JPS5811856B2 - 2 4-bis (2'-acetoxybenzamide) - Google Patents
2 4-bis (2'-acetoxybenzamide)Info
- Publication number
- JPS5811856B2 JPS5811856B2 JP8533275A JP8533275A JPS5811856B2 JP S5811856 B2 JPS5811856 B2 JP S5811856B2 JP 8533275 A JP8533275 A JP 8533275A JP 8533275 A JP8533275 A JP 8533275A JP S5811856 B2 JPS5811856 B2 JP S5811856B2
- Authority
- JP
- Japan
- Prior art keywords
- type
- bis
- benzoic acid
- acetoxybenzamido
- crystals
- 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
Links
Description
【発明の詳細な説明】
本発明は２，４−ビス（２′−アセトキシベンズアミド
）安息香酸の吸収性の良い結晶の形成法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for forming highly absorbable crystals of 2,4-bis(2'-acetoxybenzamido)benzoic acid.
２．４−ビス（２′−アセトキシベンズアミド）安息香
酸は先に本発明者らにより初めて製造され、且つこのも
のが免疫反応異常に基づく各種の疾患に対して優れた作
用を有することが見出され、医薬として期待される物質
である。2.4-Bis(2'-acetoxybenzamido)benzoic acid was previously produced for the first time by the present inventors, and was found to have excellent effects on various diseases based on abnormal immune reactions. It is a substance that is expected to be used as a medicine.
しかしながら、その後の動物実験において、生体内吸収
の上で必ずしも満足できるものとは言えず、種々検討の
結果、通常得られる結晶（融点１９４〜５℃、以下α型
結晶という）の他に結晶析出条件によっては低融点の異
結晶（融点１７０〜５°Ｃ１以下β型結晶という）を形
成することおよび該結晶形のものは生体内吸収が極めて
良好であるとの新知見が得られた。However, in subsequent animal experiments, it could not be said that the absorption in the body was necessarily satisfactory, and as a result of various studies, it was found that crystals precipitated in addition to the normally obtained crystals (melting point 194-5℃, hereinafter referred to as α-type crystals). New findings have been obtained that, depending on the conditions, a heterocrystal with a low melting point (melting point of 170 to 5° C. or less, referred to as a β-type crystal) is formed, and that this crystal form is extremely well absorbed in the living body.
本発明はこの新知見に基づき、β型結晶を選択的に製造
する方法について検討を加え本発明を完成した。Based on this new knowledge, the present invention has been completed by studying a method for selectively producing β-type crystals.
すなわち本発明はα型２，４−ビス（２′−アセトキシ
ベンズアミド）安息香酸を一般式Ｒ−ＣＮ（式中Ｒは低
級アルキル基を示す）で表わされる溶媒を用いて再結晶
せしめることを特徴とするβ型２，４−ビス（２′−ア
セトキシベンズアミド）安息香酸の製造法である。That is, the present invention is characterized in that α-type 2,4-bis(2'-acetoxybenzamido)benzoic acid is recrystallized using a solvent represented by the general formula R-CN (wherein R represents a lower alkyl group). This is a method for producing β-type 2,4-bis(2'-acetoxybenzamido)benzoic acid.
本発明により得られるβ型結晶について、α型結晶を対
照として経口投与後の血中濃度を調査した結果は第５図
のとおりであった。The blood concentration of the β-type crystal obtained by the present invention after oral administration was investigated using the α-type crystal as a control, and the results are shown in FIG.
測定は下記の方法により行なった。Measurements were performed using the following method.
（１）被験者：健常な男性６人を本人の同意を得た後被
験者とした。(1) Subjects: Six healthy men were used as subjects after obtaining their consent.
（２）薬剤投与法；６人を３人宛２群に分け、α錠およ
びβ錠をクロスオーバー法にて２回投与した。(2) Drug administration method; 6 people were divided into 2 groups of 3 people, and α tablets and β tablets were administered twice in a crossover method.
すなわち、第一回目の実験では第一群にα錠、第二群に
β錠を投与し、２日間の間隔を置いて、今度は第二回目
の実験では第一群にβ錠を、第二群にはα錠を投与した
。That is, in the first experiment, α tablets were administered to the first group and β tablets to the second group, and after a two-day interval, in the second experiment, β tablets were administered to the first group, and β tablets were administered to the second group. The second group received α tablets.
従って被験者の６人は２日間々隔でα錠、β錠を各−回
投与された事になる。Therefore, the six subjects received one dose of the α tablet and one dose of the β tablet at two-day intervals.
各々の実験において実験日の朝食は摂取しなかった。Breakfast on the experimental day was not consumed in each experiment.
実験日当日は午前８時４５分より薬剤投与前（盲検値）
の採血を行い、実験は午前９時に開始し、各々の錠剤を
コツプ一杯の水と共に経口服用させた。On the day of the experiment, from 8:45 a.m. before drug administration (blinded value)
The experiment started at 9 am, and each tablet was taken orally with a glass of water.
投与量は一人当り２００ｍｇ（５０ｍｇ／１錠）である
。The dose is 200 mg (50 mg/tablet) per person.
採血は午前１０時、１１時、１２時に毎回約６ｍｌ宛採
血し、ヘパリンを加え遠心分離後２〜３ｍｌの血漿を得
た。Approximately 6 ml of blood was collected each time at 10:00 am, 11:00 am, and 12:00 am, and after adding heparin and centrifugation, 2 to 3 ml of plasma was obtained.
（３）血漿中濃度の測定法；蛍光定量法にて行った。(3) Measuring method of plasma concentration: Fluorometric assay was used.
実施例 １
α型２，４−ビス（２′−アセトキシベンズアミド）安
息香酸３７ｇをアセトニＩ−ＩＪル１１に加熱溶解し、
ろ過後ν液を冷却し析出物を戸数乾燥してβ型２，４−
ビス（２′−アセトキシベンズアミド）安息香酸３０ｇ
を得た。Example 1 37 g of α-type 2,4-bis(2'-acetoxybenzamido)benzoic acid was dissolved in acetonyl I-IJ 11 by heating.
After filtration, the ν liquid is cooled and the precipitate is dried several times to obtain β-type 2,4-
Bis(2'-acetoxybenzamide)benzoic acid 30g
I got it.
融点１７０〜５℃実施例 ２
実施例１で用いたアセトニトリルに代えてプロピオニト
リルを用いて同様に処理して同様の結果を得た。Melting point: 170-5°C Example 2 The same procedure was carried out using propionitrile in place of the acetonitrile used in Example 1, and similar results were obtained.
得られた結晶を実施例１で得たものと混融しても融点降
下を示さない。Even when the obtained crystals are mixed with those obtained in Example 1, the melting point does not decrease.
第１図および第２図はそれぞれα型およびβ型結晶の粉
末Ｘ線回折図であり、第３図および第４図はそれぞれα
型およびβ型結晶の赤外線吸収スペクトル図であり、第
５図はα型およびβ型結晶を投与したときの血中濃度の
変化を示す図である。Figures 1 and 2 are powder X-ray diffraction patterns of α-type and β-type crystals, respectively, and Figures 3 and 4 are α-type and β-type crystals, respectively.
FIG. 5 is a graph showing changes in blood concentration when α-type and β-type crystals are administered.
Claims (1)
香酸（α型）を一般式Ｒ−ＣＮ（式中Ｒは低級アルキル
基を示す）で表わされる溶媒を用いて再結晶せしめるこ
とを特徴とする２、４ビス（２′−アセトキシベンズア
ミド）安息香酸の異形結晶（β型）の製造法。It is characterized by recrystallizing 12,4-bis(2'-acetoxybenzamido)benzoic acid (α type) using a solvent represented by the general formula R-CN (wherein R represents a lower alkyl group). A method for producing modified crystals (β type) of 2,4bis(2'-acetoxybenzamido)benzoic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8533275A JPS5811856B2 (en) | 1975-07-14 | 1975-07-14 | 2 4-bis (2'-acetoxybenzamide) |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8533275A JPS5811856B2 (en) | 1975-07-14 | 1975-07-14 | 2 4-bis (2'-acetoxybenzamide) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5210231A JPS5210231A (en) | 1977-01-26 |
| JPS5811856B2 true JPS5811856B2 (en) | 1983-03-04 |
Family
ID=13855669
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8533275A Expired JPS5811856B2 (en) | 1975-07-14 | 1975-07-14 | 2 4-bis (2'-acetoxybenzamide) |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5811856B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03104947U (en) * | 1990-02-16 | 1991-10-30 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5634403B2 (en) * | 1972-01-17 | 1981-08-10 | ||
| EP1469827B1 (en) | 2002-01-09 | 2017-12-27 | Emisphere Technologies, Inc. | Polymorphs of sodium 4- (4-chloro-2-hydroxybenzoyl)amino butanoate |
-
1975
- 1975-07-14 JP JP8533275A patent/JPS5811856B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03104947U (en) * | 1990-02-16 | 1991-10-30 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5210231A (en) | 1977-01-26 |
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