JP3167763B2 - Wound healing promoter - Google Patents
Wound healing promoterInfo
- Publication number
- JP3167763B2 JP3167763B2 JP31993991A JP31993991A JP3167763B2 JP 3167763 B2 JP3167763 B2 JP 3167763B2 JP 31993991 A JP31993991 A JP 31993991A JP 31993991 A JP31993991 A JP 31993991A JP 3167763 B2 JP3167763 B2 JP 3167763B2
- Authority
- JP
- Japan
- Prior art keywords
- wound healing
- pbn
- healing promoter
- present
- rats
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000029663 wound healing Effects 0.000 title claims description 18
- VCUVETGKTILCLC-UHFFFAOYSA-N 5,5-dimethyl-1-pyrroline N-oxide Chemical compound CC1(C)CCC=[N+]1[O-] VCUVETGKTILCLC-UHFFFAOYSA-N 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 150000002832 nitroso derivatives Chemical class 0.000 claims description 5
- -1 nitrone compound Chemical class 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- MANKOBPDSPNOFP-UHFFFAOYSA-N 1-tert-butyl-2-nitrosobenzene Chemical compound CC(C)(C)C1=CC=CC=C1N=O MANKOBPDSPNOFP-UHFFFAOYSA-N 0.000 claims description 2
- 241000700159 Rattus Species 0.000 description 11
- 206010052428 Wound Diseases 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 230000022558 protein metabolic process Effects 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 206010021033 Hypomenorrhoea Diseases 0.000 description 1
- RNRMWTCECDHNQU-XYOKQWHBSA-N N-tert-butyl-1-(1-oxidopyridin-1-ium-4-yl)methanimine oxide Chemical compound CC(C)(C)[N+](\[O-])=C/C1=CC=[N+]([O-])C=C1 RNRMWTCECDHNQU-XYOKQWHBSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- OEFVJAZWSLPDEP-UHFFFAOYSA-N n-(2,2-dimethylpropylidene)hydroxylamine Chemical compound CC(C)(C)C=NO OEFVJAZWSLPDEP-UHFFFAOYSA-N 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Pyrrole Compounds (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、創傷治癒促進剤、また
活性酸素を捕捉・消去することにより創傷治癒を促進す
る方法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a wound healing promoter and a method for promoting wound healing by capturing and eliminating active oxygen.
【０００２】[0002]
【従来の技術】従来より、創傷治療剤は数多くあるが、
いずれも治癒が遅く効果が明確でなかった。また創傷治
癒を促進するものは知られておらず、本発明は新規な創
傷治癒促進剤を提供するものである。2. Description of the Related Art There have been many wound treatments.
All were slow to heal and their effects were not clear. There is no known agent that promotes wound healing, and the present invention provides a novel agent for promoting wound healing.
【０００３】[0003]
【課題を解決するための手段】そこで、本発明者らは、
創傷治癒促進剤について鋭意研究した結果、活性酸素あ
るいはフリー・ラジカルを消去すれば、蛋白質代謝、細
胞の再生等がおき、また老年者の代謝を活発にして創傷
治癒を促進しすることを見出し、また、ニトロン化合
物、ニトロソ仕合物等のいずれか、又はこれらの混合物
が活性酸素あるいはフリー・ラジカルを捕捉・消去し、
創傷治癒を促進するとの知見を得て本発明を完成した。Means for Solving the Problems Accordingly, the present inventors have:
As a result of diligent research on wound healing promoters, it was found that eliminating active oxygen or free radicals leads to protein metabolism, cell regeneration, etc., and also promotes wound healing by activating the elderly metabolism. In addition, any one of the nitrone compound, the nitroso compound and the like, or a mixture thereof captures and eliminates active oxygen or free radicals,
The present invention has been completed based on the finding that wound healing is promoted.
【０００４】本発明に係わる創傷治癒の促進とは、ヒト
を含む哺乳動物の外傷、火傷、移植、手術などの傷の治
療を促進するものである。[0004] The promotion of wound healing according to the present invention is to promote the treatment of wounds such as trauma, burns, transplants, and operations in mammals including humans.
【０００５】本発明の創傷治癒促進剤は、ニトロン化合
物として、ＰＢＮ（α−フェニル−Ｎ−ｔ−ブチルニト
ロン）、ＤＭＰＯ（５，５−ジメチルピロリンＮオキシ
ド）、ＰＯＢＮ（α−４−ピリジル１−オキシド−Ｎ−
ｔブチルニトロン）のいずれか、またはこれらの１種以
上の混合物が挙げられ、またニトロソ化合物としては、
ｔＮＢ（ｔ−ニトロソブタン）、ＢＮＢ（ｔ−ブチルニ
トロソベンゼン）のいずれか、またはこれらの１種以上
の混合物が挙げられる。The wound healing promoter of the present invention comprises, as nitrones, PBN (α-phenyl-Nt-butylnitrone), DMPO (5,5-dimethylpyrroline N oxide), and POBN (α-4-pyridyl 1). -Oxide-N-
As either, or mixtures of one or more thereof, with also a nitroso compound of t-butyl nitrone),
Either tNB (t-nitrosobutane) or BNB (t-butylnitrosobenzene), or a mixture of one or more of these.
【０００６】また、本発明はこれらのニトロン化合物、
ニトロソ化合物のいずれか、またはこれらの１種以上の
混合物を主成分とする組成物で、ＰＢＮ、ＤＭＰＯなど
を活性成分とするものであり、適当な薬理学的に許容さ
れる添加剤（増量剤、希釈剤）等と混合して適当な医薬
組成物とすることが可能である。The present invention also relates to these nitrones,
A composition mainly containing any of the nitroso compounds or a mixture of at least one of them, containing PBN, DMPO, or the like as an active ingredient, and containing a suitable pharmacologically acceptable additive (bulking agent). , A diluent) and the like to obtain a suitable pharmaceutical composition.
【０００７】また、ＰＢＮ等の毒性は低く、マウスおよ
びラットにおけるＬＤ５０は１．１ｇ／ｋｇ以上である
ので、人体に用いても副作用がすくない。Further, the toxicity of PBN and the like is low, and the LD50 in mice and rats is 1.1 g / kg or more.
【０００８】この組成物は、有効成分を生理学的に許容
されうる担体、賦形剤、結合剤、希釈剤と混合し、たと
えば顆粒剤、粉剤、硬カプセル剤、軟カプセル剤、塗布
剤、シロップ、坐剤、注射剤として経口または非経口的
に投与される。The composition is prepared by mixing the active ingredient with a physiologically acceptable carrier, excipient, binder and diluent, for example, granules, powders, hard capsules, soft capsules, coatings and syrups. Orally or parenterally as suppositories or injections.
【０００９】本発明の組成物の投与量は、疾病の種類、
症状、年齢、投与方法などにより異なるが、経口的に用
いる場合は、ラットの場合、０．３２〜７５ｍｇ／ｋｇ
体重、従って、成人（６０ｋｇ標準体重）一日当り１９
ｍｇ〜４５００ｍｇ、好ましくは７０〜９６０ｍｇの範
囲になるように投与される。叉、本発明の組成物を生理
食塩水と混合するときはＰＢＮおよびＤＭＰＯいずれの
場合も０．５〜１．０％の割合で溶解することが好まし
い。The dose of the composition of the present invention depends on the type of the disease,
Depending on symptoms, age, administration method, etc., when used orally, 0.32-75 mg / kg for rats
Body weight, and therefore 19 (60 kg standard body weight) per day
mg-4500 mg, preferably 70-960 mg. When the composition of the present invention is mixed with physiological saline, it is preferable that PBN and DMPO be dissolved at a ratio of 0.5 to 1.0%.
【００１０】[0010]
【作用】活性酸素が捕捉・消去されると過酸化資質がで
きにくくなり、さらにタンパク質又はＤＮＡの架橋結合
ができにくくなって血管拡張作用と血流改善が生じて各
種創傷の治癒を促進するものと考えられる。[Action] When active oxygen is trapped and eliminated, it is difficult to form a peroxide substance, and it is also difficult to cross-link proteins or DNA, resulting in vasodilatory action and improved blood flow to promote healing of various wounds. it is conceivable that.
【００１１】また、本発明は、ＰＢＮあるいはＤＭＰＯ
等を経口投与あるいは静脈注射、腹腔内注射などでヒト
あるいはペットなどの哺乳動物に投与することによっ
て、活性酸素あるいはフリー・ラジカルを捕捉・消去
し、また血管を拡張して血流を改善し各種創傷の治癒を
促進する。Further, the present invention relates to PBN or DMPO
Is administered orally or intravenously or intraperitoneally to humans or mammals such as pets to capture and eliminate active oxygen or free radicals and to dilate blood vessels to improve blood flow. Promotes wound healing.
【００１２】[0012]
【効果】本発明は、老齢者あるいはペットの老齢個体の
蛋白質代謝、細胞の再性能を改善し、ヒトを含む哺乳動
物の外傷、火傷、移植、手術などの傷の治療を促進する
効果がある。The present invention has the effect of improving protein metabolism and cell re-performance of the elderly or pet aged individuals and promoting the treatment of wounds such as trauma, burns, transplants, and surgery in mammals including humans. .
【００１３】[0013]
【実施例】以下、本発明を実施例に基づきさらに具体的
に説明する。The present invention will be described more specifically below with reference to examples.
【００１４】［動物］ 実験には、６から１０週齢及び５から６ヶ月齢の若齢動
物と２４ヵ月齢の老齢動物、Ｆ３４４系（チャールス・
リバー）およびウィスター系ラット（ＳＲＬ）を用い
た。動物は、入手後すべて１２時間明暗サイクル（午前
７時から午後７時まで明期）の室温２４±１℃、相対湿
度５５±５％の飼育室で餌（オリエンタル酵母、固形飼
料）および水を自由摂取下で飼育した。[Animals] In the experiments, young animals aged 6 to 10 weeks and 5 to 6 months and old animals aged 24 months, F344 strain (Charles
River) and Wistar rats (SRL) were used. All animals were fed (oriental yeast, chow) and water in a breeding room at room temperature 24 ± 1 ° C. and 55 ± 5% relative humidity on a 12 hour light / dark cycle (light period from 7:00 am to 7:00 pm). They were bred under free access.
【００１５】［薬剤］ ＰＢＮを生理食塩水に３．２ｍｇ／ｍｌ［０．３２％
（ｗ／ｖ）］の割合で、ＤＭＰＯを生理食塩水に２ｍｇ
／ｍｌ［０．２％（ｗ／ｖ）］の割合で溶解し投与し
た。投与量はラット体重１００ｇあたり１．０ｍｌとし
た。[Drug] PBN was added to a physiological saline solution at 3.2 mg / ml [0.32%
(W / v)] and 2 mg of DMPO in physiological saline.
/ Ml [0.2% (w / v)]. The dose was 1.0 ml per 100 g of rat body weight.
【００１６】［薬剤の投与］ ＰＢＮを投与したラット１０匹をＰＢＮ投与群、ＤＭＰ
Ｏを投与したラット１０匹をＤＭＰＯ投与群とし、また
生理食塩水だけを投与したマウス１０匹をコントロール
群とした。[Administration of Drugs] Ten rats to which PBN had been administered were administered with
10 rats to which O was administered were set as a DMPO administration group, and 10 mice to which only saline was administered were set as a control group.
【００１７】［創傷治癒の促進］ ラットの皮膚に人工的に傷口を作製し、傷が治癒するま
での期間を測定した。図１に示すように、ＰＢＮを投与
した若齢ラットと老齢ラットの創傷治癒に要する日数
は、老齢ラットでは若齢動物とほぼ同じレベルとなっ
た。このことは、ＰＢＮによって蛋白質の代謝あるいは
細胞の再生が著しく促進して、創傷治癒の促進効果が生
じたものと考えられる。[Promotion of Wound Healing] A wound was artificially formed on the skin of a rat, and the period until the wound healed was measured. As shown in FIG. 1, the days required for wound healing of the young rats and the old rats to which PBN was administered were almost the same in the old rats as in the young animals. This is considered to be due to the fact that PBN markedly promoted protein metabolism or cell regeneration, resulting in an effect of promoting wound healing.
【００１８】ＰＢＮ同様にＤＭＰＯを用いてラットの創
傷治癒の促進を測定し、その結果を表１に示す。The promotion of wound healing in rats was measured using DMPO in the same manner as in PBN, and the results are shown in Table 1.
【表１】表１より、ＤＭＰＯを投与した場合も老齢動物
の創傷治癒に要する日数が短縮でききることが判明し
た。Table 1 shows that even when DMPO was administered, the number of days required for wound healing of aged animals could be shortened.
【図１】ラット皮膚の傷の治癒期間を示す図。FIG. 1 is a diagram showing the healing period of wounds on rat skin.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 国際公開92／22290（ＷＯ，Ａ１) Ｉｎｔ．Ｊ．Ｔｉｓｓｕｅ Ｒｅａｃ ｔ．，Ｖｏｌ．10，Ｎｏ．６（1988) ｐ．373−379 (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 31/04 A61K 31/06 A61K 31/40 A61K 31/44 A61P 17/02 ＣＡ（ＳＴＮ) ＥＭＢＡＳＥ（ＳＴＮ) ＭＥＤＬＩＮＥ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on the front page (56) References International Publication 92/22290 (WO, A1) Int. J. Tissue React. , Vol. 10, No. 6 (1988) p. 373-379 (58) Fields surveyed (Int. Cl. 7 , DB name) A61K 31/04 A61K 31/06 A61K 31/40 A61K 31/44 A61P 17/02 CA (STN) EMBASE (STN) MEDLINE (STN )
Claims (2)
合物を主成分とする創傷治癒促進剤。1. A wound healing promoter comprising a nitrone compound and / or a nitroso compound as a main component.
ＰＢＮ（α−フェニル−Ｎ−ｔ−ブチルニトロン）、Ｄ
ＭＰＯ（５，５−ジメチルピロリンＮオキシド）、ＰＯ
ＢＮ（α−４−ピリジル１−オキシド−Ｎ−ｔブチルニ
トロン）のいずれか、またはこれらの１種以上の混合物
で、ニトロソ化合物がｔＮＢ（ｔ−ニトロソブタン）、
ＢＮＢ（ｔ−ブチルニトロソベンゼン）のいずれか、ま
たはこれらの１種以上の混合物である創傷治癒促進剤。2. The method according to claim 1, wherein the nitrone compound is
PBN (α-phenyl-Nt-butylnitrone), D
MPO (5,5-dimethylpyrroline N oxide), PO
BN (alpha-4-pyridyl 1-oxide -N-t-butyl-D <br/> Tron) either, or a mixture of one or more of these, nitroso compounds TNB (t-nitroso butane),
A wound healing promoter which is any of BNB (t-butylnitrosobenzene) or a mixture of one or more of them.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31993991A JP3167763B2 (en) | 1991-11-07 | 1991-11-07 | Wound healing promoter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP31993991A JP3167763B2 (en) | 1991-11-07 | 1991-11-07 | Wound healing promoter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05221856A JPH05221856A (en) | 1993-08-31 |
| JP3167763B2 true JP3167763B2 (en) | 2001-05-21 |
Family
ID=18115931
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP31993991A Expired - Fee Related JP3167763B2 (en) | 1991-11-07 | 1991-11-07 | Wound healing promoter |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3167763B2 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6175435B1 (en) | 1995-11-22 | 2001-01-16 | Fujitsu Limited | Optical communication system using optical phase conjugation to suppress waveform distortion caused by chromatic dispersion and optical kerr effect |
| JP2001139477A (en) * | 1999-11-17 | 2001-05-22 | Coherent Technology:Kk | Tissue cell growth promoting solution at the wound site |
| JP5189754B2 (en) * | 2006-10-25 | 2013-04-24 | 花王株式会社 | S100A8 expression promoter |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992022290A1 (en) | 1991-06-18 | 1992-12-23 | Oklahoma Medical Research Foundation | Use of spin trapping for the treatment of diseases associated with oxidation of lipids and proteins |
-
1991
- 1991-11-07 JP JP31993991A patent/JP3167763B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992022290A1 (en) | 1991-06-18 | 1992-12-23 | Oklahoma Medical Research Foundation | Use of spin trapping for the treatment of diseases associated with oxidation of lipids and proteins |
Non-Patent Citations (1)
| Title |
|---|
| Ｉｎｔ．Ｊ．Ｔｉｓｓｕｅ Ｒｅａｃｔ．，Ｖｏｌ．１０，Ｎｏ．６（１９８８）ｐ．３７３−３７９ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05221856A (en) | 1993-08-31 |
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