JPH078800B2 - Aqueous suspension composition of macrolide antibiotics - Google Patents
Aqueous suspension composition of macrolide antibioticsInfo
- Publication number
- JPH078800B2 JPH078800B2 JP63159256A JP15925688A JPH078800B2 JP H078800 B2 JPH078800 B2 JP H078800B2 JP 63159256 A JP63159256 A JP 63159256A JP 15925688 A JP15925688 A JP 15925688A JP H078800 B2 JPH078800 B2 JP H078800B2
- Authority
- JP
- Japan
- Prior art keywords
- amorphous solid
- water suspension
- sucrose
- suspension composition
- composition
- 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 - Lifetime
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 (産業上の利用分野) 本発明は医薬品用組成物に係り、殊にマクロライド系抗
生物質の水懸濁組成物に係る。TECHNICAL FIELD The present invention relates to a pharmaceutical composition, and more particularly to an aqueous suspension composition of a macrolide antibiotic.
(従来の技術及び課題) マクロライド系抗生物質は中範囲の抗菌スペクトルを有
しており、経口投与により吸収され、毒性が低いために
有用な抗生物質として汎用され、殊に小児用に多く使用
されている。(Prior art and problems) Macrolide antibiotics have a mid-range antibacterial spectrum and are commonly used as useful antibiotics because they are absorbed orally and have low toxicity, and are often used especially for children. Has been done.
小児用として用いられる場合に、この種の抗生物質は通
例ドライシロップ剤又はシロップ剤として製剤化される
が、シロップ剤の方が嗜好性において優れている。マク
ロライド系抗生物質の非晶質固体粉末を用いて慣用の方
法によりシロップ剤として製剤化する場合に、即ち甘味
料としての白糖を含有する水溶液に非晶質固体原末を添
加し、分散させることにより水懸濁物になした場合に、
この懸濁物は調製当初においては流動性を有しているが
経時的にゲル状態に変化して流動性が失われる点に課題
を有していた。このゲル化は、保存温度が高い程早期に
生じる。When used for children, antibiotics of this kind are usually formulated as dry syrups or syrups, but syrups have a better palatability. When the amorphous solid powder of macrolide antibiotics is used for formulation as a syrup by a conventional method, that is, the amorphous solid bulk powder is added to and dispersed in an aqueous solution containing sucrose as a sweetener. If it becomes an aqueous suspension,
This suspension had fluidity at the initial stage of preparation, but had a problem in that it changed into a gel state with time and lost fluidity. This gelation occurs earlier at higher storage temperatures.
(課題を解決する手段及び作用) 本発明者等は、上記の課題を解決するために鋭意検討を
重ねた結果、意外にも、マクロライド系抗生物質の非晶
質固体原末に、水溶性セルロース系ポリマーと蔗糖とが
組み合わされて配合され、かつ蔗糖が、マクロライド系
抗生物質の非晶質固体原末2重量%に対して、20〜40重
量%の割合で配合されているマクロライド系抗生物質の
水懸濁組成物は長期間保存しても安定であり、ゲル化し
ないことを見い出して本発明を完成するに至った。(Means and Actions for Solving the Problems) The inventors of the present invention have, as a result of intensive studies to solve the above problems, surprisingly found that the amorphous solid bulk powder of the macrolide antibiotic is water-soluble. Macrolide in which cellulosic polymer and sucrose are combined and blended, and sucrose is blended in a proportion of 20 to 40% by weight with respect to 2% by weight of amorphous solid bulk powder of macrolide antibiotics. The present invention was completed by finding that an aqueous suspension composition of antibiotics is stable even after long-term storage and does not gel.
本発明による水懸濁組成物を調製する場合に用いられる
水溶性セルロース系ポリマーとしては、ハイドロオキシ
プロピルメチルセルロース、ハイドロオキシプロピルセ
ルロース等を例示することができる。本発明による水懸
濁組成物におけるマクロライド系抗生物質と、水溶性セ
ルロース系ポリマーと、蔗糖との量割合は選択された抗
生物質やポリマーの種類等に依存して異なるが、一般的
にはマクロライド系抗生物質の非晶質固体原末2重量%
に対して、水溶性セルロース系ポリマーが0.7-1.5重量
%、蔗糖が20-40重量%程度であるのが好ましい。Examples of the water-soluble cellulose-based polymer used when preparing the water suspension composition according to the present invention include hydroxypropylmethyl cellulose and hydroxypropyl cellulose. The amount ratio of the macrolide antibiotic, the water-soluble cellulose polymer, and the sucrose in the water suspension composition according to the present invention varies depending on the kind of the selected antibiotic or polymer, but generally, Amorphous solid bulk powder of macrolide antibiotics 2% by weight
On the other hand, it is preferable that the water-soluble cellulose-based polymer is 0.7-1.5% by weight and the sucrose is 20-40% by weight.
尚、本発明による水懸濁組成物を製剤化してシロップ剤
になす場合には芳香剤、着色剤、保存剤、安定剤、懸濁
化剤、粘稠化剤等の通例の添加物を配合することができ
る。When the water suspension composition according to the present invention is formulated into a syrup, a usual additive such as a fragrance, a coloring agent, a preservative, a stabilizer, a suspending agent and a thickening agent is added. can do.
(製造例等) 次に、製造例及び比較例により本発明を更に具体的に説
明する。(Manufacturing Example, etc.) Next, the present invention will be described more specifically with reference to Manufacturing Examples and Comparative Examples.
製造例1及び比較例1 10-アセチル‐3″‐アセチルミデカマイシン(商品
名:ミオカマイシン)10gを、エチルセルロース1g含有
ジオキサン溶液100mlに溶解させた。この溶液を‐40℃
で凍結させた後に、100mmHg以下の減圧下で溶媒を昇華
除去して10-アセチル‐3″‐アセチルミデカマイシン
の完全な非晶質固体を得た。Production Example 1 and Comparative Example 1 10 g of 10-acetyl-3 ″ -acetylmidecamycin (trade name: myokamycin) was dissolved in 100 ml of a dioxane solution containing 1 g of ethyl cellulose. The solution was -40 ° C.
After freezing at 10 ° C., the solvent was removed by sublimation under reduced pressure of 100 mmHg or less to obtain a completely amorphous solid of 10-acetyl-3 ″ -acetylmidecamycin.
この非晶質固体2gを採取し、ハイドロオキシプロピルメ
チルセルロース0.5g及び蔗糖30gを含有する水溶液100ml
中に添加し混合して充分に分散させることにより水懸濁
組成物を得た。2 g of this amorphous solid was collected, and 100 ml of an aqueous solution containing 0.5 g of hydroxypropylmethyl cellulose and 30 g of sucrose.
An aqueous suspension composition was obtained by adding the ingredients to the mixture and mixing them to sufficiently disperse them.
この水懸濁組成物を25℃及び40℃の温度条件下でそれぞ
れ1年間保存した後に調べた処、依然として安定な水懸
濁状態を維持していた。When this water suspension composition was stored under the temperature conditions of 25 ° C. and 40 ° C. for 1 year and then examined, it was found that a stable water suspension state was still maintained.
一方、ハイドロオキシプロピルメチルセルロース及び蔗
糖を含有しない単なる水に上記の非晶質固体を上記と同
様に分散させて水懸濁組成物(対照組成物)を調製し
た。この対照組成物を25℃の温度条件下に保存した処、
24時間後にはゲル状態を呈していた。On the other hand, the above amorphous solid was dispersed in mere water containing no hydroxypropylmethylcellulose and sucrose in the same manner as above to prepare a water suspension composition (control composition). When this control composition was stored under a temperature condition of 25 ° C,
After 24 hours, it was in a gel state.
製造例2及び比較例2 10-アセチル‐3″‐アセチルミデカマイシン10gをジオ
キサン溶液100mlに溶解させた。この溶液を‐40℃で凍
結させた後に、100mmHg以下の減圧下で溶媒を昇華除去
して10-アセチル‐3″‐アセチルミデカマイシンの完
全な非晶質固体を得た。Preparation Example 2 and Comparative Example 2 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of dioxane solution. This solution was frozen at −40 ° C., and then the solvent was removed by sublimation under reduced pressure of 100 mmHg or less. To give a completely amorphous solid of 10-acetyl-3 "-acetylmidecamycin.
この非晶質固体2gを採取し、ハイドロオキシプロピルメ
チルセルロース0.5g、蔗糖15g及びアクリル酸重合体0.0
5gを含有する水溶液100ml中に添加し混合して充分に分
散させることにより水懸濁組成物を得た。2 g of this amorphous solid was collected, and 0.5 g of hydroxypropyl methylcellulose, 15 g of sucrose and 0.05 of the acrylic acid polymer.
An aqueous suspension composition was obtained by adding to 100 ml of an aqueous solution containing 5 g, mixing and thoroughly dispersing.
この水懸濁組成物を25℃及び40℃の温度条件下でそれぞ
れ1年間保存した後に調べた処、依然として安定な水懸
濁状態を維持していた。When this water suspension composition was stored under the temperature conditions of 25 ° C. and 40 ° C. for 1 year and then examined, it was found that a stable water suspension state was still maintained.
一方、ハイドロオキシプロピルメチルセルロース、蔗糖
及びアクリル酸重合体を含有しない単なる水に上記の非
晶質固体を上記と同様に分散させて水懸濁組成物(対照
組成物)を調製した。この対照組成物を25℃の温度条件
下に保存した処、24時間後にはゲル状態を呈していた。On the other hand, an aqueous suspension composition (control composition) was prepared by dispersing the above amorphous solid in mere water containing no hydroxypropylmethylcellulose, sucrose and acrylic acid polymer in the same manner as above. When this control composition was stored under the temperature condition of 25 ° C., it exhibited a gel state after 24 hours.
製造例3及び比較例3 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジクロロメタン溶液100mlに溶解
させた。この溶液を常法により噴霧乾燥させて10-アセ
チル‐3″‐アセチルミデカマイシンの完全な非晶質固
体を得た。Preparation Example 3 and Comparative Example 3 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dichloromethane solution containing 1 g of ethyl cellulose. This solution was spray-dried by a conventional method to obtain 10-acetyl-3 ″ -acetyl. A completely amorphous solid of midecamycin was obtained.
この非晶質固体2gを採取し、ハイドロオキシプロピルメ
チルセルロース1.0g及び蔗糖40gを含有する水溶液100ml
中に添加し混合して充分に分散させることにより水懸濁
組成物を得た。2 g of this amorphous solid was collected and 100 ml of an aqueous solution containing 1.0 g of hydroxypropylmethyl cellulose and 40 g of sucrose.
An aqueous suspension composition was obtained by adding the ingredients to the mixture and mixing them to sufficiently disperse them.
この水懸濁組成物を25℃及び40℃の温度条件下でそれぞ
れ1年間保存した後に調べた処、依然として安定な水懸
濁状態を維持していた。When this water suspension composition was stored under the temperature conditions of 25 ° C. and 40 ° C. for 1 year and then examined, it was found that a stable water suspension state was still maintained.
一方、ハイドロオキシプロピルメチルセルロース及び蔗
糖を含有しない単なる水に上記の非晶質固体を上記と同
様に分散させて水懸濁組成物(対照組成物)を調製し
た。この対照組成物を25℃の温度条件下に保存した処、
24時間後にはゲル状態を呈していた。On the other hand, the above amorphous solid was dispersed in mere water containing no hydroxypropylmethylcellulose and sucrose in the same manner as above to prepare a water suspension composition (control composition). When this control composition was stored under a temperature condition of 25 ° C,
After 24 hours, it was in a gel state.
製造例4及び比較例4 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジクロロメタン溶液100mlに溶解
させた。この溶液を常法により噴霧乾燥させて10-アセ
チル‐3″‐アセチルミデカマイシンの完全な非晶質固
体を得た。Production Example 4 and Comparative Example 4 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dichloromethane solution containing 1 g of ethyl cellulose. This solution was spray-dried by a conventional method to obtain 10-acetyl-3 ″ -acetyl. A completely amorphous solid of midecamycin was obtained.
この非晶質固体2gを採取し、ハイドロオキシプロピルメ
チルセルロース1.0g及び蔗糖35gを含有する水溶液100ml
中に添加し混合して充分に分散させることにより水懸濁
組成物を得た。2 g of this amorphous solid was collected and 100 ml of an aqueous solution containing 1.0 g of hydroxypropylmethyl cellulose and 35 g of sucrose.
An aqueous suspension composition was obtained by adding the ingredients to the mixture and mixing them to sufficiently disperse them.
この水懸濁組成物を25℃及び40℃の温度条件下でそれぞ
れ1年間保存した後に調べた処、依然として安定な水懸
濁状態を維持していた。When this water suspension composition was stored under the temperature conditions of 25 ° C. and 40 ° C. for 1 year and then examined, it was found that a stable water suspension state was still maintained.
一方、ハイドロオキシプロピルメチルセルロース及び蔗
糖を含有しない単なる水に上記の非晶質固体を上記と同
様に分散させて水懸濁組成物(対照組成物)を調製し
た。この対照組成物を25℃の温度条件下に保存した処、
24時間後にはゲル状態を呈していた。On the other hand, the above amorphous solid was dispersed in mere water containing no hydroxypropylmethylcellulose and sucrose in the same manner as above to prepare a water suspension composition (control composition). When this control composition was stored under a temperature condition of 25 ° C,
After 24 hours, it was in a gel state.
製造例5及び比較例5 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジクロロメタン溶液100mlに溶解
させた。この溶液を常法により噴霧乾燥させて10-アセ
チル‐3″‐アセチルミデカマイシンの完全な非晶質固
体を得た。Preparation Example 5 and Comparative Example 5 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dichloromethane solution containing 1 g of ethyl cellulose. This solution was spray-dried by a conventional method to obtain 10-acetyl-3 ″ -acetyl. A completely amorphous solid of midecamycin was obtained.
この非晶質固体1gを採取し、ハイドロオキシプロピルメ
チルセルロース0.7g、蔗糖10g及びアラビアゴム0.5gを
含有する水溶液50ml中に添加し混合して充分に分散させ
ることにより水懸濁組成物を得た。1 g of this amorphous solid was collected and added to 50 ml of an aqueous solution containing 0.7 g of hydroxypropylmethylcellulose, 10 g of sucrose and 0.5 g of gum arabic, mixed and sufficiently dispersed to obtain a water suspension composition. .
この水懸濁組成物を25℃及び40℃の温度条件下でそれぞ
れ1年間保存した後に調べた処、依然として安定な水懸
濁状態を維持していた。When this water suspension composition was stored under the temperature conditions of 25 ° C. and 40 ° C. for 1 year and then examined, it was found that a stable water suspension state was still maintained.
一方、アラビアゴムを含有し、ハイドロオキシプロピル
メチルセルロース及び蔗糖を含有しない水溶液に上記の
非晶質固体を上記と同様に分散させて水懸濁組成物(対
照組成物)を調製した。この対照組成物を25℃の温度条
件下に保存した処、24時間後にはゲル状態を呈してい
た。On the other hand, the above amorphous solid was dispersed in an aqueous solution containing gum arabic but not containing hydroxypropylmethylcellulose and sucrose in the same manner as above to prepare a water suspension composition (control composition). When this control composition was stored under the temperature condition of 25 ° C., it exhibited a gel state after 24 hours.
製造例6及び比較例6 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジクロロメタン溶液100mlに溶解
させた。この溶液を常法により噴霧乾燥させて10-アセ
チル‐3″‐アセチルミデカマイシンの完全な非晶質固
体を得た。Production Example 6 and Comparative Example 6 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dichloromethane solution containing 1 g of ethyl cellulose. This solution was spray-dried by a conventional method to obtain 10-acetyl-3 ″ -acetyl. A completely amorphous solid of midecamycin was obtained.
この非晶質固体1gを採取し、ハイドロオキシプロピルメ
チルセルロース1.5g、蔗糖30g及び安息香酸0.5gを含有
する水溶液50ml中に添加し混合して充分に分散させるこ
とにより水懸濁組成物を得た。1 g of this amorphous solid was collected and added to 50 ml of an aqueous solution containing 1.5 g of hydroxypropylmethylcellulose, 30 g of sucrose and 0.5 g of benzoic acid, mixed and sufficiently dispersed to obtain a water suspension composition. .
この水懸濁組成物を25℃及び40℃の温度条件下でそれぞ
れ1年間保存した後に調べた処、依然として安定な水懸
濁状態を維持していた。When this water suspension composition was stored under the temperature conditions of 25 ° C. and 40 ° C. for 1 year and then examined, it was found that a stable water suspension state was still maintained.
一方、安息香酸を含有し、ハイドロオキシプロピルメチ
ルセルロース及び蔗糖を含有しない水溶液に上記の非晶
質固体を上記と同様に分散させて水懸濁組成物(対照組
成物)を調製した。この対照組成物を25℃の温度条件下
に保存した処、24時間後にはゲル状態を呈していた。On the other hand, the above amorphous solid was dispersed in an aqueous solution containing benzoic acid and not containing hydroxypropylmethylcellulose and sucrose in the same manner as above to prepare a water suspension composition (control composition). When this control composition was stored under the temperature condition of 25 ° C., it exhibited a gel state after 24 hours.
製造例7及び比較例7 10-アセチル‐3″‐アセチルミデカマイシン10gをジク
ロロメタン溶液100mlに溶解させた。この溶液を常法に
より噴霧乾燥させて10-アセチル‐3″‐アセチルミデ
カマイシンの完全な非晶質固体を得た。Preparation Example 7 and Comparative Example 7 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dichloromethane solution. This solution was spray-dried by a conventional method to obtain 10-acetyl-3 ″ -acetylmidecamycin. A completely amorphous solid was obtained.
この非晶質固体2gを採取し、ハイドロオキシプロピルメ
チルセルロース1.0g、蔗糖30g及びアクリル酸重合体0.0
5gを含有する水溶液100ml中に添加し混合して充分に分
散させることにより水懸濁組成物を得た。2 g of this amorphous solid was collected, and 1.0 g of hydroxypropylmethyl cellulose, 30 g of sucrose and 0.0
An aqueous suspension composition was obtained by adding to 100 ml of an aqueous solution containing 5 g, mixing and thoroughly dispersing.
この水懸濁組成物を25℃及び40℃の温度条件下でそれぞ
れ1年間保存した後に調べた処、依然として安定な水懸
濁状態を維持していた。When this water suspension composition was stored under the temperature conditions of 25 ° C. and 40 ° C. for 1 year and then examined, it was found that a stable water suspension state was still maintained.
一方、ハイドロオキシプロピルメチルセルロース、蔗糖
及びアクリル酸重合体を含有しない単なる水に上記の非
晶質固体を上記と同様に分散させて水懸濁組成物(対照
組成物)を調製した。この対照組成物を25℃の温度条件
下に保存した処、24時間後にはゲル状態を呈していた。On the other hand, an aqueous suspension composition (control composition) was prepared by dispersing the above amorphous solid in mere water containing no hydroxypropylmethylcellulose, sucrose and acrylic acid polymer in the same manner as above. When this control composition was stored under the temperature condition of 25 ° C., it exhibited a gel state after 24 hours.
製造例8及び比較例8 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジオキサン溶液100mlに溶解させ
た。この溶液を‐40℃で凍結させた後に、100mmHg以下
の減圧下で溶媒を昇華除去して、10-アセチル‐3″‐
アセチルミデカマイシンの完全な非晶質固体を得た。Preparation Example 8 and Comparative Example 8 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dioxane solution containing 1 g of ethyl cellulose. The solution was frozen at −40 ° C. and then under reduced pressure of 100 mmHg or less. After removing the solvent by sublimation, 10-acetyl-3 ″-
A completely amorphous solid of acetylmidecamycin was obtained.
この非晶質固体2gを採取し、ハイドロオキシプロピルメ
チルセルロース0.5g及び蔗糖25gを含有する水溶液100ml
中に添加し混合して充分に分散させることにより水懸濁
組成物を得た。2 g of this amorphous solid was collected, and 100 ml of an aqueous solution containing 0.5 g of hydroxypropylmethyl cellulose and 25 g of sucrose.
An aqueous suspension composition was obtained by adding the ingredients to the mixture and mixing them to sufficiently disperse them.
一方、ハイドロオキシプロピルメチルセルロースを含有
し、蔗糖を含有しない水溶液に上記の非晶質固体を上記
と同様に分散させて水懸濁組成物(対照組成物)を調製
した。On the other hand, an aqueous suspension composition (control composition) was prepared by dispersing the above amorphous solid in an aqueous solution containing hydroxypropylmethylcellulose and not containing sucrose in the same manner as above.
これらの水懸濁組成物を50℃の温度条件下でそれぞれ保
存し経時的に調べた処、対照組成物は3日間でゲル状態
に呈したのに対して本発明による水懸濁組成物は2週間
経過後にも安定な水懸濁状態を維持していた。When these water suspension compositions were each stored under a temperature condition of 50 ° C. and examined over time, the control composition exhibited a gel state in 3 days, whereas the water suspension composition according to the present invention A stable water suspension state was maintained even after 2 weeks had passed.
製造例9及び比較例9 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジオキサン溶液100mlに溶解させ
た。この溶液を‐40℃で凍結させた後に、100mmHg以下
の減圧下で溶媒を昇華除去して10-アセチル‐3″‐ア
セチルミデカマイシンの完全な非晶質固体を得た。Preparation Example 9 and Comparative Example 9 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dioxane solution containing 1 g of ethyl cellulose. The solution was frozen at −40 ° C. and then under reduced pressure of 100 mmHg or less. The solvent was removed by sublimation to obtain a completely amorphous solid of 10-acetyl-3 "-acetylmidecamycin.
この非晶質固体2gを採取し、ハイドロオキシプロピルセ
ルロース0.5g及び蔗糖35gを含有する水溶液100ml中に添
加し混合して充分に分散させることにより水懸濁組成物
を得た。2 g of this amorphous solid was collected, added to 100 ml of an aqueous solution containing 0.5 g of hydroxypropylcellulose and 35 g of sucrose, mixed and sufficiently dispersed to obtain a water suspension composition.
一方、ハイドロオキシプロピルセルロースを含有し、蔗
糖を含有しない水溶液に上記の非晶質固体を上記と同様
に分散させて水懸濁組成物(対照組成物)を調製した。On the other hand, the above amorphous solid was dispersed in an aqueous solution containing hydroxypropyl cellulose but not sucrose in the same manner as above to prepare a water suspension composition (control composition).
これらの水懸濁組成物を50℃の温度条件下でそれぞれ保
存し経時的に調べた処、対照組成物は3日間でゲル状態
を呈したのに対して本発明による水懸濁組成物は2週間
経過後にも安定な水懸濁状態を維持していた。When these water suspension compositions were respectively stored under a temperature condition of 50 ° C. and examined over time, the control composition exhibited a gel state in 3 days, whereas the water suspension composition of the present invention showed a gel state. A stable water suspension state was maintained even after 2 weeks had passed.
製造例10及び比較例10 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジオキサン溶液100mlに溶解させ
た。この溶液を‐40℃で凍結させた後に、100mmHg以下
の減圧下で溶媒を昇華除去して10-アセチル‐3″‐ア
セチルミデカマイシンの完全な非晶質固体を得た。Preparation Example 10 and Comparative Example 10 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dioxane solution containing 1 g of ethyl cellulose. The solution was frozen at −40 ° C. and then under reduced pressure of 100 mmHg or less. The solvent was removed by sublimation to obtain a completely amorphous solid of 10-acetyl-3 "-acetylmidecamycin.
この非晶質固体2gを採取し、ハイドロオキシプロピルセ
ルロース1.5g及び蔗糖40gを含有する水溶液100ml中に添
加し混合して充分に分散させることにより水懸濁組成物
を得た。2 g of this amorphous solid was collected, added to 100 ml of an aqueous solution containing 1.5 g of hydroxypropyl cellulose and 40 g of sucrose, mixed and sufficiently dispersed to obtain a water suspension composition.
一方、蔗糖を含有し、ハイドロオキシプロピルセルロー
スを含有しない水溶液に上記の非晶質固体を上記と同様
に分散させて水懸濁組成物(対照組成物)を調製した。On the other hand, the above amorphous solid was dispersed in an aqueous solution containing sucrose but not hydroxypropylcellulose in the same manner as above to prepare a water suspension composition (control composition).
これらの水懸濁組成物を50℃の温度条件下でそれぞれ保
存し経時的に調べた処、対照組成物は24時間でゲル状態
を呈したのに対して本発明による水懸濁組成物は2週間
経過後にも安定な水懸濁状態を維持していた。When these water suspension compositions were respectively stored under a temperature condition of 50 ° C. and examined over time, the control composition exhibited a gel state in 24 hours, whereas the water suspension composition according to the present invention A stable water suspension state was maintained even after 2 weeks had passed.
製造例11及び比較例11 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジオキサン溶液100mlに溶解させ
た。この溶液を‐40℃で凍結させた後に、100mmHg以下
の減圧下で溶媒を昇華除去して10-アセチル‐3″‐ア
セチルミデカマイシンの完全な非晶質固体を得た。Production Example 11 and Comparative Example 11 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dioxane solution containing 1 g of ethyl cellulose. The solution was frozen at −40 ° C. and then under reduced pressure of 100 mmHg or less. The solvent was removed by sublimation to obtain a completely amorphous solid of 10-acetyl-3 "-acetylmidecamycin.
この非晶質固体2gを採取し、ハイドロオキシプロピルメ
チルセルロース1.0g及び蔗糖20gを含有する水溶液100ml
中に添加し混合して充分に分散させることにより水懸濁
組成物を得た。2 g of this amorphous solid was collected and 100 ml of an aqueous solution containing 1.0 g of hydroxypropylmethyl cellulose and 20 g of sucrose.
An aqueous suspension composition was obtained by adding the ingredients to the mixture and mixing them to sufficiently disperse them.
一方、蔗糖を含有し、ハイドロオキシプロピルメチルセ
ルロースを含有しない水溶液に上記の非晶質固体を上記
と同様に分散させて水懸濁組成物(対照組成物)を調製
した。On the other hand, the above amorphous solid was dispersed in an aqueous solution containing sucrose and not containing hydroxypropylmethylcellulose in the same manner as above to prepare a water suspension composition (control composition).
これらの水懸濁組成物を50℃の温度条件下でそれぞれ保
存し経時的に調べた処、対照組成物は24時間でゲル状態
を呈したのに対して本発明による水懸濁組成物は2週間
経過後にも安定な水懸濁状態を維持していた。When these water suspension compositions were respectively stored under a temperature condition of 50 ° C. and examined over time, the control composition exhibited a gel state in 24 hours, whereas the water suspension composition according to the present invention A stable water suspension state was maintained even after 2 weeks had passed.
製造例12及び比較例12 10-アセチル‐3″‐アセチルミデカマイシン10gを、エ
チルセルロース1g含有ジオキサン溶液100mlに溶解させ
た。この溶液を‐40℃で凍結させた後に、100mmHg以下
の減圧下で溶媒を昇華除去して10-アセチル‐3″‐ア
セチルミデカマイシンの完全な非晶質固体を得た。Preparation Example 12 and Comparative Example 12 10 g of 10-acetyl-3 ″ -acetylmidecamycin was dissolved in 100 ml of a dioxane solution containing 1 g of ethyl cellulose. The solution was frozen at −40 ° C. and then under reduced pressure of 100 mmHg or less. The solvent was removed by sublimation to obtain a completely amorphous solid of 10-acetyl-3 "-acetylmidecamycin.
この非晶質固体2gを採取し、ハイドロオキシプロピルセ
ルロース0.5g、蔗糖20g、カルボキシメチルセルロース
ナトリウム0.5g、安息香酸ナトリウム0.5g、クエン酸緩
衝液30g及び食用黄色5号0.01gを含有する水溶液100ml
中に添加し混合して充分に分散させることにより水懸濁
組成物を得た。2 g of this amorphous solid was collected and 100 ml of an aqueous solution containing 0.5 g of hydroxypropyl cellulose, 20 g of sucrose, 0.5 g of sodium carboxymethyl cellulose, 0.5 g of sodium benzoate, 30 g of citrate buffer and 0.01 g of edible yellow No. 5
An aqueous suspension composition was obtained by adding the ingredients to the mixture and mixing them to sufficiently disperse them.
一方、ハイドロオキシプロピルセルロースを含有せず、
他の上記諸成分を含有する水溶液に上記の非晶質固体を
上記と同様に分散させて水懸濁組成物(対照組成物)を
調製した。On the other hand, containing no hydroxypropyl cellulose,
The above amorphous solid was dispersed in an aqueous solution containing the above other components in the same manner as above to prepare a water suspension composition (control composition).
これらの水懸濁組成物を50℃の温度条件下でそれぞれ保
存し経時的に調べた処、対照組成物は24時間でゲル状態
を呈したのに対して本発明による水懸濁組成物は2週間
経過後にも安定な水懸濁状態を維持していた。When these water suspension compositions were respectively stored under a temperature condition of 50 ° C. and examined over time, the control composition exhibited a gel state in 24 hours, whereas the water suspension composition according to the present invention A stable water suspension state was maintained even after 2 weeks had passed.
製造例13及び比較例13 ミデカマイシン(商品名:メデマイシン)5gをジクロロ
メタン溶液100mlに溶解させた。この溶液を常法により
噴霧乾燥させてミデカマイシンの完全な非晶質固体を得
た。Production Example 13 and Comparative Example 13 5 g of midecamycin (trade name: medemycin) was dissolved in 100 ml of a dichloromethane solution. This solution was spray dried by a conventional method to obtain a completely amorphous solid of midecamycin.
この非晶質固体1gを採取し、ハイドロオキシプロピルメ
チルセルロース1.0g及び蔗糖30gを含有する水溶液100ml
中に添加し混合して充分に分散させることにより水懸濁
組成物を得た。1 g of this amorphous solid was collected and 100 ml of an aqueous solution containing 1.0 g of hydroxypropylmethylcellulose and 30 g of sucrose.
An aqueous suspension composition was obtained by adding the ingredients to the mixture and mixing them to sufficiently disperse them.
一方、ハイドロオキシプロピルメチルセルロース及び蔗
糖を含有しない単なる水に上記の非晶質固体を上記と同
様に分散させて水懸濁組成物(対照組成物)を調製し
た。On the other hand, the above amorphous solid was dispersed in mere water containing no hydroxypropylmethylcellulose and sucrose in the same manner as above to prepare a water suspension composition (control composition).
これらの水懸濁組成物を40℃の温度条件下でそれぞれ保
存し経時的に調べた処、対照組成物は1週間でゲル状態
を呈したのに対して本発明による水懸濁組成物は1年間
保存後にも安定な水懸濁状態を維持していた。When these water suspension compositions were respectively stored under a temperature condition of 40 ° C. and examined over time, the control composition exhibited a gel state in one week, whereas the water suspension composition according to the present invention showed a gel state. The stable water suspension state was maintained even after storage for 1 year.
(発明の効果) マクロライド系抗生物質をシロップ剤として製剤化する
場合に、常法に従い、その非晶質固体原末を蔗糖含有水
溶液に分散させて得られる水懸濁組成物は経時的にゲル
化して流動性を失うが、本発明方法により水溶性セルロ
ース系ポリマーを共存させることによりゲル化を阻止乃
至著しく遅延させることができる。(Effect of the Invention) When a macrolide antibiotic is formulated as a syrup, an aqueous suspension composition obtained by dispersing the amorphous solid bulk powder in a sucrose-containing aqueous solution is prepared according to a conventional method. Although it loses fluidity by gelling, gelling can be prevented or significantly delayed by coexisting a water-soluble cellulose-based polymer by the method of the present invention.
従って、本発明は安定なマクロライド系抗生物質含有シ
ロップ剤の製造を可能にするものであり、その保存管理
を容易ならしめる。Therefore, the present invention enables the production of a stable macrolide antibiotic-containing syrup, and facilitates its storage management.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 村田 信二郎 神奈川県川崎市幸区堀川町580番地 明治 製菓株式会社薬品開発研究所内 (56)参考文献 特開 昭56−5412(JP,A) 特開 昭53−145906(JP,A) ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Shinjiro Murata 580, Horikawa-cho, Sachi-ku, Kawasaki-shi, Kanagawa Meiji Confectionery Co., Ltd., Pharmaceutical Development Laboratory (56) Reference JP-A-56-542 (JP, A) JP Sho 53-145906 (JP, A)
Claims (1)
に、水溶性セルロース系ポリマーと蔗糖とが組み合わさ
れて配合され、かつ蔗糖が、マクロライド系抗生物質の
非晶質固体原末2重量%に対して、20〜40重量%の割合
で配合されているマクロライド系抗生物質の水懸濁組成
物。1. A non-crystalline solid bulk powder of a macrolide antibiotic, wherein a water-soluble cellulose polymer and sucrose are combined and blended, and the sucrose is an amorphous solid bulk powder of the macrolide antibiotic. A water suspension composition of a macrolide antibiotic compounded in a proportion of 20 to 40% by weight with respect to 2% by weight.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP63159256A JPH078800B2 (en) | 1988-06-29 | 1988-06-29 | Aqueous suspension composition of macrolide antibiotics |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP63159256A JPH078800B2 (en) | 1988-06-29 | 1988-06-29 | Aqueous suspension composition of macrolide antibiotics |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH029821A JPH029821A (en) | 1990-01-12 |
JPH078800B2 true JPH078800B2 (en) | 1995-02-01 |
Family
ID=15689782
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP63159256A Expired - Lifetime JPH078800B2 (en) | 1988-06-29 | 1988-06-29 | Aqueous suspension composition of macrolide antibiotics |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH078800B2 (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4211021C2 (en) * | 1992-04-02 | 1996-02-29 | Kaltenbach & Voigt | Dental articulator |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS53145906A (en) * | 1977-05-25 | 1978-12-19 | Yamanouchi Pharmaceut Co Ltd | Stable aqueous dispersion of 10-propionyl gosamycin |
JPS565412A (en) * | 1979-05-19 | 1981-01-20 | Meiji Seika Kaisha Ltd | Pharmaceutical composition |
-
1988
- 1988-06-29 JP JP63159256A patent/JPH078800B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
JPH029821A (en) | 1990-01-12 |
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