Anti-nasal allergy gel and preparation method thereof

Abstract

The present invention discloses an anti-nasal allergy gel, which comprises the following components in parts by weight: 0.1-2 parts of cellulose; 0.05-1 parts of chitosan salt or chitosan derivative; 0.1-0.2 parts of potassium sorbate or sodium sorbate; 0.8-0.9 parts of sea salt; 0.1-0.5 parts of xylitol, and 100 parts of deionized water; the chitosan salt is a substance shown in formula (1), wherein R is CI-, COO- or HSO4-, x and n are natural numbers, 0<x≤107, 102≤n≤107. Compared with the prior art, the present invention has the following advantages: the anti-nasal allergy gel can form a protective layer on the surface of the nasal mucosa, reduce and block dust, pathogens and other external irritants from direct contact with the nasal mucosa, and is used for daily health care of patients with nasal discomfort caused by various allergies or prone to allergic rhinitis, and can effectively reduce and prevent the incidence of allergic rhinitis.

Description

Technical Field

[0001] The invention relates to the technical field of nasal gel, in particular to an anti-nasal allergy gel and a preparation method thereof. Background Art

[0002] There are two types of nasal allergies. One is the well-known allergic rhinitis, which has symptoms such as watery nasal discharge, nasal congestion, and sneezing. In severe cases, people may also experience nasal root pain, itching of the nose, eyes, and ears, dizziness, and difficulty concentrating. The other is vasomotor rhinitis, which is mainly caused by the disorder of the autonomic nervous system, which makes the parasympathetic nerves strong and causes various symptoms similar to allergic rhinitis. It is not caused by specific antigens, but may be caused by emotional tension, increased stress, or various physical changes.

[0003] Statistics show that the prevalence of allergic rhinitis has been increasing year by year in the world in recent years, and the number of patients with allergic rhinitis in my country has also been rising year by year, which not only has a negative impact on people's physical and mental health and quality of life, but also creates a certain burden on the social economy, and is increasingly becoming a health issue of concern to the general public. Allergic rhinitis, also known as allergic rhinitis, refers to a non-infectious inflammatory disease of the nasal mucosa in which atopic individuals are exposed to allergens, mainly through the release of IgE-mediated mediators (mainly histamine), and the participation of a variety of immune-active cells and cytokines. There are three necessary conditions for its occurrence: specific antigens, that is, substances that cause the body's immune response; atopic individuals, that is, so-called individual differences and allergic constitutions; and the encounter between specific antigens and atopic individuals. Allergic rhinitis is a global health problem that can lead to many diseases and loss of labor.

[0004] Allergic rhinitis does not cause systemic symptoms such as fever, but can cause various discomfort symptoms in the ears, nose, throat and eyes, mainly including recurrent nasal itching, sneezing, clear nasal discharge and nasal congestion, which may be accompanied by itchy eyes, itchy throat and cough. It is partly related to the season, and is more common in spring and autumn. The symptoms gradually subside after the season. Nasal corticosteroids and oral antiallergic drugs can prevent and relieve the symptoms.

[0005] Allergic rhinitis not only affects the patient's quality of life due to the above-mentioned discomfort symptoms caused by repeated attacks, but more importantly, it may also induce allergic conjunctivitis, allergic dermatitis, chronic sinusitis, nasal polyps, secretory otitis media, and in severe cases may even induce asthma and endanger life. At present, allergic rhinitis cannot be completely and thoroughly cured, but through standardized comprehensive prevention and treatment, clinical control can be achieved and maintained, and symptoms can be effectively relieved. Therefore, how to prepare a nasal preparation that can effectively prevent and improve the discomfort symptoms caused by nasal allergies and does not contain irritating drugs is a technical problem that urgently needs to be solved in this field. Summary of the invention

[0006] The purpose of the present invention is to overcome the problems of the prior art and provide an anti-nasal allergy gel and a preparation method thereof.

[0007] In order to achieve the above object, the present invention adopts the following scheme:

[0008] An anti-nasal allergy gel comprises the following components in parts by weight: 0.1-2 parts of cellulose; 0.05-1 parts of chitosan salt or chitosan derivative; 0.1-0.2 parts of potassium sorbate or sodium sorbate; 0.8-0.9 parts of sea salt; 0.1-0.5 parts of xylitol, and deionized water is added to make up to 100 parts;

[0009] Chitosan salt is a substance represented by formula (1):

[0010]

[0011] Where R is Cl - 、COO - or HSO4 - , x, n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 .

[0012] Furthermore, the chitosan derivative includes one or more of the substances represented by formula (2), formula (3), formula (4), formula (5) and formula (6):

[0013]

[0014] In formula (2), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ;

[0015]

[0016] In formula (4), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ;

[0017]

[0018] In formula (5), x and n are natural numbers, 0<x≤10 7 , 0<y≤10 7 , 10 2 ≤n≤10 7 ;

[0019]

[0020] In formula (6), x and n are natural numbers, 0<x≤10 7 , 0<y≤10 7 , 10 2 ≤n≤10 7 .

[0021] In the molecular structures of formulae (1) to (6) above, the arrangement order of the repeating units is not completely in accordance with the order marked in the structure, but is arranged and combined in the polymer chain in an irregular manner.

[0022] Furthermore, the cellulose is hydroxyethyl cellulose.

[0023] A method for preparing an anti-nasal allergy gel comprises the following steps:

[0024] S10: weigh the following ingredients by weight: 0.1-2 parts of cellulose; 0.05-1 parts of chitosan salt or chitosan derivative; 0.1-0.2 parts of potassium sorbate or sodium sorbate; 0.8-0.9 parts of sea salt; 0.1-0.5 parts of xylitol, and make up to 100 parts of deionized water;

[0025] S20: mixing the raw materials and stirring them thoroughly to completely dissolve them to obtain an anti-nasal allergy gel mother solution;

[0026] S30 sterilizes the anti-nasal allergy gel mother solution by high pressure or irradiation to obtain the anti-nasal allergy gel.

[0027] Furthermore, step S20 also includes:

[0028] S21: mixing chitosan salt or chitosan derivative with deionized water, and stirring to fully dissolve them to obtain a first mixed solution;

[0029] S22: mixing cellulose and deionized water, and stirring to fully dissolve them, to obtain a second mixed solution;

[0030] S23: mixing the remaining components with the remaining amount of deionized water, and stirring them evenly to fully dissolve them, to obtain a third mixed solution;

[0031] S24: Mix the first mixed liquid, the second mixed liquid and the third mixed liquid together, and stir them evenly to obtain the anti-nasal allergy gel mother liquid.

[0032] Furthermore, in steps S20 and S30, the mixture is first heated to a temperature between room temperature and 80° C. and then stirred to fully dissolve the mixture.

[0033] Furthermore, the cellulose is hydroxyethyl cellulose.

[0034] Compared with the existing technology, the present invention has the following advantages: the main functional material chitosan salt and its derivatives contained in the anti-nasal allergy gel provided by the present invention are a modified natural polysaccharide, which has excellent biocompatibility, antibacterial and anti-inflammatory repair-promoting properties, and is non-irritating and non-sensitizing. Hydroxyethyl cellulose can undergo physical cross-linking with chitosan to form a gel, and xylitol is added as a wetting regulator, together with sea salt, to provide an isotonic moist environment inside the nasal cavity, and better protect the nasal mucosa from damage. The anti-nasal allergy gel can form a film on the surface of the nasal mucosa to form a protective layer, reduce and block external irritants such as dust and pathogens from direct contact with the nasal mucosa, and is used for daily health care of patients with nasal discomfort caused by various allergies or prone to allergic rhinitis, and can effectively reduce and prevent the incidence of allergic rhinitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The present application is further described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0036] Figure 1 This is a graph showing the test results of the cytotoxicity of the anti-nasal allergy gel of the present invention on mouse fibroblasts (L929).

[0037] Figure 2 This is a three-dimensional fluorescent image of the thin film formed by the anti-nasal allergy gel A prepared in Example 1 isolating the silica spheres from the transparent substrate.

[0038] Figure 3 This is a three-dimensional fluorescent image of the thin film formed by the anti-nasal allergy gel B prepared in Example 2 isolating Escherichia coli from the transparent substrate.

[0039] Figure 4 This is a picture of the appearance of the mouse nasal cavity in the mouse nasal cavity experiment.

[0040] Figure 5 The present invention is a scanning electron microscope photograph a of the nasal mucosa environment of a mouse that has not been sprayed with the anti-nasal allergy gel of the present invention, and a scanning electron microscope photograph b of the nasal mucosa environment of a mouse that has been sprayed with the anti-nasal allergy gel of the present invention.

[0041] Figure 6 is a scanning electron microscope photograph of the mouse nasal mucosal environment after the anti-nasal allergy gel of the present invention was sprayed into the nasal cavity and the bacterial solution was dripped, and (b) is an enlarged view of the frame part in (a). DETAILED DESCRIPTION

[0042] The specific implementation of the present invention is further described in detail below in conjunction with the accompanying drawings and examples. The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0043] Embodiment 1

[0044] An anti-nasal allergy gel has the following formula: 0.1 g of hydroxyethyl cellulose, 1 g of chitosan salt of formula (1), 0.2 g of potassium sorbate, 0.9 g of sea salt, 0.5 g of xylitol, and 97.3 g of deionized water.

[0045]

[0046] Where R is Cl - 、COO - or HSO4 - , x, n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 .

[0047] A method for preparing an anti-nasal allergy gel comprises the following steps:

[0048] S10: mixing the hydroxyethyl cellulose and 37.3 g of deionized water, and stirring at room temperature to fully dissolve the hydroxyethyl cellulose to obtain a first mixed solution;

[0049] S21: mixing the chitosan salt of formula (1) with 30 g of deionized water, then heating to 80° C. and stirring to fully dissolve the chitosan salt to obtain a second mixed solution;

[0050] S22: Mix the remaining components with the remaining 30 g of deionized water, and stir evenly to fully dissolve, to obtain a third mixed solution;

[0051] S23: mixing the first, second and third mixed solutions together and stirring evenly to obtain an anti-nasal allergy gel mother solution;

[0052] S30: sterilize the mother liquid obtained in step S23 by high pressure or irradiation to obtain the anti-nasal allergy gel A.

[0053] Embodiment 2

[0054] An anti-nasal allergy gel has the following formula: 0.2 g of hydroxyethyl cellulose, 0.7 g of chitosan monoguanidine salt of formula (2), 0.2 g of potassium sorbate, 0.9 g of sea salt, 0.4 g of xylitol, and 97.6 g of deionized water.

[0055]

[0056] In formula (2), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 .

[0057] A method for preparing an anti-nasal allergy gel comprises the following steps:

[0058] S10: mixing the hydroxyethyl cellulose and 37.6 g of deionized water, heating to 40° C., and stirring to fully dissolve the hydroxyethyl cellulose to obtain a first mixed solution;

[0059] S21: Mix the chitosan salt of formula (2) and 30 g of deionized water, and stir them thoroughly at 70° C. to dissolve them, to obtain a second mixed solution;

[0060] S22: Mix the remaining components with the remaining 30 g of deionized water, and stir evenly to fully dissolve, to obtain a third mixed solution;

[0061] S23: mixing the first, second and third mixed solutions together and stirring evenly to obtain an anti-nasal allergy gel mother solution;

[0062] S30: sterilize the mother liquid obtained in step S23 by high pressure or irradiation to obtain the anti-nasal allergy gel B.

[0063] Embodiment 3

[0064] An anti-nasal allergy gel has the following formula: 0.5 g of hydroxyethyl cellulose, 0.5 g of chitosan biguanide salt of formula (3), 0.15 g of sodium sorbate, 0.85 g of sea salt, 0.2 g of xylitol, and 97.8 g of deionized water.

[0065]

[0066] In formula (3), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ;

[0067] A method for preparing an anti-nasal allergy gel comprises the following steps:

[0068] S10: mixing the hydroxyethyl cellulose and 37.8 g of deionized water, heating to 50° C., and stirring to fully dissolve the hydroxyethyl cellulose to obtain a first mixed solution;

[0069] S21: Mix the chitosan salt of formula (1) and 30 g of deionized water, and stir them thoroughly at 60° C. to dissolve them, to obtain a second mixed solution;

[0070] S22: Mix the remaining components with the remaining 30 g of deionized water, and stir evenly to fully dissolve, to obtain a third mixed solution;

[0071] S23: mixing the first, second and third mixed solutions together and stirring evenly to obtain an anti-nasal allergy gel mother solution;

[0072] S30: sterilize the mother liquid obtained in step S23 by high pressure or irradiation to obtain the anti-nasal allergy gel C.

[0073] Embodiment 4

[0074] An anti-nasal allergy gel has the following formula: 1.0 g of hydroxyethyl cellulose, 0.3 g of carboxymethyl chitosan of formula (4), 0.15 g of sodium sorbate, 0.85 g of sea salt, 0.2 g of xylitol, and 97.5 g of deionized water.

[0075]

[0076] In formula (4), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ;

[0077] A method for preparing an anti-nasal allergy gel comprises the following steps:

[0078] S10: mixing the hydroxyethyl cellulose and 37.5 g of deionized water, heating to 60° C., and stirring to fully dissolve the hydroxyethyl cellulose to obtain a first mixed solution;

[0079] S21: Mix the carboxymethyl chitosan of formula (4) with 30 g of deionized water, and stir thoroughly at 50° C. to dissolve the mixture, to obtain a second mixed solution;

[0080] S22: Mix the remaining components with the remaining 30 g of deionized water, and stir evenly to fully dissolve, to obtain a third mixed solution;

[0081] S23: mixing the first, second and third mixed solutions together and stirring evenly to obtain an anti-nasal allergy gel mother solution;

[0082] S30: sterilize the mother liquid obtained in step S23 by high pressure or irradiation to obtain the anti-nasal allergy gel D.

[0083] Embodiment 5

[0084] An anti-nasal allergy gel has the following formula: 1.5 g hydroxyethyl cellulose, 0.1 g double-modified chitosan derivative of formula (5), 0.15 g sodium sorbate, 0.85 g sea salt, 0.2 g xylitol and 97.2 g deionized water.

[0085]

[0086] In formula (5), x and n are natural numbers, 0<x≤10 7 , 0<y≤10 7 , 10 2 ≤n≤10 7 ;

[0087] A method for preparing an anti-nasal allergy gel comprises the following steps:

[0088] S10: mixing the hydroxyethyl cellulose and 37.2 g of deionized water, heating to 70° C., and stirring to fully dissolve the hydroxyethyl cellulose to obtain a first mixed solution;

[0089] S21: mixing the double-modified chitosan derivative of formula (5) with 30 g of deionized water, and stirring them thoroughly at 40° C. to dissolve them, to obtain a second mixed solution;

[0090] S22: Mix the remaining components with the remaining 30 g of deionized water, and stir evenly to fully dissolve, to obtain a third mixed solution;

[0091] S23: mixing the first, second and third mixed solutions together and stirring evenly to obtain an anti-nasal allergy gel mother solution;

[0092] S30: sterilize the mother liquid obtained in step S23 by high pressure or irradiation to obtain the anti-nasal allergy gel E.

[0093] Embodiment 6

[0094] An anti-nasal allergy gel has the following formula: 2 grams of hydroxyethyl cellulose, 0.05 grams of a double-modified chitosan derivative of formula (6), 0.1 grams of sodium sorbate, 0.85 grams of sea salt, 0.1 grams of xylitol, and 96.9 grams of deionized water.

[0095]

[0096] In formula (6), x and n are natural numbers, 0<x≤10 7 , 0<y≤10 7 , 10 2 ≤n≤10 7 .

[0097] A method for preparing an anti-nasal allergy gel comprises the following steps:

[0098] S10: mixing the hydroxyethyl cellulose and 36.9 g of deionized water, stirring at 80° C. to fully dissolve the hydroxyethyl cellulose, to obtain a first mixed solution;

[0099] S21: Mix the double-modified chitosan derivative of formula (6) and 30 g of deionized water, and then stir them thoroughly at room temperature to dissolve them, to obtain a second mixed solution;

[0100] S22: Mix the remaining components with the remaining 30 g of deionized water, and stir evenly to fully dissolve, to obtain a third mixed solution;

[0101] S23: mixing the first, second and third mixed solutions together and stirring evenly to obtain an anti-nasal allergy gel mother solution;

[0102] S30: sterilize the mother liquid obtained in step S23 by high pressure or irradiation to obtain the anti-nasal allergy gel F.

[0103] Cytotoxicity Tests of Examples 1 to 6

[0104] Figure 1 The cytotoxicity test results of the anti-nasal allergy gel prepared in Examples 1 to 6 of the present invention on mouse fibroblasts (L929) are shown in the figure. As can be seen from the figure, the test results show that the anti-nasal allergy gel prepared in the present invention has basically no cytotoxicity and even has a certain promoting effect on cell proliferation, which means that the anti-nasal allergy gel has good biosafety.

[0105] Pollen dust barrier simulation experiment

[0106] In order to prove that the anti-nasal allergy gel prepared by the present invention can form a protective layer to reduce and block the contact between pollen dust and nasal mucosa after use, we use silica beads to simulate pollen dust. First, the anti-nasal allergy gel A prepared in Example 1 stained with rhodamine B (displayed in red) is sprayed on a transparent substrate. After it dries to form a film, the silica beads stained with fluorescein (displayed in green) are sprinkled on the film produced by this product; then a laser scanning confocal microscope (model ARsiMP-LSM-Kit-LegendElite-USX, Nikon) is used to observe the three-dimensional fluorescent image. Figure 2 As shown, the red film formed by the product completely isolates the green silica spheres from the substrate, avoiding direct contact between the two. This proves that the protective layer formed by the product of the present invention can reduce the direct contact between dust and the nasal mucosa.

[0107] Escherichia coli pathogens barrier simulation experiment

[0108] In order to verify that the anti-nasal allergy gel of the present invention can form a protective film and block the contact between pathogens and nasal mucosa, we used Escherichia coli (a bacterial pathogen) to conduct a simulation experiment. First, the anti-nasal allergy gel B (displayed in red) prepared in Example 2 stained with rhodamine was dripped onto a transparent substrate. After it dried to form a film, the stained Escherichia coli (displayed in green) was sprinkled onto the film produced by this product; then a laser scanning confocal microscope (model ARsiMP-LSM-Kit-LegendElite-USX, Nikon) was used to observe the three-dimensional fluorescence image. Figure 3 As shown in the figure, the red film produced by this product completely isolates the green E. coli from the substrate, avoiding direct contact between the two. This experiment proves that the protective layer formed by this product can reduce the direct contact between pathogens and the nasal mucosa.

[0109] Mouse nasal cavity experiment

[0110] We used mice as test animals and Pseudomonas aeruginosa as a typical representative of external irritants such as dust and pathogens to verify that the anti-nasal allergy gel of the present invention can form a protective film in the moist nasal cavity and block allergens.

[0111] The anti-nasal allergy gel AF prepared in Examples 1 to 6 of the present invention was sprayed into the nasal cavities of 6 mice 3 times using a press-type spray bottle (one gel product was sprayed into the nasal cavity of each mouse), and after 30 minutes, a Pseudomonas aeruginosa liquid (bacterial concentration: 1×109 CFU / mL) was dripped into the nasal cavities. After another 30 minutes, the mice were killed, and the nasal cavities were taken and fixed (the appearance of the nasal cavities was as follows Figure 4 The morphology of the mucosal area inside the nasal cavity was observed using a field emission gun environmental scanning electron microscope (instrument model: QuantaFEG250; manufacturer: FEI Company, USA).

[0112] Figure 5 Photo a in the middle is a scanning electron microscope photo of the mouse nasal mucosa environment that has not been sprayed with this product. As can be seen from the photo, the surface of the mouse nasal mucosa is wrinkled. Figure 5 Photo b in the middle is an environmental scanning electron micrograph of the nasal mucosa of mice after the anti-nasal allergy gel A prepared in Example 1 of the present invention was sprayed in the nasal cavity. In the figure, it can be seen that the wrinkled morphology on the surface of the nasal mucosa of the mice has been covered, indicating that this product forms a film on the surface of the nasal mucosa of the mice (scanning electron micrographs of the nasal mucosa of five other mice showed similar results and are not shown here).

[0113] Figure 6 This is a scanning electron microscope photo of the nasal mucosa of mice after the anti-nasal allergy gel A prepared in Example 1 of the present invention was sprayed into the nasal cavity and the bacterial solution was added. It can be seen in the figure that Pseudomonas aeruginosa ( Figure 6 The white arrow in b) is located in the film formed by this product ( Figure 6 The white arrow in a) points to the top of the nasal mucosa and has no direct contact with the nasal mucosa (scanning electron microscopy photos of the nasal mucosa of five other mice showed similar results and are not shown here).

[0114] The above test results show that the anti-nasal allergy gel prepared in the embodiment of the present invention can form a film in the nasal cavity of mice, and can block external irritants such as dust and pathogens represented by Pseudomonas aeruginosa from direct contact with the nasal mucosa, thereby playing a role in protecting the nasal mucosa.

[0115] The above is only a preferred implementation of the present application. It should be pointed out that for ordinary technicians in this technical field, several improvements and substitutions can be made without departing from the technical principles of the present application. These improvements and substitutions should also be regarded as the scope of protection of the present application.

Claims

1. An anti-nasal allergy gel, characterized in that: The invention comprises the following components in parts by weight: 0.1-2 parts of cellulose; 0.05-1 parts of chitosan salt or chitosan derivative; 0.1-0.2 parts of potassium sorbate or sodium sorbate; 0.8-0.9 parts of sea salt; 0.1-0.5 parts of xylitol, and deionized water is added to make up to 100 parts; The chitosan salt is a substance represented by formula (1): Where R is Cl - 、COO - or HSO4 - , x, n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ; The chitosan derivative includes one or more of the substances represented by formula (2), formula (3), formula (4), formula (5) and formula (6): In formula (2), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ; In formula (3), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ; In formula (4), x and n are natural numbers, 0<x≤10 7 , 10 2 ≤n≤10 7 ; In formula (5), x and n are natural numbers, 0<x≤10 7 , 0<y≤10 7 , 10 2 ≤n≤10 7 ; In formula (6), x and n are natural numbers, 0<x≤10 7 , 0<y≤10 7 , 10 2 ≤n≤10 7 ; The cellulose is hydroxyethyl cellulose.

2. A method for preparing the anti-nasal allergy gel according to claim 1, characterized in that: The following steps are involved: S10: weigh the following ingredients by weight: 0.1-2 parts of cellulose; 0.05-1 parts of chitosan salt or chitosan derivative; 0.1-0.2 parts of potassium sorbate or sodium sorbate; 0.8-0.9 parts of sea salt; 0.1-0.5 parts of xylitol, and make up to 100 parts of deionized water; S20: mixing the raw materials and stirring them thoroughly to completely dissolve them to obtain an anti-nasal allergy gel mother solution; S30 sterilizes the anti-nasal allergy gel mother solution by high pressure or irradiation to obtain the anti-nasal allergy gel.

3. The method for preparing an anti-nasal allergy gel according to claim 2, characterized in that: The step S20 further includes: S21: mixing the chitosan salt or chitosan derivative with the deionized water, and stirring to fully dissolve them to obtain a first mixed solution; S22: mixing the cellulose and the deionized water, and stirring to fully dissolve the cellulose, to obtain a second mixed solution; S23: mixing the remaining components with the remaining amount of the deionized water, and stirring them evenly to fully dissolve them, to obtain a third mixed solution; S24: Mix the first mixed liquid, the second mixed liquid and the third mixed liquid together, stir them evenly, and obtain the anti-nasal allergy gel mother liquid.

4. The method for preparing an anti-nasal allergy gel according to claim 2, characterized in that: In the step S20, the mixture is first heated to a temperature between room temperature and 80° C. and then stirred to fully dissolve the mixture.

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