Senalbuphine depot preparation

A technology of nalbuphine and storage, which is applied in the field of medicine, can solve the problems of increasing drug loading and reducing the viscosity of injection compositions, and achieve the effects of high drug loading, reducing the occurrence of allergic reactions, and low surfactant components

Pending Publication Date: 2021-12-17
SUZHOU NHWA PHARM RES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the composition can only introduce a maximum of 20 wt% active agent
In addition, in order to increase the drug loading and reduce the viscosity of the injection composition, the surfactant content is relatively high, and there is a certain risk of hemolysis for long-acting sustained-release injection preparations
[0010] To sum up, the current long-acting injection of nalbuphine sebacate cannot meet the clinical needs, and there is still an urgent need for improvement in terms of increasing drug loading, reducing injection pain, and avoiding hemolysis and allergic reactions.

Method used

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  • Senalbuphine depot preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0096] Embodiment 1 solubility test

[0097] In the present invention, the present invention has been found through research (referring to the solubility determination method of the fourth part of the Chinese Pharmacopoeia 2015 edition ), the active ingredient nalbuphine sebacate and its metabolite Nabu in the described reservoir precursor composition There is a large difference in morphine, and the solubility of nalbuphine sebacate and nalbuphine in different buffers is different, and the specific solubility differences are shown in Table 1 below.

[0098] Table 1 Solubility difference between senalbuphine and nalbuphine

[0099]

[0100] result

[0101] It can be seen from the above table 1 that the solubility of nalbuphine and senalbuphine in the simulated human buffer solution is quite different, and the solubility of the active ingredient is of great significance in the research of formulation prescriptions. There is little reference to Senerbuphine.

Embodiment 2

[0102] The influence of embodiment 2 solvent on the stability of senalbuphine

[0103] Weigh an appropriate amount of senalbuphine, configure it with pH 3.8 acetate buffer solution to about 3 μg / mL, add 2% (v / v) ethanol or NMP, and perform HPLC detection at 0 min, 10 min, 30 min, and 60 min respectively. The method is the same as described below.

[0104] Liquid chromatography detection (Agilent 1260), chromatographic column ZORBAX SB-Aq, 4.6×150, 5 μm. Chromatographic conditions: Phase A (weigh 3.85g ammonium acetate and add it to 1000mL ultrapure water, ultrasonically dissolve, add 3mL acetic acid, pass through a 0.45μm filter membrane, and wait for use after ultrasonication for 15min)-phase B (acetonitrile) = 40%: 60 %; column oven: 40°C; injector: 25°C; flow rate: 1.5mL / min; wavelength: 278nm. The injection volume was 10 μL. According to the external standard method, the peak area of ​​different sampling time points relative to the peak area percentage of 0 min was used ...

Embodiment 3

[0111] Example 3 Preparation method of senalbuphine depot precursor composition

[0112] method 1

[0113] Senebupine, soybean lecithin, glyceryl dioleate and Tween 20 were dissolved in the solvent NMP to prepare the senabupine reservoir precursor composition, and the liquid prepared by this method was in the form of suspension.

[0114] Method 2

[0115] (1) Weigh the soybean lecithin and diolein in the proportion of the prescription, and mix them, take about half of the NMP of the prescription, and dissolve the mixture of soybean lecithin and diolein in NMP;

[0116] (2) Senerbuphine and Tween 20 of the prescription ratio are weighed, mixed with the NMP of the remaining prescription quantity, and dissolved;

[0117] (3) Mix the obtained liquids of (1) and (2) before use to obtain a senbuphine depot precursor composition, and the liquid is in the state of a clear and transparent solution. Mix (1) and (2) before use to prepare the senbuphine reservoir precursor composition,...

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Abstract

The invention relates to a senalbuphine depot preparation, belongs to the field of medical treatment, and particularly relates to a low-viscosity nalbuphine sebacate depot precursor composition which comprises acylglycerol, phosphatidylcholine, at least one oxygen-containing organic solvent, at least one nonionic stable amphiphilic substance and nalbuphine sebacate, the obtained low-viscosity depot precursor composition has higher drug loading capacity and smaller injection volume, and can reduce pain and stimulation of an injection site.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a storage preparation of senbuphine, a preparation method thereof and an application in the pharmaceutical industry. [0002] technical background [0003] Nalbuphine sebacate (dinalbuphine sebacate, DNS) is also called senalbuphine, which is a dimer of nalbuphine. Its chemical structure is as follows. Nalbuphine), a prodrug of nalbuphine, is mainly used for the treatment of moderate to severe postoperative pain. Because nalbuphine must be injected every 4 to 6 hours, DNS, as a prodrug of nalbuphine, can be slowly degraded and has the potential to be prepared into a sustained-release preparation. [0004] [0005] Due to the risk of dependence and addiction of opioid drugs, the drug concentration of opioid drugs administered needs to be just right to achieve analgesic effect but try to avoid the risk of drug dependence. In addition, because postoperative pain, cancer pain ...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K31/485A61K47/10A61K47/26A61K47/28A61K47/44A61P19/02A61P25/00A61P29/00
CPCA61K31/485A61K47/10A61K47/28A61K47/26A61K47/44A61P29/00A61P19/02A61P25/00A61K9/1075A61K9/0019
Inventor赵振坤蒋钰钱桦江李雄
OwnerSUZHOU NHWA PHARM RES CO LTD