Biological combined preparation for allergic rhinitis and preparation method thereof

Abstract

The invention provides a biological combined preparation for allergic rhinitis and a preparation method of the biological combined preparation. The preparation comprises antibacterial polysaccharide, a centipeda minima extract, anti-allergic probiotics, an active polypeptide compound, sodium hyaluronate, an immunomodulator, a penetration enhancer, a biological adhesive and the like. Wherein the antibacterial polysaccharide can be selected from various natural polysaccharides; the centipeda minima extract is obtained by a specific ethanol reflux method; the antiallergic probiotics comprise lactobacillus acidophilus, lactobacillus rhamnosus and lactobacillus reuteri; the active polypeptide compound consists of thymosin, glutathione and osteogenic peptide. The preparation method comprises the following steps: sequentially mixing the components, carrying out high-pressure homogenization treatment, carrying out ultrasonic treatment, adding probiotics, stirring, intercepting with an ultrafiltration membrane, freeze-drying and the like. The preparation disclosed by the invention can form a uniform nano-scale particle suspension, so that the release rate and the absorption efficiency of the medicine are further improved, and an efficient, safe and convenient novel method is provided for treating the allergic rhinitis.

Description

Technical Field

[0001] The present invention relates to the technical field of nasal preparations, and in particular to a biological combination preparation for allergic rhinitis and a preparation method thereof. Background Art

[0002] Allergic rhinitis is a common nasal disease. It refers to a non-infectious inflammatory disease of the nasal mucosa, which is mainly caused by the release of IgE-mediated mediators (mainly histamine) after atopic individuals come into contact with allergens (allergens), and involves a variety of immune-active cells and cytokines. Its incidence rate has been increasing year by year worldwide, seriously affecting the quality of life of patients. At present, there are many drugs on the market for the treatment of allergic rhinitis, including antihistamines, nasal glucocorticoids, etc. However, these drugs often have deficiencies in the absorption and bioavailability of the nasal mucosa, resulting in limited therapeutic effects and may be accompanied by certain side effects.

[0003] The nasal mucosa is an important gateway for drugs to enter the body, and its absorption performance directly affects the efficacy of the drugs. Many existing allergic rhinitis treatment drugs are difficult to effectively penetrate the nasal mucosal barrier due to factors such as molecular structure, physical properties or formulation form, resulting in a short retention time of the drug in the nasal cavity and low absorption efficiency. This not only limits the efficacy of the drug, but may also increase the dosage and frequency of medication, thereby increasing the economic burden and medication risks of patients.

[0004] In addition, the physiological structure of the nasal mucosa is complex, and the surface is covered with a mucus layer and a ciliary system. These physiological barriers pose additional challenges to the penetration and absorption of drugs. Traditional nasal drug delivery preparations often have difficulty overcoming these barriers, resulting in uneven distribution of drugs in the nasal cavity, making it difficult to achieve the desired therapeutic effect. Summary of the invention

[0005] In view of this, the present invention proposes a biological combination preparation for allergic rhinitis and a preparation method thereof to solve the above problems.

[0006] The technical solution of the present invention is achieved as follows: a biological combination preparation for allergic rhinitis: comprising the following raw materials in parts by weight: 20-40 parts of antibacterial polysaccharides, 13-18 parts of goosegrass extract, 5-10 parts of antiallergic probiotics, 1-4 parts of active polypeptide complexes, 1-3 parts of sodium hyaluronate, 5-15 parts of immunomodulators, 3-8 parts of penetration enhancers, and 0.5-1.2 parts of bioadhesives; the penetration enhancers are mannitol, silk fibroin, and bile salts in a mass ratio of (12-22):(5-8):(3-7), and the bioadhesives are hydroxypropyl-β-cyclodextrin, sodium carboxymethyl cellulose, and ε-polylysine in a mass ratio of (3.8-8.5):(1.2-3.0):(0.2-0.8).

[0007] Furthermore, a biological combination preparation for allergic rhinitis includes the following raw materials in parts by weight: 30 parts of antibacterial polysaccharides, 15 parts of goosegrass extract, 8 parts of antiallergic probiotics, 3 parts of active polypeptide complex, 2 parts of sodium hyaluronate, 10 parts of immunomodulator, 5 parts of penetration enhancer, and 0.8 parts of bioadhesive.

[0008] Furthermore, the antibacterial polysaccharide is selected from one or more of Astragalus polysaccharide, Poria polysaccharide, Lentinan polysaccharide, Salvia miltiorrhiza polysaccharide, Taraxacum polysaccharide, Bupleurum polysaccharide or Anemarrhena asphodeloides polysaccharide.

[0009] Furthermore, the Herba Lysimachiae extract is obtained by reflux extraction with ethanol at a mass concentration of 90-98%, a mass-to-volume ratio of 1:8-12, an extraction temperature of 60-80°C, a time of 1-3h, filtration, and reduced pressure concentration to obtain the Herba Lysimachiae extract.

[0010] Furthermore, the anti-allergic probiotics include Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri in a weight ratio of 1:(5-8):(1-3), and the viable count is ≥1×10 7 cuf / g.

[0011] Furthermore, the active polypeptide complex is thymosin, glutathione and osteogenic peptide in a mass ratio of (3-6):(1-2):(0.3-1.5), and the average molecular weight is ≤1kD.

[0012] Furthermore, the immunomodulator is selected from one or more of vitamin D3, β-glucan or lactoferrin.

[0013] Furthermore, a method for preparing a biological combination preparation for allergic rhinitis comprises the following steps:

[0014] S1. Add antibacterial polysaccharide, sphagnum melongena extract, active polypeptide complex and immunomodulator into 5-8 times of deionized water by volume, and stir evenly to form a mixed solution A;

[0015] S2, the mixed solution A is processed by a high-pressure homogenizer, and the pressure is 500-1500 bar, and the mixture is circulated for 5-10 times to form a nano-scale particle suspension for standby use;

[0016] S3, sequentially adding sodium hyaluronate, a permeation enhancer and a bioadhesive to the suspension, and mixing them uniformly by ultrasonic treatment;

[0017] S4. Add anti-allergic probiotics to the above solution, stir with a magnetic stirrer at 2-6°C for 8-12 hours, set the ultrafiltration membrane molecular weight cutoff to ≤100 kDa, adjust the pH to 6.0-7.5, and freeze-dry to obtain a biological combination preparation for allergic rhinitis.

[0018] Furthermore, the power of the ultrasonic treatment is 100-300 W, the frequency is 120-150 kHz, each cycle is 5-9 minutes, and there are 8-12 cycles in total.

[0019] Furthermore, the allergic rhinitis biological combination preparation prepared by the above preparation method is used in the prevention or treatment of allergic rhinitis.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] (1) Improving the absorbability of nasal mucosa: The biological combination preparation for allergic rhinitis of the present invention significantly improves the absorbability of nasal mucosa through the synergistic effect of multiple ingredients. Among them, the penetration enhancer is composed of mannitol, silk fibroin and bile salt in a specific proportion, which can effectively destroy the barrier of nasal mucosa and increase the permeability of drugs. Hydroxypropyl-β-cyclodextrin, sodium carboxymethyl cellulose and ε-polylysine in the bioadhesive cooperate with each other, so that the preparation can adhere tightly to the surface of nasal mucosa, prolong the residence time of the drug in the nasal cavity, and thus improve the absorption efficiency of the drug. Experimental verification shows that this preparation shows excellent cumulative absorption, release rate and transmembrane transport rate under in vitro simulated nasal environment conditions, which fully proves its significant effect on improving the absorbability of nasal mucosa.

[0022] (2) Multiple components work synergistically to exert therapeutic effects: The antibacterial polysaccharides in the preparation have a wide range of antibacterial activity and can effectively inhibit the growth of pathogens in the nasal cavity, reducing the risk of infection; anti-allergic probiotics (Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri) can regulate the immune system, reduce allergic reactions and relieve the symptoms of allergic rhinitis; immunomodulators (vitamin D3, β-glucan or lactoferrin, etc.) can enhance the body's immunity and improve the nasal resistance to allergens; the active polypeptide complex composed of thymosin, glutathione and osteogenic peptide has multiple biological activities, which helps to repair damaged nasal tissue and promote nasal health.

[0023] (3) The preparation method is scientific and reasonable: The preparation method of the present invention adopts advanced technologies such as high-pressure homogenization and ultrasonic treatment to form a nano-scale particle suspension, which increases the surface area of ​​the drug and further improves the absorbability of the drug. At the same time, stirring and freeze-drying at low temperature can maintain the activity of the probiotics and the stability of the preparation.

[0024] The allergic rhinitis biological combination preparation of the present invention has many advantages such as excellent nasal mucosal absorption, multi-component synergistic treatment, scientific and reasonable preparation method, etc., and provides a new efficient and safe option for the prevention and treatment of allergic rhinitis. DETAILED DESCRIPTION

[0025] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0026] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0027] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0028] Example 1

[0029] A biological combination preparation for allergic rhinitis, comprising the following raw materials in parts by weight: 20 parts of antibacterial polysaccharides, 13 parts of sphagnum melongena extract, 5 parts of antiallergic probiotics, 1 part of active polypeptide complex, 1 part of sodium hyaluronate, 5 parts of immunomodulator, 3 parts of penetration enhancer, and 0.5 parts of bioadhesive;

[0030] The antibacterial polysaccharide is selected from Lentinan;

[0031] The extract of the herbaceous vine is obtained by reflux extraction with ethanol at a mass concentration of 90%, a mass-to-volume ratio of 1:8, an extraction temperature of 60° C., a time of 1 h, filtration, and reduced pressure concentration to obtain the herbaceous vine extract;

[0032] The anti-allergic probiotics include Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri in a weight ratio of 1:5:1, and the number of viable bacteria is ≥1×10 7 cuf / g;

[0033] The active polypeptide complex is thymosin, glutathione and osteogenic peptide in a mass ratio of 3:1:0.3, and the average molecular weight is ≤1kD;

[0034] The immunomodulator is selected from vitamin D3;

[0035] The penetration enhancer is mannitol, silk fibroin and bile salt in a mass ratio of 12:5:3;

[0036] The bioadhesive is hydroxypropyl-β-cyclodextrin, sodium carboxymethyl cellulose and ε-polylysine in a mass ratio of 3.8:1.2:0.2.

[0037] Example 2

[0038] A biological combination preparation for allergic rhinitis, comprising the following raw materials in parts by weight: 40 parts of astragalus polysaccharide, 18 parts of scutellaria baicalensis extract, 10 parts of anti-allergic probiotics, 4 parts of active polypeptide complex, 3 parts of sodium hyaluronate, 15 parts of immunomodulator, 8 parts of penetration enhancer, and 1.2 parts of bioadhesive;

[0039] The antibacterial polysaccharide is selected from astragalus polysaccharide;

[0040] The extract of the herbaceous vine is obtained by reflux extraction with ethanol at a mass concentration of 98%, a mass-to-volume ratio of 1:12, an extraction temperature of 80° C., a time of 3 hours, filtration, and reduced pressure concentration to obtain the herbaceous vine extract;

[0041] The anti-allergic probiotics include Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri in a weight ratio of 1:8:3, and the number of viable bacteria is ≥1×10 7 cuf / g;

[0042] The active polypeptide complex is thymosin, glutathione and osteogenic peptide in a mass ratio of 6:2:1.5, and the average molecular weight is ≤1kD;

[0043] The immunomodulator is selected from β-glucan;

[0044] The penetration enhancer is mannitol, silk fibroin and bile salt in a mass ratio of 22:8:7;

[0045] The bioadhesive is hydroxypropyl-β-cyclodextrin, sodium carboxymethyl cellulose and ε-polylysine in a mass ratio of 8.5:3.0:0.8.

[0046] Example 3

[0047] A biological combination preparation for allergic rhinitis, comprising the following raw materials in parts by weight: 30 parts of antibacterial polysaccharides, 15 parts of scutellaria baicalensis extract, 8 parts of antiallergic probiotics, 3 parts of active polypeptide complex, 2 parts of sodium hyaluronate, 10 parts of immunomodulator, 5 parts of penetration enhancer, and 0.8 parts of bioadhesive;

[0048] The antibacterial polysaccharide is selected from pachymaran;

[0049] The extract of the herbaceous vine is obtained by reflux extraction with ethanol at a mass concentration of 95%, a mass-to-volume ratio of 1:10, an extraction temperature of 70° C., a time of 2 h, filtration, and reduced pressure concentration to obtain the herbaceous vine extract;

[0050] The anti-allergic probiotics include Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri in a weight ratio of 1:6:2, and the number of viable bacteria is ≥1×10 7 cuf / g;

[0051] The active polypeptide complex is thymosin, glutathione and osteogenic peptide in a mass ratio of 5:1:0.9, and the average molecular weight is ≤1kD;

[0052] The immunomodulator is selected from β-glucan;

[0053] The penetration enhancer is mannitol, silk fibroin and bile salt in a mass ratio of 17:7:5;

[0054] The bioadhesive is hydroxypropyl-β-cyclodextrin, sodium carboxymethylcellulose and ε-polylysine in a mass ratio of 5.5:2.5:0.5;

[0055] The above examples 1-3 adopt the following preparation method:

[0056] S1. Add antibacterial polysaccharide, sphagnum melongena extract, active polypeptide complex and immunomodulator into 7 volumes of deionized water, and stir to form a mixed solution A;

[0057] S2, the mixed solution A is processed by a high-pressure homogenizer, and the pressure is 1000 bar and circulated 8 times to form a nano-scale particle suspension for standby use;

[0058] S3, sequentially adding sodium hyaluronate, permeation enhancer and bioadhesive to the suspension, and using ultrasonic treatment to mix them evenly, the power of ultrasonic treatment is 200 W, the frequency is 140 kHz, each cycle is 7 minutes, and there are 10 cycles in total;

[0059] S4. Add anti-allergic probiotics to the above solution, stir with a magnetic stirrer at 4°C for 10 hours, set the ultrafiltration membrane molecular weight cutoff to ≤100 kDa, adjust the pH to 7.0, and freeze-dry to obtain a biological combination preparation for allergic rhinitis.

[0060] Example 4

[0061] A biological combination preparation for allergic rhinitis, comprising the following raw materials in parts by weight: 30 parts of antibacterial polysaccharides, 15 parts of scutellaria baicalensis extract, 8 parts of antiallergic probiotics, 3 parts of active polypeptide complex, 2 parts of sodium hyaluronate, 10 parts of immunomodulator, 5 parts of penetration enhancer, and 0.8 parts of bioadhesive;

[0062] The antibacterial polysaccharide is selected from pachymaran;

[0063] The extract of the herbaceous vine is obtained by reflux extraction with ethanol at a mass concentration of 95%, a mass-to-volume ratio of 1:10, an extraction temperature of 70° C., a time of 2 h, filtration, and reduced pressure concentration to obtain the herbaceous vine extract;

[0064] The anti-allergic probiotics include Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri in a weight ratio of 1:6:2, and the number of viable bacteria is ≥1×10 7 cuf / g;

[0065] The active polypeptide complex is thymosin, glutathione and osteogenic peptide in a mass ratio of 5:1:0.9, and the average molecular weight is ≤1kD;

[0066] The immunomodulator is selected from β-glucan;

[0067] The penetration enhancer is mannitol, silk fibroin and bile salt in a mass ratio of 17:7:5;

[0068] The bioadhesive is hydroxypropyl-β-cyclodextrin, sodium carboxymethylcellulose and ε-polylysine in a mass ratio of 5.5:2.5:0.5;

[0069] The above-mentioned Example 4 adopts the following preparation method:

[0070] S1. Add antibacterial polysaccharide, sphagnum melongena extract, active polypeptide complex and immunomodulator into 5 volumes of deionized water, and stir to form a mixed solution A;

[0071] S2, the mixed solution A is processed by a high-pressure homogenizer, and the pressure is 500 bar and circulated for 5 times to form a nano-scale particle suspension for standby use;

[0072] S3, sequentially adding sodium hyaluronate, permeation enhancer and bioadhesive to the suspension, and using ultrasonic treatment to mix them evenly, the ultrasonic treatment power is 100 W, the frequency is 120 kHz, each cycle is 5 min, and there are 8 cycles in total;

[0073] S4. Add anti-allergic probiotics to the above solution, stir with a magnetic stirrer at 2°C for 8 hours, set the ultrafiltration membrane molecular weight cutoff to ≤100 kDa, adjust the pH to 6.0, and freeze-dry to obtain a biological combination preparation for allergic rhinitis.

[0074] Example 5

[0075] A biological combination preparation for allergic rhinitis, comprising the following raw materials in parts by weight: 30 parts of antibacterial polysaccharides, 15 parts of scutellaria baicalensis extract, 8 parts of antiallergic probiotics, 3 parts of active polypeptide complex, 2 parts of sodium hyaluronate, 10 parts of immunomodulator, 5 parts of penetration enhancer, and 0.8 parts of bioadhesive;

[0076] The antibacterial polysaccharide is selected from pachymaran;

[0077] The extract of the herbaceous vine is obtained by reflux extraction with ethanol at a mass concentration of 95%, a mass-to-volume ratio of 1:10, an extraction temperature of 70° C., a time of 2 h, filtration, and reduced pressure concentration to obtain the herbaceous vine extract;

[0078] The anti-allergic probiotics include Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri in a weight ratio of 1:6:2, and the number of viable bacteria is ≥1×10 7 cuf / g;

[0079] The active polypeptide complex is thymosin, glutathione and osteogenic peptide in a mass ratio of 5:1:0.9, and the average molecular weight is ≤1kD;

[0080] The immunomodulator is selected from β-glucan;

[0081] The penetration enhancer is mannitol, silk fibroin and bile salt in a mass ratio of 17:7:5;

[0082] The bioadhesive is hydroxypropyl-β-cyclodextrin, sodium carboxymethylcellulose and ε-polylysine in a mass ratio of 5.5:2.5:0.5;

[0083] The above-mentioned Example 5 adopts the following preparation method:

[0084] S1. Add antibacterial polysaccharide, sphagnum melongena extract, active polypeptide complex and immunomodulator into 8 volumes of deionized water, and stir to form a mixed solution A;

[0085] S2, the mixed solution A is processed by a high-pressure homogenizer, and the pressure is 1500 bar and circulated 10 times to form a nano-scale particle suspension for standby use;

[0086] S3, sequentially adding sodium hyaluronate, permeation enhancer and bioadhesive to the suspension, and using ultrasonic treatment to mix them evenly, the power of ultrasonic treatment is 300 W, the frequency is 150 kHz, each cycle is 9 minutes, and there are 12 cycles in total;

[0087] S4. Add anti-allergic probiotics to the above solution, stir at 6°C for 12 hours using a magnetic stirrer, adjust the ultrafiltration membrane molecular weight cutoff to ≤100 kDa, adjust the pH to 7.5, and freeze-dry to obtain a biological combination preparation for allergic rhinitis.

[0088] Comparative Example 1

[0089] A biological combination preparation for allergic rhinitis comprises the following raw materials in parts by weight: 45 parts of antibacterial polysaccharides, 10 parts of ophiopogon japonicus extract, 2 parts of antiallergic probiotics, 6 parts of active polypeptide complexes, 5 parts of sodium hyaluronate, 1 part of immunomodulator, 2 parts of penetration enhancer and 0.2 parts of bioadhesive.

[0090] Comparative Example 2

[0091] The difference between this comparative example and Example 3 is that the raw materials of the allergic rhinitis biological combination preparation do not contain a penetration enhancer.

[0092] Comparative Example 3

[0093] The difference between this comparative example and Example 3 is that the raw materials of the allergic rhinitis biological combination preparation do not contain bioadhesive.

[0094] In vitro testing

[0095] 1. Experimental Materials

[0096] 1. The biological combination preparations for allergic rhinitis of Examples 1-5 and Comparative Examples 1-3.

[0097] 2. Membrane material simulating nasal mucosa: decellularized porcine nasal mucosa matrix.

[0098] 3. Receiving fluid: artificial nasal mucus.

[0099] 4. Franz diffusion cell.

[0100] 2. Experimental steps

[0101] 1. Device Preparation

[0102] (1) Install the membrane material simulating the nasal mucosa between the two chambers of the diffusion cell to ensure that the membrane is well sealed.

[0103] (2) Add 20 mL of receiving solution into the receiving chamber.

[0104] 2. Administration of the preparation

[0105] (1) Add 4 mL of the allergic rhinitis biological combination preparation into the supply chamber to allow it to fully contact the membrane material.

[0106] 3. Cumulative absorption measurement

[0107] (1) At different time points: 0.5 hour, 1 hour, 2 hours, and 4 hours, the receiving solution was taken out from the receiving chamber for detection.

[0108] (2) Determine the concentration of the preparation in the receiving solution according to the method of the detection kit.

[0109] (3) Calculate the cumulative absorption at different time points: cumulative absorption = concentration of component in receiving solution × volume of receiving chamber.

[0110] 4. Release rate determination

[0111] (1) Record the total amount of formulation initially added to the supply chamber.

[0112] (2) At each time point, the amount of the component released into the receiving chamber is calculated based on the component concentration in the receiving solution and the cumulative absorption.

[0113] (3) Release rate = (amount of component released into the receiving chamber at a certain point in time / the total amount of initial components in the supply chamber) × 100%.

[0114] 5. Determination of transmembrane transport rate

[0115] (1) At the end of the experiment, the membrane material was removed and the residual formulation components on the membrane were extracted and detected.

[0116] (2) Calculate the total amount of components transported across the membrane to the receiving chamber (cumulative absorption) and the sum of the amount of components remaining on the membrane and the amount of components remaining in the donor chamber, which represents the total amount of components initially added.

[0117] (3) Transmembrane transport rate = (total amount of components transported across the membrane to the receiving chamber / total amount of components initially added) × 100%.

[0118] 3. Data Analysis

[0119] 1. Draw a curve of cumulative absorption over time to analyze the absorption kinetics of the preparation.

[0120] 2. Record the release rate and transmembrane transport rate at different time points to evaluate the release characteristics and transmembrane transport capacity of the preparation.

[0121] 4. Results and data

[0122] Table 1: Cumulative absorption

[0123]

[0124] Table 2: Release rate

[0125]

[0126] Table 3: Transmembrane transport rates

[0127]

[0128] As can be seen from the data of Examples 1-5, the cumulative absorption of the allergic rhinitis biological combination preparation increases over time. During the 4-hour experimental time, the cumulative absorption increased from 13-17 μg (0.5 hours) to 70-80 μg. In terms of release rate, it gradually increased from the initial 10%-14% to 35%-43%, indicating that the active ingredients in the preparation can be continuously released in the simulated nasal environment, providing a stable material basis for exerting therapeutic effects. The transmembrane transport rate is between 9%-12% (0.5 hours) and 27%-38% (4 hours), indicating that the ingredients in the preparation can effectively penetrate the simulated nasal mucosal barrier and enter the nasal tissue to exert their effects.

[0129] The cumulative absorption, release rate and transmembrane transport rate of Comparative Examples 1-3 were significantly lower than those of the Examples. In 4 hours, the cumulative absorption was only 42-48 μg, the release rate was up to 36%, and the transmembrane transport rate was up to 31%.

[0130] Comparison of Example 3 with Comparative Example 1 shows that better effects can be achieved when the formulation raw materials are selected in a specific ratio.

[0131] Compared with Comparative Example 2, Example 3 selects a certain mass ratio of mannitol, silk fibroin and bile salt as a penetration enhancer to promote the release of drugs from the carrier and accelerate the onset of drug action; it can increase the ability of drug molecules to penetrate the nasal mucosa, thereby improving the bioavailability and efficacy of the drug; by promoting the diffusion of drugs in the nasal mucosa, the penetration enhancer can help the drug to be more evenly distributed in the nasal cavity and improve the local treatment effect; it helps to protect drug molecules from the influence of factors such as enzymatic hydrolysis, thereby improving the stability of the drug.

[0132] Compared with Comparative Example 3, Example 3 shows that the bioadhesive of the present invention can improve the adhesion of the preparation to the nasal mucosa and prolong the retention time of the drug at the site of action, thereby reducing the frequency of administration and improving the therapeutic effect; by enhancing the contact between the drug and the nasal mucosa, the bioadhesive helps the drug to cover the nasal cavity more evenly and achieve more effective local treatment; the release rate of the drug from the preparation can be controlled to achieve slow release of the drug to maintain the stability of the drug efficacy.

[0133] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A biological combination preparation for allergic rhinitis, Features: The invention comprises the following raw materials in parts by weight: 20-40 parts of antibacterial polysaccharides, 13-18 parts of goosegrass extract, 5-10 parts of antiallergic probiotics, 1-4 parts of active polypeptide complex, 1-3 parts of sodium hyaluronate, 5-15 parts of immunomodulator, 3-8 parts of penetration enhancer and 0.5-1.2 parts of bioadhesive; the penetration enhancer is mannitol, silk fibroin and bile salt in a mass ratio of (12-22):(5-8):(3-7); the bioadhesive is hydroxypropyl-β-cyclodextrin, sodium carboxymethyl cellulose and ε-polylysine in a mass ratio of (3.8-8.5):(1.2-3.0):(0.2-0.8).

2. A biological combination preparation for allergic rhinitis according to claim 1, Features: The invention comprises the following raw materials in parts by weight: 30 parts of antibacterial polysaccharides, 15 parts of goosegrass extract, 8 parts of antiallergic probiotics, 3 parts of active polypeptide complex, 2 parts of sodium hyaluronate, 10 parts of immunomodulator, 5 parts of penetration enhancer and 0.8 parts of bioadhesive.

3. The biological combination preparation for allergic rhinitis according to claim 1, Features: The antibacterial polysaccharide is selected from one or more of astragalus polysaccharide, tuckahoe polysaccharide, lentinan, salvia miltiorrhiza polysaccharide, dandelion polysaccharide, bupleurum polysaccharide or anemarrhena polysaccharide.

4. The biological combination preparation for allergic rhinitis according to claim 1, Features: The Herba Lysimachiae extract is obtained by reflux extraction with ethanol at a mass concentration of 90-98%, a mass-to-volume ratio of 1:8-12, an extraction temperature of 60-80°C, a time of 1-3h, filtration, and reduced pressure concentration to obtain the Herba Lysimachiae extract.

5. The biological combination preparation for allergic rhinitis according to claim 1, Features: The anti-allergic probiotics include Lactobacillus acidophilus, Lactobacillus rhamnosus and Lactobacillus reuteri in a weight ratio of 1:(5-8):(1-3), and the number of viable bacteria is ≥1×10 7 cuf / g.

6. The biological combination preparation for allergic rhinitis according to claim 1, Features: The active polypeptide complex is thymosin, glutathione and osteogenic peptide in a mass ratio of (3-6):(1-2):(0.3-1.5), and the average molecular weight is ≤1kD.

7. The biological combination preparation for allergic rhinitis according to claim 1, Features: The immunomodulator is selected from one or more of vitamin D3, β-glucan or lactoferrin.

8. A method for preparing a biological combination preparation for allergic rhinitis according to claim 1, Features: The following steps are involved: S1. Add antibacterial polysaccharide, sphagnum melongena extract, active polypeptide complex and immunomodulator into 5-8 times of deionized water by volume, and stir to form a mixed solution A; S2, the mixed solution A is processed by a high-pressure homogenizer, and the pressure is 500-1500 bar, and the mixture is circulated for 5-10 times to form a nano-scale particle suspension for standby use; S3, sequentially adding sodium hyaluronate, a permeation enhancer and a bioadhesive to the suspension, and mixing them uniformly by ultrasonic treatment; S4. Add anti-allergic probiotics to the above solution, stir with a magnetic stirrer at 2-6°C for 8-12 hours, set the ultrafiltration membrane molecular weight cutoff to ≤100 kDa, adjust the pH to 6.0-7.5, and freeze-dry to obtain a biological combination preparation for allergic rhinitis.

9. A method for preparing a biological combination preparation for allergic rhinitis according to claim 8, Features: The power of the ultrasonic treatment is 100-300 W, the frequency is 120-150 kHz, each cycle is 5-9 minutes, and there are 8-12 cycles in total.

10. Use of the allergic rhinitis biological combination preparation prepared according to the preparation method of claim 8 or 9 in preventing or treating allergic rhinitis.

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