JPS6327429A - Production of freeze-dried substance of meclofenoxate hydrochloride for injection - Google Patents
Production of freeze-dried substance of meclofenoxate hydrochloride for injectionInfo
- Publication number
- JPS6327429A JPS6327429A JP16881286A JP16881286A JPS6327429A JP S6327429 A JPS6327429 A JP S6327429A JP 16881286 A JP16881286 A JP 16881286A JP 16881286 A JP16881286 A JP 16881286A JP S6327429 A JPS6327429 A JP S6327429A
- Authority
- JP
- Japan
- Prior art keywords
- freeze
- meclofenoxate hydrochloride
- injection
- dried substance
- dried
- 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
- XZTYGFHCIAKPGJ-UHFFFAOYSA-N Meclofenoxate Chemical compound CN(C)CCOC(=O)COC1=CC=C(Cl)C=C1 XZTYGFHCIAKPGJ-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 229960001637 meclofenoxate hydrochloride Drugs 0.000 title claims abstract description 19
- 238000002347 injection Methods 0.000 title claims abstract description 11
- 239000007924 injection Substances 0.000 title claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- 239000000126 substance Substances 0.000 title abstract 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 18
- 239000007864 aqueous solution Substances 0.000 claims abstract description 11
- 239000011780 sodium chloride Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 abstract description 10
- 238000004108 freeze drying Methods 0.000 abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 239000012153 distilled water Substances 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 238000007710 freezing Methods 0.000 abstract description 3
- 230000008014 freezing Effects 0.000 abstract description 3
- 239000012528 membrane Substances 0.000 abstract description 3
- 238000004321 preservation Methods 0.000 abstract 1
- 235000012970 cakes Nutrition 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 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 2
- 239000004471 Glycine Substances 0.000 description 2
- 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 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000022540 Consciousness disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003920 antivertigo agent Substances 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000021463 dry cake Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000003227 neuromodulating effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は塩酸メクロフェノキサートの注射剤用凍結乾燥
物の製法、更に詳細には、乾燥物のケーキ容積が大きく
、シかも長期間保存してもケーキの収縮をきたさない当
該凍結乾燥物を製造する方法に関する。[Detailed Description of the Invention] [Field of Industrial Application] The present invention relates to a method for producing a freeze-dried product of meclofenoxate hydrochloride for injection, and more specifically, a method for producing a freeze-dried product of meclofenoxate hydrochloride for injection, and more specifically, a method for producing a freeze-dried product of meclofenoxate hydrochloride, which has a large cake volume and can be stored for a long period of time. The present invention relates to a method for producing the freeze-dried product that does not cause cake shrinkage even when the freeze-dried product is used.
ｔｌＡＭ）クロフェノキサートは、脳組織の代謝を促進
する作用を有し、その結果、神経調節効果によシ意識水
準への回復が得られ、意識障害の回復、あるいは抗めま
い剤として有用な薬物である。tlAM) Clofenoxate has the effect of promoting the metabolism of brain tissue, and as a result, recovery to a level of consciousness is achieved through neuromodulatory effects, making it a useful drug for recovering from consciousness disorders or as an anti-vertigo agent. It is.
しかし、塩酸メクロフエノキサートは水溶液中で不安定
であるため、これを注射剤とするには、非水溶液製剤と
するか、あるいは粉末小分は製剤又は凍結乾燥物製剤と
する必要がある。However, meclofenoxate hydrochloride is unstable in an aqueous solution, so in order to make it into an injection, it is necessary to formulate a non-aqueous solution, or form a small powder into a preparation or a lyophilizate preparation.
しかしながら、非水溶液製剤の場合には１用いる溶剤に
よる安全性が問題となると共に、静脈内投与ができない
という欠点がある。また、粉末小分は製剤の場合には、
その製造工程中の無菌保持が困難である。However, in the case of non-aqueous preparations, safety is a problem due to the solvent used, and there are disadvantages in that intravenous administration is not possible. In addition, in the case of powdered small portions and preparations,
It is difficult to maintain sterility during the manufacturing process.
斯かる理由から、凍結乾燥物製剤とするのが最も好まし
い方法であるが、この方法においても、塩酸メクロフエ
ノキサート水溶液を常法によって凍結乾燥すると、ケー
キが著しく収縮して極めて容積の小さい乾燥物しか得ら
れないと共に、この乾燥物は非結晶性であるため、力価
の低下や変色を起こし易く、品質的に問題があった。For these reasons, the most preferable method is to prepare a freeze-dried product, but even in this method, when an aqueous solution of meclofenoxate hydrochloride is freeze-dried by a conventional method, the cake shrinks significantly and the dry product has an extremely small volume. In addition, since this dried product is amorphous, it is prone to a decrease in titer and discoloration, resulting in quality problems.
斯かる問題を解決するため予備凍結によシ、まず急速な
冷却を行ない、その後加温して形成された核のみを残し
、その後再度冷却するという方法がとられている。しか
し、この方法も、充分な冷却能力を有する冷却機を必要
とすると共に、温度制御が難しく、更に、たとえ凍結乾
燥直後において容積の大きなものが得られたとしても、
長期間の保存中に収縮を起こす不良品が含まれるという
欠点があった０
そこで、本発明者は、凍結乾燥製剤の製法に一般に使用
されている賦形剤、例えばマンニトール、乳糖、グリシ
ン等を用いる方法について検討したが、この場合も、乾
燥物のケーキ容積が小さくて仕上り状態が悪く、品質的
に満足なものは得られなかった。In order to solve this problem, a method of pre-freezing is used in which rapid cooling is first performed, then only the core formed by heating is left behind, and then cooling is performed again. However, this method also requires a cooler with sufficient cooling capacity and is difficult to control the temperature.Furthermore, even if a large volume can be obtained immediately after freeze-drying,
There was a drawback that some defective products caused shrinkage during long-term storage.Therefore, the present inventor developed a method that uses excipients commonly used in the manufacturing process of lyophilized preparations, such as mannitol, lactose, and glycine. We investigated the method used, but in this case as well, the cake volume of the dried product was small and the finished product was poor, and we could not obtain a product that was satisfactory in terms of quality.
斯かる実状において、本発明者は上記欠点を克服せんと
鋭意研究を行なった結果、塩酸メクロフェノキサート水
溶液を凍結乾燥するに際し、当該水溶液に塩化ナトリウ
ムを含ませておけば、ケーキ容積が大きく、シかも保存
中収縮をきたすことのない凍結乾燥物が得られることを
見出し、本発明を完成した。Under such circumstances, the present inventor conducted intensive research to overcome the above-mentioned drawbacks and found that when freeze-drying an aqueous solution of meclofenoxate hydrochloride, if the aqueous solution contains sodium chloride, the cake volume can be increased. They discovered that it is possible to obtain a lyophilized product that does not shrink during storage, and completed the present invention.
すなわち、本発明は、塩化ナトリウムを含有せしめた塩
酸メクロフエノキサートの水溶液を凍結乾燥することを
特徴とする塩酸メクセフエノキサートの注射剤用凍結乾
燥物の製法を提供するものである。That is, the present invention provides a method for producing a lyophilized product of meclofenoxate hydrochloride for injection, which comprises lyophilizing an aqueous solution of meclofenoxate hydrochloride containing sodium chloride.
本発明を実施するには、塩酸メクロフェノキサートおよ
び塩化ナトリウムを水に溶解せしめ、得られた水溶液を
常法に従って凍結乾燥することにより行なわれる。The present invention is carried out by dissolving meclofenoxate hydrochloride and sodium chloride in water and freeze-drying the resulting aqueous solution according to a conventional method.
例えば、塩酸メクロフエノキサート１重量部に対し、０
．０５〜２００重量部の塩化ナトリウムを注射用蒸留水
に溶解せしめ、得られた水溶液をメンブランフィルタ−
を用いて無菌ろ過した後バイアル瓶に所定量分注し、凍
結乾燥装置にて凍結乾燥すればよい。For example, for 1 part by weight of meclofenoxate hydrochloride, 0
．． 05 to 200 parts by weight of sodium chloride is dissolved in distilled water for injection, and the resulting aqueous solution is passed through a membrane filter.
After sterile filtration using a sterile filter, a predetermined amount may be dispensed into a vial and freeze-dried using a freeze-drying device.
斯くして得られた本発明の塩酸メクロフエノキサートの
注射用凍結乾燥物は、乾燥物ケーキの容積が大きく、か
つ保存過程においてもケーキ収縮のない品質的に満足で
きるものである。しかも本発明方法は、凍結工程等に特
殊な温度制御等をする必要がないため再現性がよく、か
つ操作が簡便である。The thus obtained lyophilized meclofenoxate hydrochloride for injection of the present invention has a large dry cake volume and is satisfactory in quality with no cake shrinkage during storage. In addition, the method of the present invention has good reproducibility and is easy to operate since there is no need for special temperature control during the freezing process.
次に実施例を挙げて本発明を説明する。 Next, the present invention will be explained with reference to Examples.
実施例
塩酸メクロフェノキサー）２５０ｍｙと第１表に示す量
の塩化ナトリウムとを注射用蒸留水２．５１Ｅ／に溶解
する。これを０．２２μｍのメンブランフィルタ−を用
いてろ過し、１０ｄ無色バイアル瓶に充填し、凍結乾燥
した。得られ７’（凍結乾燥製剤の容積を測定し、その
結果を第１表に示した。なお、第１表には、無添加の場
合、およびマンニトール、乳糖またはグリシンを龜加し
て上記と同様に凍結乾燥した場合の結果も併せて示した
。Example Meclofenoxer hydrochloride (250 my) and sodium chloride in the amount shown in Table 1 are dissolved in 2.51 E/distilled water for injection. This was filtered using a 0.22 μm membrane filter, filled into a 10D colorless vial, and freeze-dried. The volume of the obtained 7' (freeze-dried preparation) was measured and the results are shown in Table 1.Table 1 shows the case without additives and the above with addition of mannitol, lactose or glycine. The results when similarly freeze-dried are also shown.
その結果、塩酸メクロフエノキサート凍結乾燥製剤は、
塩化す） ＩＪウムの添加によυ乾燥物ケーキの容積が
大きく増加し顕著に改善されたことがわかる。As a result, meclofenoxate hydrochloride lyophilized formulation
It can be seen that the volume of the dry matter cake increased greatly and was significantly improved by adding IJium (IJ chloride).
以下余白Margin below
Claims (1)
サートの水溶液を凍結乾燥することを特徴とする塩酸メ
クロフエノキサートの注射剤用凍結乾燥物の製法。 ２、塩化ナトリウムの量が塩酸メクロフエノキサート１
重量部に対し０．０５〜２００重量部である特許請求の
範囲第１項記載の製法。[Scope of Claims] 1. A method for producing a lyophilized product of meclofenoxate hydrochloride for injection, which comprises lyophilizing an aqueous solution of meclofenoxate hydrochloride containing sodium chloride. 2. The amount of sodium chloride is meclofenoxate hydrochloride 1
The manufacturing method according to claim 1, wherein the amount is 0.05 to 200 parts by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16881286A JPH0713015B2 (en) | 1986-07-17 | 1986-07-17 | Process for producing freeze-dried meclofenoxate hydrochloride for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP16881286A JPH0713015B2 (en) | 1986-07-17 | 1986-07-17 | Process for producing freeze-dried meclofenoxate hydrochloride for injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6327429A true JPS6327429A (en) | 1988-02-05 |
| JPH0713015B2 JPH0713015B2 (en) | 1995-02-15 |
Family
ID=15874949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16881286A Expired - Fee Related JPH0713015B2 (en) | 1986-07-17 | 1986-07-17 | Process for producing freeze-dried meclofenoxate hydrochloride for injection |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0713015B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6134337A (en) * | 1996-12-11 | 2000-10-17 | Bell Tech Co., Ltd. | Loudspeaker |
| CN105287409A (en) * | 2015-12-01 | 2016-02-03 | 青岛华之草医药科技有限公司 | Medicinal meclofenoxate hydrochloride composition freeze-dried powder injection for treating senile dementia |
| CN113133975A (en) * | 2021-04-22 | 2021-07-20 | 海南通用三洋药业有限公司 | Preparation method of meclofenoxate hydrochloride freeze-dried powder injection |
-
1986
- 1986-07-17 JP JP16881286A patent/JPH0713015B2/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6134337A (en) * | 1996-12-11 | 2000-10-17 | Bell Tech Co., Ltd. | Loudspeaker |
| CN105287409A (en) * | 2015-12-01 | 2016-02-03 | 青岛华之草医药科技有限公司 | Medicinal meclofenoxate hydrochloride composition freeze-dried powder injection for treating senile dementia |
| CN113133975A (en) * | 2021-04-22 | 2021-07-20 | 海南通用三洋药业有限公司 | Preparation method of meclofenoxate hydrochloride freeze-dried powder injection |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0713015B2 (en) | 1995-02-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |