A pharmaceutical composition for preventing and treating allergic rhinitis and use thereof

Abstract

The present application relates to a kind of pharmaceutical compositions for preventing and treating allergic rhinitis symptoms, with glycerin 1%~10%, polysorbate 80 0.1%~2%, sodium edetate 0.01%~1% and pharmaceutically acceptable carrier in composition by weight percentage.The composition of the present application scientifically screens components and proportion, can form long-lasting antibiofilm protective layer on nasal mucosa, regulate the rhinitis caused by nasal mucus secretion abnormality due to environment or disease and the like, and has the advantages of good biocompatibility, fast effect, good stability, long-acting water-locking, long-acting, no side effects and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to a pharmaceutical composition for preventing and treating allergic rhinitis, a preparation method thereof and application thereof. BACKGROUND

[0002] The nasal cavity is easily attacked by bacteria, viruses, inhaled pollutants, dust, harmful substances, etc., and causes allergic rhinitis. Allergic rhinitis (also known as anaphylactic rhinitis, AR) is a non-infectious inflammatory disease of the nasal mucosa. Allergens closely contact the skin mucosa and nasal mucosa, and cause the degranulation of mast cells through the "bridging" of IGE receptors on the surface of the mast cells, so that inflammatory factors such as histamine, leukotrienes and bradykinin are released in the local skin, mucosa or blood vessels, causing local capillary dilation, increased vascular permeability, smooth muscle contraction and increased glandular secretion. Symptoms include sneezing, clear nasal discharge, nasal congestion, nasal itching, etc., and are prone to cause nasal flora disorder and breed harmful bacteria. According to the survey data of WHO, the global prevalence rate of allergic rhinitis is as high as 11%, and the prevalence rate of allergic rhinitis in Chinese population is 10%-15%, with a total of 240 million patients. Sea salt irrigation of the nasal cavity is a common way to relieve the symptoms of allergic rhinitis. However, this method has the problems of short water locking time, the need for repeated irrigation, and the difficulty in solving the problems of multiple allergic reactions and nasal bacterial breeding. Therefore, there is an urgent need for a safe and effective pharmaceutical composition for preventing and treating the symptoms of allergic rhinitis in the clinic. SUMMARY

[0003] The present application aims to provide a pharmaceutical composition for preventing and treating the symptoms of allergic rhinitis. The composition contains 1%-10% of glycerol, 0.1%-2% of polysorbate 80, 0.01%-1% of sodium edetate and a pharmaceutically acceptable carrier by weight percentage.

[0004] In a preferred technical solution of the present application, the composition contains 1%-4.5% of glycerol, 0.1%-0.5% of polysorbate 80 and 0.01%-0.1% of sodium edetate by weight percentage.

[0005] In a preferred technical solution of the present application, the pharmaceutically acceptable carrier optionally includes any one or a combination of preservatives, osmotic pressure regulators, acid-base regulators, high molecular materials, emulsifiers, oil phases.

[0006] In a preferred technical solution of the present application, the preservative is selected from any one or a combination of polyhexamethylene biguanide, nano-silver, benzalkonium chloride, potassium sorbate, sodium benzoate, sodium dehydroacetate, calcium propionate, sodium diacetate, sodium lactate, povidone iodine, propyl paraben, nisin, and nipagin ester.

[0007] In the preferred technical solution of the present application, the composition contains 0.00001% to 0.01% of the preservative, preferably 0.00005% to 0.001% by weight.

[0008] In the preferred technical solution of the present application, the osmotic pressure regulator is selected from any one or combination of sodium chloride, glucose, sorbitol, polyethylene glycol, propylene glycol, and mannitol.

[0009] In the preferred technical solution of the present application, the osmotic pressure regulator is used in an amount to adjust the osmotic pressure of the composition to isotonicity.

[0010] In the preferred technical solution of the present application, the acid-base regulator is any one or combination of citrate buffer, acetate buffer, carbonate buffer, phosphate buffer, citric acid, potassium citrate, sodium citrate, citric acid, sodium citrate, potassium citrate, malic acid, sodium malate, potassium malate, potassium hydroxide, sodium bicarbonate, sodium hydroxide, potassium carbonate, sodium carbonate, phosphoric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, monoethanolamine, diethanolamine, triethanolamine, lactic acid, sodium lactate, potassium lactate, acetic acid, sodium acetate, potassium acetate, propionic acid, sodium propionate, potassium propionate, tartaric acid, sodium tartrate, sodium fumarate, potassium tartrate, potassium fumarate, fumaric acid, or a hydrate thereof.

[0011] In the preferred technical solution of the present application, the acid-base regulator is used in an amount to adjust the pH of the composition to 6.0-8.0, preferably 6.5-7.5.

[0012] In the preferred technical solution of the present application, the composition is a solution, which contains 1% to 10% of glycerol, 0.1% to 2% of polysorbate 80, 0.01% to 1% of sodium edetate, and 0.00001% to 2% of preservative by weight, and the pH of the composition is 6.0-8.0.

[0013] In the preferred technical solution of the present application, the composition is a solution, which contains 1% to 4.5% of glycerol, 0.1% to 1% of polysorbate 80, 0.01% to 0.1% of sodium edetate, and 0.00005% to 0.2% of preservative by weight, and the pH of the composition is 6.5-7.5.

[0014] In the preferred technical solution of the present application, the composition contains 1% of glycerol, 0.1% of polysorbate 80, 0.01% of sodium edetate, 0.9% of sodium chloride, and 5ppm of polyhexamethylene biguanide by weight, and the pH of the composition is 6.5-7.5.

[0015] In the preferred technical solution of the present application, the composition contains 3% of glycerol, 0.5% of polysorbate 80, 0.05% of sodium edetate, 0.9% of sodium chloride, 5ppm of polyhexamethylene biguanide, and the rest is water, and the pH of the composition is 6.5-7.5.

[0016] In the preferred technical solution of the present application, the composition contains 4.5% of glycerol, 0.8% of polysorbate 80, 0.08% of sodium edetate, 5% of glucose, 0.2% of potassium sorbate, and the rest is water, and the pH of the composition is 6.5-7.5.

[0017] In the preferred technical solution of the present application, the composition contains 4% of glycerol, 1% of polysorbate 80, 0.1% of sodium edetate, 5% of glucose, 0.2% of potassium sorbate, and the rest is water, and the pH of the composition is 6.5-7.5.

[0018] In the preferred technical solution of the present application, the composition contains 1.5% of glycerol, 1% of polysorbate 80, 0.1% of sodium edetate, 5% of glucose, 0.2% of potassium sorbate, and the rest is water, and the pH of the composition is 6.5-7.5.

[0019] In the preferred technical solution of the present application, the composition contains 1% of glycerol, 0.1% of polysorbate 80, 0.01% of sodium edetate, 0.9% of sodium chloride, and the rest is water, and the pH of the composition is 6.5-7.5.

[0020] In the preferred technical solution of the present application, the composition optionally contains a high molecular material.

[0021] In the preferred technical solution of the present application, the high molecular material is selected from any one or combination of starch, cellulose, alginic acid, hyaluronic acid, chitosan, collagen, poly-L-lysine, poly-L-glutamic acid, polyacrylic acid, polymethacrylic acid, polyacrylamide, and poly-N-polyacrylamide.

[0022] In the preferred technical solution of the present application, the composition contains 0.1%-5% of the high molecular material, and preferably 0.5%-2% of the high molecular material.

[0023] In the preferred technical solution of the present application, the composition is a gel, and the composition contains 1%-10% of glycerol, 0.1%-2% of polysorbate 80, 0.01%-1% of sodium edetate, 0.1%-5% of the high molecular material, and 0.00001%-2% of the preservative, and the pH of the composition is 6.0-8.0.

[0024] In the preferred technical solution of the present application, the composition is a gel, and the composition comprises 1-4.5% of glycerol, 0.1-1% of polysorbate 80, 0.01-0.1% of sodium edetate, 0.5-2% of a high molecular material and 0.00001-2% of a preservative, by weight percentage, and the pH of the composition is 6.0-8.0.

[0025] In the preferred technical solution of the present application, the composition optionally comprises any one or a combination of an oil phase and an emulsifier.

[0026] In the preferred technical solution of the present application, the oil phase is selected from any one or a combination of liquid paraffin, peanut oil, cottonseed oil, hydrogenated vegetable oil, methyl silicone oil and soybean oil.

[0027] In the preferred technical solution of the present application, the composition comprises 15-35% of the oil phase, preferably 20-30%, by weight percentage.

[0028] In the preferred technical solution of the present application, the emulsifier is selected from any one or a combination of sucrose ester, sorbitol ester, soybean phospholipid, lauric acid monoglyceride, propylene glycol fatty acid ester, sodium lauryl sulfate, sodium dodecyl sulfonate, polysorbate and sorbitan oleate.

[0029] In the preferred technical solution of the present application, the composition comprises 0.1-4% of the emulsifier, preferably 0.1-0.6%, by weight percentage.

[0030] In the preferred technical solution of the present application, the composition is an emulsion, and the composition comprises 1-10% of glycerol, 0.1-2% of polysorbate 80, 0.01-1% of sodium edetate, 15-35% of an oil phase, 0.1-4% of an emulsifier and 0.00001-2% of a preservative, by weight percentage, and the pH of the composition is 6.0-8.0.

[0031] In the preferred technical solution of the present application, the composition is an emulsion, and the composition comprises 1-4.5% of glycerol, 0.1-1% of polysorbate 80, 0.01-0.1% of sodium edetate, 20-25% of an oil phase, 0.1-1% of an emulsifier and 0.00001-2% of a preservative, by weight percentage, and the pH of the composition is 6.0-8.0.

[0032] In the preferred technical solution of the present application, the composition comprises 4.5% of glycerol, 0.9% of polysorbate 80, 0.02% of sodium edetate, 1.5% of hydroxypropyl methyl cellulose and 0.21% of nano-silver, by weight percentage, and the pH of the composition is 6.0-8.0.

[0033] In the preferred technical solution of the present application, the composition contains glycerin 3.5%, polysorbate 80 0.6%, sodium edetate 0.1%, mannitol 2.1%, polyacrylamide 2.0%, streptococcal 0.25%, and the balance is water, in percentage by weight; and the pH of the composition is 6.0-8.0.

[0034] In the preferred technical solution of the present application, the composition contains glycerin 1.0%, polysorbate 80 0.6%, sodium edetate 0.08%, liquid paraffin 25%, sodium dodecyl sulfonate 0.5%, glucose 3.05%, polyhexamethylene biguanide 1.6ppm, and the balance is water, in percentage by weight; and the pH of the composition is 6.0-8.0.

[0035] In the preferred technical solution of the present application, the composition contains glycerin 1.5%, polysorbate 80 0.6%, sodium edetate 0.04%, cottonseed oil 26%, lauric acid monoglyceride 0.55%, polyhexamethylene biguanide 1.4ppm, and the balance is water, in percentage by weight; and the pH of the composition is 6.0-8.0.

[0036] Another object of the present application is to provide a preparation method of a pharmaceutical composition for preventing and treating allergic rhinitis, which contains glycerin 1%-10%, polysorbate 80 0.1%-2%, sodium edetate 0.01%-1%, and a pharmaceutically acceptable carrier, in percentage by weight, and the preparation method comprises the following steps: weighing the required amount of glycerin, polysorbate 80, sodium edetate, and the pharmaceutically acceptable carrier, dissolving them in water, and filtering, thereby obtaining the composition, wherein the composition is a solution.

[0037] In the preferred technical solution of the present application, the filtering is sequentially through 0.45um and 0.22um filter membranes.

[0038] Another object of the present application is to provide a preparation method of the pharmaceutical composition for preventing and treating allergic rhinitis symptoms according to the present application, and the preparation method of the composition is:

[0039] (1) swelling the required amount of high molecular material in the appropriate amount of water to obtain a gel solution;

[0040] (2) mixing glycerin, polysorbate 80, sodium edetate, and other pharmaceutically acceptable carriers except the high molecular material in the appropriate amount of water, mixing them again with the gel solution, adding the balance of water, and vacuuming for 30 minutes under the condition that the vacuum degree is not higher than -50Kpa, thereby obtaining the composition.

[0041] In the preferred technical solution of the present application, the high molecular material is selected from any one or combination of starch, cellulose, alginic acid, hyaluronic acid, chitosan, collagen, poly-L-lysine, poly-L-glutamic acid, polyacrylic acid, polymethacrylic acid, polyacrylamide, and poly-N-polyacrylamide.

[0042] In the preferred technical solution of the present application, the composition contains 0.1% to 5% of the high molecular material, preferably 0.5% to 2% by weight.

[0043] In the preferred technical solution of the present application, the composition contains 1% to 10% of glycerol, 0.1% to 2% of polysorbate 80, 0.01% to 1% of sodium edetate, 0.1% to 5% of the high molecular material and 0.00001% to 2% of the preservative by weight, and the composition has a pH of 6.0 to 8.0.

[0044] In the preferred technical solution of the present application, the composition contains 1% to 4.5% of glycerol, 0.1% to 1% of polysorbate 80, 0.01% to 0.1% of sodium edetate, 0.5% to 2% of the high molecular material and 0.00001% to 2% of the preservative by weight, and the composition has a pH of 6.0 to 8.0.

[0045] Another object of the present application is to provide a preparation method of the pharmaceutical composition for preventing and treating allergic rhinitis, which is an emulsion, and the preparation method comprises the following steps:

[0046] (1) adding glycerol, polysorbate 80, sodium edetate, an emulsifier and a pharmaceutically acceptable carrier into water, stirring and mixing uniformly, and heating to 50-60℃ to obtain an aqueous phase;

[0047] (2) heating the oil phase to 50-60℃, adding it into the aqueous phase, and homogenously emulsifying at 1500-2500 rpm for 30-60 min to obtain the emulsion.

[0048] In the preferred technical solution of the present application, the oil phase is selected from any one or combination of liquid paraffin, peanut oil, cottonseed oil, hydrogenated vegetable oil, methyl silicone oil and soybean oil.

[0049] In the preferred technical solution of the present application, the composition contains 15% to 35% of the oil phase by weight, preferably 20% to 30%.

[0050] In the preferred technical solution of the present application, the emulsifier is selected from any one or combination of sucrose ester, sorbitol ester, soybean phospholipid, lauric acid monoglyceride, propylene glycol fatty acid ester, sodium dodecyl sulfate, sodium dodecyl sulfonate, polysorbate and sorbitan oleate.

[0051] In the preferred technical solution of the present application, the composition contains 0.1% to 4% of the emulsifier by weight, preferably 0.1% to 0.6%.

[0052] In the preferred technical solution of the present application, the composition contains 1-10% of glycerin, 0.1-2% of polysorbate 80, 0.01-1% of sodium edetate, 15-35% of oil phase, 0.1-4% of emulsifier and 0.00001-2% of preservative, and the pH of the composition is 6.0-8.0.

[0053] In the preferred technical solution of the present application, the composition contains 1-4.5% of glycerin, 0.1-1% of polysorbate 80, 0.01-0.1% of sodium edetate, 20-25% of oil phase, 0.1-1% of emulsifier and 0.00001-2% of preservative, and the pH of the composition is 6.0-8.0.

[0054] Another object of the present application is to provide the use of the pharmaceutical composition for preventing or treating allergic rhinitis according to the present application in the preparation of a product for preventing or treating any one of allergic rhinitis, sinusitis, chronic rhinitis and acute rhinitis.

[0055] Another object of the present application is to provide the use of a pharmaceutical composition for preventing or alleviating the symptoms of allergic rhinitis in the preparation of a product for preventing or treating any one of nasal congestion, nasal dryness, discomfort caused by the intervention of nasal surgery instruments and nasal allergy or a combination thereof.

[0056] The present application aims to provide the use of the pharmaceutical composition for preventing or alleviating the symptoms of allergic rhinitis according to the present application in the preparation of a product for regulating the viscosity of nasal mucus, wherein 2-5 ml of the composition is applied to the nasal cavity to regulate the viscosity of the nasal mucus to 500 mPa.s-25000 mPa.s.

[0057] In the preferred technical solution of the present application, the regulation of the viscosity of the nasal mucus is any one of increasing the viscosity of the dry nasal cavity to achieve nasal moistening and reducing the viscosity of the nasal mucus to alleviate nasal congestion.

[0058] Unless otherwise specified, the percentage referred to in the present application between liquids is volume / volume percentage; the percentage referred to in the present application between a liquid and a solid is volume / weight percentage; the percentage referred to in the present application between a solid and a liquid is weight / volume percentage; and the rest is weight / weight percentage.

[0059] Compared with the prior art, the present application has the following beneficial technical effects:

[0060] 1. The pharmaceutical composition of the present invention uses scientifically screened components and proportions. The composition can form a long-lasting anti-biofilm protective layer on the nasal mucosa and has the advantages of rapid onset of action, good biocompatibility, good stability, long-lasting water retention, long duration of action, safety and effectiveness, and no side effects. It can also bidirectionally regulate abnormal nasal mucus secretion caused by environmental factors or diseases. When excessive nasal mucus secretion causes discomfort symptoms such as nasal congestion and nasal mucosal swelling, it can quickly reduce the viscosity of nasal mucus, thin the mucus, and promote mucus discharge. When insufficient nasal mucus secretion causes discomfort symptoms such as nasal dryness and nosebleeds, it can quickly increase the viscosity of nasal mucus, moisturize the nasal mucosa, lock in moisture for a long time, reduce the abnormal proliferation of harmful bacteria in the patient's nasal cavity, and relieve nasal allergy symptoms.

[0061] 2. The preparation method of the composition of the present invention has the characteristics of simple operation, mild reaction, short production cycle, high yield, green and environmentally friendly, better cost, and suitable for industrial production. Attached Figure Description

[0062] Figure 1 Comparison of TEWL levels among groups in Experiment Example 1;

[0063] Figure 2 shows the comparison of harmful bacterial diversity in each group in Experiment Example 3. Figure (a) shows the difference in Simpson index before and after rinsing, Figure (b) shows the difference in Shannon index before and after rinsing, and Figure (c) shows the difference in error between Simpson index and Shannon index before and after rinsing.

[0064] Figure 3 Comparison of allergic reactions among the groups in Experiment Example 3. Detailed Implementation

[0065] The present invention will be described in detail below with reference to specific embodiments. These embodiments are merely illustrative of the technical solutions of the present invention and are not intended to limit the scope of the invention.

[0066] Example 1: Preparation of the composition of the present invention

[0067] The composition of the 100g pharmaceutical composition of the present invention is as follows:

[0068]

[0069] The preparation of the pharmaceutical composition of the present invention includes the following steps:

[0070] Weigh out the required amounts of glycerol, polysorbate 80, sodium edetate, sodium chloride, and polyhexamethylene biguanide. Dissolve them in water under stirring conditions, add water, and bring the volume to 100 ml. Filter the resulting solution through 0.45 μm and 0.22 μm filter membranes in sequence to obtain the final product.

[0071] Example 2: Preparation of the composition of the present invention

[0072] The composition of 100g of the pharmaceutical composition of the present application is as follows:

[0073]

[0074] The preparation of the pharmaceutical composition of the present application comprises the following steps:

[0075] The required amount of glycerin, polysorbate 80, sodium edetate, sodium chloride and potassium sorbate is weighed, and dissolved in water under stirring, water is added, and the volume is made up to 100ml. The resulting solution is filtered through 0.45um and 0.22um filter membranes in sequence, and the product is obtained.

[0076] Preparation of the composition of the present application in Example 3

[0077] The composition of 100g of the pharmaceutical composition of the present application is as follows:

[0078]

[0079] The preparation of the pharmaceutical composition of the present application comprises the following steps:

[0080] The required amount of glycerin, polysorbate 80, sodium edetate, sodium chloride and potassium sorbate is weighed, and dissolved in water under stirring, water is added, and the volume is made up to 100ml. The resulting solution is filtered through 0.45um and 0.22um filter membranes in sequence, and the product is obtained.

[0081] Preparation of the composition of the present application in Example 4

[0082] The composition of 100g of the pharmaceutical composition of the present application is as follows:

[0083]

[0084] The preparation of the pharmaceutical composition of the present application comprises the following steps:

[0085] The required amount of glycerin, polysorbate 80, sodium edetate, sodium chloride and polyhexamethylene biguanide is weighed, and dissolved in water under stirring, water is added, and the volume is made up to 100ml. The resulting solution is filtered through 0.45um and 0.22um filter membranes in sequence, and the product is obtained.

[0086] Example 5

[0087] The composition of 100g of the pharmaceutical composition of the present application is as follows:

[0088]

[0089] The preparation of the pharmaceutical composition of the present application comprises the following steps:

[0090] The required amount of glycerin, polysorbate 80, sodium edetate, glucose and potassium sorbate is weighed, dissolved in water under stirring, water is added, and the volume is made up to 100 ml. The resulting solution is filtered through 0.45 um and 0.22 um filter membranes in sequence, and the filtrate is obtained.

[0091] Example 6

[0092] The composition of 100 g of the pharmaceutical composition of the present application is as follows:

[0093]

[0094] The preparation of the pharmaceutical composition of the present application comprises the following steps:

[0095] The required amount of glycerin, polysorbate 80, sodium edetate, glucose and potassium sorbate is weighed, dissolved in water under stirring, water is added, and the volume is made up to 100 ml. The resulting solution is filtered through 0.45 um and 0.22 um filter membranes in sequence, and the filtrate is obtained.

[0096] Example 7

[0097] The composition of 100 g of the pharmaceutical composition of the present application is as follows:

[0098]

[0099] The preparation of the pharmaceutical composition of the present application comprises the following steps:

[0100] The required amount of glycerin, polysorbate 80, sodium edetate, glucose and potassium sorbate is weighed, dissolved in water under stirring, water is added, and the volume is made up to 100 ml. The resulting solution is filtered through 0.45 um and 0.22 um filter membranes in sequence, and the filtrate is obtained.

[0101] Example 8

[0102] The composition of 100 g of the pharmaceutical composition of the present application is as follows:

[0103]

[0104] The preparation of the pharmaceutical composition of the present application comprises the following steps:

[0105] The required amount of glycerin, polysorbate 80, sodium edetate, glucose and potassium sorbate is weighed, dissolved in water under stirring, water is added, and the volume is made up to 100 ml. The resulting solution is filtered through 0.45 um and 0.22 um filter membranes in sequence, and the filtrate is obtained.

[0106] Example 1 Study on the effect of the composition of the present application on the degree of water loss (TEWL) of nasal mucosa

[0107] Test 50 Bama miniature pigs (30 males and 20 females) weighing 15-25 kg were selected. The experimental pigs had no recent medication history, no nasal cavity organic lesions and no upper respiratory tract infection. The test animals were randomly divided into five groups according to the male to female ratio, 10 in each group. Test group 1 sprayed the composition of Example 1, test group 2 sprayed the composition of Example 2, test group 3 sprayed the composition of Example 3, the blank group sprayed normal saline, and the positive control group sprayed B-HA hyaluronic acid spray. Each test animal was sprayed with 100 μL each time, once a day.

[0108] Before the test, the test pigs were placed in a (21℃, 45% RH) condition for 15 min. Using an Eppendorf pipette, 100 μL of the test product was sprayed on the mucosa surface of the lower turbinate of each test pig according to the grouping. After 5 minutes, the effect of the test product on the water loss degree (TEWL) of the nasal mucosa of the test animals was detected and analyzed. The TEWL of the test animals was detected by a closed chamber device, and each test was performed in triplicate (expressed as g / m 2 / h), and each measurement was 3 min. The data were analyzed using V6.0 software. The results are shown in Table 1. Figure 1 Compared with the positive control group, test groups 1-3 had significant differences (p<0.05), and compared with test groups 2-3, test group 1 had significant differences (p<0.05). It shows that the pharmaceutical composition of the present application can effectively prevent the loss of water from the nasal mucosa, has the effects of long-acting water reduction and moisturizing the nasal cavity, and relieving the discomfort symptoms caused by nasal dryness.

[0109] Test Example 2 Inhibitory effect of the composition of the present application on microbial growth

[0110] 100 Bama miniature pigs (60 males and 40 females) weighing 15-25 kg were selected. The experimental pigs had no recent medication history, were infected with acute rhinitis, and had clear nasal discharge, sneezing, 2-3 days of grayish white viscous liquid, rapid abdominal breathing, nasal cavity filled with yellow viscous or blood-streaked nasal fluid around the nostrils, and blood scabs. The test animals were randomly divided into five groups, test group 1 sprayed the composition of Example 1, test group 2 sprayed the composition of Example 2, test group 3 sprayed the composition of Example 3, the blank group sprayed normal saline, and the positive control group sprayed a biological chitosan quaternary ammonium salt medical nasal cavity repair liquid dressing.

[0111] Culture of secretions: The nasal cavity mucosa surface secretions of all sick pigs were collected on the same day, and a sterile cotton swab was used to rotate 2 weeks and a half on the lateral side of the middle turbinate of the sick pigs, i.e. in the middle nasal meatus, to collect the surface flora. During the sampling process, the nasal cavity side wall and the nasal vestibule were avoided to be contacted, and the obtained specimen tube was prepared in an Ep tube for standby.

[0112] ​Bacterial flora analysis: The total DNA of the sample bacterial flora was extracted using a rapid DNA extraction detection kit, and 16S rRNA sequencing was performed for bacterial flora identification. Uparse software was used to cluster the obtained raw sequences according to 97% sequence similarity. Mothur software was used to analyze the bacterial flora alpha diversity; the microbial colony composition of the two groups of samples was analyzed using multiple sample comparison analysis (beta diversity); the Emperor software was used to draw a principal coordinate analysis graph to determine the differences in community structure between groups; linear discriminant coupling effect analysis was used to further find the bacterial genera with significant differences between samples, and linear discriminant analysis was used to evaluate the size of the effect of the species abundance of each group.

[0113] BF qualitative and quantitative determination: The preserved bacteria were inoculated in trypticase soy broth medium for enrichment, and when the concentration was adjusted to 0.5 McFarland unit, they were inoculated in a 96-well plate and cultured in a 37°C constant temperature incubator for 24h, then washed with PBS for 3 times, fixed with methanol, added with glacial acetic acid, and the absorbance was determined at 590mm wavelength using an enzyme-labeled instrument.

[0114] Film-producing ability result determination: the A value of each test strain was the average value of its A 590 value minus the A 590 value of the blank control group well, and the A value of the standard strain and 3 times the standard deviation were used as the boundary value Ac, and the A value of the test strain > Ac was determined to have film-producing ability, that is, BF positive. Each strain was made into 3 duplicate wells.

[0115] The test data were processed and analyzed using SPSS 20.0 software. Count data was expressed as examples (n), and X 2 test was used for comparison between groups. Measurement data was expressed as (X ± S), and t test was used for comparison between groups. The test level α = 0.05. The results are shown in FIG. 2(a), FIG. 2(b), and FIG. 2(c). There was a significant difference in the positive control group before and after washing, p < 0.05; there was a significant difference in test groups 1-3 before and after washing, p < 0.05; and there was a significant difference between test groups 1-3 and the positive control group, p < 0.05. It shows that the composition of the application can effectively reduce the diversity of harmful bacterial flora (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus warneri, Pseudomonas aeruginosa) in the nasal mucosa, significantly inhibit the abnormal proliferation of harmful bacteria, and prevent pathogenic bacteria from forming bacterial biofilm.

[0116] Example 3: Anti-allergy test of the composition of the application on animal nasal mucosa

[0117] 58 healthy guinea pigs with body weight of 236-425 g and age of 2-3 months, including 30 females and 28 males, were raised under the condition of 24-29℃. The 58 guinea pigs were scored for health, and the guinea pigs with similar scores were selected and randomly divided into 5 groups according to the score results, 12 guinea pigs in the first 4 groups, half male and half female; 10 guinea pigs in the 5th group, 4 males and 6 females.

[0118] The animals were modeled for allergic rhinitis. The modeling method was as follows: 10% olive oil solution was dropped into the bilateral anterior nares of the guinea pigs (5ul per side) by using a micropipette, once a day, for 5 days, then every other day for 19 days (maintaining the administration period), for a total of 24 days. The blank group was given normal saline for nasal drops (5ul per side), once a day, until the end of the test. The model was determined as follows: the nasal symptoms and signs were the main observation contents. From the start of administration, the severity, frequency, time length of nasal itching, sneezing and rhinorrhea were scored and recorded according to the scoring criteria in Table 1.

[0119] Table 1: Allergic reaction behavior score table

[0120]

[0121] After the allergic rhinitis model was established, the test group 1 was sprayed with the composition of Example 1, the test group 2 was sprayed with the composition of Example 2, the test group 3 was sprayed with the composition of Example 3, the blank group was sprayed with normal saline, and the positive control group was sprayed with Binuo nasal spray (containing 1.1 mg of triamcinolone acetonide per 1 ml). The test groups 1-3 were added with samples in the nostrils 3 times a day, 5ul per nostril each time; the positive control group was given Binuo nasal spray 2 times a day, 5ul per nostril each time; the blank group was only given normal saline 5ul in the nostrils 2 times a day. The animals in each test group were continuously administered for 2 weeks.

[0122] Observation items and methods: the symptom integral superposition scoring method (see the model determination scoring table) was used to compare the differences between groups. The measurement data was represented by t, and the significance of the difference between the means of each group was tested by t test using SPSS software. The results are shown in Figure 3 Compared with the positive control group, the test groups 1-3 had significant differences (p<0.05). Compared with the test groups 2-3, the test group 1 had significant differences (p<0.05). It is shown that the pharmaceutical composition of the present application has obvious therapeutic effect on sneezing, nasal itching and clear rhinorrhea of allergic rhinitis, and is superior to the curative effect of triamcinolone acetonide.

[0123] The above description of the specific embodiments of the present application does not limit the present application, and various changes or modifications can be made to the present application by those skilled in the art without departing from the spirit of the present application, which shall fall within the scope of protection of the claims of the present application.

Claims

1. A pharmaceutical composition for preventing allergic rhinitis symptoms, comprising, in weight percent, 1-4.5% glycerin, 0.1-0.5% polysorbate 80, 0.01-0.1% sodium edetate, and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable carrier is a combination of 0.00001-0.01% preservative and an osmotic pressure regulator.

3. The pharmaceutical composition of claim 2, wherein the preservative is selected from the group consisting of polyhexamethylene biguanide, nano silver, benzalkonium chloride, potassium sorbate, sodium benzoate, sodium dehydroacetate, calcium propionate, sodium diacetate, sodium lactate, povidone iodine, propyl paraben, nisin, nipagin, or a combination thereof.

4. The pharmaceutical composition of claim 2, wherein the preservative is contained in an amount of 0.00005-0.001% by weight percent.

5. The pharmaceutical composition of claim 1, wherein the composition has a pH of 6.0-8.

0.

6. The pharmaceutical composition of claim 5, wherein the composition has a pH of 6.5-7.

5.

7. The pharmaceutical composition of claim 2, wherein the osmotic pressure regulator is selected from the group consisting of sodium chloride, dextrose, sorbitol, polyethylene glycol, propylene glycol, mannitol, or a combination thereof.

8. The pharmaceutical composition of claim 2, wherein the composition is isotonic.

9. The pharmaceutical composition of claim 1, comprising, in weight percent, 1-10% glycerin, 0.1-2% polysorbate 80, 0.01-1% sodium edetate, and 0.00001-2% preservative, and the composition is a solution having a pH of 6.0-8.

0.

10. The pharmaceutical composition of claim 9, comprising, in weight percent, 1-4.5% glycerin, 0.1-1% polysorbate 80, 0.01-0.1% sodium edetate, and 0.00005-0.2% preservative, and the composition is a solution having a pH of 6.5-7.

5.

11. The pharmaceutical composition of claim 1, comprising, in weight percent, 1% glycerin, 0.1% polysorbate 80, 0.01% sodium edetate, 0.9% sodium chloride, 5 ppm polyhexamethylene biguanide, and the balance being water.

12. The pharmaceutical composition of claim 1, comprising, in weight percent, 3% glycerin, 0.5% polysorbate 80, 0.05% sodium edetate, 0.9% sodium chloride, 5 ppm polyhexamethylene biguanide, and the balance being water.

13. The pharmaceutical composition of claim 1, comprising, in weight percent, 4.5% glycerin, 0.8% polysorbate 80, 0.08% sodium edetate, 5% dextrose, 0.2% potassium sorbate, and the balance being water.

14. The pharmaceutical composition of claim 1, comprising glycerin 4%, polysorbate 80 1%, sodium edetate 0.1%, glucose 5%, potassium sorbate 0.2% by weight percentage, and the balance being water.

15. The pharmaceutical composition of claim 1, comprising glycerin 1.5%, polysorbate 80 1%, sodium edetate 0.1%, glucose 5%, potassium sorbate 0.2% by weight percentage, and the balance being water.

16. The pharmaceutical composition of claim 1, comprising glycerin 1%, polysorbate 80 0.1%, sodium edetate 0.01%, sodium chloride 0.9% by weight percentage, and the balance being water.

17. The pharmaceutical composition of claim 1, optionally comprising a high molecular material.

18. The pharmaceutical composition of claim 17, wherein the high molecular material is selected from any one or a combination of starch, cellulose, alginic acid, hyaluronic acid, chitosan, collagen, poly-L-lysine, poly-L-glutamic acid, polyacrylic acid, polymethacrylic acid, polyacrylamide, and poly-N-polyacrylamide.

19. The pharmaceutical composition of claim 17, comprising the high molecular material 0.1%-5% by weight percentage.

20. The pharmaceutical composition of claim 19, comprising the high molecular material 0.5%-2% by weight percentage.

21. The pharmaceutical composition of any one of claims 17-20, wherein the composition is a gel comprising 1%-10% glycerin, 0.1%-2% polysorbate 80, 0.01%-1% sodium edetate, 0.1%-5% high molecular material, and 0.00001%-2% preservative by weight percentage, and the composition has a pH of 6.0-8.

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22. The pharmaceutical composition of claim 21, wherein the composition is a gel comprising 1%-4.5% glycerin, 0.1%-1% polysorbate 80, 0.01%-0.1% sodium edetate, 0.5%-2% high molecular material, and 0.00001%-2% preservative by weight percentage, and the composition has a pH of 6.0-8.

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23. The pharmaceutical composition of claim 21, comprising glycerin 3.5%, polysorbate 80 0.6%, sodium edetate 0.1%, mannitol 2.1%, polyacrylamide 2.0%, nisin 0.25%, and the balance being water by weight percentage, and the composition has a pH of 6.0-8.

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24. The pharmaceutical composition of claim 21, comprising glycerin 4.5%, polysorbate 80 0.9%, sodium edetate 0.02%, hydroxypropyl methyl cellulose 1.5%, nano-silver 0.21%, and the balance being water by weight percentage, and the composition has an osmotic pressure of 280-320 mmol / L, and the composition has a pH of 6.0-8.

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25. The pharmaceutical composition of claim 1, optionally comprising any one or a combination of an oil phase and an emulsifier.

26. The pharmaceutical composition as claimed in claim 25, wherein the oil phase is selected from any one of liquid paraffin, peanut oil, cottonseed oil, hydrogenated vegetable oil, methyl silicone oil, soybean oil or a combination thereof.

27. The pharmaceutical composition as claimed in claim 25, wherein the composition comprises the oil phase in an amount of 15-35% by weight.

28. The pharmaceutical composition as claimed in claim 27, wherein the composition comprises the oil phase in an amount of 20-30% by weight.

29. The pharmaceutical composition as claimed in claim 25, wherein the emulsifier is selected from any one of sucrose ester, sorbitol ester, soybean phospholipid, lauric acid monoglyceride, propylene glycol fatty acid ester, sodium dodecyl sulfate, sodium dodecyl sulfonate, polysorbate, sorbitan oleate or a combination thereof.

30. The pharmaceutical composition as claimed in claim 29, wherein the composition comprises the emulsifier in an amount of 0.1-4% by weight.

31. The pharmaceutical composition as claimed in claim 30, wherein the composition comprises the emulsifier in an amount of 0.1-0.6% by weight.

32. The pharmaceutical composition as claimed in any one of claims 25-31, wherein the composition is an emulsion comprising 1-10% of glycerin, 0.1-2% of polysorbate 80, 0.01-1% of sodium edetate, 15-35% of the oil phase, 0.1-4% of the emulsifier and 0.00001-2% of the preservative, and the composition has a pH of 6.0-8.

0.

33. The pharmaceutical composition as claimed in claim 32, wherein the composition is an emulsion comprising 1-4.5% of glycerin, 0.1-1% of polysorbate 80, 0.01-0.1% of sodium edetate, 20-25% of the oil phase, 0.1-1% of the emulsifier and 0.00001-2% of the preservative, and the composition has a pH of 6.0-8.

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34. The pharmaceutical composition as claimed in claim 33, wherein the composition comprises glycerin 1.0%, polysorbate 80 0.6%, sodium edetate 0.08%, liquid paraffin 25%, sodium dodecyl sulfonate 0.5%, glucose 3.05%, polyhexamethylene biguanide 1.6 ppm, and the balance is water, and the composition has a pH of 6.0-8.

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35. The pharmaceutical composition as claimed in claim 33, wherein the composition comprises glycerin 1.5%, polysorbate 80 0.6%, sodium edetate 0.04%, cottonseed oil 26%, lauric acid monoglyceride 0.55%, polyhexamethylene biguanide 1.4 ppm, and the balance is water, and the composition has a pH of 6.0-8.

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36. A method for preparing the pharmaceutical composition as claimed in any one of claims 1-16, wherein the composition is prepared from 1-10% of glycerin, 0.1-2% of polysorbate 80, 0.01-1% of sodium edetate and a pharmaceutically acceptable carrier, and the preparation of the composition comprises the steps of dissolving the required amounts of glycerin, polysorbate 80, sodium edetate and the pharmaceutically acceptable carrier in water, and filtering.

37. The preparation method of claim 36, wherein the filtration is sequentially through 0.45 um and 0.22 um filter membranes.

38. The preparation method of the pharmaceutical composition of any one of claims 17-24, wherein the composition is a gel, and the preparation method comprises the following steps: (1) swelling a desired amount of the high molecular material in an appropriate amount of water to obtain a gel solution; (2) mixing glycerol, polysorbate 80, sodium edetate, and other pharmaceutically acceptable carriers except the high molecular material in water, and then mixing with the gel solution, adding the remaining amount of water, and vacuuming at a vacuum degree of not higher than -50 KPa for 30 minutes to obtain the gel.

39. The preparation method of the pharmaceutical composition of any one of claims 25-35, wherein the composition is an emulsion, and the preparation method comprises the following steps: (1) adding glycerol, polysorbate 80, sodium edetate, an emulsifying agent, and other pharmaceutically acceptable carriers into water, stirring and mixing uniformly, and heating to 50-60 °C to obtain an aqueous phase; (2) heating an oil phase to 50-60 °C, adding to the aqueous phase, and homogenously emulsifying at 1500-2500 rpm for 30-60 min to obtain the emulsion.

40. Use of the pharmaceutical composition of any one of claims 1-35 for preparing a product for preventing and treating a nasal cavity disease, wherein the nasal cavity disease is selected from any one of allergic rhinitis, sinusitis, chronic rhinitis, and acute rhinitis.

41. Use of the pharmaceutical composition of any one of claims 1-35 for preparing a product for preventing and treating a nasal cavity discomfort, wherein the nasal cavity discomfort is selected from any one or a combination of nasal congestion, nasal cavity dryness, discomfort caused by nasal cavity surgical instrument intervention, and nasal cavity allergy. ​ ​ ​ ​

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