Pharmaceutical composition for treating chronic rhinitis and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical compositions, and particularly discloses a pharmaceutical composition for treating chronic rhinitis and a preparation method thereof.The pharmaceutical composition comprises a first medicine and a second medicine, and the first medicine comprises medical polymer gel and colloidal particles evenly dispersed in the medical polymer gel; the medical polymer gel comprises a polymer gel matrix and a first drug component, the colloidal particles comprise probiotics and a traditional Chinese medicine composition; the second medicine comprises traditional Chinese medicine powder and traditional Chinese medicine ointment. According to the invention, colloidal particles containing probiotics are added into the gel matrix, western medicine components in the gel matrix firstly act on the nose, the colloidal particle structure collapses in a warm and humid environment in the nasal cavity, and the traditional Chinese medicine components and the probiotics are sequentially and gradually released, so that the inflammation of the nose is durably and mildly repaired; and the probiotics can continuously grow in the nasal cavity, so that the reproduction of harmful bacteria is inhibited, the ecological balance of the flora of the nose is fundamentally maintained, and the traditional Chinese medicine composition is more suitable for treating chronic rhinitis and has a lasting and remarkable curative effect.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical compositions, and specifically relates to a pharmaceutical composition for treating chronic rhinitis and a preparation method thereof. Background Art

[0002] Chronic rhinitis is a common nasal disease, and its main symptoms include: nasal congestion, increased nasal secretions, thickened nasal conchas, swollen nose, decreased sense of smell, etc., which are often accompanied by symptoms such as dizziness and headache, causing great inconvenience and pain to the patient's daily life. At the same time, if chronic rhinitis has not been effectively treated, it will also cause lesions in other parts of the body, leading to complications, causing multi-faceted damage to the patient's body.

[0003] The causes of chronic rhinitis are complex and diverse, mainly local causes of the nose, external environmental stimulation or systemic causes of the body. Therefore, it is difficult to have an effective treatment plan. It is necessary to comprehensively consider the patient's specific situation and cause, and develop personalized treatment methods to fundamentally treat chronic rhinitis.

[0004] Among all the causes of chronic rhinitis, allergic inflammation caused by external environmental stimulation is the most common. There are many technical solutions for treating allergic rhinitis in the prior art. For example, the invention patent application with publication number CN117797191A (a nasal spray for treating allergic rhinitis and its preparation method) discloses a nasal spray, including 0.02-0.05% oxymetazoline hydrochloride, 0.1-1% sodium chloride, and 0.01-0.02% modified mangosteen peel extract, which has the advantages of good stability and low irritation. However, the drug has a relatively single component and a single efficacy, and is difficult to be applied to the treatment of chronic rhinitis with complex causes and severe symptoms.

[0005] In the treatment of chronic rhinitis, in addition to surgical treatment, conservative treatment with drugs is also a common method. For example, in the invention patent application with publication number CN117338872A (a Chinese medicine ointment for treating chronic rhinitis and its preparation method), a Chinese medicine ointment made of Xanthium sibiricum, Magnolia officinalis, Angelica dahurica, Cinnamomum cassia, Galla chinensis, Borneolum, Astragalus, Kelpia, Honeysuckle, Scutellaria baicalensis, Codonopsis pilosula, Elephant shell, and Vaseline is disclosed. When used, it is placed inside the nasal cavity through a cotton swab, and the medication is simple, with little trauma and high safety. Another example is the invention patent application with publication number CN118477035 (a combination nasal drops for treating chronic rhinitis and its preparation method), a nasal drop is disclosed, including a Chinese medicine extract containing Gleditsia sinensis, Xanthium sibiricum, Bupleurum chinense, Chrysanthemum indici, Licorice and Angelica dahurica, as well as Ecdoin and sodium hyaluronate, which is directly dripped into the nasal cavity when used to treat chronic rhinitis. However, both of the above-mentioned schemes use pure Chinese herbal medicine ingredients, which are mild and have relatively few side effects. However, the effect of pure Chinese medicine is relatively slow, and the treatment effect varies for people with different physical conditions.

[0006] Although there are many drug explorations for nasal diseases and chronic rhinitis in the prior art, they either have single ingredients and limited efficacy, or have slow efficacy and poor universality. Therefore, it is necessary to develop a drug composition for the treatment of chronic rhinitis with significant efficacy and strong universality. Summary of the invention

[0007] In order to solve the problems raised in the above background technology, the present invention provides a pharmaceutical composition for treating chronic rhinitis and a preparation method thereof.

[0008] To achieve the above object, the present invention provides the following technical solution: a pharmaceutical composition for treating chronic rhinitis, comprising a first drug and a second drug, wherein the first drug comprises a medical polymer gel and colloid particles uniformly dispersed in the medical polymer gel;

[0009] The medical polymer gel comprises a polymer gel matrix and a first drug component; the first drug component comprises an anti-inflammatory agent and an antibacterial agent;

[0010] The anti-inflammatory agent includes one or more of fluticasone propionate, mometasone furoate, triamcinolone acetonide, and budesonide;

[0011] The antibacterial agent includes one or more of baicalein, wogonin, eugenol, emodin, myrsinol, cinnamaldehyde, berberine, and tea polyphenols;

[0012] The colloid particles include a core layer, a barrier layer, an intermediate layer and an outer layer from the inside to the outside, the core layer includes probiotics, the barrier layer is a first colloid layer, the intermediate layer includes a traditional Chinese medicine composition, and the outer layer is a second colloid layer;

[0013] The Chinese medicine composition comprises: Xanthium sibiricum, Magnolia flower, Angelica dahurica, Asarum, Menthus fragrans, Licorice root, Saposhnikovia divaricata, Scutellaria baicalensis;

[0014] The second medicine includes Chinese medicine powder and Chinese medicine ointment.

[0015] Furthermore, the polymer gel matrix includes one or more of cellulose, chitin, hyaluronic acid, polyethylene glycol, polylactic acid, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyacrylamide, polyacrylate, poly-N-polyacrylamide, starch, sodium alginate, chitosan, collagen, poly-L-lysine, and poly-L-glutamic acid.

[0016] Furthermore, the mass ratio of the anti-inflammatory agent to the antibacterial agent is 1:0.5-1.5.

[0017] Furthermore, the materials of the first gelatin layer and the second gelatin layer may be the same or different, and may be selected from one or more of polyvinyl alcohol, cellulose, chitin, starch, chitosan, sodium alginate, and collagen.

[0018] Furthermore, the medical polymer gel also includes a pH regulator, which includes one or more of acetic acid, citric acid, sorbic acid, malic acid, tartaric acid, phosphoric acid, citric acid, maleic acid, sodium bicarbonate, sodium citrate, potassium carbonate, phosphate buffer, borate buffer, and boric acid buffer.

[0019] Furthermore, the Chinese medicine composition comprises, by weight: 15-25 parts of Xanthium sibiricum fruit; 8-15 parts of magnolia flower; 8-15 parts of angelica dahurica; 3-10 parts of asarum; 3-10 parts of mint; 3-10 parts of liquorice; 3-10 parts of siler; and 3-15 parts of scutellaria baicalensis.

[0020] Furthermore, the probiotics include one or more of lactobacilli and bifidobacteria.

[0021] Further, the second medicine includes No. 1 powder, No. 2 ointment and No. 3 ointment;

[0022] The No. 1 powder comprises: 0.3-1 part of magnolia flower; 1-3 parts of Sichuan coptis root; 0.8-2 parts of notopterygium root; 1-3 parts of forsythia; 0.6-2.5 parts of divaricate cortex; 1-3 parts of siler; 0.3-1.5 parts of xanthium sibiricum;

[0023] The No. 2 ointment comprises: 1-3 parts of Angelica dahurica; 2-3.5 parts of Scutellaria baicalensis; 1-3.2 parts of Dioscorea opposita; 1-3 parts of Schisandra chinensis; 0.3-1.5 parts of Herba Glechomae;

[0024] The No. 3 ointment comprises: 1-3 parts of Hedyotis diffusa; 0.5-3 parts of leech; 2-5 parts of Pueraria root; 1-3 parts of mint; 0.3-1.2 parts of raw liquorice; and 1-3 parts of Nepeta tenuifolia.

[0025] Further, the No. 1 powder includes: 0.8 parts of magnolia flower; 2 parts of Sichuan coptis root; 1.5 parts of notopterygium root; 1.5 parts of forsythia; 1.4 parts of divaricate cortex; 2 parts of siler; 0.8 parts of xanthium sibiricum;

[0026] The No. 2 ointment comprises: 2 parts of Angelica dahurica; 2.8 parts of Scutellaria baicalensis; 2.2 parts of Dioscorea opposita; 2.2 parts of Schisandra chinensis; 0.8 parts of Herba Glechomae;

[0027] The ointment No. 3 comprises: 2 parts of Hedyotis diffusa; 1 part of leech; 3 parts of Pueraria root; 2 parts of mint; 0.7 parts of raw licorice; and 1.3 parts of Nepeta tenuifolia.

[0028] The present invention also claims a method for preparing the above-mentioned pharmaceutical composition for treating chronic rhinitis.

[0029] The preparation of the first drug comprises the following steps:

[0030] 1. Preparation of colloid particles:

[0031] (1) culturing probiotic strains in a culture medium, collecting probiotic strains, adding them to an aqueous solution containing a first polymer colloidal material, mixing them evenly, and obtaining probiotic microparticles by spray drying to form a core layer;

[0032] (2) uniformly coating the first colloid layer solution on the surface of the core layer particles and curing to form a barrier layer;

[0033] (3) adding the decoction and concentration of the traditional Chinese medicine composition to the aqueous solution containing the second polymer colloidal material, mixing them evenly, and then coating them evenly on the surface of the barrier layer, and curing them to form an intermediate layer;

[0034] (4) coating the second colloid layer solution evenly on the surface of the middle layer and curing it to form an outer layer;

[0035] 2. Preparation of the First Drug

[0036] (1) preparing a medical polymer gel: adding a prescribed amount of an anti-inflammatory agent and an antibacterial agent to a polymer gel matrix solution, mixing the mixture evenly, and obtaining a medical polymer gel;

[0037] (2) adding the colloid particles to the medical polymer gel, mixing them evenly, and packaging them to obtain the finished product;

[0038] The preparation of the second drug comprises the following steps:

[0039] The Chinese medicinal materials are respectively made into Chinese medicinal powder and Chinese medicinal ointment.

[0040] When the pharmaceutical composition of the present invention is used for the first time, the first drug is first applied to the patient's nose, and after 1-1.5 hours, the No. 1 powder and the No. 2 ointment are evenly mixed and applied to the patient's nose; in subsequent use, the first drug is first applied to the patient's nose, and after 1-1.5 hours, the No. 1 powder and the No. 3 ointment are evenly mixed and applied to the patient's nose.

[0041] Compared with the prior art, the present invention has the following beneficial effects:

[0042] The present invention adopts a combination of traditional Chinese medicine and western medicine, and adds colloid particles containing probiotics into a gel matrix. First, the western medicine components in the gel matrix act on the nose. In the warm and humid environment of the nasal cavity, the colloid particle structure collapses, and the traditional Chinese medicine components and probiotics are gradually released in turn, which can repair nasal inflammation in a lasting and gentle manner. Moreover, the probiotics can continue to grow in the nasal cavity, thereby inhibiting the reproduction of harmful bacteria, fundamentally maintaining the ecological balance of the nasal flora, and is more suitable for the treatment of chronic rhinitis, with a long-lasting and significant therapeutic effect.

[0043] Meanwhile, the pharmaceutical composition of the present invention adopts the combination of the first drug and the second drug, and the second drug is a pure Chinese medicine component, which is more conducive to the fundamental treatment of chronic rhinitis. DETAILED DESCRIPTION

[0044] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] A pharmaceutical composition for treating chronic rhinitis comprises a first drug and a second drug, wherein the first drug comprises a medical polymer gel and colloid particles uniformly dispersed in the medical polymer gel, wherein the size of the colloid particles is 0.5-1.5 mm, and the second drug comprises a traditional Chinese medicine powder and a traditional Chinese medicine ointment.

[0046] Among them, the medical polymer gel includes a polymer gel matrix and a first drug component, and the polymer gel matrix includes one or more of cellulose, chitin, hyaluronic acid, polyethylene glycol, polylactic acid, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyacrylamide, poly-N-polyacrylamide, starch, alginate, chitosan, collagen, poly-L-lysine, and poly-L-glutamic acid.

[0047] In a specific embodiment, the polymer gel matrix can be selected from one or more of polyacrylic acid, hyaluronic acid, polyvinyl alcohol, polyethylene glycol, polyacrylamide, chitosan, and cellulose.

[0048] The first drug component includes an anti-inflammatory agent and an antibacterial agent, wherein the mass ratio of the anti-inflammatory agent to the antibacterial agent is 1:0.5-1.5.

[0049] The anti-inflammatory agent includes one or more of fluticasone propionate, mometasone furoate, triamcinolone acetonide and budesonide.

[0050] The antibacterial agent includes one or more of baicalein, wogonin, eugenol, emodin, myrsinol, cinnamaldehyde, berberine, and tea polyphenols.

[0051] In order to adjust the pH of the pharmaceutical composition so that it acts more gently on the nose, a pH regulator is added to the pharmaceutical composition of the present invention according to specific circumstances. Specifically, the pH regulator includes one or more of acetic acid, citric acid, sorbic acid, malic acid, tartaric acid, phosphoric acid, citric acid, maleic acid, sodium bicarbonate, sodium citrate, potassium carbonate, phosphate buffer, borate buffer, and boric acid buffer.

[0052] The colloid particles include a core layer, a barrier layer, an intermediate layer and an outer layer from the inside to the outside, wherein the core layer includes probiotics, the barrier layer is the first colloid layer, the intermediate layer includes the Chinese medicine composition, and the outer layer is the second colloid layer.

[0053] Among them, probiotics include one or more of lactobacilli and bifidobacteria.

[0054] The Chinese medicine composition comprises: 15-25 parts of Xanthium sibiricum fruit, 8-15 parts of magnolia flower, 8-15 parts of angelica dahurica, 3-10 parts of asarum, 3-10 parts of mint, 3-10 parts of liquorice, 3-10 parts of siler, and 3-10 parts of scutellaria.

[0055] The materials of the first gelatin layer and the second gelatin layer may be the same or different, and may be selected from one or more of polyvinyl alcohol, cellulose, chitin, starch, chitosan, and collagen.

[0056] Among them, the second medicine includes powder No. 1, cream No. 2 and cream No. 3;

[0057] Powder No. 1 includes: 0.3-1 part of magnolia flower; 1-3 parts of Sichuan coptis root; 0.8-2 parts of angelica root; 1-3 parts of forsythia; 0.6-2.5 parts of white peony root; 1-3 parts of saposhnikovia root; 0.3-1.5 parts of Xanthium sibiricum; Paste No. 2 includes: 1-3 parts of angelica dahurica; 2-3.5 parts of scutellaria baicalensis; 1-3.2 parts of yam; 1-3 parts of schisandra chinensis; 0.3-1.5 parts of cape wormwood; Paste No. 3 includes: 1-3 parts of oldenlandia diffusa; 0.5-3 parts of leech; 2-5 parts of kudzu root; 1-3 parts of mint; 0.3-1.2 parts of raw licorice; 1-3 parts of schizonepeta tenuifolia.

[0058] Preferably, powder No. 1 includes: 0.8 parts of magnolia flower; 2 parts of Sichuan coptis root; 1.5 parts of angelica root; 1.5 parts of forsythia; 1.4 parts of Dictamni cortex; 2 parts of Saposhnikovia divaricata; 0.8 parts of Xanthium sibiricum; paste No. 2 includes: 2 parts of Angelica dahurica; 2.8 parts of Scutellaria baicalensis; 2.2 parts of Chinese yam; 2.2 parts of Schisandra chinensis; 0.8 parts of Herba Capillaris; paste No. 3 includes: 2 parts of Hedyotis diffusa; 1 part of leech; 3 parts of Pueraria root; 2 parts of mint; 0.7 parts of raw licorice; 1.3 parts of Schizonepeta tenuifolia.

[0059] When preparing the pharmaceutical composition for treating chronic rhinitis of the present invention, the preparation of the first drug comprises the following steps:

[0060] 1. Preparation of colloid particles:

[0061] (1) culturing probiotic strains in a culture medium, collecting probiotic strains, adding them to an aqueous solution containing a first polymer colloidal material, mixing them evenly, and obtaining probiotic microparticles by spray drying to form a core layer;

[0062] (2) uniformly coating the first colloid layer solution on the surface of the core layer particles and curing to form a barrier layer;

[0063] (3) adding the decoction and concentration of the traditional Chinese medicine composition to the aqueous solution containing the second polymer colloidal material, mixing them evenly, and then coating them evenly on the surface of the barrier layer, and curing them to form an intermediate layer;

[0064] (4) The second colloid layer solution is evenly coated on the surface of the middle layer and solidified to form an outer layer.

[0065] The first polymer colloid material is the same or different from the material of the first colloid layer, and the second polymer colloid material is the same or different from the material of the second colloid layer, and can be selected from one or more of polyvinyl alcohol, cellulose, chitin, starch, chitosan, and collagen.

[0066] 2. Preparation of the First Drug

[0067] (1) preparing a medical polymer gel: adding a prescribed amount of an anti-inflammatory agent and an antibacterial agent to a polymer gel matrix solution, mixing the mixture evenly, and obtaining a medical polymer gel;

[0068] (2) After adding the colloid particles to the medical polymer gel, mix them evenly, and then add a pH adjuster to adjust the pH to 5.5-6.6. Finally, mix them evenly and package them to obtain the finished product.

[0069] The preparation of the second drug comprises the following steps:

[0070] The Chinese medicinal materials are respectively made into Chinese medicinal powders and Chinese medicinal ointments according to the above formulas, specifically into No. 1 medicinal powder, No. 2 ointment and No. 3 ointment.

[0071] When the pharmaceutical composition of the present invention is used, the nasal cavity is first cleaned with physiological saline to remove secretions and other dirt in the nasal cavity.

[0072] Then, when using it for the first time, first apply the first medicine to the nasal cavity with a clean cotton swab. After 1-1.5 hours, mix No. 1 powder and No. 2 ointment evenly and apply it to the patient's nose. During subsequent use, first apply the first medicine to the patient's nose. After 1-1.5 hours, mix No. 1 powder and No. 3 ointment evenly and apply it to the patient's nose.

[0073] When No. 1 powder and No. 2 paste are used, the mass ratio of No. 1 powder to No. 2 paste is 1:10-50; when No. 1 powder and No. 3 paste are used, the mass ratio of No. 1 powder to No. 3 paste is 1:10-50. Mix evenly before use.

[0074] The first drug component of the drug composition will first act on the affected area of ​​the nose for preliminary treatment. In the warm and humid environment of the nasal cavity, the colloidal structure gradually collapses, and the Chinese medicine composition and probiotics are slowly released in turn, which can repair nasal inflammation in a long-lasting and gentle manner. Moreover, the probiotics can continue to grow in the nasal cavity, thereby inhibiting the reproduction of harmful bacteria, fundamentally maintaining the ecological balance of the nasal flora, and being more suitable for the treatment of chronic rhinitis, with long-lasting and significant therapeutic effects. At the same time, combined with the Chinese medicine ingredients in the second drug, it is more conducive to the fundamental treatment of chronic rhinitis.

[0075] Before the experiment, the present invention firstly cultured probiotics by the following method:

[0076] The strains of lactobacillus and bifidobacterium were co-cultured in a culture medium. Before the culture, the culture medium was sterilized by high pressure, and then the strains were inoculated and cultured continuously at 37°C under anaerobic conditions for 30 hours. The probiotic slurry was obtained by centrifugation and then dispersed in sterile physiological saline, and the number of viable bacteria was adjusted so that the total number of viable bacteria was greater than or equal to 2.5×10 9 CFU / mL, for future use.

[0077] Among them, Lactobacillus and Bifidobacterium strains were purchased from Weikang Probiotics (Suzhou) Co., Ltd., among which the optional strains of Lactobacillus are: Lactobacillus acidophilus LA85, Lactobacillus acidophilus LA88 / LA05, Lactobacillus acidophilus LA18, Lactobacillus rhamnosus LRa05, Lactobacillus rhamnosus LRa66, Lactobacillus rhamnosus LRa09, Lactobacillus rhamnosus LRa16, Lactobacillus plantarum LP05, Lactobacillus plantarum LP10, and Lactobacillus plantarum CW006; the optional strains of Bifidobacterium are: Bifidobacterium longum subspecies longum BL21, Bifidobacterium breve BBr16, and Bifidobacterium breve BBr96.

[0078] When culturing probiotics, one or several lactobacilli mentioned above may be selected and cultured together with one or several bifidobacteria mentioned above.

[0079] The second drug can be prepared in advance for standby use, and the specific preparation method is as follows:

[0080] Preparation of Chinese herbal medicine raw materials:

[0081] No. 1 powder includes: 0.8 parts of magnolia flower; 2 parts of Sichuan coptis root; 1.5 parts of notopterygium root; 1.5 parts of forsythia; 1.4 parts of licorice root; 2 parts of siler; 0.8 parts of xanthium sibiricum fruit;

[0082] No. 2 ointment includes: 2 parts of Angelica dahurica; 2.8 parts of Scutellaria baicalensis; 2.2 parts of Dioscorea opposita; 2.2 parts of Schisandra chinensis; 0.8 parts of Herba Capillaris;

[0083] Ointment No. 3 includes: 2 parts of Hedyotis diffusa; 1 part of leech; 3 parts of Pueraria root; 2 parts of mint; 0.7 parts of raw licorice; 1.3 parts of Schizonepeta tenuifolia.

[0084] The raw materials of No. 1 powder are washed, dried, ground into powder, sieved and set aside. The raw materials of No. 2 paste and No. 3 paste are boiled into pastes according to the conventional method and set aside.

[0085] Example 1

[0086] 1. Preparation of colloid particles:

[0087] (1) Select Lactobacillus acidophilus LA85 and Bifidobacterium longum subspecies longum BL21 for co-culturing to obtain a physiological saline solution containing the strains for later use.

[0088] Slowly add 4 parts by mass of polyvinyl alcohol 1788 to 100 parts by mass of sterile hot water at 85°C, mix evenly, then slowly add 4 parts by mass of carboxymethyl cellulose, mix evenly; then cool to 45°C, add 40 parts by mass of physiological saline containing probiotics, vacuum to remove bubbles, mix evenly to form a mixed solution; spray dry the mixed solution to obtain probiotic microparticles to form a core layer. The particle size of the probiotic microparticles is controlled to be 0.1-0.3 mm.

[0089] (2) Slowly add 6 parts by mass of polyvinyl alcohol 1788 into 100 parts by mass of hot water at 85° C., mix evenly, and then cool to 45° C. to obtain a first gelatinous layer solution; spray the first gelatinous layer solution evenly on the surface of the probiotic particles forming the core layer, and then quickly cool to 10° C. to solidify the first gelatinous layer solution to form a barrier layer.

[0090] (3) Weigh 15 parts of Xanthium sibiricum, 10 parts of Magnolia floret, 10 parts of Angelica dahurica, 5 parts of Asarum, 5 parts of Mentha, 5 parts of Licorice, 10 parts of Saposhnikovia divaricata, and 10 parts of Scutellaria baicalensis respectively, add 5 times the weight of water, soak for 25 minutes, boil until boiling, then simmer for 30 minutes, filter to obtain the first decoction; continue to add 4 times the weight of water to the residue, boil until boiling, then simmer for 30 minutes, filter to obtain the second decoction; the two decoctions are combined and filtered again, and concentrated to 1 / 3 of the volume of the decoction.

[0091] Slowly add 6 parts by mass of polyvinyl alcohol 1788 to 100 parts by mass of hot water at 85°C and mix evenly. Then add 40 parts by mass of concentrated decoction and mix evenly. Then cool to 45°C to form a Chinese medicine composition gel. Evenly spray the Chinese medicine composition gel on the surface of the probiotic particles with a barrier layer, then quickly cool to 10°C to solidify the Chinese medicine composition gel to form an intermediate layer.

[0092] (4) 8 parts by weight of polyvinyl alcohol 1788 is slowly added to 100 parts by weight of hot water at 85° C., mixed evenly, and then cooled to 45° C. to obtain a second gelatinous layer solution; the second gelatinous layer solution is evenly sprayed on the surface of the probiotic particles having an intermediate layer, and then quickly cooled to 10° C. to solidify the second gelatinous layer solution to form an outer layer.

[0093] The rubber particles are obtained, and the particle size of the rubber particles is controlled to be 0.3-0.8mm.

[0094] 2. Preparation of the First Drug

[0095] (1) Preparation of medical polymer gel: 5 parts by weight of chitosan and 5 parts by weight of carboxymethyl chitosan were added into sterile deionized water at 85° C., mixed evenly, and cooled to 45° C. to prepare a 1 wt % hydrogel matrix solution;

[0096] Add the anti-inflammatory agent (1 part by mass of fluticasone propionate) and the antibacterial agent (1 part by mass of baicalin) in the formulated amount into the hydrogel matrix under stirring, mix them evenly, and obtain the medical polymer gel.

[0097] (2) Add the colloid particles to the medical polymer gel under stirring, control the amount of the colloid particles added to be 3-5% of the mass of the medical polymer gel, and mix them evenly, add a pH adjuster to adjust the pH to 6.5, finally mix them evenly, quickly cool to 10° C., and package to obtain the finished product.

[0098] Example 2

[0099] 1. Preparation of colloid particles:

[0100] (1) Select Lactobacillus acidophilus LA85, Lactobacillus rhamnosus LRa05 and Bifidobacterium breve BBr16 for co-culturing to obtain a physiological saline containing the strains for later use.

[0101] 6 parts by mass of sodium alginate are slowly added to 100 parts by mass of sterile hot water at 90°C, and the mixture is evenly mixed. Then 4 parts by mass of carboxymethyl cellulose are slowly added and the mixture is evenly mixed. Then the mixture is cooled to 40°C, 50 parts by mass of physiological saline containing probiotics are added, the mixture is vacuumed to remove bubbles, and the mixture is evenly mixed to form a mixed solution. The mixed solution is spray-dried to obtain probiotic microparticles and form a core layer. The particle size of the probiotic microparticles is controlled to be 0.1-0.3 mm.

[0102] (2) Slowly adding 6 parts by weight of sodium alginate into 100 parts by weight of hot water at 90° C., mixing evenly, and then cooling to 40° C. to obtain a first gelatinous layer solution; spraying the first gelatinous layer solution evenly on the surface of the probiotic particles forming the core layer, and then rapidly cooling to 10° C. to solidify the first gelatinous layer solution to form a barrier layer.

[0103] (3) Weigh 22.5 parts of Xanthium sibiricum, 15 parts of Magnolia flos, 15 parts of Angelica dahurica, 7.5 parts of Asarum, 7.5 parts of Mentha, 7.5 parts of Licorice, 15 parts of Saposhnikovia divaricata, and 15 parts of Scutellaria baicalensis respectively, add 5 times the weight of water, soak for 25 minutes, boil until boiling, then simmer for 30 minutes, filter to obtain the first decoction; continue to add 4 times the weight of water to the residue, boil until boiling, then simmer for 30 minutes, filter to obtain the second decoction; the two decoctions are combined and filtered again, and concentrated to 1 / 3 of the volume of the decoction.

[0104] Slowly add 6 parts by mass of sodium alginate into 100 parts by mass of hot water at 90°C and mix evenly, then add 40 parts by mass of concentrated decoction and mix evenly, then cool to 40°C to form a Chinese medicine composition gel, evenly spray the Chinese medicine composition gel on the surface of the probiotic particles with a barrier layer, then quickly cool to 10°C to solidify the Chinese medicine composition gel to form an intermediate layer.

[0105] (4) 8 parts by weight of sodium alginate is slowly added to 100 parts by weight of hot water at 90° C., mixed evenly, and then cooled to 45° C. to obtain a second gelatinous layer solution; the second gelatinous layer solution is evenly sprayed on the surface of the probiotic particles having an intermediate layer, and then quickly cooled to 10° C. to solidify the second gelatinous layer solution to form an outer layer.

[0106] The rubber particles are obtained, and the particle size of the rubber particles is controlled to be 0.3-0.8mm.

[0107] 2. Preparation of the First Drug

[0108] (1) Preparation of medical polymer gel: 10 parts by weight of starch was added to 90° C. sterile deionized water, mixed evenly, and cooled to 40° C. to prepare a 30 wt % hydrogel matrix solution;

[0109] Add the formulated amount of anti-inflammatory agent (1 part by mass of fluticasone propionate and 1 part by mass of mometasone furoate) and antibacterial agent (1.5 parts by mass of wogonin) into the hydrogel matrix under stirring, mix well, and obtain a medical polymer gel.

[0110] (2) Add the colloid particles to the medical polymer gel under stirring, control the amount of the colloid particles added to be 3-5% of the mass of the medical polymer gel, and mix them evenly, add a pH adjuster to adjust the pH to 6.5, finally mix them evenly, quickly cool to 10° C., and package to obtain the finished product.

[0111] Example 3

[0112] 1. Preparation of colloid particles:

[0113] (1) Select Lactobacillus acidophilus LA88, Lactobacillus rhamnosus LRa66 and Bifidobacterium breve BBr16 for co-culturing to obtain a physiological saline containing the strains for later use.

[0114] 8 parts by weight of carboxymethyl cellulose are slowly added to 100 parts by weight of sterile hot water at 90°C and mixed evenly; then cooled to 40°C, 50 parts by weight of physiological saline containing probiotics are added, vacuumed to remove bubbles, and mixed evenly to form a mixed solution; the mixed solution is spray-dried to obtain probiotic microparticles to form a core layer. The particle size of the probiotic microparticles is controlled to be 0.1-0.3 mm.

[0115] (2) Slowly adding 7 parts by weight of sodium alginate into 100 parts by weight of hot water at 90° C., mixing evenly, and then cooling to 40° C. to obtain a first gelatinous layer solution; spraying the first gelatinous layer solution evenly on the surface of the probiotic particles forming the core layer, and then rapidly cooling to 10° C. to solidify the first gelatinous layer solution to form a barrier layer.

[0116] (3) Weigh 22.5 parts of Xanthium sibiricum, 15 parts of Magnolia floret, 15 parts of Angelica dahurica, 7.5 parts of Asarum, 7.5 parts of Mentha, 7.5 parts of Licorice, 10 parts of Saposhnikovia divaricata, and 10 parts of Scutellaria baicalensis respectively, add 5 times the weight of water, soak for 25 minutes, boil until boiling, then simmer for 30 minutes, filter to obtain the first decoction; continue to add 4 times the weight of water to the residue, boil until boiling, then simmer for 30 minutes, filter to obtain the second decoction; the two decoctions are combined and filtered again, and concentrated to 1 / 3 of the volume of the decoction.

[0117] Slowly add 6 parts by mass of sodium alginate into 100 parts by mass of hot water at 90°C and mix evenly, then add 40 parts by mass of concentrated decoction and mix evenly, then cool to 40°C to form a Chinese medicine composition gel, evenly spray the Chinese medicine composition gel on the surface of the probiotic particles with a barrier layer, then quickly cool to 10°C to solidify the Chinese medicine composition gel to form an intermediate layer.

[0118] (4) 8 parts by weight of carboxymethyl cellulose are slowly added to 100 parts by weight of hot water at 90° C., mixed evenly, and then cooled to 45° C. to obtain a second gelatinous layer solution; the second gelatinous layer solution is evenly sprayed on the surface of the probiotic particles having an intermediate layer, and then quickly cooled to 10° C. to solidify the second gelatinous layer solution to form an outer layer.

[0119] The rubber particles are obtained, and the particle size of the rubber particles is controlled to be 0.3-0.8mm.

[0120] 2. Preparation of the First Drug

[0121] (1) preparing a medical polymer gel: adding 1 part by weight of carbomer and 5 parts by weight of glycerol to 100 parts of sterile deionized water, and mixing evenly to prepare a hydrogel matrix solution;

[0122] Add the formulated amount of anti-inflammatory agent (1 part by mass of triamcinolone acetonide) and antibacterial agent (1.5 parts by mass of berberine) into the hydrogel matrix under stirring, mix them evenly, and obtain a medical polymer gel.

[0123] (2) Add the colloid particles to the medical polymer gel under stirring, control the amount of the colloid particles added to be 3-5% of the mass of the medical polymer gel, and mix them evenly, add a pH adjuster to adjust the pH to 6.5, finally mix them evenly, quickly cool to 10° C., and package to obtain the finished product.

[0124] Example 4

[0125] 1. Preparation of colloid particles:

[0126] (1) Select Lactobacillus acidophilus LA18 and Bifidobacterium breve BBr16 for co-culturing to obtain a physiological saline solution containing the strains for later use.

[0127] 8 parts by weight of sodium alginate are slowly added to 100 parts by weight of sterile hot water at 90°C, and the mixture is evenly mixed. Then 2 parts by weight of carboxymethyl cellulose are slowly added, and the mixture is evenly mixed. Then the mixture is cooled to 40°C, 50 parts by weight of physiological saline containing probiotics are added, the mixture is vacuumed to remove bubbles, and the mixture is evenly mixed to form a mixed solution. The mixed solution is spray-dried to obtain probiotic microparticles to form a core layer. The particle size of the probiotic microparticles is controlled to be 0.1-0.3 mm.

[0128] (2) Slowly adding 7 parts by weight of PVA1788 into 100 parts by weight of hot water at 90° C., mixing evenly, and then cooling to 40° C. to obtain a first gelatinous layer solution; spraying the first gelatinous layer solution evenly on the surface of the probiotic particles forming the core layer, and then rapidly cooling to 10° C. to solidify the first gelatinous layer solution to form a barrier layer.

[0129] (3) Weigh 10 parts of Xanthium sibiricum, 15 parts of Magnolia floret, 15 parts of Angelica dahurica, 2 parts of Asarum, 2 parts of Mentha, 2 parts of Licorice, 2 parts of Saposhnikovia divaricata, and 2 parts of Scutellaria baicalensis, add 5 times the weight of water, soak for 25 minutes, boil until boiling, then simmer for 30 minutes, filter to obtain the first decoction; continue to add 4 times the weight of water to the residue, boil until boiling, then simmer for 30 minutes, filter to obtain the second decoction; the two decoctions are combined and filtered again, and concentrated to 1 / 3 of the volume of the decoction.

[0130] Slowly add 6 parts by mass of carboxymethyl cellulose to 100 parts by mass of hot water at 90°C and mix evenly, then add 40 parts by mass of concentrated decoction and mix evenly, then cool to 40°C to form a Chinese medicine composition gel, evenly spray the Chinese medicine composition gel on the surface of the probiotic particles with a barrier layer, then quickly cool to 10°C to solidify the Chinese medicine composition gel to form an intermediate layer.

[0131] (4) 8 parts by weight of PVA1788 were slowly added to 100 parts by weight of hot water at 90° C., mixed evenly, and then cooled to 45° C. to obtain a second gelatinous layer solution; the second gelatinous layer solution was evenly sprayed on the surface of the probiotic particles having an intermediate layer, and then quickly cooled to 10° C. to solidify the second gelatinous layer solution to form an outer layer.

[0132] The rubber particles are obtained, and the particle size of the rubber particles is controlled to be 0.3-0.8mm.

[0133] 2. Preparation of the First Drug

[0134] (1) Preparation of medical polymer gel: 3 parts by weight of carboxymethyl chitosan and 5 parts by weight of sodium alginate were added into 100 parts of sterile deionized water at 90° C., mixed evenly, and cooled to 40° C. to prepare a hydrogel matrix solution;

[0135] Add the formulated amount of anti-inflammatory agent (1 part by mass of triamcinolone acetonide) and antibacterial agent (1.5 parts by mass of berberine) into the hydrogel matrix under stirring, mix them evenly, and obtain a medical polymer gel.

[0136] (2) Add the colloid particles to the medical polymer gel under stirring, control the amount of the colloid particles added to be 3-5% of the mass of the medical polymer gel, and mix them evenly, add a pH adjuster to adjust the pH to 6.5, finally mix them evenly, quickly cool to 10° C., and package to obtain the finished product.

[0137] Comparative Example 1

[0138] A medical polymer gel without colloid particles is prepared as the first drug.

[0139] 5 parts by weight of chitosan and 5 parts by weight of carboxymethyl chitosan were added into 85° C. sterile deionized water, mixed evenly, and cooled to 45° C. to prepare a 1 wt% hydrogel matrix solution;

[0140] Under stirring, add a formulated amount of anti-inflammatory agent (1 part by mass of fluticasone propionate) and antibacterial agent (1 part by mass of baicalin) to the hydrogel matrix, mix evenly, add a pH adjuster to adjust the pH to 6.5, finally mix evenly to obtain a medical polymer gel, and then cool to 4°C and package to obtain the finished product.

[0141] Comparative Example 2

[0142] The micelle in the first drug has only a core layer and a barrier layer.

[0143] 1. Preparation of colloid particles:

[0144] (1) Select Lactobacillus acidophilus LA85, Lactobacillus rhamnosus LRa05 and Bifidobacterium breve BBr16 for co-culturing to obtain a physiological saline containing the strains for later use.

[0145] 7 parts by weight of PVA1788 are slowly added to 100 parts by weight of sterile hot water at 90°C, and the mixture is evenly mixed. Then 3 parts by weight of methylcellulose are slowly added, and the mixture is evenly mixed. Then the mixture is cooled to 40°C, 50 parts by weight of physiological saline containing probiotics are added, the mixture is vacuumed to remove bubbles, and the mixture is evenly mixed to form a mixed solution. The mixed solution is spray-dried to obtain probiotic microparticles to form a core layer. The particle size of the probiotic microparticles is controlled to be 0.1-0.3 mm.

[0146] (2) Slowly adding 6 parts by weight of sodium alginate into 100 parts by weight of hot water at 90° C., mixing evenly, and then cooling to 40° C. to obtain a first gelatinous layer solution; spraying the first gelatinous layer solution evenly on the surface of the probiotic particles forming the core layer, and then rapidly cooling to 10° C. to solidify the first gelatinous layer solution to form a barrier layer.

[0147] That is, the rubber particles are obtained, and the particle size of the rubber particles is controlled to be 0.2-0.5mm.

[0148] 2. Preparation of the First Drug

[0149] (1) Preparation of medical polymer gel: 9 parts by weight of starch was added into 90° C. sterile deionized water, mixed evenly, and cooled to 40° C. to prepare a 30 wt % hydrogel matrix solution;

[0150] Add the formulated amount of anti-inflammatory agent (1 part by mass of fluticasone propionate and 1 part by mass of mometasone furoate) and antibacterial agent (1.5 parts by mass of wogonin) into the hydrogel matrix under stirring, mix well, and obtain a medical polymer gel.

[0151] (2) Add the colloid particles to the medical polymer gel under stirring, control the amount of the colloid particles added to be 3-5% of the mass of the medical polymer gel, and mix them evenly, add a pH adjuster to adjust the pH to 6.5, finally mix them evenly, quickly cool to 4° C., and package to obtain the finished product.

[0152] Clinical Research

[0153] In this study, 130 patients with chronic rhinitis aged 20-55 were selected and randomly divided into 13 groups. Group A and Group C were treatment groups, and the patients were treated with the pharmaceutical composition of the present invention for chronic rhinitis. In Group A, 10 patients were treated with the first and second drugs in Examples 1-4 and Comparative Examples 1-2, respectively, and in Group C, 10 patients were treated with the first drugs in Examples 1-4 and Comparative Examples 1-2, respectively, alone. Group B was the control group, with a total of 10 patients.

[0154] The research methods of each group are as follows:

[0155] Group A: First, use normal saline drops to the nose to remove dirt in the nasal cavity. When used for the first time, apply the first drug to the patient's nose first. After 1-1.5 hours, mix No. 1 powder and No. 2 ointment in a mass ratio of 1:10 and apply an appropriate amount to the patient's nose; in the subsequent use, first apply the first drug to the patient's nose. After 1-1.5 hours, mix No. 1 powder and No. 3 ointment in a mass ratio of 1:10 and apply to the patient's nose.

[0156] Take twice a day, 15 days as a course of treatment.

[0157] Group B: Use normal saline drops to remove dirt from the nasal cavity, and then do not use any drugs or treatment methods, twice a day, and a course of treatment is 15 days.

[0158] Group C: First, drip physiological saline into the nose to remove dirt in the nasal cavity, then dip a clean cotton swab in the first drug in the above embodiment and comparative example, and gently apply it to the nasal concha, twice a day, and 15 days as a course of treatment.

[0159] During the treatment period, patients in groups A, B and C all ate a light diet and avoided spicy and greasy food. After two courses of treatment, the efficacy was evaluated through observation and questioning.

[0160] The evaluation was carried out in accordance with the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases - Standards for Diagnosis and Efficacy of Otolaryngology Diseases" (ZY / T001.6-94).

[0161] Therapeutic index = (pre-treatment score - post-treatment score) / pre-treatment score × 100%.

[0162] The evaluation criteria are as follows:

[0163] 1. Cured: Nasal congestion is completely relieved, sense of smell is normal, there is no abnormal secretion in the nasal cavity, swelling of the nasal mucosa subsides, and there is no swelling of the inferior turbinate. The efficacy index is ≥ 90%.

[0164] 2. Significant effect: The above symptoms and signs are basically relieved. The efficacy is 66-90%.

[0165] 3. Effective: The above symptoms and signs are relieved, but not stable. The efficacy index is 26-66%.

[0166] 4. Ineffective: No significant changes in the above symptoms and signs. The efficacy index is less than 26%.

[0167] According to the TCM symptom quantification table, before and after treatment, the doctor will ask and examine the patient's condition and score according to the symptoms and signs. The scoring criteria are shown in Table 1.

[0168] Table 1 Scoring criteria

[0169]

[0170]

[0171] The treatment effects are shown in Table 2.

[0172] Table 2 Diagnosis and treatment effects

[0173]

[0174] It can be seen that the pharmaceutical composition of the present invention has a good therapeutic effect on chronic rhinitis. Although the embodiments of the present invention have been shown and described, it is understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is limited by the attached claims and their equivalents.

Claims

1. A pharmaceutical composition for treating chronic rhinitis, characterized in that: It comprises a first drug and a second drug, wherein the first drug comprises a medical polymer gel and colloidal particles uniformly dispersed in the medical polymer gel; The medical polymer gel comprises a polymer gel matrix and a first drug component; the first drug component comprises an anti-inflammatory agent and an antibacterial agent; The anti-inflammatory agent includes one or more of fluticasone propionate, mometasone furoate, triamcinolone acetonide, and budesonide; The antibacterial agent includes one or more of baicalein, wogonin, eugenol, emodin, myrsinol, cinnamaldehyde, berberine, and tea polyphenols; The colloid particles include a core layer, a barrier layer, an intermediate layer and an outer layer from the inside to the outside, the core layer includes probiotics, the barrier layer is a first colloid layer, the intermediate layer includes a traditional Chinese medicine composition, and the outer layer is a second colloid layer; The Chinese medicine composition comprises: Xanthium sibiricum, Magnolia flower, Angelica dahurica, Asarum, Menthus fragrans, Licorice root, Saposhnikovia divaricata, Scutellaria baicalensis; The second medicine includes Chinese medicine powder and Chinese medicine ointment.

2. The pharmaceutical composition for treating chronic rhinitis according to claim 1, characterized in that: The polymer gel matrix includes one or more of cellulose, chitin, hyaluronic acid, polyethylene glycol, polylactic acid, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, polyacrylamide, polyacrylate, poly-N-polyacrylamide, starch, sodium alginate, chitosan, collagen, poly-L-lysine, and poly-L-glutamic acid.

3. The pharmaceutical composition for treating chronic rhinitis according to claim 1, characterized in that: The mass ratio of the anti-inflammatory agent to the antibacterial agent is 1:0.5-1.

5.

4. The pharmaceutical composition for treating chronic rhinitis according to claim 1, characterized in that: The materials of the first gelatin layer and the second gelatin layer are the same or different, and are selected from one or more of polyvinyl alcohol, cellulose, chitin, starch, chitosan, sodium alginate, and collagen.

5. The pharmaceutical composition for treating chronic rhinitis according to claim 1, characterized in that: The medical polymer gel also includes a pH regulator, which includes one or more of acetic acid, citric acid, sorbic acid, malic acid, tartaric acid, phosphoric acid, citric acid, maleic acid, sodium bicarbonate, sodium citrate, potassium carbonate, phosphate buffer, borate buffer, and boric acid buffer.

6. The pharmaceutical composition for treating chronic rhinitis according to claim 1, characterized in that: The traditional Chinese medicine composition comprises, by weight: 15-25 parts of Xanthium sibiricum fruit; 8-15 parts of magnolia flower; 8-15 parts of angelica dahurica; 3-10 parts of asarum; 3-10 parts of mint; 3-10 parts of liquorice; 3-10 parts of siler; and 3-15 parts of scutellaria baicalensis.

7. The pharmaceutical composition for treating chronic rhinitis according to claim 1, characterized in that: The probiotics include one or more of lactobacilli and bifidobacteria.

8. The pharmaceutical composition for treating chronic rhinitis according to claim 1, characterized in that: The second medicine includes No. 1 powder, No. 2 ointment and No. 3 ointment; The No. 1 powder comprises: 0.3-1 part of magnolia flower; 1-3 parts of Sichuan coptis root; 0.8-2 parts of notopterygium root; 1-3 parts of forsythia; 0.6-2.5 parts of divaricate cortex; 1-3 parts of siler; 0.3-1.5 parts of xanthium sibiricum; The No. 2 ointment comprises: 1-3 parts of Angelica dahurica; 2-3.5 parts of Scutellaria baicalensis; 1-3.2 parts of Dioscorea opposita; 1-3 parts of Schisandra chinensis; 0.3-1.5 parts of Herba Glechomae; The No. 3 ointment comprises: 1-3 parts of Hedyotis diffusa; 0.5-3 parts of leech; 2-5 parts of Pueraria root; 1-3 parts of mint; 0.3-1.2 parts of raw liquorice; and 1-3 parts of Nepeta tenuifolia.

9. The pharmaceutical composition for treating chronic rhinitis according to claim 8, characterized in that: The No. 1 powder comprises: 0.8 parts of magnolia flower; 2 parts of Sichuan coptis root; 1.5 parts of notopterygium root; 1.5 parts of forsythia; 1.4 parts of divaricate cortex; 2 parts of siler; 0.8 parts of xanthium sibiricum; The No. 2 ointment comprises: 2 parts of Angelica dahurica; 2.8 parts of Scutellaria baicalensis; 2.2 parts of Dioscorea opposita; 2.2 parts of Schisandra chinensis; 0.8 parts of Herba Capillaris; The ointment No. 3 comprises: 2 parts of Hedyotis diffusa; 1 part of leech; 3 parts of Pueraria root; 2 parts of mint; 0.7 parts of raw licorice; and 1.3 parts of Nepeta tenuifolia.

10. A method for preparing a pharmaceutical composition for treating chronic rhinitis according to any one of claims 1 to 9, characterized in that: The preparation of the first drug comprises the following steps:

1. Preparation of colloid particles: (1) culturing probiotic strains in a culture medium, collecting probiotic strains, adding them to an aqueous solution containing a first polymer colloidal material, mixing them evenly, and obtaining probiotic microparticles by spray drying to form a core layer; (2) uniformly coating the first colloid layer solution on the surface of the core layer particles and curing to form a barrier layer; (3) adding the decoction and concentration of the traditional Chinese medicine composition to the aqueous solution containing the second polymer colloidal material, mixing them evenly, and then coating them evenly on the surface of the barrier layer, and curing them to form an intermediate layer; (4) coating the second colloid layer solution evenly on the surface of the middle layer and curing it to form an outer layer; 2. Preparation of the First Drug (1) preparing a medical polymer gel: adding a prescribed amount of an anti-inflammatory agent and an antibacterial agent to a polymer gel matrix solution, mixing the mixture evenly, and obtaining a medical polymer gel; (2) adding the colloid particles to the medical polymer gel, mixing them evenly, and packaging them to obtain the finished product; The preparation of the second drug comprises the following steps: The Chinese medicinal materials are respectively made into Chinese medicinal powder and Chinese medicinal ointment.

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