JPS63104926A - Remedy or preventive agent against senile dementia - Google Patents

Remedy or preventive agent against senile dementia

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Publication number
JPS63104926A
JPS63104926A JP24837686A JP24837686A JPS63104926A JP S63104926 A JPS63104926 A JP S63104926A JP 24837686 A JP24837686 A JP 24837686A JP 24837686 A JP24837686 A JP 24837686A JP S63104926 A JPS63104926 A JP S63104926A
Authority
JP
Japan
Prior art keywords
senile dementia
vitamin
active
remedy
agent
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
Application number
JP24837686A
Other languages
Japanese (ja)
Other versions
JPH0443886B2 (en
Inventor
Yuji Makino
悠治 牧野
Yoshiki Suzuki
嘉樹 鈴木
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.)
Teijin Ltd
Original Assignee
Teijin Ltd
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 Teijin Ltd filed Critical Teijin Ltd
Priority to JP24837686A priority Critical patent/JPS63104926A/en
Publication of JPS63104926A publication Critical patent/JPS63104926A/en
Publication of JPH0443886B2 publication Critical patent/JPH0443886B2/ja
Granted legal-status Critical Current

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Abstract

PURPOSE:To obtain a remedy or preventive agent against senile dementia, especially Alzheimer's senile dementia containing active vitamin D3 as an active ingredient. CONSTITUTION:Active vitamins D3 having great ability capable of normalizing calcium metabolism by promotion of adsorption from an enteric canal of calcium are contained and milk sugar, starch, talc, magnesium stearate, succharides, alcohol, physiological saline, surfactant, antioxidant, preservatives, adsorption- promoting agent, etc., are added and the mixture is formulated to provide the aimed product. Above-mentioned vitamin D3 is for example 1alpha-hydroxy vitamin D3 or 1alpha, 24(R)-dihydroxy vitamin D3. The remedy or agent can be orally parenterally administered and dose thereof is 0.05-20.0mug, preferably 0.1-5.0mug/ head/day based on the active vitamins D3.

Description

【発明の詳細な説明】 〈産業上の利用分野〉 本発明は新規の老年性痴呆症治療又は予防剤に関する。[Detailed description of the invention] <Industrial application field> The present invention relates to a novel agent for treating or preventing senile dementia.

更に詳しくは、活性型ビタミンD3類を有効成分とする
老年性痴呆症治療又は予防剤に関する。
More specifically, the present invention relates to a treatment or prevention agent for senile dementia containing active vitamin D3 as an active ingredient.

〈従来技術とその問題点〉 医療技術の進歩は人間の寿命を延長した。各種の薬物の
開発、物理療法の進展、外科手法の進歩等により感染症
、^血圧、癌等の治療法は確実に進歩してきた。そして
、人間の寿命は、今後も徐々にではあるが着実に延長し
つづけていくようである。
<Prior art and its problems> Advances in medical technology have extended human lifespans. Treatment methods for infectious diseases, blood pressure, cancer, etc. have steadily progressed due to the development of various drugs, advances in physical therapy, advances in surgical techniques, etc. And it appears that human lifespans will continue to increase gradually but steadily.

しかるに、上記のような肉体的な疾患は克服されつつあ
る一方、精神的な疾患が社会問題化している。なかでも
社会が高齢化するに伴い、高齢者の精神疾患が増加して
いる。精神疾患の中でも老年性痴呆症は患者自身の人格
の喪失、家族の犠牲。
However, while the physical illnesses mentioned above are being overcome, mental illnesses are becoming a social problem. In particular, as society ages, mental illnesses among the elderly are increasing. Among mental illnesses, senile dementia causes the patient to lose his or her own personality and sacrifices his or her family.

有効な治療法の欠如、病因の不明等の理由で重大な問題
といえよう。
This is a serious problem due to the lack of effective treatments and the unknown etiology.

従来、老年性痴呆症の治療法としては脳血流循環改善剤
、脳代謝賦活剤等の薬物療法が試みられてきた。そして
老年性痴呆症の中でも脳血管型老年性痴呆症には、脳血
流循環改善剤と脳代謝賦活剤の併用により、症状の若干
の改善がみられるといわれている。
Conventionally, drug treatments such as cerebral blood circulation improving agents and cerebral metabolism activating agents have been attempted as treatments for senile dementia. Among senile dementias, it is said that some improvement in the symptoms of cerebrovascular senile dementia can be seen by the combined use of a cerebral blood flow improving agent and a cerebral metabolism activator.

しかしながら老年性痴呆症の原因が明らかでないので、
実際には、十分に有効な薬物がないのが現状である。
However, since the cause of senile dementia is not clear,
In reality, there are currently no sufficiently effective drugs.

さらに、老年性痴呆症の別の型であるアルツハイマー型
老年性痴呆症は全く原因が不明であり、はとんど全く有
効な薬物がないといわれている。
Furthermore, the cause of Alzheimer's senile dementia, which is another type of senile dementia, is completely unknown, and it is said that there are almost no effective drugs available.

したがって、老年性痴呆症に有効な薬剤、特にアルツハ
イマー型老年性痴呆症に有効な薬剤が望まれている。
Therefore, there is a desire for a drug that is effective against senile dementia, especially a drug that is effective against senile dementia of the Alzheimer's type.

く問題点を解決するための手段〉 近年DelucaおよびKOdiCekらによってなさ
れたビタミンD3の代謝産物の分離・同定および代謝経
路の解明の結果、ビタミン03は最初肝臓において25
位が水酸化され25−ヒドロキシビタミンD3に変換し
、次いで腎臓において更に24位あるいは1α位の水酸
化が行なわれ24.25−ジヒドロキシビタミンD3や
ホルモン活性を有する1α。
As a result of recent efforts by Deluca and KOdiCek et al. to isolate and identify the metabolites of vitamin D3 and to elucidate the metabolic pathway, vitamin 03 is initially produced in the liver at 25
It is hydroxylated at the 25-hydroxyvitamin D3 position and converted to 25-hydroxyvitamin D3, and then further hydroxylated at the 24th or 1α position in the kidney, resulting in 24.25-dihydroxyvitamin D3 and 1α, which has hormonal activity.

25−ジヒドロキシビタミンD3および1α、24゜2
5−トリヒドロキシビタミンD3に代謝されることが明
らかになった。そして、これらの代謝産物およびその合
成アナローブである1α−ヒドロキシビタミンD3等が
腸管からのカルシウム輸送能および骨塩動員能を促進し
種々のカルシウム代謝異常に基づく疾患の治療薬として
有用であることはよく知られている。
25-dihydroxyvitamin D3 and 1α, 24°2
It has been revealed that it is metabolized to 5-trihydroxyvitamin D3. Furthermore, these metabolites and their synthetic analogues, such as 1α-hydroxyvitamin D3, promote the ability to transport calcium from the intestinal tract and the ability to mobilize bone minerals, and are useful as therapeutic agents for various diseases caused by abnormal calcium metabolism. well known.

本発明者らは、これらビタミンD3の代謝産物等の、す
なわち活性型ビタミンD3類の骨粗髭症への治療効果を
確認するための臨床試験を実施した際に、驚くべきこと
に、活性型ビタミンD3類が老年性痴呆症、特にアルツ
ハイマー型老年性痴呆症の治療に有効であることを知見
した。
Surprisingly, when the present inventors conducted a clinical trial to confirm the therapeutic effects of these vitamin D3 metabolites, that is, active vitamin D3, on osteoporosis, we found that It has been found that vitamin D3 is effective in treating senile dementia, particularly senile dementia of the Alzheimer's type.

これらの活性型ビタミン03類が、何故、老年性痴呆症
、特にアルツハイマー型老年性痴呆症に有効であるが、
現在のところ不明である。しかしながら、本発明者らは
アルツハイマー型老年性痴呆症の患者の脳内に、アルミ
ノケイ酸塩が異常に多く発見されること、カルシウムが
不足すると体内にアルミニウムがとり込まれやすくなる
こと、及び活性型ビタミンD3類が腸管からのカルシウ
ムの吸収を促進すること、等から考えて、活性型ビタミ
ンD3類がアルツハイマー型老年性痴呆症患者のカルシ
ウム代謝を正常化し、これによって脳内のアルミノケイ
酸塩を低減化するものと推定し、活性型ビタミンD3類
の老年性痴呆症への治療効果を調べたところ、これらが
、老年性痴呆症の治療又は予防剤として有効であること
を見い出したものである。しかして、本発明は活性型ビ
タミンD3類を有効成分とする老年性痴呆症治療又は予
防剤である。
Why are these three active vitamins effective against senile dementia, especially Alzheimer's type senile dementia?
It is currently unknown. However, the present inventors found that an abnormally large amount of aluminosilicate is found in the brains of patients with Alzheimer's type senile dementia, that a lack of calcium makes it easier for the body to take up aluminum, and that active Considering that vitamin D3 promotes the absorption of calcium from the intestinal tract, active vitamin D3 normalizes calcium metabolism in patients with Alzheimer's type senile dementia, thereby reducing aluminosilicate in the brain. When we investigated the therapeutic effects of active vitamin D3 on senile dementia, we found that these are effective as therapeutic or preventive agents for senile dementia. Therefore, the present invention is a senile dementia treatment or prevention agent containing active vitamin D3 as an active ingredient.

本発明の活性型ビタミン03類を有効成分とする老年性
痴呆症治療又は予防剤は、老年性痴呆症のなかでも、特
にアルツハイマー型老年性痴呆症に著効がある。
The senile dementia treatment or prevention agent containing active vitamin 03 as an active ingredient of the present invention is particularly effective against senile dementia of the Alzheimer's type among senile dementias.

本発明に用いられる活性型ビタミンD3類としては、カ
ルシウム代謝を正常化するものであれば何れでもよく、
例えば1α−ヒドロキシビタミンD1,1α、25−ジ
ヒドロキシビタミン03,1α、24(R)−ジヒドロ
キシビタミンD3.1α。
The active vitamin D3 used in the present invention may be any vitamin D3 that normalizes calcium metabolism.
For example, 1α-hydroxyvitamin D1,1α, 25-dihydroxyvitamin 03,1α, 24(R)-dihydroxyvitamin D3.1α.

24(S)−ジヒドロキシビタミンD3,1α、24゜
25−トリヒドロキシビタミンD3.1α−ヒドロキシ
−24−オキソビタミンD3.1α、25−ジヒドロキ
シ−26,26,26,27,27,27−ヘキサフル
オロビタミンD3,1α、25−ジヒドロキシ−24゜
24−ジフルオロビタミンD31α、25−ジヒドロキ
シビタミン[)3−26.23−ラクトン等の1α位に
水酸基を有する活性型ビタミンD3類:24,25−ジ
ヒドロキシビタミンQ3,24−ヒト0キシビタミンD
3,25−ヒドロキシビタミン03.ビタミンD3−2
6.23−チクトン等の1α位に水酸基を有しない活性
型ビタミンD3類が挙げられる。
24(S)-dihydroxyvitamin D3,1α, 24°25-trihydroxyvitamin D3.1α-hydroxy-24-oxovitamin D3.1α, 25-dihydroxy-26,26,26,27,27,27-hexafluoro Vitamin D3,1α, 25-dihydroxy-24゜24-difluorovitamin D31α, 25-dihydroxyvitamin [)3-26.Activated vitamin D3 types having a hydroxyl group at the 1α-position such as 23-lactone: 24,25-dihydroxyvitamin Q3,24-human oxyvitamin D
3,25-Hydroxyvitamin 03. Vitamin D3-2
Examples include active vitamin D3s that do not have a hydroxyl group at the 1α position, such as 6.23-tictone.

これらの活性型ビタミンD3類は公知の化合物であり、
公知の方法によって製造し得る[有機合成化学、第37
巻、 NQ9. 755(1979) ;有機合成化学
、第37巻、社10. 809(1979)  ] 。
These active vitamin D3s are known compounds,
It can be produced by a known method [Organic Synthetic Chemistry, No. 37]
Volume, NQ9. 755 (1979); Organic Synthetic Chemistry, Volume 37, Sha 10. 809 (1979)].

上記活性型ビタミンD3類のなかでも、カルシウムの腸
管からの吸収促進により、カルシウム代謝を正常化する
能力の大きい1α−とドロキシビタミンD3,1α、2
4(R)−ジヒドロキシビタミンD3,1α、25−ジ
ヒドロキシビタミンD3゜1α、25−ジヒドロキシ−
24,24−ジフルオロビタミンD3,1α、25−ジ
ヒドロキシ−26,26゜26、27.27.27−へ
キサフルオロビタミンD3が好ましく、特に1α−ヒド
ロキシビタミンD3゜1.24(R)−ジヒドロキシビ
タミンD3が好ましい。
Among the active vitamin D3 types mentioned above, 1α- and droxyvitamin D3, 1α, and 2 have the greatest ability to normalize calcium metabolism by promoting calcium absorption from the intestinal tract.
4(R)-dihydroxyvitamin D3,1α, 25-dihydroxyvitamin D3°1α, 25-dihydroxy-
24,24-difluorovitamin D3,1α, 25-dihydroxy-26,26°26,27.27.27-hexafluorovitamin D3 are preferred, especially 1α-hydroxyvitamin D3°1.24(R)-dihydroxyvitamin D3 is preferred.

本発明の老年性痴呆症治療又は予防剤は、上記活性型ビ
タミンD3類を含有し、下記に示す種々の製剤形態によ
って、経口、非経口のいずれでも投与され得る。非経口
投与は筋肉内、皮下、静脈内、直腸投与を含む。
The senile dementia treatment or prevention agent of the present invention contains the above-mentioned active vitamin D3 and can be administered either orally or parenterally using various formulations shown below. Parenteral administration includes intramuscular, subcutaneous, intravenous, and rectal administration.

製剤形態としては、例えば、軟カプセル剤0錠剤゛、硬
カプセル剤、散剤、顆粒剤、液剤、注射剤。
Examples of dosage forms include soft capsules, hard capsules, powders, granules, liquids, and injections.

外用剤半割等があげられる。その他の成分として、乳糖
、でんぷん、タルク、ステアリン酸マグネシウム、糖又
はその誘導体、アルコール、生理食塩水、界面活性剤、
抗酸化剤、防腐剤、吸収促進剤等を、本発明の活性型ビ
タミンD3類と併用し得る。
Topical preparations can be given in half. Other ingredients include lactose, starch, talc, magnesium stearate, sugar or its derivatives, alcohol, physiological saline, surfactant,
Antioxidants, preservatives, absorption enhancers, etc. may be used in combination with the active vitamin D3s of the present invention.

本発明の老年性痴呆症治療又予防剤の有効成分である、
これらの活性型ビタミン03類の投与量は、通常1人1
日当りO,OSμg〜20.0μ9.好ましくは1人1
日当り0.1μ9〜°5.0μ9である。
The active ingredient of the senile dementia treatment or prevention agent of the present invention,
The dosage of these active vitamins 03 is usually 1 per person.
O,OSμg~20.0μ9 per day. Preferably 1 per person
It is 0.1 μ9 to °5.0 μ9 per day.

製剤中の活性型ビタミンD3類の含有値は、上記の投与
量から、用いる製剤の単位必要量に応じて適宜法められ
る。
The content of active vitamin D3 in the preparation is determined as appropriate from the above-mentioned dosage depending on the required unit amount of the preparation used.

〈発明の効果〉 本発明によれば、活性型ビタミンD3類を有効成分とす
る老年性痴呆症治療又は予防剤が提供され、かかる治療
又は予防剤は、老年性痴呆症特にアルツハイマー型老年
性痴呆症の治療又は予防に有効である。
<Effects of the Invention> According to the present invention, a treatment or prevention agent for senile dementia containing active vitamin D3 as an active ingredient is provided, and such treatment or prevention agent can be used to treat or prevent senile dementia, particularly senile dementia of the Alzheimer type. It is effective in treating or preventing diseases.

〈実施例〉 以下本発明を実施例により更に詳細に説明する。<Example> The present invention will be explained in more detail below with reference to Examples.

実施例1゜ 1α−ごドロキシビタミンD3を含有する経口剤(ソフ
トカプセル剤)を、長谷用式簡易痴呆診査で痴呆と判定
された老年性痴呆症患者7人に、1日1人1μ9を長期
間投与して、投与前侵の痴呆診査の点数を比較し、1α
−ヒドロキシビタミンD3の治療効果を調べた。
Example 1 An oral preparation (soft capsule) containing 1α-godroxyvitamin D3 was given to 7 senile dementia patients who were determined to have dementia using Hase's simple dementia test, at a dose of 1 μ9 per person per day. After administering the drug for a period of time, we compared the scores on the pre-administration dementia examination, and found that 1α
- The therapeutic effect of hydroxyvitamin D3 was investigated.

結果を第1表に示す。第1表より1α−ヒドロキシビタ
ミンD3の老年性痴呆症に対する良好な治療効果が明ら
かとなった。
The results are shown in Table 1. Table 1 reveals that 1α-hydroxyvitamin D3 has a good therapeutic effect on senile dementia.

なお、長谷用式簡易診査は次のような質問が行われた。The following questions were asked in the Hase type simple examination.

質問内容            配点1、きようは何
日か? 何月何日 何曜日             
 0,32、ここはどこですか’i’        
               0.2.53、年齢は
?(3〜4年以内は正)0.24、最近起こった出来事
から何年(何か月)位経ちましたか?あるいはいつごろ
でしたか7                  0.
2.55、生まれたのはどこですか(出生地)0,26
、大東亜戦争が終わった(または関東大震災があった)
のはいつですか?(3〜4年以内は正)       
                0.3.57.1年
は何日ですか(または1時間は何分ですか)     
     0.2.58、日本の総理大臣は?0.3 9.100カら7を順に引イテ下サイ。100−7−9
3 93−7−86    0.2,410、数の逆唱
(6−8−2,3−5−2−9)          
    0,2,411.5つの物品テスト5つの物品
を1ずつ言わせてそれらをかくして何があったかを問う
                      0,5
. 1.52.5. 3.5 所要時間15分以内 満点32.5点 合計点数 評価 >31  nomal  (正常) 30.5〜22 5ubnoul (境界)21.5〜
10.5  predeaientia  (準痴呆)
10>  deIlentia(痴呆)第1表 実施例2゜ 中鎖脂肪酸トリグリセライドエステル1 、5 Kgに
1α−とドロキシビタミンD310■を溶解し、1カプ
セル中に1α−ヒドロキシビタミンD3を1.0μ9含
有するように下記剤皮成分を加温溶解し、軟カプセル製
造機を用いて常法により軟カプセル剤を製造した。
Question content Points: 1. What day is it today? What month, what day, what day of the week?
0,32, where is this 'i'
0.2.53, how old are you? (Correct within 3-4 years) 0.24 How many years (months) have passed since the recent event? Or when was it?7 0.
2.55, where were you born? (place of birth) 0,26
, the Greater East Asia War ended (or the Great Kanto Earthquake occurred)
When is it? (Correct within 3-4 years)
0.3.57. How many days in a year (or how many minutes in an hour)
0.2.58, Who is the Prime Minister of Japan? 0.3 9. Draw 7 from 100 in order. 100-7-9
3 93-7-86 0.2,410, reciting numbers backwards (6-8-2, 3-5-2-9)
0, 2, 411. 5 Objects Test Ask students to name 5 objects one by one and ask them what happened. 0, 5
.. 1.52.5. 3.5 Required time within 15 minutes Total score of 32.5 points Evaluation > 31 normal (normal) 30.5 ~ 22 5ubnoul (border) 21.5 ~
10.5 predeaientia (semi-dementia)
10> deIlentia (dementia) Table 1 Example 2 Medium chain fatty acid triglyceride ester 1.1α- and droxyvitamin D310■ are dissolved in 5 kg, and 1 capsule contains 1.0μ9 of 1α-hydroxyvitamin D3. The following shell components were dissolved by heating, and soft capsules were produced in a conventional manner using a soft capsule making machine.

剤皮処方例 ゼラチン          10  重量部製グリセ
リン        2 防腐剤(エチルパラベン+プロピルパラベン)0.05
 N 水                      0.
2  〃(最終形態に於ける重量部)
Shell formulation example Gelatin 10 parts by weight Glycerin 2 Preservatives (ethylparaben + propylparaben) 0.05
N water 0.
2 (Weight part in final form)

Claims (1)

【特許請求の範囲】 1、活性型ビタミンD_3類を有効成分とする老年性痴
呆症治療又は予防剤。 2、活性型ビタミンD_3類が1α−ヒドロキシビタミ
ンD_3であることを特徴とする特許請求の範囲第1項
記載の老年性痴呆症治療又は予防剤。 3、活性型ビタミンD_3類が1α,24(R)−ジヒ
ドロキシビタミンD_3であることを特徴とする特許請
求の範囲第1項記載の老年性痴呆症治療又は予防剤。 4、老年性痴呆症がアルツハイマー型老年性痴呆症であ
る特許請求の範囲第1項ないし第3項のいずれか1項に
記載の老年性痴呆症治療又は予防剤。
[Scope of Claims] 1. A senile dementia treatment or prevention agent containing active vitamin D_3 as an active ingredient. 2. The agent for treating or preventing senile dementia according to claim 1, wherein the active vitamin D_3 is 1α-hydroxyvitamin D_3. 3. The agent for treating or preventing senile dementia according to claim 1, wherein the active vitamin D_3 is 1α,24(R)-dihydroxyvitamin D_3. 4. The agent for treating or preventing senile dementia according to any one of claims 1 to 3, wherein the senile dementia is Alzheimer's type senile dementia.
JP24837686A 1986-10-21 1986-10-21 Remedy or preventive agent against senile dementia Granted JPS63104926A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP24837686A JPS63104926A (en) 1986-10-21 1986-10-21 Remedy or preventive agent against senile dementia

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP24837686A JPS63104926A (en) 1986-10-21 1986-10-21 Remedy or preventive agent against senile dementia

Publications (2)

Publication Number Publication Date
JPS63104926A true JPS63104926A (en) 1988-05-10
JPH0443886B2 JPH0443886B2 (en) 1992-07-20

Family

ID=17177180

Family Applications (1)

Application Number Title Priority Date Filing Date
JP24837686A Granted JPS63104926A (en) 1986-10-21 1986-10-21 Remedy or preventive agent against senile dementia

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995002409A3 (en) * 1993-07-15 1995-04-27 Univ Pennsylvania Use of vitamin d and derivatives thereof for the manufacture of a medicament for protection against neuron loss
WO1997029740A1 (en) * 1996-02-13 1997-08-21 Wisconsin Alumni Research Foundation Multiple sclerosis treatment
US6479474B2 (en) 1999-07-08 2002-11-12 Wisconsin Alumni Research Foundation Dietary calcium as a supplement to vitamin D compound treatment of multiple sclerosis
JP5789339B2 (en) * 2013-01-21 2015-10-07 レジリオ株式会社 Therapeutic drugs and therapeutic methods involving 1,25D3-MARRS for neurological diseases including Alzheimer's disease, etc.
US10232008B1 (en) * 2015-10-05 2019-03-19 Michael P. Moran Multi-purpose nutritional supplement composition

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995002409A3 (en) * 1993-07-15 1995-04-27 Univ Pennsylvania Use of vitamin d and derivatives thereof for the manufacture of a medicament for protection against neuron loss
US5939407A (en) * 1993-07-15 1999-08-17 University Of Kentucky Research Foundation Method of protecting against neuron loss
WO1997029740A1 (en) * 1996-02-13 1997-08-21 Wisconsin Alumni Research Foundation Multiple sclerosis treatment
US5716946A (en) * 1996-02-13 1998-02-10 Wisconsin Alumni Research Foundation Multiple sclerosis treatment
US6479474B2 (en) 1999-07-08 2002-11-12 Wisconsin Alumni Research Foundation Dietary calcium as a supplement to vitamin D compound treatment of multiple sclerosis
JP5789339B2 (en) * 2013-01-21 2015-10-07 レジリオ株式会社 Therapeutic drugs and therapeutic methods involving 1,25D3-MARRS for neurological diseases including Alzheimer's disease, etc.
EP2946792A4 (en) * 2013-01-21 2016-09-28 Resilio Company Ltd THERAPEUTIC AGENT AND THERAPEUTIC METHOD RELATING TO 1,25D3-MARRS FOR NEUROLOGICAL DISEASE SUCH AS ALZHEIMER'S DISEASE& xA;
US10232008B1 (en) * 2015-10-05 2019-03-19 Michael P. Moran Multi-purpose nutritional supplement composition

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