Slow-release soluble microneedle delivery system for mite-allergen-loaded microspheres

A delivery system and allergen technology, which is applied in the field of sustained-release soluble microneedle delivery system, can solve problems such as uncertainty, decline in mechanical properties of microneedles, and differences in mechanical properties of soluble microneedles, so as to prolong release time and reduce drug delivery. The effect of medication frequency and increased compliance

Pending Publication Date: 2021-10-26
微缔医药科技(杭州)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] By consulting the literature and patents at home and abroad, there are literature and patent reports that mite allergens are directly loaded into soluble microneedles: for example, Kim et al. prepared soluble microneedles with hyaluronic acid to deliver mite allergens (Kim J H, Shin J U, Kim et al. S H, etal.Successful transdermal allergen delivery and allergen-specificimmunotherapy using biodegradable microneedle patches[J].Biomaterials,2018,150:38-48); such as the Japanese patent with publication number JP2014156433A and the Chinese patent with publication number CN109715075A, which describe Material selection when soluble microneedles are directly loaded with allergens, but none of them involve the related content of mite allergen slow-release microneedles
[0006] In addition, there is no mite allergen microsphere delivery at present, although there are microsphere delivery of pollen allergen and bee venom allergen (AProtective Allergy Vaccine Based on CpG-and Protamine-Containing PLGA Microparticles[J].Pharmaceutical Research, 2007 , 24(10):1927-1935.), but there are compositional differences between the protein components of mite allergen vaccines and pollen allergens, bee venom allergens, etc., how to have a good loading effect on mite allergens still remains Unce...

Method used

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  • Slow-release soluble microneedle delivery system for mite-allergen-loaded microspheres
  • Slow-release soluble microneedle delivery system for mite-allergen-loaded microspheres
  • Slow-release soluble microneedle delivery system for mite-allergen-loaded microspheres

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 Preparation of slow-release soluble microneedles for mite allergens

[0024] The mite allergen slow-release soluble microneedle to be prepared in the present invention is composed of mite allergen microspheres and microneedle matrix materials.

[0025] Among the many microsphere preparation methods, the double emulsion solvent evaporation method has the advantages of simple operation, convenient control of process parameters, no need to adjust pH and large temperature changes, and greatly improves the drug loading and encapsulation efficiency of microspheres compared with the single emulsion system. , has the advantages of controlled release and is often used to encapsulate water-soluble core materials. Therefore, the present invention adopts double emulsion solvent evaporation method to prepare mite allergen microspheres, and the specific method is as follows:

[0026] The capsule wall material and a small amount of Span 60 are dissolved in dichloromethane a...

Embodiment 2

[0031] Example 2 Related Determination of Mite Allergen Slow Release Soluble Microneedles

[0032] 1. Particle size of mite allergen microspheres

[0033] Precisely weigh the prepared dry microspheres and spread them evenly on the glass slide, observe the morphology with an optical microscope with a micrometer and count the particle size (μm) of 300 microspheres, divide the particle size range and calculate the average particle size through statistical processing. path.

[0034] When the average particle size of the microspheres is less than 30 μm, the microspheres are more likely to be distributed on the tip of the microneedle, which is considered to meet the requirements and can be used for subsequent preparations.

[0035] 2. Determination of Encapsulation Efficiency of Mite Allergen Microspheres

[0036] The total protein content of 10ml mite allergen vaccine solution was measured by Coomassie brilliant blue (CBB) method, and recorded as W1. Subsequently, the prepared mit...

Embodiment 3

[0048] Example 3 Effect of Component Types and Contents of Mite Allergen Microspheres on Mite Allergen Loading

[0049] In this example, the mite allergen microspheres consist of an oil phase, an inner water phase, and an outer water phase to form a three-phase system. The water phase is an aqueous solution of mite allergens, and the external water phase is a 0.5% concentration of polyvinyl alcohol (PVA) aqueous solution. By changing the type of cyst wall material, the volume ratio of the oil phase to the internal water phase, the results are shown in Table 1. Effects of mite allergen microspheres constructed of different materials on encapsulation efficiency and particle size.

[0050] In this embodiment, the capsule wall material is selected as polylactic acid-glycolic acid copolymer (PLGA), polyethylene glycol-polylactic acid acrylic acid copolymer (PEG-PLGA), polyethylene glycol-polylactic acid copolymer (PEG-PLA ), one of poly 3-hydroxybutyrate (PHB); the content ratio o...

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Abstract

The invention discloses a slow-release soluble microneedle delivery system for mite-allergen-loaded microspheres. The system comprises a needle body and a backing, wherein the needle body comprises the mite allergen microspheres and a matrix material, the matrix material is a mixture of a methyl vinyl ether-maleic anhydride copolymer and polyethylene glycol, and the content ratio of the methyl vinyl ether-maleic anhydride copolymer to the polyethylene glycol is (2:1)-(1:1). According to the system, the specific component types and content ratio of the mite allergen microspheres are selected, so that the prepared mite allergen slow-release microspheres are excellent in performance and can well load mite allergen; and the specific component types and content ratio of the matrix material and the specific drug loading ratio are selected, so that the prepared mite allergen slow-release soluble microneedle is excellent in formability, mechanical strength and other performance, the release time of the drug is greatly prolonged, the treatment effect is superior to that of a non-slow-release mite allergen soluble microneedle, the administration frequency of the mite allergen can be reduced, and the compliance of a patient can be improved.

Description

technical field [0001] The invention relates to the technical field of administration of mite allergens, in particular to a slow-release soluble microneedle delivery system loaded with mite allergen microspheres. Background technique [0002] Mites are an important source of allergens that induce allergic diseases such as asthma, allergic rhinitis, and eczema. In recent years, investigations and studies in many countries such as the United States, New Zealand, and Australia have successively confirmed that the close relationship between mite-derived allergens and allergic diseases is the cause of allergic diseases such as allergic asthma; desensitization treatment has become the most effective treatment for such diseases. treatment method. However, mite allergens are currently mostly administered in the form of injections, and long-term injections lead to poor patient compliance. Therefore, a new dosage form for the delivery of mite allergens is urgently needed. [0003] A...

Claims

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Application Information

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IPC IPC(8): A61K39/35A61K9/00A61K47/10A61K47/32A61P33/14
CPCA61K39/35A61K9/0021A61K47/10A61K47/32A61P33/14
Inventor 不公告发明人
Owner 微缔医药科技(杭州)有限公司
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