Gel for nasal allergy and preparation method thereof

Abstract

The invention relates to the technical field of gels, in particular to a gel for nasal cavity allergy and a preparation method thereof.The gel for nasal cavity allergy is prepared from, by weight, 15-20 parts of temperature-sensitive matrix; 1.5 to 3.0 parts of aldehyde cellulose / chitosan composite fiber; 0.5 to 1.0 part of a non-ionic surface active agent; 4.5 to 5.5 parts of glycerol; 0.1 to 0.2 part of disodium ethylene diamine tetraacetate; 0.1 to 0.3 part of p-hydroxyacetophenone; 2.0 to 3.0 parts of trehalose; and 60-80 parts of water. According to the application, the particularity of the nasal cavity is combined, the formyl cellulose / chitosan composite fiber is introduced into the system, a main body system with the temperature-sensitive matrix as a continuous phase and the formyl cellulose / chitosan composite fiber reinforced phase is formed, a physical network is formed to intercept cilia swing and reduce the removal rate, and the adhesive strength of the gel is enhanced through chemical combination; therefore, the residence time is prolonged through physical and chemical dual effects.

Description

Technical Field

[0001] This invention relates to the field of gel technology, and more particularly to a gel for nasal allergies and its preparation method. Background Technology

[0002] Common symptoms of allergic rhinitis include nasal itching, clear nasal discharge, nasal congestion, decreased sense of smell, and headache, which seriously affect patients' quality of life.

[0003] Since allergic rhinitis cannot be completely cured, symptoms are usually relieved effectively through daily care. One common daily care method for allergic rhinitis is rinsing the nasal cavity with saline solution. Although this method can remove allergens from the nasal cavity to some extent, the nasal mucosa is still exposed to air containing allergens after rinsing. Therefore, it can only relieve symptoms for a short time and cannot maintain clinical control.

[0004] Meanwhile, gel formulations have attracted widespread attention because they can cover the mucous membrane and form a protective layer on the nasal mucosa. However, existing nasal gels generally suffer from insufficient retention time in the nasal cavity, which limits their application. Summary of the Invention

[0005] To address the problem of short retention time of nasal gels in the nasal cavity in existing technologies, this invention provides a nasal allergy gel. This gel provides a three-dimensional mesh scaffold by introducing composite fibers into the raw materials, thereby enhancing adhesion strength and prolonging retention time, thus solving the problem of short retention time of nasal gels in the nasal cavity in existing technologies.

[0006] The technical solution adopted by this invention to solve its technical problem is:

[0007] A nasal allergy gel, by weight, comprises the following components:

[0008]

[0009] Optionally, the aldehyde-based cellulose / chitosan composite fiber is obtained by electrospinning with aldehyde-based cellulose and chitosan as spinning solution, followed by pulverization.

[0010] Optionally, the diameter of the aldehyde-modified cellulose / chitosan composite fiber is 150-250 nm.

[0011] Optionally, the length of the aldehyde-modified cellulose / chitosan composite fiber is 50-100 μm.

[0012] Optionally, the mass ratio of aldehyde-modified cellulose to chitosan in the spinning solution is 1:(3-4).

[0013] Optionally, the temperature-sensitive matrix is ​​poloxamer 407.

[0014] Optionally, the nonionic surfactant is polyethylene glycol-15 hydroxystearate.

[0015] Another object of the present invention is to provide a method for preparing a nasal allergy gel as described above, comprising the following steps:

[0016] S1: Disperse the aldehyde-modified cellulose / chitosan composite fiber in glycerol according to the formula to obtain a suspension;

[0017] S2: Add disodium ethylenediaminetetraacetate and trehalose to water to obtain a reaction solution;

[0018] S3: Poloxamer is added to the reaction solution at 4-8℃ and stirred to swell, thereby obtaining the poloxamer matrix;

[0019] S4: After adding the suspension to the poloxamer matrix, add the nonionic surfactant and p-hydroxyacetophenone in sequence, adjust the pH to 5.8-6.2, and obtain a nasal allergy gel.

[0020] The beneficial effects of this invention are:

[0021] The nasal allergy gel provided in this application, taking into account the special characteristics of the nasal cavity, introduces aldehyde-modified cellulose / chitosan composite fibers into the system to form a main system with a temperature-sensitive matrix as the continuous phase and aldehyde-modified cellulose / chitosan composite fibers as the reinforcing phase. By forming a physical network to intercept ciliary movement and reduce the clearance rate, and by chemically binding to enhance the gel adhesion strength, the retention time is prolonged and the therapeutic effect is improved through the dual action of physicochemical methods. Detailed Implementation

[0022] The present invention will now be described in further detail. The embodiments described below are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0023] Due to the unique characteristics of the nasal cavity, the cilia of the nasal mucosa clear mucus by directional movement. This means that traditional water-soluble gels are easily and quickly removed after being applied to the nasal cavity, resulting in a short retention time.

[0024] To address the short retention time of nasal gels in the nasal cavity in existing technologies, this invention provides a nasal allergy gel, comprising the following components by weight:

[0025]

[0026]

[0027] In this system, by introducing a temperature-sensitive matrix, the nasal allergy gel can be sprayed into the nasal cavity in a liquid spray form, then gels within the nasal cavity, achieving in-situ molding and solid coverage of the nasal cavity, physically isolating allergens. To resist ciliary clearance, this application introduces aldehyde-modified cellulose / chitosan composite fibers into the raw materials, embedding these fibers within the gel to form a three-dimensional network scaffold. This scaffold physically intercepts ciliary movement, reducing the clearance rate; furthermore, the aldehyde groups of the aldehyde-modified cellulose covalently bind to the disulfide bonds of mucin, enhancing adhesion strength and further prolonging retention time. Moreover, the introduced aldehyde-modified cellulose / chitosan composite fibers also serve as a reinforcing phase, improving the system's mechanical strength.

[0028] In addition, this application introduces trehalose for osmotic pressure regulation and repair of the mucosal barrier; introduces nonionic surfactants to improve bioavailability; introduces glycerol to enhance low-temperature sprayability and synergistically improves moisturizing properties with trehalose; and introduces disodium ethylenediaminetetraacetate to chelate metal ions (such as Ca2+). 2+ / Mg 2+ This prevents nasal mucus electrolytes from damaging the gel network; the introduction of p-hydroxyacetophenone as a natural antioxidant protects aldehyde activity and drug stability, thereby ensuring the formation of an isolation protective layer on the nasal mucosa through the synergistic effect of each component, while prolonging the retention time and maintaining long-term clinical control.

[0029] The nasal allergy gel provided in this application, taking into account the special characteristics of the nasal cavity, introduces aldehyde-modified cellulose / chitosan composite fibers into the system to form a main system with a temperature-sensitive matrix as the continuous phase and aldehyde-modified cellulose / chitosan composite fibers as the reinforcing phase. By forming a physical network to intercept ciliary movement and reduce the clearance rate, and by chemically binding to enhance the gel adhesion strength, the retention time is prolonged and the therapeutic effect is improved through the dual action of physicochemical methods.

[0030] The aldehyde-modified cellulose / chitosan composite fiber in this application is obtained by electrospinning with aldehyde-modified cellulose and chitosan as spinning solution, followed by pulverization.

[0031] To reduce the clearance rate while avoiding foreign body sensation and improving comfort, this application preferably uses aldehyde-modified cellulose / chitosan composite fibers with a diameter of 150-250 nm and a length of 50-100 μm.

[0032] Furthermore, in order to balance the spinnability, mechanical strength and biological function of the fiber, this application preferably uses a mass ratio of aldehyde-modified cellulose to chitosan in the spinning solution of 1:(3-4).

[0033] The preparation method of aldehyde-modified cellulose in this invention can refer to the corresponding existing technology; the degree of deacetylation of chitosan is preferably ≥85% in this invention.

[0034] The preferred temperature-sensitive matrix of this invention is poloxamer 407. With poloxamer 407 as the temperature-sensitive matrix, since the gelation temperature of poloxamer 407 is 34°C, the temperature-sensitive matrix can be gelled in situ at the nasal cavity temperature, thereby achieving coverage of the nasal mucosa.

[0035] Furthermore, the present invention preferably uses polyethylene glycol-15 hydroxystearate (Solutol HS15) as the nonionic surfactant.

[0036] Another object of the present invention is to provide a method for preparing a nasal allergy gel as described above, the method comprising the following steps:

[0037] S1: Disperse the aldehyde-modified cellulose / chitosan composite fiber in glycerol according to the formula to obtain a suspension;

[0038] Preferably, this step involves dispersing the aldehyde-modified cellulose / chitosan composite fibers in glycerol (300W, 10 minutes) using ultrasound to form a homogeneous suspension.

[0039] S2: Add disodium ethylenediaminetetraacetate and trehalose to water to obtain a reaction solution;

[0040] S3: Poloxamer was added to the reaction solution at 4-8℃ and stirred to swell, thus obtaining the poloxamer matrix;

[0041] S4: After adding the suspension to the poloxamer matrix, add the nonionic surfactant and p-hydroxyacetophenone in sequence, adjust the pH to 5.8-6.2, and obtain a gel for nasal allergies;

[0042] Preferably, in this step, after adding the suspension to the poloxamer matrix, a nonionic surfactant is slowly added, and finally p-hydroxyacetophenone is added;

[0043] It is preferable to use a trace amount of triethanolamine to adjust the pH to 5.8-6.2 to achieve the optimal pH range for the nasal cavity.

[0044] Furthermore, in addition to its pH-regulating effect, the addition of triethanolamine in this application also serves to reduce the apparent cation density of chitosan by consuming the free amino groups on its surface after electrospinning. When aldehyde-modified cellulose / chitosan composite fibers are used in nasal gels, the presence of triethanolamine in the system regulates the pH, allowing the treated chitosan fibers to expose more of the previously shielded amino groups, thereby further increasing the cation density of chitosan.

[0045] The method for preparing nasal allergy gel provided in this application is simple. Taking into account the special characteristics of the nasal cavity, aldehyde-modified cellulose / chitosan composite fibers are introduced into the system to form a main system with a temperature-sensitive matrix as the continuous phase and aldehyde-modified cellulose / chitosan composite fibers as the reinforcing phase. By forming a physical network to intercept ciliary movement and reduce the clearance rate, and by chemically binding to enhance the gel adhesion strength, the retention time is prolonged and the therapeutic effect is improved through the dual action of physicochemical methods.

[0046] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below.

[0047] Unless otherwise specified, the aldehyde-modified cellulose in the embodiments of the present invention is prepared according to the following method:

[0048] Add microcrystalline cellulose to deionized water at a mass ratio of 1:66. Sonicate in an ice-water bath (300W, 30min) until translucent. Add 0.1M HCl dropwise while magnetically stirring (500rpm) until the pH reaches the target level. 3.0±0.5, to obtain a suspension; preheat the suspension to 45℃; under light-protected conditions, dissolve NaIO4 in water, with a NaIO4 to water mass ratio of 1:24 and a NaIO4 to microcrystalline cellulose mass ratio of 1:1, and magnetically stir (500 rpm, 30 min) in the dark until completely dissolved, then slowly add it dropwise to the suspension, stir for 3 hours under light-protected conditions, and add ethylene glycol to terminate the reaction; the molar ratio of ethylene glycol to NaIO4 is 1.5:1; dialyze the obtained reaction solution for 2 days (deionized water, water changed every 4 hours) to remove iodate and small molecule byproducts, to obtain the dialyzed product; sonicate the dialyzed product in an ice-water bath (240W, 20 min) to prevent aggregation, centrifuge (6000-10000 rpm, 30 min) to collect the supernatant, to obtain a DACNCs dispersion; pre-freeze the DACNCs dispersion at -50℃ for 24 hours, and vacuum dry at -80℃ for 48 hours to obtain aldehyde-modified cellulose.

[0049] Unless otherwise specified, the aldehyde-modified cellulose / chitosan composite fibers in the embodiments of the present invention are prepared by coaxial electrospinning. A mixture of chitosan, aldehyde-modified cellulose, and a solvent is used as the inner layer propulsion fluid, wherein the solvent is a 1% (w / w) aqueous solution of acetic acid. The chitosan concentration in the spinning solution is 16%, and the aldehyde-modified cellulose concentration is 4%. A 5% (w / w) polyvinyl alcohol solution is used as the outer layer propulsion fluid. The propulsion speed of the inner layer is 1.0 mL / h, and the propulsion speed of the outer layer is 0.5 mL / h. The voltage of the inner layer is 18 kV, and the voltage of the outer layer is 15 kV. The receiving distance between the inner and outer layers is 15 cm. The fibers are vacuum dried at 40°C for 24 h, and then mechanically pulverized to a fiber length of 50–100 μm to obtain the aldehyde-modified cellulose / chitosan composite fibers.

[0050] The nasal allergy gels in each embodiment of this application are prepared according to the following method:

[0051] S1: According to the formula, disperse the aldehyde-modified cellulose / chitosan composite fiber in glycerol by ultrasound (300W, 10 minutes) to form a homogeneous suspension.

[0052] S2: Add disodium ethylenediaminetetraacetate and trehalose to pure water to obtain a reaction solution;

[0053] S3: Poloxamer was added to the reaction solution at 5°C and stirred to swell, thus obtaining the poloxamer matrix;

[0054] S4: After adding the suspension to the poloxamer matrix, slowly add polyethylene glycol-15 hydroxystearate, and finally add p-hydroxyacetophenone. Adjust the pH to 5.8-6.2 with triethanolamine to obtain a nasal allergy gel.

[0055] S5: Sterilized by gamma rays (25kGy) and filled at 10℃.

[0056] Example 1

[0057] This embodiment provides a nasal allergy gel, which, by weight, comprises the following components:

[0058]

[0059] Example 2

[0060] This embodiment provides a nasal allergy gel, which, by weight, comprises the following components:

[0061]

[0062] Example 3

[0063] This embodiment provides a nasal allergy gel, which, by weight, comprises the following components:

[0064]

[0065] The adhesiveness of the nasal allergy gels prepared in the above embodiments was tested using the following methods:

[0066] Place a smooth glass plate at a 45° angle to the horizontal plane. Place two drops of gelled nasal allergy gel on the glass plate and let them slide down naturally. Record the time it takes for the gel droplets to slide 1 cm. The experimental temperature is room temperature (20℃).

[0067] The test results are shown in Table 1.

[0068] Table 1

[0069] Example 1 Example 2 Example 3 Time (s) 172 227 246

[0070] The data in the table shows that the nasal allergy gels prepared in the various embodiments of this application have moderate adhesion, which allows the nasal allergy gels to remain in the nasal cavity for a certain period of time.

[0071] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A nasal allergy gel, characterized in that, The raw materials, by weight, include the following components:

2. The nasal allergy gel as described in claim 1, characterized in that, The aldehyde-modified cellulose / chitosan composite fiber is obtained by electrospinning with aldehyde-modified cellulose and chitosan as spinning solution, followed by pulverization.

3. The nasal allergy gel as described in claim 2, characterized in that, The diameter of the aldehyde-modified cellulose / chitosan composite fiber is 150-250 nm.

4. The nasal allergy gel as described in claim 2, characterized in that, The length of the aldehyde-modified cellulose / chitosan composite fiber is 50-100 μm.

5. The nasal allergy gel as described in claim 2, characterized in that, The mass ratio of aldehyde-modified cellulose to chitosan in the spinning solution is 1:(3-4).

6. The nasal allergy gel according to any one of claims 1-5, characterized in that, The temperature-sensitive matrix is ​​poloxamer 407.

7. The nasal allergy gel according to any one of claims 1-5, characterized in that, The nonionic surfactant is polyethylene glycol-15 hydroxystearate.

8. A method for preparing a nasal allergy gel as described in any one of claims 1-7, characterized in that, Includes the following steps: S1: Disperse the aldehyde-modified cellulose / chitosan composite fiber in glycerol according to the formula to obtain a suspension; S2: Add disodium ethylenediaminetetraacetate and trehalose to water to obtain a reaction solution; S3: Poloxamer is added to the reaction solution at 4-8℃ and stirred to swell, thereby obtaining the poloxamer matrix; S4: After adding the suspension to the poloxamer matrix, add the nonionic surfactant and p-hydroxyacetophenone in sequence, adjust the pH to 5.8-6.2, and obtain a nasal allergy gel.

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