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Butylphthalide composition and application thereof

A technology of butylphthalide and composition, which is applied in the field of pharmaceutical composition, can solve problems such as easy precipitation, long-term stability of tablets or difficulty in content uniformity control, slow dispersion and dissolution rate, etc., to prevent rapid precipitation, Effect of improving dissolution stability

Pending Publication Date: 2022-07-01
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the solid tablet made with Gelucire 44 / 14 as matrix has a slow sublingual dispersion and dissolution rate, and the butylphthalide solubilized with Gelucire 44 / 14 is not stable in artificial saliva and is easy to precipitate, affecting Sublingual Absorption and Bioavailability
Moreover, after butylphthalide and lauric acid macrogol glyceride are mixed, the effect of adsorption and solidification by lactose and silica gel is not good (there is still the phenomenon of separating out butylphthalide), and the requirements for the tableting process are relatively high, and the actual preparation Or the production is more difficult; in addition, it is more difficult to control the long-term stability or content uniformity of the prepared tablets
Finally, the butylphthalide raw material itself has a strong pungent smell and acrid taste, coupled with the application of a large amount of macrogol glyceride laurate with a greasy feeling in the mouth, the actual clinical application compliance is poor, and flavor correction is required
[0011] Therefore, there are many defects in the disclosed sublingual mucosal delivery technology of butylphthalide, and it is still necessary to improve the existing oral mucosal delivery technology of butylphthalide, so as to improve the bioavailability of butylphthalide delivered through the oral mucosa and improve the quality of life of patients. medication compliance

Method used

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  • Butylphthalide composition and application thereof
  • Butylphthalide composition and application thereof
  • Butylphthalide composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0070] According to an embodiment of the present disclosure, there is provided a preparation method of a butylphthalide composition, characterized in that it comprises the following steps:

[0071] Stir and dissolve the dissolved butylphthalide and the dissolution stabilizer with a diluent solvent, further add a flavoring agent, an antioxidant and a preservative, and continue to stir, mix and dissolve to obtain a liquid form of the butylphthalide composition.

[0072] The butylphthalide composition in liquid form can be packed into a device for quantitatively delivering a drug or a soft capsule for use.

[0073] According to an embodiment of the present disclosure, there is provided a preparation method of another butylphthalide composition, which is characterized in that comprising the following steps:

[0074] a) Add the butylphthalide, surfactant, flavoring agent, film-forming material, plasticizer and adhesive in the recipe quantity, add an appropriate and appropriate amou...

Embodiment 1

[0079] Example 1: Butylphthalide Composition Containing Long Chain Solubility Stabilizer Kolliphor EL

[0080] Table 1

[0081]

[0082] Weigh the prescribed amount of propylene glycol, Kolliphor EL, flavoring agent and butylphthalide, etc., stir, mix and dissolve to obtain a clear and transparent solution.

[0083] Take 20 mg of the equivalent preparation, put it in a 2 ml transparent glass bottle, add 0.5 ml of artificial saliva, vortex and mix for 1 min at 300 rpm, and then stand to observe the precipitation of the drug.

[0084] Preparation method of artificial saliva: lactic acid 3.0g, urea 0.2g, sodium chloride 4.5g, potassium chloride 0.3g, sodium sulfate 0.3g, ammonium chloride 0.4g, ultrapure water to 1000ml, 1mol / L hydroxide Sodium adjusts pH to 6.8.

[0085] The components, contents, and the precipitation of the drugs in the formulations 1 and 2 are listed in Table 1 above.

experiment Embodiment 1

[0093] With the prescription 1, prescription 2 in the embodiment 1 prepared above, and the comparative prescription 1-contrast prescription 3 in the comparative example 1, carry out the sublingual administration (20mg / dog) of the dog, investigate the dissolving stabilizer of different prescription quantities The absorption of Kolliphor EL's butylphthalide composition, see results figure 1 and Table 3 below.

[0094] The pharmacokinetic parameters of the butylphthalide composition of the dissolution stabilizer Kolliphor EL in table 3

[0095]

[0096]

[0097] Note: Oral 100mg for reference: commercially available NBP soft capsules (100mg / capsule) (the same below).

[0098] Sublingual absorption in dogs is investigated as follows:

[0099] Beagle dogs weighing about 10 kg were randomly divided into groups, fasted for 12 h before administration, and had free access to water.

[0100] The reference oral preparation was taken orally at a dose of 100 mg / dog. Before admini...

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Abstract

The invention provides a butylphthalide composition delivered through oral mucosa. The composition comprises the following components in parts by weight: 100 parts of butylphthalide, 50-1000 parts of a dissolution stabilizer and 0.1-200 parts of a flavoring agent, wherein the dissolution stabilizer is a fatty alcohol or fatty acid-based surfactant capable of remarkably improving the dissolution stability of butylphthalide in saliva. The butylphthalide composition disclosed by the invention can be delivered through oral buccal mucosa and sublingual mucosa, and the absorption and bioavailability of butylphthalide are remarkably improved.

Description

technical field [0001] The present disclosure relates to a pharmaceutical composition and use thereof, in particular, the present disclosure relates to a butylphthalide composition delivered through oral mucosa and use thereof. Background technique [0002] Butylphthalide (3-n-butylphthalide, also known as apigenin A), and its two enantiomers (D-butylphthalide and L-butylphthalide), are light yellow and clear oily liquids with strong volatility , There is a special pungent odor in the mouth, and a spicy feeling, the boiling point is about 290 ℃. [0003] At present, the listed butylphthalide products, including NBP soft capsule (oral) and NBP injection (intravenous infusion) developed by CSPC, are used to treat mild and moderate acute ischemia respectively. stroke and improve neurological deficits in patients with acute ischemic stroke. The latest research shows that butylphthalide has a therapeutic effect on mild cognitive impairment and amyotrophic lateral sclerosis, and...

Claims

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Application Information

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IPC IPC(8): A61K9/70A61K9/12A61K9/48A61K9/20A61K31/365A61K47/14A61K47/26A61K47/32A61K47/36A61K47/38A61K47/44A61P9/04A61P9/10A61P25/28A61P21/00
CPCA61K9/006A61K9/48A61K9/20A61K31/365A61K47/14A61K47/44A61K47/38A61K47/32A61K47/36A61K47/26A61P9/10A61P25/28A61P9/04
Inventor 甘勇朱全垒郭仕艳
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI