dosage unit is administered in one dosage unit per day. It should be used.
本発明の組成物は、さらに、ビタミン類も投与されるように用いられるとよい。ビタミン類は、ビタミンＡ、β−カロテン、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ビタミンＣ、ナイアシン、葉酸、ビタミンＤ３、ビタミンＥ、ビオチン、並びにパントテン酸からなる群より選択される少なくとも１種であるとよい。 The composition of the present invention may be used so that vitamins are also administered. The vitamins are at least one selected from the group consisting of vitamin A, β-carotene, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, niacin, folic acid, vitamin D3, vitamin E, biotin, and pantothenic acid. It is good to be a seed.
ビタミンＡ、β-カロテン、ビタミンＣ、ビタミンＥなどの抗酸化ビタミンは、手術に伴う酸化的ストレスに対して強力な還元作用を有する抗酸化剤としての作用が期待される。これら抗酸化ビタミンは、作用するステージが異なることから、いずれか単独で使用するのではなく、同時に使用することが好ましい。また、上記抗酸化ビタミンの一つであるビタミンＣは、抗酸化剤として作用するのみならず、ｃAMP亢進、脂質可溶化作用に直接関与し、また、コラーゲン形成、生体異物解毒、インタフェロン産生誘導、抗ヒスタミン作用、免疫機能増強、抗ウイルス、抗細菌などの種々の作用を有することから、抗酸化ビタミンとして、少なくともビタミンＣを含めることが好ましい。ビタミンＡは、抗酸化ビタミンとしての機能のほか、細胞分化・増殖を促す機能をも有する。細胞増殖・分化を促進させることにより、Ｔ細胞などの免疫細胞の増殖をも促すことが可能となるため、免疫力を向上させ、感染に対する防御力を高めることが可能となる。 Antioxidant vitamins such as vitamin A, β-carotene, vitamin C and vitamin E are expected to act as antioxidants having a strong reducing action against oxidative stress associated with surgery. Since these antioxidant vitamins act at different stages, it is preferable to use these antioxidant vitamins simultaneously rather than using them alone. Vitamin C, one of the antioxidant vitamins, not only acts as an antioxidant, but is directly involved in cAMP enhancement and lipid solubilization, as well as collagen formation, xenobiotic detoxification, and induction of interferon production. Since it has various actions such as antihistaminic action, immune function enhancement, antiviral and antibacterial, it is preferable to include at least vitamin C as an antioxidant vitamin. Vitamin A has a function of promoting cell differentiation and proliferation in addition to the function as an antioxidant vitamin. By promoting cell proliferation / differentiation, it becomes possible to promote the proliferation of immune cells such as T cells, so that the immunity can be improved and the defense against infection can be enhanced.
ビタミンＢ１、Ｂ２、Ｂ６、Ｂ１２、ナイアシン、葉酸、パントテン酸は、代謝補助因子としての作用が期待される。これら代謝を補助するビタミン群は、糖質、脂質、アミノ酸の代謝に関する補酵素としての役割を有し、生命活動に重要な成分である。例えば、ビタミンＢ１はＴＰＰ（チアミンピロリン酸）として、Ｂ２はＦＭＮ（フラビンモノヌクレオチド）、ＦＡＤ（フラビンアデニンジヌクレオチド）として、解糖系、ＴＣＡ回路、β酸化の調節に関与する。ビタミンＢ６はピリドキサールリン酸などとしてアミノ酸代謝に関与する。ナイアシンは、ＮＡＤ、ＮＡＤＰとして、解糖系、脂質代謝に関与する。また、パントテン酸はＣｏＡとして、ＴＣＡ回路、アミノ酸代謝、脂質代謝に関与する。葉酸はＦＨ４として、アミノ酸代謝、核酸代謝に携わる。ビタミンＢ１２はＣoＢ１２として、アミノ酸代謝に関与する。従って、これらビタミン群は、それぞれ異なる補酵素を構成する成分であることから、上記代謝補助因子として、上述したビタミン群の全てを用いることが好ましい。特に、これらビタミン群の摂取量は、エネルギー、蛋白質摂取の量により依存的に左右され、食物摂取量の少ない術後患者において全体的に不足する傾向がある。そのため、術後患者において必要となる細胞内のエネルギー供給を効率的に行わせるためには、上記全てのビタミン群を組成物に添加することが好ましい。 Vitamins B 1 , B 2 , B 6 , B 12 , niacin, folic acid, and pantothenic acid are expected to act as metabolic cofactors. These vitamins that support metabolism have a role as coenzymes for the metabolism of carbohydrates, lipids, and amino acids, and are important components for life activities. For example, vitamin B 1 represents a TPP (thiamine pyrophosphate), B 2 is FMN (flavin mononucleotide), as FAD (flavin adenine dinucleotide), glycolytic pathway, TCA cycle, involved in the regulation of β-oxidation. Vitamin B 6 is involved in amino acid metabolism as such pyridoxal phosphate. Niacin is involved in glycolysis and lipid metabolism as NAD and NADP. Moreover, pantothenic acid is involved in the TCA cycle, amino acid metabolism, and lipid metabolism as CoA. Folic acid is involved in amino acid metabolism and nucleic acid metabolism as FH4. Vitamin B 12 is as CoB12, involved in amino acid metabolism. Therefore, since these vitamin groups are components constituting different coenzymes, it is preferable to use all of the above-described vitamin groups as the metabolic cofactors. In particular, the intake of these vitamin groups depends on the amount of energy and protein intake and tends to be deficient overall in postoperative patients with low food intake. Therefore, in order to efficiently perform intracellular energy supply required in postoperative patients, it is preferable to add all the above vitamin groups to the composition.
また、葉酸、ビタミンＢ1２、β−カロテン、亜鉛などは、細胞の分化、増殖を促し得る細胞成長促進因子としての作用も期待できる。細胞増殖・分化を促進させることにより、リンパ球の一つであるＴ細胞などの免疫細胞の増殖をも促すことが可能となるため、免疫力を向上させ、手術による創傷や吻合からの治癒力や感染に対する防御力を高めることが可能となる。 In addition, folic acid, vitamin B 12 , β-carotene, zinc, and the like can be expected to act as cell growth promoting factors that can promote cell differentiation and proliferation. By promoting cell proliferation / differentiation, it is also possible to promote the proliferation of immune cells such as T cells, which are one of lymphocytes. Therefore, the immunity is improved and the healing power from wounds and anastomoses by surgery is improved. And defense against infection can be increased.
また、上記ビタミン以外にも、カルシウムの吸収を促進するためのビタミンＤ（例えば、ビタミンＤ3）などを添加することもできる。その他にも、ビオチンを添加してもよい。ビオチンは脂肪酸代謝作用を有する補酵素であり、欠乏すると皮膚炎や脱毛が生じることがある。 In addition to the above vitamins, vitamin D (for example, vitamin D 3 ) for promoting calcium absorption can also be added. In addition, biotin may be added. Biotin is a coenzyme having a fatty acid metabolism, and if it is deficient, dermatitis and hair loss may occur.
本発明の組成物を用いてビタミン類を投与する場合、１日あたりの投与量として、ビタミンＡ及び/又はβ−カロテンは、20〜2,700μg（レチノール活性等量）が適当であり（例えば、ビタミンＡが0〜2,700 μｇ、β−カロテンが0〜32.4mg）、50〜850μg（レチノール活性等量）が好ましく（例えば、ビタミンＡが0〜850 μｇ、β−カロテンが0〜10.2mg）、ビタミンＢ１は、0.1〜20 ｍgが適当であり、0.5〜10 ｍgが好ましく、ビタミンＢ２は、0.1〜20 ｍgが適当であり、0.5〜10 ｍg が好ましく、ビタミンＢ６は、1.0〜55 ｍgが適当であり、1.5〜20 ｍgが好ましく、ビタミンＢ１２は、2.0〜100 μgが適当であり、5.0〜30μgが好ましく、ビタミンＣは、40〜1,500 ｍgが適当であり、60〜1,000 ｍgが好ましく、ナイアシンは、2.0〜350 ｍgが適当であり、5.0〜30 ｍgが好ましく、葉酸は、100〜1,000 μgが適当であり、150〜900μgが好ましく、ビタミンＤ3は、0.2〜100μgが適当であり、0.5〜50μgが好ましく、ビタミンＥは、5〜850 ｍgが適当であり、10〜500 ｍgが好ましく、ビオチンは、5.0〜200 μgが適当であり、10〜150μgが好ましく、パントテン酸は、2.0〜100 ｍgが適当であり、5.0〜30 ｍgが好ましく、例えば、１日あたりの投与量を１投与単位として含む組成物を１日１回投与するように用いられるとよい。本発明の組成物の好ましい使用態様では、１日あたり、300±250μg（レチノール活性等量）のビタミンＡ及び/又はβ−カロテン（例えば、ビタミンＡが0〜550 μｇ、β−カロテンが0〜6.6 mg）、3.0±1.5mgのビタミンＢ１、3.0±1.5mgのビタミンＢ２、5.0±2.5mgのビタミンＢ６、10±5μgの-ビタミンＢ１２、500±250mgのビタミンＣ、15±7.5mgのナイアシン、550±275μgの葉酸、5.5±2.75μgのビタミンＤ３、20±10mgのビタミンＥ、50±25μgのビオチン、並びに10±5mgのパントテン酸からなる群より選択される少なくとも１種のビタミン類が投与されるように用いられ、例えば、１投与単位あたり、300±250μg（レチノール活性等量）のビタミンＡ及び/又はβ−カロテン（例えば、ビタミンＡが0〜550 μｇ、β−カロテンが0〜6.6 mg）、3.0±1.5mgのビタミンＢ１、3.0±1.5mgのビタミンＢ２、5.0±2.5mgのビタミンＢ６、10±5μgの-ビタミンＢ１２、500±250mgのビタミンＣ、15±7.5mgのナイアシン、550±275μgの葉酸、5.5±2.75μgのビタミンＤ３、20±10mgのビタミンＥ、50±25μgのビオチン、並びに10±5mgのパントテン酸を含む組成物が、１日あたり１投与単位で投与されるように用いられるとよい。 When vitamins are administered using the composition of the present invention, 20 to 2,700 μg (equivalent to retinol activity) of vitamin A and / or β-carotene is appropriate as the daily dose (for example, Vitamin A is 0-2,700 μg, β-carotene is 0-32.4 mg), 50-850 μg (equivalent to retinol activity) is preferable (for example, vitamin A is 0-850 μg, β-carotene is 0-0.2 mg), Vitamin B 1 is suitably 0.1-20 mg, preferably 0.5-10 mg, vitamin B 2 is suitably 0.1-20 mg, preferably 0.5-10 mg, and vitamin B 6 is 1.0-55. mg is suitable, 1.5-20 mg is preferred, vitamin B 12 is suitably 2.0-100 μg, 5.0-30 μg is preferred, vitamin C is suitably 40-1,500 mg, 60-1,000 mg Niacin is suitably 2.0 to 350 mg, preferably 5.0 to 30 mg, and leaves Is 100 to 1,000 [mu] g are suitable, preferably 150～900Myug, vitamin D 3 is 0.2～100Myug are suitable, preferably 0.5～50Myug, vitamin E is appropriately mg five to eight hundred fifty, 10 -500 mg is preferred, biotin is suitably 5.0-200 μg, preferably 10-150 μg, pantothenic acid is suitably 2.0-100 mg, preferably 5.0-30 mg, for example per day It may be used so that a composition containing a dose as one dosage unit is administered once a day. In a preferred embodiment of the composition of the present invention, 300 ± 250 μg (equivalent to retinol activity) of vitamin A and / or β-carotene (for example, 0 to 550 μg of vitamin A, 0 to 6.6 mg), 3.0 ± 1.5 mg vitamin B 1 , 3.0 ± 1.5 mg vitamin B 2 , 5.0 ± 2.5 mg vitamin B 6 , 10 ± 5 μg-vitamin B 12 , 500 ± 250 mg vitamin C, 15 ± 7.5 at least one selected from the group consisting of mg niacin, 550 ± 275 μg folic acid, 5.5 ± 2.75 μg vitamin D 3 , 20 ± 10 mg vitamin E, 50 ± 25 μg biotin, and 10 ± 5 mg pantothenic acid Vitamins are used to be administered, for example, 300 ± 250 μg (equivalent to retinol activity) of vitamin A and / or β-carotene (for example, 0 to 550 μg of vitamin A, β-carotene per dosage unit) There mg 0~6.6), 3.0 ± 1.5mg of vitamin B 1, of 3.0 ± 1.5mg bi Min B 2, 5.0 of ± 2.5 mg vitamin B 6, 10 ± of 5 [mu] g - Vitamin B 12, 500 Vitamin C, 15 ± 7.5 mg of niacin ± 250 mg, folic acid 550 ± 275μg, of 5.5 ± 2.75μg vitamin D 3 A composition comprising 20 ± 10 mg vitamin E, 50 ± 25 μg biotin, and 10 ± 5 mg pantothenic acid may be used to be administered in one dosage unit per day.
さらに、本発明の組成物は、コエンザイムＱ１０、ガラクトオリゴ糖などを含有させてよい。コエンザイムＱ１０は、強い抗酸化作用を有するため、手術に伴う酸化的ストレスに対して強力な還元作用を有する抗酸化剤としての作用を期待できる。また、ATP産生に関与する成分であるため、補充することで栄養素の代謝が円滑に行われる効果も期待できる。ガラクトオリゴ糖は、消化管内でビフィズス菌を増加させ、整腸作用を示す機能性のオリゴ糖であり、補充することで消化管の状態を正常に保ち円滑な栄養素の吸収が期待できる。 Furthermore, the composition of the present invention may contain coenzyme Q10, galactooligosaccharide, and the like. Since coenzyme Q10 has a strong antioxidant action, it can be expected to act as an antioxidant having a strong reducing action against oxidative stress associated with surgery. In addition, since it is a component involved in ATP production, supplementation can also be expected to have an effect of smooth metabolism of nutrients. Galacto-oligosaccharide is a functional oligosaccharide that increases bifidobacteria in the digestive tract and exhibits an intestinal regulating action. By supplementing it, the state of the digestive tract can be kept normal and smooth nutrient absorption can be expected.
本発明の組成物を用いて投与する場合、一日あたりの投与量として、コエンザイムＱ１０は、3〜30 mgが適当であり、5〜25 mgが好ましく、ガラクトオリゴ糖は、0〜10 gが適当であり、0〜5 gが好ましく、例えば、１日あたりの投与量を１投与単位として含む組成物を１日１回投与するように用いられるとよい。 When administered using the composition of the present invention, as a daily dose, coenzyme Q10 is suitably 3 to 30 mg, preferably 5 to 25 mg, and galactooligosaccharide is suitably 0 to 10 g. 0 to 5 g is preferable, and for example, a composition containing a daily dose as one dosage unit may be used so as to be administered once a day.
本発明の組成物の投与は、経口で行われるとよい。場合によっては経鼻経管、胃瘻、腸瘻など経腸的な投与方法でも構わない。 Administration of the composition of the present invention may be performed orally. In some cases, enteral administration methods such as nasal tube, gastrostomy, intestinal fistula may be used.
本発明の組成物は、上記各成分を混合し、粉末、顆粒、錠剤、液剤などの剤形に構成することもできるが、術後患者が容易に摂取可能とするためには、液状（ドリンクタイプ）もしくはゲル状（ゼリータイプ）、粉末製品とすることが好ましい。液状もしくはゲル状、粉末製品とすれば、経口で摂取できる術後患者は経口にて、摂取することが可能となる。 The composition of the present invention can be prepared by mixing the above-described components into a dosage form such as powder, granule, tablet, liquid, etc. Type) or gel (jelly type), preferably a powder product. If it is a liquid, gel, or powder product, a postoperative patient who can be taken orally can take it orally.
また、ゲル状製品とする場合に、水にゲル化剤を溶解し、これに組成物の各成分を配合した後、容器に充填して、冷却するとよい。必要により、ゲル化剤を水に溶解させるために加熱をしたり、容器を密封したり、組成物を加熱等により殺菌するとよい。 Moreover, when setting it as a gel-like product, after melt | dissolving a gelatinizer in water and mix | blending each component of a composition with this, it is good to fill with a container and to cool. If necessary, heating may be performed to dissolve the gelling agent in water, the container may be sealed, or the composition may be sterilized by heating or the like.
経口で摂取する際の味覚を向上させるためには、水の代わりに果汁や野菜汁などを用いることができる。本発明の組成物への添加量は、一投与単位あたりの含有量として、水、果汁又は野菜汁は、10〜500 gが適当であり、35〜250 gが好ましい。果汁または野菜汁としては、ブルーベリー果汁、ぶどう果汁、グレープフルーツ果汁、レモン果汁、みかん（オレンジ）果汁、キャロット汁、リンゴ果汁、パイナップル果汁、桃果汁、バナナ果汁などを挙げることができ、ビタミンC、ビタミンB群の酸味、臭いを和らげることができるという点から、キャロット汁、ブルーベリー果汁やぶどう果汁が好ましい。液状製品の場合、一投与単位あたりの容量は、20〜250 mlが適当であり、30〜150 mlが好ましく、125±25 mLがより好ましい。また、液状製品の場合の水分含量は、例えば、一投与単位あたり、110±22.0 g程度とすることができる。ゲル状製品の場合、一投与単位あたりの質量は、20〜250 gが適当であり、30〜150 gが好ましく、80±16 gがより好ましい。また、ゲル状製品の場合の水分含量は、例えば、一投与単位あたり、53±10.6 g程度とすることができる。 In order to improve the taste when taken orally, fruit juice or vegetable juice can be used instead of water. The amount added to the composition of the present invention is suitably 10 to 500 g, preferably 35 to 250 g of water, fruit juice or vegetable juice as the content per dosage unit. Examples of fruit juice or vegetable juice include blueberry juice, grape juice, grapefruit juice, lemon juice, orange juice, carrot juice, apple juice, pineapple juice, peach juice, banana juice, etc., vitamin C, vitamin Carrot juice, blueberry juice and grape juice are preferred from the viewpoint that the acidity and smell of Group B can be relieved. In the case of a liquid product, the volume per dosage unit is suitably 20 to 250 ml, preferably 30 to 150 ml, more preferably 125 ± 25 ml. The water content in the case of a liquid product can be, for example, about 110 ± 22.0 g per dosage unit. In the case of a gel product, the mass per dosage unit is suitably 20 to 250 g, preferably 30 to 150 g, more preferably 80 ± 16 g. Moreover, the water content in the case of a gel-like product can be about 53 ± 10.6 g per dosage unit, for example.
ゲル化剤としては、デキストリン、寒天、キサンタンガム、ローカストビーンガム、カラギーナン、ペクチンなどの増粘多糖類、ジェランガム、サイリュームシードガム、タラガム、グアガム、グルコマンナンアルギン酸、タマリンドシードガム、セルロースなどを用いることができ、１種又は２種以上の増粘多糖類を用いることが好ましい。本発明の組成物への添加量は、一投与単位あたりの含有量として、ゲル化剤は、0.5〜5.0 gが適当であり、0.75〜2.0 gが好ましく、0.82±0.16gがより好ましい。 As gelling agents, it is possible to use thickening polysaccharides such as dextrin, agar, xanthan gum, locust bean gum, carrageenan, pectin, gellan gum, silium seed gum, tara gum, guar gum, glucomannan alginic acid, tamarind seed gum, cellulose, etc. It is possible to use one or more thickening polysaccharides. The amount added to the composition of the present invention is suitably 0.5 to 5.0 g, preferably 0.75 to 2.0 g, more preferably 0.82 ± 0.16 g, as the content per dosage unit.
ゲル状製品のゲル強度は、術後患者が摂取できる限り、特に限定されるわけではないが、20℃におけるゲル強度が7,200±2,000 N/m2であることが好ましい。 The gel strength of the gel product is not particularly limited as long as it can be ingested by the patient after surgery, but the gel strength at 20 ° C. is preferably 7,200 ± 2,000 N / m 2 .
また、ゲル強度が7,200±2,000 N/m2のとき、付着エネルギーが50.3±40 J/m3であり、凝集性が0.23±0.5 J/m3であることがより好ましい。このように付着性が低く、凝集性が高いゲルは優れた嚥下適性を有する。 Further, when the gel strength is 7,200 ± 2,000 N / m 2 , it is more preferable that the adhesion energy is 50.3 ± 40 J / m 3 and the cohesiveness is 0.23 ± 0.5 J / m 3 . Thus, a gel with low adhesiveness and high cohesion has excellent swallowability.
ゲル強度は、以下のようにして測定することができる。ゲル強度測定機器としては、山電テクスチュロメーター及びφ20ｍｍ×8ｍｍのプランジャーを用い、測定温度20℃、圧縮速度（プランジャーを押し込む速度）10ｍｍ/s、プランジャーを押し込む回数2回にて測定を行う。 The gel strength can be measured as follows. As a gel strength measuring instrument, Yamaden Texturometer and φ20mm × 8mm plunger are used. Measurement temperature is 20 ° C, compression speed (plunger pushing speed) is 10mm / s, and the plunger is pushed twice. I do.
付着エネルギーは上記ゲル強度測定において、1回押し込んだ後、プランジャーを引き抜くときの負のエネルギーとして測定する。 In the gel strength measurement, the adhesion energy is measured as a negative energy when the plunger is pulled out after being pushed once.
凝集性は上記ゲル強度測定において、2回押し込んだ時に1回目と2回目のエネルギーの比率として測定する。 In the above gel strength measurement, the cohesiveness is measured as the ratio of the first and second energy when pressed twice.
さらに、本発明の組成物には、ブドウ糖、砂糖、香料、酸味料、甘味料（アセスルファムＫ、スクラロースなど）などを添加してもよい。また、必要に応じて、賦形剤、結合剤、増量剤、崩壊剤、界面活性剤、滑沢剤、分散剤、緩衝剤、防腐剤、コーティング剤、保存剤、着色剤、可塑剤などを添加してもよい。 Furthermore, you may add glucose, sugar, a fragrance | flavor, a sour agent, a sweetener (Acesulfame K, sucralose etc.) etc. to the composition of this invention. If necessary, excipients, binders, extenders, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, coating agents, preservatives, colorants, plasticizers, etc. It may be added.
本発明の組成物のエネルギー量は、一投与単位あたり、10〜200kcalが適当であり、20〜125kcalが好ましい。また、一般成分については、例えば、一投与単位当たり、たんぱく質の含有量は5〜50 g程度、炭水化物の含有量は3〜30 g程度、ナトリウムの含有量は1〜500 mg程度、水分の含有量は30〜150 g程度とするとよい。 The amount of energy of the composition of the present invention is suitably 10 to 200 kcal, preferably 20 to 125 kcal per dosage unit. In addition, for general components, for example, per unit dosage, protein content is about 5-50 g, carbohydrate content is about 3-30 g, sodium content is about 1-500 mg, water content The amount should be about 30-150 g.
本発明の組成物の標準成分表(ドリンクタイプ1本125mL±25 mL又はゼリータイプ１個80 g±16 g中)の例を下記の表１に示す。 Table 1 below shows an example of a standard ingredient table of the composition of the present invention (in one drink type 125 mL ± 25 mL or one jelly type 80 g ± 16 g).
原材料としては、コラーゲンペプチド（ゼラチン）、ガラクトオリゴ糖、砂糖、ブドウ糖、果汁（オレンジ、リンゴ、パインアップル、ピーチ、バナナ）、乾燥酵母、コエンザイムＱ１０、ビタミンＣ、乳酸Ｃａ、香料、酸味料、ビタミンＥ、増粘多糖類、クエン酸鉄Ｎａ，甘味料（アセスルファムＫ、スクラロース）、ナイアシン、パントテン酸Ｃａ、ビタミンＢ６、ビタミンＤ、ビタミンＡ、ビタミンＢ２、ビタミンＢ１、β-カロテン、葉酸、ビタミンＢ１２などを挙げることができる。 Raw materials include collagen peptide (gelatin), galactooligosaccharide, sugar, glucose, fruit juice (orange, apple, pineapple, peach, banana), dry yeast, coenzyme Q10, vitamin C, calcium lactate, flavor, acidulant, vitamin E , Thickening polysaccharide, iron Na citrate, sweetener (acesulfame K, sucralose), niacin, pantothenic acid Ca, vitamin B 6 , vitamin D, vitamin A, vitamin B 2 , vitamin B 1 , β-carotene, folic acid, Vitamin B 12 etc. can be mentioned.
本発明の組成物は、原材料に由来するカリウム、カルシウム、マグネシウム、リンなどの電解質を含有してもよい。カリウム、カルシウム、マグネシウム、リンなどの電解質成分は、日本人の食事摂取基準（男性の50〜59歳レベル）を超えないような量で含むことが望ましい。
ナトリウム（目標量（塩化ナトリウム相当量）：8 g未満）
カリウム（目安量：2500 mg、目標量：3000 mg以上）
カルシウム（推奨量：700 mg）
マグネシウム（推奨量：350 mg）
リン（耐容上限量：3000 mg、目安量：1000 mg）
The composition of the present invention may contain an electrolyte such as potassium, calcium, magnesium, phosphorus derived from raw materials. It is desirable to include electrolyte components such as potassium, calcium, magnesium, and phosphorus in amounts that do not exceed Japanese dietary intake standards (male 50-59 year old levels).
Sodium (target amount (sodium chloride equivalent): less than 8 g)
Potassium (reference amount: 2500 mg, target amount: 3000 mg or more)
Calcium (recommended amount: 700 mg)
Magnesium (Recommended amount: 350 mg)
Phosphorus (tolerable upper limit: 3000 mg, approximate amount: 1000 mg)
以下、実施例に基づいて本発明を詳細に説明するが、本発明はこれらの実施例に限定されるものではない。
〔実施例１〕
要約
本試験では，周術期の術後早期回復への臨床的応用を目指し，創傷治癒作用について，ラットの切創モデルを用いて，創傷部位のコラーゲンの生成を指標に検討を行った．
切創モデルは8週齢のSlc:SD (SPF)ラットの背部正中に約7cmの切創を作製し，スポンジを挿入後縫合し作製した．
群構成は，2日摘出群，4日摘出群及び6日摘出群それぞれに被験物質であるCP10群，比較対照物質として注射用水群及びアルジネード群を設定した．
その結果， CP10群の血清CRPにおいて6日摘出群で有意な低値が認められ，創傷部位のコラーゲンの生成の指標であるコラーゲンI及びIIIの遺伝子発現に高値傾向が認められた．また，ヒドロキシプロリン含量に有意差又は増加傾向は認められなかったが，炎症期に観察される既存コラーゲンの分解によるヒドロキシプロリンの速やかな減少が認められた．
炎症期にはコラーゲンが炎症細胞によって分解され減少を示し，その後の線維化期にコラーゲンが増加を示すことが知られており，コラーゲンI及びIIIの遺伝子発現において2及び4日摘出群と比較し6日摘出群でいずれの投与群においても増加を示している．よって，ヒドロキシプロリンについては，炎症期のためコラーゲンが分解され減少した結果である可能性が考えられた．
CP10群では，上述のとおり血清CRPが6日摘出群で有意な低値を示した．これはCP10を投与することによりコラーゲンI及びIIIの遺伝子発現が増加し，炎症期の創傷治癒が促進した結果，注射用水及びアルジネード群よりも早期に炎症が治まった可能性が考えられた．
炎症が早期に治まる場合，速やかに線維化期に移行すると考えられ，線維芽細胞の増殖により早期にコラーゲン量の増加を示す可能性が示唆された．
以上のことを総括すると，本試験条件下においてコラーゲンペプチド摂取により炎症期が短縮する可能性が示唆された．その結果，速やかに線維化期に移行し創傷治癒作用を示す可能性が示唆された．
EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to these Examples.
[Example 1]
In this study, aiming at clinical application to early postoperative recovery in the perioperative period, we examined the wound healing effect using a rat incision model with collagen production as an index.
The incision model was prepared by making an approximately 7cm incision in the midline of the back of an 8-week-old Slc: SD (SPF) rat, inserting a sponge, and suturing.
The group composition consisted of the CP10 group as the test substance in the 2-day, 4-day, and 6-day groups, respectively, and the water group for injection and the alginate group as the comparative control substances.
As a result, serum CRP in CP10 group showed a significantly low value in the 6-day excised group, and a high tendency was observed in the expression of collagen I and III genes, which are indicators of collagen production at the wound site. There was no significant difference or increase in hydroxyproline content, but there was a rapid decrease in hydroxyproline due to degradation of existing collagen observed in the inflammatory phase.
It is known that collagen is degraded and decreased by inflammatory cells in the inflammatory phase, and collagen is increased in the subsequent fibrosis phase. Compared with the 2- and 4-day excised groups in the expression of collagen I and III genes. The 6-day excision group showed an increase in all treatment groups. Therefore, hydroxyproline may be a result of degradation and degradation of collagen during the inflammatory period.
In the CP10 group, serum CRP was significantly lower in the 6-day excised group as described above. CP10 administration increased collagen I and III gene expression and promoted wound healing in the inflammatory phase, suggesting that inflammation was cured earlier than the water for injection and alginate group.
When inflammation subsides early, it is thought that the fibrosis phase is promptly changed, and it is suggested that fibroblast proliferation may cause an early increase in collagen content.
To summarize the above, it was suggested that ingestion of collagen peptide may shorten the inflammatory phase under the test conditions. As a result, it was suggested that it may shift to the fibrosis stage and show wound healing.
試験目的
周術期の術後早期回復への臨床的応用を目指し，創傷治癒作用について，ラットの切創モデルを用いて，創傷部位のコラーゲンの生成（遺伝子発現及びタンパク質量）を指標に検討を行った．
Purpose of the study Aiming at clinical application to early postoperative recovery in the perioperative period, the wound healing effect was examined using the rat incision model with collagen production (gene expression and protein content) as an index. went.
適用した基準
当該試験は厚生労働省における医薬品GLP省令の対象外とした．
本試験は以下の法律，基準及び指針を準用した．
・ 動物の愛護及び管理に関する法律
〔法律第105号，昭和48年10月1日（平成26年5月30日最終改正：法律第46号）〕
・ 実験動物の飼養及び保管並びに苦痛の軽減に関する基準
〔環境省告示第88号，平成18年4月28日（平成25年8月30日最終改正：環境省告示第84号）〕
・ 動物の殺処分方法に関する指針
〔総理府告示第40号，平成7年7月4日（平成19年11月12日一部改正：環境省告示第105号）〕
なお，当該試験は試験実施施設内の動物実験委員会が規定する動物実験計画書（審議No. 151201B）の審議・承認を得た後に実施した．
Criteria applied The study was excluded from the GLP Ministerial Ordinance of the Ministry of Health, Labor and Welfare.
The following laws, standards and guidelines were applied to this study.
・ Act on the protection and management of animals [Law No. 105, October 1, 1973 (Last revision on May 30, 2014: Law No. 46)]
・ Standards for the breeding and storage of laboratory animals and pain relief [Ministry of the Environment Notification No. 88, April 28, 2006 (Final revision on August 30, 2013: Ministry of the Environment Notification No. 84)]
・ Guidelines on how to kill animals [Primary Office Notification No. 40, July 4, 1995 (November 12, 2007, partial revision: Ministry of the Environment Notification No. 105)]
This test was conducted after obtaining the deliberation and approval of the animal experiment plan (Deliberation No. 151201B) prescribed by the animal experiment committee in the study facility.
試験材料及び器材
１．被験物質，比較対照物質及び試薬
被験物質であるCP10（ロット番号：4E31/STB）は，1本（125 mL）中にコラーゲンペプチドを10 g含有する液体（30本入手）であった．
比較対照物質であるアルジネード（ロット番号：5281/0856）は，1本（125 mL）中にアルギニンを2.5 g含有する液体（24本入手）であった．
被験物質及び比較対照物質はいずれも2015年12月21日にニュートリー株式会社より入手し，試験期間を通じて被験物質保存庫IVにて常温・暗所（許容範囲：許容温度：10〜30℃，実測値：22〜25℃）で保存した．
試薬である注射用水（大塚蒸留水）「ロット番号：K4I72，(株)大塚製薬工場」，塩酸メデトミジン（ドルベネ注）「ロット番号：310906，共立製薬(株)」，ミダゾラム（ミダゾラム注射液）「ロット番号：C14037，テバ製薬(株)」，ブトルファノール（べトルファール）「ロット番号：36，Meiji Seikaファルマ(株)」はいずれも室温保存した．
Test materials and equipment Test substance, control substance and reagent Test substance CP10 (lot number: 4E31 / STB) was a liquid (30 bottles) containing 10 g of collagen peptide in one bottle (125 mL).
Arginade (lot number: 5281/0856), a comparative control substance, was a liquid containing 2.5 g of arginine in one bottle (125 mL) (24 bottles available).
Both the test substance and the comparative control substance were obtained from Newtory Co., Ltd. on December 21, 2015, and kept at room temperature in the test substance storage room IV throughout the test period (allowable range: allowable temperature: 10-30 ° C, (Measured value: 22-25 ° C.)
Reagent water for injection (Otsuka distilled water) “Lot number: K4I72, Otsuka Pharmaceutical Factory”, Medetomidine hydrochloride (Dolbene Note) “Lot number: 310906, Kyoritsu Pharmaceutical Co., Ltd.”, Midazolam (Midazolam Injection) Lot No .: C14037, Teva Pharmaceutical Co., Ltd. and Butorphanol (Betofaru) “Lot No. 36, Meiji Seika Pharma Co., Ltd.” were all stored at room temperature.
２．使用動物
7週齢（モデル作製時週齢：8週齢）のSlc:SD (SPF)ラット，雄性63匹（発注数：雄性60匹）を日本エスエルシー(株)（引佐支所）より，2016年1月19日に入手した．
動物は入荷から群分け日までは馴化を行った．ただし，入荷日を0日として5日までの期間は検疫を行った．一般状態観察は毎日行い，体重はパーソナル電子天秤（EW-12Ki，(株)エー・アンド・デイ）を使用して，入荷1（入荷翌日），3及び5日に測定した．
動物は入荷日に耳パンチ法により個体を識別した．各ケージには試験番号，性別及び個体識別番号（耳パンチ番号）を記入したカードを付けた．群分け後は群及び動物番号を追記した．
2. Animal used
Slc: SD (SPF) rats 7 weeks old (8 weeks old at the time of model creation), 63 males (ordered: 60 males) from Japan SLC Co., Ltd. (Hisa Branch), 2016 I got it on March 19th.
The animals were acclimatized from arrival until the grouping date. However, quarantine was conducted for a period of up to 5 days with the arrival date as 0 days. The general condition was observed every day, and the body weight was measured on arrival 1 (the day after arrival), 3 and 5 days using a personal electronic balance (EW-12Ki, A & D Co., Ltd.).
The animals were identified on the day of arrival by ear punching. Each cage was given a card with the test number, gender and individual identification number (ear punch number). After grouping, group and animal numbers were added.
３．飼育方法
動物は111動物室に温度22±3℃（実測値：19.8〜22.0℃），湿度50±20%（実測値：40.5〜52.7%），換気回数13〜17回／時間（HEPAフィルターでろ過したオールフレッシュ方式），照明時間8:00〜20:00（明12時間，暗12時間）の飼育環境下で，ステンレス製可動ラック（1790W×470D×1650H mm）に装着したステンレス製金網2連ケージの1区画（255W×185D×200H mm）に個別に収容した．
飼料はステンレス製固型飼料給餌器により固型飼料ラボMRストック（ロット番号：20151081，日本農産工業(株)）を，試験期間を通じ自由に与えた．
飲料水はポリサルフォン製給水器（先管ステンレス製）により水道水を，試験期間を通じ自由に与えた．
器材はいずれも使用に先立ってオートクレーブで高圧蒸気滅菌し，汚物受け皿は3回/週以上，給水器は2回／週，その他は2回/月の頻度で交換した．
飼料については，ロットごとに有害物質は（一財）東京顕微鏡院で，栄養分析及び微生物検査はオリエンタル酵母工業(株)で分析した成績書を，いずれも日本農産工業(株)より入手し，標準操作手順書に定めた基準値の許容範囲内であることを確認した．また，飲料水については，水道水の一般検査を隔月ごとに(一財)北海道薬剤師会公衆衛生検査センターに依頼し，成績書を入手して検査結果が標準操作手順書に定めた基準値の許容範囲内であることを確認した．また，上記一般検査実施月以外には残留塩素（遊離残留塩素濃度）測定を実施し，標準操作手順書に定めた基準値の許容範囲内であることを確認した．
3. Breeding method Animals should be kept in 111 animal rooms at a temperature of 22 ± 3 ° C (actual value: 19.8-22.0 ° C), humidity 50 ± 20% (actual value: 40.5-52.7%), ventilation rate 13-17 times / hour (with HEPA filter) Stainless steel wire mesh mounted on a stainless steel movable rack (1790W x 470D x 1650H mm) in a breeding environment of 8: 00-20: 00 (light hours 12 hours, dark hours 12 hours). It was housed individually in one compartment (255W x 185D x 200H mm) of the continuous cage.
For the feed, a solid feed laboratory MR stock (lot number: 20151081, Nippon Agricultural Industry Co., Ltd.) was freely given throughout the test period using a stainless steel solid feed feeder.
Drinking water was given freely through a polysulfone water supply (made of stainless steel), throughout the test period.
Prior to use, all the equipment was autoclaved in an autoclave, the septic pan was replaced more than 3 times / week, the water supply was changed 2 times / week, and the others were changed 2 times / month.
For feeds, the toxic substances for each lot were obtained from Tokyo Microscope, and the nutrition analysis and microbiological tests were analyzed by Oriental Yeast Co., Ltd., both from Nippon Agricultural Industry Co., Ltd. It was confirmed that it was within the allowable range of the standard value specified in the standard operating procedure. In addition, for drinking water, a general inspection of tap water is requested every other month from the Hokkaido Pharmacists Association Public Health Inspection Center, and results are obtained and the inspection results are within the standard values set in the standard operating procedure manual. It was confirmed that it was within the allowable range. Other than the above general inspection month, residual chlorine (free residual chlorine concentration) was measured, and it was confirmed that it was within the allowable range of the reference value defined in the standard operating procedure.
試験方法
１．投与物質の調製
被験物質及び比較対照物質は，そのまま使用した．
Test method 1. Preparation of administered substance The test substance and the control substance were used as they were.
２．動物の選択及び群分け法
検疫・馴化期間が終了し，一般状態に異常のみられなかった7週齢のラット（個体識別番号37の動物は，左上切歯破折のため，群分けから除外した．）を使用した．検疫期間の最終日に測定した体重を指標として，層別連続無作為化法を用いて，下記に記載した群構成表に基づき群分けを行った．
2. Animal selection and grouping 7-week-old rats whose quarantine and acclimatization period had ended and no abnormalities were observed in the general state (the animal with individual identification number 37 was excluded from the grouping due to fracture of the left upper incisor) .)It was used. Using the weight measured on the last day of the quarantine period as an index, grouping was performed using the stratified randomization method based on the group composition table described below.
３．被験物質の投与
被験物質及び比較対照物質は，群分け後より，1日1回，摘出日まで，胃ゾンデを用いて胃内に強制投与を行った．
投与液量は，5 mL/kg/dayとして，最新体重を基に算出し，小数点以下2桁を四捨五入し，小数点以下1桁で表示した．
投与量については，有効性が期待される投与量に設定した．
3. Administration of test substance The test substance and the control substance were forcibly administered into the stomach using a gastric sonde once a day until the excision date after grouping.
The dose volume was calculated as 5 mL / kg / day based on the latest body weight, rounded off to the first decimal place, and displayed to the first decimal place.
The dose was set to the dose expected to be effective.
４．切創モデルの作製
被験物質及び比較対照物質投与開始4日目の投与翌日にモデル作製を行った．
ラットを塩酸メデトミジン0.15 mg/kg，ミダゾラム2 mg/kg，ブトルファノール2.5 mg/kg混合液麻酔下（腹腔内投与）（麻酔が浅い場合は，麻酔の追加投与を実施した）で腹臥位に固定し，背部をシェーバーで剃毛した．肩甲骨直下より背部正中に約7cmの切創を作製し，スポンジ（セルローススポンジ，富士ケミカル(株)，長さ6cm，幅0.2cm，高さ0.5cm）を挿入後，中央部を縫合し，更に頭部側及び尾部側をそれぞれ約0.5cm間隔で縫合した．創面に防水シートを貼付し，ガーゼ及び粘着包帯で固定した．
切創の作製条件及び用いるスポンジについては，事前の検討試験[「ラット切創モデルを用いたCP-10の創傷治癒作用の評価（検討試験）」，試験番号：15064，株式会社新薬リサーチセンター]により確認を行った．なお，検討試験において，切創作製及びスポンジ挿入による動物への悪影響は認められなかった．
モデル作製後も被験物質及び比較対照物質の投与は継続した．
4). Creation of a cut model A model was prepared the day after administration on the 4th day after administration of the test substance and control substance.
Rats were fixed in the prone position under anesthesia (intraperitoneal administration) with a mixture of medetomidine hydrochloride 0.15 mg / kg, midazolam 2 mg / kg, butorphanol 2.5 mg / kg (when anesthesia was shallow, additional anesthesia was administered) The back was shaved with a shaver. A cut of about 7cm was made in the midline of the back from just below the scapula. After inserting a sponge (cellulose sponge, Fuji Chemical Co., Ltd., length 6cm, width 0.2cm, height 0.5cm), the center was sutured. Furthermore, the head and tail sides were sutured at intervals of approximately 0.5 cm. A waterproof sheet was applied to the wound surface and fixed with gauze and adhesive bandages.
Regarding the preparation conditions of the wound and the sponge to be used, a preliminary examination test ["Evaluation of wound healing action of CP-10 using rat cut wound model (examination test)", test number: 15064, Shinyaku Research Center, Inc.] This was confirmed by In the study, there were no adverse effects on animals due to the creation of cuts and insertion of sponges.
Administration of the test substance and control substance continued after the model was prepared.
５．摘出及び採血
切創モデル作製日を0日とし，2，4あるいは6日のそれぞれ，被験物質及び比較対照物質の投与後に採血及びスポンジの摘出を実施した．すなわち，ガーゼ及び粘着包帯を除去後，塩酸メデトミジン0.15 mg/kg，ミダゾラム2 mg/kg，ブトルファノール2.5 mg/kg混合液麻酔下（腹腔内投与）（麻酔が浅かったため，全例について麻酔の追加投与を実施した）で腹大動脈より注射針（テルモ(株)）及び注射筒（テルモ(株)）を用いて全採血を行った．得られた血液は，血清を分取し，CRPの測定に用いた．採血終了後，腹大動脈より放血安楽死させ，縫合糸を外してスポンジを摘出した．
摘出したスポンジは，上下に2等分して，一方を遺伝子解析用に，一方をヒドロキシプロリン定量用に使用した．なお，解析に使用するまでのスポンジは，-80℃以下で保存した．
5. Extraction and blood sampling The cut model creation date was 0 days, and blood sampling and sponge extraction were performed after administration of the test substance and control substance on days 2, 4 and 6, respectively. That is, after removing gauze and adhesive bandage, medetomidine hydrochloride 0.15 mg / kg, midazolam 2 mg / kg, butorphanol 2.5 mg / kg mixed anesthesia (intraperitoneal administration) The whole blood was collected from the abdominal aorta using an injection needle (Terumo) and a syringe (Terumo). Serum was collected from the obtained blood and used for CRP measurement. After blood collection, he was euthanized from the abdominal aorta, the suture was removed, and the sponge was removed.
The extracted sponge was divided into two equal parts, one for gene analysis and one for hydroxyproline determination. The sponges used for analysis were stored at -80 ° C or lower.
６．一般状態観察
一般状態観察は，1日1回，摘出日までを行った．
6). General state observation General state observation was performed once a day until the excision date.
７．摂餌量測定
摂餌量は，投与開始より摘出日まで，1日あたり摂餌量を毎日測定した．
7). Food intake measurement The food intake was measured daily from the start of administration until the day of excision.
８．体重測定
体重測定は，被験物質投与開始日，切創作製当日の術前及び解剖前に行った．
8). Body weight measurement Body weight measurement was performed on the day of test substance administration, on the day of cut preparation, before surgery and before dissection.
９．血清CRPの測定
得られた血清を用いて，ELISA法によりCRPの測定を行った．（Rat High-sensitive CRP ELISA Kit（KAMIYA BIOMEDICAL COMPANY））
9. Measurement of serum CRP CRP was measured by ELISA using the obtained serum. (Rat High-sensitive CRP ELISA Kit (KAMIYA BIOMEDICAL COMPANY))
１０．コラーゲンI及びIIIの遺伝子発現解析
摘出したスポンジは長さ約0.5cmにトリミング後，コラーゲンI及びIII型の遺伝子発現解析を行った．
10. Collagen I and III gene expression analysis The extracted sponges were trimmed to about 0.5 cm in length and then analyzed for collagen I and III type gene expression.
１１．ヒドロキシプロリンの定量
摘出したスポンジより細胞の抽出を行い，ELISA法により，ヒドロキシプロリンの定量を行った．
11. Quantification of hydroxyproline Cells were extracted from the excised sponge, and hydroxyproline was quantified by ELISA.
１２．試験スケジュール
12 Exam schedule
１３．動物の愛護／動物実験計画書（審議No. 151201B）
人道的エンドポイント（実験動物を激しい苦痛から解放するための安楽死のタイミング）について，適用した動物は発生しなかった．
13. Animal Protection / Animal Experiment Plan (Deliberation No. 151201B)
No animals were applied for humane endpoints (timing of euthanasia to release experimental animals from severe pain).
１４．統計処理
得られた数値は各群で平均値及び標準誤差を算出した．
統計処理は，A〜C群（2日摘出群），D〜F群（4日摘出群）及びG〜I群間（6日摘出群）で，それぞれ行った．
A（注射用水群「Control」）とB（CP10群）及びC群（アルジネード群「Arg」），D（注射用水群「Control」）とE（CP10群）及びF群（アルジネード群「Arg」），G（注射用水群「Control」）とH（CP10群）及びI群（アルジネード群「Arg」）間の比較は，Bartlett法により等分散性の検定を行い，等分散の場合は更に一元配置分散分析を行い，有意な場合はTukey法により平均値の比較を行った．不等分散の場合はKruskal-WallisのH検定を行い，有意な場合はTukey法により平均順位の比較を行った．
Bartlett法，一元配置分散分析及びKruskal-WallisのH検定については有意水準を危険率5%，Tukey法については有意水準を危険率5%及び1%とした．
14 Statistical processing The average values and standard errors were calculated for each group.
Statistical processing was performed between groups A to C (2-day excision group), D to F group (4-day excision group), and G to I group (6-day excision group).
A (water group for injection “Control”) and B (CP10 group) and C group (alginate group “Arg”), D (water group for injection “Control”) and E (CP10 group) and F group (alginate group “Arg”) ), G (injection water group “Control”) and H (CP10 group) and I group (arginade group “Arg”) are tested for equivariance by the Bartlett method. A variance analysis was performed, and if significant, the mean values were compared by the Tukey method. In the case of unequal variance, Kruskal-Wallis H test was performed, and when significant, the average rank was compared by Tukey method.
For the Bartlett method, one-way analysis of variance and Kruskal-Wallis H test, the significance level was 5% and the significance level was 5% and 1% for the Tukey method.
１５．群分けから除外された動物の処置
群分け後の残余動物については，群分け終了後に試験から除外し，塩酸メデトミジン0.15 mg/kg，ミダゾラム2 mg/kg，ブトルファノール2.5 mg/kg混合液麻酔下（腹腔内投与）で腹大動脈より放血安楽死させた．
15. Treatment of animals excluded from grouping Residual animals after grouping were excluded from the study after grouping and under anesthesia with a mixture of medetomidine hydrochloride 0.15 mg / kg, midazolam 2 mg / kg, butorphanol 2.5 mg / kg ( He was euthanized from the abdominal aorta.
試験結果
１．一般状態観察
いずれの群においても試験期間を通じて異常は認められなかった．
Test results 1. General condition observation No abnormalities were observed in any group throughout the study period.
２．摂餌量
結果を図1，表1に示した．
2日摘出群，4日摘出群及び6日摘出群間いずれもほぼ同様に推移し試験期間を通じて有意差は認められなかった．
2. Food intake The results are shown in Fig. 1 and Table 1.
The 2-day, 4-day, and 6-day groups showed similar changes, and no significant difference was observed throughout the study period.
３．体重
結果を図2，表2に示した．
2日摘出群，4日摘出群及び6日摘出群間いずれもほぼ同様に推移し試験期間を通じて有意差は認められなかった．
3. Body weight The results are shown in Fig. 2 and Table 2.
The 2-day, 4-day, and 6-day groups showed similar changes, and no significant difference was observed throughout the study period.
４．血清CRP
結果を図3，表3に示した．
6日摘出注射用水群と比較し，CP10群で有意な低値が認められた．
2日摘出群及び4日摘出群では，有意差は認められなかった．
4). Serum CRP
The results are shown in Fig. 3 and Table 3.
The CP10 group showed a significantly lower value compared to the 6-day excised water group for injection.
There was no significant difference between the 2-day and 4-day groups.
５．コラーゲンI及びIIIの遺伝子発現解析
結果を図4〜7，表4に示した．
リアルタイムPCRの実施基準をRNA Integrity Number（RIN）値7.0以上とし，品質確認を実施した結果，いずれの検体においてもRIN値7.0以上（実測値：7.8〜9.8）を満たしていた．
内部標準遺伝子はActb及びGapdhとし，コラーゲンI（Col1a1）及びコラーゲンIII（Col3a1）のRQ（相対値）を算出した．
なお，2日摘出注射用水群の平均相対値を1とし，それぞれの摘出日における検体の相対値を算出した．
その結果，2日摘出群，4日摘出群及び6日摘出群間，いずれの項目においても有意差は認められなかった．しかし，CP10群の4日摘出群及び6日摘出群において高値傾向が認められた．
また，参考データとするためAとB及びC群，DとE及びF群，GとH及びI群間の比較をMann-WhitneyのU検定で行ったが，いずれの群間も有意差は認められなかった．
5. The results of gene expression analysis of collagen I and III are shown in Figs.
The standard of real-time PCR was set to an RNA Integrity Number (RIN) value of 7.0 or higher, and as a result of quality confirmation, the RIN value of 7.0 or higher (actual values: 7.8 to 9.8) was satisfied in all samples.
The internal standard genes were Actb and Gapdh, and the RQ (relative value) of collagen I (Col1a1) and collagen III (Col3a1) was calculated.
The average relative value of the 2-day excised water group for injection was set to 1, and the relative value of the specimen on each excision date was calculated.
As a result, there was no significant difference between the 2-day, 4-day, and 6-day groups. However, a high trend was observed in the 4-day and 6-day groups of CP10.
For reference data, the A and B and C groups, the D and E and F groups, and the G and H and I groups were compared using the Mann-Whitney U test. I was not able to admit.
６．ヒドロキシプロリンの定量
結果を図8，表5に示した．
2日摘出群，4日摘出群及び6日摘出群間，いずれも有意差は認められなかった．
6). The results of quantification of hydroxyproline are shown in Fig. 8 and Table 5.
There were no significant differences between the 2-day, 4-day, and 6-day groups.
考察
本試験では，周術期の術後早期回復への臨床的応用を目指し，創傷治癒作用について，ラットの切創モデルを用いて，創傷部位のコラーゲンの生成（遺伝子発現及びタンパク質量）を指標に検討を行った．
切創モデルは8週齢のSlc:SD (SPF)ラットに肩甲骨直下より背部正中に約7cmの切創を作製し，スポンジを挿入後，中央部，頭部側及び尾部側をそれぞれ約0.5cm間隔で縫合し作製した．
群構成は，2日摘出群，4日摘出群及び6日摘出群それぞれに被験物質であるCP10（コラーゲンペプチドとして400 mg/kg/day）群，比較対照物質として注射用水群及びアルジネード（アルギニンとして100 mg/kg/day）群を設定した．
その結果， CP10群の血清CRPにおいて6日摘出群で有意な低値が認められ，創傷部位のコラーゲンの生成の指標であるコラーゲンI及びIIIの遺伝子発現に高値傾向が認められた．しかし，ヒドロキシプロリン含量に有意差又は増加傾向は認められなかったが，炎症期に観察される既存コラーゲンの分解によるヒドロキシプロリンの速やかな減少が認められた．
丸山らの報告（丸山 圭一, 伊藤 一二, 三輪 潔, 北島 政樹, 橋本 正夫, 田畑 健久ら. 消化管吻合の原理からみた縫合不全の対策微細血管像Collagen量などによる検討. 日消外会誌. 1974; 7(1): 18-25.）において炎症期にはコラーゲンが炎症細胞によって分解され減少を示すが，その後の線維化期に線維芽細胞の増殖によりコラーゲンが産生され増加を示すとあり，コラーゲン量の指標であるヒドロキシプロリンは一旦減少を示し，その後増加を示すというデータが示されている．また，コラーゲンI及びIIIの遺伝子発現において2及び4日摘出群と比較し6日摘出群でいずれの投与群においても増加を示している．よって，ヒドロキシプロリンについては，炎症期のためコラーゲンが分解され減少した結果である可能性が考えられた．以上の結果から，本試験では炎症期の治癒反応が観察されたと考えられた．
CP10群では，上述のとおり血清CRPが6日摘出群で有意な低値を示した．これはCP10を投与することにより炎症期の速やかなコラーゲンの分解及びコラーゲンI及びIIIの遺伝子発現が増加し，炎症期の創傷治癒が促進した結果，注射用水及びアルジネード群よりも早期に炎症が治まった可能性が考えられた．
炎症が早期に治まる場合，速やかに線維化期に移行すると考えられ，線維芽細胞の増殖により早期にコラーゲン量の増加を示す可能性が示唆された．
以上のことを総括すると，本試験条件下においてコラーゲンペプチド摂取により炎症期が短縮する可能性が示唆された．その結果，速やかに線維化期に移行し創傷治癒作用を示す可能性が示唆された．
Discussion In this study, with the aim of clinical application to early postoperative recovery in the perioperative period, the wound healing action was indexed by using the wound model of rats and the collagen production (gene expression and protein content) at the wound site. We examined the above.
The incision model was prepared by making an approximately 7cm incision in the midline of the back of the 8-week-old Slc: SD (SPF) rat directly under the scapula. After inserting the sponge, the center, head, and tail sides were approximately 0.5 mm each. Sutures were made at intervals of cm.
The group composition was CP10 (400 mg / kg / day as a collagen peptide) group as the test substance in the 2-day, 4-day, and 6-day groups, respectively, and water for injection and alginate (as arginine) as the comparison substance. 100 mg / kg / day) group was set.
As a result, serum CRP in CP10 group showed a significantly low value in the 6-day excised group, and a high tendency was observed in the expression of collagen I and III genes, which are indicators of collagen production at the wound site. However, there was no significant difference or increase in hydroxyproline content, but there was a rapid decrease in hydroxyproline due to degradation of existing collagen observed in the inflammatory phase.
Report by Maruyama et al. (Keiichi Maruyama, Keiji Ito, Kiyoshi Miwa, Masaki Kitajima, Masao Hashimoto, Takehisa Tabata et al. Examination based on the amount of collagen microvascular image Collagen etc. from the viewpoint of digestive tract anastomosis 1974; 7 (1): 18-25.) In the inflammatory phase, collagen is degraded and decreased by inflammatory cells, but in the subsequent fibrosis phase, collagen is produced and increased due to the proliferation of fibroblasts. There is data indicating that hydroxyproline, which is an index of collagen content, once decreased and then increased. Collagen I and III gene expression was increased in both treatment groups in the 6-day excision group compared to the 2- and 4-day excision groups. Therefore, hydroxyproline may be a result of degradation and degradation of collagen during the inflammatory period. From these results, it was considered that a healing reaction in the inflammatory phase was observed in this study.
In the CP10 group, serum CRP was significantly lower in the 6-day excised group as described above. As a result of administration of CP10, rapid collagen degradation during the inflammatory phase and increased gene expression of collagen I and III promoted wound healing during the inflammatory phase. As a result, the inflammation subsided earlier than the water for injection and the alginate group. The possibility was considered.
When inflammation subsides early, it is thought that the fibrosis phase is promptly changed, and it is suggested that fibroblast proliferation may cause an early increase in collagen content.
To summarize the above, it was suggested that ingestion of collagen peptide may shorten the inflammatory phase under the test conditions. As a result, it was suggested that it may shift to the fibrosis stage and show wound healing.
本発明は、術後の創傷部の回復促進に利用可能である。 The present invention can be used for promoting recovery of a wound after surgery.
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| WO2020069695A1 (en) * | 2018-10-01 | 2020-04-09 | sanaFactur GmbH | Nutrition-based support for the body's own wound healing processes |
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