JPH0228119A - Biological function activator - Google Patents
Biological function activatorInfo
- Publication number
- JPH0228119A JPH0228119A JP63177583A JP17758388A JPH0228119A JP H0228119 A JPH0228119 A JP H0228119A JP 63177583 A JP63177583 A JP 63177583A JP 17758388 A JP17758388 A JP 17758388A JP H0228119 A JPH0228119 A JP H0228119A
- Authority
- JP
- Japan
- Prior art keywords
- biological function
- substance
- function activator
- improver
- active ingredient
- 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.)
- Granted
Links
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Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、感染組織より抽出される生理活性物質を有効
成分として含有する生体機能賦活剤に関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a biological function activator containing as an active ingredient a physiologically active substance extracted from infected tissue.
（従来の技術）
動脈硬化等の器質的な血管の病変や寒冷、身体的及び精
神的ストレス、薬物等の各種誘因によって生体局所の血
流障害が生じ、虚血状態に陥った組織や臓器の機能障害
、これに伴う冷感、しびれ、痛み、知覚鈍麻等の症状が
現れる。この状態が長＜読りと局所組織は萎縮、変性、
ついには壊死に陥る。(Prior technology) Blood flow disturbances in local areas of the body occur due to organic vascular lesions such as arteriosclerosis, cold temperatures, physical and mental stress, drugs, etc., and tissues and organs that have become ischemic. Symptoms such as functional impairment and accompanying cold sensation, numbness, pain, and hypoesthesia appear. If this state lasts for a long time, the local tissues may undergo atrophy, degeneration,
Eventually it succumbs to necrosis.
高齢化社会を迎え、日常多くの患者が、特に老齢者にお
いて、しびれ、痛み、機能障害等の症状に悩まされてい
る。従って、病態局所の血流を改善し低下した組織の機
能修復作用を有し、且つ副作用がない安全な薬剤の開発
が望まれている。BACKGROUND OF THE INVENTION As we enter an aging society, many patients, especially elderly people, are suffering from symptoms such as numbness, pain, and functional impairment on a daily basis. Therefore, it is desired to develop a safe drug that has the effect of improving blood flow in pathological local areas and restoring decreased tissue function, and that has no side effects.
本発明者は、各種ウィルスを動物又は培ｉｍ織に接種し
て起炎させた感染動物組織（以下これらを単に感染ＭＬ
ｖａという）より抽出した生理活性物質について探索研
究を行った結果、本発明物質が優れた病態局所の血流改
善作用を有することを見い出し本発明を完成した。The present inventor inoculated various viruses into animals or cultured tissues to cause inflammation of infected animal tissues (hereinafter referred to simply as infected ML).
As a result of conducting exploratory research on physiologically active substances extracted from (referred to as ``va''), it was discovered that the substance of the present invention has an excellent effect of improving blood flow in pathological local areas, and the present invention was completed.
（発明が解決しようとする問題点）
本発明の目的は、感染組織より抽出される生理活性物質
を有効成分として含有する生体機能賦活剤を提供するこ
とにある。(Problems to be Solved by the Invention) An object of the present invention is to provide a biological function activator containing a physiologically active substance extracted from infected tissue as an active ingredient.
（問題点を解決するための手段）
本発明治療剤は、感染組織を磨砕し、抽出溶媒を加えて
組織片を除去した後、除蛋白処理を行い、これを吸着剤
に吸着せしめ、次いで吸着成分を溶出することにより得
られる生理活性物質を有効成分として含有するものであ
る。(Means for Solving the Problems) The therapeutic agent of the present invention is prepared by grinding infected tissue, adding an extraction solvent to remove tissue fragments, and then performing protein removal treatment, adsorbing this to an adsorbent, and then It contains as an active ingredient a physiologically active substance obtained by eluting the adsorbed component.
本発明に用いるウィルスとしては、起炎作用を有するウ
ィルス類、好ましくは、ワクチニアウィルス、生石ウィ
ルス、痘癒ウィルス、エフトロメリアウィルス、サルポ
ックスウィルス等のオルソポックスウィルス、オーツウ
ィルス、パラワクチニアウィルス、ウシ乳頭状口内炎ウ
ィルス等のパラポックスウィルス、ヒツジポックスウィ
ルス、ヤギポックスウィルス、塊皮病ウィルス等のヤギ
ポックスウィルス、ニワトリポックスウィルス、ノウサ
ギ線維腫ウィルス等のトリポックスウィルス、ウサギ粘
液腫ウィルス、ウサギ線維腫ウィルス等のウサギポック
スウィルス、その他豚痘ウィルス、Ｙａｖａサル腫瘍ウ
ィルス、Ｔａｒａポックスウィルスなどポックスウィル
ス科に属するウィルス類を挙げることができる。Viruses used in the present invention include viruses having an inflammatory effect, preferably orthopoxviruses such as vaccinia virus, Oiseki virus, smallpox virus, eftromelia virus, and sarpoxvirus, oat virus, and paravaccinia virus. , parapoxviruses such as bovine papillary stomatitis virus, ovine poxviruses, goat poxviruses, goat poxviruses such as lumpworm virus, chicken poxviruses, avian poxviruses such as hare fibroma virus, rabbit myxoma virus, and rabbits. Examples include rabbit poxviruses such as fibroma virus, and viruses belonging to the poxviridae family, such as swinepox virus, Yava monkey tumor virus, and Tara poxvirus.
感染組織を得るための動物としては、ウサギ、ヒツジ、
ヤギ、ブタ、ウシ、ウマ、サル、ハムスターモルモット
、ラット、マウス、ニワトリなど種々の哺乳動物や鳥類
を用いることができ、ポックスウィルスの種類や目的に
応じて選択できる。Animals used to obtain infected tissue include rabbits, sheep,
Various mammals and birds such as goats, pigs, cows, horses, monkeys, hamsters, guinea pigs, rats, mice, and chickens can be used, and can be selected depending on the type of poxvirus and the purpose.
又、培ＩＩ組織としては、使用する種類のポックスウィ
ルスが増殖可能な培養細胞を用いることができ、例えば
、ウサギ、ヒツジ、ヤギ、ブタ、ウシ、ウマ、サル、ハ
ムスター、モルモット、ラット、マウス及びそれら胎児
の腎臓、皮膚、肺臓、翠丸、肝臓、筋肉、副腎、甲状腺
、脳、神経細胞、血球など各組織の培養細胞や腫瘍細胞
培養株、Ｈｅ１ａ細胞等のヒト由来の培養組織、並びに
卵漿尿膜などが挙げられる。Furthermore, cultured cells in which the type of poxvirus to be used can proliferate can be used as the culture II tissue, such as rabbit, sheep, goat, pig, cow, horse, monkey, hamster, guinea pig, rat, mouse, and Cultured cells of fetal kidneys, skin, lungs, suisumaru, liver, muscles, adrenal glands, thyroid, brain, nerve cells, blood cells, etc., cultured tumor cell lines, human-derived cultured tissues such as He1a cells, and eggs. Examples include the chorioallantoic membrane.
これら感染ｍｍを無菌的に採取して摩砕し、その１乃至
５倍量の抽出溶媒を加えて乳化懸濁液とする。These infected mm are aseptically collected and ground, and 1 to 5 times the amount of extraction solvent is added thereto to form an emulsified suspension.
抽出溶媒としては、蒸留水、生理食塩水、弱酸性乃至弱
塩基性の緩衝液などを用いることができ、グリセリン等
の安定化剤、フェノール等の殺菌・防腐剤、塩化ナトリ
ウム、塩化カリウム、塩化マグネシウム等の無機塩類な
どを適宜添加してもよい、この時、凍結融解、超音波、
細胞１１ＩＪ溶解酵素又は界面活性剤等の処理により細
胞組織を破壊して抽出を容易にすることができる。Distilled water, physiological saline, weakly acidic or weakly basic buffers, etc. can be used as extraction solvents, stabilizers such as glycerin, disinfectants and preservatives such as phenol, sodium chloride, potassium chloride, chloride, etc. Inorganic salts such as magnesium may be added as appropriate. At this time, freeze-thaw, ultrasonic,
Cell tissue can be destroyed by treatment with a cell 11IJ lytic enzyme or a surfactant to facilitate extraction.
得られた乳状抽出液を濾過又は遠心分離して１１片を除
去した後、除蛋白処理を行う。除蛋白は、公知の方法に
より実施でき、加熱、超音波、蛍白ｆ変性剤、例えば、
酸、塩基、尿素、グアニジン、有機溶媒、界面活性剤等
による処理、等電点沈澱、塩析等の方法を適用すること
ができる。次いで、濾紙（セルロース、ニトロセルロー
ス等）、グラスフィルター、セライト、ザイツ濾過板等
を用いた濾過、限外濾過、ゲル濾過、イオン交換樹脂、
遠心分離などにより析出してきた不溶蛋白質を除去する
。The obtained milky extract is filtered or centrifuged to remove 11 pieces, and then subjected to protein removal treatment. Protein removal can be carried out by known methods, such as heating, ultrasound, fluorescent denaturing agents, etc.
Methods such as treatment with acids, bases, urea, guanidine, organic solvents, surfactants, etc., isoelectric precipitation, and salting out can be applied. Next, filtration using filter paper (cellulose, nitrocellulose, etc.), glass filter, Celite, Seitz filter plate, etc., ultrafiltration, gel filtration, ion exchange resin,
Remove precipitated insoluble proteins by centrifugation, etc.
こうして得られた有効成分含有抽出液を、塩酸、硫酸、
臭化水素酸等の酸を用いて酸性、好ましくはｐＨ３，５
乃至５．５に調整し、吸着剤への吸着操作を行う、使用
可能な吸着剤としては、活性炭、カオリン、イオン交換
樹脂などを挙げることができ、抽出液中に吸着剤を添加
し攪拌するか、吸着剤を充填したカラムを通過させるこ
とにより、有効成分を吸着させることができる。The extract containing the active ingredient thus obtained is treated with hydrochloric acid, sulfuric acid,
Acidic using an acid such as hydrobromic acid, preferably pH 3.5
Adjust to 5.5 to 5.5 and perform the adsorption operation on the adsorbent. Usable adsorbents include activated carbon, kaolin, ion exchange resin, etc. The adsorbent is added to the extract and stirred. Alternatively, the active ingredient can be adsorbed by passing it through a column packed with an adsorbent.
吸着成分より、本発明物質を溶出するには、前記吸着剤
に溶出溶媒を加え、室温又は適宜加熱して或いは攪拌し
て溶出し、濾過等の通常の方法で吸着剤を除去して達成
できる。用いられる溶出溶媒としては、水、メタノール
、エタノール、イソプロパツール等又はこれらの適当な
混合溶液、或いは塩基性溶媒、好ましくはｐＨ９乃至１
２に調整した前記溶媒を使用することができる。Elution of the substance of the present invention from the adsorbed component can be achieved by adding an elution solvent to the adsorbent, eluting it at room temperature or by heating or stirring as appropriate, and removing the adsorbent by a conventional method such as filtration. . The elution solvent used is water, methanol, ethanol, isopropanol, etc. or a suitable mixed solution thereof, or a basic solvent, preferably pH 9 to 1.
The solvent adjusted to 2 can be used.
このようにして得られた溶出液を、好ましくはｐＨ６，
５乃至８．５の中性付近に調整した後、減圧下に蒸発乾
固又は凍結乾燥することによって、目的とする生理活性
物質を得ることができる。The eluate thus obtained is preferably adjusted to pH 6,
After adjusting the neutrality to around 5 to 8.5, the target physiologically active substance can be obtained by evaporating to dryness or freeze-drying under reduced pressure.
前記操作によって抽出、精製された本発明有効成分は以
下の物理化学的性質を有する。The active ingredient of the present invention extracted and purified by the above procedure has the following physicochemical properties.
■性状：淡黄褐色無定形の吸湿性粉末
■溶解性：水、メタノール、エタノールに可溶■紫外部
吸収： ｔＪ Ｖａａｘ ２５５〜２Ｔ５ｎｓ■ニン
ヒドリン反応：陽性
■本発明物質を２■をとり、過塩素酸１−を加え、液が
無色となるまで加熱し、希硫酸３−１塩酸アミトール０
．４ｇ及び亜ｆＬ酸水素ナトリウム８ｇに水ｌＯ〇−加
えて溶かした液２−、モリブデン酸アンモニウム１ｇに
水３０−を加えて溶かした液２−を加え放置するとき、
液は青色を呈する。■Properties: Pale yellowish brown amorphous hygroscopic powder ■Solubility: Soluble in water, methanol, ethanol ■Ultraviolet absorption: tJ Vaax 255-2T5ns ■Ninhydrin reaction: Positive ■Take 2■ of the substance of the present invention and Add 1-chloric acid, heat until the liquid becomes colorless, add 3-1 diluted sulfuric acid, 0-amitol hydrochloride
．． When adding liquid 2-, which was prepared by adding 4 g and fL sodium hydrogenite to 8 g of sodium hydrogenite and dissolving it, and liquid 2-, which was obtained by adding 30 - of water to 1 g of ammonium molybdate and dissolving it, and leaving it to stand,
The liquid appears blue.
■本発明物質５■をとり、水を加えて溶かし１０−とじ
、この液ｔ＋ａｔにオルシン０．２ｇ及び硫酸第二鉄ア
ンモニウム０．１３５ ｇにエタノール５−を加えて溶
かし、この液を塩酸８３ｄに加え、水を加えて１００−
とした液３−を加え沸騰水浴中で加熱するとき、液は緑
色を呈するや
■本発明物質の水溶液は硝酸銀試薬で沈澱を生じる。■ Take the substance of the present invention 5, add water and dissolve it. 10- Close. To this solution t+at, add 0.2 g of orcine and 0.135 g of ferric ammonium sulfate to dissolve ethanol 5-. Add this solution to 83 d of hydrochloric acid. Add water to 100-
When the above solution 3- is added and heated in a boiling water bath, the solution turns green and the aqueous solution of the substance of the present invention precipitates with the silver nitrate reagent.
■核酸塩基類を含有する。■Contains nucleic acid bases.
■本発明物質に対する各種蛋白検出反応は陰性である。■Various protein detection reactions for the substance of the present invention are negative.
以下は、本発明物質の製造方法の実施例である。The following are examples of methods for producing the substances of the invention.
但し、これらは本発明の範囲を限定するものではない。However, these do not limit the scope of the present invention.
（実施例）
実施例１゜
健康な成熟家兎の皮膚にワクチニアウィルスを接種し感
染させた後、発痘した皮層を無菌的に剥出しこれを細切
した後フェノール加グリセリン水を加え、ホモゲナイザ
ーで磨砕し乳状とした９次いでこれを遠心濾過し、得た
濾液を塩酸で弱酸性（約ＰＨ４，５乃至５．５）に調整
した後、流通蒸気下１００℃で加熱処理し濾過した。濾
液はさらにザイツ濾仮を用いて濾過した後、水酸化ナト
リウムで弱アルカリ性（約ｐＨ８，５乃至１０．０）と
し、さらに１００℃で加熱処理した後濾過した。濾液を
塩酸でｐＨ４，５とし、活性炭１．５％を加えて１乃至
５時間撹拌した後濾過した。(Example) Example 1 After inoculating and infecting the skin of a healthy adult rabbit with vaccinia virus, the infected skin layer was aseptically exfoliated and cut into small pieces, and then phenol-added glycerol water was added. It was ground into a milky state by using a homogenizer.9 This was then centrifugally filtered, and the obtained filtrate was adjusted to weak acidity (about PH4.5 to 5.5) with hydrochloric acid, and then heated at 100°C under flowing steam and filtered. . The filtrate was further filtered using a Seitz filter, made weakly alkaline (about pH 8.5 to 10.0) with sodium hydroxide, further heated at 100° C., and then filtered. The filtrate was adjusted to pH 4.5 with hydrochloric acid, 1.5% activated carbon was added, stirred for 1 to 5 hours, and then filtered.
濾取した活性炭に水を加え水酸化ナトリウムでｐＨ９，
４乃至ＩＯに調整し、３乃至５時間撹拌した後、濾過し
た。濾液を塩酸で約ｐＨ７の中性付近に中和し、減圧下
に濃縮乾固して本発明物質を得た。Add water to the filtered activated carbon and adjust the pH to 9 with sodium hydroxide.
The solution was adjusted to 4 to IO, stirred for 3 to 5 hours, and then filtered. The filtrate was neutralized with hydrochloric acid to a neutral pH of about 7, and concentrated to dryness under reduced pressure to obtain the substance of the present invention.
実施例２゜
実施例１と同様にして得た吸着活性炭にメタノールを加
え、１時間攪拌した後濾過した。ｉｊ！圧下に乾固して
有効成分を得た。Example 2 Methanol was added to adsorbent activated carbon obtained in the same manner as in Example 1, stirred for 1 hour, and then filtered. ij! The active ingredient was obtained by drying under pressure.
（作用）
次に本発明治療剤の毒性試験及び臨床試験の結果の一例
を示す。(Effect) Next, an example of the results of a toxicity test and a clinical test of the therapeutic agent of the present invention will be shown.
（１）毒性試験
１１１Ｍマウス及び雌雄ラットに本発明治療剤の有効成
分である生理活性物質を経口、皮下、腹腔内、静脈内等
の経路で投与し、急性毒性試験を行った。(1) Toxicity test The physiologically active substance, which is the active ingredient of the therapeutic agent of the present invention, was administered orally, subcutaneously, intraperitoneally, intravenously, etc. to 111M mice and male and female rats, and an acute toxicity test was conducted.
その結果、動物種及び性差に関係なく、いずれの投与経
路においても、本発明物質のＬＤｓ。は５，０００■／
ｋｇ以上であった。As a result, the LDs of the substance of the present invention can be obtained by any administration route, regardless of animal species and gender. is 5,000■/
It was more than kg.
また、亜急性毒性及び生殖試験など各種の安全性試験を
行ったが、各臓器で全く異常は認められず、生ＴＮ１試
験においても、母体、胎仔、新生仔及び出生仔の生殖能
力に対して全く影響を与えなかった。In addition, we conducted various safety tests such as subacute toxicity and reproductive tests, but no abnormalities were observed in any organ, and live TN1 tests also showed that the reproductive ability of mothers, fetuses, neonates, and newborns was affected. It had no impact at all.
（２）血流改善作用
Ｗｉｓｔａｒ系雄性ラット（体重約２００ ｇ ）に本
発明物ｖ５０乃至４００■／ｋｉｒを経口投与した。１
時間後に１部位当り０．１−の０．２％カラゲニンを右
後肢皮下投与し、４８時間後まで足肢皮膚温をサーモグ
ラフィーを用いて測定した。(2) Blood flow improvement effect The present invention was orally administered at v50 to 400 μ/kir to Wistar male rats (body weight approximately 200 g). 1
After an hour, 0.1-0.2% carrageenan was subcutaneously administered to each site on the right hind leg, and the skin temperature of the leg was measured using thermography until 48 hours later.
その結果、本発明物質はカラゲニン投与４５分乃至３時
間までに生じた足肢皮膚温の低下を用量依存的に改善し
、優れた血流改善作用を有することが認められた。As a result, the substance of the present invention was found to improve the decrease in foot and limb skin temperature that occurred from 45 minutes to 3 hours after administration of carrageenan in a dose-dependent manner, and to have an excellent blood flow improving effect.
（３）Ｐ床試験
しびれ、疼痛、四肢冷感、知覚異常等の症状に悩むレイ
ノー症候群、糖尿病性神経障害、スモン後遺症などの患
者に対し、本発明治療剤を投与し上記症状の改善につき
調べた０本発明物質は、例えば注射剤の場合、１日３乃
至１２＊を１日乃至２週間静脈内投与した。(3) P bed test The therapeutic agent of the present invention was administered to patients suffering from Raynaud's syndrome, diabetic neuropathy, SMON sequelae, etc. who suffer from symptoms such as numbness, pain, cold sensation in the extremities, and paresthesia, and the improvement of the above symptoms was investigated. For example, in the case of an injection, the substance of the present invention was administered intravenously at 3 to 12* a day for 1 to 2 weeks.
総合改善度において、しびれ、疼痛、四肢冷感、知覚異
常等の症状に対してブラセボと比して明らかに存意な改
善効果が得られ、−例を挙げると、７割で中等度改善以
上、９割で軽度改外以上の効果が得られた試験例があっ
た。In terms of overall improvement, there was clearly a significant improvement in symptoms such as numbness, pain, coldness in the extremities, and paresthesia compared to Blacebo, with 70% achieving moderate improvement or higher. There were test cases in which 90% of cases showed mild or better effects.
尚、上記臨床試験において、重篤な副作用はもちろん、
不眠、発汗、口渇、消化器官異常など軽度な副作用もほ
とんど認められなかった。In addition, in the above clinical trial, there were not only serious side effects, but also
Mild side effects such as insomnia, sweating, dry mouth, and gastrointestinal abnormalities were rarely observed.
（効果）
上記試験結果から明らかなように、本発明物質は心臓等
に負担を与えることなく、血流障害により虚血状態に陥
った各種組織の血流改善を促し＆［Ｉ織機能を正常化す
る優れた作用を有する。(Efficacy) As is clear from the above test results, the substance of the present invention promotes the improvement of blood flow in various tissues that are in an ischemic state due to blood flow disorder and [normalizes I tissue function] without putting a burden on the heart etc. It has an excellent effect of converting.
従って、振動病、白ろう病、閉塞性動脈硬化症、閉塞性
血栓血管症、進行性筋萎縮症、脳血管障害、結節性動脈
周囲炎、全身性エリスマトーデス、リウマチ性関節炎、
大動脈炎症候群等のレイノー症候群や糖尿病性神経障害
、スモン後遺症、虚血性神経症、凍癒、凍傷、耳鳴、難
聴、ｗ４膜中心動脈閉塞痙などの血流障害に伴う各種疾
患及び冷感、しびれ、痛み、知覚鈍麻、機能障害、萎縮
、壊死など上記疾患の随伴症状を治療或いは緩和するた
めの治療剤として、本発明治療剤は非常に有用である。Therefore, vibration disease, white wax disease, arteriosclerosis obliterans, thromboangiopathy obliterans, progressive muscular atrophy, cerebrovascular disorders, periarteritis nodosa, systemic erythromatosus, rheumatoid arthritis,
Raynaud's syndrome such as aortitis syndrome, diabetic neuropathy, SMON aftereffects, ischemic neuropathy, freezing, frostbite, tinnitus, hearing loss, various diseases associated with blood flow disorders such as W4 membranous central artery occlusive spasm, cold sensation, and numbness. The therapeutic agent of the present invention is very useful as a therapeutic agent for treating or alleviating accompanying symptoms of the above-mentioned diseases, such as pain, hypoesthesia, dysfunction, atrophy, and necrosis.
本発明治療剤は、血流障害に陥り機能低下した病態状態
においてのみ働き組織を賦活化し正常状態に復元する作
用を有し、低毒性で副作用がなく経口投与可能なため、
安全に長期的な使用ができ、特に慢性的な疾患を治療す
るのに有利である。The therapeutic agent of the present invention has the effect of activating working tissues and restoring them to a normal state only in pathological conditions where blood flow disorder has occurred and the function has decreased, and because it has low toxicity and no side effects and can be administered orally,
It is safe for long-term use and is particularly advantageous for treating chronic diseases.
（実施例）
本発明物質を活性成分として含有する生体機能賦活剤は
、例えば錠剤、カプセル剤、散剤、顆粒剤、粉末、液剤
、注射剤、座剤等の形態とすることができる。(Example) A biological function activator containing the substance of the present invention as an active ingredient can be in the form of, for example, a tablet, capsule, powder, granule, powder, liquid, injection, or suppository.
処方にあたっては本発明物質を単独で用いてもよいし、
また他の医薬活性成分との配合剤とすることも可能であ
る。In the formulation, the substance of the present invention may be used alone,
It is also possible to formulate a compound with other pharmaceutically active ingredients.
経口投与製剤には、そのまま或いは適当な添加剤、例え
ば乳糖、マンニット、トウモロコシデンプン、バレイシ
ョデンブン等の慣用の賦形剤と共に、結晶セルロース、
セルロース誘導体、アラビアゴム、トウモロコシデンプ
ン、ゼラチン等の結合剤、トウモロコシデンプン、バレ
イショデンブン、カルボキシメチルセルロースカルシウ
ム等の崩壊剤、タルク、ステアリン酸マグネシウム等の
滑沢剤、その他増量剤、湿潤化剤、緩衝剤、保存剤、香
料等を適宜組み合わせて錠剤、散剤、顆粒剤或いはカプ
セル剤とすることができる。Oral preparations include crystalline cellulose, as it is or with suitable additives, such as conventional excipients such as lactose, mannitol, corn starch, potato starch, etc.
Binders such as cellulose derivatives, gum arabic, corn starch, and gelatin; disintegrants such as corn starch, potato starch, and carboxymethylcellulose calcium; lubricants such as talc and magnesium stearate; other fillers; wetting agents; and buffers. Tablets, powders, granules, or capsules can be prepared by appropriately combining agents, preservatives, fragrances, and the like.
注射剤としては、注射用蒸留水、生理食塩水、５乃至２
０％ブドウ糖注射液等の水性溶剤、又は植物油、合成脂
肪酸グリセリド、高級脂肪酸エステル、プロピレングリ
コール等の非水性溶剤の溶液、懸濁液若しくは乳化液と
することができ、必要に応じ溶解補助剤、等張化剤、懸
濁化剤、乳化剤、安定剤、保存剤等の通常用いられる添
加剤を適宜加えてもよい。Injections include distilled water for injection, physiological saline, 5 to 2
It can be a solution, suspension, or emulsion in an aqueous solvent such as 0% glucose injection, or a non-aqueous solvent such as vegetable oil, synthetic fatty acid glyceride, higher fatty acid ester, propylene glycol, etc., and if necessary, a solubilizing agent, Commonly used additives such as tonicity agents, suspending agents, emulsifying agents, stabilizers, and preservatives may be added as appropriate.
又、凍結乾燥製剤としてバイアル瓶等に入れ、使用時に
上記溶媒で適宜溶解して使用することもできる。Alternatively, it can be placed in a vial as a lyophilized preparation and dissolved appropriately in the above-mentioned solvent before use.
さらに本発明物質は、各種基剤、例えば乳剤性基剤又は
水溶性基剤と混和して坐剤としたり、その他吸入剤、エ
アゾール剤などに製剤化することができる。Furthermore, the substance of the present invention can be mixed with various bases, such as emulsion bases or water-soluble bases, to form suppositories, or otherwise formulated into inhalants, aerosols, and the like.
本発明治療剤の望ましい投与量は、投与対象、剤形、投
与方法、投与期間等によって変わるが、所望の効果を得
るには、一般に成人に対して有効成分量で一日に１乃至
１００■、好ましくは４乃至４０ｆｆｉｇ経口投与する
ことができる。The desired dosage of the therapeutic agent of the present invention varies depending on the subject to be administered, dosage form, method of administration, administration period, etc., but in order to obtain the desired effect, it is generally necessary for adults to administer an active ingredient dose of 1 to 100 mg per day. , preferably 4 to 40 ffig can be administered orally.
非経口投与（例えば注射剤）の場合、−日投与量は前記
投与量の３乃至１０分の１の用量レベルのものが好まし
い。In the case of parenteral administration (eg, injection), the daily dose is preferably at a dose level of 3 to 10 times the above-mentioned dose.
以下に本発明治療剤の処方例を示す。Prescription examples of the therapeutic agent of the present invention are shown below.
処方例１． （錠剤）
成 分 １錠当り （ｆｆ１
ｒ）本発明物質 ４乳
糖 １０６結晶セ
ルロース ４０ステアリン酸マグネ
シウム １０成 分
本発明物質
乳 糖
タルク
１カプセル当り（＊）
計２５０ ｗｇｒ
処方例３．（注射剤）
本発明物質
塩化ナトリウム
注射用蒸留水
通量
適量Prescription example 1. (tablet) Ingredients per tablet (ff1
r) Invention substance 4 milk
Sugar 106 Crystalline Cellulose 40 Magnesium Stearate 10 Ingredients Inventive Substance Milk Sugar Talc Per Capsule (*) Total 250 wgr Prescription Example 3. (Injection) Appropriate amount of distilled water for injection of sodium chloride, the substance of the present invention
Claims (1)
として含有する生体機能賦活剤。（２）血流改善剤であ
る特許請求の範囲第１項記載の生体機能賦活剤。 （３）しびれ改善剤である特許請求の範囲第１項記載の
生体機能賦活剤。 （４）機能障害に伴う疼痛を治療する特許請求の範囲第
１項記載の生体機能賦活剤。 （５）冷感改善剤である特許請求の範囲第１項記載の生
体機能賦活剤。 （６）知覚異常改善剤である特許請求の範囲第１項記載
の生体機能賦活剤。[Scope of Claims] (1) A biological function activator containing a physiologically active substance extracted from infected tissue as an active ingredient. (2) The biological function activator according to claim 1, which is a blood flow improving agent. (3) The biological function activator according to claim 1, which is a numbness improving agent. (4) The biological function activator according to claim 1, which treats pain associated with functional disorders. (5) The biological function activator according to claim 1, which is a cold sensation improving agent. (6) The biological function activator according to claim 1, which is a paresthesia improving agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63177583A JP2539669B2 (en) | 1988-07-15 | 1988-07-15 | Diabetic neuropathy treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63177583A JP2539669B2 (en) | 1988-07-15 | 1988-07-15 | Diabetic neuropathy treatment |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7348817A Division JP2732379B2 (en) | 1995-12-18 | 1995-12-18 | Perceptual disorder improver |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0228119A true JPH0228119A (en) | 1990-01-30 |
| JP2539669B2 JP2539669B2 (en) | 1996-10-02 |
Family
ID=16033514
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63177583A Expired - Fee Related JP2539669B2 (en) | 1988-07-15 | 1988-07-15 | Diabetic neuropathy treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2539669B2 (en) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08225452A (en) * | 1995-12-18 | 1996-09-03 | Nippon Zoki Pharmaceut Co Ltd | Ameliorative agent to abnormal perception |
| WO2004039383A1 (en) * | 2002-10-31 | 2004-05-13 | Nippon Zoki Pharmaceutical Co., Ltd. | Remedy for fibromyalgia |
| US7083820B2 (en) * | 2000-09-29 | 2006-08-01 | Schilling Marvin L | Method for producing biologically active products |
| WO2007114230A1 (en) | 2006-03-30 | 2007-10-11 | Kyoto University | Thioredoxin production promoting agent |
| WO2009028605A1 (en) | 2007-08-31 | 2009-03-05 | Kyushu University, National University Corporation | Prophylactic or alleviating agent for peripheral nerve disorder induced by anti-cancer agent |
| WO2011111770A1 (en) | 2010-03-11 | 2011-09-15 | 日本臓器製薬株式会社 | Ameliorating or therapeutic agent for chronic prostatitis, interstitial cystitis and/or urination disorders |
| WO2011162317A1 (en) | 2010-06-25 | 2011-12-29 | 日本臓器製薬株式会社 | Method for determination or evaluation of substance of interest |
| US8293280B2 (en) | 2004-12-17 | 2012-10-23 | Nippon Zoki Pharmaceutical Co., Ltd. | Method for treatment of HIV infection |
| US8568789B2 (en) | 2004-12-01 | 2013-10-29 | Nippon Zoki Pharmaceutical Co., Ltd. | Dried product and a process for manufacturing the product |
| CN105663166A (en) * | 2016-03-02 | 2016-06-15 | 中国人民解放军疾病预防控制所 | Bioactive preparation of specific anti-variola virus infection model strain and application of bioactive preparation |
| US9884077B2 (en) | 2013-04-30 | 2018-02-06 | Nippon Zoki Pharmaceutical Co., Ltd. | Extract and preparation containing said extract |
| US10711292B2 (en) | 2010-10-14 | 2020-07-14 | Nikkon Zoki Pharmaceutical Co., Ltd. | Method for promoting the synthesis of collagen and proteoglycan in chondrocytes |
| US11129976B2 (en) | 2016-02-24 | 2021-09-28 | Osaka University | Test method |
| US11207354B2 (en) | 2016-09-23 | 2021-12-28 | Osaka University | Schwann cell differentiation promoting agent and a peripheral nerve regeneration promoting agent |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01230520A (en) * | 1987-11-06 | 1989-09-14 | Nippon Zoki Pharmaceut Co Ltd | Novel physiologically active substance |
-
1988
- 1988-07-15 JP JP63177583A patent/JP2539669B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01230520A (en) * | 1987-11-06 | 1989-09-14 | Nippon Zoki Pharmaceut Co Ltd | Novel physiologically active substance |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08225452A (en) * | 1995-12-18 | 1996-09-03 | Nippon Zoki Pharmaceut Co Ltd | Ameliorative agent to abnormal perception |
| US7083820B2 (en) * | 2000-09-29 | 2006-08-01 | Schilling Marvin L | Method for producing biologically active products |
| WO2004039383A1 (en) * | 2002-10-31 | 2004-05-13 | Nippon Zoki Pharmaceutical Co., Ltd. | Remedy for fibromyalgia |
| US7148012B2 (en) | 2002-10-31 | 2006-12-12 | Nippon Zoki Pharmaceutical Co., Ltd. | Therapeutic agent for fibromyalgia |
| US7238487B2 (en) | 2002-10-31 | 2007-07-03 | Nippon Zoki Pharmaceutical Co., Ltd. | Therapeutic agent for fibromyalgia |
| US7435547B2 (en) | 2002-10-31 | 2008-10-14 | Nippon Zoki Pharmaceutical Co., Ltd. | Therapeutic agent for fibromyalgia |
| US8568789B2 (en) | 2004-12-01 | 2013-10-29 | Nippon Zoki Pharmaceutical Co., Ltd. | Dried product and a process for manufacturing the product |
| US8293280B2 (en) | 2004-12-17 | 2012-10-23 | Nippon Zoki Pharmaceutical Co., Ltd. | Method for treatment of HIV infection |
| WO2007114230A1 (en) | 2006-03-30 | 2007-10-11 | Kyoto University | Thioredoxin production promoting agent |
| US8338108B2 (en) | 2006-03-30 | 2012-12-25 | Kyoto University | Agent for promoting the production of thioredoxin |
| WO2009028605A1 (en) | 2007-08-31 | 2009-03-05 | Kyushu University, National University Corporation | Prophylactic or alleviating agent for peripheral nerve disorder induced by anti-cancer agent |
| US8613962B2 (en) | 2007-08-31 | 2013-12-24 | Kyushu University, National University Corporation | Prophylactic or alleviating agent for peripheral nerve disorder induced by anti-cancer agent |
| WO2011111770A1 (en) | 2010-03-11 | 2011-09-15 | 日本臓器製薬株式会社 | Ameliorating or therapeutic agent for chronic prostatitis, interstitial cystitis and/or urination disorders |
| US9011849B2 (en) | 2010-03-11 | 2015-04-21 | Nippon Zoki Pharmaceutical Co., Ltd. | Ameliorating or therapeutic agent for chronic prostatitis, interstitial cystitis and/or urination disorders |
| WO2011162317A1 (en) | 2010-06-25 | 2011-12-29 | 日本臓器製薬株式会社 | Method for determination or evaluation of substance of interest |
| US9447466B2 (en) | 2010-06-25 | 2016-09-20 | Nippon Zoki Pharmaceutical Co., Ltd. | Method for determination or evaluation of test substance |
| US10711292B2 (en) | 2010-10-14 | 2020-07-14 | Nikkon Zoki Pharmaceutical Co., Ltd. | Method for promoting the synthesis of collagen and proteoglycan in chondrocytes |
| US9884077B2 (en) | 2013-04-30 | 2018-02-06 | Nippon Zoki Pharmaceutical Co., Ltd. | Extract and preparation containing said extract |
| US11129976B2 (en) | 2016-02-24 | 2021-09-28 | Osaka University | Test method |
| CN105663166A (en) * | 2016-03-02 | 2016-06-15 | 中国人民解放军疾病预防控制所 | Bioactive preparation of specific anti-variola virus infection model strain and application of bioactive preparation |
| CN105663166B (en) * | 2016-03-02 | 2020-04-17 | 中国人民解放军疾病预防控制所 | Bioactive preparation of specific anti-smallpox virus infection model strain and application thereof |
| US11207354B2 (en) | 2016-09-23 | 2021-12-28 | Osaka University | Schwann cell differentiation promoting agent and a peripheral nerve regeneration promoting agent |
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| Publication number | Publication date |
|---|---|
| JP2539669B2 (en) | 1996-10-02 |
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