Nasal mucosa repairing liquid and preparation method thereof

Abstract

The invention provides nasal mucosa repair liquid and a preparation method thereof, and relates to the technical field of mucosa repair. The nasal mucosa repairing liquid comprises recombinant humanized collagen, mini peptide, sodium hyaluronate, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, auxiliary materials and purified water, and the amino acid sequence of the mini peptide is alanine-proline-glycine. The recombinant humanized collagen is added to repair the damaged nasal mucosa, the protein can be utilized only through amino acid small molecule conversion, and the mini peptide is added to improve the utilization rate of the recombinant humanized collagen and accelerate the repair of the damaged skin; sodium hyaluronate has hydrophilicity and moisture retention, can regulate diffusion and transport of recombinant humanized collagen and sodium chloride, promotes mucous membrane healing, and accelerates nasal mucous membrane repair.

Description

Technical Field

[0001] The present invention relates to the technical field of mucosal repair, and in particular to a nasal mucosal repair liquid and a preparation method thereof. Background Art

[0002] The number of patients with various respiratory diseases caused by environmental factors continues to rise. Some harmful substances in the environment are very harmful to people with poor resistance, and are prone to cause rhinitis, sinusitis, etc. As patients with rhinitis and sinusitis pay more attention to nasal care, the demand for nasal care products is increasing. Most of these products on the market are nasal wash solutions, the main ingredient of which is sea salt water, which can relieve discomfort by flushing the nasal cavity. However, most nasal wash solution products have a single liquid component, and the surface of the nasal mucosa is dry after flushing, which slows down the repair of damaged nasal mucosa. Summary of the invention

[0003] The problem solved by the invention is how to solve the problem that the existing nasal cleaning solution slows down the repair of damaged nasal mucosa.

[0004] In order to solve the above problems, the present invention provides a nasal mucosa repair liquid and a preparation method thereof.

[0005] In a first aspect, the present invention provides a nasal mucosal repair liquid, comprising recombinant humanized collagen, mini peptide, sodium hyaluronate, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, auxiliary materials and purified water, wherein the amino acid sequence of the mini peptide is alanine-proline-glycine.

[0006] Optionally, the nasal mucosa repair solution includes, by weight, 1-5% recombinant humanized collagen, 0.1-0.5% mini peptide, 0.05-0.5% sodium hyaluronate, 0.9-2.5% sodium chloride, 0.003%-0.030% sodium dihydrogen phosphate, 0.002%-0.020% sodium hydrogen phosphate, 0.008-0.08% excipients and 70-100% purified water.

[0007] Optionally, the excipients include methylparaben and ethylparaben, the mass fraction of methylparaben in the nasal mucosa repair liquid is 0.005-0.05%, and the mass fraction of ethylparaben in the nasal mucosa repair liquid is 0.003-0.03%.

[0008] Optionally, the recombinant humanized collagen is a mixture of one or more of type I, type II, type III, type IV, and type XVII.

[0009] Optionally, the molecular weight of sodium hyaluronate is 8,000-1,500,000.

[0010] Optionally, the pH value of the nasal mucosal repair solution is 4.0-7.5.

[0011] Optionally, the osmotic pressure molar concentration of the nasal mucosal repair fluid is 270mOsmol / L-350mOsmol / L.

[0012] In a second aspect, the present invention provides a method for preparing a nasal mucosal repair solution as described in any one of the above items, comprising the following steps:

[0013] S1: Add sodium hyaluronate to purified water, stir to dissolve, and soak until the sodium hyaluronate is completely swollen, as phase A;

[0014] S2: Add sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate into purified water and stir until dissolved uniformly, as phase B;

[0015] S3: Add the excipients into purified water and stir until dissolved uniformly, as phase C;

[0016] S4: Add phase B, phase C, mini peptide and recombinant humanized collagen to phase A, stir evenly to obtain nasal mucosal repair solution.

[0017] Optionally, phase B, phase C, mini peptides and recombinant humanized collagen in step S4 are added to phase A, stirred evenly, and then kept at 70°C-90°C for 60min-120min for sterilization.

[0018] Optionally, after the heat preservation is completed, the temperature is cooled to 40°C-50°C, filtered using a 100-mesh-200-mesh filter cloth to obtain a nasal mucosa repair liquid, and canned.

[0019] The beneficial effects of the nasal mucosa repairing liquid and the preparation method thereof of the present invention are as follows: adding recombinant humanized collagen can repair damaged nasal mucosa, and the protein needs to be converted into small molecules of amino acids before it can be utilized. Adding mini peptides can improve the utilization rate of recombinant humanized collagen and accelerate the repair of damaged skin; sodium chloride can dehydrate and shrink the edematous nasal mucosa, reduce the edematous state of the nasal mucosa, and relieve the symptoms of nasal congestion; adding sodium hyaluronate as a moisturizer and film-forming agent can form a thin film on the surface of the nasal mucosa when cleaning the nasal cavity, reduce the stimulation of pathogenic allergens and inflammatory mediators to the nasal mucosa, thereby relieving symptoms such as rhinitis and sinusitis, and at the same time, sodium hyaluronate has hydrophilicity and moisturizing properties, can regulate the diffusion and transport of recombinant humanized collagen and sodium chloride, promote mucosal healing, and accelerate the repair of nasal mucosa; adding phosphate buffer sodium dihydrogen phosphate and disodium hydrogen phosphate to maintain the stability of the repairing liquid. DETAILED DESCRIPTION

[0020] In order to make the above-mentioned purposes, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below. It should be understood that the embodiments of the present invention are only used for exemplary purposes and are not used to limit the scope of protection of the present invention.

[0021] Unless otherwise defined, all technical and scientific terms used in this application have the same meanings as those commonly understood by those skilled in the art to which this application belongs; the terms used in the specification of this application are only for the purpose of describing specific implementation methods and are not intended to limit this application;

[0022] The term "including" and its variations used in this article are open inclusions, that is, "including but not limited to"; the term "based on" is "based at least in part on"; the term "one embodiment" means "at least one embodiment"; the term "another embodiment" means "at least one other embodiment"; the term "some embodiments" means "at least some embodiments"; the term "optionally" means "optional embodiments". The relevant definitions of other terms will be given in the following description. It should be noted that the concepts of "first" and "second" mentioned in the present invention are used to distinguish different objects, rather than to describe a specific order or a primary and secondary relationship. In addition, the terms "first" and "second" are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of this application, unless otherwise specified, the meaning of "multiple" is two or more.

[0023] In the relevant technology, collagen is the main component of the extracellular matrix. It is the most widely distributed and abundant protein in animals, and is mainly distributed in the connective tissue of mammals. Collagen levels are closely related to mucosal repair, cell support and regeneration, but mucosal damage will be accompanied by a large loss of collagen, so the main way to repair mucosa is to supplement collagen. Studies have shown that recombinant humanized collagen can promote full-thickness wound healing and angiogenesis, promote the orderly arrangement of collagen fibers in the new dermis, and has the function of repairing skin trauma and improving the quality of wound healing.

[0024] Amino acids are an important material basis for living organisms. Even proteins need to be converted into small molecules of amino acids before they can be used. Amino acids also have a good effect on the skin. Peptides composed of 2-10 amino acids are called oligopeptides or small molecule peptides (mini peptides).

[0025] Hyaluronic acid is a disaccharide derivative formed by β-D-glucuronic acid and N-acetyl-D-glucosamine connected by β-1,3-glycosidic bonds, and then connected to each other by β-1,4-glycosidic bonds as a repeating unit to form an acidic mucopolysaccharide. Hyaluronic acid and its derivatives are highly hydrophilic and moisturizing, and are good transdermal absorption promoters that can regulate the diffusion and transport of proteins, water, and electrolytes and promote mucosal healing. At the same time, sodium hyaluronate, as a high molecular polymer, has strong lubricity and film-forming properties, and can form a thin film on the surface of the mucosa to protect the mucosa.

[0026] In view of the problem that the nasal cleaning solution in the related art slows down the repair of damaged nasal mucosa, this embodiment provides a nasal mucosa repair solution and a preparation method thereof.

[0027] A nasal mucosal repair liquid provided in an embodiment of the present invention includes recombinant humanized collagen, mini peptide, sodium hyaluronate, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, excipients and purified water, and the amino acid sequence of the mini peptide is alanine-proline-glycine (APG, A is alanine, P is proline, and G is glycine).

[0028] In this embodiment, adding recombinant humanized collagen can repair damaged nasal mucosa. Protein needs to be converted into small molecules of amino acids before it can be used. Adding mini peptides can improve the utilization rate of recombinant humanized collagen and accelerate the repair of damaged skin; sodium chloride can dehydrate and shrink the edematous nasal mucosa, reduce the edema of the nasal mucosa, and relieve nasal congestion symptoms; adding sodium hyaluronate as a moisturizer and film-forming agent, when cleaning the nasal cavity, it can form a thin film on the surface of the nasal mucosa, reduce the stimulation of pathogenic allergens and inflammatory mediators to the nasal mucosa, thereby relieving symptoms such as rhinitis and sinusitis, and sodium hyaluronate has hydrophilicity and moisturizing properties, which can regulate the diffusion and transport of recombinant humanized collagen and sodium chloride, promote mucosal healing, and accelerate the repair of nasal mucosa; adding phosphate buffer sodium dihydrogen phosphate and disodium hydrogen phosphate to maintain the stability of the repair solution. In summary, the nasal mucosal repair solution provided in this embodiment can not only relieve symptoms such as rhinitis and sinusitis, but also accelerate the repair of damaged nasal mucosa.

[0029] Optionally, the nasal mucosa repair solution includes, by weight, 1-5% recombinant humanized collagen, 0.1-0.5% mini peptide, 0.05-0.5% sodium hyaluronate, 0.9-2.5% sodium chloride, 0.003%-0.030% sodium dihydrogen phosphate, 0.002%-0.020% sodium hydrogen phosphate, 0.008-0.08% excipients and 70-100% purified water.

[0030] In this optional embodiment, recombinant humanized collagen and mini peptides are in liquid form, and the nasal mucosal repair solution made of sodium hyaluronate with different molecular weights can achieve film formation. The nasal mucosal repair solution has good film-forming properties and can form a protective layer on the surface of the nasal mucosa, acting as a physical barrier. Sodium dihydrogen phosphate and disodium hydrogen phosphate are used as phosphate buffer salts, and adding a small amount of sodium dihydrogen phosphate and disodium hydrogen phosphate can maintain the stability of the repair solution.

[0031] Optionally, the excipients include methylparaben and ethylparaben, the mass fraction of methylparaben in the nasal mucosa repair liquid is 0.005-0.05%, and the mass fraction of ethylparaben in the nasal mucosa repair liquid is 0.003-0.03%.

[0032] Optionally, the recombinant humanized collagen is a mixture of one or more of type I, type II, type III, type IV, and type XVII.

[0033] Specifically, type I, type II, type III, type IV, and type XVII recombinant humanized collagen are collagens obtained using recombinant DNA technology. Their gene sequences are consistent with human collagen gene sequences, and they have the characteristics of good water solubility, low immunogenicity, and high safety. Because they contain a large number of hydrophilic groups to form ionic bonds, hydrogen bonds and other forces, they have good water absorption and water retention properties, and thus have good moisturizing function.

[0034] Optionally, the molecular weight of sodium hyaluronate is 8,000-1,500,000.

[0035] In this optional embodiment, sodium hyaluronate with a molecular weight of 8,000-1.5 million can form a thin film on the surface of the nasal mucosa and has excellent hydrophilicity and moisturizing properties.

[0036] Optionally, the pH value of the nasal mucosal repair solution is 4.0-7.5.

[0037] In this optional embodiment, the pH value of a normal nasal cavity is generally around 6.5 to 7.5, and the pH value of the nasal cavity of a rhinitis patient tends to be alkaline. The pH value of the repair fluid is set to 4.0-7.5 to neutralize the alkaline environment of the nasal cavity of a rhinitis patient and accelerate the repair of damaged skin.

[0038] Optionally, the osmotic pressure molar concentration of the nasal mucosal repair fluid is 270mOsmol / L-350mOsmol / L.

[0039] In this optional embodiment, the osmotic pressure molar concentration is 270mOsmol / L-350mOsmol / L, so that the nasal mucosal repair fluid can quickly diffuse and penetrate into the nasal mucosa, promote mucosal healing, and accelerate the repair of the nasal mucosa.

[0040] An embodiment of the present invention provides a method for preparing a nasal mucosal repair solution as described in any one of the above items, comprising the following steps:

[0041] S1: Add sodium hyaluronate to purified water, stir to dissolve, and soak until the sodium hyaluronate is completely swollen, as phase A;

[0042] S2: Add sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate into purified water and stir until dissolved uniformly, as phase B;

[0043] S3: Add the excipients into purified water and stir until dissolved uniformly, as phase C;

[0044] S4: Add phase B, phase C, mini peptide and recombinant humanized collagen to phase A, stir evenly to obtain nasal mucosal repair solution.

[0045] Specifically, the raw materials are dissolved and physically mixed according to their physical properties such as solubility, dissolution conditions and polarity; sodium hyaluronate can be completely swollen after being immersed for more than 30 minutes.

[0046] Optionally, phase B, phase C, mini peptides and recombinant humanized collagen in step S4 are added to phase A, stirred evenly, and then kept at 70°C-90°C for 60min-120min for sterilization.

[0047] In this optional embodiment, the intermediate microorganisms are sterilized by heating and keeping warm at a temperature of 70°C-90°C. During the intermediate processing, heating and keeping warm are used as key steps in product processing. This not only promotes the uniform mixing of the raw materials, but also controls the intermediate microorganisms to obtain a microbially controllable nasal mucosal repair fluid, thereby avoiding introducing microorganisms to the mucosa and affecting mucosal repair.

[0048] Optionally, after the heat preservation is completed, the temperature is cooled to 40°C-50°C, filtered using a 100-mesh-200-mesh filter cloth to obtain a nasal mucosa repair liquid, and canned.

[0049] In this optional embodiment, insoluble impurities are removed by filtration.

[0050] The present invention is further described below in conjunction with specific embodiments.

[0051] Example 1

[0052] The nasal mucosal repair liquid includes, by mass, 0.5% mini peptide, 5% recombinant type III humanized collagen, 0.05% sodium hyaluronate (molecular weight 200,000), 0.9% sodium chloride, 0.018% sodium dihydrogen phosphate, 0.004% disodium hydrogen phosphate, 0.05% methylparaben, 0.025% ethylparaben, and 93.453% purified water.

[0053] The preparation method of nasal mucosa repair liquid comprises the following steps:

[0054] S1: Weigh the raw materials of each formula, including mini peptides, recombinant humanized collagen type III, sodium hyaluronate, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, methylparaben, ethylparaben, and purified water, and place them aside after weighing according to the ratio;

[0055] S2: Add sodium hyaluronate to 70% purified water, stir and soak for 30 minutes until completely swollen, as phase A;

[0056] S3: Add sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate into 5% purified water and stir until dissolved uniformly, as phase B;

[0057] S4: Add methylparaben and ethylparaben to the remaining 18.453% purified water and stir until dissolved uniformly to form phase C;

[0058] S5: Add phase B, phase C, mini peptides, and recombinant humanized collagen to phase A, stir evenly, and keep at 70°C for 120 min for sterilization;

[0059] S6: After the heat preservation, cool down to 40°C and filter with a 200-mesh filter cloth to remove insoluble impurities;

[0060] S7: Fill and package the nasal mucosa repair liquid obtained in S6.

[0061] Comparative Example 1

[0062] Nasal mucosa repair fluid, including 5% recombinant humanized type III collagen, 0.1% sodium hyaluronate (200,000 Da), 2.5% sodium chloride, 0.025% sodium dihydrogen phosphate, 0.002% disodium hydrogen phosphate, 0.05% methylparaben, 0.025% ethylparaben, and 92.298 purified water.

[0063] The preparation method of nasal mucosa repair liquid comprises the following steps:

[0064] S1: Weighing: weigh the raw materials of each formula, including recombinant humanized type III collagen, sodium hyaluronate, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, methylparaben, ethylparaben, and purified water, and place them aside after weighing according to the ratio;

[0065] S2: Add sodium hyaluronate to 70% purified water, stir and soak for 30 minutes until completely swollen, as phase A;

[0066] S3: Add sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate into 5% purified water and stir until dissolved uniformly, as phase B;

[0067] S4: Add methylparaben and ethylparaben to the remaining 17.298% purified water and stir until dissolved uniformly to form phase C;

[0068] S5: Add phase B, phase C, and recombinant humanized type III collagen to phase A, stir evenly, and keep at 85°C for 90 minutes for sterilization;

[0069] S6: After the heat preservation, cool down to 40°C and filter with a 200-mesh filter cloth to remove insoluble impurities;

[0070] S7: Fill and package the nasal mucosa repair liquid obtained in S6.

[0071] Comparative Example 2

[0072] Nasal mucosa repair fluid, including sodium hyaluronate (200,000) 0.1%, sodium chloride 2.5%, sodium dihydrogen phosphate 0.025%, disodium hydrogen phosphate 0.002%, methylparaben 0.05%, ethylparaben 0.025%, purified water 97.298%.

[0073] The preparation method of nasal mucosa repair liquid comprises the following steps:

[0074] S1: Weighing: weigh the raw materials of each formula, including sodium hyaluronate, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, methylparaben, ethylparaben, and purified water, and place them aside after weighing according to the proportion;

[0075] S2: Add sodium hyaluronate to 70% purified water, stir and soak until completely swollen, as phase A;

[0076] S3: Add sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate into 5% purified water and stir until dissolved uniformly, as phase B;

[0077] S4: Add methylparaben and ethylparaben into 22.298% purified water and stir until dissolved uniformly, as phase C;

[0078] S5: Add phase B and phase C into phase A, stir evenly, and keep at 85℃ for 90min for sterilization;

[0079] S6: After the heat preservation, cool down to 40°C and filter with a 200-mesh filter cloth to remove insoluble impurities;

[0080] S7: Fill and package the nasal mucosa repair liquid obtained in S6.

[0081] Experiment 1: 30 volunteers with rhinitis and sinusitis were randomly selected, 15 men and 15 women, aged between 20 and 70 years old, and were evenly divided into 3 groups, with 5 men and 5 women in each group. The clinical use effects of the samples prepared in the above embodiments (Example 1: Group 1; Comparative Example 1: Group 2; Comparative Example 2: Group 3) were compared: the comparison results are shown in Table 1.

[0082] Table 1 Comparison of clinical effects of nasal mucosal repair liquid

[0083]

[0084]

[0085]

[0086]

[0087] As can be seen from Table 1, the nasal mucosa repair liquid of the present application can repair damaged nasal mucosa, reduce nasal mucosal edema, relieve nasal congestion symptoms, and relieve rhinitis, sinusitis and other symptoms. After 15 days of use, the symptom relief efficiency can reach 70%.

[0088] Although the present invention is disclosed as above, the protection scope of the present invention is not limited thereto. Those skilled in the art may make various changes and modifications without departing from the spirit and scope of the present invention, and these changes and modifications will fall within the protection scope of the present invention.

Claims

1. A nasal mucosal repair solution, characterized in that: The invention comprises recombinant humanized collagen, mini peptide, sodium hyaluronate, sodium chloride, sodium dihydrogen phosphate, sodium dihydrogen phosphate, auxiliary materials and purified water. The amino acid sequence of the mini peptide is alanine-proline-glycine.

2. The nasal mucosa repair solution according to claim 1, characterized in that: By weight, the nasal mucosa repair solution includes 1-5% recombinant humanized collagen, 0.1-0.5% mini peptide, 0.05-0.5% sodium hyaluronate, 0.9-2.5% sodium chloride, 0.003%-0.030% sodium dihydrogen phosphate, 0.002%-0.020% disodium hydrogen phosphate, 0.008-0.08% excipients and 70-100% purified water.

3. The nasal mucosa repair solution according to claim 2, characterized in that: The auxiliary materials include methylparaben and ethylparaben, wherein the mass fraction of the methylparaben in the nasal mucosa repairing liquid is 0.005-0.05%, and the mass fraction of the ethylparaben in the nasal mucosa repairing liquid is 0.003-0.03%.

4. The nasal mucosa repairing liquid according to claim 1, characterized in that: The recombinant humanized collagen is a mixture of one or more of type I, type II, type III, type IV, and type XVII.

5. The nasal mucosa repairing liquid according to claim 1, characterized in that: The molecular weight of the sodium hyaluronate is 8,000-1,500,000.

6. The nasal mucosa repairing liquid according to claim 1, characterized in that: The pH value of the nasal mucosa repair liquid is 4.0-7.

5.

7. The nasal mucosa repairing liquid according to claim 1, characterized in that: The osmotic pressure molar concentration of the nasal mucosal repair fluid is 270mOsmol / L-350mOsmol / L.

8. A method for preparing the nasal mucosa repair solution according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1: adding sodium hyaluronate to purified water, stirring to dissolve, and soaking until the sodium hyaluronate is completely swollen, as phase A; S2: Add sodium chloride, sodium dihydrogen phosphate and disodium hydrogen phosphate into purified water and stir until dissolved uniformly, as phase B; S3: Add the excipients into purified water and stir until dissolved uniformly, as phase C; S4: Add the phase B, the phase C, the mini peptide and the recombinant humanized collagen to the phase A, stir evenly, and obtain a nasal mucosa repair solution.

9. The method for preparing the nasal mucosa repairing liquid according to claim 8, characterized in that: The phase B, the phase C, the mini peptide and the recombinant humanized collagen in the step S4 are added to the phase A, stirred evenly, and then kept at a temperature of 70° C. to 90° C. for 60 min to 120 min for sterilization.

10. The method for preparing the nasal mucosa repairing liquid according to claim 9, characterized in that: After the heat preservation is completed, the mixture is cooled to 40° C.-50° C. and filtered using a 100-mesh to 200-mesh filter cloth to obtain the nasal mucosa repair liquid.

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