JPS637779A - Cell activator - Google Patents

Cell activator

Info

Publication number
JPS637779A
JPS637779A JP15094786A JP15094786A JPS637779A JP S637779 A JPS637779 A JP S637779A JP 15094786 A JP15094786 A JP 15094786A JP 15094786 A JP15094786 A JP 15094786A JP S637779 A JPS637779 A JP S637779A
Authority
JP
Japan
Prior art keywords
group
silicon compound
cell
methyltrisilanol
cell activator
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.)
Pending
Application number
JP15094786A
Other languages
Japanese (ja)
Inventor
Seiji Noda
野田 誠二
Yoshio Nagaoka
長岡 嘉雄
Tomoko Yasumasu
安増 知子
Moriaki Higo
盛明 肥後
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lion Corp
Original Assignee
Lion Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Lion Corp filed Critical Lion Corp
Priority to JP15094786A priority Critical patent/JPS637779A/en
Publication of JPS637779A publication Critical patent/JPS637779A/en
Pending legal-status Critical Current

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  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

PURPOSE:To obtain a cell activator having improved cell activating action with hardly any fluctuation in quality, etc., by using a silicon compound having at least one silanol group in the molecule as an active ingredient. CONSTITUTION:A silicon compound, having at least one silanol group in the molecule and expressed by the general formula RnSi(OH)4-n (R is the same or different 1-12C alkyl group, aralkyl group, alkenyl group, cycloalkyl group or alkoxy group; n is an integer of 0-3), e.g. methyltrisilanol or a dehydration condensate thereof, as an active ingredient is directly used or dissolved or dispersed in a solvent, e.g. water ethanol, etc., for use.

Description

【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、細胞を賦活化することによって創傷の治癒を
促進したり、細胞培養系に添加して細胞の増殖を促進さ
せることができる細胞賦活剤に関するものである。
[Detailed Description of the Invention] [Industrial Application Field] The present invention provides cells that can be used to promote wound healing by activating cells or to promote cell proliferation by being added to a cell culture system. It concerns an activator.

〔従来の技術〕[Conventional technology]

近年、組織培養技術の急速な進歩により、生体の組織レ
ベルでの種々の変化を細胞レベルで解明することが可能
になってきた。特に細胞培養法の急速な発達により多く
の生命現象が、明らかにされつつある。ところで、細胞
培養法では細胞を生存させ、かつ増殖させるために、ビ
タミン、糖、アミノ酸等を配合した合成培地に、通常、
血清を10%程度添加することが行なわれている。これ
は、血清が有する細胞増殖作用を利用するものであるが
、血清は品質の振れが大きいといった問題がある。そこ
で、最近では、血清を用いる不便さを解消するために無
血清培地の開発が要望されており、そのための適切な栄
v源、及びホルモン以外の新しい細り包成長因子の開発
が望まれている。
In recent years, rapid advances in tissue culture technology have made it possible to elucidate various changes at the tissue level of living organisms at the cellular level. In particular, many biological phenomena are being clarified due to the rapid development of cell culture methods. By the way, in cell culture methods, in order to keep cells alive and proliferate, a synthetic medium containing vitamins, sugars, amino acids, etc. is usually used.
It is common practice to add about 10% serum. This utilizes the cell proliferation effect of serum, but there is a problem in that the quality of serum varies widely. Therefore, recently there has been a demand for the development of a serum-free medium to eliminate the inconvenience of using serum, and for this purpose, it is desired to develop an appropriate nutritional source and a new growth factor other than hormones. .

尚、従来から知られているホルモンやタンパク質などの
細胞増慝因子を用いたのでは、未だ効果が十分ではない
といった問題があった。
However, the use of conventionally known cell-promoting factors such as hormones and proteins has been problematic in that the effects are not sufficient.

こ発明が解決しようとする問題点〕 従って、本発明は、品質等の振れが少な゛く、すぐれた
細胞賦活作用を有する細胞賦活剤、すなわち合成の細胞
賦活剤を提供することを目的とする。
[Problems to be Solved by the Present Invention] Therefore, an object of the present invention is to provide a cell activator having excellent cell activating effects with less variation in quality, that is, a synthetic cell activator. .

口問題点を解決するための手段〕 本発明は、種々の化合物について幅広い研究を行なった
結果、特定のケイ素化合物が細胞培養系にとどまるず種
々の系において幅広くすぐれた細胞賦活作用を有すると
の知見に基づいてなされたのである。
[Means for Solving the Problems] The present invention has been made based on extensive research on various compounds, and has revealed that a specific silicon compound has a wide range of excellent cell activating effects not only in cell culture systems but also in various systems. This was done based on knowledge.

すなわち、本発明は、分子内にシラノール基を少くとも
一個有するケイ素化合物を含有することを特徴とする細
胞賦活剤を提供する。
That is, the present invention provides a cell activator characterized by containing a silicon compound having at least one silanol group in the molecule.

本発明で用しするケイ素化合物は、分子中に少なくとも
1つのシラノール基を有するケイ素化合物であればいず
れでもよいが、好ましくは一般式%式%): (式中、Rは、炭素数1〜12、好ましくは1〜6のア
ルキル基、アラルキル基、アルケニル基、シクロアルキ
ル基、またはアルコキシ基であり、2以上のRは互いに
同一でも異なっても良く、nは0〜3、好ましくは1〜
3の整数である。) で表わされる化合物又はこれらの脱水縮合体を用いるの
がよい。これらのケイ素化合物として、具体的には、メ
チルトリシラノール、ジメチルジシラノール、トリメチ
ルシラノール、エチルトリシラノール、ジエチルジシラ
ノール、プロピルトリシラノール、オクチルトリシラノ
ール、ドデシルトリシラノール、ベンジルトリシラノー
ル、フェニルエチルトリシラノール、プロペニルトリシ
ラノール、シクロへキシルトリシラノール、メトキント
リシラノール、エトキシトリシラノールの1種又は2種
以上の混合物があげられる。又、メチル) IJシラノ
ールの脱水縮合2量体、同3量体なども使用可能である
。上記各種化合物のうち、本発明では、特にメチルトリ
シラノールを用いるのが好ましい。
The silicon compound used in the present invention may be any silicon compound as long as it has at least one silanol group in the molecule, but is preferably of the general formula (%): (wherein, R represents 1 to 1 carbon atoms. 12, preferably 1 to 6 alkyl, aralkyl, alkenyl, cycloalkyl, or alkoxy groups, two or more R's may be the same or different, and n is 0 to 3, preferably 1 to
It is an integer of 3. ) or dehydrated condensates thereof are preferably used. Specifically, these silicon compounds include methyltrisilanol, dimethyldisilanol, trimethylsilanol, ethyltrisilanol, diethyldisilanol, propyltrisilanol, octyltrisilanol, dodecyltrisilanol, benzyltrisilanol, and phenylethyltrisilanol. , propenyltrisilanol, cyclohexyltrisilanol, metquintrisilanol, and ethoxytrisilanol, or a mixture of two or more thereof. Furthermore, dehydrated condensed dimers and trimers of methyl) IJ silanol can also be used. Among the various compounds mentioned above, it is particularly preferable to use methyltrisilanol in the present invention.

上記シラノール基を有するケイ素化合物は、(1)対応
するハロゲン化プランを加水分解し、金属水酸化物と反
応させて得られるシリコネートを、カチオン交換樹脂あ
るいは各種酸にてpHを4〜5に調整して製造するか、
あるいは(ii)  N応するアルコキンシランの加水
分解によって製造することができる。
The above-mentioned silicon compound having a silanol group can be obtained by (1) hydrolyzing the corresponding halogenated plan, reacting it with a metal hydroxide, and adjusting the pH to 4 to 5 using a cation exchange resin or various acids; or manufacture it by
Alternatively, (ii) N can be produced by hydrolysis of a corresponding alkoxysilane.

これろのケイ素化合物は、そのまま又は水、エタノール
などの溶媒に溶解又は分散させた形態で使用可能である
These silicon compounds can be used as they are or in a form dissolved or dispersed in a solvent such as water or ethanol.

本発明で用′7)るケイ素化合物は安全性上問題がない
っ次に該ケイ素化合物の安全性データを示す。
The silicon compound used in the present invention has no safety problems, and the safety data of the silicon compound are shown below.

(フッi文r′イ父→) 〔発明の効果〕 本発明で用いるケイ素化合物が有する細胞賦活作用の作
用機能は不明であるが、本発明によればすぐれた細胞賦
活剤が提供される。そこで、細胞を賦活化する結果とし
て、細胞の増斌作用を促進し、ヒアルロン酸合成等細胞
が有する種々の機能を促進させることができる。又、罰
偏部位の細胞の増殖をも促進させることができる。
(Effects of the Invention) Although the cell activation function of the silicon compound used in the present invention is unknown, the present invention provides an excellent cell activation agent. Therefore, as a result of activating cells, it is possible to promote cell growth and promote various functions possessed by cells, such as hyaluronic acid synthesis. It can also promote the proliferation of cells in the affected area.

従って、本発明の細胞賦活剤は、例えば細胞培養用の添
加剤として、そのまま又はアミノ酸等の各種栄養源とと
もに使用することができる。尚、この際、本発明の細胞
賦活剤を10−8〜10−’Mの濃度で培地に用いるの
がよい。又、本発明の細 ・胞賦活剤は、釧傷治療用外
用剤として、例えば0.01〜10重量%含有し、かつ
殺菌・消毒薬などを含む形態として有効に利用できる。
Therefore, the cell activator of the present invention can be used as it is or together with various nutritional sources such as amino acids, for example, as an additive for cell culture. In this case, it is preferable to use the cell activator of the present invention in the culture medium at a concentration of 10-8 to 10-'M. Further, the cell activator of the present invention can be effectively used as an external preparation for treating chisel wounds, for example, in a form containing 0.01 to 10% by weight and containing a bactericidal/disinfectant.

さらj二本発明の細胞賦活剤は、細胞の機能を活性化で
きる種々の用途、例えばリューマチ、強皮症、皮膚弛緩
症、荒れ肌、火傷、ひび、赤ぎれ、老人性乾皮症、痔戻
の予防と治療及び胃腸薬などに用いることができる。
Furthermore, the cell activator of the present invention can be used for various purposes that can activate cell functions, such as rheumatism, scleroderma, cutis laxa, rough skin, burns, cracks, redness, senile xeroderma, and hemorrhoid recovery. It can be used for the prevention and treatment of cancer and as a gastrointestinal medicine.

次に本発明を実施例により説明するが、本発明はこれら
に限定されるものではない。
Next, the present invention will be explained by examples, but the present invention is not limited thereto.

〔実施例〕〔Example〕

実施例1 メチルトリシラノールを次の方法により製造し、ヒトの
皮、百線准芽細胞を培養した時の細胞増殖能を測定した
Example 1 Methyltrisilanol was produced by the following method, and its cell proliferation ability was measured when human skin and 100-centoblast cells were cultured.

メチルトリシラノールのM a方法 メチルトリクロルシランを加水分解して生じた沈殿を回
収、水洗、乾燥して、ポリマーを1等だ。
M a method for methyltrisilanol The precipitate produced by hydrolyzing methyltrichlorosilane is collected, washed with water, and dried to obtain a polymer.

これを3倍モルの水酸化ナトリウム溶液に、溶解して、
トリソジウムメチルンリコ不−ト水溶液を調整した。こ
の水溶液を水で希釈し、陽イオン交換樹脂あるいは各種
酸にて、pHを4〜5に調整し、メチルトリシラノール
水溶液を得た。
Dissolve this in 3 times molar sodium hydroxide solution,
An aqueous solution of trisodium methylphosphonate was prepared. This aqueous solution was diluted with water, and the pH was adjusted to 4 to 5 using a cation exchange resin or various acids to obtain a methyltrisilanol aqueous solution.

細り包増殖能の測定 A T CC(American Type Cu1t
ure Co1ection)登録細胞の中からヒトの
真皮由来の正常線維芽細胞(細胞名CRL−1513)
を選定して試験に供した。35mmシャーレに5万/d
ishずつ細胞を植え込み、10%血清で24時間培養
後、血清濃度を2%に落とし、各種1度のメチルトリシ
ラノールを添加して、培養し、6日後のDNA量を測定
した。D N A量の測定法はジアミノ安息香酸による
螢光法を用いた。尚シャーレ;ま一検体当り4点ずつ調
製した。結果を表−1に示す。
Measurement of thin follicle proliferation ability ATCC (American Type Cult)
Human dermis-derived normal fibroblasts (cell name CRL-1513) from registered cells
were selected and tested. 50,000/d for 35mm petri dish
After culturing in 10% serum for 24 hours, the serum concentration was lowered to 2%, 1 degree of each type of methyltrisilanol was added, cultured, and the amount of DNA was measured 6 days later. The amount of DNA was measured using a fluorescence method using diaminobenzoic acid. Four Petri dishes were prepared for each specimen. The results are shown in Table-1.

主   −1 ±はS−Eを表わす *I コントロール *2 コントロールに対し5 %危険率で有意差あり 表−1から明らかなように、特にメチルトリシラノール
濃度10−8〜104Mですぐれた細胞の増殖効果が得
られることがわかる。
Main -1 ± represents S-E *I Control *2 Significant difference from control at 5% significance rate As is clear from Table 1, particularly at methyltrisilanol concentrations of 10-8 to 104M, excellent cell activity was observed. It can be seen that a proliferation effect can be obtained.

実施例2 ラット表皮細胞におけるヒアルロン酸合成能を次の手順
により測定した。
Example 2 Hyaluronic acid synthesis ability in rat epidermal cells was measured by the following procedure.

まず、ウィスター(Wister )系ラブドより表皮
細胞を採取し、24wellの7ヤーレに表皮細胞を2
、2 X I O5/dishずつ及び!Jt、C−3
T 3細抱を6、6 X 10’  /dishずつ植
え込んで培養したところ、約6日後に密集した状p (
confluent)となった。植え込んで8日後に薬
物を添加して24時間前処理した後、0.5 μci/
well の14C−グルコサミンを添加して、6時間
インキュベートした。
First, epidermal cells were collected from Wistar rhabdo, and 2 epidermal cells were placed in 7 wells of 24 wells.
, 2 X I O5/dish each and! Jt, C-3
When 6.6 x 10'/dish of T3 clumps were planted and cultured, after about 6 days, a dense p (
It became confluent). Eight days after implantation, the drug was added and pretreated for 24 hours, followed by 0.5 μci/
14C-glucosamine was added to the well and incubated for 6 hours.

培養液を常法により分画してムコ多糖中のヒアルロン酸
合成に取り込まれたグルコサミンの放MfiMを測定し
た。結果を表−2に示す。
The culture solution was fractionated using a conventional method, and the released MfiM of glucosamine incorporated into the synthesis of hyaluronic acid in mucopolysaccharide was measured. The results are shown in Table-2.

表  −2 *1 コントロール *25%危険率でコントロールに対し、有意であること
を示す。
Table 2 *1 Control * Indicates significance compared to control at 25% risk rate.

表−2に示したようにメチルトリシラノール濃度10−
8〜10−’Mで特にヒアルロン酸合成のすぐれた促進
効果が得られた。
As shown in Table-2, methyltrisilanol concentration 10-
Particularly excellent promoting effects on hyaluronic acid synthesis were obtained at 8 to 10-'M.

実施例3 メチルトリシラノールの創傷治應促進効果を次のように
して測定した。
Example 3 The wound healing promoting effect of methyltrisilanol was measured as follows.

ウィスター系ラットの雄(6週令)を4日間予備飼育し
、背中に直径12.5mmの欠損傷を作成した。傷口に
薬物を100μl/匹ずつ2回7日ぬりつけ、傷口面積
を毎日測定した。尚−群は8匹である。結果を表−3に
示す。尚、薬物の内容は、コントロールは、生理食塩水
のみであり、メチルトリシラノールとしては生理食塩水
+メチルトリシラノール0.5%を用いた。
Male Wistar rats (6 weeks old) were preliminarily housed for 4 days, and a defective wound with a diameter of 12.5 mm was created on the back. The drug was applied to the wound twice for 7 days at 100 μl/mouse, and the wound area was measured every day. There were 8 animals in the group. The results are shown in Table-3. Regarding the drug contents, the control was only physiological saline, and the methyltrisilanol used was physiological saline + 0.5% methyltrisilanol.

表  −3 実施例4 次に本発明の細胞賦活剤を添加した各種組成物を示す。Table-3 Example 4 Next, various compositions to which the cell activator of the present invention is added are shown.

細胞用培地 イーグル(Eagle)の最小必須培地にメチルトリシ
ラノールを添加して調整したものであり、10倍希釈し
て使用する。
It is prepared by adding methyltrisilanol to Eagle's minimum essential medium for cells, and is used after being diluted 10 times.

Claims (3)

【特許請求の範囲】[Claims] (1)分子内にシラノール基を少くとも一個有するケイ
素化合物を含有することを特徴とする細胞賦活剤。
(1) A cell activator characterized by containing a silicon compound having at least one silanol group in the molecule.
(2)ケイ素化合物が、一般式( I ): R_nSi(OH)_4_−_n・・・( I )(式中
、Rは炭素数1〜12のアルキル基、アラルキル基、ア
ルケニル基、シクロアルキル基、またはアルコキシ基で
あり、2以上のRは互いに同一でも異なっても良く、n
は0〜3の整数である。) で表わされる化合物又はこれらの脱水縮合体である特許
請求の範囲第(1)項記載の細胞賦活剤。
(2) The silicon compound has the general formula (I): R_nSi(OH)_4_-_n...(I) (wherein R is an alkyl group having 1 to 12 carbon atoms, an aralkyl group, an alkenyl group, a cycloalkyl group) , or an alkoxy group, two or more R's may be the same or different, and n
is an integer from 0 to 3. ) or a dehydrated condensate thereof.
(3)ケイ素化合物がメチルトリシラノールである特許
請求の範囲第(1)項記載の細胞賦活剤。
(3) The cell activator according to claim (1), wherein the silicon compound is methyltrisilanol.
JP15094786A 1986-06-27 1986-06-27 Cell activator Pending JPS637779A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP15094786A JPS637779A (en) 1986-06-27 1986-06-27 Cell activator

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP15094786A JPS637779A (en) 1986-06-27 1986-06-27 Cell activator

Publications (1)

Publication Number Publication Date
JPS637779A true JPS637779A (en) 1988-01-13

Family

ID=15507895

Family Applications (1)

Application Number Title Priority Date Filing Date
JP15094786A Pending JPS637779A (en) 1986-06-27 1986-06-27 Cell activator

Country Status (1)

Country Link
JP (1) JPS637779A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2645863A1 (en) * 1989-04-12 1990-10-19 Voisin Philippe Silicon compounds and process for the manufacture thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2645863A1 (en) * 1989-04-12 1990-10-19 Voisin Philippe Silicon compounds and process for the manufacture thereof

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