JPH02311422A - Activator for choline acetyltransferase - Google Patents
Activator for choline acetyltransferaseInfo
- Publication number
- JPH02311422A JPH02311422A JP1131439A JP13143989A JPH02311422A JP H02311422 A JPH02311422 A JP H02311422A JP 1131439 A JP1131439 A JP 1131439A JP 13143989 A JP13143989 A JP 13143989A JP H02311422 A JPH02311422 A JP H02311422A
- Authority
- JP
- Japan
- Prior art keywords
- acetylcholine
- drug
- radix
- activator
- present
- 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
- 239000012190 activator Substances 0.000 title claims abstract description 5
- 108010058699 Choline O-acetyltransferase Proteins 0.000 title claims description 12
- 102100023460 Choline O-acetyltransferase Human genes 0.000 title claims description 12
- 230000000694 effects Effects 0.000 claims description 17
- 239000008704 toki-shakuyaku-san Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 27
- 229940079593 drug Drugs 0.000 abstract description 24
- 239000000843 powder Substances 0.000 abstract description 19
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 abstract description 12
- 229960004373 acetylcholine Drugs 0.000 abstract description 12
- 239000000203 mixture Substances 0.000 abstract description 10
- 201000010099 disease Diseases 0.000 abstract description 7
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- 230000007160 gastrointestinal dysfunction Effects 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 15
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 8
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
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- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
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- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
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- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- JJCWKVUUIFLXNZ-UHFFFAOYSA-M 2-hydroxyethyl(trimethyl)azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCO JJCWKVUUIFLXNZ-UHFFFAOYSA-M 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
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- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 102000003914 Cholinesterases Human genes 0.000 description 1
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 229940100228 acetyl coenzyme a Drugs 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
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- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
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- 235000001465 calcium Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
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- 230000008859 change Effects 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 229940048961 cholinesterase Drugs 0.000 description 1
- 230000035601 cold sensitivity Effects 0.000 description 1
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- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 1
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Landscapes
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Abstract
Description
【発明の詳細な説明】
U産業上の利用分野J
本発明は、生体内におけるアセチルコリン合成に重要な
働きを持つコリン・アセチル転移酵素の活性賦活剤に関
するものである。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application J The present invention relates to an activity enhancer of choline acetyltransferase, which has an important role in acetylcholine synthesis in vivo.
[従来の技術および課題]
アセチルコリンは、コリンとアセチル補酵素A(以下、
アセチルCoAと称する。)からコリン・アセチル転移
酵素により合成されるコリン作動性神経繊維の伝達物質
であり、種々の生体反応に関与している極めて重要な生
体内物質である。このアセチルコリンは、諸疾患の発症
に関与している。[Prior art and problems] Acetylcholine is a combination of choline and acetyl coenzyme A (hereinafter referred to as
It is called acetyl-CoA. ) is a cholinergic nerve fiber transmitter synthesized by choline acetyltransferase, and is an extremely important in-vivo substance involved in various biological reactions. This acetylcholine is involved in the onset of various diseases.
例えば、自己免疫疾患である重症筋無力症は、骨格筋の
アセチルコリン受容体が減少しており、ソナブス間隙ア
セチルコリン量を増加することにより症状が緩解する。For example, in myasthenia gravis, which is an autoimmune disease, the number of acetylcholine receptors in skeletal muscles decreases, and symptoms are alleviated by increasing the amount of acetylcholine in the interstitial sonabus.
また、アルツハイマー病およびアルツハイマー型痴呆症
の患者においては、大脳皮質中のアセデルコリンの減少
が認められており、脳内のアセデルコリン量を増加する
ことにより、症状が改善−1)〜るといわれている。Furthermore, in patients with Alzheimer's disease and Alzheimer's type dementia, a decrease in acedercholine in the cerebral cortex has been observed, and symptoms are said to improve by increasing the amount of acedercholine in the brain. .
さらにアセデルコリンは、胃酸の分泌を刺激し、胃腸管
の運動を亢進するため、消化管でのアセデルコリン量を
増加さければ、低下した胃腸機能は緩解する。Furthermore, acedercholine stimulates the secretion of gastric acid and enhances the motility of the gastrointestinal tract, so if the amount of acedercholine in the gastrointestinal tract is avoided, the decreased gastrointestinal function will be alleviated.
従って、生体組織でのアセデルコリン濃度を高める方法
が諸疾患の治療法として有望視されている。Therefore, a method of increasing acedercholine concentration in living tissues is viewed as a promising method for treating various diseases.
アセチルコリンは生体内のあらゆる組織中で合成される
ものであり、現在、組織中のアセチルコリン濃度を高め
るために、以下に示す方法が用いられている。Acetylcholine is synthesized in all tissues in the body, and the following methods are currently used to increase acetylcholine concentration in tissues.
■アセチルコリンの原料となろコリンの前駆物質を与え
、アセデルコリンの生合成を促進する。■Provides a precursor of acetylcholine, a precursor to narocholine, and promotes the biosynthesis of acedercholine.
■コリン・アセデル転移酵素活性を賦活し、アセチルコ
リンの生合成を促進する。■Activates choline acedertransferase activity and promotes acetylcholine biosynthesis.
■アセチルコリンの分解酵素であるコリンエステラーゼ
の酵素活性を阻害して分解を抑制する。■Inhibits the enzyme activity of cholinesterase, which is an enzyme that decomposes acetylcholine, thereby suppressing its decomposition.
しかし、■に関しては、浸れた薬効を有する薬剤はなく
、コリン・アセチル転移酵素活性を賦活する薬剤の開発
か望まれていた。However, with regard to (2), there is no drug with significant medicinal efficacy, and it has been desired to develop a drug that activates choline acetyltransferase activity.
[課題を解決するための手段]
本発明者等は、コリン・アセチル転移酵素活性を賦活す
る薬剤を開発すべく鋭意研究を行った結果、漢方処方で
ある当帰勺薬故に優れた賦活効果を見いだし本発明を完
成した。すなわち、本発明は当帰芍薬散よりなるコリン
・アセチル転移酵素活性賦活剤(以下、本発明の薬剤と
いう。)である。[Means for Solving the Problems] The present inventors conducted intensive research to develop a drug that activates choline acetyltransferase activity, and as a result, they found that the drug, which is a Chinese herbal prescription, has an excellent activation effect. This discovery was made and the present invention was completed. That is, the present invention is a choline acetyltransferase activity activator (hereinafter referred to as the drug of the present invention) comprising Tokishakuyakusan.
本発明の薬剤は、漢方処方の古典である会同要路にその
構成生薬、分量、抽出法等が記載されており、冷え症、
貧血、腹痛等の諸疾患に使用されているが、コリン・ア
セチル転移酵素活性を賦活する作用のあることは従来全
く知られていなかったことである。The drug of the present invention has its constituent herbal medicines, amounts, extraction methods, etc. described in the classic Chinese herbal formula, Kaidou Koro, and is effective against cold sensitivity,
It is used to treat various diseases such as anemia and abdominal pain, but it was completely unknown until now that it had the effect of activating choline acetyltransferase activity.
本発明の薬剤の構成生薬や構成比率は漢方の古典に則っ
て決められるが、漢方の古典には構成生薬の比率に幅が
あり、また生薬は産地、採取時期、自然条件等によって
含有される成分の量が変化するものであるため、各構成
生薬の混合比は適宜増減する必要がある。The constituent crude drugs and composition ratios of the drug of the present invention are determined in accordance with the classical Chinese medicine, but the proportions of the constituent crude drugs vary in the classical Chinese medicine, and the crude drugs contained vary depending on the place of production, time of collection, natural conditions, etc. Since the amounts of the ingredients change, the mixing ratio of each component herbal medicine needs to be increased or decreased as appropriate.
従って本発明の薬剤は、荀薬:凧:沢瀉:訣苓:用荀・
当帰(4〜6:4〜6;4〜6:4〜6:3〜4:3〜
4)の範囲を満足すればいかなる混合比率で乙構わない
。Therefore, the drug of the present invention is
Return (4-6:4-6; 4-6:4-6:3-4:3-
Any mixing ratio may be used as long as it satisfies the range of 4).
さらに本発明の薬剤として特に好ましい混合比率は、荀
薬:准:沢瀉、訣苓、用笥:当帰(4・4:4.4:3
:3)であり、これを10〜20倍量の水で煎じ、滓を
取り去ることにより本発明の薬剤を得ろことができる。Furthermore, a particularly preferable mixing ratio for the drug of the present invention is:
:3), and the drug of the present invention can be obtained by decocting this with 10 to 20 times the amount of water and removing the dregs.
また、携帯の便+11さ、服用のしやすさ等を考慮して
、荀薬:〕毘:沢瀉:沃苓:用荷・当帰(4・4:4・
4・3.3)の割合で混合した生薬から、熱抽出、同夜
分離、濃縮、乾燥の過程を経て得られた乾燥エキス粉末
に賦形剤等を加え、製剤の通則に従つて顆粒剤、カプセ
ル剤、錠剤等の剤型としても差し支えない。In addition, considering portability + 11, ease of administration, etc.,
Add excipients, etc. to the dry extract powder obtained from the herbal medicine mixed in the ratio of 4.3.3) through the process of thermal extraction, overnight separation, concentration, and drying, and make granules according to the general rules for formulation. , capsules, tablets, and other dosage forms.
本発明の薬剤の製造の具体例を示すと以下の如くである
。A specific example of the production of the drug of the present invention is as follows.
具体例1
荀薬49、蒼、t49、沢瀉49、決苓4り、用荀39
、当帰3gの混合生薬に220dの水を加えて1時間、
100℃で加熱抽出し、得られた抽出液を濾過後、スプ
レードライして3.89の乾燥エキス粉末を得た。Specific example 1 Xunyaku 49, Ao, t49, Sawabashi 49, Kessei 4ri, Yoshu 39
, Add 220 d of water to 3 g of mixed herbal medicine for 1 hour.
Extraction was carried out by heating at 100°C, and the resulting extract was filtered and then spray-dried to obtain a dry extract powder with a weight of 3.89.
[発明の効果コ
次に本発明の薬剤がコリン・アセチル転移酵素活性を何
することを実験例を挙げて説明する。[Effects of the Invention] Next, the effects of the drug of the present invention on choline acetyltransferase activity will be explained using experimental examples.
実験例!
SD系老齢ラット(15〜20ケ月)を2群(2週間投
与群およびコントロール群)にわけ、これに具体例で得
た乾燥エキス粉末を1日19/に9の割合で餌に混入し
、飲料水と共に経口投与した。Experimental example! SD old rats (15 to 20 months old) were divided into two groups (2-week administration group and control group), and the dried extract powder obtained in the specific example was mixed into their feed at a ratio of 19/9 in a day. It was administered orally with drinking water.
コントロール群には飲料水のみを投与した。乾燥エキス
粉末の段毎終了後、ラットを断頭し、脳を取り出し、大
脳皮質の部分に0.2%ポリオキソエチレン(lO)オ
クヂルフェニルエーテルを加えてホモジナイズし、以下
に示す組成の混合液を添加して37℃で15分間インキ
ュベートした。The control group received drinking water only. After finishing each stage of dry extract powder, the rat was decapitated, the brain was taken out, 0.2% polyoxoethylene (lO) ocdyl phenyl ether was added to the cerebral cortex, homogenized, and a mixed solution with the composition shown below was prepared. was added and incubated at 37°C for 15 minutes.
10mMリン酸水素ナトリウム緩衝液を加えて反応を止
め、0.5%テトラフェニルボロンのアセトニトリル溶
液、次いで0.4%ブチルPL3Dのトルエン溶液を加
えて分配し、トルエン層の放射活性を液体ノンチレーシ
ョンカウンターで測定し、コリン・アセチル転移酵素活
性とした。The reaction was stopped by adding 10 mM sodium hydrogen phosphate buffer, partitioned by adding 0.5% tetraphenylboron in acetonitrile, then 0.4% butyl PL3D in toluene, and the radioactivity in the toluene layer was removed by liquid non-tillation. It was measured with a counter and defined as choline acetyltransferase activity.
混合液組成
14GアセチルCoA 507
J2.5醋 アセチルCoA
2500.1M エチレンジアミン四酢酸−Naz
1000.4M シアン化ナトリウム
500、 l M 臭化コリン
1005、OM 塩化ナトリウム
100034Mリン酸水素ナトリウム
300フィゾスチグミン−So、
10□ 牛血清アルブまノー□−」−免一10
0(lzρ
その結果、コントロール群のコリン・アセチル転移酵素
活性は1.55±0,11μ−/9/hであるのに対し
、2週間投与群のそれは、1.80±0.24μ−/9
/hであり、酵素活性の賦活が確認された。Mixed liquid composition 14G acetyl CoA 507
J2.5 Acetyl CoA
2500.1M Ethylenediaminetetraacetic acid-Naz
1000.4M Sodium Cyanide
500, l M choline bromide
1005, OM Sodium Chloride
100034M Sodium Hydrogen Phosphate
300 physostigmine-So,
10□ Bovine Serum Album No□-” - Menichi 10
0 (lzρ) As a result, the choline acetyltransferase activity in the control group was 1.55 ± 0.11 μ-/9/h, while that in the 2-week treatment group was 1.80 ± 0.24 μ-/h. 9
/h, and activation of enzyme activity was confirmed.
さらに本発明の薬剤の急性毒性試験についてddY系雄
性マウスを用いて行ったところ、いずれも15g/&g
(投与限界)の経口投与でも死亡例はなかった。Furthermore, when the acute toxicity test of the drug of the present invention was carried out using ddY male mice, both
There were no deaths even after oral administration (dose limit).
上記の結果より本発明の薬剤は、コリン・アセチル転移
酵素の活性を賦活し、毒性が低く安全性の極めて高いも
のであることが確認された。From the above results, it was confirmed that the drug of the present invention activates the activity of choline acetyltransferase, has low toxicity, and is extremely safe.
従って本発明の薬剤は、生体組織のアセチルコリンの低
下によって起こる、あらゆる疾患の治療に有用である。Therefore, the drug of the present invention is useful for treating all diseases caused by a decrease in acetylcholine in living tissues.
次に、本発明の薬剤の投与量および製剤化について説明
する。Next, the dosage and formulation of the drug of the present invention will be explained.
本発明の薬剤はそのまま、あるいは慣用の製剤担体と共
に動物および人に投与することができる。The drug of the present invention can be administered to animals and humans as is or together with a conventional pharmaceutical carrier.
投与形態としては、必要に応じ適宜選択して使用され、
錠剤、カプセル剤、顆粒剤、細粒剤、散剤等の経口剤が
挙げられる。The dosage form is selected and used as appropriate,
Oral preparations such as tablets, capsules, granules, fine granules, and powders can be mentioned.
経口剤として所期の効果を発揮するためには、但各の年
令、体重、疾患の程度により異なるが、通常成人で本発
明の薬剤の有効成分である乾燥エキス粉末の重量として
1〜159を、1日数回に分けての服用が適当と思われ
る。In order to exert the desired effect as an oral agent, the weight of the dry extract powder, which is the active ingredient of the drug of the present invention, for an adult is usually 1 to 159, although it varies depending on the age, body weight, and severity of the disease. It seems appropriate to take the drug in divided doses several times a day.
経口剤は、例えばデンプン、乳糖、白糖、マンニット、
カルボキシメチルセルロース、コーンスターチ、無機塩
類等を用いて常法に従って製造される。Oral agents include, for example, starch, lactose, sucrose, mannitol,
It is manufactured using conventional methods using carboxymethyl cellulose, corn starch, inorganic salts, etc.
この種の製剤には、適宜前記斌形剤の他に、結合剤、崩
壊剤、界面活性剤、滑沢剤、流動性促進剤、矯味剤、着
色剤、香料等を使用することができる。それぞれの具体
例は以下に示す如くである。In addition to the above-mentioned injection molding agent, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a flavoring agent, a coloring agent, a fragrance, and the like can be appropriately used in this type of preparation. Specific examples of each are shown below.
[結合剤1
デンプン、デキストリン、アラヒアゴム末、ゼラチン、
ヒドロキノプロピルスターチ、メチルセルロース、カル
ボキシメチルセルロースナトリウム、ヒドロキンプロピ
ルセル〔l−ス、結晶セルロース、エヂルセルロース、
ポリビニルピロリドン、マクロゴール。[Binder 1 Starch, dextrin, arahia gum powder, gelatin,
Hydroquinopropyl starch, methylcellulose, sodium carboxymethylcellulose, hydroquinpropylcellulose, crystalline cellulose, edylcellulose,
Polyvinylpyrrolidone, macrogol.
[崩壊剤]
デンプン、ヒドロキノプロピルスターチ、カルポキシメ
ヂルセルロースナトリウム、カルボキノメチルセルロー
スカルシウム、カルボキシメチルセルロース、低置換ヒ
ドロキノプロピルセルロース。[Disintegrant] Starch, hydroquinopropyl starch, sodium carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethylcellulose, low-substituted hydroquinopropylcellulose.
[界面活性剤コ
ラウリル硫酸ナトリウム、大豆レシチン、ショ糖脂肪酸
エステル、ポリソルベート 80゜[滑沢剤]
タルク、ロウ類、水素添加植物油、ショ糖脂肪酸エステ
ル、ステアリン酸マグネシウム、ステアリン酸カルシウ
ム、ステアリン酸アルミニウム、ポリエチレングリコー
ル。[Surfactant Sodium colauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80° [Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, polyethylene glycol.
[流動性促進剤]
軽質無水ケイ酸、乾燥水酸化アルミニウムゲル、合成ケ
イ酸アルミニウム、ケイ酸マグネシウム。[Fluidity promoter] Light anhydrous silicic acid, dry aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.
また、本発明の薬剤は、懸濁液、エマルジョン剤、ンロ
ツブ剤、エリキシル剤としても投与することができ、こ
れらの各種網形には、矯味矯臭剤、着色剤を含有してら
よい。The drug of the present invention can also be administered as a suspension, emulsion, tablet, or elixir, and these various forms may contain flavoring agents and coloring agents.
次に実施例を挙げてさらに詳細に説明するが、本発明は
ごれにより回答制限されるものではない。Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited by this.
実施例I
■コーンスターチ 44g■結晶セルロー
ス 44g
■カルボキシメチル
セルロースカルシウム toy
■軽質無水ケイ酸 1g
■ステアリン酸マグネンウム I9
1且淋例11先友也丘@ 1009計 2
009
上記の処方に従って■〜■を均一に琵合し、打錠機にて
圧縮成型して一錠20019の錠剤を得た。Example I ■Corn starch 44g ■Crystalline cellulose 44g ■Carboxymethylcellulose calcium toy ■Light anhydrous silicic acid 1g ■Magnenium stearate I9 1 and Hinoki Example 11 Sentomoyaoka @ 1009 total 2
009 According to the above recipe, ① to ② were uniformly kneaded and compressed using a tablet machine to obtain one tablet of 20019.
この錠剤−錠には、具体例Iで得た化合物10011f
Iが含有されており、成人1日IO〜25錠を数回にわ
けて服用する。This tablet contains the compound 10011f obtained in Example I.
Adults should take IO to 25 tablets a day in several doses.
実施例2
■結晶セルロース 899
■ステアリン酸マグネシウム 19
■カルボキシメチル
セルロースカルシウム 109
■具体例1で得た粉末 1009
計 200g
上記の処方に従っての、■および■の一部を均一に混合
し、圧縮成型した後、粉砕し、■および■の残量を加え
て混合し、打錠機にて圧縮成型して一部200スタの錠
剤を得た。Example 2 ■ Crystalline cellulose 899 ■ Magnesium stearate 19 ■ Calcium carboxymethyl cellulose 109 ■ Powder obtained in specific example 1 1009 Total 200 g After uniformly mixing ■ and part of ■ according to the above recipe and compression molding. The mixture was pulverized, the remaining amounts of ① and ③ were added and mixed, and the mixture was compressed using a tablet machine to obtain 200 star tablets.
この錠剤−錠には、具体例1で得た粉末100 j!9
が含有されており、成人1日lO〜25錠を数回にわけ
て服用する。This tablet contains 100 j! of the powder obtained in Example 1! 9
It contains 10 to 25 tablets per day for adults, divided into several doses.
実施例3
■結晶セルロース 509
■lO%ヒドロキンプロピル
セルロースエタノール溶液 399
■カルボキシメヂル
セルロースカルシウム 109
■ステアリン酸マグネシウム 10
0具体例1で得た粉末 101
計 200g
上記の処方に従って■、■および■を均一に混合し、常
法によりねつ和し、押し出し造粒機により造粒し、乾燥
・解砕した後、■および■を混合し、打鍵機にて圧縮成
型して一部200179の錠剤を得た。Example 3 ■ Crystalline cellulose 509 ■ 10% hydroquinepropyl cellulose ethanol solution 399 ■ Calcium carboxymethyl cellulose 109 ■ Magnesium stearate 10 0 Powder obtained in Example 1 101 Total 200 g Prepare ■, ■, and ■ according to the above recipe. After uniformly mixing, neutering by a conventional method, granulating with an extrusion granulator, drying and crushing, ① and ② were mixed, and compression molded with a key press to make some 200179 tablets. Obtained.
この錠剤−錠には、具体例1で得た粉末100肩9が含
有されており、成人1日5〜40錠を数回にわけて服用
する。This tablet contains the powder 100 tablets obtained in Example 1, and is taken by adults in 5 to 40 tablets a day in several doses.
実施例4
■コーンスターチ 399
■ステアリン酸マグネシウム 50?
■カルボキシメチル
セルロースカルシウム 109
■軽質無水ケイ酸 1g
屯し県−1伜]1で得た粉末 1ooy計
2009
上記の処方に従って■〜■を均一に混合し、圧縮成型機
にて圧縮成型後、破砕機により粉砕し、篩別して顆粒剤
を得た。Example 4 ■Corn starch 399 ■Magnesium stearate 50? ■Carboxymethylcellulose calcium 109 ■Light silicic anhydride 1g Powder obtained in 1) 1ooy total
2009 According to the above recipe, (1) to (2) were uniformly mixed, compression molded using a compression molding machine, crushed using a crusher, and sieved to obtain granules.
この顆粒剤I9には、具体例1で得た粉末500 M9
が含有されており、成人1日4〜209を数回にわけて
服用する。This granule I9 contains powder 500 M9 obtained in Example 1.
It contains 4 to 209 doses per day for adults, divided into several doses.
実施例5
■結晶セルロース 659
■lO%ヒドロキンプロピル
セルロースエタノール溶液359
]且茎PI lで得た粉末 100g計
2009
上記の処方に従って■〜■を均一に混合し、ねつ和した
。押し出し造粒機に上り造粒後、乾燥し、篩別して顆粒
剤を得た。Example 5 ■Crystalline cellulose 659 ■1O% hydroquinepropyl cellulose ethanol solution 359] Powder obtained from stem PI l 100g total
2009 According to the above recipe, ① to ② were uniformly mixed and made into a paste. After going into an extrusion granulator and granulating, the mixture was dried and sieved to obtain granules.
この顆粒剤19には、具体例1で得た粉末500句が含
有されており、成人1日2〜5gを数回にわけて服用す
る。This granule 19 contains 500 pieces of the powder obtained in Example 1, and is taken by adults in 2 to 5 g per day in several doses.
実施例6
■コーンスターチ 999
■軽質無水ケイ酸 19
■具体例1で得た粉末 1009
計 2009
上記の処方に従って■〜■を均一に混合し、200 #
9を2号カプセルに充填した。Example 6 ■Corn starch 999 ■Light silicic anhydride 19 ■Powder obtained in specific example 1 1009 Total 2009 ■~■ were mixed uniformly according to the above recipe, and 200 #
9 was filled into a No. 2 capsule.
このカプセル剤!カプセルには、具体例Iで得た粉末1
001119が含有されており、成人1日IO〜25カ
プセルを数回にわけて服用する。This capsule! The capsules contain powder 1 obtained in Example I.
001119, and adults should take IO to 25 capsules a day in several doses.
Claims (1)
剤Choline acetyl transferase activity activator consisting of Tokishakuyakusan
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1131439A JPH0643337B2 (en) | 1989-05-26 | 1989-05-26 | Choline / acetyltransferase activity enhancer |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1131439A JPH0643337B2 (en) | 1989-05-26 | 1989-05-26 | Choline / acetyltransferase activity enhancer |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH02311422A true JPH02311422A (en) | 1990-12-27 |
JPH0643337B2 JPH0643337B2 (en) | 1994-06-08 |
Family
ID=15057990
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP1131439A Expired - Lifetime JPH0643337B2 (en) | 1989-05-26 | 1989-05-26 | Choline / acetyltransferase activity enhancer |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH0643337B2 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04275224A (en) * | 1991-03-02 | 1992-09-30 | Kissei Pharmaceut Co Ltd | Therapeutic agent for dementia |
JPH0987187A (en) * | 1995-07-13 | 1997-03-31 | Hagino Nobuyoshi | Apoptosis inhibitor |
WO1997029764A1 (en) * | 1996-02-15 | 1997-08-21 | Daiichi Pharmaceutical Co., Ltd. | Brain activators |
-
1989
- 1989-05-26 JP JP1131439A patent/JPH0643337B2/en not_active Expired - Lifetime
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04275224A (en) * | 1991-03-02 | 1992-09-30 | Kissei Pharmaceut Co Ltd | Therapeutic agent for dementia |
JPH0987187A (en) * | 1995-07-13 | 1997-03-31 | Hagino Nobuyoshi | Apoptosis inhibitor |
WO1997029764A1 (en) * | 1996-02-15 | 1997-08-21 | Daiichi Pharmaceutical Co., Ltd. | Brain activators |
Also Published As
Publication number | Publication date |
---|---|
JPH0643337B2 (en) | 1994-06-08 |
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