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Temperature and ion dual-sensitive in-situ gel nasal cavity drug delivery system

A temperature-sensitive, in-situ gel technology, used in pharmaceutical formulations, medical preparations with inactive ingredients, organic active ingredients, etc., can solve the problem of short duration of action on nasal mucosa, unfavorable drug effect, and easy loss of sprays, etc. problem, to achieve the effect of favorable drug absorption, good drug sustained release, and good sprayability

Inactive Publication Date: 2013-06-26
GENERAL HOSPITAL OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the spray is easy to lose, and the local action time in the nasal mucosa is short, which is not conducive to the efficacy of the drug

Method used

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  • Temperature and ion dual-sensitive in-situ gel nasal cavity drug delivery system
  • Temperature and ion dual-sensitive in-situ gel nasal cavity drug delivery system
  • Temperature and ion dual-sensitive in-situ gel nasal cavity drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1. Preparation of ion-sensitive nasal in situ gel

[0036]Weigh an appropriate amount of gellan gum, add an appropriate amount of deionized water to the beaker, fully swell in a hot water bath at 70-80°C, and then obtain a clear solution in a refrigerator at 4°C, and prepare the quality of gellan gum respectively Gel matrix with fractions of 0.2%, 0.5%, 0.75%, 1.0% (w / v), in a constant temperature water bath at 36.5°C, mixed with artificial nasal fluid (v / v=1:1) to observe each gel The gel condition of the matrix, the results are shown in Table 1.

[0037] Table 1 Gel conditions after mixing different mass fractions of gellan gum and artificial nasal solution

[0038]

[0039] The results show that when gellan gum is simply used as the in-situ gel matrix for nasal use, the gel cannot be formed at all when the concentration is too low; if the concentration is too high, the fluidity is poor and nasal spray administration cannot be performed. Therefore, it n...

Embodiment 2

[0040] Example 2. Changes in gelation time of composite in situ gels with different concentrations

[0041] Take an appropriate amount of gellan gum in a beaker, add an appropriate amount of deionized water, fully swell in a hot water bath at 70-80°C, and then place it in a refrigerator at 4°C to obtain a clear solution; another appropriate amount of poloxamer 407, Add it to the above solution, stir evenly, and place it at 4°C for 48 hours to prepare a composite gel. Prepare 0.1% gellan gum + 18% poloxamer 407, 0.2% gellan gum + 18% poloxamer 407, 0.3% gellan gum + 18% poloxamer 407, 0.4% gellan gum + 18% Poloxamer 407, 14% Poloxamer 407+0.3% Gellan Gum, 16% Poloxamer 407+0.3% Gellan Gum, 18% Poloxamer 407+0.3% Gellan Gum, Composite gel of 20% poloxamer 407+0.3% gellan gum, V 复合型凝胶 :V 人工鼻液 =4:1, in a 36.5°C constant temperature water bath, investigate the gelation time of each composite gel, the results are shown in Table 2.

[0042] Table 2 The gelation time of differen...

Embodiment 3

[0048] Example 3. Changes in the viscosity of the composite in situ gel at different concentrations

[0049] Mix the composite gel with the artificial nasal fluid, and use a thermometer to control the reaction temperature to 36.5°C under a circulating water bath, and measure its viscosity value with RVDVIII (rotational viscometer). See image 3 . With the increase of gellan gum solution concentration, the in situ gel viscosity increased significantly.

[0050] See Figure 4 . With the increase of poloxamer 407 concentration, the in situ gel viscosity increased significantly.

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Abstract

The invention discloses a temperature and ion dual-sensitive in-situ gel nasal cavity drug delivery system, comprising a main drug and a temperature and ion dual-sensitive in-situ gel matrix, wherein the temperature and ion dual-sensitive in-situ gel matrix is mainly prepared from the following raw materials of temperature sensitive in-situ gel matrix, ion sensitive in-situ gel matrix, and a penetration enhancer. The drug delivery system disclosed by the invention is especially suitable for a drug of achieving the central pivot through a BBB (blood brain barrier) to play a role, has good sprayable property and good in-situ gel property and drug slow-release effect, and benefits for playing the drug effect.

Description

technical field [0001] The invention relates to a local drug delivery system, in particular to a temperature- and ion-sensitive in-situ gel nasal cavity drug delivery system. Background technique [0002] The blood-brain barrier (Blood-Brain Barriers, BBB) is the most important barrier for drugs to enter the brain, and nasal administration can bypass the BBB. The nasal cavity is anatomically closely connected with the brain. Drug molecules are absorbed by the mucous membrane of the olfactory area, enter the cerebrospinal fluid through the olfactory bulb, and then enter the brain through the cerebrospinal fluid-brain barrier to exert their drug effects. Since the blocking effect of the cerebrospinal fluid-brain barrier on drugs is about 5000 times weaker than that of the BBB, the nasal drug delivery system has obvious advantages in brain drug delivery. [0003] In recent years, the research on temperature-sensitive in situ gel and ion-sensitive in situ gel nasal drug deliver...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K47/44A61K47/38A61K47/36A61K47/34A61K47/32A61K31/407A61K31/515A61K31/19A61K31/445A61K31/352A61K31/4985A61K31/55A61K31/439
Inventor 李欣杜丽娜王辰允金义光
Owner GENERAL HOSPITAL OF PLA
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