Panax notoginseng total saponin oral spray and processing method thereof

Abstract

The invention relates to the field of medicine, and discloses a panax notoginseng total saponin oral spray and a processing method.The panax notoginseng total saponin oral spray comprises a first spray body and a second spray body, and the preparation method comprises the steps that an active ingredient A with the anti-inflammatory effect is dissolved in a chitosan solution, then a sodium tripolyphosphate solution is added, and nanoparticles containing the active ingredient A are obtained through centrifugation; nanoparticles containing an active component A are dispersed in a carbomer solution to obtain a first spray, the active component A comprises panax notoginseng saponins, and a component B with a hemostatic effect is dissolved in water to obtain a second spray. The component B capable of rapidly stopping bleeding is prepared into the spray and can be directly sprayed to rapidly stop bleeding, the active component A with an anti-inflammatory effect is prepared into nanoparticles and then dispersed in a carbomer solution, and chitosan is used for loading and slowly releasing the active component A, so that the long-acting release of the active component A in the oral cavity is realized.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a Panax notoginseng saponin oral spray and a processing method thereof. Background Art

[0002] Oral inflammation, including pharyngitis, gingivitis, and oral ulcers, can easily damage the oral mucosa, causing significant pain and even affecting eating and speaking. It is a common health ailment. Traditional treatments rely on anti-inflammatory drugs such as metronidazole, acyclovir, and chlorethidine acetate. While these Western medications have strong anti-inflammatory properties, frequent use can easily lead to drug resistance.

[0003] In recent years, with the rise of research and development of traditional Chinese medicine, a large number of traditional Chinese medicine anti-inflammatory drugs have been produced. These drugs generally come from traditional Chinese herbal medicines and are mainly composed of natural ingredients (such as honeysuckle, borneol, coptis chinensis, etc.). Because of their small side effects and in line with consumer preferences, they occupy a large market share. However, due to the complex oral environment, such as saliva flushing and pH fluctuations, the active ingredients are easily degraded or lost, affecting the duration of the therapeutic effect. Summary of the Invention

[0004] The purpose of the present invention is to overcome the problem of easy degradation or loss of active ingredients in existing oral sprays, and to provide a Panax notoginseng total saponin oral spray and a processing method.

[0005] In order to achieve the above object, the first aspect of the present invention provides a method for preparing a Panax notoginseng saponin oral spray, wherein the Panax notoginseng saponin oral spray comprises a first spray and a second spray, and the preparation method comprises:

[0006] Dissolving an active ingredient A having an anti-inflammatory effect in a chitosan solution, adding a sodium tripolyphosphate solution, and centrifuging to obtain nanoparticles containing the active ingredient A. Dispersing the nanoparticles containing the active ingredient A in a carbomer solution to obtain a first spray, wherein the active ingredient A includes Panax notoginseng total saponins;

[0007] The second spray is obtained by dissolving component B having a hemostatic effect in water.

[0008] The second aspect of the present invention provides a Panax notoginseng saponin oral spray prepared by the preparation method according to the first aspect of the present invention, wherein the method for using the Panax notoginseng saponin oral spray comprises:

[0009] Spray the second spray on the affected surface, wait for a preset time, and then spray the first spray again.

[0010] Compared with the prior art, the present invention has the following beneficial effects:

[0011] The present invention prepares component B that can quickly stop bleeding into a spray that can be directly sprayed for quick hemostasis. Active ingredient A with an anti-inflammatory effect is prepared into nanoparticles and then dispersed in a carbomer solution. Chitosan is used to load and slowly release the active ingredient A. Meanwhile, the carbomer solution can form an adhesion layer in the oral cavity, thereby achieving a slow release of the active ingredient A in the oral cavity, allowing it to stay in the oral cavity for a long time and not be easily washed away by saliva, thereby playing an anti-inflammatory role and significantly improving the anti-inflammatory efficiency and shortening the recovery time.

[0012] In addition, since the first spray can adhere to the wound surface in the oral cavity for a long time, it isolates the stimulation of oral saliva on the wound surface and possible friction, and unexpectedly can significantly reduce the pain. DETAILED DESCRIPTION

[0013] The specific embodiments of the present invention are described in detail below with reference to the examples and comparative examples. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention.

[0014] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0015] The endpoints of the ranges and any values disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0016] In addition, the term "and / or" in the specification and claims is used to describe an association relationship between associated objects, indicating that three possible relationships exist. For example, "A and / or B" can represent three situations: A exists alone, A and B exist simultaneously, and B exists alone. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0017] In order to achieve the above object, the first aspect of the present invention provides a method for preparing a Panax notoginseng saponin oral spray, wherein the Panax notoginseng saponin oral spray comprises a first spray and a second spray, and the preparation method comprises:

[0018] Dissolving an active ingredient A having an anti-inflammatory effect in a chitosan solution, adding a sodium tripolyphosphate solution, and centrifuging to obtain nanoparticles containing the active ingredient A. Dispersing the nanoparticles containing the active ingredient A in a carbomer solution to obtain a first spray, wherein the active ingredient A includes Panax notoginseng total saponins;

[0019] The second spray is obtained by dissolving component B having a hemostatic effect in water.

[0020] Preferably, the preparation method further comprises: dispersing the nanoparticles containing the active ingredient A in a carbomer solution, and then adding sodium alginate to obtain the first spray. After the sodium alginate enters the oral cavity, it cross-links into a gel upon encountering calcium ions in saliva, forming a double adhesion barrier with the carbomer solution, further increasing the residence time of the active ingredient A in the oral cavity.

[0021] Preferably, the amount of the sodium alginate is 0.1-0.2 wt.% based on the total amount of the carbomer solution.

[0022] Preferably, the amount of active ingredient A is 5-10 wt.% based on the total amount of the chitosan solution. The amount of active ingredient A can be any value between any two numbers between 5 wt.%, 6 wt.%, 7 wt.%, 8 wt.%, 9 wt.%, and 10 wt.% based on the total amount of the chitosan solution.

[0023] Preferably, the amount of the nanoparticles containing the active ingredient A is 1-5 wt.% based on the total amount of the carbomer solution. The amount of the nanoparticles containing the active ingredient A can be any value between any two numbers between 1 wt.%, 2 wt.%, 3 wt.%, 4 wt.%, and 5 wt.% based on the total amount of the carbomer solution.

[0024] Preferably, the active ingredient A further comprises tea polyphenols, honeysuckle chlorogenic acid and baicalin.

[0025] Preferably, the mass ratio of Panax notoginseng total saponins, tea polyphenols, honeysuckle chlorogenic acid and baicalin is 5-10:1:2-5:5-10. The mass ratio of Panax notoginseng total saponins, tea polyphenols, honeysuckle chlorogenic acid and baicalin can be any value between any two numbers between 5:1:2:10, 6:1:2:10, 7:1:2:10, 8:1:2:10, 9:1:2:10, 10:1:2:10, 5:1:3:10, 5:1:4:10, 5:1:5:10, 5:1:2:9, 5:1:2:8, 5:1:2:7, 5:1:2:6, and 5:1:2:5.

[0026] Preferably, the mass volume ratio of the component B having a hemostatic effect to water is 1-5: 100. The mass volume ratio of the component B having a hemostatic effect to water can be any value between any two numbers between 1:100, 2:100, 3:100, 4:100, and 5:100.

[0027] Preferably, the component B includes Bletilla striata extract, Agrimoniae scabra extract and Thuja serrata charcoal.

[0028] Preferably, the component B further comprises probiotic powder, and the preparation method of the component B comprises:

[0029] Lactobacillus paracasei, Lactobacillus reuteri and Streptococcus salivarius are mixed in a ratio of 2-5:1:1 to obtain a mixed bacteria;

[0030] dissolving trehalose, cyclodextrin and gelatin in water to obtain a protective agent, wherein, based on the total amount of the protective agent, the amount of trehalose is 2-5 wt.%, the amount of cyclodextrin is 0.1-0.5 wt.%, and the amount of gelatin is 0.5-1 wt.%;

[0031] The mixed bacteria and the protective agent are mixed in a ratio of 1:1-2 and then spray-dried to obtain probiotic powder;

[0032] The probiotic powder is mixed with Bletilla striata extract, Agrimoniae herb extract and Pleurotus ostreatus charcoal to obtain the component B, wherein the mass ratio of the probiotic powder, Bletilla striata extract, Agrimoniae herb extract and Pleurotus ostreatus charcoal is 0.5-1:2-5:1-2:1.

[0033] Lactobacillus paracasei has the function of inhibiting harmful bacteria in the oral cavity and balancing the microecology; Lactobacillus reuteri can reduce dental plaque and relieve bad breath; Streptococcus salivarius can secrete antimicrobial peptides and prevent throat infections. The present invention compounds the three bacterial agents and uses trehalose and gelatin to protect the probiotics, which is beneficial to improving their survival rate. This can provide a comprehensive probiotic supplement for the oral cavity and has a significant effect on relieving oral inflammation and accelerating recovery.

[0034] The mass ratio of probiotic powder, Bletilla striata extract, Herba Agrimoniae extract and Pleurotus ostreatus charcoal can be any value between any two numbers between 0.5:2:1:1, 0.5:3:1:1, 0.5:4:1:1, 0.5:5:1:1, 0.5:2:2:1, 1:2:2:1, 1:3:1:1, 1:4:1:1, 1:5:1:1, 1:2:2:1 and 0.7:2:2:1.

[0035] Preferably, the chitosan solution has a concentration of 0.5-1 wt.% based on the total amount of the chitosan solution. The chitosan solution includes chitosan as a solute and glacial acetic acid solution as a solvent. The concentration of the glacial acetic acid solution is 0.5-1 wt.% based on the total amount of the glacial acetic acid solution.

[0036] Preferably, the concentration of the sodium tripolyphosphate solution is 0.01-0.1 wt.% based on the total amount of the sodium tripolyphosphate solution.

[0037] Preferably, the concentration of the carbomer solution is 0.5-2 wt.% based on the total amount of the carbomer solution.

[0038] Preferably, the volume ratio of the sodium tripolyphosphate solution to the chitosan solution is 1-2: 1. The volume ratio of the sodium tripolyphosphate solution to the chitosan solution can be any value between any two numbers between 1:1, 1.5:1, and 2:1.

[0039] The second aspect of the present invention provides a Panax notoginseng saponin oral spray prepared by the preparation method according to the first aspect of the present invention, wherein the method for using the Panax notoginseng saponin oral spray comprises:

[0040] Spray the second spray on the affected surface, wait for a preset time, and then spray the first spray again.

[0041] There is no particular limitation on the preset time, and it may be 30-60 seconds, for example.

[0042] When the present invention is used, the second spray is first sprayed, and then the first spray is sprayed. Rapid hemostasis is achieved through the second spray. At the same time, the probiotics rich in the second spray can also form a probiotic layer on the affected surface, inhibiting the reproduction of harmful bacteria and helping to speed up recovery. Then the first anti-inflammatory spray is sprayed. The first spray can stay on the affected surface for a long time, achieving the purpose of long-term anti-inflammatory.

[0043] The present invention sprays a spray that stops bleeding, inhibits bacteria and supplements beneficial bacteria, and a spray that reduces inflammation, respectively. The second spray acts directly on the bleeding site to achieve the purpose of rapid hemostasis. The second spray can stay on the affected surface for a long time, and the active ingredients with anti-inflammatory effects are gradually and slowly released to achieve the purpose of long-lasting anti-inflammatory. This solves the problem that traditional sprays are susceptible to pH fluctuations or easy degradation or loss of active ingredients due to saliva washing, and the duration of therapeutic effect is significantly improved. The probiotics rich in the spray can inhibit the reproduction of harmful bacteria, further improving the efficiency of alleviating oral inflammation and accelerating the recovery process.

[0044] The present invention will be further described below with reference to specific embodiments.

[0045] In the following examples and comparative examples, unless otherwise specified, all reagents or instruments used without manufacturer identification are commercially available. If specific conditions are not specified in the examples, conventional conditions or those recommended by the manufacturer were followed.

[0046] Preparation Example 1

[0047] S1, grinding dried agrimony through a 30-mesh sieve to obtain agrimony powder.

[0048] The agrimony powder and 70% ethanol were mixed at a solid-liquid ratio of 1:20, 0.1 wt.% citric acid solution was added based on the total amount of the mixed liquid, and the mixture was refluxed and extracted at 80° C. for 1.5 h, and filtered to obtain a first filtrate and a filter residue.

[0049] The filter residue and water were mixed at a solid-liquid ratio of 1:10, and acetic acid was added to adjust the pH to 5.0. The mixture was extracted at 80° C. for 40 minutes and filtered to obtain a second filtrate.

[0050] The first filtrate and the second filtrate were mixed, concentrated under reduced pressure at 60° C. to a relative density of 1.20 (measured at 60° C.), and the concentrate was spray-dried to obtain the Agrimony Root extract.

[0051] S2, grinding the dried tubers of Bletilla striata through a 60-mesh sieve to obtain Bletilla striata powder.

[0052] The Bletilla striata powder and 90% ethanol were mixed at a solid-liquid ratio of 1:12, and the mixture was refluxed and extracted at 80° C. for 1.5 h, and filtered to obtain a first filtrate and a filter residue.

[0053] The filter residue and water were mixed at a solid-liquid ratio of 1:12, extracted at 90° C. for 60 min, and filtered to obtain a second filtrate.

[0054] The first filtrate and the second filtrate were mixed, concentrated under reduced pressure at 60° C. to a relative density of 1.15 (measured at 60° C.), and the concentrated solution was spray-dried to obtain a Bletilla striata extract.

[0055] S3, taking dried truncatum leaves, calcining them at 180°C for 30 min, and then crushing them through a 100-mesh sieve to obtain truncatum leaf charcoal.

[0056] Example 1

[0057] S10, preparing the first spray:

[0058] Weigh 0.7 g of chitosan, dissolve it in 100 mL of 1% glacial acetic acid solution, and stir until it is completely dissolved to obtain a chitosan solution.

[0059] Weigh 0.15 g of sodium tripolyphosphate, dissolve it in 150 mL of ultrapure water, and stir until it is completely dissolved to obtain a sodium tripolyphosphate solution.

[0060] Weigh 1 g of carbomer, dissolve it in 100 mL of ultrapure water at 70° C., and stir until it is completely dissolved to obtain a carbomer solution.

[0061] Notoginseng total saponins, tea polyphenols, honeysuckle chlorogenic acid and baicalin were mixed in a mass ratio of 10:1:3:5 to obtain active ingredient A. 9.5 g of the active ingredient A was added to the chitosan solution, and then dropped into the sodium tripolyphosphate solution within 30 minutes while stirring. The mixture was then centrifuged and freeze-dried to obtain a nanoparticle powder containing active ingredient A.

[0062] Disperse 4.2 g of nanoparticle powder containing active ingredient A into 100 mL of the carbomer solution, then add 0.15 g of sodium alginate, stir until dissolved, and filter through a 0.22 μm microporous filter membrane to obtain a first spray. The first spray should be stored in a light-proof spray bottle.

[0063] S20: Prepare the second spray:

[0064] Lactobacillus paracasei, Lactobacillus reuteri and Streptococcus salivarius were mixed in a ratio of 2:1:1 to obtain a mixed bacteria.

[0065] 3 g of trehalose, 0.3 g of cyclodextrin and 1 g of gelatin were dissolved in 100 mL of water, and the mixture was heated at 50° C. and stirred until completely dissolved to obtain a protective agent.

[0066] The mixed bacteria and the protective agent are mixed in a ratio of 1:1 and then spray-dried to obtain probiotic powder.

[0067] The probiotic powder, the Bletilla striata extract of Preparation Example 1, the Agrimoniae herb extract and the Pleurotus ostreatus charcoal were mixed in a mass ratio of 0.5:3:2:1 to obtain component B.

[0068] Mix 4.5g of component B with 100mL of ultrapure water and filter through a 0.22μm microporous filter membrane to obtain the second spray. The second spray should be stored in a light-proof spray bottle.

[0069] When using, spray the second spray first, wait 30 seconds and then spray the first spray. Do not drink water for 30 minutes after spraying the first spray.

[0070] Example 2

[0071] S10, preparing the first spray:

[0072] Weigh 0.78 g of chitosan, dissolve it in 100 mL of 1% glacial acetic acid solution, and stir until it is completely dissolved to obtain a chitosan solution.

[0073] Weigh 0.09 g of sodium tripolyphosphate, dissolve it in 150 mL of ultrapure water, and stir until it is completely dissolved to obtain a sodium tripolyphosphate solution.

[0074] Weigh 0.6 g of carbomer, dissolve it in 100 mL of ultrapure water at 70° C., and stir until it is completely dissolved to obtain a carbomer solution.

[0075] Notoginseng total saponins, tea polyphenols, honeysuckle chlorogenic acid and baicalin were mixed in a mass ratio of 8:1:2:10 to obtain active ingredient A. 5.5 g of the active ingredient A was added to the chitosan solution, and then dropped into the sodium tripolyphosphate solution within 30 minutes while stirring. The mixture was then centrifuged and freeze-dried to obtain a nanoparticle powder containing the active ingredient A.

[0076] Disperse 2.1 g of nanoparticle powder containing active ingredient A into 100 mL of the carbomer solution, then add 0.18 g of sodium alginate, stir until dissolved, and filter through a 0.22 μm microporous filter membrane to obtain a first spray. The first spray should be stored in a light-proof spray bottle.

[0077] S20: Prepare the second spray:

[0078] Lactobacillus paracasei, Lactobacillus reuteri and Streptococcus salivarius were mixed in a ratio of 3:1:1 to obtain a mixed bacteria.

[0079] 2.2 g of trehalose, 0.4 g of cyclodextrin and 0.8 g of gelatin were dissolved in 100 mL of water, heated at 50° C. and stirred until completely dissolved to obtain a protective agent.

[0080] The mixed bacteria and the protective agent are mixed in a ratio of 1:2 and then spray-dried to obtain probiotic powder.

[0081] The probiotic powder, the Bletilla striata extract of Preparation Example 1, the Agrimoniae herb extract and the Pleurotus ostreatus charcoal were mixed in a mass ratio of 1:5:1:1 to obtain component B.

[0082] Mix 2.2 g of component B with 100 mL of ultrapure water and filter through a 0.22 μm microporous membrane to obtain the second spray. The second spray should be stored in a light-proof spray bottle.

[0083] When using, spray the second spray first, then spray the first spray 30 seconds later. Do not drink water for 30 minutes after spraying the first spray.

[0084] Example 3

[0085] S10, preparing the first spray:

[0086] Weigh 0.6 g of chitosan, dissolve it in 100 mL of 1% glacial acetic acid solution, and stir until it is completely dissolved to obtain a chitosan solution.

[0087] Weigh 0.12 g of sodium tripolyphosphate, dissolve it in 150 mL of ultrapure water, and stir until it is completely dissolved to obtain a sodium tripolyphosphate solution.

[0088] 1.4 g of carbomer was weighed and dissolved in 100 mL of ultrapure water at 70° C., and stirred until completely dissolved to obtain a carbomer solution.

[0089] Notoginseng total saponins, tea polyphenols, honeysuckle chlorogenic acid and baicalin were mixed in a mass ratio of 5:1:5:8 to obtain active ingredient A. 7.5 g of the active ingredient A was added to the chitosan solution, and then dropped into the sodium tripolyphosphate solution within 30 minutes while stirring. The mixture was then centrifuged and freeze-dried to obtain a nanoparticle powder containing the active ingredient A.

[0090] Disperse 1.5 g of nanoparticle powder containing active ingredient A into 100 mL of the carbomer solution, then add 0.15 g of sodium alginate, stir until dissolved, and filter through a 0.22 μm microporous filter membrane to obtain a first spray. The first spray should be stored in a light-proof spray bottle.

[0091] S20: Prepare the second spray:

[0092] Lactobacillus paracasei, Lactobacillus reuteri and Streptococcus salivarius were mixed in a ratio of 5:1:1 to obtain a mixed bacteria.

[0093] 5 g of trehalose, 0.3 g of cyclodextrin and 0.6 g of gelatin were dissolved in 100 mL of water, heated at 50° C. and stirred until completely dissolved to obtain a protective agent.

[0094] The mixed bacteria and the protective agent are mixed in a ratio of 1:1.6 and then spray-dried to obtain probiotic powder.

[0095] The probiotic powder, the Bletilla striata extract of Preparation Example 1, the Agrimoniae herb extract and the Pleurotus ostreatus charcoal were mixed in a mass ratio of 0.7:2:1.5:1 to obtain component B.

[0096] Mix 1.2 g of component B with 100 mL of ultrapure water and filter through a 0.22 μm microporous membrane to obtain the second spray. The second spray should be stored in a light-proof spray bottle.

[0097] When using, spray the second spray first, then spray the first spray 30 seconds later. Do not drink water for 30 minutes after spraying the first spray.

[0098] Example 4

[0099] The method of Example 1 is the same, except that the method of use is different:

[0100] When using, spray the first spray first, then spray the second spray after 30 seconds. Do not drink water for 30 minutes after spraying.

[0101] Comparative Example 1

[0102] As a comparative example of Example 1, the method of Example 1 is followed except that:

[0103] The active ingredient A was not loaded, that is, the total saponins of Panax notoginseng, tea polyphenols, chlorogenic acid from honeysuckle and baicalin were directly mixed in a mass ratio of 10:1:3:5 to obtain the active ingredient A, and 4.2 g of the active ingredient A was mixed with the second spray to obtain a control spray.

[0104] Comparative Example 2

[0105] As a comparative example of Example 1, the method of Example 1 is followed except that:

[0106] The first spray and the second spray were mixed in a volume ratio of 1:1 to obtain a control spray.

[0107] Comparative Example 3

[0108] As a comparative example of Example 1, the method of Example 1 was followed except that the active ingredient A, component B, and mixed bacteria were all loaded on chitosan and then prepared into a spray. The specific steps were as follows:

[0109] Weigh 0.7 g of chitosan, dissolve it in 100 mL of 1% glacial acetic acid solution, and stir until it is completely dissolved to obtain a chitosan solution.

[0110] Weigh 0.15 g of sodium tripolyphosphate, dissolve it in 150 mL of ultrapure water, and stir until it is completely dissolved to obtain a sodium tripolyphosphate solution.

[0111] Weigh 1 g of carbomer, dissolve it in 100 mL of ultrapure water at 70° C., and stir until it is completely dissolved to obtain a carbomer solution.

[0112] Notoginseng total saponins, tea polyphenols, honeysuckle chlorogenic acid and baicalin were mixed in a mass ratio of 10:1:3:5 to obtain active ingredient A; Lactobacillus paracasei, Lactobacillus reuteri and Streptococcus salivarius were mixed in a ratio of 2:1:1 to obtain a mixed bacteria, and the mixed bacteria was further mixed with the Bletilla striata extract, Herba Agrimoniae extract and Pleurotus ostreatus charcoal from Preparation Example 1 in a mass ratio of 0.5:3:2:1 to obtain component B.

[0113] 9.5 g of the active ingredient A and 4.5 g of component B were added to the chitosan solution, mixed, and then dropped into the sodium tripolyphosphate solution within 30 minutes with stirring. The mixture was then centrifuged and freeze-dried to obtain a nanoparticle powder containing the mixed active ingredients. 5 g of the nanoparticle powder containing the mixed active ingredients was dispersed into 100 mL of the carbomer solution, and 0.15 g of sodium alginate was added. The mixture was stirred until dissolved and then filtered through a 0.22 μm microporous filter membrane to obtain a comparative spray.

[0114] Test Example 1

[0115] Test samples 1-4

[0116] The test samples were prepared in the manner of Examples 1-4. The preparation methods of the test samples corresponding to Examples 1-4 were carried out according to the corresponding examples, with the only difference being:

[0117] In the corresponding step S10, when the active ingredient A is added, 1 mg of sodium fluorescein is added to every 100 mL of chitosan solution.

[0118] Comparative test samples 1-2

[0119] The method of the corresponding comparative example was followed, except that fluorescein sodium was added to the comparative spray in an amount of 1 mg per 100 mL of the comparative spray.

[0120] Comparative test sample 3

[0121] The method of Comparative Example 3 is as follows, except that:

[0122] While adding active ingredient A and component B, 1 mg of sodium fluorescein was added to every 100 mL of chitosan solution.

[0123] For each sample test, three white New Zealand rabbits were selected. The oral cavity of the rabbits was cleaned with normal saline. Then, the sprays of test samples 1-4 and comparative test samples 1-comparison test sample 3 were sprayed three times on the left and right oral mucosa of each rabbit as required. For multiple sprays, each spray was sprayed three times.

[0124] The rabbit's oral cavity was irradiated with an ultraviolet fluorescent lamp every 10 minutes to observe whether there was a fluorescent reaction until the fluorescent reaction disappeared. The duration of the fluorescent reaction was recorded as the residence time of the spray. For the same rabbit, the average residence time on the left and right oral mucosa was recorded as the final residence time. Each test was repeated three times, and the average value was calculated. The results are shown in Table 1.

[0125] Test Example 2

[0126] Thirty-five 8-week-old male SD rats weighing 230±20 g were randomly divided into 9 groups: a blank group, Example 1-4 groups, and Comparative Example 1-3 groups, to test the efficacy of the spray in treating oral ulcers.

[0127] After fasting for 12 h, rats in each group were anesthetized with isoflurane at a dose of 0.4 mL / 100 g on day 0. The rats were fixed and the right oral mucosa was rinsed with normal saline. A 2 mm diameter filter paper soaked in 50% acetic acid solution was pasted on the right oral mucosa and left for 1 min. The filter paper was removed and the residual solution was rinsed with normal saline to establish the oral ulcer model.

[0128] The blank group was not sprayed with any spray. Each experimental group and the comparative example group was sprayed with the corresponding spray immediately on the affected surface according to the instructions. The time required for the affected surface to stop bleeding was recorded. The corresponding spray was then sprayed on the affected surface every 8 hours. The healing of the affected surface of each group of rats was observed daily until the affected surface was completely healed with no redness or swelling. The time required for the affected surface to heal was recorded. The results are shown in Table 1.

[0129] Table 1

[0130] name Residence time (min) Hemostasis time (s) Healing time of affected surface (d) Example 1 60 3.26 3.2 Example 2 50 4.55 3.8 Example 3 70 4.11 3.4 Example 4 50 3.45 5.0 Comparative Example 1 20 3.68 6.4 Comparative Example 2 40 6.02 5.4 Comparative Example 3 50 10.15 4.2 Blank group / 6.72 7.8

[0131] As can be seen from Table 1, compared with the blank group, the spray prepared by the method provided by the present invention has a long residence time, rapid hemostasis, and significantly shortened wound healing time. In Example 4, due to the different usage methods, the first spray sprayed first formed a certain antibacterial isolation layer on the wound surface, and the hemostatic spray sprayed later could not directly contact the wound surface, resulting in a slower hemostasis speed; while the spray prepared in Comparative Example 1 was not loaded and lacked the resistance to saliva scouring brought about by the cross-linking of sodium alginate and oral calcium ions, resulting in only a slight improvement in wound healing time compared with the blank group; Comparative Example 2 was directly mixed with the two sprays, resulting in no significant improvement in hemostasis and wound healing; Comparative Example 3, since both component B and active ingredient A were loaded and further mixed with sodium alginate and sprayed on the oral cavity, although its wound healing time was significantly improved, the release rate of component B was reduced, resulting in a longer time required for hemostasis than the blank group.

[0132] Test Example 3

[0133] The sprays of Examples 1-4 were subjected to antibacterial tests according to Appendix C of GB15979-2002. The results are shown in Table 2.

[0134] Table 2 Antibacterial test

[0135]

[0136] As can be seen from Table 2, the spray prepared by the present invention has good and long-lasting antibacterial effects on Staphylococcus aureus, Candida albicans and Escherichia coli.

[0137] Test Example 4

[0138] Perform the acute eye irritation test as follows:

[0139] Three white New Zealand rabbits weighing 2.0-2.5 kg were used. The right eye served as the treatment eye, and the left eye served as the control eye. 0.1 mL of the test substance was instilled directly into the conjunctival sac of the right eye of the animal. The control eye was given an equal amount of normal saline. The eyelids were immediately and gently closed for approximately 4 seconds. After 30 seconds, the eye was rinsed with normal saline. The animals were observed for irritation, damage, and recovery of the conjunctiva, iris, and cornea 1 hour, 24 hours, 48 hours, 72 hours, 7 days, 14 days, and 21 days after administration. If no irritation reaction occurred within 72 hours, or if the eye irritation reaction completely recovered by the 7th or 14th day, the test could be terminated early.

[0140] The sprays prepared in Examples 1-4 of the present invention showed no abnormalities in the treated eyes of any of the test animals at 1, 24, and 48 hours after administration. Continued observation up to 72 hours revealed no abnormalities in the treated eyes of any of the test animals. The average scores for the three animals in Examples 1-4 at 24, 48, and 72 hours were: conjunctival hyperemia = 0, conjunctival edema = 0, corneal lesions = 0, and iris lesions = 0. No abnormalities were observed in the control eyes. This demonstrates the good safety of the sprays prepared in the present invention.

[0141] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the specific technical features in any suitable manner. To avoid unnecessary repetition, the present invention will not further describe various possible combinations. However, these simple variations and combinations should also be considered as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. A method for preparing a Panax notoginseng saponins oral spray, characterized in that: The Panax notoginseng total saponins oral spray comprises a first spray and a second spray, and the preparation method comprises: Dissolving an active ingredient A having an anti-inflammatory effect in a chitosan solution, and then adding a sodium tripolyphosphate solution to obtain nanoparticles containing the active ingredient A; and dispersing the nanoparticles containing the active ingredient A in a carbomer solution to obtain a first spray, wherein the active ingredient A includes Panax notoginseng total saponins; The second spray is obtained by dissolving component B having a hemostatic effect in water.

2. The preparation method according to claim 1, wherein Based on the total amount of the chitosan solution, the amount of the active ingredient A is 5-10 wt.%.

3. The preparation method according to claim 1 or 2, wherein The amount of the nanoparticles comprising the active ingredient A is 1-5 wt.% based on the total amount of the carbomer solution.

4. The preparation method according to claim 3, wherein The mass volume ratio of the component B to water is 1-5:

100.

5. The preparation method according to claim 4, wherein The active ingredient A also includes tea polyphenols, honeysuckle chlorogenic acid and baicalin; And / or, the component B includes Bletilla striata extract, Agrimoniae scabra extract and Thuja serrata charcoal.

6. The preparation method according to claim 5, wherein The mass ratio of the Panax notoginseng total saponins, tea polyphenols, honeysuckle chlorogenic acid and baicalin is 5-10:1:2-5:5-10.

7. The preparation method according to claim 6, wherein The component B further comprises probiotic powder, and the preparation method of the component B comprises: Lactobacillus paracasei, Lactobacillus reuteri and Streptococcus salivarius are mixed in a ratio of 2-5:1:1 to obtain a mixed bacteria; dissolving trehalose, cyclodextrin and gelatin in water to obtain a protective agent, wherein, based on the total amount of the protective agent, the amount of trehalose is 2-5 wt.%, the amount of cyclodextrin is 0.1-0.5 wt.%, and the amount of gelatin is 0.5-1 wt.%; The mixed bacteria and the protective agent are mixed in a ratio of 1:1-2 and then spray-dried to obtain probiotic powder; The probiotic powder is mixed with Bletilla striata extract, Agrimoniae herb extract and Pleurotus ostreatus charcoal to obtain the component B, wherein the mass ratio of the probiotic powder, Bletilla striata extract, Agrimoniae herb extract and Pleurotus ostreatus charcoal is 0.5-1:2-5:1-2:

1.

8. The preparation method according to any one of claims 1, 2, 4 to 7, wherein The preparation method further comprises: dispersing the nanoparticles containing the active ingredient A in a carbomer solution, and then adding sodium alginate to obtain the first spray; Based on the total amount of the carbomer solution, the amount of the sodium alginate is 0.1-0.2 wt.%.

9. The preparation method according to claim 8, wherein The volume ratio of the sodium tripolyphosphate solution to the chitosan solution is 1-2:1; and / or, based on the total amount of the sodium tripolyphosphate solution, the concentration of the sodium tripolyphosphate solution is 0.01-0.1 wt.%; and / or, based on the total amount of the chitosan solution, the concentration of the chitosan solution is 0.5-1 wt.%; And / or, based on the total amount of the carbomer solution, the concentration of the carbomer solution is 0.5-2 wt.%.

10. A Panax notoginseng saponin oral spray prepared according to the preparation method according to any one of claims 1 to 9, characterized in that: The method for using the Panax notoginseng saponins oral spray comprises: Spray the second spray on the affected surface, wait for a preset time, and then spray the first spray again.

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