Stable butylphthalide sodium chloride injection as well as preparation method and application thereof

A technology of butylphthalide sodium chloride and phthalide sodium chloride is applied in the field of pharmaceutical preparations, which can solve the problems that cannot completely reduce the incompatibility of patients with activated carbon, cannot meet the safety requirements of clinical medication, and the pH value is not well carried out. control and other issues, to achieve the effect of good water solubility, good stability and safety, and low nephrotoxicity

Pending Publication Date: 2021-02-23
CHENGDU SHIBEIKANG BIOLOGICAL MEDICINE TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, no systematic research has been conducted on the pH of sodium chloride injection, related substances, and the degree of substitution of sulfobutyl ether-β-cyclodextrin sodium, which cannot meet the safety requirements of clinical medication.
[0010] In summary, the butylphthalide preparation process disclosed in the prior art is relatively complicated, or it is inconvenient for clinical application, and the injection preparation process uses activated carbon, which cannot completely reduce the patient's incompatibility to activated carbon, and the quality is not completely stable. Hydroxypropyl-β-cyclodextrin increases the risk of nephrotoxicity, or the pH value is not well controlled during the preparation of the injection, and the pH, related substances, sodium sulfobutyl ether-β-cyclodextrin Systematic research on the degree of substitution, etc., cannot well meet the needs of clinical application of this product

Method used

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  • Stable butylphthalide sodium chloride injection as well as preparation method and application thereof
  • Stable butylphthalide sodium chloride injection as well as preparation method and application thereof
  • Stable butylphthalide sodium chloride injection as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048]This example discloses the preparation method of biphenylphthalide injection of the niosine chloride of the present invention. The preparation prescription (100 definitions) is:

[0049]

[0050]Preparation method: Return of water, purify water, cooled to 80 ° C after boiling. The sodium sulfur-bust-free cyclodextrin (substituted 6.2 to 6.9, the average substitution degree of 6.4, the molecular weight is 2145.2 g / mol) 80 g, 90 g of sodium chloride, and 8 l 80 ° C, purified water, stir the complete dissolution. 2.5 g of biphenyl phthalide was weighed, and a sulfur dilobea cyclodextride solution was added, and the oil bath was stirred at 80 ° C for 90 minutes to completely dissolve. After cooling to room temperature, add 0.2 M hydrochloric acid solution pH to 4.5, supplement purified water to 10L. The vacuum pump was filtered through a circulating hydraulic pump. The mixed solution is filled with 100 ml / branch. After filling, at 121 ° C, high temperature was sterilized for 15 minu...

Embodiment 2

[0052]This example discloses the amount of sodium sodium sulfur-dioximale cyclodextrin to the solubilization ability of biphenylphthalide, specifically:

[0053]The sodium busenphthalide injection in accordance with Example 1 was prepared, and the difference was only different from sodium sodium sulfurine cyclodextrin. Then, the traits of each butylphthalonate injection of each butyl phthal chloride and a biphenylphtarid content in the injection. The result is shown in Table 1:

[0054]Table 1, solubilizing capacity of sodium sodium sulfur dioxide cyclodextrin solution

[0055]

[0056]

[0057]It can be seen from the above table: sulfurilataltite cyclodextride: biphenitis ratio is greater than 2.8 (numbers 1 and 4), thickebium phthalide can be completely dissolved; when molar ratio is reduced to 1.5, the remaining A small amount of butyl phthalide is reduced by molar ratio to 0.44, the remaining large quantum butyl phthalide droplets, indicating that the quantum donut is 0.44 mol of butylphthalid...

Embodiment 3

[0064]This example investigates the effect of pH value on the stability of sodium biphenyl chloride injection.

[0065]According to the method of Example 1, the busephthalide injection is prepared, and the difference is only the pH value of the adjusted biphenylphthalide injection, the specific pH value of the sodium chloride injection of the prepared Table 3 shows. The impurity content in the injection of the filling and sterilization was investigated, and the results of the examination were shown in Table 3.

[0066]Table 3, different pH affects the stability of the embodiment

[0067]

[0068]It can be seen from Table 3, but the phenylphaxa-sodium chloride injection of the pH is 4.0 to 5.0 is sterilized at 121 ° C, 15 min, and there is no significant change in impurity content, and the maximum unknown single proposal is derived from the feedstock, indicating buthen phthal chloride. The sodium sodium injection is good in the pH 4.0 ~ 5.0.Figure 1-3 Indicated. .

[0069]AppendFigure 4-6As shown, ...

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Abstract

The invention discloses a stable butylphthalide sodium chloride injection as well as a preparation method and application thereof, belongs to the technical field of pharmaceutical preparations, and solves the problems of poor safety and stability of the butylphthalide sodium chloride injection in the prior art. The stable butylphthalide sodium chloride injection comprises a sulfobutyl betacyclodextrin sodium compound, sodium chloride and water. The pH value of the butylphthalide sodium chloride injection is 4.0-5.0. The preparation method comprises the following steps of weighing a prescription amount of sulfobutyl betacyclodextrin sodium, and adding water for dissolving to prepare an auxiliary material solution; weighing a prescription amount of butylphthalide, adding the butylphthalide into the auxiliary material solution, stirring to enable the sulfobutyl betacyclodextrin sodium to include the butylphthalide, and adjusting the pH value of the solution to 4.0-5.0 after the inclusionof the butylphthalide is completed; and filtering, filling and sterilizing to obtain the product. The stable butylphthalide sodium chloride injection as well as the preparation method and applicationthereof are scientific in design and ingenious in thought, and the butylphthalide sodium chloride injection has good stability and safety.

Description

Technical field[0001]The invention belongs to the technical field of pharmaceutical preparations, in particular to a pharmaceutical preparation for the treatment of stroke, and more particularly to a stable butylphthalide sodium chloride injection, its preparation method and application.Background technique[0002]Butylphthalide: (3-n-butylphthalide, referred to as NBP), its full name is 3-butyl-1(H)-isobenzofuranone, also known as apigenin, which is extracted from celery seeds. It can also be synthesized artificially. Butylphthalide is an oily liquid, insoluble in water, and has a strong celery taste. It contains a chiral carbon atom in its molecule, so it has two optical isomers, namely L-butylphthalide and D-butylphthalide. Butylphthalide can reduce the infarcts after focal cerebral ischemia, increase cerebral blood flow in the ischemic area and improve the microcirculation in the cerebral ischemic area, protect the function of mitochondria, reduce the degree of nerve damage, and i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/08A61K31/365A61K47/69A61K47/02A61P9/10
CPCA61K31/365A61K9/0019A61K9/08A61K47/02A61K47/6951A61P9/10
Inventor 牟霞姚秋鸣易泽琴苏永文张海徐霞曾燕群
Owner CHENGDU SHIBEIKANG BIOLOGICAL MEDICINE TECH CO LTD
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